@article {pmid38534749, year = {2024}, author = {Stavchansky, VV and Yuzhakov, VV and Sevan'kaeva, LE and Fomina, NK and Koretskaya, AE and Denisova, AE and Mozgovoy, IV and Gubsky, LV and Filippenkov, IB and Myasoedov, NF and Limborska, SA and Dergunova, LV}, title = {Melanocortin Derivatives Induced Vascularization and Neuroglial Proliferation in the Rat Brain under Conditions of Cerebral Ischemia.}, journal = {Current issues in molecular biology}, volume = {46}, number = {3}, pages = {2071-2092}, doi = {10.3390/cimb46030133}, pmid = {38534749}, issn = {1467-3045}, support = {19-14-00268//Russian Science Foundation/ ; 5f.5.9.//The Thematic plan of the National Research Centre "Kurchatov Institute"/ ; }, abstract = {Stroke remains the second leading cause of death worldwide. The development of new therapeutic agents focused on restoring vascular function and neuroprotection of viable tissues is required. In this study the neuroprotective activity of melanocortin-like ACTH(4-7)PGP and ACTH(6-9)PGP peptides was investigated in rat brain at 24 h after transient middle cerebral artery occlusion (tMCAO). The severity of ischemic damage, changes in the proliferative activity of neuroglial cells and vascularization of rat brain tissue were analyzed. The administration of peptides resulted in a significant increase in the volume density of neurons in the perifocal zone of infarction compared to rats subjected to ischemia and receiving saline. Immunohistochemical analysis of the proliferative activity of neuroglia cells using PCNA antibodies showed a significant increase in the number of proliferating cells in the penumbra and in the intact cerebral cortex of rats receiving peptide treatment. The effect of peptides on vascularization was examined using CD31 antibodies under tMCAO conditions, revealing a significant increase in the volume density of vessels and their sizes in the penumbra after administration of ACTH(4-7)PGP and ACTH(6-9)PGP. These findings confirm the neuroprotective effect of peptides due to the activation of neuroglia proliferation and the enhancement of collateral blood flow.}, } @article {pmid38458749, year = {2024}, author = {Geier, A and Trost, J and Wang, K and Schmid, C and Krawczyk, M and Schiffels, S}, title = {PNPLA3 fatty liver allele was fixed in Neanderthals and segregates neutrally in humans.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2023-331594}, pmid = {38458749}, issn = {1468-3288}, abstract = {OBJECTIVE: Fat deposition is modulated by environmental factors and genetic predisposition. Genome-wide association studies identified PNPLA3 p.I148M (rs738409) as a common variant that increases risk of developing liver steatosis. When and how this variant evolved in humans has not been studied to date.

DESIGN: Here we analyse ancient DNA to track the history of this allele throughout human history. In total, 6444 published ancient (modern humans, Neanderthal, Denisovan) and 3943 published present day genomes were used for analysis after extracting genotype calls for PNPLA3 p.I148M. To quantify changes through time, logistic and, by grouping individuals according to geography and age, linear regression analyses were performed.

RESULTS: We find that archaic human individuals (Neanderthal, Denisovan) exclusively carried a fixed PNPLA3 risk allele, whereas allele frequencies in modern human populations range from very low in Africa to >50% in Mesoamerica. Over the last 15 000 years, distributions of ancestral and derived alleles roughly match the present day distribution. Logistic regression analyses did not yield signals of natural selection during the last 10 000 years.

CONCLUSION: Archaic human individuals exclusively carried a fixed PNPLA3 allele associated with fatty liver, whereas allele frequencies in modern human populations are variable even in the oldest samples. Our observation might underscore the advantage of fat storage in cold climate and particularly for Neanderthal under ice age conditions. The absent signals of natural selection during modern human history does not support the thrifty gene hypothesis in case of PNPLA3 p.I148M.}, } @article {pmid38444398, year = {2024}, author = {Hautavoine, H and Arnaud, J and Balzeau, A and Mounier, A}, title = {Quantifying hominin morphological diversity at the end of the middle Pleistocene: Implications for the origin of Homo sapiens.}, journal = {American journal of biological anthropology}, volume = {}, number = {}, pages = {e24915}, doi = {10.1002/ajpa.24915}, pmid = {38444398}, issn = {2692-7691}, abstract = {OBJECTIVES: The Middle Pleistocene (MP) saw the emergence of new species of hominins: Homo sapiens in Africa, H. neanderthalensis, and possibly Denisovans in Eurasia, whose most recent common ancestor is thought to have lived in Africa around 600 ka ago. However, hominin remains from this period present a wide range of morphological variation making it difficult to securely determine their taxonomic attribution and their phylogenetic position within the Homo genus. This study proposes to reconsider the phenetic relationships between MP hominin fossils in order to clarify evolutionary trends and contacts between the populations they represent.

MATERIALS AND METHODS: We used a Geometric Morphometrics approach to quantify the morphological variation of the calvarium of controversial MP specimens from Africa and Eurasia by using a comparative sample that can be divided into 5 groups: H. ergaster, H. erectus, H. neanderthalensis, and H. sapiens, as well as individuals from current modern human populations. We performed a Generalized Procrustes Analysis, a Principal Component Analysis, and Multinomial Principal Component Logistic Regressions to determine the phenetic affinities of the controversial Middle Pleistocene specimens with the other groups.

RESULTS: MP African and Eurasian specimens represent several populations, some of which show strong affinities with H. neanderthalensis in Europe or H. sapiens in Africa, others presenting multiple affinities.

DISCUSSION: These MP populations might have contributed to the emergence of these two species in different proportions. This study proposes a new framework for the human evolutionary history during the MP.}, } @article {pmid38434301, year = {2024}, author = {Tyrinova, T and Batorov, E and Aristova, T and Ushakova, G and Sizikova, S and Denisova, V and Chernykh, E}, title = {Decreased circulating myeloid-derived suppressor cell count at the engraftment is one of the risk factors for multiple myeloma relapse after autologous hematopoietic stem cell transplantation.}, journal = {Heliyon}, volume = {10}, number = {5}, pages = {e26362}, pmid = {38434301}, issn = {2405-8440}, abstract = {Recent studies demonstrated that myeloid-derived suppressor cells (MDSCs) are involved in the pathogenesis and progression of multiple myeloma (MM). Nevertheless, data on the quantitative and functional changes in MDSCs during standard MM treatment remain poorly understood. Here, we determined that monocytic MDSCs (M-MDSC; CD14[+]HLA-DR[low/-]) and granulocytic MDSCs (PMN-MDSC; Lin[-]HLA-DR[-]CD33[+]CD66b[+]) in MM patients in remission following induction therapy (IT) were significantly increased, while early MDSCs (E-MDSCs; Lin[-]HLA-DR[-]CD33[+]CD66b[-]) were decreased compared to the donor group. In progression, MM patients had the most pronounced decrease in E-MDSCs and enhanced levels of PMN-MDSCs. IT was accompanied with a decrease in the expression of arginase-1 (Arg-1). In MM patients with relapse or resistance to IT, Arg-1[+] cell frequency in M-MDSCs and E-MDSCs, as well as PD-L1[+] M-MDSCs, was increased, which may facilitate tumor immunosuppression. G-CSF administration led to a significant increment in the MDSC subsets. At the engraftment, circulating M-MDSC and PMN-MDSCs were temporarily increased, with a gradual decline to the pre-transplant levels in 12 months. The percentage of E-MDSCs was decreased at the leukocyte recovery. Patients with a higher (>Me) M-MDSC count at the engraftment had a shorter post-transplant leukopenia duration (Me 11 vs. 13 days; pU = 0.0086). The advanced MM stage, depth of response, and lower relative count of circulating E-MDSCs at the engraftment were independent risk factors associated with a lower progression-free survival. The obtained data allow us to hypothesize that MDSCs may play a positive role at the stage of leukocyte recovery by ameliorating the long-term anti-tumor response in MM.}, } @article {pmid38405782, year = {2024}, author = {Kerdoncuff, E and Skov, L and Patterson, N and Zhao, W and Lueng, YY and Schellenberg, GD and Smith, JA and Dey, S and Ganna, A and Dey, AB and Kardia, SLR and Lee, J and Moorjani, P}, title = {50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.15.580575}, pmid = {38405782}, abstract = {India has been underrepresented in whole genome sequencing studies. We generated 2,762 high coverage genomes from India - including individuals from most geographic regions, speakers of all major languages, and tribal and caste groups - providing a comprehensive survey of genetic variation in India. With these data, we reconstruct the evolutionary history of India through space and time at fine scales. We show that most Indians derive ancestry from three ancestral groups related to ancient Iranian farmers, Eurasian Steppe pastoralists and South Asian hunter-gatherers. We uncover a common source of Iranian-related ancestry from early Neolithic cultures of Central Asia into the ancestors of Ancestral South Indians (ASI), Ancestral North Indians (ANI), Austro-asiatic-related and East Asian-related groups in India. Following these admixtures, India experienced a major demographic shift towards endogamy, resulting in extensive homozygosity and identity-by-descent sharing among individuals. At deep time scales, Indians derive around 1-2% of their ancestry from gene flow from archaic hominins, Neanderthals and Denisovans. By assembling the surviving fragments of archaic ancestry in modern Indians, we recover ~1.5 Gb (or 50%) of the introgressing Neanderthal and ~0.6 Gb (or 20%) of the introgressing Denisovan genomes, more than any other previous archaic ancestry study. Moreover, Indians have the largest variation in Neanderthal ancestry, as well as the highest amount of population-specific Neanderthal segments among worldwide groups. Finally, we demonstrate that most of the genetic variation in Indians stems from a single major migration out of Africa that occurred around 50,000 years ago, with minimal contribution from earlier migration waves. Together, these analyses provide a detailed view of the population history of India and underscore the value of expanding genomic surveys to diverse groups outside Europe.}, } @article {pmid38367615, year = {2024}, author = {Zeberg, H and Jakobsson, M and Pääbo, S}, title = {The genetic changes that shaped Neandertals, Denisovans, and modern humans.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2023.12.029}, pmid = {38367615}, issn = {1097-4172}, abstract = {Modern human ancestors diverged from the ancestors of Neandertals and Denisovans about 600,000 years ago. Until about 40,000 years ago, these three groups existed in parallel, occasionally met, and exchanged genes. A critical question is why modern humans, and not the other two groups, survived, became numerous, and developed complex cultures. Here, we discuss genetic differences among the groups and some of their functional consequences. As more present-day genome sequences become available from diverse groups, we predict that very few, if any, differences will distinguish all modern humans from all Neandertals and Denisovans. We propose that the genetic basis of what constitutes a modern human is best thought of as a combination of genetic features, where perhaps none of them is present in each and every present-day individual.}, } @article {pmid38361267, year = {2024}, author = {Denisova, SA and Shchenkov, SV and Lebedenkov, VV}, title = {Microanatomy and ultrastructure of the nervous system of adult Renicola parvicaudatus (Digenea: Renicolidae).}, journal = {Journal of morphology}, volume = {285}, number = {2}, pages = {e21672}, doi = {10.1002/jmor.21672}, pmid = {38361267}, issn = {1097-4687}, support = {//Russian Science Foundation/ ; }, abstract = {The digenean complex life cycle includes various morphological forms with different locomotory and behavioral activities, and the functional specialization of their nervous system is of importance for the transmission of these parasites. Adult digeneans acquire many adaptive features associated with the final settlement in a vertebrate host. Our study describes the general morphology and ultrastructure of the nervous system of the adult renicolid digenean Renicola parvicaudatus parasitizing the renal tubules of herring gulls. Using immunocytochemical and electron microscopic methods, we identified the distinctive characteristics of ganglia and synapses in the studied species. A comparative analysis of the organization of the nervous system of adult individuals and their continuously-swimming stylet cercariae revealed a number of stage-related differences in the composition of ganglia, the distribution of serotonin- and FMRFamide-immunoreactive neurons, the cytomorphology of neuron somata and free sensory endings. Thus, in adults, the presence of FMRFamide-positive neuron somata, accessory muscle bundles in the ganglionic cortex, and eight types of neuronal vesicles was detected, but no glia-like elements were identified. Their neurons are characterized by a larger volume of cytoplasm and also show greater ultrastructural diversity. Although the sensory papillae of adults do not vary in their external morphology as much as those of larvae, their sensory bulbs are more diverse in cytomorphology. Following our previous data on the "support" cell processes related to various tissues of the larvae and considered as glia-like structures, we also briefly present the identified features of the parenchyma, attachment organs and excretory system of adult individuals. The excretory system of adult R. parvicaudatus is characterized by the presence of unique terminal cells with several flame tufts, which are not typical either for the larvae of this species or for other digeneans studied so far. We also used molecular phylogenetic analysis to clarify species identification.}, } @article {pmid38357193, year = {2024}, author = {Denisová, N and Piercey, SJ and Wälle, M}, title = {Mineralogy and mineral chemistry of the ABM replacement-style volcanogenic massive sulfide deposit, Finlayson Lake district, Yukon, Canada.}, journal = {Mineralium deposita}, volume = {59}, number = {3}, pages = {473-503}, pmid = {38357193}, issn = {1432-1866}, abstract = {UNLABELLED: The ABM deposit is a bimodal-felsic, replacement-style volcanogenic massive sulfide deposit (VMS) that is hosted by back-arc affinity rocks of the Yukon-Tanana terrane in the Finlayson Lake VMS district, Yukon, Canada. Massive sulfide zones occur as stacked and stratabound lenses subparallel to the volcanic stratigraphy, surrounded by pervasive white mica and/or chlorite alteration. Remnant clasts of volcanic rocks and preserved bedding occur locally within the massive sulfide lenses and indicate that mineralization formed through subseafloor replacement of pre-existing strata. Three mineral assemblages occur at the ABM deposit: (1) a pyrite-chalcopyrite-magnetite-pyrrhotite assemblage that is associated with Cu-Bi-Se-Co-enrichment and occurs at the center of the massive sulfide lenses; (2) a pyrite-sphalerite assemblage, which occurs more commonly towards lens margins and is enriched in Zn-Pb-Ag-Au-Hg-As-Sb-Ba; and (3) a minor assemblage comprising chalcopyrite-pyrrhotite-pyrite stringers associated with pervasive chlorite alteration, which occurs mostly at the sulfide lens margins. Petrographic observations of preserved primary, zone refining, and metamorphic textures in combination with in situ geochemistry show that the pyrite-sphalerite assemblage formed at lower temperatures (< 270 °C) than the other two mineral assemblages (~ 270-350 °C), and that mineral chemistry in all mineral assemblages was affected by greenschist facies metamorphism, although the effects are limited to recrystallization, small-scale remobilization (< 1 m) and trace element redistribution.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00126-023-01217-4.}, } @article {pmid38337062, year = {2024}, author = {Végh, EI and Douka, K}, title = {SpecieScan: Semi-Automated taxonomic identification of bone collagen peptides from MALDI-ToF MS spectra.}, journal = {Bioinformatics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/bioinformatics/btae054}, pmid = {38337062}, issn = {1367-4811}, abstract = {MOTIVATION: Zooarchaeology by Mass Spectrometry (ZooMS) is a palaeoproteomics method for the taxonomic determination of collagen, which traditionally involves challenging manual spectra analysis with limitations in quantitative results. As the ZooMS reference database expands, a faster and reproducible identification tool is necessary. This paper presents SpecieScan, an open-access algorithm for automating taxa identification from raw MALDI-ToF Mass Spectrometry (MS) data.

RESULTS: SpecieScan was developed using R (pre-processing) and Python (automation). The algorithm's output includes identified peptide markers, closest matching taxonomic group (taxon, family, order), correlation scores with the reference databases, and contaminant peaks present in the spectra. Testing on original MS data from bones discovered at several archaeological sites, including Denisova Cave, as well as publicly available externally produced data, achieved >90% accuracy at the genus-level and ∼92% accuracy at the family-level for data of mammalian bone collagen previously analysed using manual methods.

SUPPLEMENTARY INFORMATION: The SpecieScan algorithm, original raw data, results, reference databases, and contamination lists are freely available on the web and can be found on Github (https://github.com/mesve/SpecieScan).}, } @article {pmid38278971, year = {2024}, author = {Larivière, D and Abueg, L and Brajuka, N and Gallardo-Alba, C and Grüning, B and Ko, BJ and Ostrovsky, A and Palmada-Flores, M and Pickett, BD and Rabbani, K and Antunes, A and Balacco, JR and Chaisson, MJP and Cheng, H and Collins, J and Couture, M and Denisova, A and Fedrigo, O and Gallo, GR and Giani, AM and Gooder, GM and Horan, K and Jain, N and Johnson, C and Kim, H and Lee, C and Marques-Bonet, T and O'Toole, B and Rhie, A and Secomandi, S and Sozzoni, M and Tilley, T and Uliano-Silva, M and van den Beek, M and Williams, RW and Waterhouse, RM and Phillippy, AM and Jarvis, ED and Schatz, MC and Nekrutenko, A and Formenti, G}, title = {Scalable, accessible and reproducible reference genome assembly and evaluation in Galaxy.}, journal = {Nature biotechnology}, volume = {}, number = {}, pages = {}, pmid = {38278971}, issn = {1546-1696}, } @article {pmid38213708, year = {2023}, author = {Borodko, DD and Zhenilo, SV and Sharko, FS}, title = {Search for differentially methylated regions in ancient and modern genomes.}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {27}, number = {7}, pages = {820-828}, doi = {10.18699/VJGB-23-95}, pmid = {38213708}, issn = {2500-0462}, abstract = {Currently, active research is focused on investigating the mechanisms that regulate the development of various pathologies and their evolutionary dynamics. Epigenetic mechanisms, such as DNA methylation, play a significant role in evolutionary processes, as their changes have a faster impact on the phenotype compared to mutagenesis. In this study, we attempted to develop an algorithm for identifying differentially methylated regions associated with metabolic syndrome, which have undergone methylation changes in humans during the transition from a hunter-gatherer to a sedentary lifestyle. The application of existing whole-genome bisulfite sequencing methods is limited for ancient samples due to their low quality and fragmentation, and the approach to obtaining DNA methylation profiles differs significantly between ancient hunter-gatherer samples and modern tissues. In this study, we validated DamMet, an algorithm for reconstructing ancient methylomes. Application of DamMet to Neanderthal and Denisovan genomes showed a moderate level of correlation with previously published methylation profiles and demonstrated an underestimation of methylation levels in the reconstructed profiles by an average of 15-20 %. Additionally, we developed a new Python-based algorithm that allows for the comparison of methylomes in ancient and modern samples, despite the absence of methylation profiles in modern bone tissue within the context of obesity. This analysis involves a two-step data processing approach, where the first step involves the identification and filtration of tissue-specific methylation regions, and the second step focuses on the direct search for differentially methylated regions in specific areas associated with the researcher's target condition. By applying this algorithm to test data, we identified 38 differentially methylated regions associated with obesity, the majority of which were located in promoter regions. The pipeline demonstrated sufficient efficiency in detecting these regions. These results confirm the feasibility of reconstructing DNA methylation profiles in ancient samples and comparing them with modern methylomes. Furthermore, possibilities for further methodological development and the implementation of a new step for studying differentially methylated positions associated with evolutionary processes are discussed.}, } @article {pmid38189581, year = {2024}, author = {Ziv, I and Avni, I and Dinstein, I and Meiri, G and Bonneh, YS}, title = {Oculomotor randomness is higher in autistic children and increases with the severity of symptoms.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {}, number = {}, pages = {}, doi = {10.1002/aur.3083}, pmid = {38189581}, issn = {1939-3806}, support = {657/21//Israel Science Foundation/ ; 1150/20//Israel Science Foundation/ ; }, abstract = {A variety of studies have suggested that at least some children with autism spectrum disorder (ASD) view the world differently. Differences in gaze patterns as measured by eye tracking have been demonstrated during visual exploration of images and natural viewing of movies with social content. Here we analyzed the temporal randomness of saccades and blinks during natural viewing of movies, inspired by a recent measure of "randomness" applied to micro-movements of the hand and head in ASD (Torres et al., 2013; Torres & Denisova, 2016). We analyzed a large eye-tracking dataset of 189 ASD and 41 typically developing (TD) children (1-11 years old) who watched three movie clips with social content, each repeated twice. We found that oculomotor measures of randomness, obtained from gamma parameters of inter-saccade intervals (ISI) and blink duration distributions, were significantly higher in the ASD group compared with the TD group and were correlated with the ADOS comparison score, reflecting increased "randomness" in more severe cases. Moreover, these measures of randomness decreased with age, as well as with higher cognitive scores in both groups and were consistent across repeated viewing of each movie clip. Highly "random" eye movements in ASD children could be associated with high "neural variability" or noise, poor sensory-motor control, or weak engagement with the movies. These findings could contribute to the future development of oculomotor biomarkers as part of an integrative diagnostic tool for ASD.}, } @article {pmid38169863, year = {2023}, author = {Ojomoko, LO and Kryukova, EV and Egorova, NS and Salikhov, AI and Epifanova, LA and Denisova, DA and Khomutov, AR and Sukhov, DA and Vassilevski, AA and Khomutov, MA and Tsetlin, VI and Shelukhina, IV}, title = {Inhibition of nicotinic acetylcholine receptors by oligoarginine peptides and polyamine-related compounds.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1327603}, doi = {10.3389/fphar.2023.1327603}, pmid = {38169863}, issn = {1663-9812}, abstract = {Oligoarginine peptides, known mostly for their cell-penetrating properties, are also inhibitors of the nicotinic acetylcholine receptors (nAChRs). Since octa-arginine (R8) inhibits α9α10 nAChR and suppresses neuropathic pain, we checked if other polycationic compounds containing amino and/or guanidino groups could be effective and tested the activity of the disulfide-fixed "cyclo"R8, a series of biogenic polyamines (putrescine, spermidine, and spermine), C-methylated spermine analogs, agmatine and its analogs, as well as acylpolyamine argiotoxin-636 from spider venom. Their inhibitory potency on muscle-type, α7 and α9α10 nAChRs was determined using radioligand analysis, electrophysiology, and calcium imaging. "Cyclo"R8 showed similar activity to that of R8 against α9α10 nAChR (IC50 ≈ 60 nM). Biogenic polyamines as well as agmatine and its analogs displayed low activity on muscle-type Torpedo californica, as well as α7 and α9α10 nAChRs, which increased with chain length, the most active being spermine and its C-methylated derivatives having IC50 of about 30 μM against muscle-type T. californica nAChR. Argiotoxin-636, which contains a polyamine backbone and terminal guanidino group, also weakly inhibited T. californica nAChR (IC50 ≈ 15 μM), but it revealed high potency against rat α9α10 nAChR (IC50 ≈ 200 nM). We conclude that oligoarginines and similar polycationic compounds effectively inhibiting α9α10 nAChR may serve as a basis for the development of analgesics to reduce neuropathic pain.}, } @article {pmid38166646, year = {2024}, author = {Levinstein Hallak, K and Rosset, S}, title = {Dating ancient splits in phylogenetic trees, with application to the human-Neanderthal split.}, journal = {BMC genomic data}, volume = {25}, number = {1}, pages = {4}, pmid = {38166646}, issn = {2730-6844}, support = {2180/20//Israeli Science Foundation grant/ ; }, abstract = {BACKGROUND: We tackle the problem of estimating species TMRCAs (Time to Most Recent Common Ancestor), given a genome sequence from each species and a large known phylogenetic tree with a known structure (typically from one of the species). The number of transitions at each site from the first sequence to the other is assumed to be Poisson distributed, and only the parity of the number of transitions is observed. The detailed phylogenetic tree contains information about the transition rates in each site. We use this formulation to develop and analyze multiple estimators of the species' TMRCA. To test our methods, we use mtDNA substitution statistics from the well-established Phylotree as a baseline for data simulation such that the substitution rate per site mimics the real-world observed rates.

RESULTS: We evaluate our methods using simulated data and compare them to the Bayesian optimizing software BEAST2, showing that our proposed estimators are accurate for a wide range of TMRCAs and significantly outperform BEAST2. We then apply the proposed estimators on Neanderthal, Denisovan, and Chimpanzee mtDNA genomes to better estimate their TMRCA with modern humans and find that their TMRCA is substantially later, compared to values cited recently in the literature.

CONCLUSIONS: Our methods utilize the transition statistics from the entire known human mtDNA phylogenetic tree (Phylotree), eliminating the requirement to reconstruct a tree encompassing the specific sequences of interest. Moreover, they demonstrate notable improvement in both running speed and accuracy compared to BEAST2, particularly for earlier TMRCAs like the human-Chimpanzee split. Our results date the human - Neanderthal TMRCA to be [Formula: see text] years ago, considerably later than values cited in other recent studies.}, } @article {pmid38158904, year = {2023}, author = {Ivchenko, GS and Lobzhanidze, NN and Rusina, DS and Denisova, EV and Ivchenko, AA}, title = {[Mild post-COVID syndrome in young patients].}, journal = {Terapevticheskii arkhiv}, volume = {95}, number = {8}, pages = {674-678}, doi = {10.26442/00403660.2023.08.202349}, pmid = {38158904}, issn = {0040-3660}, abstract = {BACKGROUND: Many COVID-19 survivors suffer from post-COVID syndrome, which significantly worsens the quality of life. Its presentation is quite diverse, with cognitive disorders being of particular importance. Liver injury due to the direct virus action and the treatment of the new coronavirus infection can persist for a long time during the recovery period and lead to hyperammonemia, which can cause cognitive disorders, including minimal hepatic encephalopathy.

AIM: To study cognitive disorders in post-COVID syndrome and the possibility of their treatment with L-ornithine-L-aspartate.

MATERIALS AND METHODS: The study included 30 students from 18 to 24 years old who had COVID-19 and decreased attention, memory impairment, and other cognitive disorders inherent in hepatic encephalopathy of latent (grade 0) or mild (grade 1) severity, without pronounced impairment of intelligence, memory, speech, and learning ability. Hyperammonemia, elevated alanine aminotransferase, aspartate aminotransferase, and ã-glutamyl transpeptidase, signs of hepatic encephalopathy according to psychometric tests, were reported in young people. All patients in the study were treated with L-ornithine-L-aspartate to correct the ammonia blood level and improve signs of hepatic encephalopathy and the general condition.

RESULTS AND CONCLUSION: An improvement in the objective findings, liver enzymes, a decrease in ammonia level, and an improvement in testing results for changes in cognitive functions were reported.}, } @article {pmid38110796, year = {2023}, author = {Zhao, H and Liu, LL and Sun, J and Jin, L and Xie, HB and Li, JB and Xu, H and Wu, DD and Zhuang, XL and Peng, MS and Guo, YJ and Qian, WZ and Otecko, NO and Sun, WJ and Qu, LH and He, J and Chen, ZL and Liu, R and Chen, CS and Zhang, YP}, title = {A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {38110796}, issn = {1869-1889}, abstract = {Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.}, } @article {pmid38095367, year = {2023}, author = {Velazquez-Arcelay, K and Colbran, LL and McArthur, E and Brand, CM and Rinker, DC and Siemann, JK and McMahon, DG and Capra, JA}, title = {Archaic Introgression Shaped Human Circadian Traits.}, journal = {Genome biology and evolution}, volume = {15}, number = {12}, pages = {}, doi = {10.1093/gbe/evad203}, pmid = {38095367}, issn = {1759-6653}, abstract = {When the ancestors of modern Eurasians migrated out of Africa and interbred with Eurasian archaic hominins, namely, Neanderthals and Denisovans, DNA of archaic ancestry integrated into the genomes of anatomically modern humans. This process potentially accelerated adaptation to Eurasian environmental factors, including reduced ultraviolet radiation and increased variation in seasonal dynamics. However, whether these groups differed substantially in circadian biology and whether archaic introgression adaptively contributed to human chronotypes remain unknown. Here, we traced the evolution of chronotype based on genomes from archaic hominins and present-day humans. First, we inferred differences in circadian gene sequences, splicing, and regulation between archaic hominins and modern humans. We identified 28 circadian genes containing variants with potential to alter splicing in archaics (e.g., CLOCK, PER2, RORB, and RORC) and 16 circadian genes likely divergently regulated between present-day humans and archaic hominins, including RORA. These differences suggest the potential for introgression to modify circadian gene expression. Testing this hypothesis, we found that introgressed variants are enriched among expression quantitative trait loci for circadian genes. Supporting the functional relevance of these regulatory effects, we found that many introgressed alleles have associations with chronotype. Strikingly, the strongest introgressed effects on chronotype increase morningness, consistent with adaptations to high latitude in other species. Finally, we identified several circadian loci with evidence of adaptive introgression or latitudinal clines in allele frequency. These findings identify differences in circadian gene regulation between modern humans and archaic hominins and support the contribution of introgression via coordinated effects on variation in human chronotype.}, } @article {pmid38051947, year = {2023}, author = {Wroblewski, TH and Witt, KE and Lee, SB and Malhi, RS and Peede, D and Huerta-Sánchez, E and Villanea, FA and Claw, KG}, title = {Pharmacogenetic variation in Neanderthals and Denisovans and implications for human health and response to medications.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evad222}, pmid = {38051947}, issn = {1759-6653}, abstract = {Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes - genes responsible for the processing of exogenous substances such as food, pollutants, and medications - as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore eleven key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these eleven CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.}, } @article {pmid38020913, year = {2023}, author = {Agata, A and Ohtsuka, S and Noji, R and Gotoh, H and Ono, K and Nomura, T}, title = {A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice.}, journal = {Frontiers in cell and developmental biology}, volume = {11}, number = {}, pages = {1247361}, pmid = {38020913}, issn = {2296-634X}, abstract = {Changes in genomic structures underlie phenotypic diversification in organisms. Amino acid-changing mutations affect pleiotropic functions of proteins, although little is known about how mutated proteins are adapted in existing developmental programs. Here we investigate the biological effects of a variant of the GLI3 transcription factor (GLI3[R1537C]) carried in Neanderthals and Denisovans, which are extinct hominins close to modern humans. R1537C does not compromise protein stability or GLI3 activator-dependent transcriptional activities. In contrast, R1537C affects the regulation of downstream target genes associated with developmental processes. Furthermore, genome-edited mice carrying the Neanderthal/Denisovan GLI3 mutation exhibited various alterations in skeletal morphology. Our data suggest that an extinct hominin-type GLI3 contributes to species-specific anatomical variations, which were tolerated by relaxed constraint in developmental programs during human evolution.}, } @article {pmid38003007, year = {2023}, author = {Mikhailova, SV and Ivanoshchuk, DE and Orlov, PS and Bairqdar, A and Anisimenko, MS and Denisova, DV}, title = {Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis.}, journal = {Genes}, volume = {14}, number = {11}, pages = {}, pmid = {38003007}, issn = {2073-4425}, support = {22-28-00866//Russian Science Foundation/ ; }, mesh = {Child ; Humans ; *Stress, Psychological/genetics ; Russia ; Socioeconomic Factors ; *Protein Serine-Threonine Kinases/genetics ; }, abstract = {BACKGROUND: A socioeconomic crisis in Russia lasted from 1991 to 1998 and was accompanied by a sharp drop in the birth rate. The main factor that influenced the refusal to have children during this period is thought to be prolonged social stress.

METHODS: comparing frequencies of common gene variants associated with stress-induced diseases among generations born before, after, and during this crisis may show which genes may be preferred under the pressure of natural selection during periods of increased social stress in urban populations.

RESULTS: In the "crisis" group, a statistically significant difference from the other two groups was found in rs6557168 frequency (p = 0.001); rs4522666 was not in the Hardy-Weinberg equilibrium in this group, although its frequency did not show a significant difference from the other groups (p = 0.118). Frequencies of VNTRs in SLC6A3 and MAOA as well as common variants rs17689918 in CRHR1, rs1360780 in FKBP5, rs53576 in OXTR, rs12720071 and rs806377 in CNR1, rs4311 in ACE, rs1800497 in ANKK1, and rs7412 and rs429358 in APOE did not differ among the groups.

CONCLUSIONS: a generation born during a period of prolonged destructive events may differ from the rest of the gene pool of the population in some variants associated with personality traits or stress-related disorders.}, } @article {pmid38001562, year = {2023}, author = {Denisova, K}, title = {Reply to Silber: on discoveries in science.}, journal = {Sleep}, volume = {}, number = {}, pages = {}, doi = {10.1093/sleep/zsad292}, pmid = {38001562}, issn = {1550-9109}, support = {R01 MH121605/MH/NIMH NIH HHS/United States ; R01MH121605/MH/NIMH NIH HHS/United States ; }, } @article {pmid38000592, year = {2023}, author = {Rzhepakovsky, I and Piskov, S and Avanesyan, S and Sizonenko, M and Timchenko, L and Anfinogenova, O and Nagdalian, A and Blinov, A and Denisova, E and Kochergin, S and Kubanov, S and Shakhbanov, M and Shariati, MA and Mubarak, MS}, title = {Composite of bacterial cellulose and gelatin: A versatile biocompatible scaffold for tissue engineering.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {128369}, doi = {10.1016/j.ijbiomac.2023.128369}, pmid = {38000592}, issn = {1879-0003}, abstract = {Synthesis of 0.4 ± 0.03 g/L per day of pure and porous bacterial cellulose (BC) scaffolds (scaffBC) and BC scaffolds modified with gelatin (scaffBC/Gel) was carried out using the Medusomyces gisevii Sa-28 bacterial strain. FT-IR spectroscopy and X-ray diffraction analysis showed that the scaffolds largely consist of crystalline cellulose I (Iα, Iß). Heating of BC with gelatin to 60 °C with subsequent lyophilization led to its modification by adsorption and binding of low-molecular fractions of gelatin and the formation of small pores between the fibers, which increased the biocompatibility and solubility of BC. The solubility of scaffBC and scaffBC/Gel was 20.8 % and 44.4 %, respectively, which enhances degradation in vivo. Light microscopy, scanning electron microscopy, and microcomputed tomography showed a uniform distribution of pores with a diameter of 100-500 μm. The chicken chorioallantoic membrane (CAM) model and subcutaneous implantation in rats confirmed low immunogenicity and intense formation of collagen fibers in both scaffolds and active germination of new blood vessels in scaffBC and scaffBC/Gel. The proliferative cellular activity of fibroblasts confirmed the safety of scaffolds. Taken together, the results obtained show that scaffBC/Gel can be used for the engineering of hard and soft tissues, which opens opportunities for further research.}, } @article {pmid37947446, year = {2023}, author = {Marshenya, SN and Dembitskiy, AD and Fedorov, DS and Scherbakov, AG and Trussov, IA and Emelianova, O and Aksyonov, DA and Buzlukov, AL and Zhuravlev, NA and Denisova, TA and Medvedeva, NI and Abakumov, AM and Antipov, EV and Fedotov, SS}, title = {NaGaPO4F - a KTiOPO4-structured solid sodium-ion conductor.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {52}, number = {46}, pages = {17426-17437}, doi = {10.1039/d3dt03107a}, pmid = {37947446}, issn = {1477-9234}, abstract = {Advanced ionic conductors are crucial for a large variety of contemporary technologies spanning solid state ion batteries, fuel cells, gas sensors, water desalination, etc. In this work, we report on a new member of KTiOPO4-structured materials, NaGaPO4F, with sodium-ion conductivity. NaGaPO4F has been obtained for the first time via a facile two-step synthesis consisting of a hydrothermal preparation of an ammonia-based precursor, NH4GaPO4F, followed by an ion exchange reaction with NaNO3. Its crystal structure was precisely refined using a combination of synchrotron X-ray powder diffraction and electron diffraction tomography. The material is thermally stable upon 450 °C showing no significant structural transformations or degradation but only a ∼1% cell volume expansion. Na-ion mobility in NaGaPO4F was investigated by a joint experimental and computational approach comprising solid-state nuclear magnetic resonance (NMR) and density functional theory (DFT). DFT and bond-valence site energy (BVSE) calculations reveal 3D diffusion of sodium in the [GaPO4F] framework with migration barriers amounting to 0.22 and 0.44 eV, respectively, while NMR yields 0.3-0.5 eV that, being coupled with a calculated bandgap of ∼4.25 eV, makes NaGaPO4F a promising fast Na-ion conductor.}, } @article {pmid37942592, year = {2023}, author = {Katargina, LA and Chesnokova, NB and Denisova, EV and Geraskina, EA and Pavlenko, TA and Beznos, OV and Lisovskaja, OA}, title = {[The role of endothelin-1 in the pathogenesis of familial exudative vitreoretinopathy].}, journal = {Vestnik oftalmologii}, volume = {139}, number = {5}, pages = {14-18}, doi = {10.17116/oftalma202313905114}, pmid = {37942592}, issn = {0042-465X}, mesh = {Humans ; Familial Exudative Vitreoretinopathies/genetics ; Endothelin-1/genetics ; *Eye Diseases, Hereditary/diagnosis/genetics ; Mutation ; *Retinal Diseases ; Pedigree ; }, abstract = {UNLABELLED: Familial exudative vitreoretinopathy (FEVR) is a rare hereditary disease characterized by pathological retinal vascularization with a progressive and variable course. The mechanisms of disease progression remain unclear. One substance that plays an important role in the pathogenesis of retinal vascular diseases is endothelin (ET). It was found that tissue hypoxia enhances the expression of the gene encoding ET-1, and ET-1 can be locally produced in the eye.

PURPOSE: The study evaluates the possible role of endothelin-1 in the pathogenesis of FEVR.

MATERIAL AND METHODS: The study included 85 patients with FEVR aged from 1 months to 17 years who were examined in Helmholtz National Medical Research Center of Eye Diseases. The concentration of ET-1 was evaluated in 19 patients with FEVR in the blood serum (n=17), lacrimal fluid (n=18) and 16 patients from the control group.

RESULTS: The median of ET-1 in the lacrimal fluid in patients with FEVR was 13.74 pg/mL, respectively, which exceeded the same indicator of the control group 4.66 pg/mL by 2.5 times (p<0.001). The median of ET-1 in the blood serum exceeded the control group by 2.4 times (21.61 pg/mL and 9.21 pg/mL, respectively, p<0.001).

CONCLUSIONS: An increase in the concentration of ET-1 in the lacrimal fluid and blood serum of patients with FEVR in comparison with the control group indicates its involvement in the pathogenesis of the disease.}, } @article {pmid37924480, year = {2023}, author = {Gaggiano, C and Gupta, V and Agrawal, R and De Smet, MD and Frediani, B and Tosi, GM and Paroli, MP and Sridharan, S and Pavesio, CE and Pleyer, U and Denisova, EV and Babu, K and de-la-Torre, A and Yang, P and Davis, JL and Cunningham, ET and Carreño, E and Goldstein, D and Fonollosa, A and Cantarini, L and Sobrin, L and Fabiani, C}, title = {Knowledge and Current Practices in Monogenic Uveitis: An International Survey by IUSG and AIDA Network.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, pmid = {37924480}, issn = {2193-8245}, abstract = {INTRODUCTION: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts.

METHODS: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey.

RESULTS: Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors.

CONCLUSIONS: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.}, } @article {pmid37861908, year = {2023}, author = {Danchenko, EA and Ertuzun, IA and Bugaeva, LI and Lebedeva, SA and Denisova, TD and Lavrova, EB and Korzhova, TM and Tarasov, SA}, title = {Analysis of General Toxicity of Ergoferon.}, journal = {Bulletin of experimental biology and medicine}, volume = {175}, number = {5}, pages = {644-648}, pmid = {37861908}, issn = {1573-8221}, mesh = {Rats ; Animals ; *Antiviral Agents/pharmacology ; *Antibodies/pharmacology ; Toxicity Tests, Acute ; }, abstract = {For antibody-based drugs, it is important and relevant to study their toxic effects, which can often become limiting when prescribing this type of therapy. General toxicity of antiviral drug Ergoferon based on technologically processed antibodies was studied on sexually mature animals. Analysis of acute toxicity showed the absence of lethal outcomes when the drug was administered to adult rats at the maximum tolerated doses. In a study of repeated dose toxicity, no adverse effects of the drug were detected.}, } @article {pmid37853790, year = {2023}, author = {Sokolov, S and Shchenkov, S and Frolov, E and Denisova, S and Gordeev, I}, title = {Molecular and morphological screening of Podocotyle spp. (Trematoda: Opecoelidae) sheds light on their diversity in Northwest Pacific and eastern European Arctic.}, journal = {Journal of helminthology}, volume = {97}, number = {}, pages = {e78}, doi = {10.1017/S0022149X23000603}, pmid = {37853790}, issn = {1475-2697}, mesh = {Animals ; Phylogeny ; *Trematoda ; Fishes ; Life Cycle Stages ; DNA, Ribosomal/genetics ; }, abstract = {Podocotyle is a genus of marine opecoelid digeneans that parasitize a wide variety of fish as adults. We present the first phylogenetic analysis of several Podocotyle isolates using nuclear 28S rDNA and mitochondrial cox1 DNA regions. New sequences were obtained for Podocotyle specimens from fish caught in the Sea of Okhotsk and the White Sea. Based on morphological and molecular data, eight Podocotyle lineages of species rank were revealed. However, this diversity is poorly formalized within the current taxonomic model of the genus. As a result, we identified Podocotyle cf. angulata, Podocotyle cf. atomon, Podocotyle cf. reflexa, Podocotyle atomon of Sokolov et al., 2019, Podocotyle sp. of Denisova et al., 2023, Podocotyle sp. 1, Podocotyle sp. 2 and Podocotyle sp. 3. We also highlight the unresolved question of the life cycles of representatives of Podocotyle whose intramolluscan stages parasitize the intertidal snails Littorina spp.}, } @article {pmid37832473, year = {2024}, author = {Alenkina, IV and Chukin, AV and Leitus, G and Denisova, OV and Gracheva, M and Felner, I and Kuzmann, E and Homonnay, Z and Oshtrakh, MI}, title = {Analysis of the iron states in iron-containing pharmaceutical products using Mössbauer spectroscopy.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {237}, number = {}, pages = {115745}, doi = {10.1016/j.jpba.2023.115745}, pmid = {37832473}, issn = {1873-264X}, mesh = {Spectroscopy, Mossbauer ; *Iron/chemistry ; Ferric Compounds/chemistry ; *Iron Compounds ; Pharmaceutical Preparations ; }, abstract = {Iron-containing pharmaceuticals, namely: (i) PreNatal with ferrous fumarate, (ii) Tardyferon® with ferrous sulfate, (iii) Fenules with water free ferrous sulfate, (iv) Iron Complex with iron glycinate, citrate, (v) Gentle Iron, (vi) Hema-Plex® and (vii) Iron Bisglycinate with iron (ferrous) bisglycinate chelate (iron compounds are given as declared by the manufactures) were studied by [57]Fe Mössbauer spectroscopy with X-ray diffraction and magnetization measurements for analysis of the iron state. The obtained results demonstrate that the iron compound announced by the manufacturer in each pharmaceutical is not homogeneous and exists as some modifications of this compound or results of its transformation/oxidation probably due to its instability. The presence of ferrous and ferric compounds is observed, and the relative ferric iron fractions are roughly determined for each pharmaceutical product. This analysis clearly shows the differences between the iron compounds proclaimed by the manufacturers and those obtained by Mössbauer spectroscopy. That justifies as to why this technique should be used for the control and analysis of the iron-containing pharmaceuticals.}, } @article {pmid37808839, year = {2023}, author = {Villanea, FA and Peede, D and Kaufman, EJ and Añorve-Garibay, V and Witt, KE and Villa-Islas, V and Zeloni, R and Marnetto, D and Moorjani, P and Jay, F and Valdmanis, PN and Ávila-Arcos, MC and Huerta-Sánchez, E}, title = {The MUC19 gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37808839}, abstract = {All humans carry a small fraction of archaic ancestry across the genome, the legacy of gene flow from Neanderthals, Denisovans, and other hominids into the ancestors of modern humans. While the effects of Neanderthal ancestry on human fitness and health have been explored more thoroughly, there are fewer examples of adaptive introgression of Denisovan variants. Here, we study the gene MUC19, for which some modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions, from lubrication to immunity. We find the diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals among global population, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that some Neanderthals--Vindija and Chagyrskaya--carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression. Finally, we find that the Denisovan-like MUC19 haplotype carries a higher copy number of a 30 base-pair variable number tandem repeat relative to the Human-like haplotype, and that copy numbers of this repeat are exceedingly high in American populations. Our results suggest that the Denisovan-like MUC19 haplotype served as the raw genetic material for positive selection as American populations adapted to novel environments during their movement from Beringia into North and then South America.}, } @article {pmid37794804, year = {2023}, author = {Solovev, AS and Denisova, EM and Kurbatova, EA and Kutsevalova, OY and Boronina, LG and Ageevets, VA and Sidorenko, SV and Krylov, VB and Nifantiev, NE}, title = {Synthesis of methylphosphorylated oligomannosides structurally related to lipopolysaccharide O-antigens of Klebsiella pneumoniae serotype O3 and their application for detection of specific antibodies in rabbit and human sera.}, journal = {Organic & biomolecular chemistry}, volume = {21}, number = {41}, pages = {8306-8319}, doi = {10.1039/d3ob01203d}, pmid = {37794804}, issn = {1477-0539}, mesh = {Animals ; Humans ; Rabbits ; *Lipopolysaccharides ; *O Antigens/chemistry ; Klebsiella pneumoniae ; Serogroup ; Oligosaccharides ; Galactans ; Antibodies ; }, abstract = {Methylphosphorylated mono-, di- and trimannosides structurally related to the lipopolysaccharide (LPS) O-antigens of Klebsiella pneumoniae of serotype O3 were synthesized and conjugated with a biotin tag. The stereo- and regioselective assembly of target carbohydrate chains was conducted using uniform monosaccharide synthetic blocks. After that, a methylphosphate group was introduced by coupling with a methyl-H-phosphonate reagent followed by oxidation and deprotection to give the target oligosaccharides. The [1]H and [13]C NMR spectra of the obtained compounds showed a good fit with the spectrum of the corresponding natural polysaccharide. The newly prepared biotinylated oligosaccharides along with the previously reported biotinylated glycoconjugates related to galactan I and galactan II of K. pneumoniae LPS were used for the ELISA detection of antibodies in anti-K. pneumoniae rabbit sera. Anti-O3 serum antibodies specifically recognized the synthesized oligosaccharide ligands with terminal methylphosphomannosyl residues, whereas anti-O1 serum antibodies recognized the oligosaccharide related to K. pneumoniae galactan II. The analysis of human sera from patients with confirmed Klebsiella infection also revealed the presence of antibodies against the synthesized oligosaccharides in clinical cases. Thus, the described compounds together with other Klebsiella related antigenic oligosaccharides could be potentially used as molecular probes for K. pneumoniae serological diagnostics development and strain serotyping.}, } @article {pmid37790518, year = {2023}, author = {Yee, SW and Ferrández-Peral, L and Alentorn, P and Fontsere, C and Ceylan, M and Koleske, ML and Handin, N and Artegoitia, VM and Lara, G and Chien, HC and Zhou, X and Dainat, J and Zalevsky, A and Sali, A and Brand, CM and Capra, JA and Artursson, P and Newman, JW and Marques-Bonet, T and Giacomini, KM}, title = {Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37790518}, abstract = {SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.}, } @article {pmid37758744, year = {2023}, author = {Bacon, AM and Bourgon, N and Dufour, E and Demeter, F and Zanolli, C and Westaway, KE and Joannes-Boyau, R and Duringer, P and Ponche, JL and Morley, MW and Suzzoni, E and Frangeul, S and Boesch, Q and Antoine, PO and Boualaphane, S and Sichanthongtip, P and Sihanam, D and Huong, NTM and Tuan, NA and Fiorillo, D and Tombret, O and Patole-Edoumba, E and Zachwieja, A and Luangkhoth, T and Souksavatdy, V and Dunn, TE and Shackelford, L and Hublin, JJ}, title = {Palaeoenvironments and hominin evolutionary dynamics in southeast Asia.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {16165}, pmid = {37758744}, issn = {2045-2322}, mesh = {Animals ; Laos ; *Forests ; *Biological Evolution ; Caves ; China ; }, abstract = {Secure environmental contexts are crucial for hominin interpretation and comparison. The discovery of a Denisovan individual and associated fauna at Tam Ngu Hao 2 (Cobra) Cave, Laos, dating back to 164-131 ka, allows for environmental comparisons between this (sub)tropical site and the Palearctic Denisovan sites of Denisova Cave (Russia) and Baishiya Karst Cave (China). Denisovans from northern latitudes foraged in a mix of forested and open landscapes, including tundra and steppe. Using stable isotope values from the Cobra Cave assemblage, we demonstrate that, despite the presence of nearby canopy forests, the Denisovan individual from Cobra Cave primarily consumed plants and/or animals from open forests and savannah. Using faunal evidence and proxy indicators of climates, results herein highlight a local expansion of rainforest at ~ 130 ka, raising questions about how Denisovans responded to this local climate change. Comparing the diet and habitat of the archaic hominin from Cobra Cave with those of early Homo sapiens from Tam Pà Ling Cave (46-43 ka), Laos, it appears that only our species was able to exploit rainforest resources.}, } @article {pmid37747921, year = {2023}, author = {Roca-Umbert, A and Garcia-Calleja, J and Vogel-González, M and Fierro-Villegas, A and Ill-Raga, G and Herrera-Fernández, V and Bosnjak, A and Muntané, G and Gutiérrez, E and Campelo, F and Vicente, R and Bosch, E}, title = {Human genetic adaptation related to cellular zinc homeostasis.}, journal = {PLoS genetics}, volume = {19}, number = {9}, pages = {e1010950}, pmid = {37747921}, issn = {1553-7404}, mesh = {Animals ; Humans ; HEK293 Cells ; *Hominidae/genetics ; Homeostasis/genetics ; Zinc ; Human Genetics ; Selection, Genetic ; Haplotypes ; Genome, Human ; }, abstract = {SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.}, } @article {pmid37723347, year = {2023}, author = {Peyrégne, S and Slon, V and Kelso, J}, title = {More than a decade of genetic research on the Denisovans.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, pmid = {37723347}, issn = {1471-0064}, abstract = {Denisovans, a group of now extinct humans who lived in Eastern Eurasia in the Middle and Late Pleistocene, were first identified from DNA sequences just over a decade ago. Only ten fragmentary remains from two sites have been attributed to Denisovans based entirely on molecular information. Nevertheless, there has been great interest in using genetic data to understand Denisovans and their place in human history. From the reconstruction of a single high-quality genome, it has been possible to infer their population history, including events of admixture with other human groups. Additionally, the identification of Denisovan DNA in the genomes of present-day individuals has provided insights into the timing and routes of dispersal of ancient modern humans into Asia and Oceania, as well as the contributions of archaic DNA to the physiology of present-day people. In this Review, we synthesize more than a decade of research on Denisovans, reconcile controversies and summarize insights into their population history and phenotype. We also highlight how our growing knowledge about Denisovans has provided insights into our own evolutionary history.}, } @article {pmid37713634, year = {2023}, author = {Ge, X and Lu, Y and Chen, S and Gao, Y and Ma, L and Liu, L and Liu, J and Ma, X and Kang, L and Xu, S}, title = {Genetic Origins and Adaptive Evolution of the Deng People on the Tibetan Plateau.}, journal = {Molecular biology and evolution}, volume = {40}, number = {10}, pages = {}, pmid = {37713634}, issn = {1537-1719}, mesh = {Humans ; Adaptor Proteins, Signal Transducing ; Altitude ; *Asian People/genetics ; Haplotypes ; Tibet ; }, abstract = {The Tibetan Plateau is populated by diverse ethnic groups, but most of them are underrepresented in genomics studies compared with the Tibetans (TIB). Here, to gain further insight into the genetic diversity and evolutionary history of the people living in the Tibetan Plateau, we sequenced 54 whole genomes of the Deng people with high coverage (30-60×) and analyzed the data together with that of TIB and Sherpas, as well as 968 ancient Asian genomes and available archaic and modern human data. We identified 17.74 million novel single-nucleotide variants from the newly sequenced genomes, although the Deng people showed reduced genomic diversity and a relatively small effective population size. Compared with the other Tibetan highlander groups which are highly admixed, the Deng people are dominated by a sole ancestry that could be traced to some ancient northern East Asian populations. The divergence between Deng and Tibetan people (∼4,700-7,200 years) was more recent than that between highlanders and the Han Chinese (Deng-HAN, ∼9,000-14,000 years; TIB-HAN, 7,200-10,000 years). Adaptive genetic variants (AGVs) identified in the Deng are only partially shared with those previously reported in the TIB like HLA-DQB1, whereas others like KLHL12 were not reported in TIB. In contrast, the top candidate genes harboring AGVs as previously identified in TIB, like EPAS1 and EGLN1, do not show strong positive selection signals in Deng. Interestingly, Deng also showed a different archaic introgression scenario from that observed in the TIB. Our results suggest that convergent adaptation might be prevalent on the Tibetan Plateau.}, } @article {pmid37676865, year = {2023}, author = {Flegontov, P and Işıldak, U and Maier, R and Yüncü, E and Changmai, P and Reich, D}, title = {Modeling of African population history using f-statistics is biased when applying all previously proposed SNP ascertainment schemes.}, journal = {PLoS genetics}, volume = {19}, number = {9}, pages = {e1010931}, pmid = {37676865}, issn = {1553-7404}, support = {R01 HG012287/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Black People/genetics ; Chromosome Mapping ; Genotype ; Neanderthals/genetics ; *Phylogeny ; *Polymorphism, Single Nucleotide/genetics ; *African People/genetics ; *Demography/history ; Biological Variation, Population/genetics ; Models, Statistical ; Bias ; }, abstract = {f-statistics have emerged as a first line of analysis for making inferences about demographic history from genome-wide data. Not only are they guaranteed to allow robust tests of the fits of proposed models of population history to data when analyzing full genome sequencing data-that is, all single nucleotide polymorphisms (SNPs) in the individuals being analyzed-but they are also guaranteed to allow robust tests of models for SNPs ascertained as polymorphic in a population that is an outgroup in a phylogenetic sense to all groups being analyzed. True "outgroup ascertainment" is in practice impossible in humans because our species has arisen from a substructured ancestral population that does not descend from a homogeneous ancestral population going back many hundreds of thousands of years into the past. However, initial studies suggested that non-outgroup-ascertainment schemes might produce robust enough results using f-statistics, and that motivated widespread fitting of models to data using non-outgroup-ascertained SNP panels such as the "Affymetrix Human Origins array" which has been genotyped on thousands of modern individuals from hundreds of populations, or the "1240k" in-solution enrichment reagent which has been the source of about 70% of published genome-wide data for ancient humans. In this study, we show that while analyses of population history using such panels work well for studies of relationships among non-African populations and one African outgroup, when co-modeling more than one sub-Saharan African and/or archaic human groups (Neanderthals and Denisovans), fitting of f-statistics to such SNP sets is expected to frequently lead to false rejection of true demographic histories, and failure to reject incorrect models. Analyzing panels of SNPs polymorphic in archaic humans, which has been suggested as a solution for the ascertainment problem, has limited statistical power and retains important biases. However, by carrying out simulations of diverse demographic histories, we show that bias in inferences based on f-statistics can be minimized by ascertaining on variants common in a union of diverse African groups; such ascertainment retains high statistical power while allowing co-analysis of archaic and modern groups.}, } @article {pmid37616382, year = {2023}, author = {Denisova, K}, title = {English translation of the first study reporting cyclical periods of increased respiration and eye and body motility during sleep in infants in 1926, with commentary.}, journal = {Sleep}, volume = {}, number = {}, pages = {}, doi = {10.1093/sleep/zsad219}, pmid = {37616382}, issn = {1550-9109}, support = {R01 MH121605/MH/NIMH NIH HHS/United States ; }, abstract = {This is the first English translation of the work Periodic phenomena in the sleep in children, published in 1926 in the Journal Novoe v refleksologii i fiziologii nervnoi sistemy (Vol. 2, pp. 338-345) by Maria Denisova and Nicholai Figurin; it is the first study to report data on what is currently termed Rapid Eye Movement (REM) sleep. The authors acquired continuous quantitative respiration data, as well as eye and body movements during sleep in children for up to 6 hours, and discovered several novel features of sleep cycles in healthy infants from birth to about 1 year of age.First, the study reports cyclical periods of increased respiration and eye and body movements, with rapid ocular movements visible under relaxed eyelids (separation:0.5-1 mm). These observations suggest atonia of REM sleep.Second, the length of the complete cycle (alternating active and quiet sleep phases or states) is about 50 minutes, an estimate that is consistent with later work.Third, the study identifies infant-specific ordering of sleep states, with the active phase beginning after sleep onset, followed by the quiescence phase. Importantly, these published data on sleep cycles precede all published studies related to the state now termed REM sleep by about 30 years (i.e.publishing in Science and in the Journal of Applied Physiology in the 1950s by Eugene Aserinski and Nathaniel Kleitman). In the historical commentary accompanying this translation, the findings of those later works are carefully compared to the original data on respiration and ocular and body motility cycles during sleep in infants, first reported and published by Denisova and Figurin(1926).}, } @article {pmid37609337, year = {2023}, author = {Yee, SW and Ferrández-Peral, L and Alentorn, P and Fontsere, C and Ceylan, M and Koleske, ML and Handin, N and Artegoitia, VM and Lara, G and Chien, HC and Zhou, X and Dainat, J and Zalevsky, A and Sali, A and Brand, CM and Capra, JA and Artursson, P and Newman, JW and Marques-Bonet, T and Giacomini, KM}, title = {Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37609337}, abstract = {SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.}, } @article {pmid37589132, year = {2023}, author = {Essel, E}, title = {Releasing secrets bound to ancient remains with modern DNA extraction techniques: an interview with Elena Essel.}, journal = {BioTechniques}, volume = {75}, number = {2}, pages = {42-46}, doi = {10.2144/btn-2023-0067}, pmid = {37589132}, issn = {1940-9818}, mesh = {Humans ; Female ; *DNA, Ancient ; *Anthropology ; Body Remains ; Sequence Analysis, DNA ; Universities ; }, abstract = {Elena Essel (Msc) spoke to Ebony Torrington, Managing Editor of BioTechniques. Essel is a molecular biologist in Matthias Meyer's Advanced DNA Sequencing Techniques group at the Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany). Essel studied biology at University of Erlangen-Nuremberg (Erlangen, Germany) for her bachelor's and in Martin-Luther-University Halle-Wittenberg (Halle an der Saale, Germany) for her master's. Essel worked in Meyer's group on DNA extraction of very degraded material for her master's thesis. Meyer is an expert in developing new cutting-edge methods for researching ancient DNA, with a focus on skeletal remains, and more recently on sediment remains. Essel now focusses on DNA sampling and extraction aspects of the pipeline at Meyer's lab for the ancient DNA workflow.}, } @article {pmid37571106, year = {2023}, author = {Cherkashina, NI and Pavlenko, ZV and Pushkarskaya, DV and Denisova, LV and Domarev, SN and Ryzhikh, DA}, title = {Synthesis and Properties of Polystyrene Composite Material with Hazelnut Shells.}, journal = {Polymers}, volume = {15}, number = {15}, pages = {}, pmid = {37571106}, issn = {2073-4360}, support = {FZWN-2021-0015//State Assignment of the Ministry of Education and Science of the Russian Federation/ ; }, abstract = {In this study we evaluated the potential use of hazelnut shell powder in the production of a composite material. Polystyrene was used as a polymer matrix. This work presents the results of modifying hazelnut powder particles to create a polystyrene shell on their surfaces. Modification of the filler increased its contact angle wetted with water from θ=60.16±1.03° to θ=87.02±1.10°. Composite materials containing from 10 to 50 wt.% of modified hazelnut shell powder were prepared and studied. As a result of the experiments, it was found that the composites have optimal physical, mechanical, and operational properties at the following ratio: polystyrene 60-80 wt.%, modified hazelnut shell powder 20-40 wt.%. If the introduction of polystyrene was more than 90 wt.%, the flexural strength and Vickers hardness were quite low at the load of 200 g, and accordingly, the durability of such materials was not satisfactory. These samples are characterized by small percentages of hazelnut shells; therefore, the resulting material will be of pale, unsaturated color. The upper limit of the working temperature range for the composite lies between 265.0-376.0 °C, depending on the percentage of the hazelnut shell powder filling.}, } @article {pmid37561879, year = {2023}, author = {Ruan, J and Timmermann, A and Raia, P and Yun, KS and Zeller, E and Mondanaro, A and Di Febbraro, M and Lemmon, D and Castiglione, S and Melchionna, M}, title = {Climate shifts orchestrated hominin interbreeding events across Eurasia.}, journal = {Science (New York, N.Y.)}, volume = {381}, number = {6658}, pages = {699-704}, doi = {10.1126/science.add4459}, pmid = {37561879}, issn = {1095-9203}, mesh = {Animals ; Humans ; Fossils ; Gene Flow ; *Neanderthals/genetics ; *Climate Change ; }, abstract = {When, where, and how often hominin interbreeding happened is largely unknown. We study the potential for Neanderthal-Denisovan admixture using species distribution models that integrate extensive fossil, archaeological, and genetic data with transient coupled general circulation model simulations of global climate and biomes. Our Pleistocene hindcast of past hominins' habitat suitability reveals pronounced climate-driven zonal shifts in the main overlap region of Denisovans and Neanderthals in central Eurasia. These shifts, which influenced the timing and intensity of potential interbreeding events, can be attributed to the response of climate and vegetation to past variations in atmospheric carbon dioxide and Northern Hemisphere ice-sheet volume. Therefore, glacial-interglacial climate swings likely played an important role in favoring gene flow between archaic humans.}, } @article {pmid37516110, year = {2023}, author = {Maasch, JRMA and Torres, MDT and Melo, MCR and de la Fuente-Nunez, C}, title = {Molecular de-extinction of ancient antimicrobial peptides enabled by machine learning.}, journal = {Cell host & microbe}, volume = {31}, number = {8}, pages = {1260-1274.e6}, doi = {10.1016/j.chom.2023.07.001}, pmid = {37516110}, issn = {1934-6069}, mesh = {Animals ; Humans ; Mice ; *Antimicrobial Peptides ; *Anti-Infective Agents ; Peptides/pharmacology ; Anti-Bacterial Agents/pharmacology ; Machine Learning ; Peptide Hydrolases ; Microbial Sensitivity Tests ; }, abstract = {Molecular de-extinction could offer avenues for drug discovery by reintroducing bioactive molecules that are no longer encoded by extant organisms. To prospect for antimicrobial peptides encrypted within extinct and extant human proteins, we introduce the panCleave random forest model for proteome-wide cleavage site prediction. Our model outperformed multiple protease-specific cleavage site classifiers for three modern human caspases, despite its pan-protease design. Antimicrobial activity was observed in vitro for modern and archaic protein fragments identified with panCleave. Lead peptides showed resistance to proteolysis and exhibited variable membrane permeabilization. Additionally, representative modern and archaic protein fragments showed anti-infective efficacy against A. baumannii in both a skin abscess infection model and a preclinical murine thigh infection model. These results suggest that machine-learning-based encrypted peptide prospection can identify stable, nontoxic peptide antibiotics. Moreover, we establish molecular de-extinction through paleoproteome mining as a framework for antibacterial drug discovery.}, } @article {pmid37513038, year = {2023}, author = {Tkachenko, OV and Evseeva, NV and Kargapolova, KY and Denisova, AY and Pozdnyakova, NN and Kulikov, AA and Burygin, GL}, title = {Rhizobacteria Increase the Adaptation Potential of Potato Microclones under Aeroponic Conditions.}, journal = {Microorganisms}, volume = {11}, number = {7}, pages = {}, pmid = {37513038}, issn = {2076-2607}, support = {22-26-00087//Russian Science Foundation/ ; }, abstract = {Adaptation ex vitro is strongly stressful for microplants. Plant-growth-promoting rhizobacteria (PGPR) help to increase the adaptation potential of microplants transplanted from test tubes into the natural environment. We investigated the mechanisms of antioxidant protection of PGPR-inoculated potato microclones adapting to ex vitro growth in an aeroponic system. Potato (Solanum tuberosum L. cv. Nevsky) microplants were inoculated in vitro with the bacteria Azospirillum baldaniorum Sp245 and Ochrobactrum cytisi IPA7.2. On days 1 and 7 of plant growth ex vitro, catalase and peroxidase activities in the leaves of inoculated plants were 1.5-fold higher than they were in non-inoculated plants. The activity of ascorbate peroxidase was reduced in both in vitro and ex vitro treatments, and this reduction was accompanied by a decrease in the leaf content of hydrogen peroxide and malondialdehyde. As a result, inoculation contributed to the regulation of the plant pro/antioxidant system, lowering the oxidative stress and leading to better plant survival ex vitro. This was evidenced by the higher values of measured morphological and physiological variables of the inoculated plants, as compared with the values in the control treatment. Thus, we have shown some PGPR-mediated mechanisms of potato plant protection from adverse environmental factors under aeroponic conditions.}, } @article {pmid37510352, year = {2023}, author = {Shpetko, YY and Filippenkov, IB and Denisova, AE and Stavchansky, VV and Gubsky, LV and Limborska, SA and Dergunova, LV}, title = {Isoflurane Anesthesia's Impact on Gene Expression Patterns of Rat Brains in an Ischemic Stroke Model.}, journal = {Genes}, volume = {14}, number = {7}, pages = {}, pmid = {37510352}, issn = {2073-4425}, mesh = {Animals ; Male ; Rats ; Anesthesia ; *Brain/metabolism ; Disease Models, Animal ; *Gene Expression ; Gene Expression Regulation ; *Ischemia/genetics ; Isoflurane ; Magnetic Resonance Imaging ; Rats, Wistar ; RNA, Messenger/genetics ; *Stroke/genetics ; }, abstract = {BACKGROUND: Ischemic stroke (IS) is one of the most severe brain diseases. Animal models with anesthesia are actively used to study stroke genomics and pathogenesis. However, the anesthesia-related gene expression patterns of ischemic rat brains remain poorly understood. In this study, we sought to elucidate the impact of isoflurane (ISO) anesthesia on the extent of ischemic brain damage and gene expression changes associated with stroke.

METHODS: We used the transient middle cerebral artery occlusion (tMCAO) model under long-term and short-term ISO anesthesia, magnetic resonance imaging (MRI), RNA sequencing, and bioinformatics.

RESULTS: We revealed that the volume of cerebral damage at 24 h after tMCAO was inversely proportional to the duration of ISO anesthesia. Then, we revealed hundreds of overlapping ischemia-related differentially expressed genes (DEGs) with a cutoff of >1.5; Padj < 0.05, and 694 and 1557 DEGs only under long-term and short-term anesthesia, respectively, using sham-operated controls. Concomitantly, unique DEGs identified under short-term anesthesia were mainly associated with neurosignaling systems, whereas unique DEGs identified under long-term anesthesia were predominantly related to the inflammatory response.

CONCLUSIONS: We were able to determine the effects of the duration of anesthesia using isoflurane on the transcriptomes in the brains of rats at 24 h after tMCAO. Thus, specific genome responses may be useful in developing potential approaches to reduce damaged areas after cerebral ischemia and neuroprotection.}, } @article {pmid37510287, year = {2023}, author = {Filippenkov, IB and Remizova, JA and Stavchansky, VV and Denisova, AE and Gubsky, LV and Myasoedov, NF and Limborska, SA and Dergunova, LV}, title = {Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period.}, journal = {Genes}, volume = {14}, number = {7}, pages = {}, pmid = {37510287}, issn = {2073-4425}, mesh = {Rats ; Animals ; Rats, Wistar ; *Brain Ischemia/drug therapy/genetics/metabolism ; Prospective Studies ; *Stroke/drug therapy/genetics/metabolism ; Infarction, Middle Cerebral Artery/drug therapy/genetics/metabolism ; Adrenocorticotropic Hormone/pharmacology ; Brain/metabolism ; }, abstract = {Ischemic stroke is an acute local decrease in cerebral blood flow due to a thrombus or embolus. Of particular importance is the study of the genetic systems that determine the mechanisms underlying the formation and maintenance of a therapeutic window (a time interval of up to 6 h after a stroke) when effective treatment can be provided. Here, we used a transient middle cerebral artery occlusion (tMCAO) model in rats to study two synthetic derivatives of adrenocorticotropic hormone (ACTH). The first was ACTH(4-7)PGP, which is known as Semax. It is actively used as a neuroprotective drug. The second was the ACTH(6-9)PGP peptide, which is elucidated as a prospective agent only. Using RNA-Seq analysis, we revealed hundreds of ischemia-related differentially expressed genes (DEGs), as well as 131 and 322 DEGs related to the first and second peptide at 4.5 h after tMCAO, respectively, in dorsolateral areas of the frontal cortex of rats. Furthermore, we showed that both Semax and ACTH(6-9)PGP can partially prevent changes in the immune- and neurosignaling-related gene expression profiles disturbed by the action of ischemia at 4.5 h after tMCAO. However, their different actions with regard to predominantly immune-related genes were also revealed. This study gives insight into how the transcriptome depends on the variation in the structure of the related peptides, and it is valuable from the standpoint of the development of measures for early post-stroke therapy.}, } @article {pmid37508659, year = {2023}, author = {Deņisova, A and Pilmane, M and Kažoka, D}, title = {Antimicrobial Peptides and Interleukins in Cleft Soft Palate.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {37508659}, issn = {2227-9067}, abstract = {Cleft palate is one of the most common and well-studied congenital anomalies; however, the role of protective tissue factors in its pathophysiology is still debated. The aim of our study was to evaluate interleukin and antimicrobial peptide appearance and distribution in cleft palate. Eight soft palate samples were obtained during veloplasty procedures. Immunohistochemical staining was applied to detect HBD-2-, HBD-3-, HBD-4-, LL-37-, IL-10-, and CD-163-positive cells via light microscopy. For statistical evaluation, the Mann-Whitney U test and Spearman's rank correlation coefficient were used. A significant difference between study groups was observed for HBD-2 and IL-10 in epithelial and connective tissue as well as HBD-4 in connective tissue. The number of HBD-3-positive cells was moderate in the patients, and few were observed in the controls. The number of LL-37-positive cells varied from a moderate amount to a numerous amount in both study groups, whilst CD-163 marked a moderate number of positive cells in patients, and a few-to-moderate amount was observed in the controls. Numerous correlations between studied factors were revealed in cleft tissues. The increase in antimicrobial peptides HBD-2 and HBD-4 and anti-inflammatory cytokine IL-10 suggested a wide compensatory elevation of the local immune system against cleft-raised tissue changes. The correlations between the studied factors (HBD-2, HBD-3, HBD-4, LL-37, and IL-10) proved the synergistic involvement of common local defense factors in postnatal cleft palate morphopathogenesis.}, } @article {pmid37500909, year = {2023}, author = {Pawar, H and Rymbekova, A and Cuadros-Espinoza, S and Huang, X and de Manuel, M and van der Valk, T and Lobon, I and Alvarez-Estape, M and Haber, M and Dolgova, O and Han, S and Esteller-Cucala, P and Juan, D and Ayub, Q and Bautista, R and Kelley, JL and Cornejo, OE and Lao, O and Andrés, AM and Guschanski, K and Ssebide, B and Cranfield, M and Tyler-Smith, C and Xue, Y and Prado-Martinez, J and Marques-Bonet, T and Kuhlwilm, M}, title = {Ghost admixture in eastern gorillas.}, journal = {Nature ecology & evolution}, volume = {7}, number = {9}, pages = {1503-1514}, pmid = {37500909}, issn = {2397-334X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Humans ; Gorilla gorilla/genetics ; Pan paniscus/genetics ; Bayes Theorem ; *Hominidae/genetics ; Pan troglodytes ; *Neanderthals/genetics ; }, abstract = {Archaic admixture has had a substantial impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. In great apes, archaic admixture has been identified in chimpanzees and bonobos but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole-genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using approximate Bayesian computation with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, probably more than 40 thousand years ago and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.}, } @article {pmid37496485, year = {2023}, author = {Pigolkin, YI and Shigeev, SV and Denisova, AV and Natarova, KV and Krupin, KN}, title = {[Forensic medical assessment of lidocaine and bupivacaine systemic toxicity].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {66}, number = {4}, pages = {62-66}, doi = {10.17116/sudmed20236604162}, pmid = {37496485}, issn = {0039-4521}, mesh = {Humans ; *Bupivacaine/toxicity ; *Lidocaine ; Anesthetics, Local/toxicity ; }, abstract = {Was to assess the lidocaine and bupivacaine systemic toxicity in forensic medical practice. The number of patients' clinical observations equal three with local anesthetic systemic toxicity (LAST) from the practice of forensic medical experts were studied, and a search of scientific publications for the last 5 years in PubMed database was conducted. The amount of publications, describing cases with LAST, equal four were selected. Differential diagnostic features between LAST and anaphylaxis were considered. The literature data about relationship between lidocaine's concentration in the blood serum and clinical features are shown. The forensic medical assessment of LAST is proposed.}, } @article {pmid37495858, year = {2023}, author = {Kaulen, LD and Denisova, E and Hinz, F and Hai, L and Friedel, D and Henegariu, O and Hoffmann, DC and Ito, J and Kourtesakis, A and Lehnert, P and Doubrovinskaia, S and Karschnia, P and von Baumgarten, L and Kessler, T and Baehring, JM and Brors, B and Sahm, F and Wick, W}, title = {Integrated genetic analyses of immunodeficiency-associated Epstein-Barr virus- (EBV) positive primary CNS lymphomas.}, journal = {Acta neuropathologica}, volume = {146}, number = {3}, pages = {499-514}, pmid = {37495858}, issn = {1432-0533}, mesh = {Humans ; Herpesvirus 4, Human/genetics ; *Epstein-Barr Virus Infections/genetics/metabolism ; Mutation ; Prognosis ; *Lymphoma/genetics ; Tumor Microenvironment ; }, abstract = {Immunodeficiency-associated primary CNS lymphoma (PCNSL) represents a distinct clinicopathological entity, which is typically Epstein-Barr virus-positive (EBV[+]) and carries an inferior prognosis. Genetic alterations that characterize EBV-related CNS lymphomagenesis remain unclear precluding molecular classification and targeted therapies. In this study, a comprehensive genetic analysis of 22 EBV[+] PCNSL, therefore, integrated clinical and pathological information with exome and RNA sequencing (RNASeq) data. EBV[+] PCNSL with germline controls carried a median of 55 protein-coding single nucleotide variants (SNVs; range 24-217) and 2 insertions/deletions (range 0-22). Genetic landscape was largely shaped by aberrant somatic hypermutation with a median of 41.01% (range 31.79-53.49%) of SNVs mapping to its target motifs. Tumors lacked established SNVs (MYD88, CD79B, PIM1) and copy number variants (CDKN2A, HLA loss) driving EBV[-] PCNSL. Instead, EBV[+] PCNSL were characterized by SOCS1 mutations (26%), predicted to disinhibit JAK/STAT signaling, and mutually exclusive gain-of-function NOTCH pathway SNVs (26%). Copy number gains were enriched on 11q23.3, a locus directly targeted for chromosomal aberrations by EBV, that includes SIK3 known to protect from cytotoxic T-cell responses. Losses covered 5q31.2 (STING), critical for sensing viral DNA, and 17q11 (NF1). Unsupervised clustering of RNASeq data revealed two distinct transcriptional groups, that shared strong expression of CD70 and IL1R2, previously linked to tolerogenic tumor microenvironments. Correspondingly, deconvolution of bulk RNASeq data revealed elevated M2-macrophage, T-regulatory cell, mast cell and monocyte fractions in EBV[+] PCNSL. In addition to novel insights into the pathobiology of EBV[+] PCNSL, the data provide the rationale for the exploration of targeted therapies including JAK-, NOTCH- and CD70-directed approaches.}, } @article {pmid37458534, year = {2023}, author = {Denisova, OV and Merisaari, J and Huhtaniemi, R and Qiao, X and Yetukuri, L and Jumppanen, M and Kaur, A and Pääkkönen, M and von Schantz-Fant, С and Ohlmeyer, M and Wennerberg, K and Kauko, O and Koch, R and Aittokallio, T and Taipale, M and Westermarck, J}, title = {PP2A-based triple-strike therapy overcomes mitochondrial apoptosis resistance in brain cancer cells.}, journal = {Molecular oncology}, volume = {17}, number = {9}, pages = {1803-1820}, pmid = {37458534}, issn = {1878-0261}, mesh = {Humans ; Proto-Oncogene Proteins c-akt/metabolism ; Protein Phosphatase 2/metabolism ; *Cytostatic Agents/therapeutic use ; *Brain Neoplasms/drug therapy ; Apoptosis ; Brain ; Cell Line, Tumor ; }, abstract = {Mitochondrial glycolysis and hyperactivity of the phosphatidylinositol 3-kinase-protein kinase B (AKT) pathway are hallmarks of malignant brain tumors. However, kinase inhibitors targeting AKT (AKTi) or the glycolysis master regulator pyruvate dehydrogenase kinase (PDKi) have failed to provide clinical benefits for brain tumor patients. Here, we demonstrate that heterogeneous glioblastoma (GB) and medulloblastoma (MB) cell lines display only cytostatic responses to combined AKT and PDK targeting. Biochemically, the combined AKT and PDK inhibition resulted in the shutdown of both target pathways and priming to mitochondrial apoptosis but failed to induce apoptosis. In contrast, all tested brain tumor cell models were sensitive to a triplet therapy, in which AKT and PDK inhibition was combined with the pharmacological reactivation of protein phosphatase 2A (PP2A) by NZ-8-061 (also known as DT-061), DBK-1154, and DBK-1160. We also provide proof-of-principle evidence for in vivo efficacy in the intracranial GB and MB models by the brain-penetrant triplet therapy (AKTi + PDKi + PP2A reactivator). Mechanistically, PP2A reactivation converted the cytostatic AKTi + PDKi response to cytotoxic apoptosis, through PP2A-elicited shutdown of compensatory mitochondrial oxidative phosphorylation and by increased proton leakage. These results encourage the development of triple-strike strategies targeting mitochondrial metabolism to overcome therapy tolerance in brain tumors.}, } @article {pmid37452091, year = {2023}, author = {Yang, C and Zhou, Y and Song, Y and Wu, D and Zeng, Y and Nie, L and Liu, P and Zhang, S and Chen, G and Xu, J and Zhou, H and Zhou, L and Qian, X and Liu, C and Tan, S and Zhou, C and Dai, W and Xu, M and Qi, Y and Wang, X and Guo, L and Fan, G and Wang, A and Deng, Y and Zhang, Y and Jin, J and He, Y and Guo, C and Guo, G and Zhou, Q and Xu, X and Yang, H and Wang, J and Xu, S and Mao, Y and Jin, X and Ruan, J and Zhang, G}, title = {The complete and fully-phased diploid genome of a male Han Chinese.}, journal = {Cell research}, volume = {33}, number = {10}, pages = {745-761}, pmid = {37452091}, issn = {1748-7838}, mesh = {Humans ; Male ; Asian People/genetics ; *Diploidy ; *East Asian People/ethnology/genetics ; *Genome, Human/genetics ; Genomics ; *Telomere/genetics ; }, abstract = {Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population.}, } @article {pmid37425881, year = {2023}, author = {Larivière, D and Abueg, L and Brajuka, N and Gallardo-Alba, C and Grüning, B and Ko, BJ and Ostrovsky, A and Palmada-Flores, M and Pickett, BD and Rabbani, K and Balacco, JR and Chaisson, M and Cheng, H and Collins, J and Denisova, A and Fedrigo, O and Gallo, GR and Giani, AM and Gooder, GM and Jain, N and Johnson, C and Kim, H and Lee, C and Marques-Bonet, T and O'Toole, B and Rhie, A and Secomandi, S and Sozzoni, M and Tilley, T and Uliano-Silva, M and van den Beek, M and Waterhouse, RM and Phillippy, AM and Jarvis, ED and Schatz, MC and Nekrutenko, A and Formenti, G}, title = {Scalable, accessible, and reproducible reference genome assembly and evaluation in Galaxy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37425881}, support = {U01 CA253481/CA/NCI NIH HHS/United States ; U24 CA231877/CA/NCI NIH HHS/United States ; U24 HG010263/HG/NHGRI NIH HHS/United States ; U41 HG006620/HG/NHGRI NIH HHS/United States ; }, abstract = {Improvements in genome sequencing and assembly are enabling high-quality reference genomes for all species. However, the assembly process is still laborious, computationally and technically demanding, lacks standards for reproducibility, and is not readily scalable. Here we present the latest Vertebrate Genomes Project assembly pipeline and demonstrate that it delivers high-quality reference genomes at scale across a set of vertebrate species arising over the last ~500 million years. The pipeline is versatile and combines PacBio HiFi long-reads and Hi-C-based haplotype phasing in a new graph-based paradigm. Standardized quality control is performed automatically to troubleshoot assembly issues and assess biological complexities. We make the pipeline freely accessible through Galaxy, accommodating researchers even without local computational resources and enhanced reproducibility by democratizing the training and assembly process. We demonstrate the flexibility and reliability of the pipeline by assembling reference genomes for 51 vertebrate species from major taxonomic groups (fish, amphibians, reptiles, birds, and mammals).}, } @article {pmid37390055, year = {2023}, author = {Shevchenko, JA and Perik-Zavodskii, RY and Nazarov, KV and Denisova, VV and Perik-Zavodskaya, OY and Philippova, YG and Alsalloum, A and Sennikov, SV}, title = {Immunoregulatory properties of erythroid nucleated cells induced from CD34+ progenitors from bone marrow.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0287793}, pmid = {37390055}, issn = {1932-6203}, mesh = {*Bone Marrow ; Antigens, CD34 ; *Erythroid Cells ; Bone Marrow Cells ; Cell Adhesion Molecules ; }, abstract = {CD 71+ erythroid nucleated cells have pronounced immunoregulatory properties in normal and pathological conditions. Many populations of cells with immunoregulatory properties are considered candidates for cellular immunotherapy for various pathologies. This study characterized the immunoregulatory properties of CD71+ erythroid cells derived from CD34-positive bone marrow cells under the influence of growth factors that stimulate differentiation into erythroid cells. CD34-negative bone marrow cells were used to isolate CD71+ erythroid nuclear cells. The resulting cells were used to assess the phenotype, determine the mRNA spectrum of the genes responsible for the main pathways and processes of the immune response, and obtain culture supernatants for the analysis of immunoregulatory factors. It was found that CD71+ erythroid cells derived from CD34+ cells carry the main markers of erythroid cells, but differ markedly from natural bone marrow CD71+ erythroid cells. The main differences are in the presence of the CD45+ subpopulation, distribution of terminal differentiation stages, transcriptional profile, secretion of certain cytokines, and immunosuppressive activity. The properties of induced CD71+ erythroid cells are closer to the cells of extramedullary erythropoiesis foci than to natural bone marrow CD71+ erythroid cells. Thus, when cultivating CD71+ erythroid cells for clinical experimental studies, it is necessary to take into account their pronounced immunoregulatory activity.}, } @article {pmid37316650, year = {2023}, author = {Derenko, M and Denisova, G and Litvinov, A and Dambueva, I and Malyarchuk, B}, title = {Mitogenomics of the Koryaks and Evens of the northern coast of the Sea of Okhotsk.}, journal = {Journal of human genetics}, volume = {68}, number = {10}, pages = {705-712}, pmid = {37316650}, issn = {1435-232X}, support = {22-24-00264//Russian Science Foundation (RSF)/ ; }, mesh = {Humans ; *DNA, Mitochondrial/genetics ; Genetic Variation/genetics ; *Genomics ; *North Asian People/ethnology/genetics ; Phylogeography ; Indigenous Peoples/genetics ; }, abstract = {Due to the geographical proximity of the northern coast of the Sea of Okhotsk and Kamchatka Peninsula to the Beringia, the indigenous populations of these territories are of great interest for elucidating the human settlement history of northern Asia and America. Meanwhile, there is a clear shortage of genetic studies of the indigenous populations of the northern coast of the Sea of Okhotsk. Here, in order to examine their fine-scale matrilineal genetic structure, ancestry and relationships with neighboring populations, we analyzed 203 complete mitogenomes (174 of which are new) from population samples of the Koryaks and Evens of the northern coast of the Sea of Okhotsk and the Chukchi of the extreme northeast Asia. The patterns observed underscore the reduced level of genetic diversity found in the Koryak, Even, and Chukchi populations, which, along with the high degree of interpopulation differentiation, may be the result of genetic drift. Our phylogeographic analysis reveals common Paleo-Asiatic ancestry for 51.1% of the Koryaks and 17.8% of the Evens. About third of the mitogenomes found in the Koryaks and Evens might be considered as ethno-specific, as these are virtually absent elsewhere in North, Central and East Asia. Coalescence ages of most of these lineages coincide well with the emergence and development of the Tokarev and Old Koryak archaeological cultures associated with the formation of the Koryaks, as well as with the period of separation and split of the North Tungusic groups migrated northwards from the Lake Baikal or the Amur River area.}, } @article {pmid37313765, year = {2023}, author = {Shunatova, N and Denisova, S and Shchenkov, S and Filippov, A}, title = {Colonial system of integration and communication pores in a polymorphic bryozoan Dendrobeania fruticosa (Bryozoa: Cheilostomata).}, journal = {Journal of morphology}, volume = {284}, number = {7}, pages = {e21601}, doi = {10.1002/jmor.21601}, pmid = {37313765}, issn = {1097-4687}, mesh = {Animals ; *Bryozoa ; Cecum ; Epidermal Cells ; Extracellular Matrix ; *Gastropoda ; }, abstract = {Bryozoan colonies are composed of zooids, which can differ in structure and function. Autozooids supply heteromorphic zooids with nutrients, which are usually unable to feed. To date, the ultrastructure of the tissues providing nutrient transfer is almost unexplored. Here, we present a detailed description of the colonial system of integration (CSI) and the different types of pore plates in Dendrobeania fruticosa. All cells of the CSI are joined by tight junctions that isolate its lumen. The lumen of the CSI is not a single structure, but a dense network of small interstices filled with a heterogeneous matrix. In autozooids, the CSI is composed of two types of cells: elongated and stellate. Elongated cells form the central part of the CSI, including two main longitudinal cords and several main branches to the gut and pore plates. Stellate cells compose the peripheral part of the CSI, which is a delicate mesh starting from the central part and reaching various structures of autozooids. Autozooids have two tiny muscular funiculi, which start from the caecum apex and run to the basal wall. Each funiculus includes a central cord of extracellular matrix and two longitudinal muscle cells; together they are enveloped with a layer of cells. The rosette complexes of all types of pore plates in D. fruticosa display a similar cellular composition: a cincture cell and a few special cells; limiting cells are absent. Special cells have bidirectional polarity in interautozooidal and avicularian pore plates. This is probably due to the need for bidirectional transport of nutrients during degeneration-regeneration cycles. Cincture cells and epidermal cells of pore plates contain microtubules and inclusions resembling dense-cored vesicles, which are typical of neurons. Probably, cincture cells are involved in the signal transduction from one zooid to another and can be a part of the colony-wide nervous system.}, } @article {pmid37308668, year = {2023}, author = {Rigaud, S and Rybin, EP and Khatsenovich, AM and Queffelec, A and Paine, CH and Gunchinsuren, B and Talamo, S and Marchenko, DV and Bolorbat, T and Odsuren, D and Gillam, JC and Izuho, M and Fedorchenko, AY and Odgerel, D and Shelepaev, R and Hublin, JJ and Zwyns, N}, title = {Symbolic innovation at the onset of the Upper Paleolithic in Eurasia shown by the personal ornaments from Tolbor-21 (Mongolia).}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {9545}, pmid = {37308668}, issn = {2045-2322}, mesh = {Humans ; Infant, Newborn ; Mongolia ; Africa ; *Archaeology ; Europe ; }, abstract = {Figurative depictions in art first occur ca. 50,000 years ago in Europe, Africa, and Southeast Asia. Considered by most as an advanced form of symbolic behavior, they are restricted to our species. Here, we report a piece of ornament interpreted as a phallus-like representation. It was found in a 42,000 ca.-year-old Upper Paleolithic archaeological layer at the open-air archaeological site of Tolbor-21, in Mongolia. Mineralogical, microscopic, and rugosimetric analyses points toward the allochthonous origin of the pendant and a complex functional history. Three-dimensional phallic pendants are unknown in the Paleolithic record, and this discovery predates the earliest known sexed anthropomorphic representation. It attests that hunter-gatherer communities used sex anatomical attributes as symbols at a very early stage of their dispersal in the region. The pendant was produced during a period that overlaps with age estimates for early introgression events between Homo sapiens and Denisovans, and in a region where such encounters are plausible.}, } @article {pmid37304756, year = {2023}, author = {Kou, SH and Li, J and Tam, B and Lei, H and Zhao, B and Xiao, F and Wang, SM}, title = {TP53 germline pathogenic variants in modern humans were likely originated during recent human history.}, journal = {NAR cancer}, volume = {5}, number = {3}, pages = {zcad025}, pmid = {37304756}, issn = {2632-8674}, abstract = {TP53 is crucial for maintaining genome stability and preventing oncogenesis. Germline pathogenic variation in TP53 damages its function, causing genome instability and increased cancer risk. Despite extensive study in TP53, the evolutionary origin of the human TP53 germline pathogenic variants remains largely unclear. In this study, we applied phylogenetic and archaeological approaches to identify the evolutionary origin of TP53 germline pathogenic variants in modern humans. In the phylogenic analysis, we searched 406 human TP53 germline pathogenic variants in 99 vertebrates distributed in eight clades of Primate, Euarchontoglires, Laurasiatheria, Afrotheria, Mammal, Aves, Sarcopterygii and Fish, but we observed no direct evidence for the cross-species conservation as the origin; in the archaeological analysis, we searched the variants in 5031 ancient human genomes dated between 45045 and 100 years before present, and identified 45 pathogenic variants in 62 ancient humans dated mostly within the last 8000 years; we also identified 6 pathogenic variants in 3 Neanderthals dated 44000 to 38515 years before present and 1 Denisovan dated 158 550 years before present. Our study reveals that TP53 germline pathogenic variants in modern humans were likely originated in recent human history and partially inherited from the extinct Neanderthals and Denisovans.}, } @article {pmid37269363, year = {2023}, author = {Garcia-Heras, J}, title = {The 2022 Nobel Prize in Physiology or Medicine.}, journal = {Journal of the Association of Genetic Technologists}, volume = {49}, number = {2}, pages = {56-67}, pmid = {37269363}, issn = {1523-7834}, abstract = {The Nobel Assembly at the Karolinska Institute awarded the 2022 Nobel Prize in Physiology or Medicine to Svante Pääbo (Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany). This award acknowledged his discoveries about the genomes of extinct hominins (Neandertal man and the Denisovans), the molecular genetic insights of human origin and evolutionary history, and the understanding of phylogenetic relationships between archaic hominins and modern humans. The scientific advances included detection of Neandertal and Denisovan DNA carried by modern humans due to past admixture events, which in turn stimulated active research about the functional and phenotypic significance of such archaic ancestry on non-disease and disease phenotypic features in modern populations. In addition, comparative genomic studies started to delineate the genes and genetic regulation mechanisms that distinguish modern-day humans from the archaic hominins and our immediate ancestors, the anatomically modern humans. These breakthroughs allowed a more thorough understanding of ancestral and modern human population genetics, and propelled the take-off of human paleogenomics as a new scientific discipline in its own right.}, } @article {pmid37192163, year = {2023}, author = {Rong, S and Neil, CR and Welch, A and Duan, C and Maguire, S and Meremikwu, IC and Meyerson, M and Evans, BJ and Fairbrother, WG}, title = {Large-scale functional screen identifies genetic variants with splicing effects in modern and archaic humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {21}, pages = {e2218308120}, pmid = {37192163}, issn = {1091-6490}, support = {R01 GM127472/GM/NIGMS NIH HHS/United States ; }, mesh = {Male ; Animals ; Humans ; *Neanderthals/genetics ; Semen ; *Hominidae/genetics ; Alleles ; Gene Expression Regulation ; Genome, Human ; }, abstract = {Humans coexisted and interbred with other hominins which later became extinct. These archaic hominins are known to us only through fossil records and for two cases, genome sequences. Here, we engineer Neanderthal and Denisovan sequences into thousands of artificial genes to reconstruct the pre-mRNA processing patterns of these extinct populations. Of the 5,169 alleles tested in this massively parallel splicing reporter assay (MaPSy), we report 962 exonic splicing mutations that correspond to differences in exon recognition between extant and extinct hominins. Using MaPSy splicing variants, predicted splicing variants, and splicing quantitative trait loci, we show that splice-disrupting variants experienced greater purifying selection in anatomically modern humans than that in Neanderthals. Adaptively introgressed variants were enriched for moderate-effect splicing variants, consistent with positive selection for alternative spliced alleles following introgression. As particularly compelling examples, we characterized a unique tissue-specific alternative splicing variant at the adaptively introgressed innate immunity gene TLR1, as well as a unique Neanderthal introgressed alternative splicing variant in the gene HSPG2 that encodes perlecan. We further identified potentially pathogenic splicing variants found only in Neanderthals and Denisovans in genes related to sperm maturation and immunity. Finally, we found splicing variants that may contribute to variation among modern humans in total bilirubin, balding, hemoglobin levels, and lung capacity. Our findings provide unique insights into natural selection acting on splicing in human evolution and demonstrate how functional assays can be used to identify candidate causal variants underlying differences in gene regulation and phenotype.}, } @article {pmid37177303, year = {2023}, author = {Adzhieva, OA and Gringolts, ML and Denisova, YI and Shandryuk, GA and Litmanovich, EA and Nikiforov, RY and Belov, NA and Kudryavtsev, YV}, title = {Effect of Chain Structure on the Various Properties of the Copolymers of Fluorinated Norbornenes with Cyclooctene.}, journal = {Polymers}, volume = {15}, number = {9}, pages = {}, pmid = {37177303}, issn = {2073-4360}, support = {20-03-00703//Russian Foundation for Basic Research/ ; }, abstract = {Fluorinated polymers are attractive due to their special thermal, surface, gas separation, and other properties. In this study, new diblock, multiblock, and random copolymers of cyclooctene with two fluorinated norbornenes, 5-perfluorobutyl-2-norbornene and N-pentafluorophenyl-exo-endo-norbornene-5,6-dicarboximide, are synthesized by ring-opening metathesis copolymerization and macromolecular cross-metathesis in the presence of the first- to third-generation Grubbs' Ru-catalysts. Their thermal, surface, bulk, and solution characteristics are investigated and compared using differential scanning calorimetry, water contact angle measurements, gas permeation, and light scattering, respectively. It is demonstrated that they are correlated with the chain structure of the copolymers. The properties of multiblock copolymers are generally closer to those of diblock copolymers than of random ones, which can be explained by the presence of long blocks capable of self-organization. In particular, diblock and multiblock fluorine-imide-containing copolymers show a tendency to form micelles in chloroform solutions well below the overlap concentration. The results obtained may be of interest to a wide range of researchers involved in the design of functional copolymers.}, } @article {pmid37142741, year = {2023}, author = {Brand, CM and Colbran, LL and Capra, JA}, title = {Resurrecting the alternative splicing landscape of archaic hominins using machine learning.}, journal = {Nature ecology & evolution}, volume = {7}, number = {6}, pages = {939-953}, pmid = {37142741}, issn = {2397-334X}, support = {R35 GM127087/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Hominidae/genetics ; *Neanderthals/genetics ; Alternative Splicing ; Genome, Human ; Population Density ; }, abstract = {Alternative splicing contributes to adaptation and divergence in many species. However, it has not been possible to directly compare splicing between modern and archaic hominins. Here, we unmask the recent evolution of this previously unobservable regulatory mechanism by applying SpliceAI, a machine-learning algorithm that identifies splice-altering variants (SAVs), to high-coverage genomes from three Neanderthals and a Denisovan. We discover 5,950 putative archaic SAVs, of which 2,186 are archaic-specific and 3,607 also occur in modern humans via introgression (244) or shared ancestry (3,520). Archaic-specific SAVs are enriched in genes that contribute to traits potentially relevant to hominin phenotypic divergence, such as the epidermis, respiration and spinal rigidity. Compared to shared SAVs, archaic-specific SAVs occur in sites under weaker selection and are more common in genes with tissue-specific expression. Further underscoring the importance of negative selection on SAVs, Neanderthal lineages with low effective population sizes are enriched for SAVs compared to Denisovan and shared SAVs. Finally, we find that nearly all introgressed SAVs in humans were shared across the three Neanderthals, suggesting that older SAVs were more tolerated in human genomes. Our results reveal the splicing landscape of archaic hominins and identify potential contributions of splicing to phenotypic differences among hominins.}, } @article {pmid37138083, year = {2023}, author = {Essel, E and Zavala, EI and Schulz-Kornas, E and Kozlikin, MB and Fewlass, H and Vernot, B and Shunkov, MV and Derevianko, AP and Douka, K and Barnes, I and Soulier, MC and Schmidt, A and Szymanski, M and Tsanova, T and Sirakov, N and Endarova, E and McPherron, SP and Hublin, JJ and Kelso, J and Pääbo, S and Hajdinjak, M and Soressi, M and Meyer, M}, title = {Ancient human DNA recovered from a Palaeolithic pendant.}, journal = {Nature}, volume = {618}, number = {7964}, pages = {328-332}, pmid = {37138083}, issn = {1476-4687}, mesh = {Animals ; Female ; Humans ; Archaeology/methods ; *Bone and Bones/chemistry ; Deer/genetics ; *DNA, Ancient/analysis/isolation & purification ; DNA, Mitochondrial/analysis/isolation & purification ; History, Ancient ; Siberia ; *Tooth/chemistry ; Caves ; Russia ; }, abstract = {Artefacts made from stones, bones and teeth are fundamental to our understanding of human subsistence strategies, behaviour and culture in the Pleistocene. Although these resources are plentiful, it is impossible to associate artefacts to specific human individuals[1] who can be morphologically or genetically characterized, unless they are found within burials, which are rare in this time period. Thus, our ability to discern the societal roles of Pleistocene individuals based on their biological sex or genetic ancestry is limited[2-5]. Here we report the development of a non-destructive method for the gradual release of DNA trapped in ancient bone and tooth artefacts. Application of the method to an Upper Palaeolithic deer tooth pendant from Denisova Cave, Russia, resulted in the recovery of ancient human and deer mitochondrial genomes, which allowed us to estimate the age of the pendant at approximately 19,000-25,000 years. Nuclear DNA analysis identifies the presumed maker or wearer of the pendant as a female individual with strong genetic affinities to a group of Ancient North Eurasian individuals who lived around the same time but were previously found only further east in Siberia. Our work redefines how cultural and genetic records can be linked in prehistoric archaeology.}, } @article {pmid37103242, year = {2023}, author = {Witt, KE and Funk, A and Añorve-Garibay, V and Fang, LL and Huerta-Sánchez, E}, title = {The Impact of Modern Admixture on Archaic Human Ancestry in Human Populations.}, journal = {Genome biology and evolution}, volume = {15}, number = {5}, pages = {}, pmid = {37103242}, issn = {1759-6653}, support = {R35 GM128946/GM/NIGMS NIH HHS/United States ; T32 GM128596/GM/NIGMS NIH HHS/United States ; EHS 1R35GM128946-01/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; DNA ; Genome, Human ; *Hominidae/genetics ; *Neanderthals/genetics ; }, abstract = {Admixture, the genetic merging of parental populations resulting in mixed ancestry, has occurred frequently throughout the course of human history. Numerous admixture events have occurred between human populations across the world, which have shaped genetic ancestry in modern humans. For example, populations in the Americas are often mosaics of different ancestries due to recent admixture events as part of European colonization. Admixed individuals also often have introgressed DNA from Neanderthals and Denisovans that may have come from multiple ancestral populations, which may affect how archaic ancestry is distributed across an admixed genome. In this study, we analyzed admixed populations from the Americas to assess whether the proportion and location of admixed segments due to recent admixture impact an individual's archaic ancestry. We identified a positive correlation between non-African ancestry and archaic alleles, as well as a slight increase of Denisovan alleles in Indigenous American segments relative to European segments in admixed genomes. We also identify several genes as candidates for adaptive introgression, based on archaic alleles present at high frequency in admixed American populations but low frequency in East Asian populations. These results provide insights into how recent admixture events between modern humans redistributed archaic ancestry in admixed genomes.}, } @article {pmid36982684, year = {2023}, author = {Makarova, E and Dubinina, A and Denisova, E and Kazantseva, A}, title = {Genetic Obesity in Pregnant A[y] Mice Does Not Affect Susceptibility to Obesity and Food Choice in Offspring.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982684}, issn = {1422-0067}, support = {20-015-00469-A//Russian Foundation for Basic Research/ ; }, mesh = {Pregnancy ; Mice ; Animals ; Female ; Male ; Humans ; *Lactation ; Obesity/genetics/metabolism ; Leptin/metabolism ; Diet ; Liver/metabolism ; Food Preferences ; Diet, High-Fat/adverse effects ; *Prenatal Exposure Delayed Effects/genetics/metabolism ; }, abstract = {Maternal diet and obesity (MO) may influence taste preferences and increase the susceptibility to obesity in offspring, but the impact of MO per se to these influences is poorly understood. We evaluated the influence of MO on food choice and susceptibility to obesity in offspring when mothers consumed a standard diet (SD). Mice with the Lethal yellow mutation (A[y]/a) develop obesity consuming an SD. Metabolic parameters were assessed in pregnant and lactating A[y]/a (obesity) and a/a (control) mothers. Metabolic response to the consumption of a sweet-fat diet (SFD: SD, lard, and sweet biscuits) and the choice of components of this diet were evaluated in their male and female offspring. Compared to control mothers, pregnant obese mothers had higher levels of insulin, leptin, and FGF21. MO increased food intake and liver expression of lipogenesis genes in male offspring consuming the SD. SFD consumption caused obesity development and insulin resistance, increased liver expression of glycolytic and lipogenesis genes, and affected hypothalamic expression of anorexigenic and orexigenic genes. In offspring of both sexes, MO had no effect on food choice and metabolic response to SFD intake. Therefore, when obese mothers consume a balanced diet, MO does not affect food choice and development of diet-induced obesity in offspring.}, } @article {pmid36980999, year = {2023}, author = {Toncheva, D and Marinova, M and Chobanov, T and Serbezov, D}, title = {Pathogenic Variants Associated with Rare Monogenic Diseases Established in Ancient Neanderthal and Denisovan Genome-Wide Data.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36980999}, issn = {2073-4425}, mesh = {Animals ; Humans ; Infant, Newborn ; *Neanderthals/genetics ; Rare Diseases/genetics ; *Hominidae/genetics ; Genome, Human ; DNA ; }, abstract = {Ancient anatomically modern humans (AMHs) encountered other archaic human species, most notably Neanderthals and Denisovans, when they left Africa and spread across Europe and Asia ~60,000 years ago. They interbred with them, and modern human genomes retain DNA inherited from these interbreeding events. High quality (high coverage) ancient human genomes have recently been sequenced allowing for a direct estimation of individual heterozygosity, which has shown that genetic diversity in these archaic human groups was very low, indicating low population sizes. In this study, we analyze ten ancient human genome-wide data, including four sequenced with high-coverage. We screened these ancient genome-wide data for pathogenic mutations associated with monogenic diseases, and established unusual aggregation of pathogenic mutations in individual subjects, including quadruple homozygous cases of pathogenic variants in the PAH gene associated with the condition phenylketonuria in a ~120,000 years old Neanderthal. Such aggregation of pathogenic mutations is extremely rare in contemporary populations, and their existence in ancient humans could be explained by less significant clinical manifestations coupled with small community sizes, leading to higher inbreeding levels. Our results suggest that pathogenic variants associated with rare diseases might be the result of introgression from other archaic human species, and archaic admixture thus could have influenced disease risk in modern humans.}, } @article {pmid36979362, year = {2023}, author = {Xiao, F and Li, J and Lagniton, PNP and Kou, SH and Lei, H and Tam, B and Wang, SM}, title = {Evolutionary Origin of MUTYH Germline Pathogenic Variations in Modern Humans.}, journal = {Biomolecules}, volume = {13}, number = {3}, pages = {}, pmid = {36979362}, issn = {2218-273X}, mesh = {Animals ; Humans ; *Adenomatous Polyposis Coli/genetics/pathology ; *Colorectal Neoplasms/genetics ; Genetic Predisposition to Disease ; Germ Cells ; Germ-Line Mutation ; Mutation ; *Neanderthals/genetics ; Oxidative Stress ; }, abstract = {MUTYH plays an essential role in preventing oxidation-caused DNA damage. Pathogenic germline variations in MUTYH damage its function, causing intestinal polyposis and colorectal cancer. Determination of the evolutionary origin of the variation is essential to understanding the etiological relationship between MUTYH variation and cancer development. In this study, we analyzed the origins of pathogenic germline variants in human MUTYH. Using a phylogenic approach, we searched MUTYH pathogenic variants in modern humans in the MUTYH of 99 vertebrates across eight clades. We did not find pathogenic variants shared between modern humans and the non-human vertebrates following the evolutionary tree, ruling out the possibility of cross-species conservation as the origin of human pathogenic variants in MUTYH. We then searched the variants in the MUTYH of 5031 ancient humans and extinct Neanderthals and Denisovans. We identified 24 pathogenic variants in 42 ancient humans dated between 30,570 and 480 years before present (BP), and three pathogenic variants in Neanderthals dated between 65,000 and 38,310 years BP. Data from our study revealed that human MUTYH pathogenic variants mostly arose in recent human history and partially originated from Neanderthals.}, } @article {pmid36977120, year = {2023}, author = {Primak, AL and Orlov, NA and Peigneur, S and Tytgat, J and Ignatova, AA and Denisova, KR and Yakimov, SA and Kirpichnikov, MP and Nekrasova, OV and Feofanov, AV}, title = {AgTx2-GFP, Fluorescent Blocker Targeting Pharmacologically Important Kv1.x (x = 1, 3, 6) Channels.}, journal = {Toxins}, volume = {15}, number = {3}, pages = {}, pmid = {36977120}, issn = {2072-6651}, mesh = {Animals ; Amino Acid Sequence ; Protein Binding/physiology ; *Escherichia coli/metabolism ; Ligands ; *Peptides/pharmacology/metabolism ; Potassium Channel Blockers/chemistry ; Kv1.3 Potassium Channel/genetics/metabolism ; Mammals/metabolism ; }, abstract = {The growing interest in potassium channels as pharmacological targets has stimulated the development of their fluorescent ligands (including genetically encoded peptide toxins fused with fluorescent proteins) for analytical and imaging applications. We report on the properties of agitoxin 2 C-terminally fused with enhanced GFP (AgTx2-GFP) as one of the most active genetically encoded fluorescent ligands of potassium voltage-gated Kv1.x (x = 1, 3, 6) channels. AgTx2-GFP possesses subnanomolar affinities for hybrid KcsA-Kv1.x (x = 3, 6) channels and a low nanomolar affinity to KcsA-Kv1.1 with moderate dependence on pH in the 7.0-8.0 range. Electrophysiological studies on oocytes showed a pore-blocking activity of AgTx2-GFP at low nanomolar concentrations for Kv1.x (x = 1, 3, 6) channels and at micromolar concentrations for Kv1.2. AgTx2-GFP bound to Kv1.3 at the membranes of mammalian cells with a dissociation constant of 3.4 ± 0.8 nM, providing fluorescent imaging of the channel membranous distribution, and this binding depended weakly on the channel state (open or closed). AgTx2-GFP can be used in combination with hybrid KcsA-Kv1.x (x = 1, 3, 6) channels on the membranes of E. coli spheroplasts or with Kv1.3 channels on the membranes of mammalian cells for the search and study of nonlabeled peptide pore blockers, including measurement of their affinity.}, } @article {pmid36911042, year = {2023}, author = {Alexeeva, E and Krekhova, E and Dvoryakovskaya, T and Isaeva, K and Chomakhidze, A and Chistyakova, E and Lomakina, O and Denisova, R and Mamutova, A and Fetisova, A and Gautier, M and Vankova, D and Kriulin, I and Saygitov, R}, title = {Efficacy and safety of canakinumab as a second line biologic after tocilizumab treatment failure in children with systemic juvenile idiopathic arthritis: A single-centre cohort study using routinely collected health data.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1114207}, pmid = {36911042}, issn = {2296-2360}, abstract = {BACKGROUND: A significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (bDMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required.

METHODS: Patients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the paediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS-71 = 0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up from time first canakinumab dose administered was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from electronic outpatient medical records.

RESULTS: During the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at baseline was 8.2 [interquartile range (IQR) 4.0-12.9] years, with the median sJIA duration being 1.8 (IQR 0.8-5.8) years; 37 (80%) patients received at least one conventional DMARD (cDMARD; oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (IQR 282-404) days. During the follow-up, 1 patient discontinued canakinumab due to tuberculosis detection and the dose was reduced or the injection interval increased in 4 (9%) patients. In total, 27 (60%) patients continued to receive at least one cDMARD. Improvement according to the ACR30 criteria was achieved in 43 patients [96%; 95% confidence interval (CI) 85-99], inactive disease in 42 (93%; 95%CI 82-98), and remission in 37 (82%; 95% CI 69-91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 AEs (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases.

CONCLUSIONS: One-year canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA.}, } @article {pmid36823244, year = {2023}, author = {Wang, PY and Yang, Y and Shi, XQ and Chen, Y and Liu, SD and Wang, HY and Peng, T and Shi, Q and Zhang, W and Sun, C}, title = {Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {3134}, pmid = {36823244}, issn = {2045-2322}, mesh = {Animals ; Female ; Humans ; Breast Neoplasms/genetics ; *Genetics, Population ; Genome, Human ; *Glucuronosyltransferase/genetics ; Hominidae/genetics ; Neanderthals/genetics ; Phenotype ; }, abstract = {Our previous work identified one region upstream human UGT2B4 (UDP glucuronosyltransferase family 2 member B4) which is associated with breast cancer and under balancing selection. However, the distribution, functional variation and molecular mechanism underlying breast cancer and balancing selection remain unclear. In current study, the two haplotypes with deep divergence are described by analyzing 1000 genomes project data and observed to be with high frequencies in all human populations. Through population genetics analysis and genome annotation, the potential functional region is identified and verified by reporter gene assay. Further mutagenesis indicates that the functional mutations are rs66862535 and rs68096061. Both SNPs can alter the interaction efficiency of transcription factor POU2F1 (POU class 2 homeobox 1). Through chromosome conformation capture, it is identified that the enhancer containing these two SNPs can interact with UGT2B4 promoter. Expression quantitative trait loci analysis indicates that UGT2B4 expression is dependent on the genotype of this locus. The common haplotype in human is lost in four genomes of archaic hominins, which suggests that Neanderthal and Denisovan should present relatively lower UGT2B4 expression and further higher steroid hormone level. This study provides new insight into the contribution of ancient population structure to human phenotypes.}, } @article {pmid36778254, year = {2023}, author = {Velazquez-Arcelay, K and Colbran, LL and McArthur, E and Brand, C and Rinker, D and Siemann, J and McMahon, D and Capra, JA}, title = {Archaic Introgression Shaped Human Circadian Traits.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36778254}, support = {T32 GM080178/GM/NIGMS NIH HHS/United States ; F30 HG011200/HG/NHGRI NIH HHS/United States ; T32 HG009495/HG/NHGRI NIH HHS/United States ; R01 GM117650/GM/NIGMS NIH HHS/United States ; R35 GM127087/GM/NIGMS NIH HHS/United States ; }, abstract = {INTRODUCTION: When the ancestors of modern Eurasians migrated out of Africa and interbred with Eurasian archaic hominins, namely Neanderthals and Denisovans, DNA of archaic ancestry integrated into the genomes of anatomically modern humans. This process potentially accelerated adaptation to Eurasian environmental factors, including reduced ultra-violet radiation and increased variation in seasonal dynamics. However, whether these groups differed substantially in circadian biology, and whether archaic introgression adaptively contributed to human chronotypes remains unknown.

RESULTS: Here we traced the evolution of chronotype based on genomes from archaic hominins and present-day humans. First, we inferred differences in circadian gene sequences, splicing, and regulation between archaic hominins and modern humans. We identified 28 circadian genes containing variants with potential to alter splicing in archaics (e.g., CLOCK, PER2, RORB, RORC), and 16 circadian genes likely divergently regulated between present-day humans and archaic hominins, including RORA. These differences suggest the potential for introgression to modify circadian gene expression. Testing this hypothesis, we found that introgressed variants are enriched among eQTLs for circadian genes. Supporting the functional relevance of these regulatory effects, we found that many introgressed alleles have associations with chronotype. Strikingly, the strongest introgressed effects on chronotype increase morningness, consistent with adaptations to high latitude in other species. Finally, we identified several circadian loci with evidence of adaptive introgression or latitudinal clines in allele frequency.

CONCLUSIONS: These findings identify differences in circadian gene regulation between modern humans and archaic hominins and support the contribution of introgression via coordinated effects on variation in human chronotype.}, } @article {pmid36776693, year = {2023}, author = {Hagymási, K}, title = {The Nobel prize in physiology and medicine - 2022.}, journal = {Structural chemistry}, volume = {34}, number = {2}, pages = {733-736}, pmid = {36776693}, issn = {1040-0400}, abstract = {The Nobel Assembly at Karolinska Institutet awarded the 2022 Nobel Prize in Physiology or Medicine to a Swedish geneticist, Svante Pääbo, for his discoveries concerning the genomes of extinct hominins and human evolution, for the sequencing of the genome of the Neanderthal, the discovery of a previously unknown hominin, Denisova, and the establishment of a new scientific discipline, paleogenomics.}, } @article {pmid36761718, year = {2022}, author = {Ermakov, PN and Vorobyeva, EV and Denisova, EG and Yavna, DV and Babenko, VV and Kovsh, EM and Alekseeva, DS}, title = {Recognition of Emotional and Neutral Visual Scenes in Carriers of the MAOA, COMT, DRD4, and 5HT2A Gene Polymorphisms.}, journal = {Psychology in Russia : state of the art}, volume = {15}, number = {4}, pages = {159-169}, pmid = {36761718}, issn = {2307-2202}, abstract = {BACKGROUND: It is known that some genes regulate neurochemical metabolism, and their polymorphisms affect cognitive performance, including the ability to categorize emotionally significant information.

OBJECTIVE: The aim of our study was to analyze the recognition of emotional and neutral visual scenes in carriers of different polymorphic variants of the MAOA, COMT, DRD4, and 5HT2A genes.

DESIGN: The study sample consisted of 87 university students (Caucasians, women 63%, average age 20.4±2.6 years). The genotypes of the COMT, 5HT2A, and DRD4 genes were determined by polymerase chain reaction. Agarose gel electrophoresis was used to determine the number of tandem repeats of the MAOA gene. Three hundred sixty (360) photographic images of scenes of different emotional valence (positive, negative, and neutral - 120 images for each category) were used as stimuli. These images were classified by expert assessments. The images were presented in a random sequence. The exposure time was 700 ms. The research participants were asked to determine the emotional valence of each scene.

RESULTS: We found that only the COMT gene genotype affected the recognition of emotional and neutral visual scenes. Carriers of the COMT Val/Val genotype, which causes dopamine to stay in the synaptic space for a shorter time, are better in recognizing and demonstrate higher sensitivity to the emotional content of scenes. Carriers of the Val/Met genotype demonstrated the worst ability to differentiate the emotional valence of visual scenes.

CONCLUSION: This study has shown that the length of stay of monoamines in the synaptic space regulated by the COMT gene affects the recognition of emotional visual information.}, } @article {pmid36738924, year = {2023}, author = {Cheng, T and Wang, F and Denisova, K and Barmettler, A}, title = {Normative exophthalmometry values in Hispanic individuals.}, journal = {Archivos de la Sociedad Espanola de Oftalmologia}, volume = {98}, number = {4}, pages = {199-205}, doi = {10.1016/j.oftale.2023.02.002}, pmid = {36738924}, issn = {2173-5794}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Ethnicity ; *Exophthalmos ; Hispanic or Latino ; Prospective Studies ; Aged ; }, abstract = {PURPOSE: Normative exophthalmometry values have been established in Caucasians, Asians, and Black individuals. While prior studies have examined periocular measurements in different racial and ethnic groups, this study is the first to establish a set of normative exophthalmometry values in a Hispanic population in New York City.

METHODS: This prospective, cross-sectional cohort study was IRB approved and HIPAA compliant. Adult patients self-identifying as Hispanic were included. The degree of ocular prominence (exophthalmometry value, EV) and the inter-orbital distance (Hertel's base, IOD) was obtained by Hertel exophthalmometry. Differences in EV between sexes were evaluated using two sample t-tests. Multivariable linear regression was utilized to determine the effect of age, sex, and body mass index (BMI) on EV.

RESULTS: Of the 277 Hispanic individuals included, 189 (68.2%) were female and the mean age was 63.0 years (SD = 15.0). The mean Hertel's base and mean EV for all participants was 92.0 mm (SD = 4.1) and 16.7 mm (SD = 2.4), respectively. Average exophthalmometry values for men were significantly higher than women's (17.6 mm and 16.2 mm, respectively, p ≤ 0.001). Higher EVs were positively associated with male gender (ß = -1.60, p < 0.0001) and BMI (ß = 0.084, p = 0.001), but not age.

CONCLUSIONS: The mean EV in Hispanic individuals is 16.7 mm, higher than that reported for most Caucasians and Asians, but less than that of Black individuals. Higher EV is significantly associated with male sex and increased BMI. This study is the first to create a set of normative exophthalmometry values in a Hispanic population, which may serve as a valuable tool for clinicians to reference when diagnosing and monitoring orbital disease.}, } @article {pmid36719311, year = {2023}, author = {Borshchevskaya, VN and Denisova, AV and Todorov, SS and Berezovsky, DP and Shigeev, SV and Pigolkin, YI}, title = {[Forensic medical assessment of venous thromboembolic complications of mechanical injury of the lower limb after surgery].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {66}, number = {1}, pages = {35-38}, doi = {10.17116/sudmed20236601135}, pmid = {36719311}, issn = {0039-4521}, mesh = {*Forensic Medicine ; *Lower Extremity ; }, abstract = {In forensic medical practice, venous thromboembolic complications (VTEC) are relatively rare, due to hereditary and acquired factors. The issue of expert evaluation of the VTEC after the performed surgical intervention as an alleged defect in medical care causes discussion. The purpose of this publication is to demonstrate an expert case in the assessment of VTEC mechanical injury of the lower limb after surgery. The above case with the development of PATE after surgery clearly demonstrates the possibility of the appearance of a «medical case». The key to the correct expert assessment of the alleged defect of medical care during the forensic medical examination is not only a thorough and scrupulous study of medical documentation, but also a qualitatively performed forensic medical examination of the corpse.}, } @article {pmid36711923, year = {2023}, author = {Flegontov, P and Işıldak, U and Maier, R and Yüncü, E and Changmai, P and Reich, D}, title = {Modeling of African population history using f -statistics can be highly biased and is not addressed by previously suggested SNP ascertainment schemes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36711923}, abstract = {f -statistics have emerged as a first line of analysis for making inferences about demographic history from genome-wide data. These statistics can provide strong evidence for either admixture or cladality, which can be robust to substantial rates of errors or missing data. f -statistics are guaranteed to be unbiased under "SNP ascertainment" (analyzing non-randomly chosen subsets of single nucleotide polymorphisms) only if it relies on a population that is an outgroup for all groups analyzed. However, ascertainment on a true outgroup that is not co-analyzed with other populations is often impractical and uncommon in the literature. In this study focused on practical rather than theoretical aspects of SNP ascertainment, we show that many non-outgroup ascertainment schemes lead to false rejection of true demographic histories, as well as to failure to reject incorrect models. But the bias introduced by common ascertainments such as the 1240K panel is mostly limited to situations when more than one sub-Saharan African and/or archaic human groups (Neanderthals and Denisovans) or non-human outgroups are co-modelled, for example, f 4 -statistics involving one non-African group, two African groups, and one archaic group. Analyzing panels of SNPs polymorphic in archaic humans, which has been suggested as a solution for the ascertainment problem, cannot fix all these problems since for some classes of f -statistics it is not a clean outgroup ascertainment, and in other cases it demonstrates relatively low power to reject incorrect demographic models since it provides a relatively small number of variants common in anatomically modern humans. And due to the paucity of high-coverage archaic genomes, archaic individuals used for ascertainment often act as sole representatives of the respective groups in an analysis, and we show that this approach is highly problematic. By carrying out large numbers of simulations of diverse demographic histories, we find that bias in inferences based on f -statistics introduced by non-outgroup ascertainment can be minimized if the derived allele frequency spectrum in the population used for ascertainment approaches the spectrum that existed at the root of all groups being co-analyzed. Ascertaining on sites with variants common in a diverse group of African individuals provides a good approximation to such a set of SNPs, addressing the great majority of biases and also retaining high statistical power for studying population history. Such a "pan-African" ascertainment, although not completely problem-free, allows unbiased exploration of demographic models for the widest set of archaic and modern human populations, as compared to the other ascertainment schemes we explored.}, } @article {pmid36711776, year = {2023}, author = {Witt, KE and Funk, A and Fang, LL and Huerta-Sanchez, E}, title = {The impact of modern admixture on archaic human ancestry in human populations.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36711776}, abstract = {Admixture, the genetic merging of parental populations resulting in mixed ancestry, has occurred frequently throughout the course of human history. Numerous admixture events have occurred between human populations across the world, as well as introgression between humans and archaic humans, Neanderthals and Denisovans. One example are genomes from populations in the Americas, as these are often mosaics of different ancestries due to recent admixture events as part of European colonization. In this study, we analyzed admixed populations from the Americas to assess whether the proportion and location of admixed segments due to recent admixture impact an individual’s archaic ancestry. We identified a positive correlation between non-African ancestry and archaic alleles, as well as a slight enrichment of Denisovan alleles in Indigenous American segments relative to European segments in admixed genomes. We also identify several genes as candidates for adaptive introgression, based on archaic alleles present at high frequency in admixed American populations but low frequency in East Asian populations. These results provide insights into how recent admixture events between modern humans redistributed archaic ancestry in admixed genomes.}, } @article {pmid36691623, year = {2023}, author = {de March, CA and Matsunami, H and Abe, M and Cobb, M and Hoover, KC}, title = {Genetic and functional odorant receptor variation in the Homo lineage.}, journal = {iScience}, volume = {26}, number = {1}, pages = {105908}, pmid = {36691623}, issn = {2589-0042}, abstract = {Humans, Neanderthals, and Denisovans independently adapted to a wide range of geographic environments and their associated food odors. Using ancient DNA sequences, we explored the in vitro function of thirty odorant receptor genes in the genus Homo. Our extinct relatives had highly conserved olfactory receptor sequence, but humans did not. Variations in odorant receptor protein sequence and structure may have produced variation in odor detection and perception. Variants led to minimal changes in specificity but had more influence on functional sensitivity. The few Neanderthal variants disturbed function, whereas Denisovan variants increased sensitivity to sweet and sulfur odors. Geographic adaptations may have produced greater functional variation in our lineage, increasing our olfactory repertoire and expanding our adaptive capacity. Our survey of olfactory genes and odorant receptors suggests that our genus has a shared repertoire with possible local ecological adaptations.}, } @article {pmid36681659, year = {2022}, author = {Zhou, Z and M A Swagemakers, S and S Lourens, M and Suratannon, N and J van der Spek, P and A S H Dalm, V and A Dik, W and IJspeert, H and van Hagen, PM}, title = {Did variants in inborn errors of immunity genes contribute to the extinction of Neanderthals?.}, journal = {Asian Pacific journal of allergy and immunology}, volume = {40}, number = {4}, pages = {422-434}, doi = {10.12932/AP-251022-1489}, pmid = {36681659}, issn = {0125-877X}, mesh = {Humans ; Animals ; *Neanderthals/genetics ; Genome ; Genome, Human ; Membrane Proteins/genetics ; }, abstract = {BACKGROUND: Neanderthals were a species of archaic humans that became extinct around 40,000 years ago. Modern humans have inherited 1-6% of Neanderthal DNA as a result of interbreeding. These inherited Neanderthal genes have paradoxical influences, while some can provide protection to viral infections, some others are associated with autoimmune/auto-inflammatory diseases.

OBJECTIVE: We aim to investigate whether genetic variants with strong detrimental effects on the function of the immune system could have potentially contributed to the extinction of the Neanderthal population.

METHODS: We used the publically available genome information from an Altai Neanderthal and filtered for potentially damaging variants present in genes associated with inborn errors of immunity (IEI) and checked whether these variants were present in the genomes of the Denisovan, Vindija and Chagyrskaya Neanderthals.

RESULTS: We identified 24 homozygous variants and 15 heterozygous variants in IEI-related genes in the Altai Neanderthal. Two homozygous variants in the UNC13D gene and one variant in the MOGS gene were present in all archaic genomes. Defects in the UNC13D gene are known to cause a severe and often fatal disease called hemophagocytic lymphohistiocystosis (HLH). One of these variants p.(N943S) has been reported in patients with HLH. Variants in MOGS are associated with glycosylation defects in the immune system affecting the susceptibility for infections.

CONCLUSIONS: Although the exact functional impact of these three variants needs further elucidation, we speculate that they could have resulted in an increased susceptibility to severe diseases and may have contributed to the extinction of Neanderthals after exposure to specific infections.}, } @article {pmid36661490, year = {2022}, author = {Mikhailova, SV and Ivanoshchuk, DE and Yushkevich, EA and Bairqdar, A and Anisimenko, MS and Shcherbakova, LV and Denisova, DV and Orlov, PS}, title = {Prevalence of Common Alleles of Some Stress Resilience Genes among Adolescents Born in Different Periods Relative to the Socioeconomic Crisis of the 1990s in Russia.}, journal = {Current issues in molecular biology}, volume = {45}, number = {1}, pages = {51-65}, pmid = {36661490}, issn = {1467-3045}, support = {22-28-00866//Russian Science Foundation/ ; }, abstract = {Social stress is common among people and is considered one of the causes of the declining birth rate. Predisposition to stress and stress-induced disorders is largely determined genetically. We hypothesized that due to differences in stress resistance, carriers of different genetic variants of genes associated with stress resilience and stress-induced diseases may have dissimilar numbers of offspring under conditions of long-term social stress. To test this hypothesis, a comparative analysis of frequencies of seven common polymorphic regions [exon 3 variable number of tandem repeats (VNTR) of the DRD4 gene, rs4680 of COMT, STin2 VNTR and the 5-HTTLPR (rs774676466) insertion/deletion polymorphism of SLC6A4, rs4570625 of TPH2, rs6265 of BDNF, and rs258747 of NR3C1] was performed on standardized groups of randomly selected adolescents born before, during, and after severe socioeconomic deprivation (the crisis of the 1990s in Russia). There were significant differences in frequencies of "long" alleles of the DRD4 gene (p = 0.020, χ[2] = 5.492) and rs4680 (p = 0.022, χ[2] = 5.289) in the "crisis" group as compared to the combined "noncrisis" population. It is possible that the dopaminergic system had an impact on the successful adaptation of a person to social stress.}, } @article {pmid36631528, year = {2023}, author = {Filippenkov, IB and Remizova, JA and Denisova, AE and Stavchansky, VV and Golovina, KD and Gubsky, LV and Limborska, SA and Dergunova, LV}, title = {Differential gene expression in the contralateral hemisphere of the rat brain after focal ischemia.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {573}, pmid = {36631528}, issn = {2045-2322}, mesh = {Rats ; Animals ; Brain/metabolism ; *Stroke/complications ; *Brain Ischemia/metabolism ; Infarction, Middle Cerebral Artery/complications ; Transcriptome ; Disease Models, Animal ; }, abstract = {Ischemic stroke is one of the most severe polygenic brain diseases. Here, we performed further functional genetic analysis of the processes occurring in the contralateral hemisphere (CH) after ischemia-reperfusion injury in rat brain. Comparison of RNA sequencing data for subcortical samples from the ipsilateral hemisphere (IH) and CH after 90 min of transient middle cerebral artery occlusion (tMCAO) and corresponding sham-operated (SO) controls showed four groups of genes that were associated with ischemic processes in rat brain at 24 h after tMCAO. Among them, 2672 genes were differentially expressed genes (DEGs) for IH but non-DEGs for CH, 34 genes were DEGs for CH but non-DEGs for IH, and 114 genes had codirected changes in expression in both hemispheres. The remaining 16 genes exhibited opposite changes at the mRNA level in the two brain hemispheres after tMCAO. These findings suggest that the ischemic process caused by a focal ischemia induces complex bilateral reactions at the transcriptome level in the rat brain. We believe that specific genome responses in the CH and IH may provide a useful model for the study of the potential for brain repair after stroke.}, } @article {pmid36625544, year = {2023}, author = {Aqil, A and Speidel, L and Pavlidis, P and Gokcumen, O}, title = {Balancing selection on genomic deletion polymorphisms in humans.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {36625544}, issn = {2050-084X}, support = {220457/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Humans ; Genome-Wide Association Study ; *Hominidae/genetics ; Polymorphism, Genetic ; Genome ; Genomics ; *Neanderthals/genetics ; Selection, Genetic ; }, abstract = {A key question in biology is why genomic variation persists in a population for extended periods. Recent studies have identified examples of genomic deletions that have remained polymorphic in the human lineage for hundreds of millennia, ostensibly owing to balancing selection. Nevertheless, genome-wide investigation of ancient and possibly adaptive deletions remains an imperative exercise. Here, we demonstrate an excess of polymorphisms in present-day humans that predate the modern human-Neanderthal split (ancient polymorphisms), which cannot be explained solely by selectively neutral scenarios. We analyze the adaptive mechanisms that underlie this excess in deletion polymorphisms. Using a previously published measure of balancing selection, we show that this excess of ancient deletions is largely owing to balancing selection. Based on the absence of signatures of overdominance, we conclude that it is a rare mode of balancing selection among ancient deletions. Instead, more complex scenarios involving spatially and temporally variable selective pressures are likely more common mechanisms. Our results suggest that balancing selection resulted in ancient deletions harboring disproportionately more exonic variants with GWAS (genome-wide association studies) associations. We further found that ancient deletions are significantly enriched for traits related to metabolism and immunity. As a by-product of our analysis, we show that deletions are, on average, more deleterious than single nucleotide variants. We can now argue that not only is a vast majority of common variants shared among human populations, but a considerable portion of biologically relevant variants has been segregating among our ancestors for hundreds of thousands, if not millions, of years.}, } @article {pmid36617238, year = {2023}, author = {Zhang, X and Kim, B and Singh, A and Sankararaman, S and Durvasula, A and Lohmueller, KE}, title = {MaLAdapt Reveals Novel Targets of Adaptive Introgression From Neanderthals and Denisovans in Worldwide Human Populations.}, journal = {Molecular biology and evolution}, volume = {40}, number = {1}, pages = {}, pmid = {36617238}, issn = {1537-1719}, support = {F32 GM135998/GM/NIGMS NIH HHS/United States ; R35 GM125055/GM/NIGMS NIH HHS/United States ; R00 GM143466/GM/NIGMS NIH HHS/United States ; K99 GM143466/GM/NIGMS NIH HHS/United States ; R35 GM119856/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Neanderthals/genetics ; Reproducibility of Results ; Genetics, Population ; Adaptation, Physiological ; Selection, Genetic ; Genome, Human ; }, abstract = {Adaptive introgression (AI) facilitates local adaptation in a wide range of species. Many state-of-the-art methods detect AI with ad-hoc approaches that identify summary statistic outliers or intersect scans for positive selection with scans for introgressed genomic regions. Although widely used, approaches intersecting outliers are vulnerable to a high false-negative rate as the power of different methods varies, especially for complex introgression events. Moreover, population genetic processes unrelated to AI, such as background selection or heterosis, may create similar genomic signals to AI, compromising the reliability of methods that rely on neutral null distributions. In recent years, machine learning (ML) methods have been increasingly applied to population genetic questions. Here, we present a ML-based method called MaLAdapt for identifying AI loci from genome-wide sequencing data. Using an Extra-Trees Classifier algorithm, our method combines information from a large number of biologically meaningful summary statistics to capture a powerful composite signature of AI across the genome. In contrast to existing methods, MaLAdapt is especially well-powered to detect AI with mild beneficial effects, including selection on standing archaic variation, and is robust to non-AI selective sweeps, heterosis from deleterious mutations, and demographic misspecification. Furthermore, MaLAdapt outperforms existing methods for detecting AI based on the analysis of simulated data and the validation of empirical signals through visual inspection of haplotype patterns. We apply MaLAdapt to the 1000 Genomes Project human genomic data and discover novel AI candidate regions in non-African populations, including genes that are enriched in functionally important biological pathways regulating metabolism and immune responses.}, } @article {pmid36553646, year = {2022}, author = {Stavchansky, VV and Filippenkov, IB and Remizova, JA and Denisova, AE and Mozgovoy, IV and Gubsky, LV and Myasoedov, NF and Andreeva, LA and Limborska, SA and Dergunova, LV}, title = {Insight into Glyproline Peptides' Activity through the Modulation of the Inflammatory and Neurosignaling Genetic Response Following Cerebral Ischemia-Reperfusion.}, journal = {Genes}, volume = {13}, number = {12}, pages = {}, pmid = {36553646}, issn = {2073-4425}, mesh = {Rats ; Animals ; Rats, Wistar ; *Interleukin-6 ; Peptides/genetics/pharmacology/therapeutic use ; *Brain Ischemia/drug therapy/genetics/metabolism ; Cerebral Infarction ; }, abstract = {Glyprolines are Gly-Pro (GP)- or Pro-Gly (PG)-containing biogenic peptides. These peptides can act as neutrophil chemoattractants, or atheroprotective, anticoagulant, and neuroprotective agents. The Pro-Gly-Pro (PGP) tripeptide is an active factor of resistance to the biodegradation of peptide drugs. The synthetic Semax peptide, which includes Met-Glu-His-Phe (MEHF) fragments of adrenocorticotropic hormone and the C-terminal tripeptide PGP, serves as a neuroprotective drug for the treatment of ischemic stroke. Previously, we revealed that Semax mostly prevented the disruption of the gene expression pattern 24 h after a transient middle cerebral artery occlusion (tMCAO) in a rat brain model. The genes of this pattern were grouped into an inflammatory cluster (IC) and a neurotransmitter cluster (NC). Here, using real-time RT-PCR, the effect of other PGP-containing peptides, PGP and Pro-Gly-Pro-Leu (PGPL), on the expression of a number of genes in the IC and NC was studied 24 h after tMCAO. Both the PGP and PGPL peptides showed Semax-unlike effects, predominantly without changing gene expression 24 h after tMCAO. Moreover, there were IC genes (iL1b, iL6, and Socs3) for PGP, as well as IC (iL6, Ccl3, Socs3, and Fos) and NC genes (Cplx2, Neurod6, and Ptk2b) for PGPL, that significantly changed in expression levels after peptide administration compared to Semax treatment under tMCAO conditions. Furthermore, gene enrichment analysis was carried out, and a regulatory gene network was constructed. Thus, the spectra of the common and unique effects of the PGP, PGPL, and Semax peptides under ischemia-reperfusion were distinguished.}, } @article {pmid36542350, year = {2023}, author = {Rochkind, S and Ferraresi, S and Denisova, N and Garozzo, D and Heinen, C and Alimehmeti, R and Capone, C and Barone, DG and Zdunczyk, A and Pedro, MT and Antoniadis, G and Kaiser, R and Dubuisson, A and Pondaag, W and Kretschmer, T and Rasulic, L and Dengler, NF}, title = {Thoracic Outlet Syndrome Part II: Consensus on the Management of Neurogenic Thoracic Outlet Syndrome by the European Association of Neurosurgical Societies' Section of Peripheral Nerve Surgery.}, journal = {Neurosurgery}, volume = {92}, number = {2}, pages = {251-257}, doi = {10.1227/neu.0000000000002232}, pmid = {36542350}, issn = {1524-4040}, mesh = {Humans ; *Thoracic Outlet Syndrome/diagnosis/surgery ; Treatment Outcome ; Prospective Studies ; Neurosurgical Procedures/adverse effects ; Decompression, Surgical/adverse effects ; Peripheral Nerves/surgery ; Observational Studies as Topic ; }, abstract = {BACKGROUND: In the first part of this report, the European Association of Neurosurgical Societies' section of peripheral nerve surgery presented a systematic literature review and consensus statements on anatomy, classification, and diagnosis of thoracic outlet syndrome (TOS) along with a subclassification system of neurogenic TOS (nTOS). Because of the lack of level 1 evidence, especially regarding the management of nTOS, we now add a consensus statement on nTOS treatment among experienced neurosurgeons.

OBJECTIVE: To document consensus and controversy on nTOS management, with emphasis on timing and types of surgical and nonsurgical nTOS treatment, and to support patient counseling and clinical decision-making within the neurosurgical community.

METHODS: The literature available on PubMed/MEDLINE was systematically searched on February 13, 2021, and yielded 2853 results. Screening and classification of abstracts was performed. In an online meeting that was held on December 16, 2021, 14 recommendations on nTOS management were developed and refined in a group process according to the Delphi consensus method.

RESULTS: Five RCTs reported on management strategies in nTOS. Three prospective observational studies present outcomes after therapeutic interventions. Fourteen statements on nonsurgical nTOS treatment, timing, and type of surgical therapy were developed. Within our expert group, the agreement rate was high with a mean of 97.8% (± 0.04) for each statement, ranging between 86.7% and 100%.

CONCLUSION: Our work may help to improve clinical decision-making among the neurosurgical community and may guide nonspecialized or inexperienced neurosurgeons with initial patient management before patient referral to a specialized center.}, } @article {pmid36520391, year = {2023}, author = {Gorgé, O and Bennett, EA and Massilani, D and Daligault, J and Geigl, EM and Grange, T}, title = {Analysis of Ancient Microbial DNA.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2605}, number = {}, pages = {103-131}, pmid = {36520391}, issn = {1940-6029}, mesh = {Animals ; Humans ; DNA, Ancient ; Body Remains ; *Hominidae/genetics ; DNA/genetics ; Genome, Microbial ; *Neanderthals/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {The development of next-generation sequencing has led to a breakthrough in the analysis of ancient genomes, and the subsequent genomic analyses of ancient human skeletal remains have revolutionized our understanding of human evolution. This research led to the discovery of a new hominin lineage, and demonstrated multiple admixture events with more distantly related archaic human populations such as Neandertals and Denisovans over the last 100,000 years. Moreover, it has also yielded novel insights into the evolution of ancient pathogens. The analysis of ancient microbial genomes enables the study of their recent evolution, presently covering the last several millennia. These spectacular results have been obtained despite the degradation of DNA that takes place after the death of the host and increases with time. This cumulative degradation results in very short ancient DNA molecules, low in quantity, and highly prone to contamination by modern DNA molecules, especially from human and animal DNA present in reagents used in downstream biomolecular analyses. Finally, the minute amounts of ancient molecules are further diluted in environmental DNA from the soil microorganisms that colonize bones and teeth. Thus, ancient skeletal remains can share DNA profiles with environmental samples, and the identification of ancient microbial genomes among the more recent, presently poorly characterized, environmental microbiome is particularly challenging. Here, we describe the methods developed and/or in use in our laboratory to produce reliable and reproducible paleogenomic results from ancient skeletal remains that can be used to identify the presence of ancient microbiota.}, } @article {pmid36509726, year = {2022}, author = {Skryabin, GO and Vinokurova, SV and Elkina, NV and Denisova, DA and Beliaeva, AA and Zhordania, KI and Bagrov, DV and Enikeev, AD and Galetsky, SA and Komelkov, AV and Krasnoshekova, GI and Tchevkina, EM}, title = {Comparison of Methods for MicroRNA Isolation from Extracellular Vesicles Obtained from Ascitic Fluids.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {11}, pages = {1354-1366}, doi = {10.1134/S0006297922110141}, pmid = {36509726}, issn = {1608-3040}, mesh = {*MicroRNAs/metabolism ; Ascitic Fluid/metabolism ; *Extracellular Vesicles/metabolism ; *Exosomes/metabolism ; }, abstract = {Secreted extracellular vesicles (EVs) contain active biomolecules, including miRNAs, composition of which reflects epigenetic changes occurring in cells during pathological processes, in particular, malignant transformation. The accumulated pool of data on the role of EVs in carcinogenesis has stimulated investigations of the EV-derived cancer markers. The most important factor limiting development of this scientific direction is lack of "gold standards" both for methods of EV isolation from biological fluids and for analyzing their molecular content, including composition of miRNAs. Here we first examined efficacy of various methods for small RNA isolation from EVs contained in ascitic fluid for subsequent miRNA analysis. Comparison of different commercial kits showed advantages of the methods based on phenol-chloroform extraction: Total Exosome RNA & Protein Isolation Kit and miRNeasy Serum/Plasma Kit. Analysis of the small RNA transcriptome showed presence of various classes of molecules in the EVs, among which proportion of miRNAs averaged 6% and reaching 10% with the Total Exosome RNA & Protein Isolation Kit. The PureLink miRNA Isolation Kit demonstrated the lowest efficiency. The miRNeasy Advanced Serum/Plasma Kit showed the highest concentration of the small RNA fraction, miRNA proportion of which, however, did not exceed that obtained with the miRNeasy Serum/Plasma Kit and Total Exosome RNA & Protein Isolation Kit. Moreover, RT-PCR analysis of the individual molecules showed lower levels of each of investigated miRNAs (miR-1246, miR-200b-5p, miR-200c-3p, and miR-23a-3p) when using the miRNeasy Advanced Serum/Plasma Kit. In conclusion, Total Exosome RNA & Protein Isolation Kit and miRNeasy Serum/Plasma Kit can be considered as optimal kits in terms of performance based on combination of the studied characteristics, including small RNA concentration, percentage of microRNA according to bioanalyzer and sequencing results, and levels of individual miRNAs detected by RT-PCR.}, } @article {pmid36480515, year = {2022}, author = {Vespasiani, DM and Jacobs, GS and Cook, LE and Brucato, N and Leavesley, M and Kinipi, C and Ricaut, FX and Cox, MP and Gallego Romero, I}, title = {Denisovan introgression has shaped the immune system of present-day Papuans.}, journal = {PLoS genetics}, volume = {18}, number = {12}, pages = {e1010470}, pmid = {36480515}, issn = {1553-7404}, mesh = {Humans ; *Immune System ; *Hominidae/genetics ; *Neanderthals/genetics ; Papua New Guinea ; *Evolution, Molecular ; }, abstract = {Modern humans have admixed with multiple archaic hominins. Papuans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these introgression events remain poorly understood. Here we investigate the function of both Denisovan and Neanderthal alleles characterised within a set of 56 genomes from Papuan individuals. By comparing the distribution of archaic and non-archaic variants we assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We observe an enrichment of archaic alleles within cis-regulatory elements and transcribed regions of the genome, with Denisovan variants strongly affecting elements active within immune-related cells. We identify 16,048 and 10,032 high-confidence Denisovan and Neanderthal variants that fall within annotated cis-regulatory elements and with the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes. Lastly, we experimentally validate these predictions by testing the regulatory potential of five Denisovan variants segregating within Papuan individuals, and find that two are associated with a significant reduction of transcriptional activity in plasmid reporter assays. Together, these data provide support for a widespread contribution of archaic DNA in shaping the present levels of modern human genetic diversity, with different archaic ancestries potentially affecting multiple phenotypic traits within non-Africans.}, } @article {pmid36470093, year = {2023}, author = {Morfouace, M and Horak, P and Kreutzfeldt, S and Stevovic, A and de Rojas, T and Denisova, E and Hutter, B and Bautista, F and Oliveira, J and Defachelles, AS and White, J and Kasper, B and Preusser, M and Golfinopoulos, V and Pfister, S and Van der Graaf, W and Wardelmann, E and Shenjere, P and Fröhling, S and McCabe, MG}, title = {Comprehensive molecular profiling of sarcomas in adolescent and young adult patients: Results of the EORTC SPECTA-AYA international proof-of-concept study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {178}, number = {}, pages = {216-226}, doi = {10.1016/j.ejca.2022.10.020}, pmid = {36470093}, issn = {1879-0852}, mesh = {Adolescent ; Humans ; Young Adult ; Europe ; Exome Sequencing ; Prognosis ; *Sarcoma/genetics/therapy ; *Soft Tissue Neoplasms ; Proof of Concept Study ; }, abstract = {BACKGROUND: Adolescent and young adult (AYA) patients with cancer are poorly recruited to molecularly targeted trials and have not witnessed the advances in cancer treatment and survival seen in other age groups. We report here a pan-European proof-of-concept study to identify actionable alterations in some of the worst prognosis AYA cancers: bone and soft tissue sarcomas.

DESIGN: Patients aged 12-29 years with newly diagnosed or recurrent, intermediate or high-grade bone and soft tissue sarcomas were recruited from six European countries. Pathological diagnoses were centrally reviewed. Formalin-fixed tissues were analysed by whole exome sequencing, methylation profiling and RNA sequencing and were discussed in a multidisciplinary, international molecular tumour board.

RESULTS: Of 71 patients recruited, 48 (median 20 years, range 12-28) met eligibility criteria. Central pathological review confirmed, modified and re-classified the diagnosis in 41, 3, and 4 cases, respectively. Median turnaround time to discussion at molecular tumour board was 8.4 weeks. whole exome sequencing (n = 48), methylation profiling (n = 44, 85%) and RNA sequencing (n = 24, 50%) led to therapeutic recommendations for 81% patients, including 4 with germ line alterations. The most common were for agents targeted towards tyrosine kinases (n = 20 recommendations), DNA repair (n = 18) and the PI3K/mTOR/AKT pathway (n = 15). Recommendations were generally based on weak evidence such as activity in a different tumour type (n = 68, 61%), reflecting the dearth of relevant molecular clinical trial data in the same tumour type.

CONCLUSIONS: We demonstrate here that comprehensive molecular profiling of AYA patients' samples is feasible and deliverable in a European programme.}, } @article {pmid36437327, year = {2022}, author = {Tyrinova, TV and Batorov, EV and Aristova, TA and Ushakova, GY and Sizikova, SA and Denisova, VV and Ostanin, AA and Chernykh, ER}, title = {Expression of Inhibitory Molecules (Arginase-1, IDO, and PD-L1) by Myeloid-Derived Suppressor Cells in Multiple Myeloma Patients in Remission.}, journal = {Bulletin of experimental biology and medicine}, volume = {174}, number = {1}, pages = {71-75}, pmid = {36437327}, issn = {1573-8221}, mesh = {Humans ; *Myeloid-Derived Suppressor Cells ; B7-H1 Antigen/genetics ; *Multiple Myeloma/therapy ; HLA-DR Antigens ; }, abstract = {We studied suppressor potential of myeloid-derived suppressor cells (MDSC) in multiple myeloma patients, including before and after mobilization of hematopoietic stem cells (HSC), by evaluating the expression of arginase-1 (Arg1), indolamine-2,3-dioxygenase (IDO), and PD-L1 in MDSC subsets. The study included 20 multiple myeloma patients in remission, 5 patients with progression, as well as 10 sex-and age-matched healthy donors. The expression of Arg1, IDO, and PD-L1 in circulating granulocytic MDSC (G-MDSC, Lin[-]HLA-DR[-]CD33[+]CD66b[+]), monocytic MDSC (M-MDSC, CD14[+]HLA-DR[low/-]), and early-stage MDSC (E-MDSC, Lin[-]HLA-DR[-]CD33[+]CD66b[-]) was evaluated by flow cytometry. Multiple myeloma patients in remission were characterized by reduced expression of Arg1 in M-MDSC in comparison with donors. The expression of Arg1 in M-MDSC depended on the number of induction therapy lines performed and was significantly lower in patients who received ⩾2 lines and responded with remission. Patients with multiple myeloma progression (resistant to therapy) showed significantly increased expression of Arg1 and PD-L1 in M-MDSC, as well as increased expression of Arg1 in E-MDSC. After G-CSF-induced mobilization of HSC, the content of circulating Arg1-expressing M-MDSC increased significantly. Considering the presence of MDSC in apheresis products, MDSC suppressive activity is discussed as a factor affecting the outcomes of autologous HSC transplantation in multiple myeloma patients.}, } @article {pmid36431772, year = {2022}, author = {Šutka, A and Mežule, L and Denisova, V and Meier-Haack, J and Kulkarni, A and Bitina, S and Smits, K and Vihodceva, S}, title = {Straightforward Approach for Preparing Durable Antibacterial ZnO Nanoparticle Coatings on Flexible Substrates.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {22}, pages = {}, pmid = {36431772}, issn = {1420-3049}, support = {RTD/2021/11//M-era.Net/ ; }, mesh = {*Zinc Oxide/pharmacology/chemistry ; Polystyrenes ; Anti-Bacterial Agents/pharmacology/chemistry ; Escherichia coli ; Polymers ; Solvents ; Toluene ; }, abstract = {Flexible antibacterial materials have gained utmost importance in protection from the distribution of bacteria and viruses due to the exceptional variety of applications. Herein, we demonstrate a readily scalable and rapid single-step approach for producing durable ZnO nanoparticle antibacterial coating on flexible polymer substrates at room temperature. Substrates used are polystyrene, poly(ethylene-co-vinyl acetate) copolymer, poly(methyl methacrylate), polypropylene, high density polyethylene and a commercial acrylate type adhesive tape. The deposition was achieved by a spin-coating process using a slurry of ZnO nanoparticles in toluene. A stable modification layer was obtained when toluene was a solvent for the polymer substrates, namely polystyrene and poly(ethylene-co-vinyl acetate). These coatings show high antibacterial efficiency causing >5 log decrease in the viable counts of Gram-negative bacteria Escherichia. coli and Gram-positive bacteria Staphylococcus aureus in 120 min. Even after tapping these coated surfaces 500 times, the antibacterial properties remained unchanged, showing that the coating obtained by the presented method is very robust. In contrast to the above findings, the coatings are unstable when toluene is not a solvent for the substrate.}, } @article {pmid36428967, year = {2022}, author = {Perik-Zavodskii, R and Perik-Zavodskaia, O and Shevchenko, J and Denisova, V and Alrhmoun, S and Volynets, M and Tereshchenko, V and Zaitsev, K and Sennikov, S}, title = {Immune Transcriptome Study of Human Nucleated Erythroid Cells from Different Tissues by Single-Cell RNA-Sequencing.}, journal = {Cells}, volume = {11}, number = {22}, pages = {}, pmid = {36428967}, issn = {2073-4409}, mesh = {Adult ; Humans ; *Transcriptome/genetics ; Cell Count ; *Erythrocytes/metabolism ; Fetal Blood ; RNA/genetics/metabolism ; }, abstract = {Nucleated erythroid cells (NECs) are the precursors of erythrocytes. They can be found in various hematopoietic tissues or in the blood. Recently, they have been shown to be active players in immunosuppression through the synthesis of arginase-2 and reactive oxygen species. In this work, we studied NECs in adult bone marrow, umbilical cord blood, and foetal liver parenchyma using single-cell RNA sequencing and found that: (1) all studied NECs expressed the same set of genes, which was enriched in "GO biological process" immunity-related terms; (2) early and late NECs had differential expression of the genes associated with immunosuppression, cell cycle progression, apoptosis, and glycolysis; (3) NECs from different tissues of origin had differential expression of the genes associated with immunosuppression.}, } @article {pmid36375244, year = {2022}, author = {Harvati, K and Reyes-Centeno, H}, title = {Evolution of Homo in the Middle and Late Pleistocene.}, journal = {Journal of human evolution}, volume = {173}, number = {}, pages = {103279}, pmid = {36375244}, issn = {1095-8606}, mesh = {Animals ; Humans ; *Hominidae ; Phylogeny ; Biological Evolution ; Fossils ; *Neanderthals ; }, abstract = {The Middle and Late Pleistocene is arguably the most interesting period in human evolution. This broad period witnessed the evolution of our own lineage, as well as that of our sister taxon, the Neanderthals, and related Denisovans. It is exceptionally rich in both fossil and archaeological remains, and uniquely benefits from insights gained through molecular approaches, such as paleogenetics and paleoproteomics, that are currently not widely applicable in earlier contexts. This wealth of information paints a highly complex picture, often described as 'the Muddle in the Middle,' defying the common adage that 'more evidence is needed' to resolve it. Here we review competing phylogenetic scenarios and the historical and theoretical developments that shaped our approaches to the fossil record, as well as some of the many remaining open questions associated with this period. We propose that advancing our understanding of this critical time requires more than the addition of data and will necessitate a major shift in our conceptual and theoretical framework.}, } @article {pmid36373182, year = {2023}, author = {Denisova, K and Lin, Z}, title = {The importance of low IQ to early diagnosis of autism.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {16}, number = {1}, pages = {122-142}, pmid = {36373182}, issn = {1939-3806}, support = {R01 MH121605/MH/NIMH NIH HHS/United States ; 14242//Simons Foundation Autism Research Initiative/ ; }, mesh = {Infant, Newborn ; Infant ; Humans ; Child, Preschool ; *Autistic Disorder/complications ; *Autism Spectrum Disorder/psychology ; Cross-Sectional Studies ; Intelligence ; Cognition ; Early Diagnosis ; }, abstract = {Some individuals can flexibly adapt to life's changing demands while others, in particular those with Autism Spectrum Disorder (ASD), find it challenging. The origin of early individual differences in cognitive abilities, the putative tools with which to navigate novel information in life, including in infants later diagnosed with ASD remains unexplored. Moreover, the role of intelligence quotient (IQ) vis-à-vis core features of autism remains debated. We systematically investigate the contribution of early IQ in future autism outcomes in an extremely large, population-based study of 8000 newborns, infants, and toddlers from the US between 2 and 68 months with over 15,000 cross-sectional and longitudinal assessments, and for whom autism outcomes are ascertained or ruled out by about 2-4 years. This population is representative of subjects involved in the National Institutes of Health (NIH)-funded research, mainly on atypical development, in the US. Analyses using predetermined age bins showed that IQ scores are consistently lower in ASD relative to typically developing (TD) children at all ages (p < 0.001), and IQ significantly correlates with social, non-social, and total Calibrated Severity Scores (CSS) on the Autism Diagnostic Observation Schedule (ADOS) (p<0.01). Lower IQ is associated with greater autistic impairments. Note, verbal IQ (VIQ) is no better than the full-scale IQ to predict ASD cases. These findings raise new, compelling questions about potential atypical brain circuitry affecting performance in both verbal and nonverbal abilities and preceding an ASD diagnosis. This study is the first to establish prospectively that low early IQ is a major feature of ASD in early childhood. LAY SUMMARY: The role of IQ scores in autism remains debated. We systematically investigate the contribution of early IQ in an extremely large study of 8,000 children between 2 and 68 months with autism outcomes by about 2-4 years. We show that IQ scores are consistently lower in ASD relative to TD children. This study is the first to establish prospectively that low early IQ is a predictor for ASD diagnosis in early childhood.}, } @article {pmid36350902, year = {2022}, author = {Steinberg, Y and Wieder, MS and Denisova, K and He, C and Parsikia, A and Mbekeani, JN}, title = {Evaluation of commotio retinae in orbital fractures.}, journal = {Arquivos brasileiros de oftalmologia}, volume = {}, number = {}, pages = {}, doi = {10.5935/0004-2749.2021-0456}, pmid = {36350902}, issn = {1678-2925}, abstract = {PURPOSE: This study aimed to evaluate the mechanisms of injury and types of orbital fractures and their relation to concurrent commotio retinae.

METHODS: This retrospective study evaluated the records of patients with orbital fractures whose diagnoses had been confirmed by computer tomography between July 2017 and September 2019. Patient demographics, the circumstances of injury, ophthalmic examination results, and radiological findings were tabulated. Statistical analysis of the data used two-tailed student's t-tests, chi-squared tests, and odds ratio calculations. Statistical significance was set at p<0.05.

RESULTS: Of the 204 patients with orbital fractures included in this study, 154 (75.5%) were male. The mean age was 42.1 years. Orbital fractures involving one orbital wall (58.8%) were more common than those affecting multiple walls (41.2%). The majority of fractures affected the inferior wall (60.3%), with the medial walls being the next most frequently affected (19.6%). The most common cause of injury was assault (59.3%), and the second most common was falls (24%). Commotio retinae was observed in 20.1% of orbital fracture cases and was most associated with injuries caused by assault (OR=5.22, p<0.001) and least associated with those caused by falls (OR=0.06, p<0.001). Eye movement restrictions were more common in central than peripheral commotio (OR=3.79, p=0.015) and with medial wall fractures than fractures to other orbital walls (OR=7.16, p<0.001). The odds of commotio were not found to be higher in patients with multi-walled orbital fractures than in those with single-walled fractures (p=0.967).

CONCLUSIONS: In the study population, assault was the most common cause of orbital fractures and resulted in commotio retinae than other causes. Ophthalmologists should be aware of the likelihood of commotio retinae in patients with orbital fractures resulting from assault, regardless of the extent of the patient's injuries.}, } @article {pmid36344982, year = {2022}, author = {Koller, D and Wendt, FR and Pathak, GA and De Lillo, A and De Angelis, F and Cabrera-Mendoza, B and Tucci, S and Polimanti, R}, title = {Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {249}, pmid = {36344982}, issn = {1741-7007}, support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; R21 DC018098/DC/NIDCD NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; F32 MH122058/MH/NIMH NIH HHS/United States ; R33 DA047527/DA/NIDA NIH HHS/United States ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Animals ; *Neanderthals/genetics ; Multifactorial Inheritance ; Genome-Wide Association Study ; Genome, Human ; Asian People ; }, abstract = {BACKGROUND: Introgression from extinct Neanderthal and Denisovan human species has been shown to contribute to the genetic pool of modern human populations and their phenotypic spectrum. Evidence of how Neanderthal introgression shaped the genetics of human traits and diseases has been extensively studied in populations of European descent, with signatures of admixture reported for instance in genes associated with pigmentation, immunity, and metabolic traits. However, limited information is currently available about the impact of archaic introgression on other ancestry groups. Additionally, to date, no study has been conducted with respect to the impact of Denisovan introgression on the health and disease of modern populations. Here, we compare the way evolutionary pressures shaped the genetics of complex traits in East Asian and European populations, and provide evidence of the impact of Denisovan introgression on the health of East Asian and Central/South Asian populations.

RESULTS: Leveraging genome-wide association statistics from the Biobank Japan and UK Biobank, we assessed whether Denisovan and Neanderthal introgression together with other evolutionary genomic signatures were enriched for the heritability of physiological and pathological conditions in populations of East Asian and European descent. In EAS, Denisovan-introgressed loci were enriched for coronary artery disease heritability (1.69-fold enrichment, p=0.003). No enrichment for archaic introgression was observed in EUR. We also performed a phenome-wide association study of Denisovan and Neanderthal alleles in six ancestry groups available in the UK Biobank. In EAS, the Denisovan-introgressed SNP rs62391664 in the major histocompatibility complex region was associated with albumin/globulin ratio (beta=-0.17, p=3.57×10[-7]). Neanderthal-introgressed alleles were associated with psychiatric and cognitive traits in EAS (e.g., "No Bipolar or Depression"-rs79043717 beta=-1.5, p=1.1×10[-7]), and with blood biomarkers (e.g., alkaline phosphatase-rs11244089 beta=0.1, p=3.69×10[-116]) and red hair color (rs60733936 beta=-0.86, p=4.49×10[-165]) in EUR. In the other ancestry groups, Neanderthal alleles were associated with several traits, also including the use of certain medications (e.g., Central/South East Asia: indapamide - rs732632 beta=-2.38, p=5.22×10[-7]).

CONCLUSIONS: Our study provides novel evidence regarding the impact of archaic introgression on the genetics of complex traits in worldwide populations, highlighting the specific contribution of Denisovan introgression in EAS populations.}, } @article {pmid36341799, year = {2023}, author = {Onishchenko, G and Nikolayeva, N and Rakitskii, V and Ilnitskaya, A and Filin, A and Korolev, A and Nikitenko, E and Denisova, E and Tsakalof, A and Guseva, E and Kuzmin, S and Tsatsakis, A}, title = {Comprehensive study of health effects of plasma technology occupational environment: Exposure to high frequency and intensity noise and toxic gases.}, journal = {Environmental research}, volume = {216}, number = {Pt 3}, pages = {114691}, doi = {10.1016/j.envres.2022.114691}, pmid = {36341799}, issn = {1096-0953}, mesh = {Rats ; Animals ; Male ; Microcirculation ; Rats, Wistar ; *Ozone/toxicity ; Noise ; Technology ; }, abstract = {OBJECTIVES: To evaluate on animal models the health effects of the combined or separate exposure to main chemical and physical hazards of plasma-based material processing technology environment.

MATERIALS AND METHODS: Male Wistar rats were exposed to actual levels of hazardous factors in plasma technology occupational environment: i.e., ozone and nitrogen oxides (O3 and NOx) in respective concentrations of 0.5 mg/m[3] and 1.0 mg/m[3] and high-frequency (1000-1600 Hz) of 112 dB intensity noise for 3 h/day, 5 days/week for 12 weeks, with a recovery period of 1 month.

RESULTS: Exposure to noise or its combination with chemical factors (ozone, nitrogen oxides) causes non-specific CNS changes testifying for significant excitation dominance, especially in the case of joint exposure. Histological examination of rats' brain in experimental revealed a pronounced increase in blood filling of small vessels on the tenth day of the experiment, with subsequent intensification of vascular alterations and eventually to cerebral edema. The exposure to noise significantly reduced total thymus, bone marrow and spleen cell numbers and these was also more pronounced under the joint impact of noise and toxic gases. Thymus, but not bone marrow or spleen, mitotic activity was as well reduced under the same modes of exposure. Cytological investigation of film preparations of subcutaneous connective tissue revealed that joint exposure led to microcirculatory disorders, increased number of dark mast cells and reduced degranulation processes indicative of increased autoregulatory processes effective at microvasculature level.

CONCLUSIONS: High-frequency and intensity noise is main stressor factor that has negative impact on CNS and immune system, morphology and functioning of hematopoietic organs (spleen, bone marrow, thymus) and connective tissue. Its negative impact is significantly potentiated by concurrent exposure to ozone and nitrogen oxide, while exposure only to these toxic gases has no significant effect on the above targets.}, } @article {pmid36322514, year = {2022}, author = {Campelo Dos Santos, AL and Owings, A and Sullasi, HSL and Gokcumen, O and DeGiorgio, M and Lindo, J}, title = {Genomic evidence for ancient human migration routes along South America's Atlantic coast.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1986}, pages = {20221078}, pmid = {36322514}, issn = {1471-2954}, support = {R35 GM128590/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; History, Ancient ; Animals ; *Human Migration ; Genomics ; Genome, Human ; *Neanderthals ; Brazil ; }, abstract = {An increasing body of archaeological and genomic evidence has hinted at a complex settlement process of the Americas by humans. This is especially true for South America, where unexpected ancestral signals have raised perplexing scenarios for the early migrations into different regions of the continent. Here, we present ancient human genomes from the archaeologically rich Northeast Brazil and compare them to ancient and present-day genomic data. We find a distinct relationship between ancient genomes from Northeast Brazil, Lagoa Santa, Uruguay and Panama, representing evidence for ancient migration routes along South America's Atlantic coast. To further add to the existing complexity, we also detect greater Denisovan than Neanderthal ancestry in ancient Uruguay and Panama individuals. Moreover, we find a strong Australasian signal in an ancient genome from Panama. This work sheds light on the deep demographic history of eastern South America and presents a starting point for future fine-scale investigations on the regional level.}, } @article {pmid36286923, year = {2022}, author = {Denisova, AR and Solntseva, TD and Zarmanbetova, AS and Tkacheva, AA and Sivakova, OA and Chazova, IЕ}, title = {[The incidence of cardiovascular and cerebrovascular complications in patients with uncontrolled hypertension].}, journal = {Terapevticheskii arkhiv}, volume = {94}, number = {1}, pages = {94-99}, doi = {10.26442/00403660.2022.01.201395}, pmid = {36286923}, issn = {0040-3660}, mesh = {Humans ; *Ischemic Attack, Transient/epidemiology/etiology ; Incidence ; *Hypertension/complications/epidemiology/drug therapy ; Blood Pressure ; *Myocardial Infarction/complications ; *Stroke/etiology/complications ; Antihypertensive Agents/pharmacology ; }, abstract = {AIM: To assess the incidence of cardiovascular and cerebrovascular events in patients with controlled and uncontrolled hypertension, controlled resistant and uncontrolled resistant hypertension, refractory hypertension, and probably resistant and probably refractory hypertension.

MATERIALS AND METHODS: A telephone call was made to 256 patients with hypertension included in the database to assess the incidence of cardiovascular and cerebrovascular diseases. All responding patients were divided into 7 groups according to the classification of hypertension based on the achievement/non-achievement of target blood pressure values and the number of drugs taken (controlled and uncontrolled hypertension, controlled resistant and uncontrolled resistant hypertension, refractory hypertension, and probably resistant and probably refractory hypertension). The target blood pressure was considered to be less than 140/90 mm Hg. Patients not adhering to medication were not included in the analysis.

RESULTS: The group of controlled hypertension included 146 (57%) patients out of 256, controlled resistant hypertension 36 (14%) patients, uncontrolled hypertension 6 (2.3%) patients, resistant uncontrolled hypertension 22 (8.6%) patients, refractory hypertension 31 (12.1%) patients. The group of probably resistant hypertension 6 (2.3%) patients, probably refractory hypertension 9 (3.5%) patients. Of the 28 events that occurred, 6 were attributed to coronary artery disease (including 3 acute myocardial infarction and 2 coronary artery stenting), 3 strokes, 6 episodes of transient ischemic attack and 10 new cases of atrial fibrillation, and 2 patients had sudden cardiac death. Significantly more often, patients with refractory hypertension developed any event compared with patients with controlled (38.7% versus 3.4%; p=0.005) and resistant hypertension (38.7% versus 13.6%; p=0.04). Also, patients from the group of probably refractory hypertension were more likely to develop events than patients with controlled hypertension (33.3% versus 3.4%; p=0.045). Patients with probably refractory hypertension significantly more often had a stroke than patients with controlled hypertension (22.2% versus 0%; p0.05), and patients with refractory hypertension significantly more often had a transient ischemic attack compared with patients from the group of controlled hypertension (12.9% versus 0.7%; p=0.03).

CONCLUSION: Patients with refractory and probably refractory hypertension are significantly more likely to develop cardiovascular and cerebrovascular complications than patients with controlled hypertension.}, } @article {pmid36286869, year = {2021}, author = {Solntseva, TD and Denisova, AR and Sivakova, OA and Danilov, NM and Pevzner, DV and Chazova, IE}, title = {[The clinical case of successful combined treatment of refractory arterial hypertension. Case report].}, journal = {Terapevticheskii arkhiv}, volume = {93}, number = {9}, pages = {1086-1090}, doi = {10.26442/00403660.2021.09.201035}, pmid = {36286869}, issn = {0040-3660}, mesh = {Humans ; *Antihypertensive Agents/therapeutic use ; *Hypertension/diagnosis/drug therapy ; Blood Pressure ; Kidney ; Combined Modality Therapy ; Sympathectomy ; Treatment Outcome ; }, abstract = {In recent years, there has been an increase of patients with arterial hypertension, one of the variants of which is refractory arterial hypertension. This unfavorable clinical variant of the course of hypertension worries clinicians, due to the higher risk of developing cardiovascular complications, realizing the need for a better control of blood pressure. The presented clinical case demonstrates the successful combined treatment of refractory hypertension using antihypertensive therapy and renal denervation.}, } @article {pmid36253794, year = {2022}, author = {Bergman, J and Schierup, MH}, title = {Evolutionary dynamics of pseudoautosomal region 1 in humans and great apes.}, journal = {Genome biology}, volume = {23}, number = {1}, pages = {215}, pmid = {36253794}, issn = {1474-760X}, mesh = {Animals ; Female ; *Hominidae/genetics ; Humans ; Male ; Nucleotides ; *Pseudoautosomal Regions ; Receptor, PAR-1/genetics ; Y Chromosome/genetics ; }, abstract = {BACKGROUND: The pseudoautosomal region 1 (PAR1) is a 2.7 Mb telomeric region of human sex chromosomes. PAR1 has a crucial role in ensuring proper segregation of sex chromosomes during male meiosis, exposing it to extreme recombination and mutation processes. We investigate PAR1 evolution using population genomic datasets of extant humans, eight populations of great apes, and two archaic human genome sequences.

RESULTS: We find that PAR1 is fast evolving and closer to evolutionary nucleotide equilibrium than autosomal telomeres. We detect a difference between substitution patterns and extant diversity in PAR1, mainly driven by the conflict between strong mutation and recombination-associated fixation bias at CpG sites. We detect excess C-to-G mutations in PAR1 of all great apes, specific to the mutagenic effect of male recombination. Despite recent evidence for Y chromosome introgression from humans into Neanderthals, we find that the Neanderthal PAR1 retained similarity to the Denisovan sequence. We find differences between substitution spectra of these archaics suggesting rapid evolution of PAR1 in recent hominin history. Frequency analysis of alleles segregating in females and males provided no evidence for recent sexual antagonism in this region. We study repeat content and double-strand break hotspot regions in PAR1 and find that they may play roles in ensuring the obligate X-Y recombination event during male meiosis.

CONCLUSIONS: Our study provides an unprecedented quantification of population genetic forces governing PAR1 biology across extant and extinct hominids. PAR1 evolutionary dynamics are predominantly governed by recombination processes with a strong impact on mutation patterns across all species.}, } @article {pmid36181428, year = {2022}, author = {Huang, X and Kruisz, P and Kuhlwilm, M}, title = {sstar: A Python Package for Detecting Archaic Introgression from Population Genetic Data with S.}, journal = {Molecular biology and evolution}, volume = {39}, number = {11}, pages = {}, pmid = {36181428}, issn = {1537-1719}, mesh = {Humans ; Animals ; *Genome, Human ; *Neanderthals/genetics ; Genetics, Population ; }, abstract = {S* is a widely used statistic for detecting archaic admixture from population genetic data. Previous studies used freezing-archer to apply S*, which is only directly applicable to the specific case of Neanderthal and Denisovan introgression in Papuans. Here, we implemented sstar for a more general purpose. Compared with several tools, including SPrime, SkovHMM, and ArchaicSeeker2.0, for detecting introgressed fragments with simulations, our results suggest that sstar is robust to differences in demographic models, including ghost introgression and two-source introgression. We believe sstar will be a useful tool for detecting introgressed fragments in various scenarios and in non-human species.}, } @article {pmid36136946, year = {2022}, author = {Denisova, NN and Keshabyants, EE and Martinchik, AN}, title = {[Analysis of the diet and food structure of the daily diet of children aged 3-17 years in the Russian Federation].}, journal = {Voprosy pitaniia}, volume = {91}, number = {4}, pages = {54-63}, doi = {10.33029/0042-8833-2022-91-4-54-63}, pmid = {36136946}, issn = {0042-8833}, mesh = {Adolescent ; Child ; *Diet ; *Energy Intake ; Feeding Behavior ; Humans ; Meals ; Nutritional Status ; Sugars ; }, abstract = {A healthy diet is a necessary condition for the normal physical and mental development of children, which has a significant impact on the ability to withstand the effects of adverse environmental factors and determines the health of future generations. Healthy nutrition of children and adolescents is important not only for the normal physical and mental development of the child, but also as a factor determining the health of future generations. It is important for the preservation of the child's health to have a proper diet, that is, the distribution of the amount of food during the day (the multiplicity of meals), its energy value, chemical composition, food set for individual meals, a certain time of intake and the duration of intervals between meals. The aim of the study - to analyze the diet, nutrient and energy consumption and the structure of the food set of various meals in children aged 3-17 years. Material and methods. Analysis of the actual nutrition of about 18 000 children on the basis of primary materials obtained by the Federal State Statistics Service during the Selective observation of the diets of the population. Results. An analysis of nutrition of children aged 3-17 showed that the majority of children (67.9%) had three main meals with a hot meal (breakfast, lunch, dinner), while they accounted for the largest amounts of energy consumption in all age groups. Supplementary meals (evening snack and second breakfast) were characterized by the lowest calorie value, the afternoon snack occupied an intermediate position in terms of energy consumption. At the same time, energy consumption with the main meals as a % of the daily calorie intake did not correspond to the recommended values. A shift in energy consumption to the second half of the day, including just before bedtime, was revealed, especially in older children, which is a bad eating habit that can contribute to weight gain in a child. Bread products, cereals and cereal dishes made the greatest contribution to the daily calorie intake of children of all ages (32.4- 33.0%). Meat products occupied the second position in the share of daily calorie content (12.8-21.2%), dairy products provided 9.5-14.0% of daily energy, and among preschoolers their consumption, in contrast to meat products, was the highest, and among older schoolchildren - the lowest. An additional 8.3 to 14.9% of energy came from sugars found in non-dairy drinks, confectionery, chocolate, jams, and other sweets. Conclusion. An analysis of the diet and food structure of the daily ration of children aged 3-17 revealed deviations from the principles of healthy eating, especially in schoolchildren: energy consumption with the main meals did not meet the recommended norms, a significant proportion of the calorie intake fell on the second half of the day. Differences in the contribution of meals, as well as individual foods and dishes, to the total daily calorie value of diets in children, depending on age, have been established.}, } @article {pmid36118278, year = {2022}, author = {Gliagias, V and Denisova, K and Kang, JJ}, title = {A child with dendritiform eye lesions and developmental delay.}, journal = {American journal of ophthalmology case reports}, volume = {28}, number = {}, pages = {101701}, pmid = {36118278}, issn = {2451-9936}, abstract = {PURPOSE: Tyrosinemia Type II (Richner-Hanhart syndrome) is a rare autosomal recessive disease that occurs due to deficiency in the enzyme tyrosine aminotransferase and can result in an ulcerated keratitis. We present a case of a young patient with oculocutaneous tyrosinemia despite a negative newborn screen.

OBSERVATIONS: A 15 month old boy with an uncomplicated birth history and negative newborn screen presented with a unilateral central irregular epithelial defect and hyperkeratotic lesions on his fingertips and soles. A month later, the patient developed bilateral dendritiform epithelial erosions. Following a series of antiviral, antibiotic, and lubricating treatments, there was a waxing and waning course of epithelial healing. After the patient was lost to follow up for one year, the patient presented with a new global developmental delay prompting further workup. Tyrosine and phenylalanine levels were ordered which confirmed a diagnosis of Tyrosinemia Type II, and the patient was started on a low-protein diet. A month later, the patient's epithelial defects and ocular symptoms were resolved.

CONCLUSION AND IMPORTANCE: Presentation of a dendritiform epithelial erosion, whether unilateral or bilateral, accompanied by symptoms of developmental delay and palmoplantar hyperkeratotic lesions should prompt measurement of tyrosine and phenylalanine levels. As dermatologic lesions and variable developmental delay may not appear until later in the course of disease, diagnosis may depend on early recognition of ocular signs and symptoms even with negative newborn screening. Prompt diagnosis and diet modification is necessary to prevent developmental delay in this disease. To our knowledge, this is the first Tyrosinemia Type II case in the literature manifesting as an asynchronous bilateral eye disease.}, } @article {pmid36064759, year = {2022}, author = {Harvati, K and Ackermann, RR}, title = {Merging morphological and genetic evidence to assess hybridization in Western Eurasian late Pleistocene hominins.}, journal = {Nature ecology & evolution}, volume = {6}, number = {10}, pages = {1573-1585}, pmid = {36064759}, issn = {2397-334X}, mesh = {Animals ; DNA, Ancient ; Fossils ; *Hominidae/anatomy & histology/genetics ; Humans ; Hybridization, Genetic ; Mammals/genetics ; *Neanderthals/genetics ; }, abstract = {Previous scientific consensus saw human evolution as defined by adaptive differences (behavioural and/or biological) and the emergence of Homo sapiens as the ultimate replacement of non-modern groups by a modern, adaptively more competitive group. However, recent research has shown that the process underlying our origins was considerably more complex. While archaeological and fossil evidence suggests that behavioural complexity may not be confined to the modern human lineage, recent palaeogenomic work shows that gene flow between distinct lineages (for example, Neanderthals, Denisovans, early H. sapiens) occurred repeatedly in the late Pleistocene, probably contributing elements to our genetic make-up that might have been crucial to our success as a diverse, adaptable species. Following these advances, the prevailing human origins model has shifted from one of near-complete replacement to a more nuanced view of partial replacement with considerable reticulation. Here we provide a brief introduction to the current genetic evidence for hybridization among hominins, its prevalence in, and effects on, comparative mammal groups, and especially how it manifests in the skull. We then explore the degree to which cranial variation seen in the fossil record of late Pleistocene hominins from Western Eurasia corresponds with our current genetic and comparative data. We are especially interested in understanding the degree to which skeletal data can reflect admixture. Our findings indicate some correspondence between these different lines of evidence, flag individual fossils as possibly admixed, and suggest that different cranial regions may preserve hybridization signals differentially. We urge further studies of the phenotype to expand our ability to detect the ways in which migration, interaction and genetic exchange have shaped the human past, beyond what is currently visible with the lens of ancient DNA.}, } @article {pmid36044840, year = {2022}, author = {Kaczanowska, J and Ganglberger, F and Chernomor, O and Kargl, D and Galik, B and Hess, A and Moodley, Y and von Haeseler, A and Bühler, K and Haubensak, W}, title = {Molecular archaeology of human cognitive traits.}, journal = {Cell reports}, volume = {40}, number = {9}, pages = {111287}, doi = {10.1016/j.celrep.2022.111287}, pmid = {36044840}, issn = {2211-1247}, mesh = {Animals ; Archaeology ; Cognition/physiology ; Evolution, Molecular ; Genome, Human ; *Hominidae/genetics ; Humans ; Mammals ; *Neanderthals/genetics ; Phenotype ; }, abstract = {The brains and minds of our human ancestors remain inaccessible for experimental exploration. Therefore, we reconstructed human cognitive evolution by projecting nonsynonymous/synonymous rate ratios (ω values) in mammalian phylogeny onto the anatomically modern human (AMH) brain. This atlas retraces human neurogenetic selection and allows imputation of ancestral evolution in task-related functional networks (FNs). Adaptive evolution (high ω values) is associated with excitatory neurons and synaptic function. It shifted from FNs for motor control in anthropoid ancestry (60-41 mya) to attention in ancient hominoids (26-19 mya) and hominids (19-7.4 mya). Selection in FNs for language emerged with an early hominin ancestor (7.4-1.7 mya) and was later accompanied by adaptive evolution in FNs for strategic thinking during recent (0.8 mya-present) speciation of AMHs. This pattern mirrors increasingly complex cognitive demands and suggests that co-selection for language alongside strategic thinking may have separated AMHs from their archaic Denisovan and Neanderthal relatives.}, } @article {pmid35963891, year = {2022}, author = {Denisova, OV and Merisaari, J and Kaur, A and Yetukuri, L and Jumppanen, M and von Schantz-Fant, C and Ohlmeyer, M and Wennerberg, K and Aittokallio, T and Taipale, M and Westermarck, J}, title = {Development of actionable targets of multi-kinase inhibitors (AToMI) screening platform to dissect kinase targets of staurosporines in glioblastoma cells.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {13796}, pmid = {35963891}, issn = {2045-2322}, mesh = {*Antineoplastic Agents ; *Glioblastoma/drug therapy ; Humans ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Protein Phosphatase 2 ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Staurosporine/pharmacology ; }, abstract = {Therapeutic resistance to kinase inhibitors constitutes a major unresolved clinical challenge in cancer and especially in glioblastoma. Multi-kinase inhibitors may be used for simultaneous targeting of multiple target kinases and thereby potentially overcome kinase inhibitor resistance. However, in most cases the identification of the target kinases mediating therapeutic effects of multi-kinase inhibitors has been challenging. To tackle this important problem, we developed an actionable targets of multi-kinase inhibitors (AToMI) strategy and used it for characterization of glioblastoma target kinases of staurosporine derivatives displaying synergy with protein phosphatase 2A (PP2A) reactivation. AToMI consists of interchangeable modules combining drug-kinase interaction assay, siRNA high-throughput screening, bioinformatics analysis, and validation screening with more selective target kinase inhibitors. As a result, AToMI analysis revealed AKT and mitochondrial pyruvate dehydrogenase kinase PDK1 and PDK4 as kinase targets of staurosporine derivatives UCN-01, CEP-701, and K252a that synergized with PP2A activation across heterogeneous glioblastoma cells. Based on these proof-of-principle results, we propose that the application and further development of AToMI for clinically applicable multi-kinase inhibitors could provide significant benefits in overcoming the challenge of lack of knowledge of the target specificity of multi-kinase inhibitors.}, } @article {pmid35927700, year = {2022}, author = {Lee, B and Cyrill, SL and Lee, W and Melchiotti, R and Andiappan, AK and Poidinger, M and Rötzschke, O}, title = {Analysis of archaic human haplotypes suggests that 5hmC acts as an epigenetic guide for NCO recombination.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {173}, pmid = {35927700}, issn = {1741-7007}, mesh = {Alleles ; CpG Islands ; *DNA Methylation ; *Epigenesis, Genetic ; Haplotypes ; Humans ; }, abstract = {BACKGROUND: Non-crossover (NCO) refers to a mechanism of homologous recombination in which short tracks of DNA are copied between homologue chromatids. The allelic changes are typically restricted to one or few SNPs, which potentially allow for the gradual adaptation and maturation of haplotypes. It is assumed to be a stochastic process but the analysis of archaic and modern human haplotypes revealed a striking variability in local NCO recombination rates.

METHODS: NCO recombination rates of 1.9 million archaic SNPs shared with Denisovan hominids were defined by a linkage study and correlated with functional and genomic annotations as well as ChIP-Seq data from modern humans.

RESULTS: We detected a strong correlation between NCO recombination rates and the function of the respective region: low NCO rates were evident in introns and quiescent intergenic regions but high rates in splice sites, exons, 5'- and 3'-UTRs, as well as CpG islands. Correlations with ChIP-Seq data from ENCODE and other public sources further identified epigenetic modifications that associated directly with these recombination events. A particularly strong association was observed for 5-hydroxymethylcytosine marks (5hmC), which were enriched in virtually all of the functional regions associated with elevated NCO rates, including CpG islands and 'poised' bivalent regions.

CONCLUSION: Our results suggest that 5hmC marks may guide the NCO machinery specifically towards functionally relevant regions and, as an intermediate of oxidative demethylation, may open a pathway for environmental influence by specifically targeting recently opened gene loci.}, } @article {pmid35893329, year = {2022}, author = {Deņisova, A and Pilmane, M and Fedirko, P}, title = {Glycosaminoglycan, Antimicrobial Defence Molecule and Cytokine Appearance in Tracheal Hyaline Cartilage of Healthy Humans.}, journal = {Journal of functional morphology and kinesiology}, volume = {7}, number = {3}, pages = {}, pmid = {35893329}, issn = {2411-5142}, abstract = {Hyaline cartilage is an important tracheal structure, yet little is known about its molecular composition, complicating investigation of pathologies and replacement options. Our aim was to research tracheal hyaline cartilage structure, protective tissue factors and variations in healthy humans. The tissue material was obtained from 10 cadavers obtained from the Riga Stradins University Institute of Anatomy and Anthropology archive. Tissues were stained with Bismarck brown and PAS for glycosaminoglycans, and immunohistochemistry was performed for HBD-2, HBD-3, HBD-4, IL-10 and LL-37. The slides were inspected by light microscopy and Spearman's rank correlation coefficient was calculated. The extracellular matrix was positive across hyaline cartilage for PAS, yet Bismarck brown marked positive proliferation and growth zones. Numerous positive cells for both factors were found in all zones. All of the antimicrobial defence molecules and cytokines were found in a moderate number of cells, except in the mature cell zone with few positive cells. Spearman's rank correlation coefficient revealed strong and moderate correlations between studied factors. Hyaline cartilage is a tracheal defence structure with a moderate number of antimicrobial defence protein and cytokine immunoreactive cells as well as numerous glycosaminoglycan positive cells. The extracellular matrix glycosaminoglycans provide structural scaffolding and intercellular signalling. The correlations between the studied factors confirm the synergistic activity of them.}, } @article {pmid35893070, year = {2022}, author = {Perik-Zavodskii, R and Perik-Zavodskaya, O and Shevchenko, Y and Denisova, V and Nazarov, K and Obleuhova, I and Zaitsev, K and Sennikov, S}, title = {Immune Transcriptome and Secretome Differ between Human CD71+ Erythroid Cells from Adult Bone Marrow and Fetal Liver Parenchyma.}, journal = {Genes}, volume = {13}, number = {8}, pages = {}, pmid = {35893070}, issn = {2073-4425}, mesh = {Adult ; *Arginase ; *Bone Marrow ; Erythroid Cells ; Humans ; Liver ; RNA, Messenger ; Secretome ; Transcriptome ; }, abstract = {CD71+ erythroid cells (CECs) were only known as erythrocyte progenitors not so long ago. In present times, however, they have been shown to be active players in immune regulation, especially in immunosuppression by the means of ROS, arginase-1 and arginase-2 production. Here, we uncover organ-of-origin differences in cytokine gene expression using NanoString and protein production using Bio-Plex between CECs from healthy human adult bone marrow and from human fetal liver parenchyma. Namely, healthy human adult bone marrow CECs both expressed and produced IFN-a, IL-1b, IL-8, IL-18 and MIF mRNA and protein, while human fetal liver parenchymaCECs expressed and produced IFN-a, IL15, IL18 and TNF-b mRNA and protein. We also detected TLR2 and TLR9 gene expression in both varieties of CECs and TLR1 and NOD2 gene expression in human fetal liver parenchymaCECs only. These observations suggest that there might be undiscovered roles in immune response for CECs.}, } @article {pmid35884376, year = {2022}, author = {Skryabin, GO and Vinokurova, SV and Galetsky, SA and Elkin, DS and Senkovenko, AM and Denisova, DA and Komelkov, AV and Stilidi, IS and Peregorodiev, IN and Malikhova, OA and Imaraliev, OT and Enikeev, AD and Tchevkina, EM}, title = {Isolation and Characterization of Extracellular Vesicles from Gastric Juice.}, journal = {Cancers}, volume = {14}, number = {14}, pages = {}, pmid = {35884376}, issn = {2072-6694}, support = {22-15-00373//Russian Science Foundation/ ; }, abstract = {EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly used source of EVs for the screening of cancer markers, although the percentage of tumor-derived EVs in the blood is extremely low. In contrast, GJ, as a local biofluid, is expected to be enriched with GC-associated EVs. However, EVs from GJ have never been applied for the screening and are underinvestigated overall. Here we show that EVs can be isolated from GJ by ultracentrifugation. TEM analysis showed high heterogeneity of GJ-derived EVs, including those with exosome-like size and morphology. In addition to morphological diversity, EVs from individual GJ samples differed in the composition of exosomal markers. We also show the presence of stomatin within GJ-derived EVs for the first time. The first conducted comparison of miRNA content in EVs from GC patients and healthy donors performed using a pilot sampling revealed the significant differences in several miRNAs (-135b-3p, -199a-3p, -451a). These results demonstrate the feasibility of the application of GJ-derived EVs for screening for miRNA GC markers.}, } @article {pmid35880026, year = {2022}, author = {Brucato, N and André, M and Hudjashov, G and Mondal, M and Cox, MP and Leavesley, M and Ricaut, FX}, title = {Chronology of natural selection in Oceanian genomes.}, journal = {iScience}, volume = {25}, number = {7}, pages = {104583}, pmid = {35880026}, issn = {2589-0042}, abstract = {As human populations left Asia to first settle in Oceania around 50,000 years ago, they entered a territory ecologically separated from the Old World for millions of years. We analyzed genomic data of 239 modern Oceanian individuals to detect and date signals of selection specific to this region. Combining both relative and absolute dating approaches, we identified a strong selection pattern between 52,000 and 54,000 years ago in the genomes of descendants of the first settlers of Sahul. This strikingly corresponds to the dates of initial settlement as inferred from archaeological evidence. Loci under selection during this period, some showing enrichment in Denisovan ancestry, overlap genes involved in the immune response and diet, especially based on plants. Pathogens and natural resources, especially from endemic plants, therefore appear to have acted as strong selective pressures on the genomes of the first settlers of Sahul.}, } @article {pmid35877346, year = {2022}, author = {Denisova, KR and Orlov, NA and Yakimov, SA and Kirpichnikov, MP and Feofanov, AV and Nekrasova, OV}, title = {Atto488-Agitoxin 2-A Fluorescent Ligand with Increased Selectivity for Kv1.3 Channel Binding Site.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {35877346}, issn = {2306-5354}, support = {22-14-00406//Russian Science Foundation/ ; }, abstract = {Fluorescently labeled peptide blockers of ion channels are useful probes in studying the localization and functioning of the channels and in the performance of a search for new channel ligands with bioengineering screening systems. Here, we report on the properties of Atto488-agitoxin 2 (A-AgTx2), a derivative of the Kv1 channel blocker agitoxin 2 (AgTx2), which was N-terminally labeled with Atto 488 fluorophore. The interactions of A-AgTx2 with the outer binding sites of the potassium voltage-gated Kv1.x (x = 1, 3, 6) channels were studied using bioengineered hybrid KcsA-Kv1.x (x = 1, 3, 6) channels. In contrast to AgTx2, A-AgTx2 was shown to lose affinity for the Kv1.1 and Kv1.6 binding sites but to preserve it for the Kv1.3 site. Thus, Atto488 introduces two new functionalities to AgTx2: fluorescence and the selective targeting of the Kv1.3 channel, which is known for its pharmacological significance. In the case of A-AgTx2, fluorescent labeling served as an alternative to site-directed mutagenesis in modulating the pharmacological profile of the channel blocker. Although the affinity of A-AgTx2 for the Kv1.3 binding site was decreased as compared to the unlabeled AgTx2, its dissociation constant value was within a low nanomolar range (4.0 nM). The properties of A-AgTx2 allow one to use it for the search and study of Kv1.3 channel blockers as well as to consider it for the imaging of the Kv1.3 channel in cells and tissues.}, } @article {pmid35816093, year = {2022}, author = {Peyrégne, S and Kelso, J and Peter, BM and Pääbo, S}, title = {The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35816093}, issn = {2050-084X}, support = {694707/ERC_/European Research Council/International ; }, mesh = {Animals ; Biological Evolution ; Black People ; Fossils ; Gene Flow ; *Hominidae/genetics ; Humans ; *Neanderthals/genetics ; }, abstract = {Proteins associated with the spindle apparatus, a cytoskeletal structure that ensures the proper segregation of chromosomes during cell division, experienced an unusual number of amino acid substitutions in modern humans after the split from the ancestors of Neandertals and Denisovans. Here, we analyze the history of these substitutions and show that some of the genes in which they occur may have been targets of positive selection. We also find that the two changes in the kinetochore scaffold 1 (KNL1) protein, previously believed to be specific to modern humans, were present in some Neandertals. We show that the KNL1 gene of these Neandertals shared a common ancestor with present-day Africans about 200,000 years ago due to gene flow from the ancestors (or relatives) of modern humans into Neandertals. Subsequently, some non-Africans inherited this modern human-like gene variant from Neandertals, but none inherited the ancestral gene variants. These results add to the growing evidence of early contacts between modern humans and archaic groups in Eurasia and illustrate the intricate relationships among these groups.}, } @article {pmid35809046, year = {2022}, author = {Saha, S and Khan, N and Comi, T and Verhagen, A and Sasmal, A and Diaz, S and Yu, H and Chen, X and Akey, JM and Frank, M and Gagneux, P and Varki, A}, title = {Evolution of Human-Specific Alleles Protecting Cognitive Function of Grandmothers.}, journal = {Molecular biology and evolution}, volume = {39}, number = {8}, pages = {}, pmid = {35809046}, issn = {1537-1719}, support = {R01 GM032373/GM/NIGMS NIH HHS/United States ; R01 GM110068/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Amino Acids ; Animals ; Cognition ; *Grandparents ; *Hominidae/genetics ; Humans ; }, abstract = {The myelomonocytic receptor CD33 (Siglec-3) inhibits innate immune reactivity by extracellular V-set domain recognition of sialic acid (Sia)-containing "self-associated molecular patterns" (SAMPs). We earlier showed that V-set domain-deficient CD33-variant allele, protective against late-onset Alzheimer's Disease (LOAD), is derived and specific to the hominin lineage. We now report multiple hominin-specific CD33 V-set domain mutations. Due to hominin-specific, fixed loss-of-function mutation in the CMAH gene, humans lack N-glycolylneuraminic acid (Neu5Gc), the preferred Sia-ligand of ancestral CD33. Mutational analysis and molecular dynamics (MD)-simulations indicate that fixed change in amino acid 21 of hominin V-set domain and conformational changes related to His45 corrected for Neu5Gc-loss by switching to N-acetylneuraminic acid (Neu5Ac)-recognition. We show that human-specific pathogens Neisseria gonorrhoeae and Group B Streptococcus selectively bind human CD33 (huCD33) as part of immune-evasive molecular mimicry of host SAMPs and that this binding is significantly impacted by amino acid 21 modification. In addition to LOAD-protective CD33 alleles, humans harbor derived, population-universal, cognition-protective variants at several other loci. Interestingly, 11 of 13 SNPs in these human genes (including CD33) are not shared by genomes of archaic hominins: Neanderthals and Denisovans. We present a plausible evolutionary scenario to compile, correlate, and comprehend existing knowledge about huCD33-evolution and suggest that grandmothering emerged in humans.}, } @article {pmid35806305, year = {2022}, author = {Filippenkov, IB and Remizova, JA and Denisova, AE and Stavchansky, VV and Golovina, KD and Gubsky, LV and Limborska, SA and Dergunova, LV}, title = {Comparative Use of Contralateral and Sham-Operated Controls Reveals Traces of a Bilateral Genetic Response in the Rat Brain after Focal Stroke.}, journal = {International journal of molecular sciences}, volume = {23}, number = {13}, pages = {}, pmid = {35806305}, issn = {1422-0067}, support = {21-34-70048//RFBR and Moscow city Government/ ; 19-14-00268//Russian Science Foundation/ ; }, mesh = {Animals ; Brain/metabolism ; *Brain Ischemia/metabolism ; Disease Models, Animal ; Infarction, Middle Cerebral Artery/complications/genetics ; Rats ; Sequence Analysis, RNA ; *Stroke/etiology ; }, abstract = {Ischemic stroke is a multifactorial disease with a complex etiology and global consequences. Model animals are widely used in stroke studies. Various controls, either brain samples from sham-operated (SO) animals or symmetrically located brain samples from the opposite (contralateral) hemisphere (CH), are often used to analyze the processes in the damaged (ipsilateral) hemisphere (IH) after focal stroke. However, previously, it was shown that focal ischemia can lead to metabolic and transcriptomic changes not only in the IH but also in the CH. Here, using a transient middle cerebral artery occlusion (tMCAO) model and genome-wide RNA sequencing, we identified 1941 overlapping differentially expressed genes (DEGs) with a cutoff value >1.5 and Padj < 0.05 that reflected the general transcriptome response of IH subcortical cells at 24 h after tMCAO using both SO and CH controls. Concomitantly, 861 genes were differentially expressed in IH vs. SO, whereas they were not vs. the CH control. Furthermore, they were associated with apoptosis, the cell cycle, and neurotransmitter responses. In turn, we identified 221 DEGs in IH vs. CH, which were non-DEGs vs. the SO control. Moreover, they were predominantly associated with immune-related response. We believe that both sets of non-overlapping genes recorded transcriptome changes in IH cells associated with transhemispheric differences after focal cerebral ischemia. Thus, the specific response of the CH transcriptome should be considered when using it as a control in studies of target brain regions in diseases that induce a global bilateral genetic response, such as stroke.}, } @article {pmid35757177, year = {2022}, author = {Theofanopoulou, C and Andirkó, A and Boeckx, C and Jarvis, ED}, title = {Oxytocin and vasotocin receptor variation and the evolution of human prosociality.}, journal = {Comprehensive psychoneuroendocrinology}, volume = {11}, number = {}, pages = {100139}, pmid = {35757177}, issn = {2666-4976}, abstract = {Modern human lifestyle strongly depends on complex social traits like empathy, tolerance and cooperation. These diverse facets of social cognition have been associated with variation in the oxytocin receptor (OTR) and its sister genes, the vasotocin/vasopressin receptors (VTR1A/AVPR1A and AVPR1B/VTR1B). Here, we compared the available genomic sequences of these receptors between modern humans, archaic humans, and 12 non-human primate species, and identified sites that show heterozygous variation in modern humans and archaic humans distinct from variation in other primates, and for which we could find association studies with clinical implications. On these sites, we performed a range of analyses (variant clustering, pathogenicity prediction, regulation, linkage disequilibrium frequency), and reviewed the literature on selection data in different modern-human populations. We found five sites with modern human specific variation, where the modern human allele is the major allele in the global population (OTR: rs1042778, rs237885, rs6770632; VTR1A: rs10877969; VTR1B: rs33985287). Among them, variation in the OTR-rs6770632 site was predicted to be the most functional. Two alleles (OTR: rs59190448 and rs237888) present only in modern humans and archaic humans were putatively under positive selection in modern humans, with rs237888 predicted to be a highly functional site. Three sites showed convergent evolution between modern humans and bonobos (OTR: rs2228485 and rs237897; VTR1A: rs1042615), with OTR-rs2228485 ranking highly in terms of functionality and reported to be under balancing selection in modern humans (Schaschl, 2015) [1]. Our findings have implications for understanding hominid prosociality, as well as the similarities between modern human and bonobo social behavior.}, } @article {pmid35754742, year = {2022}, author = {Ponomarev, GV and Fatykhov, B and Nazarov, VA and Abasov, R and Shvarov, E and Landik, NV and Denisova, AA and Chervova, AA and Gelfand, MS and Kazanov, MD}, title = {APOBEC mutagenesis is low in most types of non-B DNA structures.}, journal = {iScience}, volume = {25}, number = {7}, pages = {104535}, pmid = {35754742}, issn = {2589-0042}, abstract = {While somatic mutations are known to be enriched in genome regions with non-canonical DNA secondary structure, the impact of particular mutagens still needs to be elucidated. Here, we demonstrate that in human cancers, the APOBEC mutagenesis is not enriched in direct repeats, mirror repeats, short tandem repeats, and G-quadruplexes, and even decreased below its level in B-DNA for cancer samples with very high APOBEC activity. In contrast, we observe that the APOBEC-induced mutational density is positively associated with APOBEC activity in inverted repeats (cruciform structures), where the impact of cytosine at the 3'-end of the hairpin loop is substantial. Surprisingly, the APOBEC-signature mutation density per TC motif in the single-stranded DNA of a G-quadruplex (G4) is lower than in the four-stranded part of G4 and in B-DNA. The APOBEC mutagenesis, as well as the UV-mutagenesis in melanoma samples, are absent in Z-DNA regions, owing to the depletion of their mutational signature motifs.}, } @article {pmid35729694, year = {2022}, author = {Ping, WJ and Liu, YC and Fu, QM}, title = {Exploring the evolution of archaic humans through sedimentary ancient DNA.}, journal = {Yi chuan = Hereditas}, volume = {44}, number = {5}, pages = {362-369}, doi = {10.16288/j.yczz.22-032}, pmid = {35729694}, issn = {0253-9772}, mesh = {Animals ; DNA, Ancient ; DNA, Mitochondrial/genetics ; Genome, Human ; *Hominidae/genetics ; Humans ; *Neanderthals/genetics ; }, abstract = {Recent success in the retrieval of nuclear DNA of ancient humans and animals from cave sediments paves the way for genome-wide studies of past populations directly from sediments. In three studies, nuclear genomes of different species were obtained from the sediments of multiple archeological caves and their genetic histories were revealed, including an unknown population replacement of Neanderthals from Estatuas cave in Spain, which was recovered using a new DNA capture approach. By extending sediments as a source of DNA beyond fossils, this breakthrough is of particular significance to the field of ancient human genomics, which brings about more possibilities for exploring the history of past population migration, evolution and adaptation within larger time-scales and geographical areas where no fossil remains exist. Here, we mainly review the significance of the technical advances in retrieving ancient nuclear DNA from sediments and present new insights into the genetic history of Neanderthals revealed by this technique. By combining ancient genomes retrieved from fossils and additional mitochondrial DNA extracted from sediments of archaeological sites, we may begin investigating diverse archaic populations and examine their genetic relationships, movements and replacements in detail.}, } @article {pmid35727217, year = {2022}, author = {Kulikovskaya, NS and Denisova, EA and Ananikov, VP}, title = {A novel approach to study catalytic reactions via electrophoretic NMR on the example of Pd/NHC-catalyzed Mizoroki-Heck cross-coupling reaction.}, journal = {Magnetic resonance in chemistry : MRC}, volume = {60}, number = {10}, pages = {954-962}, doi = {10.1002/mrc.5295}, pmid = {35727217}, issn = {1097-458X}, support = {20-33-90226//Russian Foundation for Basic Research/ ; }, mesh = {Catalysis ; Magnetic Resonance Spectroscopy ; *Palladium/chemistry ; }, abstract = {Investigation of catalytic reactions using nuclear magnetic resonance (NMR) is a crucial task, which is often challenging to perform due to rather complex transformations at the metal center. In this work, it was shown that electrophoretic NMR can be a suitable method for studying catalytic reactions and for observing the changes in the catalyst nature. As an important example involving palladium catalysts with N-heterocyclic carbine ligands (NHCs), the breakage of the Pd-NHC bond can occur during the catalytic process. Electrophoretic NMR allows the distinction of compounds in the spectra depending on the charge, thus bringing new opportunities to mechanistic studies. Here, we present independent evidence of R-NHC product formation in the Pd-catalyzed Mizoroki-Heck reaction-the key process for catalyst change from the molecular to nano-scale type.}, } @article {pmid35718977, year = {2022}, author = {Rusina, PV and Lisov, AA and Denisova, AA and Gandalipov, ER and Novikov, FN and Shtil, AA}, title = {Clinical CDK2 Inhibitors: Trends to Selectivity and Efficacy.}, journal = {Recent patents on anti-cancer drug discovery}, volume = {18}, number = {2}, pages = {102-107}, doi = {10.2174/1574892817666220617091700}, pmid = {35718977}, issn = {2212-3970}, mesh = {Humans ; *Cyclin-Dependent Kinase 2/metabolism ; Phosphorylation ; }, } @article {pmid35667800, year = {2022}, author = {Denisova, NP and Rzaev, JA}, title = {Psychiatric mimics of neurosurgical disorders.}, journal = {Progress in brain research}, volume = {272}, number = {1}, pages = {153-171}, doi = {10.1016/bs.pbr.2022.03.009}, pmid = {35667800}, issn = {1875-7855}, mesh = {Brain ; *Brain Diseases ; Humans ; *Nervous System Diseases/surgery ; Neurosurgical Procedures ; *Spinal Cord Injuries ; }, abstract = {Every year there are about 22.6 million people in need of neurosurgical care around the world, and one or several interventions are required to save lives and restore functional losses in more than half of these cases (13.8 million). Most neurosurgical interventions are performed in patients with traumatic brain and spinal cord injuries, strokes, central nervous system (CNS) tumors, hydrocephalus, and epilepsy. In addition to neurological symptoms, many CNS disorders are often accompanied by cognitive and/or behavioral changes. Physical and psychological symptoms can be intertwined as follows: 1) neurological symptoms may be manifested as a result of complex psychological processes; 2) psychological disorders may be manifested as neurological symptoms; 3) neurological disorders commonly cause secondary psychological responses; 4) psychological disorder may be induced more or less directly by an organic brain disease. In the present paper, we focus on the psychiatric conditions occurring in the patients with neurosurgical disorders who either get prepared for surgery or have already received it.}, } @article {pmid35622251, year = {2022}, author = {Sobolev, VV and Denisova, EV and Chebysheva, SN and Geppe, NA and Korsunskaya, IM}, title = {IL-6 Gene Expression as a Marker of Pathological State in Psoriasis and Psoriatic Arthritis.}, journal = {Bulletin of experimental biology and medicine}, volume = {173}, number = {1}, pages = {77-80}, pmid = {35622251}, issn = {1573-8221}, mesh = {*Arthritis, Psoriatic/diagnosis/genetics/metabolism ; Biomarkers/metabolism ; Gene Expression ; Humans ; *Interleukin-6/biosynthesis/genetics ; *Psoriasis/diagnosis/genetics/metabolism ; }, abstract = {The expression of the IL-6 gene in mononuclear blood cells of 45 patients with psoriatic arthritis and 31 patients with plaque psoriasis was studied for possible differential diagnosis of the pathologies. The expression level of IL-6 in psoriatic arthritis and psoriasis surpassed that in healthy controls by 192 and 147 times, respectively. Significant differences in the gene expression were revealed between the patients with psoriatic arthritis and mild psoriasis. The level of IL-6 in patients with severe psoriasis approached that in patients with psoriatic arthritis. High level of IL-6 gene expression can be a marker of possible joint damage in patients with psoriasis and a signal for revising the therapeutic approach in a particular patient.}, } @article {pmid35596005, year = {2022}, author = {Shchenkov, SV and Sokolov, SG and Tsushko, KM and Denisova, SA}, title = {Is Gymnophallus Odhner, 1900 (Trematoda: Gymnophallidae) polyphyletic? A new hypothesis based on phylogenetic position of Gymnophallus deliciosus (Olsson, 1893).}, journal = {Parasitology research}, volume = {121}, number = {7}, pages = {2157-2160}, pmid = {35596005}, issn = {1432-1955}, mesh = {Animals ; DNA, Ribosomal/genetics ; Phylogeny ; RNA, Ribosomal, 28S/genetics ; *Trematoda/genetics ; }, abstract = {Gymnophallus deliciosus is a type species of the genus Gymnophallus. We collected this trematode species from gallbladder of Larus argentatus caught in the White Sea (Kandalaksha Bay, Chupa Inlet) and obtained the sequences of its nuclear 18S and 28S rDNA genes. Our recently obtained phylogenetic data support a sister group relationship of this species with G. choledochus. However, other species of the genus Gymnophallus-G. australis (KM246854) and G. minutus (KM268111)-do not branch with the group G. choledochus + G. deliciosus or with each other. Our study revealed that the genus Gynmnophallus is probably a polyphyletic taxon, and the genus affiliation of its representatives should be re-examined in future.}, } @article {pmid35595994, year = {2022}, author = {Graham, F}, title = {Daily briefing: Tooth suggests Denisovans roamed Asia.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-022-01413-8}, pmid = {35595994}, issn = {1476-4687}, } @article {pmid35581413, year = {2022}, author = {Kreier, F}, title = {Ancient tooth suggests Denisovans ventured far beyond Siberia.}, journal = {Nature}, volume = {605}, number = {7911}, pages = {602-603}, pmid = {35581413}, issn = {1476-4687}, mesh = {Animals ; Fossils ; *Hominidae ; Population Dynamics ; Siberia ; *Tooth ; }, } @article {pmid35581187, year = {2022}, author = {Demeter, F and Zanolli, C and Westaway, KE and Joannes-Boyau, R and Duringer, P and Morley, MW and Welker, F and Rüther, PL and Skinner, MM and McColl, H and Gaunitz, C and Vinner, L and Dunn, TE and Olsen, JV and Sikora, M and Ponche, JL and Suzzoni, E and Frangeul, S and Boesch, Q and Antoine, PO and Pan, L and Xing, S and Zhao, JX and Bailey, RM and Boualaphane, S and Sichanthongtip, P and Sihanam, D and Patole-Edoumba, E and Aubaile, F and Crozier, F and Bourgon, N and Zachwieja, A and Luangkhoth, T and Souksavatdy, V and Sayavongkhamdy, T and Cappellini, E and Bacon, AM and Hublin, JJ and Willerslev, E and Shackelford, L}, title = {A Middle Pleistocene Denisovan molar from the Annamite Chain of northern Laos.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {2557}, pmid = {35581187}, issn = {2041-1723}, mesh = {Animals ; Bayes Theorem ; Female ; Fossils ; *Hominidae/anatomy & histology ; Humans ; Laos ; Molar ; }, abstract = {The Pleistocene presence of the genus Homo in continental Southeast Asia is primarily evidenced by a sparse stone tool record and rare human remains. Here we report a Middle Pleistocene hominin specimen from Laos, with the discovery of a molar from the Tam Ngu Hao 2 (Cobra Cave) limestone cave in the Annamite Mountains. The age of the fossil-bearing breccia ranges between 164-131 kyr, based on the Bayesian modelling of luminescence dating of the sedimentary matrix from which it was recovered, U-series dating of an overlying flowstone, and U-series-ESR dating of associated faunal teeth. Analyses of the internal structure of the molar in tandem with palaeoproteomic analyses of the enamel indicate that the tooth derives from a young, likely female, Homo individual. The close morphological affinities with the Xiahe specimen from China indicate that they belong to the same taxon and that Tam Ngu Hao 2 most likely represents a Denisovan.}, } @article {pmid35557944, year = {2022}, author = {Buisan, R and Moriano, J and Andirkó, A and Boeckx, C}, title = {A Brain Region-Specific Expression Profile for Genes Within Large Introgression Deserts and Under Positive Selection in Homo sapiens.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {824740}, pmid = {35557944}, issn = {2296-634X}, abstract = {Analyses of ancient DNA from extinct hominins have provided unique insights into the complex evolutionary history of Homo sapiens, intricately related to that of the Neanderthals and the Denisovans as revealed by several instances of admixture events. These analyses have also allowed the identification of introgression deserts: genomic regions in our species that are depleted of "archaic" haplotypes. The presence of genes like FOXP2 in these deserts has been taken to be suggestive of brain-related functional differences between Homo species. Here, we seek a deeper characterization of these regions and the specific expression trajectories of genes within them, taking into account signals of positive selection in our lineage. Analyzing publicly available transcriptomic data from the human brain at different developmental stages, we found that structures outside the cerebral neocortex, in particular the cerebellum, the striatum and the mediodorsal nucleus of the thalamus show the most divergent transcriptomic profiles when considering genes within large introgression deserts and under positive selection.}, } @article {pmid35546225, year = {2022}, author = {Andirkó, A and Boeckx, C}, title = {Brain region-specific effects of nearly fixed sapiens-derived alleles.}, journal = {BMC genomic data}, volume = {23}, number = {1}, pages = {36}, pmid = {35546225}, issn = {2730-6844}, mesh = {Alleles ; Animals ; Brain/metabolism ; Gene Expression Regulation ; Humans ; *Neanderthals/genetics ; }, abstract = {The availability of high-coverage genomes of our extinct relatives, the Neanderthals and Denisovans, and the emergence of large, tissue-specific databases of modern human genetic variation, offer the possibility of probing the effects of modern-derived alleles in specific tissues, such as the brain, and its specific regions. While previous research has explored the effects of introgressed variants in gene expression, the effects of Homo sapiens-specific gene expression variability are still understudied. Here we identify derived, Homo sapiens-specific high-frequency (≥90%) alleles that are associated with differential gene expression across 15 brain structures derived from the GTEx database. We show that regulation by these derived variants targets regions under positive selection more often than expected by chance, and that high-frequency derived alleles lie in functional categories related to transcriptional regulation. Our results highlight the role of these variants in gene regulation in specific regions like the cerebellum and pituitary.}, } @article {pmid35440148, year = {2022}, author = {Brand, CM and Colbran, LL and Capra, JA}, title = {Predicting Archaic Hominin Phenotypes from Genomic Data.}, journal = {Annual review of genomics and human genetics}, volume = {23}, number = {}, pages = {591-612}, pmid = {35440148}, issn = {1545-293X}, support = {R35 GM127087/GM/NIGMS NIH HHS/United States ; T32 HG009495/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; DNA, Ancient ; Genome, Human ; Genomics ; *Hominidae/genetics ; Humans ; *Neanderthals/genetics ; Phenotype ; }, abstract = {Ancient DNA provides a powerful window into the biology of extant and extinct species, including humans' closest relatives: Denisovans and Neanderthals. Here, we review what is known about archaic hominin phenotypes from genomic data and how those inferences have been made. We contend that understanding the influence of variants on lower-level molecular phenotypes-such as gene expression and protein function-is a promising approach to using ancient DNA to learn about archaic hominin traits. Molecular phenotypes have simpler genetic architectures than organism-level complex phenotypes, and this approach enables moving beyond association studies by proposing hypotheses about the effects of archaic variants that are testable in model systems. The major challenge to understanding archaic hominin phenotypes is broadening our ability to accurately map genotypes to phenotypes, but ongoing advances ensure that there will be much more to learn about archaic hominin phenotypes from their genomes.}, } @article {pmid35406627, year = {2022}, author = {Skryabin, GO and Komelkov, AV and Zhordania, KI and Bagrov, DV and Vinokurova, SV and Galetsky, SA and Elkina, NV and Denisova, DA and Enikeev, AD and Tchevkina, EM}, title = {Extracellular Vesicles from Uterine Aspirates Represent a Promising Source for Screening Markers of Gynecologic Cancers.}, journal = {Cells}, volume = {11}, number = {7}, pages = {}, pmid = {35406627}, issn = {2073-4409}, mesh = {Biomarkers/metabolism ; Early Detection of Cancer ; *Exosomes/metabolism ; *Extracellular Vesicles/metabolism ; Female ; Humans ; *MicroRNAs/metabolism ; *Neoplasms/metabolism ; Uterus/metabolism ; }, abstract = {Extracellular vesicles (EVs), including exosomes, are key factors of intercellular communication, performing both local and distant transfers of bioactive molecules. The increasingly obvious role of EVs in carcinogenesis, similarity of molecular signatures with parental cells, precise selection and high stability of cargo molecules make exosomes a promising source of liquid biopsy markers for cancer diagnosis. The uterine cavity fluid, unlike blood, urine and other body fluids commonly used to study EVs, is of local origin and therefore enriched in EVs secreted by cells of the female reproductive tract. Here, we show that EVs, including those corresponding to exosomes, could be isolated from individual samples of uterine aspirates (UA) obtained from epithelial ovarian cancer (EOC) patients and healthy donors using the ultracentrifugation technique. First, the conducted profiling of small RNAs (small RNA-seq) from UA-derived EVs demonstrated the presence of non-coding RNA molecules belonging to various classes. The analysis of the miRNA content in EVs from UA performed on a pilot sample revealed significant differences in the expression levels of a number of miRNAs in EVs obtained from EOC patients compared to healthy individuals. The results open up prospects for using UA-derived EVs as a source of markers for the diagnostics of gynecological cancers, including EOC.}, } @article {pmid35359699, year = {2022}, author = {Molodtseva, AS and Makunin, AI and Salomashkina, VV and Kichigin, IG and Vorobieva, NV and Vasiliev, SK and Shunkov, MV and Tishkin, AA and Grushin, SP and Anijalg, P and Tammeleht, E and Keis, M and Boeskorov, GG and Mamaev, N and Okhlopkov, IM and Kryukov, AP and Lyapunova, EA and Kholodova, MV and Seryodkin, IV and Saarma, U and Trifonov, VA and Graphodatsky, AS}, title = {Phylogeography of ancient and modern brown bears from eastern Eurasia.}, journal = {Biological journal of the Linnean Society. Linnean Society of London}, volume = {135}, number = {4}, pages = {722-733}, pmid = {35359699}, issn = {0024-4066}, support = {/WT_/Wellcome Trust/United Kingdom ; 206194/WT_/Wellcome Trust/United Kingdom ; }, abstract = {The brown bear (Ursus arctos) is an iconic carnivoran species of the Northern Hemisphere. Its population history has been studied extensively using mitochondrial markers, which demonstrated signatures of multiple waves of migration, arguably connected with glaciation periods. Among Eurasian brown bears, Siberian populations remain understudied. We have sequenced complete mitochondrial genomes of four ancient (~4.5-40 kya) bears from South Siberia and 19 modern bears from South Siberia and the Russian Far East. Reconstruction of phylogenetic relationships between haplotypes and evaluation of modern population structure have demonstrated that all the studied samples belong to the most widespread Eurasian clade 3. One of the ancient haplotypes takes a basal position relative to the whole of clade 3; the second is basal to the haplogroup 3a (the most common subclade), and two others belong to clades 3a1 and 3b. Modern Siberian bears retain at least some of this diversity; apart from the most common haplogroup 3a, we demonstrate the presence of clade 3b, which was previously found mainly in mainland Eurasia and Northern Japan. Our findings highlight the importance of South Siberia as a refugium for northern Eurasian brown bears and further corroborate the hypothesis of several waves of migration in the Pleistocene.}, } @article {pmid35327421, year = {2022}, author = {Sobolev, VV and Soboleva, AG and Denisova, EV and Pechatnikova, EA and Dvoryankova, E and Korsunskaya, IM and Mezentsev, A}, title = {Proteomic Studies of Psoriasis.}, journal = {Biomedicines}, volume = {10}, number = {3}, pages = {}, pmid = {35327421}, issn = {2227-9059}, abstract = {In this review paper, we discuss the contribution of proteomic studies to the discovery of disease-specific biomarkers to monitor the disease and evaluate available treatment options for psoriasis. Psoriasis is one of the most prevalent skin disorders driven by a Th17-specific immune response. Although potential patients have a genetic predisposition to psoriasis, the etiology of the disease remains unknown. During the last two decades, proteomics became deeply integrated with psoriatic research. The data obtained in proteomic studies facilitated the discovery of novel mechanisms and the verification of many experimental hypotheses of the disease pathogenesis. The detailed data analysis revealed multiple differentially expressed proteins and significant changes in proteome associated with the disease and drug efficacy. In this respect, there is a need for proteomic studies to characterize the role of the disease-specific biomarkers in the pathogenesis of psoriasis, develop clinical applications to choose the most efficient treatment options and monitor the therapeutic response.}, } @article {pmid35319532, year = {2022}, author = {Dengler, NF and Ferraresi, S and Rochkind, S and Denisova, N and Garozzo, D and Heinen, C and Alimehmeti, R and Capone, C and Barone, DG and Zdunczyk, A and Pedro, MT and Antoniadis, G and Kaiser, R and Dubuisson, A and Kretschmer, T and Rasulic, L}, title = {Thoracic Outlet Syndrome Part I: Systematic Review of the Literature and Consensus on Anatomy, Diagnosis, and Classification of Thoracic Outlet Syndrome by the European Association of Neurosurgical Societies' Section of Peripheral Nerve Surgery.}, journal = {Neurosurgery}, volume = {90}, number = {6}, pages = {653-667}, pmid = {35319532}, issn = {1524-4040}, support = {CL-2019-14-004/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Neurosurgical Procedures/adverse effects ; Peripheral Nerves ; Physical Therapy Modalities ; *Quality of Life ; *Thoracic Outlet Syndrome/diagnosis/etiology/surgery ; }, abstract = {BACKGROUND: Although numerous articles have been published not only on the classification of thoracic outlet syndrome (TOS) but also on diagnostic standards, timing, and type of surgical intervention, there still remains some controversy because of the lack of level 1 evidence. So far, attempts to generate uniform reporting standards have not yielded conclusive results.

OBJECTIVE: To systematically review the body of evidence and reach a consensus among neurosurgeons experienced in TOS regarding anatomy, diagnosis, and classification.

METHODS: A systematic literature search on PubMed/MEDLINE was performed on February 13, 2021, yielding 2853 results. Abstracts were screened and classified. Recommendations were developed in a meeting held online on February 10, 2021, and refined according to the Delphi consensus method.

RESULTS: Six randomized controlled trials (on surgical, conservative, and injection therapies), 4 "guideline" articles (on imaging and reporting standards), 5 observational studies (on diagnostics, hierarchic designs of physiotherapy vs surgery, and quality of life outcomes), and 6 meta-analyses were identified. The European Association of Neurosurgical Societies' section of peripheral nerve surgery established 18 statements regarding anatomy, diagnosis, and classification of TOS with agreement levels of 98.4 % (±3.0).

CONCLUSION: Because of the lack of level 1 evidence, consensus statements on anatomy, diagnosis, and classification of TOS from experts of the section of peripheral nerve surgery of the European Association of Neurosurgical Societies were developed with the Delphi method. Further work on reporting standards, prospective data collections, therapy, and long-term outcome is necessary.}, } @article {pmid35249383, year = {2022}, author = {Scerri, EML and Roberts, P and Yoshi Maezumi, S and Malhi, Y}, title = {Tropical forests in the deep human past.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {377}, number = {1849}, pages = {20200500}, pmid = {35249383}, issn = {1471-2970}, mesh = {Animals ; Biological Evolution ; Ecosystem ; Forests ; *Fossils ; *Hominidae ; Humans ; }, abstract = {Since Darwin, studies of human evolution have tended to give primacy to open 'savannah' environments as the ecological cradle of our lineage, with dense tropical forests cast as hostile, unfavourable frontiers. These perceptions continue to shape both the geographical context of fieldwork as well as dominant narratives concerning hominin evolution. This paradigm persists despite new, ground-breaking research highlighting the role of tropical forests in the human story. For example, novel research in Africa's rainforests has uncovered archaeological sites dating back into the Pleistocene; genetic studies have revealed very deep human roots in Central and West Africa and in the tropics of Asia and the Pacific; an unprecedented number of coexistent hominin species have now been documented, including Homo erectus, the 'Hobbit' (Homo floresiensis), Homo luzonensis, Denisovans, and Homo sapiens. Some of the earliest members of our own species to reach South Asia, Southeast Asia, Oceania and the tropical Americas have shown an unexpected rapidity in their adaptation to even some of the more 'extreme' tropical settings. This includes the early human manipulation of species and even habitats. This volume builds on these currently disparate threads and, for the first time, draws together a group of interdisciplinary, agenda-setting papers that firmly places a broader spectrum of tropical environments at the heart of the deep human past. This article is part of the theme issue 'Tropical forests in the deep human past'.}, } @article {pmid35236981, year = {2022}, author = {Wang, FG and Yang, SX and Ge, JY and Ollé, A and Zhao, KL and Yue, JP and Rosso, DE and Douka, K and Guan, Y and Li, WY and Yang, HY and Liu, LQ and Xie, F and Guo, ZT and Zhu, RX and Deng, CL and d'Errico, F and Petraglia, M}, title = {Innovative ochre processing and tool use in China 40,000 years ago.}, journal = {Nature}, volume = {603}, number = {7900}, pages = {284-289}, pmid = {35236981}, issn = {1476-4687}, mesh = {Animals ; *Archaeology ; Bone and Bones ; China ; History, Ancient ; *Hominidae ; Humans ; Neanderthals ; *Tool Use Behavior ; }, abstract = {Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding[1-4]. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown[1,5-7]. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic[8-10]. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture[2,3,6,11].}, } @article {pmid35236068, year = {2022}, author = {Zavgorudko, VN and Sidorenko, SV and Kortelev, VV and Zavgorudko, TI and Zavgorudko, GV and Senkevich, OA and Denisova, EV}, title = {[Tumnin mineral spring. History of development].}, journal = {Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury}, volume = {99}, number = {1}, pages = {64-68}, doi = {10.17116/kurort20229901164}, pmid = {35236068}, issn = {0042-8787}, mesh = {*Balneology ; Female ; Health Resorts ; Humans ; *Mineral Waters/therapeutic use ; Minerals ; *Skin Diseases/drug therapy ; }, abstract = {The article dwells upon the history of the discovery of the Tumnin mineral spring, the establishment and development of the Far Eastern health resort «Goryachy Klyuch,» located in the basin of Chope creek, a tributary of the largest river in the eastern macroslope of Sikhote Alin, Tumnin river, located 25 km from the Strait of Tartary. A historical sketch since the first mentioning of the Tumnin mineral spring from 1903 to the present day, as well as the results of hydrogeological expeditions to determine the chemical composition and α-activity of Tumnin mineral water at different periods, are presented. A contribution of a geological expedition that established a large deep-lying tectonic structure permeable to upwelling thermal water flows is described. The role of the staff of the physiotherapy and balneology department of the Khabarovsk Medical Institute in the study of the mechanism of action and clinical effectiveness of the Tumnin mineral water is addressed. A balneological characteristic of nitric and siliceous thermal water, the basic therapeutic factor of «Goryachy Klyuch» health resort, which has always been popular among the Far East residents, but gained special importance and appreciation of patients during the pandemic of new coronavirus infection, is given. Currently, in the health resort «Goryachy Klyuch», patients with skin diseases, musculoskeletal, gynecologic, neurologic diseases, digestive tract disorders, metabolic conditions, upper airways, cardiovascular disorders, occupational diseases are treated using balneotherapy and other methods of non-drug therapy. At present, the health resort «Goryachy Klyuch» is going through a difficult but interesting period of improvement of recreation opportunities for the Far East residents.}, } @article {pmid35197262, year = {2023}, author = {Yogeswaran, K and Furtado, JM and Bodaghi, B and Matthews, JM and , and Smith, JR}, title = {Current practice in the management of ocular toxoplasmosis.}, journal = {The British journal of ophthalmology}, volume = {107}, number = {7}, pages = {973-979}, doi = {10.1136/bjophthalmol-2022-321091}, pmid = {35197262}, issn = {1468-2079}, mesh = {Humans ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; *Toxoplasmosis, Ocular/diagnosis/drug therapy ; *Chorioretinitis/diagnosis ; Anti-Bacterial Agents/therapeutic use ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Ocular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice.

METHODS: 192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy.

RESULTS: For 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing-usually PCR-in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim-sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim-sulfamethoxazole was prescribed to selected patients by 69.8%.

CONCLUSION: Our report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.}, } @article {pmid35175470, year = {2022}, author = {Voron'ko, OE and Baskaev, KK and Sobolev, VV and Denisova, EV and Korsunskaya, IM}, title = {Genetic Markers of Therapeutic Efficacy of Methotrexate in Patients with Psoriasis.}, journal = {Bulletin of experimental biology and medicine}, volume = {172}, number = {4}, pages = {460-463}, pmid = {35175470}, issn = {1573-8221}, mesh = {Genetic Markers ; Genotype ; Humans ; *Methotrexate/therapeutic use ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; *Psoriasis/chemically induced/drug therapy/genetics ; Thymidylate Synthase/genetics ; }, abstract = {We studied the effect of C677T and A1298C polymorphisms of the MTHFR gene and 2R/3R polymorphisms of the TYMS gene on the sensitivity to methotrexate in patients with psoriasis (n=139). It was shown that genotype 3R/3R TYMS (OR 8.86, 95%CI 2.00-39.22) and complex genotypes MTHFR1298:A;TYMS:3R (OR 8.20, 95%CI 2.36-28.48) and MTHFR677:C;TYMS:3R (OR 5.40, 95%CI 1.95-14.94) were associated with sensitivity to methotrexate, while genotype 2R/2R TYMS (OR 8.20, 95%CI 2.36-28.48) and complex genotypes MTHFR1298:C;MTHFR677:T;TYMS:2R (OR 0.18, 95%CI 0.06-0.56) and MTHFR1298:C;MTHFR677:T (OR 0.23, 95%CI 0.09-0.59) were associated with resistance to methotrexate. The results can be used for preventive assessment of the effectiveness of methotrexate treatment in patients with psoriasis.}, } @article {pmid35163644, year = {2022}, author = {Denisova, KR and Orlov, NA and Yakimov, SA and Kryukova, EA and Dolgikh, DA and Kirpichnikov, MP and Feofanov, AV and Nekrasova, OV}, title = {GFP-Margatoxin, a Genetically Encoded Fluorescent Ligand to Probe Affinity of Kv1.3 Channel Blockers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163644}, issn = {1422-0067}, support = {Research Project N 075-15-2020-795, local identifier 13.1902.21.0027//Ministry of Science and Higher Education of Russia/ ; }, mesh = {Binding Sites ; Green Fluorescent Proteins/*metabolism ; Humans ; *Kv1.3 Potassium Channel/analysis/metabolism ; Ligands ; Peptides/*metabolism ; Potassium Channel Blockers/*metabolism ; Protein Binding ; }, abstract = {Peptide pore blockers and their fluorescent derivatives are useful molecular probes to study the structure and functions of the voltage-gated potassium Kv1.3 channel, which is considered as a pharmacological target in the treatment of autoimmune and neurological disorders. We present Kv1.3 fluorescent ligand, GFP-MgTx, constructed on the basis of green fluorescent protein (GFP) and margatoxin (MgTx), the peptide, which is widely used in physiological studies of Kv1.3. Expression of the fluorescent ligand in E. coli cells resulted in correctly folded and functionally active GFP-MgTx with a yield of 30 mg per 1 L of culture. Complex of GFP-MgTx with the Kv1.3 binding site is reported to have the dissociation constant of 11 ± 2 nM. GFP-MgTx as a component of an analytical system based on the hybrid KcsA-Kv1.3 channel is shown to be applicable to recognize Kv1.3 pore blockers of peptide origin and to evaluate their affinities to Kv1.3. GFP-MgTx can be used in screening and pre-selection of Kv1.3 channel blockers as potential drug candidates.}, } @article {pmid35160434, year = {2022}, author = {Roenko, AV and Nikiforov, RY and Gringolts, ML and Belov, NA and Denisova, YI and Shandryuk, GA and Bondarenko, GN and Kudryavtsev, YV and Finkelshtein, ES}, title = {Olefin-Metathesis-Derived Norbornene-Ethylene-Vinyl Acetate/Vinyl Alcohol Multiblock Copolymers: Impact of the Copolymer Structure on the Gas Permeation Properties.}, journal = {Polymers}, volume = {14}, number = {3}, pages = {}, pmid = {35160434}, issn = {2073-4360}, support = {20-03-00703//Russian Foundation for Basic Research/ ; }, abstract = {Commercial metathesis polynorbornene is used for the fabrication of high-damping coatings and bulk materials that dissipate vibration and impact energies. Functionalization of this non-polar polymer can improve its adhesive, gas barrier, and other properties, thereby potentially expanding its application area. With this aim, the post-modification of polynorbornene was carried out by inserting ethylene-vinyl acetate-vinyl alcohol blocks into its backbone via the cross-metathesis of polynorbornene with poly(5-acetoxy-1-octenylene) and subsequent deacetylation and hydrogenation of the obtained multiblock copolymers. For the first time, epoxy groups were introduced into the main chains of these copolymers, followed by the oxirane ring opening reaction. The influence of post-modification on the thermal, gas separation, and mechanical properties of the new copolymers was studied. It was shown that the gas permeability of the copolymer significantly depends on its composition, as well as on the amounts of hydroxyl and epoxy groups. The developed methods efficiently improve the barrier properties, reducing the oxygen permeability by 15-33 times in comparison with polynorbornene. The obtained results are promising for various applications and can be extended to a broader family of polydienes and other polymers containing backbone double bonds.}, } @article {pmid35159210, year = {2022}, author = {Grigorenko, AP and Protasova, MS and Lisenkova, AA and Reshetov, DA and Andreeva, TV and Garcias, GL and Martino Roth, MDG and Papassotiropoulos, A and Rogaev, EI}, title = {Neurodevelopmental Syndrome with Intellectual Disability, Speech Impairment, and Quadrupedia Is Associated with Glutamate Receptor Delta 2 Gene Defect.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159210}, issn = {2073-4409}, support = {19-75-30039//Russian Science Foundation/ ; }, mesh = {Adult ; Exons ; Humans ; *Intellectual Disability/genetics ; *Neurodevelopmental Disorders/genetics ; *Receptors, Glutamate/genetics ; *Speech Disorders/genetics ; Syndrome ; }, abstract = {Bipedalism, speech, and intellect are the most prominent traits that emerged in the evolution of Homo sapiens. Here, we describe a novel genetic cause of an "involution" phenotype in four patients, who are characterized by quadrupedal locomotion, intellectual impairment, the absence of speech, small stature, and hirsutism, observed in a consanguineous Brazilian family. Using whole-genome sequencing analysis and homozygous genetic mapping, we identified genes bearing homozygous genetic variants and found a homozygous 36.2 kb deletion in the gene of glutamate receptor delta 2 (GRID2) in the patients, resulting in the lack of a coding region from the fifth to the seventh exons. The GRID2 gene is highly expressed in the cerebellum cortex from prenatal development to adulthood, specifically in Purkinje neurons. Deletion in this gene leads to the loss of the alpha chain in the extracellular amino-terminal protein domain (ATD), essential in protein folding and transport from the endoplasmic reticulum (ER) to the cell surface. Then, we studied the evolutionary trajectories of the GRID2 gene. There was no sign of strong selection of the highly conservative GRID2 gene in ancient hominids (Neanderthals and Denisovans) or modern humans; however, according to in silico tests using the Mfold tool, the GRID2 gene possibly gained human-specific mutations that increased the stability of GRID2 mRNA.}, } @article {pmid35143674, year = {2022}, author = {Göllner, T and Larena, M and Kutanan, W and Lukas, H and Fieder, M and Schaschl, H}, title = {Unveiling the Genetic History of the Maniq, a Primary Hunter-Gatherer Society.}, journal = {Genome biology and evolution}, volume = {14}, number = {4}, pages = {}, pmid = {35143674}, issn = {1759-6653}, mesh = {Animals ; Asia, Southeastern ; *Asian People ; Genetics, Population ; Humans ; *Neanderthals/genetics ; Polymorphism, Single Nucleotide ; Thailand ; }, abstract = {The Maniq of southern Thailand is one of the last remaining practicing hunter-gatherer communities in the world. However, our knowledge on their genetic origins and demographic history is still largely limited. We present here the genotype data covering ∼2.3 million single nucleotide polymorphisms of 11 unrelated Maniq individuals. Our analyses reveal the Maniq to be closely related to the Semang populations of Malaysia (Malay Negritos), who altogether carry an Andamanese-related ancestry linked to the ancient Hòabìnhian hunter-gatherers of Mainland Southeast Asia (MSEA). Moreover, the Maniq possess ∼35% East Asian-related ancestry, likely brought about by recent admixture with surrounding agriculturist communities in the region. In addition, the Maniq exhibit one of the highest levels of genetic differentiation found among living human populations, indicative of their small population size and historical practice of endogamy. Similar to other hunter-gatherer populations of MSEA, we also find the Maniq to possess low levels of Neanderthal ancestry and undetectable levels of Denisovan ancestry. Altogether, we reveal the Maniq to be a Semang group that experienced intense genetic drift and exhibits signs of ancient Hòabìnhian ancestry.}, } @article {pmid35138885, year = {2022}, author = {Slimak, L and Zanolli, C and Higham, T and Frouin, M and Schwenninger, JL and Arnold, LJ and Demuro, M and Douka, K and Mercier, N and Guérin, G and Valladas, H and Yvorra, P and Giraud, Y and Seguin-Orlando, A and Orlando, L and Lewis, JE and Muth, X and Camus, H and Vandevelde, S and Buckley, M and Mallol, C and Stringer, C and Metz, L}, title = {Modern human incursion into Neanderthal territories 54,000 years ago at Mandrin, France.}, journal = {Science advances}, volume = {8}, number = {6}, pages = {eabj9496}, pmid = {35138885}, issn = {2375-2548}, abstract = {Determining the extent of overlap between modern humans and other hominins in Eurasia, such as Neanderthals and Denisovans, is fundamental to understanding the nature of their interactions and what led to the disappearance of archaic hominins. Apart from a possible sporadic pulse recorded in Greece during the Middle Pleistocene, the first settlements of modern humans in Europe have been constrained to ~45,000 to 43,000 years ago. Here, we report hominin fossils from Grotte Mandrin in France that reveal the earliest known presence of modern humans in Europe between 56,800 and 51,700 years ago. This early modern human incursion in the Rhône Valley is associated with technologies unknown in any industry of that age outside Africa or the Levant. Mandrin documents the first alternating occupation of Neanderthals and modern humans, with a modern human fossil and associated Neronian lithic industry found stratigraphically between layers containing Neanderthal remains associated with Mousterian industries.}, } @article {pmid35075148, year = {2022}, author = {Morley, MW and Goldberg, P and Uliyanov, VA and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Jacobs, Z and Roberts, RG}, title = {Author Correction: Hominin and animal activities in the microstratigraphic record from Denisova Cave (Altai Mountains, Russia).}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {1545}, doi = {10.1038/s41598-021-03251-6}, pmid = {35075148}, issn = {2045-2322}, } @article {pmid34971813, year = {2022}, author = {Shchenkov, SV and Sokolov, SG and Denisova, SA}, title = {Phylogenetic position of Atriophallophorus minutus (Trematoda: Microphallidae), the type-species of the genus Atriophallophorus Deblock & Rosé, 1964, based on partial 28S rDNA gene sequence.}, journal = {Parasitology international}, volume = {87}, number = {}, pages = {102534}, doi = {10.1016/j.parint.2021.102534}, pmid = {34971813}, issn = {1873-0329}, mesh = {Animals ; DNA, Ribosomal/genetics ; Phylogeny ; RNA, Ribosomal, 28S/genetics ; Snails/*parasitology ; Trematoda/anatomy & histology/*classification/genetics ; Trematode Infections/*parasitology ; }, abstract = {We found metacercariae of a microphallid trematode Atriophallophorus minutus in freshwater snails Bithynia tentaculata. In this study, we provide a morphological description of whole-mount specimens and semi-thin sections of experimentally grown adults of this species. Our morphological examination supports the idea that the adults of Atriophallophorus spp. have a ventral sucker with a sinistral interruption of the outer edge. In the 28S rDNA gene-based phylogenetic analyses, our specimens of A. minutus were grouped into Atriophallophorus spp. clade, as a sister taxon to Atriophallophorus winterbourni + Atriophallophorus sp. Analysis of the pairwise genetic distances between coI mtDNA gene sequences revealed a low divergence between the two specimens of A. minutus (1.1%) and a greater divergence (up to 16.6%) between them and A. winterbourni. Since other Atriophallophorus spp. are known to have a strict specificity to the polyvalent intermediate host, we suggest that A. minutus reported from different snail species may represent a complex of cryptic species.}, } @article {pmid34969841, year = {2022}, author = {Massilani, D and Morley, MW and Mentzer, SM and Aldeias, V and Vernot, B and Miller, C and Stahlschmidt, M and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Conard, NJ and Wurz, S and Henshilwood, CS and Vasquez, J and Essel, E and Nagel, S and Richter, J and Nickel, B and Roberts, RG and Pääbo, S and Slon, V and Goldberg, P and Meyer, M}, title = {Microstratigraphic preservation of ancient faunal and hominin DNA in Pleistocene cave sediments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {1}, pages = {}, pmid = {34969841}, issn = {1091-6490}, mesh = {Animals ; *Caves ; *DNA, Ancient ; *Fossils ; Hominidae/*genetics ; Neanderthals/*genetics ; }, abstract = {Ancient DNA recovered from Pleistocene sediments represents a rich resource for the study of past hominin and environmental diversity. However, little is known about how DNA is preserved in sediments and the extent to which it may be translocated between archaeological strata. Here, we investigate DNA preservation in 47 blocks of resin-impregnated archaeological sediment collected over the last four decades for micromorphological analyses at 13 prehistoric sites in Europe, Asia, Africa, and North America and show that such blocks can preserve DNA of hominins and other mammals. Extensive microsampling of sediment blocks from Denisova Cave in the Altai Mountains reveals that the taxonomic composition of mammalian DNA differs drastically at the millimeter-scale and that DNA is concentrated in small particles, especially in fragments of bone and feces (coprolites), suggesting that these are substantial sources of DNA in sediments. Three microsamples taken in close proximity in one of the blocks yielded Neanderthal DNA from at least two male individuals closely related to Denisova 5, a Neanderthal toe bone previously recovered from the same layer. Our work indicates that DNA can remain stably localized in sediments over time and provides a means of linking genetic information to the archaeological and ecological records on a microstratigraphic scale.}, } @article {pmid34964332, year = {2021}, author = {Soldatskiy, YL and Bulynko, SA and Denisova, OA and Edgem, SR and Kovalets, ES}, title = {[Features of the clinic, diagnosis and treatment of parapharyngeal abscesses in children: analysis of 121 observations].}, journal = {Vestnik otorinolaringologii}, volume = {86}, number = {6}, pages = {62-68}, doi = {10.17116/otorino20218606162}, pmid = {34964332}, issn = {0042-4668}, mesh = {Child ; Child, Preschool ; Humans ; Neck ; *Pharyngeal Diseases/diagnostic imaging/therapy ; *Retropharyngeal Abscess/diagnostic imaging/epidemiology ; Retrospective Studies ; *Tonsillectomy ; }, abstract = {UNLABELLED: Parapharyngeal and retropharyngeal abscesses (PPA) in children are a rare pathology, for the diagnosis of which it is necessary to use additional instrumental examination methods. The tactics of treating patients remains a subject of discussion.

OBJECTIVE: To analyze the features of the clinic, diagnosis and treatment of PPA in children.

MATERIAL AND METHODS: According to the hospital database, a retrospective analysis of the medical histories of children discharged from the clinic with a diagnosis of "J39.0 Retropharyngeal and parapharyngeal abscess" was carried out in the period from 01.01.14 to 31.12.19. In all cases, the diagnosis was confirmed by computed tomography (CT) data with contrast enhancement. Complaints at the time of treatment, anamnesis and instrumental diagnosis data, clinical features of the course of the disease and the effectiveness of treatment were analyzed.

RESULTS: 121 children were treated for PPA (average age 73±41 months; Me=52.5 months), which is 0.4% of all hospitalized in the otorhinolaryngological department, 0.7% of the number of emergency hospitalizations, 0.8% of the number of hospitalized children with pharyngeal diseases, and 8.3% of the number of patients with pharyngeal abscess. Abscesses were more often localized in the upper pharynx, at the level of the I-II cervical vertebrae (49.6% of all observations); abscesses were found least often in the pharyngeal space (5.8%), there was no statistically significant difference between the right-sided and left-sided location: 47.9% and 46.2%, respectively. Surgical treatment was performed in 98 (81%) patients in the presence of an abscess capsule or an abscess diameter of more than 2 cm according to CT; the remaining 23 (19%) children were treated conservatively. The opening of the abscess was performed endopharyngeal, in the case of a pronounced deep lateral location of the abscess and its proximity to large blood vessels - with access through the tonsillar niche after preliminary tonsillectomy (19.4% of those operated).

CONCLUSION: The final diagnosis of parapharyngeal and retropharyngeal abscess can be established by contrast-enhanced computed tomography. Conservative treatment is indicated for a limited group of patients at the initial stages of the disease, most patients need surgical treatment.}, } @article {pmid34946819, year = {2021}, author = {Filippenkov, IB and Stavchansky, VV and Denisova, AE and Valieva, LV and Remizova, JA and Mozgovoy, IV and Zaytceva, EI and Gubsky, LV and Limborska, SA and Dergunova, LV}, title = {Genome-Wide RNA-Sequencing Reveals Massive Circular RNA Expression Changes of the Neurotransmission Genes in the Rat Brain after Ischemia-Reperfusion.}, journal = {Genes}, volume = {12}, number = {12}, pages = {}, pmid = {34946819}, issn = {2073-4425}, mesh = {Animals ; Brain/pathology ; Infarction, Middle Cerebral Artery/*genetics ; Male ; MicroRNAs/genetics ; RNA, Circular/*genetics ; RNA, Messenger/genetics ; RNA-Seq/methods ; Rats ; Rats, Wistar ; Sequence Analysis, RNA/methods ; Signal Transduction/genetics ; Stroke/genetics ; Synaptic Transmission/*genetics ; }, abstract = {Ischemic brain stroke is one of the most serious and socially significant diseases. In addition to messenger RNAs (mRNAs), encoding protein, the study of regulatory RNAs in ischemic has exceptional importance for the development of new strategies for neuroprotection. Circular RNAs (circRNAs) have a closed structure, predominantly brain-specific expression, and remain highly promising targets of research. They can interact with microRNAs (miRNAs), diminish their activity and thereby inhibit miRNA-mediated repression of mRNA. Genome-wide RNA-Seq analysis of the subcortical structures of the rat brain containing an ischemic damage focus and penumbra area revealed 395 circRNAs changed their expression significantly at 24 h after transient middle cerebral artery occlusion model (tMCAO) conditions. Furthermore, functional annotation revealed their association with neuroactive signaling pathways. It was found that about a third of the differentially expressed circRNAs (DECs) originate from genes whose mRNA levels also changed at 24 h after tMCAO. The other DECs originate from genes encoding non-regulated mRNAs under tMCAO conditions. In addition, bioinformatic analysis predicted a circRNA-miRNA-mRNA network which was associated with the neurotransmission signaling regulation. Our results show that such circRNAs can persist as potential miRNA sponges for the protection of mRNAs of neurotransmitter genes. The results expanded our views about the neurotransmission regulation in the rat brain after ischemia-reperfusion with circRNA action.}, } @article {pmid34943946, year = {2021}, author = {Makarova, E and Kazantseva, A and Dubinina, A and Denisova, E and Jakovleva, T and Balybina, N and Bgatova, N and Baranov, K and Bazhan, N}, title = {Fibroblast Growth Factor 21 (FGF21) Administration Sex-Specifically Affects Blood Insulin Levels and Liver Steatosis in Obese A[y] Mice.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34943946}, issn = {2073-4409}, support = {17-15-01036//Russian Science Foundation/ ; }, mesh = {Animals ; Diet, High-Fat ; Energy Metabolism/genetics ; Fatty Liver/blood/*drug therapy ; Female ; Fibroblast Growth Factors/genetics/*pharmacology ; Humans ; Insulin/*blood ; Insulin Receptor Substrate Proteins/genetics ; Insulin Resistance/genetics ; Liver/*metabolism/pathology ; Male ; Melanocortins/toxicity ; Mice ; Mice, Obese ; Obesity/blood/chemically induced/*drug therapy/genetics ; Sex Characteristics ; Triglycerides/metabolism ; Uncoupling Protein 1/genetics ; }, abstract = {FGF21 is a promising candidate for treating obesity, diabetes, and NAFLD; however, some of its pharmacological effects are sex-specific in mice with the A[y] mutation that evokes melanocortin receptor 4 blockade, obesity, and hepatosteatosis. This suggests that the ability of FGF21 to correct melanocortin obesity may depend on sex. This study compares FGF21 action on food intake, locomotor activity, gene expression, metabolic characteristics, and liver state in obese A[y] males and females. A[y] mice were administered FGF21 for seven days, and metabolic parameters and gene expression in different tissues were assessed. Placebo-treated females were more obese than males and had lower levels of blood insulin and liver triglycerides, and higher expression of genes for insulin signaling in the liver, white adipose tissue (WAT) and muscles, and pro-inflammatory cytokines in the liver. FGF21 administration did not affect body weight, and increased food intake, locomotor activity, expression of Fgf21 and Ucp1 in brown fat and genes related to lipolysis and insulin action in WAT regardless of sex; however, it decreased hyperinsulinemia and hepatic lipid accumulation and increased muscle expression of Cpt1 and Irs1 only in males. Thus, FGF21's beneficial effects on metabolic disorders associated with melanocortin obesity are more pronounced in males.}, } @article {pmid34942109, year = {2022}, author = {Bouaziz, M and Cheng, T and Minuti, A and Denisova, K and Barmettler, A}, title = {Shared Decision Making in Ophthalmology: A Scoping Review.}, journal = {American journal of ophthalmology}, volume = {237}, number = {}, pages = {146-153}, doi = {10.1016/j.ajo.2021.12.005}, pmid = {34942109}, issn = {1879-1891}, mesh = {*Cataract ; Decision Making ; Decision Making, Shared ; *Glaucoma ; Humans ; *Ophthalmology ; Patient Participation ; }, abstract = {PURPOSE: Shared decision making (SDM) has been associated with improved patient satisfaction and outcomes in both medical and surgical specialties, but its role in ophthalmology has not been systematically examined. Using a scoping review of the literature, the purpose of this study was to explore the characteristics, implementation, and outcomes of SDM in ophthalmology.

DESIGN: Scoping review of the literature.

METHODS: Searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through August 2021 for SDM in ophthalmology. The resulting 1602 studies were screened by 2 independent reviewers with 57 full-text articles examined for inclusion of an ophthalmologic diagnosis, as well as discussion of SDM or patient decision aids. Nineteen studies were eligible and qualitatively coded for 11 predetermined codes, which included patient outcomes, patient and physician requests for SDM, and methods of implementation.

RESULTS: Of 19 included studies, all emphasized the value of SDM for ophthalmology and 2 studies reported improved patient outcomes. The most commonly examined topics were chronic ophthalmic diseases, such as cataracts and glaucoma. Limitations to SDM implementation were also universally discussed, including patients' lack of disease knowledge, communication barriers, and time restrictions. Although patient decision aids are an effective tool to mitigate these limitations, these have only been established for the subjects of cataracts and glaucoma.

CONCLUSION: SDM is a methodology for patient-centered care that is regarded as a potentially useful tool in the field of ophthalmology. However, significant barriers exist to its effective implementation. Evidence-based research on if and how these barriers should be attenuated, as well as the development of additional patient decision aids for different ophthalmic diseases, are needed.}, } @article {pmid34937535, year = {2021}, author = {Zhur, KV and Trifonov, VA and Prokhortchouk, EB}, title = {Progress and Prospects in Epigenetic Studies of Ancient DNA.}, journal = {Biochemistry. Biokhimiia}, volume = {86}, number = {12}, pages = {1563-1571}, doi = {10.1134/S0006297921120051}, pmid = {34937535}, issn = {1608-3040}, mesh = {Animals ; *DNA Methylation ; *DNA, Ancient ; *Epigenesis, Genetic ; Epigenomics/trends ; *Evolution, Molecular ; Human Migration ; Humans ; Neanderthals/*genetics ; }, abstract = {Development of technologies for high-throughput whole-genome sequencing and improvement of sample preparation techniques made it possible to study ancient DNA (aDNA) from archaeological samples over a million year old. The studies of aDNA have shed light on the history of human migration, replacement of populations, interbreeding of Cro-Magnons with Neanderthals and Denisovans, evolution of human pathogens, etc. Equally important is the possibility to investigate epigenetic modifications of ancient genomes, which has allowed to obtain previously inaccessible information on gene expression, nucleosome positioning, and DNA methylation. Analysis of methylation status of certain genomic sites can predict an individual's age at death and reconstruct some phenotypic features, as it was done for the Denisovan genome, and even to elucidate unfavorable environmental factors that had affected this archaic individual. In this review, we discuss current progress in epigenetic studies of aDNA, including methodological approaches and promising research directions in this field.}, } @article {pmid34937505, year = {2021}, author = {Yarmolinskaya, M and Denisova, A and Tkachenko, N and Ivashenko, T and Bespalova, O and Tolibova, G and Tral, T}, title = {Vitamin D significance in pathogenesis of endometriosis.}, journal = {Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology}, volume = {37}, number = {sup1}, pages = {40-43}, doi = {10.1080/09513590.2021.2006516}, pmid = {34937505}, issn = {1473-0766}, mesh = {Ascitic Fluid/*metabolism ; Case-Control Studies ; Endometriosis/blood/genetics/*metabolism ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; *Polymorphism, Single Nucleotide ; Receptors, Calcitriol/*genetics ; Vitamin D/*analogs & derivatives/blood ; }, abstract = {UNLABELLED: Genital endometriosis (GE) is a widespread multifactorial disease thus making it necessary to carry on studying its pathogeny in order to work out target therapy techniques. Studying vitamin D role in GE pathogeny is a new promising research trend.

PATIENTS AND TECHNIQUE: 25(ОН)D level was determined in peripheral blood (PB) of 440 patients with GE and in peritoneal fluid (PF) - in 49 GE patients; the same test in PB was performed in 30 patients of the control group with the ovulatory menstrual cycle and no gynecologic pathology. 129 patients with GE, as well as 82 women of the control, underwent examination of vitamin D receptor (VDR) polymorphism gene in BsmI, FokI, and TaqI polymorphic locus. We examined vitamin D receptor expression in the eutopic and ectopic endometrium in 32 women with GE and in the endometrium of 20 women from the control group. We also compared the efficacy of combined therapy involving colecalciferol to the standard hormone modulating therapy.

RESULTS: It was established that the prevalent GE forms are characterized by lower 25(ОН)D levels both in PB and in PF. It was also found that G/G genotype of VDR BsmI gene polymorphic variant 1.9 times increases GE occurrence risk. VDR expression was authentically lower in the ectopic endometrium compared to the eutopic endometrium. Patients with GE show no VDR expression cyclic variations in the endometrium which is contrary to the control. Therapy in combination with colecalciferol promotes a more expressed decrease of endometriosis-associated pain syndrome and psycho-emotional stabilization of GE patients compared to the standard hormone modulating therapy.

CONCLUSION: Vitamin D deficiency plays a significant role in the pathogenesis of GE and Vit D may be applied as its targeted therapy.}, } @article {pmid34919805, year = {2022}, author = {Natri, HM and Hudjashov, G and Jacobs, G and Kusuma, P and Saag, L and Darusallam, CC and Metspalu, M and Sudoyo, H and Cox, MP and Gallego Romero, I and Banovich, NE}, title = {Genetic architecture of gene regulation in Indonesian populations identifies QTLs associated with global and local ancestries.}, journal = {American journal of human genetics}, volume = {109}, number = {1}, pages = {50-65}, pmid = {34919805}, issn = {1537-6605}, mesh = {Computational Biology/methods ; DNA Methylation ; Databases, Genetic ; *Gene Expression Regulation ; *Genetics, Population ; *Genome, Human ; Genome-Wide Association Study ; Genomics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Indonesia ; Male ; Models, Genetic ; Molecular Sequence Annotation ; Multifactorial Inheritance ; *Quantitative Trait Loci ; Quantitative Trait, Heritable ; Selection, Genetic ; Whole Genome Sequencing ; }, abstract = {Lack of diversity in human genomics limits our understanding of the genetic underpinnings of complex traits, hinders precision medicine, and contributes to health disparities. To map genetic effects on gene regulation in the underrepresented Indonesian population, we have integrated genotype, gene expression, and CpG methylation data from 115 participants across three island populations that capture the major sources of genomic diversity in the region. In a comparison with European datasets, we identify eQTLs shared between Indonesia and Europe as well as population-specific eQTLs that exhibit differences in allele frequencies and/or overall expression levels between populations. By combining local ancestry and archaic introgression inference with eQTLs and methylQTLs, we identify regulatory loci driven by modern Papuan ancestry as well as introgressed Denisovan and Neanderthal variation. GWAS colocalization connects QTLs detected here to hematological traits, and further comparison with European datasets reflects the poor overall transferability of GWAS statistics across diverse populations. Our findings illustrate how population-specific genetic architecture, local ancestry, and archaic introgression drive variation in gene regulation across genetically distinct and in admixed populations and highlight the need for performing association studies on non-European populations.}, } @article {pmid34914745, year = {2021}, author = {Hayakawa, T and Terahara, M and Fujito, NT and Matsunaga, T and Teshima, KM and Hane, M and Kitajima, K and Sato, C and Takahata, N and Satta, Y}, title = {Lower promoter activity of the ST8SIA2 gene has been favored in evolving human collective brains.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0259897}, pmid = {34914745}, issn = {1932-6203}, mesh = {Animals ; Brain/*enzymology ; Databases, Genetic ; Genetic Loci ; Haplotypes ; Humans ; Neanderthals/genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Schizophrenia/genetics/pathology ; Sialyltransferases/classification/*genetics ; }, abstract = {ST8SIA2 is an important molecule regulating expression of the phenotype involved in schizophrenia. Lowered promoter activity of the ST8SIA2 gene is considered to be protective against schizophrenia by conferring tolerance to psychosocial stress. Here, we examined the promoter-type composition of anatomically modern humans (AMHs) and archaic humans (AHs; Neanderthals and Denisovans), and compared the promoter activity at the population level (population promoter activity; PPA) between them. In AMHs, the TCT-type, showing the second lowest promoter activity, was most prevalent in the ancestral population of non-Africans. However, the detection of only the CGT-type from AH samples and recombination tracts in AH sequences showed that the CGT- and TGT-types, exhibiting the two highest promoter activities, were common in AH populations. Furthermore, interspecies gene flow occurred into AMHs from AHs and into Denisovans from Neanderthals, influencing promoter-type compositions independently in both AMHs and AHs. The difference of promoter-type composition makes PPA unique in each population. East and Southeast Asian populations show the lowest PPA. This results from the selective increase of the CGC-type, showing the lowest promoter activity, in these populations. Every non-African population shows significantly lower PPA than African populations, resulting from the TCT-type having the highest prevalence in the ancestral population of non-Africans. In addition, PPA reduction is also found among subpopulations within Africa via a slight increase of the TCT-type. These findings indicate a trend toward lower PPA in the spread of AMHs, interpreted as a continuous adaptation to psychosocial stress arising in migration. This trend is considered as genetic tuning for the evolution of collective brains. The inferred promoter-type composition of AHs differed markedly from that of AMHs, resulting in higher PPA in AHs than in AMHs. This suggests that the trend toward lower PPA is a unique feature in AMH spread.}, } @article {pmid34897770, year = {2022}, author = {Shunatova, N and Serova, K and Denisova, S and Shchenkov, S and Ostrovsky, A}, title = {Small, but smart: Fine structure of an avicularium in Dendrobeania fruticosa (Bryozoa: Cheilostomata).}, journal = {Journal of morphology}, volume = {283}, number = {2}, pages = {174-206}, doi = {10.1002/jmor.21436}, pmid = {34897770}, issn = {1097-4687}, mesh = {Animals ; *Bryozoa ; Epidermal Cells ; Epidermis ; Extracellular Matrix ; Torso ; }, abstract = {Bryozoans are small benthic suspension-feeding colonial animals. Among this phylum, there are representatives showing a lesser or greater degree of polymorphism, and the most common type of polymorphic zooids is the avicularium. Here we present a detailed description of the bird's-head shaped avicularium in Dendrobeania fruticosa. The body cavity of the avicularium demonstrates an acoelomate condition: along the cystid walls, there is neither the layer of extracellular matrix toward the epidermis, nor coelomic lining. However, a layer of extracellular matrix and epithelialized cells lie under the epidermis of the tentacle sheath. Probably, such construction helps the tentacle sheath to acquire some rigidity-it is the only region of the body wall without an ectocyst. We did not find typical funicular strands in the avicularium, but there is a delicate mesh composed of stellate cells with thin and long projections, which sometimes isolate the spaces filled with a heterogeneous matrix. The proximal ends of the adductors, abductors, and polypide retractors are attached to the body wall via typical epidermal tendon cells, which possess numerous bundles of tonofilaments. The distal ends of the abductors and adductors attach to the frontal membrane or upper vestibular membrane, respectively. The inner organic layer of the ectocyst in these regions forms large protrusions, from which numerous thin outgrowths branch off. We suggest them to be a functional analogue of apodemes and apodemal filaments in arthropods. "Apodemal" tendon cells have long and thin projections that line the outgrowths of the ectocyst and surround the distal ends of the muscle cells. At these sites, "apodemal" tendon cells possess numerous tonofilaments. The vestigial polypide includes the tentacle sheath, rudimentary lophophore, cerebral ganglion, and polypide retractors. The sensory part of 5HT-positive cells of the frontal membrane is dendrite-shaped and embedded in the inner organic layer of the ectocyst.}, } @article {pmid34872977, year = {2022}, author = {Hubert, L and Paganini, J and Picard, C and Chiaroni, J and Abi-Rached, L and Pontarotti, P and Di Cristofaro, J}, title = {HLA-H*02:07 Is a Membrane-Bound Ligand of Denisovan Origin That Protects against Lysis by Activated Immune Effectors.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {208}, number = {1}, pages = {49-53}, doi = {10.4049/jimmunol.2100358}, pmid = {34872977}, issn = {1550-6606}, mesh = {Alleles ; Asian People ; Cell Membrane/*metabolism ; Cytotoxicity, Immunologic ; Evolution, Molecular ; Gene Frequency ; *Genotype ; HLA-A11 Antigen/genetics ; Haplotypes ; Hemochromatosis Protein/*genetics/metabolism ; Homeostasis ; Humans ; Immune Tolerance ; K562 Cells ; Killer Cells, Natural/*immunology ; Lymphocyte Activation ; Pseudogenes/*genetics ; White People ; }, abstract = {The biological relevance of genes initially categorized as "pseudogenes" is slowly emerging, notably in innate immunity. In the HLA region on chromosome 6, HLA-H is one such pseudogene; yet, it is transcribed, and its variation is associated with immune properties. Furthermore, two HLA-H alleles, H*02:07 and H*02:14, putatively encode a complete, membrane-bound HLA protein. Here we thus hypothesized that HLA-H contributes to immune homeostasis similarly to tolerogenic molecules HLA-G, -E, and -F. We tested if HLA-H*02:07 encodes a membrane-bound protein that can inhibit the cytotoxicity of effector cells. We used an HLA-null human erythroblast cell line transduced with HLA-H*02:07 cDNA to demonstrate that HLA-H*02:07 encodes a membrane-bound protein. Additionally, using a cytotoxicity assay, our results support that K562 HLA-H*02:07 inhibits human effector IL-2-activated PBMCs and human IL-2-independent NK92-MI cell line activity. Finally, through in silico genotyping of the Denisovan genome and haplotypic association with Denisovan-derived HLA-A*11, we also show that H*02:07 is of archaic origin. Hence, admixture with archaic humans brought a functional HLA-H allele into modern European and Asian populations.}, } @article {pmid34863581, year = {2022}, author = {Zhang, P and Zhang, X and Zhang, X and Gao, X and Huerta-Sanchez, E and Zwyns, N}, title = {Denisovans and Homo sapiens on the Tibetan Plateau: dispersals and adaptations.}, journal = {Trends in ecology & evolution}, volume = {37}, number = {3}, pages = {257-267}, pmid = {34863581}, issn = {1872-8383}, support = {K99 GM143466/GM/NIGMS NIH HHS/United States ; R35 GM128946/GM/NIGMS NIH HHS/United States ; R35 GM119856/GM/NIGMS NIH HHS/United States ; }, mesh = {Acclimatization/genetics ; *Adaptation, Physiological/genetics ; *Altitude ; Archaeology ; Humans ; Tibet ; }, abstract = {Recent archaeological discoveries suggest that both archaic Denisovans and Homo sapiens occupied the Tibetan Plateau earlier than expected. Genetic studies show that a pulse of Denisovan introgression was involved in the adaptation of Tibetan populations to high-altitude hypoxia. These findings challenge the traditional view that the plateau was one of the last places on earth colonized by H. sapiens and warrant a reappraisal of the population history of this highland. Here, we integrate archaeological and genomic evidence relevant to human dispersal, settlement, and adaptation in the region. We propose two testable models to address the peopling of the plateau in the broader context of H. sapiens dispersal and their encounters with Denisovans in Asia.}, } @article {pmid34851566, year = {2021}, author = {Koloda, YA and Denisova, YV and Podzolkova, NM}, title = {Genetic polymorphisms of reproductive hormones and their receptors in assisted reproduction technology for patients with polycystic ovary syndrome.}, journal = {Drug metabolism and personalized therapy}, volume = {37}, number = {2}, pages = {111-122}, doi = {10.1515/dmpt-2021-0123}, pmid = {34851566}, issn = {2363-8915}, mesh = {Anti-Mullerian Hormone ; Female ; Humans ; *Polycystic Ovary Syndrome/genetics ; Polymorphism, Genetic/genetics ; Pregnancy ; Reproduction ; Reproductive Techniques, Assisted ; Technology ; }, abstract = {Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of childbearing, which is defined by the accumulation of multiple, small fluid-filled ovarian cysts without the selection of a single dominant follicle. Most PCOS phenotypes are characterized by the absence of spontaneous ovulation, resistance toward ovulation inductors, the production of a large immature oocytes number, and the high prevalence of ovarian hyperstimulation syndrome, resulting in reduced assisted reproductive technologies (ART) programs effectiveness. The review analyses current data about the relationship between polymorphism genotypes of KISS genes, follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and their receptors genes, gonadotropin-releasing hormone (GnRH), estrogen, and progesterone receptors genes, the PCOS risk and the features of ovarian response to stimulation during ART cycles. The use of single nucleotide polymorphisms (SNPs) as prognostic markers of ART programs outcomes would provide a personalized approach to the drugs and doses choice for ovarian stimulation and significantly increase the chance of pregnancy.}, } @article {pmid34824388, year = {2022}, author = {Brown, S and Massilani, D and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Stoessel, A and Jope-Street, B and Meyer, M and Kelso, J and Pääbo, S and Higham, T and Douka, K}, title = {The earliest Denisovans and their cultural adaptation.}, journal = {Nature ecology & evolution}, volume = {6}, number = {1}, pages = {28-35}, pmid = {34824388}, issn = {2397-334X}, support = {694707/ERC_/European Research Council/International ; 715069/ERC_/European Research Council/International ; 324139/ERC_/European Research Council/International ; }, mesh = {Animals ; Archaeology ; Caves ; DNA, Mitochondrial/genetics ; *Hominidae/genetics ; *Neanderthals/genetics ; }, abstract = {Since the initial identification of the Denisovans a decade ago, only a handful of their physical remains have been discovered. Here we analysed ~3,800 non-diagnostic bone fragments using collagen peptide mass fingerprinting to locate new hominin remains from Denisova Cave (Siberia, Russia). We identified five new hominin bones, four of which contained sufficient DNA for mitochondrial analysis. Three carry mitochondrial DNA of the Denisovan type and one was found to carry mtDNA of the Neanderthal type. The former come from the same archaeological layer near the base of the cave's sequence and are the oldest securely dated evidence of Denisovans at 200 ka (thousand years ago) (205-192 ka at 68.2% or 217-187 ka at 95% probability). The stratigraphic context in which they were located contains a wealth of archaeological material in the form of lithics and faunal remains, allowing us to determine the material culture associated with these early hominins and explore their behavioural and environmental adaptations. The combination of bone collagen fingerprinting and genetic analyses has so far more-than-doubled the number of hominin bones at Denisova Cave and has expanded our understanding of Denisovan and Neanderthal interactions, as well as their archaeological signatures.}, } @article {pmid34795445, year = {2021}, author = {Liston, A and Humblet-Baron, S and Duffy, D and Goris, A}, title = {Human immune diversity: from evolution to modernity.}, journal = {Nature immunology}, volume = {22}, number = {12}, pages = {1479-1489}, pmid = {34795445}, issn = {1529-2916}, support = {BBS/E/B/000C0427/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/B/000C0428/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Age Factors ; Diet ; *Evolution, Molecular ; Female ; Gene-Environment Interaction ; *Genetic Variation ; Host-Pathogen Interactions ; Humans ; Immune System/immunology/metabolism/*physiology ; Male ; Microbiota/immunology ; Sex Factors ; Species Specificity ; }, abstract = {The extreme diversity of the human immune system, forged and maintained throughout evolutionary history, provides a potent defense against opportunistic pathogens. At the same time, this immune variation is the substrate upon which a plethora of immune-associated diseases develop. Genetic analysis suggests that thousands of individually weak loci together drive up to half of the observed immune variation. Intense selection maintains this genetic diversity, even selecting for the introgressed Neanderthal or Denisovan alleles that have reintroduced variation lost during the out-of-Africa migration. Variations in age, sex, diet, environmental exposure, and microbiome each potentially explain the residual variation, with proof-of-concept studies demonstrating both plausible mechanisms and correlative associations. The confounding interaction of many of these variables currently makes it difficult to assign definitive contributions. Here, we review the current state of play in the field, identify the key unknowns in the causality of immune variation, and identify the multidisciplinary pathways toward an improved understanding.}, } @article {pmid34782887, year = {2021}, author = {Denisova, EI and Savinkova, MM and Makarova, EN}, title = {Influence of leptin administration to pregnant female mice on obesity development, taste preferences, and gene expression in the liver and muscles of their male and female offspring.}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {25}, number = {6}, pages = {669-676}, doi = {10.18699/VJ21.076}, pmid = {34782887}, issn = {2500-0462}, abstract = {. The consumption of food rich in sugar and fat provokes obesity. Prenatal conditions have an impact on taste preferences and metabolism in the adult offspring, and this impact may manifest differently in different sexes. An increase in blood leptin level in pregnant females reduces the risk of obesity and insulin resistance in the offspring, although the mechanisms mediating this effect are unknown. Neither is it known whether maternal leptin affects taste preferences. In this study, we investigated the effect of leptin administration to pregnant mice on the development of diet-induced obesity, food choice, and gene expression in the liver and muscles of the offspring with regard to sex. Leptin was administered to female mice on days 11, 12, and 13 of pregnancy. In male and female offspring, growth rate and intake of standard chow after weaning, obesity development, gene expression in the liver and muscles, and food choice when kept on a high-calorie diet (standard chow, lard, sweet cookies) were recorded. Leptin administration to pregnant females reduced body weight in the female offspring fed on the standard diet. When the offspring were given a high-calorie diet, leptin administration inhibited obesity development and reduced the consumption of cookies only in males. It also increased the consumption of standard chow and the mRNA levels of genes for the insulin receptor and glucose transporter type 4 in the muscles of both male and female offspring. The results demonstrate that an increase in blood leptin levels in pregnant females has a sex-specif ic effect on the metabolism of the offspring increasing resistance to obesity only in male offspring. The mechanism underlying this effect includes a shift in food preference in favor of a balanced diet and maintenance of insulin sensitivity in muscle tissues.}, } @article {pmid34771075, year = {2021}, author = {Grin, IR and Mechetin, GV and Kasymov, RD and Diatlova, EA and Yudkina, AV and Shchelkunov, SN and Gileva, IP and Denisova, AA and Stepanov, GA and Chilov, GG and Zharkov, DO}, title = {A New Class of Uracil-DNA Glycosylase Inhibitors Active against Human and Vaccinia Virus Enzyme.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {21}, pages = {}, pmid = {34771075}, issn = {1420-3049}, support = {17-14-01190//Russian Science Foundation/ ; 0245-2021-0002//Ministry of Science and Higher Education, Russia/ ; FSUS-2020-0035//Ministry of Science and Higher Education, Russia/ ; 21-04-011//Academic Fund Program at the HSE University in 2021/ ; }, mesh = {Enzyme Inhibitors/chemistry/*pharmacology ; Humans ; Kinetics ; Ligands ; Molecular Docking Simulation ; Molecular Structure ; Pyrimidines/chemistry/*pharmacology ; Uracil-DNA Glycosidase/*antagonists & inhibitors/metabolism ; Vaccinia virus/*enzymology ; }, abstract = {Uracil-DNA glycosylases are enzymes that excise uracil bases appearing in DNA as a result of cytosine deamination or accidental dUMP incorporation from the dUTP pool. The activity of Family 1 uracil-DNA glycosylase (UNG) activity limits the efficiency of antimetabolite drugs and is essential for virulence in some bacterial and viral infections. Thus, UNG is regarded as a promising target for antitumor, antiviral, antibacterial, and antiprotozoal drugs. Most UNG inhibitors presently developed are based on the uracil base linked to various substituents, yet new pharmacophores are wanted to target a wide range of UNGs. We have conducted virtual screening of a 1,027,767-ligand library and biochemically screened the best hits for the inhibitory activity against human and vaccinia virus UNG enzymes. Although even the best inhibitors had IC50 ≥ 100 μM, they were highly enriched in a common fragment, tetrahydro-2,4,6-trioxopyrimidinylidene (PyO3). In silico, PyO3 preferably docked into the enzyme's active site, and in kinetic experiments, the inhibition was better consistent with the competitive mechanism. The toxicity of two best inhibitors for human cells was independent of the presence of methotrexate, which is consistent with the hypothesis that dUMP in genomic DNA is less toxic for the cell than strand breaks arising from the massive removal of uracil. We conclude that PyO3 may be a novel pharmacophore with the potential for development into UNG-targeting agents.}, } @article {pmid34757478, year = {2022}, author = {Derenko, M and Denisova, G and Dambueva, I and Malyarchuk, B and Bazarov, B}, title = {Mitogenomics of modern Mongolic-speaking populations.}, journal = {Molecular genetics and genomics : MGG}, volume = {297}, number = {1}, pages = {47-62}, pmid = {34757478}, issn = {1617-4623}, support = {14.W03.31.0016 "Dynamics of Peoples//Government of the Russian Federation/ ; Empires in the History of Inner Asia"//Government of the Russian Federation/ ; }, mesh = {Asian People/ethnology/genetics ; Bayes Theorem ; DNA, Mitochondrial/analysis/*genetics ; Ethnicity/*genetics ; Gene Pool ; Genetic Variation ; Genetics, Population ; Genomics/methods ; Haplotypes ; Humans ; Language ; Mongolia/epidemiology/ethnology ; Phylogeny ; Phylogeography ; }, abstract = {Here, we present a comprehensive data set of 489 complete mitogenomes (211 of which are new) from four Mongolic-speaking populations (Mongols, Barghuts, Khamnigans, and Buryats) to investigate their matrilineal genetic structure, ancestry and relationship with other ethnic groups. We show that along with very high levels of genetic diversity and lack of genetic differentiation, Mongolic-speaking populations exhibit strong genetic resemblance to East Asian populations of Chinese, Japanese, and Uyghurs. Phylogeographic analysis of complete mitogenomes reveals the presence of different components in the gene pools of modern Mongolic-speaking populations-the main East Eurasian component is represented by mtDNA lineages of East Asian, Siberian and autochthonous (the Baikal region/Mongolian) ancestry, whereas the less pronounced West Eurasian component can be ascribed to Europe and West Asia/Caucasus. We also observed that up to one third of the mtDNA subhaplogroups identified in Mongolic-speaking populations can be considered as Mongolic-specific with the coalescence age of most of them not exceeding 1.7 kya. This coincides well with the population size growth which started around 1.1 kya and is detectable only in the Bayesian Skyline Plot constructed based on Mongolic-specific mitogenomes. Our data suggest that the genetic structure established during the Mongol empire is still retained in present-day Mongolic-speaking populations.}, } @article {pmid34718708, year = {2022}, author = {Saitou, M and Masuda, N and Gokcumen, O}, title = {Similarity-Based Analysis of Allele Frequency Distribution among Multiple Populations Identifies Adaptive Genomic Structural Variants.}, journal = {Molecular biology and evolution}, volume = {39}, number = {3}, pages = {}, pmid = {34718708}, issn = {1537-1719}, mesh = {Alleles ; Gene Frequency ; *Genetics, Population ; *Genomic Structural Variation ; Haplotypes ; Phenotype ; *Selection, Genetic ; }, abstract = {Structural variants have a considerable impact on human genomic diversity. However, their evolutionary history remains mostly unexplored. Here, we developed a new method to identify potentially adaptive structural variants based on a similarity-based analysis that incorporates genotype frequency data from 26 populations simultaneously. Using this method, we analyzed 57,629 structural variants and identified 576 structural variants that show unusual population differentiation. Of these putatively adaptive structural variants, we further showed that 24 variants are multiallelic and overlap with coding sequences, and 20 variants are significantly associated with GWAS traits. Closer inspection of the haplotypic variation associated with these putatively adaptive and functional structural variants reveals deviations from neutral expectations due to: 1) population differentiation of rapidly evolving multiallelic variants, 2) incomplete sweeps, and 3) recent population-specific negative selection. Overall, our study provides new methodological insights, documents hundreds of putatively adaptive variants, and introduces evolutionary models that may better explain the complex evolution of structural variants.}, } @article {pmid34716352, year = {2021}, author = {Di Pietro, L and Barba, M and Palacios, D and Tiberio, F and Prampolini, C and Baranzini, M and Parolini, O and Arcovito, A and Lattanzi, W}, title = {Shaping modern human skull through epigenetic, transcriptional and post-transcriptional regulation of the RUNX2 master bone gene.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {21316}, pmid = {34716352}, issn = {2045-2322}, support = {Linea D1 - 2018//Università Cattolica del Sacro Cuore/ ; Linea D1 - 2017//Università Cattolica del Sacro Cuore/ ; }, mesh = {Animals ; *Biological Evolution ; Core Binding Factor Alpha 1 Subunit/*genetics/metabolism ; Cranial Sutures/growth & development ; Craniosynostoses/genetics ; Epigenesis, Genetic ; Genome, Human ; Hominidae/anatomy & histology/genetics ; Humans ; Mesenchymal Stem Cells ; MicroRNAs/genetics ; Neanderthals/anatomy & histology/genetics ; Osteogenesis/genetics ; RNA, Long Noncoding/genetics ; Skull/*anatomy & histology ; }, abstract = {RUNX2 encodes the master bone transcription factor driving skeletal development in vertebrates, and playing a specific role in craniofacial and skull morphogenesis. The anatomically modern human (AMH) features sequence changes in the RUNX2 locus compared with archaic hominins' species. We aimed to understand how these changes may have contributed to human skull globularization occurred in recent evolution. We compared in silico AMH and archaic hominins' genomes, and used mesenchymal stromal cells isolated from skull sutures of craniosynostosis patients for in vitro functional assays. We detected 459 and 470 nucleotide changes in noncoding regions of the AMH RUNX2 locus, compared with the Neandertal and Denisovan genomes, respectively. Three nucleotide changes in the proximal promoter were predicted to alter the binding of the zinc finger protein Znf263 and long-distance interactions with other cis-regulatory regions. By surface plasmon resonance, we selected nucleotide substitutions in the 3'UTRs able to affect miRNA binding affinity. Specifically, miR-3150a-3p and miR-6785-5p expression inversely correlated with RUNX2 expression during in vitro osteogenic differentiation. The expression of two long non-coding RNAs, AL096865.1 and RUNX2-AS1, within the same locus, was modulated during in vitro osteogenic differentiation and correlated with the expression of specific RUNX2 isoforms. Our data suggest that RUNX2 may have undergone adaptive phenotypic evolution caused by epigenetic and post-transcriptional regulatory mechanisms, which may explain the delayed suture fusion leading to the present-day globular skull shape.}, } @article {pmid34716342, year = {2021}, author = {Yuan, K and Ni, X and Liu, C and Pan, Y and Deng, L and Zhang, R and Gao, Y and Ge, X and Liu, J and Ma, X and Lou, H and Wu, T and Xu, S}, title = {Refining models of archaic admixture in Eurasia with ArchaicSeeker 2.0.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6232}, pmid = {34716342}, issn = {2041-1723}, mesh = {Algorithms ; Animals ; Asia ; DNA-Binding Proteins/genetics ; Europe ; *Genetic Introgression ; Genome, Human ; Hominidae/*genetics ; Humans ; Metagenomics/*methods ; *Models, Genetic ; Neanderthals/genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Siberia ; }, abstract = {We developed a method, ArchaicSeeker 2.0, to identify introgressed hominin sequences and model multiple-wave admixture. The new method enabled us to discern two waves of introgression from both Denisovan-like and Neanderthal-like hominins in present-day Eurasian populations and an ancient Siberian individual. We estimated that an early Denisovan-like introgression occurred in Eurasia around 118.8-94.0 thousand years ago (kya). In contrast, we detected only one single episode of Denisovan-like admixture in indigenous peoples eastern to the Wallace-Line. Modeling ancient admixtures suggested an early dispersal of modern humans throughout Asia before the Toba volcanic super-eruption 74 kya, predating the initial peopling of Asia as proposed by the traditional Out-of-Africa model. Survived archaic sequences are involved in various phenotypes including immune and body mass (e.g., ZNF169), cardiovascular and lung function (e.g., HHAT), UV response and carbohydrate metabolism (e.g., HYAL1/HYAL2/HYAL3), while "archaic deserts" are enriched with genes associated with skin development and keratinization.}, } @article {pmid34714000, year = {2021}, author = {Dzhafarov, VM and Guzeeva, AS and Amelina, EV and Khalepa, AA and Dmitriev, AB and Denisova, NP and Rzaev, DA}, title = {[Invasive EEG for temporal lobe epilepsy: selection of technique].}, journal = {Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko}, volume = {85}, number = {5}, pages = {23-29}, doi = {10.17116/neiro20218505123}, pmid = {34714000}, issn = {0042-8817}, mesh = {Adult ; Electrocorticography ; Electroencephalography ; *Epilepsy, Temporal Lobe/diagnosis/surgery ; Humans ; Seizures ; }, abstract = {BACKGROUND: Non-invasive EEG reveals epileptogenic zone in 70% of patients. In other cases, invasive EEG monitoring is indicated. Various implantation strategies and techniques of intracranial EEG (icEEG) potentially provide different outcomes. Choosing the optimal icEEG technique may be challenging.

OBJECTIVE: To analyze the results of icEEG in adults with temporal lobe epilepsy and to determine the algorithm for selection of optimal invasive EEG technique.

MATERIAL AND METHODS: The study included 82 patients with temporal lobe epilepsy who underwent invasive EEG. Effectiveness of invasive EEG was determined by detection of epileptogenic zone and post-resection outcomes. Postoperative results were analyzed throughout more than 6-month follow-up period using the Engel grading system. Statistical analysis was conducted using the Fisher's exact test.

RESULTS: Epileptogenic zone was revealed in 72 (88%) cases. Invasive EEG was supplemented by another modality in 3 (4%) patients. Mean follow-up period after resection was 17 months in 45 patients. Favorable outcomes were achieved in 31 (69%) cases. Statistical analysis showed that identification of epileptogenic zone depends existing of lesion and symptoms of seizures. Selection algorithm for optimal technique of invasive EEG was determined considering own results and literature data.

CONCLUSION: Invasive EEG results and post-resection outcomes demonstrated favorable efficacy of original algorithm. The last one may be used in decision-making on optimal technique of invasive EEG in adults with temporal lobe epilepsy.}, } @article {pmid34634929, year = {2021}, author = {Chen, T and Lin, YX and Zha, Y and Sun, Y and Tian, J and Yang, Z and Lin, SW and Yu, F and Chen, ZS and Kuang, BH and Lei, JJ and Nie, YJ and Xu, Y and Tian, DB and Li, YZ and Yang, B and Xu, Q and Yang, L and Zhong, N and Zheng, M and Li, Y and Zhao, J and Zhang, XY and Feng, L}, title = {A Low-Producing Haplotype of Interleukin-6 Disrupting CTCF Binding Is Protective against Severe COVID-19.}, journal = {mBio}, volume = {12}, number = {5}, pages = {e0137221}, pmid = {34634929}, issn = {2150-7511}, support = {81922049//National Natural Science Foundation of China (NSFC)/ ; 81972163//National Natural Science Foundation of China (NSFC)/ ; 201803040003//the Health & Medical Collaborative Innovation Project of Guangdong/ ; 19ykzd42//Fundamental Research Funds for Central Universities/ ; ZNSA-2020001//Guangdong Zhong Nan-shan Medical Foundation/ ; }, mesh = {A549 Cells ; COVID-19/*metabolism/*prevention & control ; Genotype ; Haplotypes/genetics ; HeLa Cells ; Humans ; Interleukin-6/genetics/*metabolism ; Polymorphism, Single Nucleotide/genetics ; Real-Time Polymerase Chain Reaction ; Software ; }, abstract = {Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.}, } @article {pmid34622284, year = {2021}, author = {Villanea, FA and Huerta-Sanchez, E and Fox, K}, title = {Corrigendum to: ABO Genetic Variation in Neanderthals and Denisovans.}, journal = {Molecular biology and evolution}, volume = {38}, number = {12}, pages = {5835}, doi = {10.1093/molbev/msab261}, pmid = {34622284}, issn = {1537-1719}, } @article {pmid34615474, year = {2021}, author = {Kraef, C and Bentzon, A and Panteleev, A and Skrahina, A and Bolokadze, N and Tetradov, S and Podlasin, R and Karpov, I and Borodulina, E and Denisova, E and Azina, I and Lundgren, J and Johansen, IS and Mocroft, A and Podlekareva, D and Kirk, O and , }, title = {Delayed diagnosis of tuberculosis in persons living with HIV in Eastern Europe: associated factors and effect on mortality-a multicentre prospective cohort study.}, journal = {BMC infectious diseases}, volume = {21}, number = {1}, pages = {1038}, pmid = {34615474}, issn = {1471-2334}, support = {MR/T001127/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Delayed Diagnosis ; Europe, Eastern/epidemiology ; *HIV Infections/complications/epidemiology ; Humans ; Middle Aged ; Prospective Studies ; *Tuberculosis/diagnosis/epidemiology ; }, abstract = {BACKGROUND: Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH).

METHODS: PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan-Meier estimates and Cox models.

FINDINGS: 480/740 patients (64.9%; 95% CI 61.3-68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. < 50 years, aOR = 2.51; 1.18-5.32; p = 0.016), injecting drug use (IDU) (vs. non-IDU aOR = 1.66; 1.21-2.29; p = 0.002), being ART naïve (aOR = 1.77; 1.24-2.54; p = 0.002), disseminated TB (vs. pulmonary TB, aOR = 1.56, 1.10-2.19, p = 0.012), and presenting with weight loss (vs. no weight loss, aOR = 1.63; 1.18-2.24; p = 0.003) were associated with delayed diagnosis. PLWH with a delayed diagnosis were at 36% increased risk of death (hazard ratio = 1.36; 1.04-1.77; p = 0.023, adjusted hazard ratio 1.27; 0.95-1.70; p = 0.103).

CONCLUSION: Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe.}, } @article {pmid34575702, year = {2021}, author = {Sobolev, V and Soboleva, A and Denisova, E and Denieva, M and Dvoryankova, E and Suleymanov, E and Zhukova, OV and Potekaev, N and Korsunskaya, I and Mezentsev, A}, title = {Differential Expression of Estrogen-Responsive Genes in Women with Psoriasis.}, journal = {Journal of personalized medicine}, volume = {11}, number = {9}, pages = {}, pmid = {34575702}, issn = {2075-4426}, abstract = {In women, the flow of psoriasis is influenced by each phase of a woman's life cycle. According to previous findings, significant changes in the levels of sex hormones affect the severity of the disease. Aim: The aim of this study was to identify the estrogen-responsive genes that could be responsible for the exacerbation of psoriasis in menopausal women. Methods: Skin samples of lesional skin donated by psoriasis patients (n = 5) were compared with skin samples of healthy volunteers (n = 5) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The set of differentially expressed proteins was subjected to protein ontology analysis to identify differentially expressed estrogen-responsive proteins. The expression of discovered proteins was validated by qPCR and ELISA on four groups of female participants. The first group included ten psoriasis patients without menopause; the second included eleven postmenopausal patients; the third included five healthy volunteers without menopause; and the fourth included six postmenopausal volunteers. Moreover, the participants' blood samples were used to assess the levels of estradiol, progesterone, and testosterone. Results: We found that the levels of estradiol and progesterone were significantly lower and the levels of testosterone were significantly higher in the blood of patients compared to the control. The protein ontology analysis of LC-MS/MS data identified six proteins, namely HMOX1, KRT19, LDHA, HSPD1, MAPK1, and CA2, differentially expressed in the lesional skin of female patients compared to male patients. ELISA and qPCR experiments confirmed differential expression of the named proteins and their mRNA. The genes encoding the named proteins were differentially expressed in patients compared to volunteers. However, KRT19 and LDHA were not differentially expressed when we compared patients with and without menopause. All genes, except MAPK1, were differentially expressed in patients with menopause compared to the volunteers with menopause. HMOX1, KRT19, HSPD1, and LDHA were differentially expressed in patients without menopause compared to the volunteers without menopause. However, no significant changes were found when we compared healthy volunteers with and without menopause. Conclusion: Our experiments discovered a differential expression of six estrogen-controlled genes in the skin of female patients. Identification of these genes and assessment of the changes in their expression provide insight into the biological effects of estrogen in lesional skin. The results of proteomic analysis are available via ProteomeXchange with identifier PXD021673.}, } @article {pmid34449702, year = {2021}, author = {Deņisova, A and Pilmane, M and Eņģelis, A and Pētersons, A}, title = {Gallbladder Interleukins in Children with Calculous Cholecystitis.}, journal = {Pediatric reports}, volume = {13}, number = {3}, pages = {470-482}, pmid = {34449702}, issn = {2036-749X}, abstract = {Calculous cholecystitis connects to inflammation and various complications. It is a common disease in the paediatric population, yet it is still uncertain how inflammation factors are involved in its morphopathogenesis. Twenty calculous cholecystitis surgery tissue samples were obtained from 20 children. As a control, seven unaffected gallbladders were used. Tissues were immunohistochemically stained for IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, and IL-17A, and the slides were inspected by light microscopy. To evaluate statistical differences and correlations between interleukins, Mann-Whitney U and Spearman's tests were used. Statistically significant difference between patient and control gallbladder epithelium was for IL-1α and IL-17A, but connective tissue-IL-1α, IL-4, IL-6, IL-7, IL-8, and IL-17A positive structures. A strong positive correlation in patients was detected between epithelial IL-1α and IL-1α in connective tissue, epithelial IL-6 and IL-7, IL-6 and IL-17A, IL-7 and IL-10, IL-7 and IL-17A, as well as between IL-6 and IL-7, IL-7 and IL-10 in connective tissue. The increase of IL-1α, IL-4, IL-6, IL-7, IL-8 and IL-17A positive structures suggests their role in the morphopathogenesis of calculous cholecystitis. The correlations between interleukins in epithelium and in connective tissues prove that the epithelial barrier function and inflammatory response in deeper layers are sustained through intercellular signalling pathways.}, } @article {pmid34445309, year = {2021}, author = {Sobolev, V and Nesterova, A and Soboleva, A and Mezentsev, A and Dvoriankova, E and Piruzyan, A and Denisova, E and Melnichenko, O and Korsunskaya, I}, title = {Analysis of PPARγ Signaling Activity in Psoriasis.}, journal = {International journal of molecular sciences}, volume = {22}, number = {16}, pages = {}, pmid = {34445309}, issn = {1422-0067}, mesh = {Adult ; Female ; Forkhead Transcription Factors/metabolism ; Humans ; Interleukin-17/metabolism ; Male ; Middle Aged ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; PPAR gamma/genetics/*metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Psoriasis/*metabolism ; STAT3 Transcription Factor/metabolism ; *Signal Transduction ; T-Lymphocytes/metabolism ; }, abstract = {In our previous work, we built the model of PPARγ dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions triggering the IL17-related signaling cascade. Skin samples of normally looking and lesional skin donated by psoriasis patients and psoriatic CD3[+] Tcells samples (n = 23) and samples of healthy CD3[+] T cells donated by volunteers (n = 10) were analyzed by real-time PCR, ELISA and immunohistochemistry analysis. We found that the expression of PPARγ is downregulated in human psoriatic skin and laser treatment restores the expression. The expression of IL17, STAT3, FOXP3, and RORC in psoriatic skin before and after laser treatment were correlated with PPARγ expression according to the reconstructed model of PPARγ pathway in psoriasis.In conclusion, we report that PPARγ weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPARγ expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.}, } @article {pmid34433944, year = {2021}, author = {Carlhoff, S and Duli, A and Nägele, K and Nur, M and Skov, L and Sumantri, I and Oktaviana, AA and Hakim, B and Burhan, B and Syahdar, FA and McGahan, DP and Bulbeck, D and Perston, YL and Newman, K and Saiful, AM and Ririmasse, M and Chia, S and Hasanuddin, and Pulubuhu, DAT and Suryatman, and Supriadi, and Jeong, C and Peter, BM and Prüfer, K and Powell, A and Krause, J and Posth, C and Brumm, A}, title = {Genome of a middle Holocene hunter-gatherer from Wallacea.}, journal = {Nature}, volume = {596}, number = {7873}, pages = {543-547}, pmid = {34433944}, issn = {1476-4687}, mesh = {Asia, Southeastern ; Australia ; Bone and Bones/metabolism ; Caves ; DNA, Ancient/*analysis ; Female ; *Fossils ; Genome, Human/*genetics ; *Genomics ; History, Ancient ; Human Migration/history ; Humans ; Indonesia/ethnology ; Islands/*ethnology ; New Guinea ; *Phylogeny ; }, abstract = {Much remains unknown about the population history of early modern humans in southeast Asia, where the archaeological record is sparse and the tropical climate is inimical to the preservation of ancient human DNA[1]. So far, only two low-coverage pre-Neolithic human genomes have been sequenced from this region. Both are from mainland Hòabìnhian hunter-gatherer sites: Pha Faen in Laos, dated to 7939-7751 calibrated years before present (yr cal BP; present taken as AD 1950), and Gua Cha in Malaysia (4.4-4.2 kyr cal BP)[1]. Here we report, to our knowledge, the first ancient human genome from Wallacea, the oceanic island zone between the Sunda Shelf (comprising mainland southeast Asia and the continental islands of western Indonesia) and Pleistocene Sahul (Australia-New Guinea). We extracted DNA from the petrous bone of a young female hunter-gatherer buried 7.3-7.2 kyr cal BP at the limestone cave of Leang Panninge[2] in South Sulawesi, Indonesia. Genetic analyses show that this pre-Neolithic forager, who is associated with the 'Toalean' technocomplex[3,4], shares most genetic drift and morphological similarities with present-day Papuan and Indigenous Australian groups, yet represents a previously unknown divergent human lineage that branched off around the time of the split between these populations approximately 37,000 years ago[5]. We also describe Denisovan and deep Asian-related ancestries in the Leang Panninge genome, and infer their large-scale displacement from the region today.}, } @article {pmid34388371, year = {2021}, author = {Larena, M and McKenna, J and Sanchez-Quinto, F and Bernhardsson, C and Ebeo, C and Reyes, R and Casel, O and Huang, JY and Hagada, KP and Guilay, D and Reyes, J and Allian, FP and Mori, V and Azarcon, LS and Manera, A and Terando, C and Jamero, L and Sireg, G and Manginsay-Tremedal, R and Labos, MS and Vilar, RD and Latiph, A and Saway, RL and Marte, E and Magbanua, P and Morales, A and Java, I and Reveche, R and Barrios, B and Burton, E and Salon, JC and Kels, MJT and Albano, A and Cruz-Angeles, RB and Molanida, E and Granehäll, L and Vicente, M and Edlund, H and Loo, JH and Trejaut, J and Ho, SYW and Reid, L and Lambeck, K and Malmström, H and Schlebusch, C and Endicott, P and Jakobsson, M}, title = {Philippine Ayta possess the highest level of Denisovan ancestry in the world.}, journal = {Current biology : CB}, volume = {31}, number = {19}, pages = {4219-4230.e10}, pmid = {34388371}, issn = {1879-0445}, mesh = {Animals ; Asia ; Asia, Southeastern ; Australia ; *Hominidae/genetics ; Humans ; *Neanderthals/genetics ; Philippines ; Racial Groups ; }, abstract = {Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ∼2.3 million genotypes from 118 ethnic groups of the Philippines, including 25 diverse self-identified Negrito populations, along with high-coverage genomes of Australopapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world-∼30%-40% greater than that of Australians and Papuans-consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.}, } @article {pmid34326389, year = {2021}, author = {Brown, S and Wang, N and Oertle, A and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Comeskey, D and Jope-Street, B and Harvey, VL and Chowdhury, MP and Buckley, M and Higham, T and Douka, K}, title = {Zooarchaeology through the lens of collagen fingerprinting at Denisova Cave.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {15457}, pmid = {34326389}, issn = {2045-2322}, mesh = {Animals ; Archaeology/*methods ; Bone and Bones/pathology ; Carnivora ; Caves ; Collagen/*chemistry ; Fossils ; Hominidae ; Humans ; Paleontology/*methods ; Siberia ; }, abstract = {Denisova Cave, a Pleistocene site in the Altai Mountains of Russian Siberia, has yielded significant fossil and lithic evidence for the Pleistocene in Northern Asia. Abundant animal and human bones have been discovered at the site, however, these tend to be highly fragmented, necessitating new approaches to identifying important hominin and faunal fossils. Here we report the results for 8253 bone fragments using ZooMS. Through the integration of this new ZooMS-based data with the previously published macroscopically-identified fauna we aim to create a holistic picture of the zooarchaeological record of the site. We identify trends associated with climate variability throughout the Middle and Upper Pleistocene as well as patterns explaining the process of bone fragmentation. Where morphological analysis of bones from the site have identified a high proportion of carnivore bones (30.2%), we find that these account for only 7.6% of the ZooMS assemblage, with large mammals between 3 and 5 more abundant overall. Our analysis suggests a cyclical pattern in fragmentation of bones which sees initial fragmentation by hominins using percussive tools and secondary carnivore action, such as gnawing and digestion, likely furthering the initial human-induced fragmentation.}, } @article {pmid34320013, year = {2021}, author = {Condemi, S and Mazières, S and Faux, P and Costedoat, C and Ruiz-Linares, A and Bailly, P and Chiaroni, J}, title = {Blood groups of Neandertals and Denisova decrypted.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0254175}, pmid = {34320013}, issn = {1932-6203}, mesh = {Alleles ; Animals ; Blood Group Antigens/*genetics ; Fossils ; Genetic Variation ; Genotype ; Hominidae/*genetics ; INDEL Mutation ; Neanderthals/*genetics ; Phenotype ; Polymorphism, Genetic ; }, abstract = {Blood group systems were the first phenotypic markers used in anthropology to decipher the origin of populations, their migratory movements, and their admixture. The recent emergence of new technologies based on the decoding of nucleic acids from an individual's entire genome has relegated them to their primary application, blood transfusion. Thus, despite the finer mapping of the modern human genome in relation to Neanderthal and Denisova populations, little is known about red cell blood groups in these archaic populations. Here we analyze the available high-quality sequences of three Neanderthals and one Denisovan individuals for 7 blood group systems that are used today in transfusion (ABO including H/Se, Rh (Rhesus), Kell, Duffy, Kidd, MNS, Diego). We show that Neanderthal and Denisova were polymorphic for ABO and shared blood group alleles recurrent in modern Sub-Saharan populations. Furthermore, we found ABO-related alleles currently preventing from viral gut infection and Neanderthal RHD and RHCE alleles nowadays associated with a high risk of hemolytic disease of the fetus and newborn. Such a common blood group pattern across time and space is coherent with a Neanderthal population of low genetic diversity exposed to low reproductive success and with their inevitable demise. Lastly, we connect a Neanderthal RHD allele to two present-day Aboriginal Australian and Papuan, suggesting that a segment of archaic genome was introgressed in this gene in non-Eurasian populations. While contributing to both the origin and late evolutionary history of Neanderthal and Denisova, our results further illustrate that blood group systems are a relevant piece of the puzzle helping to decipher it.}, } @article {pmid34272242, year = {2021}, author = {Schaefer, NK and Shapiro, B and Green, RE}, title = {An ancestral recombination graph of human, Neanderthal, and Denisovan genomes.}, journal = {Science advances}, volume = {7}, number = {29}, pages = {}, pmid = {34272242}, issn = {2375-2548}, support = {T32 HG008345/HG/NHGRI NIH HHS/United States ; T32 HG00834/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Genome, Human ; Genomics ; *Hominidae/genetics ; Humans ; *Neanderthals/genetics ; Recombination, Genetic ; }, abstract = {Many humans carry genes from Neanderthals, a legacy of past admixture. Existing methods detect this archaic hominin ancestry within human genomes using patterns of linkage disequilibrium or direct comparison to Neanderthal genomes. Each of these methods is limited in sensitivity and scalability. We describe a new ancestral recombination graph inference algorithm that scales to large genome-wide datasets and demonstrate its accuracy on real and simulated data. We then generate a genome-wide ancestral recombination graph including human and archaic hominin genomes. From this, we generate a map within human genomes of archaic ancestry and of genomic regions not shared with archaic hominins either by admixture or incomplete lineage sorting. We find that only 1.5 to 7% of the modern human genome is uniquely human. We also find evidence of multiple bursts of adaptive changes specific to modern humans within the past 600,000 years involving genes related to brain development and function.}, } @article {pmid34217618, year = {2021}, author = {Bezverbnaya, K and Moogk, D and Cummings, D and Baker, CL and Aarts, C and Denisova, G and Sun, M and McNicol, JD and Turner, RC and Rullo, AF and Foley, SR and Bramson, JL}, title = {Development of a B-cell maturation antigen-specific T-cell antigen coupler receptor for multiple myeloma.}, journal = {Cytotherapy}, volume = {23}, number = {9}, pages = {820-832}, doi = {10.1016/j.jcyt.2021.05.007}, pmid = {34217618}, issn = {1477-2566}, mesh = {*B-Cell Maturation Antigen ; Humans ; Immunotherapy, Adoptive ; *Multiple Myeloma/therapy ; Neoplasm Recurrence, Local ; Receptors, Antigen, T-Cell/genetics ; T-Lymphocytes ; }, abstract = {BACKGROUND AIMS: T cells engineered with synthetic receptors have delivered powerful therapeutic results for patients with relapsed/refractory hematologic malignancies. The authors have recently described the T-cell antigen coupler (TAC) receptor, which co-opts the endogenous T-cell receptor (TCR) and activates engineered T cells in an HLA-independent manner. Here the authors describe the evolution of a next-generation TAC receptor with a focus on developing a TAC-engineered T cell for multiple myeloma.

METHODS: To optimize the TAC scaffold, the authors employed a bona fide antigen-binding domain derived from the B-cell maturation antigen-specific monoclonal antibody C11D5.3, which has been used successfully in the clinic. The authors first tested humanized versions of the UCHT1 domain, which is used by the TAC to co-opt the TCR. The authors further discovered that the signal peptide affected surface expression of the TAC receptor. Higher density of the TAC receptor enhanced target binding in vitro, which translated into higher levels of Lck at the immunological synapse and stronger proliferation when only receptor-ligand interactions were present.

RESULTS: The authors observed that the humanized UCHT1 improved surface expression and in vivo efficacy. Using TAC T cells derived from both healthy donors and multiple myeloma patients, the authors determined that despite the influence of receptor density on early activation events and effector function, receptor density did not impact late effector functions in vitro, nor did the receptor density affect in vivo efficacy.

CONCLUSIONS: The modifications to the TAC scaffold described herein represent an important step in the evolution of this technology, which tolerates a range of expression levels without impacting therapeutic efficacy.}, } @article {pmid34210857, year = {2021}, author = {Gibbons, A}, title = {'Dragon Man' may be an elusive Denisovan.}, journal = {Science (New York, N.Y.)}, volume = {373}, number = {6550}, pages = {11-12}, doi = {10.1126/science.373.6550.11}, pmid = {34210857}, issn = {1095-9203}, } @article {pmid34201112, year = {2021}, author = {Sudarkina, OY and Filippenkov, IB and Stavchansky, VV and Denisova, AE and Yuzhakov, VV and Sevan'kaeva, LE and Valieva, LV and Remizova, JA and Dmitrieva, VG and Gubsky, LV and Myasoedov, NF and Limborska, SA and Dergunova, LV}, title = {Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34201112}, issn = {1422-0067}, support = {19-14-00268//Russian Science Foundation/ ; }, mesh = {Adrenocorticotropic Hormone/*analogs & derivatives/pharmacology ; Animals ; Brain/*drug effects/metabolism ; Brain Ischemia/metabolism/pathology/*prevention & control ; Disease Models, Animal ; Male ; Neuroprotective Agents/*pharmacology ; Peptide Fragments/*pharmacology ; Proteome/*drug effects ; RNA-Seq ; Rats ; Rats, Wistar ; Reperfusion Injury/metabolism/pathology/*prevention & control ; Transcriptome/*drug effects ; }, abstract = {The Semax (Met-Glu-His-Phe-Pro-Gly-Pro) peptide is a synthetic melanocortin derivative that is used in the treatment of ischemic stroke. Previously, studies of the molecular mechanisms underlying the actions of Semax using models of cerebral ischemia in rats showed that the peptide enhanced the transcription of neurotrophins and their receptors and modulated the expression of genes involved in the immune response. A genome-wide RNA-Seq analysis revealed that, in the rat transient middle cerebral artery occlusion (tMCAO) model, Semax suppressed the expression of inflammatory genes and activated the expression of neurotransmitter genes. Here, we aimed to evaluate the effect of Semax in this model via the brain expression profiling of key proteins involved in inflammation and cell death processes (MMP-9, c-Fos, and JNK), as well as neuroprotection and recovery (CREB) in stroke. At 24 h after tMCAO, we observed the upregulation of active CREB in subcortical structures, including the focus of the ischemic damage; downregulation of MMP-9 and c-Fos in the adjacent frontoparietal cortex; and downregulation of active JNK in both tissues under the action of Semax. Moreover, a regulatory network was constructed. In conclusion, the suppression of inflammatory and cell death processes and the activation of recovery may contribute to the neuroprotective action of Semax at both the transcriptome and protein levels.}, } @article {pmid34183844, year = {2021}, author = {Graham, F}, title = {Daily briefing: DNA in Denisova Cave soil records several human species.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-021-01771-9}, pmid = {34183844}, issn = {1476-4687}, } @article {pmid34163072, year = {2021}, author = {Zavala, EI and Jacobs, Z and Vernot, B and Shunkov, MV and Kozlikin, MB and Derevianko, AP and Essel, E and de Fillipo, C and Nagel, S and Richter, J and Romagné, F and Schmidt, A and Li, B and O'Gorman, K and Slon, V and Kelso, J and Pääbo, S and Roberts, RG and Meyer, M}, title = {Pleistocene sediment DNA reveals hominin and faunal turnovers at Denisova Cave.}, journal = {Nature}, volume = {595}, number = {7867}, pages = {399-403}, pmid = {34163072}, issn = {1476-4687}, support = {/ERC_/European Research Council/International ; }, mesh = {Animals ; Archaeology ; *Caves ; DNA, Ancient/*analysis ; DNA, Mitochondrial/analysis/genetics ; Fossils ; Geologic Sediments/*chemistry ; History, Ancient ; Hominidae/*genetics ; Neanderthals/genetics ; Siberia ; }, abstract = {Denisova Cave in southern Siberia is the type locality of the Denisovans, an archaic hominin group who were related to Neanderthals[1-4]. The dozen hominin remains recovered from the deposits also include Neanderthals[5,6] and the child of a Neanderthal and a Denisovan[7], which suggests that Denisova Cave was a contact zone between these archaic hominins. However, uncertainties persist about the order in which these groups appeared at the site, the timing and environmental context of hominin occupation, and the association of particular hominin groups with archaeological assemblages[5,8-11]. Here we report the analysis of DNA from 728 sediment samples that were collected in a grid-like manner from layers dating to the Pleistocene epoch. We retrieved ancient faunal and hominin mitochondrial (mt)DNA from 685 and 175 samples, respectively. The earliest evidence for hominin mtDNA is of Denisovans, and is associated with early Middle Palaeolithic stone tools that were deposited approximately 250,000 to 170,000 years ago; Neanderthal mtDNA first appears towards the end of this period. We detect a turnover in the mtDNA of Denisovans that coincides with changes in the composition of faunal mtDNA, and evidence that Denisovans and Neanderthals occupied the site repeatedly-possibly until, or after, the onset of the Initial Upper Palaeolithic at least 45,000 years ago, when modern human mtDNA is first recorded in the sediments.}, } @article {pmid34150310, year = {2021}, author = {Amos, W}, title = {Correlated and geographically predictable Neanderthal and Denisovan legacies are difficult to reconcile with a simple model based on inter-breeding.}, journal = {Royal Society open science}, volume = {8}, number = {6}, pages = {201229}, pmid = {34150310}, issn = {2054-5703}, abstract = {Although the presence of archaic hominin legacies in humans is taken for granted, little attention has been given as to how the data fit with how humans colonized the world. Here, I show that Neanderthal and Denisovan legacies are strongly correlated and that inferred legacy size, like heterozygosity, exhibits a strong correlation with distance from Africa. Simulations confirm that, once created, legacy size is extremely stable: it may reduce through admixture with lower legacy populations but cannot increase significantly through neutral drift. Consequently, populations carrying the highest legacies are likely to be those whose ancestors inter-bred most with archaics. However, the populations with the highest legacies are globally scattered and are unified, not by having origins within the known Neanderthal range, but instead by living in locations that lie furthest from Africa. Furthermore, the Simons Genome Diversity Project data reveal two distinct correlations between Neanderthal and Denisovan legacies, one that starts in North Africa and increases west to east across Eurasia and into some parts of Oceania, and a second, much steeper trend that starts in Africa, peaking with the San and Ju/'hoansi and which, if extrapolated, predicts the large inferred legacies of both archaics found in Oceania/Australia. Similar 'double' trends are observed for the introgression statistic f 4 in a second large dataset published by Qin and Stoneking (Qin & Stoneking 2015 Mol. Biol. Evol. 32, 2665-2674 (doi:10.1093/molbev/msv141)). These trends appear at odds with simple models of how introgression occurred though more complicated patterns of introgression could potentially generate better fits. Moreover, substituting archaic genomes with those of great apes yields similar but biologically impossible signals of introgression, suggesting that the signals these metrics capture arise within humans and are largely independent of the test group. Interestingly, the data do appear to fit a speculative model in which the loss of diversity that occurred when humans moved further from Africa created a gradient in heterozygosity that in turn progressively reduced mutation rate such that populations furthest from Africa have diverged less from our common ancestor and hence from the archaics. In this light, the two distinct trends could be interpreted in terms of two 'out of Africa' events, an early one ending in Oceania and Australia and a later one that colonized Eurasia and the Americas.}, } @article {pmid34097675, year = {2021}, author = {Dergunova, LV and Dmitrieva, VG and Filippenkov, IB and Stavchansky, VV and Denisova, AE and Yuzhakov, VV and Sevan'kaeva, LE and Valieva, LV and Sudarkina, OY and Gubsky, LV and Myasoedov, NF and Limborska, SA}, title = {[The Peptide Drug ACTH(4-7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain].}, journal = {Molekuliarnaia biologiia}, volume = {55}, number = {3}, pages = {402-411}, doi = {10.31857/S0026898421010043}, pmid = {34097675}, issn = {0026-8984}, mesh = {Adrenocorticotropic Hormone/analogs & derivatives ; Animals ; Brain ; *Brain Ischemia/drug therapy/genetics ; Ischemia ; *Neuroprotective Agents ; Peptide Fragments ; *Pharmaceutical Preparations ; RNA, Messenger/genetics ; Rats ; Rats, Wistar ; }, abstract = {Due to its nootropic, neuroprotective, and immunomodulatory effects, the peptide Semax is utilized in the treatment of ischemic stroke. Our earlier RNA-Seq analysis of the transcriptome in an ischemic model of transient occlusion of the middle cerebral artery showed an increase in the mRNA levels of many proinflammatory genes, and the suppression of their induction by Semax. However, for many relevant genes, including Il1a, Il1b, Il6 and Tnfa, the levels of their expression were too low for detailed quantitative evaluation. Here we utilize qRT-PCR to analyze the effects of the Semax peptide on the expression of weakly expressed mRNAs encoding several proinflammatory mediators, and show that exposure to Semax leads to a statistically significant decrease in the Il1a, Il1b, Il6, Ccl3, and Cxcl2 mRNAs, which compensates for the increase in the transcription of these genes induced by ischemia-reperfusion. We conclude that the observed protective effect of Semax in the model of stroke may be due to its anti-inflammatory effects. We also discuss the limitations of the RNA-Seq when applied to quantifying less abundant transcripts as compared to the real-time RT-PCR method.}, } @article {pmid34095864, year = {2021}, author = {Zhou, Y and Browning, SR}, title = {Protocol for detecting introgressed archaic variants with SPrime.}, journal = {STAR protocols}, volume = {2}, number = {2}, pages = {100550}, pmid = {34095864}, issn = {2666-1667}, support = {R01 HG010869/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; DNA, Ancient/analysis ; Genetic Introgression/*genetics ; Genomics/*methods ; Hominidae/genetics ; Humans ; Neanderthals/*genetics ; }, abstract = {The SPrime program detects the variants in current-day populations that were introgressed from an archaic source in the past. It is optimized for detecting introgression from Neanderthals and Denisovans in modern humans. We provide a protocol for detecting Neanderthal and Denisovan introgression in 1000 Genomes Project data, specifically focusing on the CHB (Han Chinese in Beijing) population. For complete details on the use and execution of this protocol, please refer to Browning et al. (2018).}, } @article {pmid34082629, year = {2021}, author = {Shtratnikova, V and Naumov, V and Bezuglov, V and Zheludkevich, A and Smigulina, L and Dikov, Y and Denisova, T and Suvorov, A and Pilsner, JR and Hauser, R and Krawetz, SA and Sergeyev, O}, title = {Optimization of small RNA extraction and comparative study of NGS library preparation from low count sperm samples.}, journal = {Systems biology in reproductive medicine}, volume = {67}, number = {3}, pages = {230-243}, doi = {10.1080/19396368.2021.1912851}, pmid = {34082629}, issn = {1939-6376}, mesh = {Gene Library ; *High-Throughput Nucleotide Sequencing ; Humans ; Male ; *MicroRNAs ; Sequence Analysis, RNA ; Spermatozoa ; }, abstract = {Recent studies demonstrate that sperm epigenome is a vehicle that conveys paternal experiences to offspring phenotype. That evidence triggers interest of both experimental and epidemiological studies of epigenetic markers in sperm. Since samples are often unique in epidemiological studies, a careful and efficient use of the material is a critical requirement. The goal of this study was to provide optimization of methods for the isolation of small RNAs from spermatozoa and library preparation for sequencing. A total 67 fractionated sperm samples from the Russian Children's Study biobank prospectively collected at 18-20 years of age were used to isolate small RNAs with median (IQR) input total sperm count 17.0 (7.4-35.9) million. Twenty-four pairs of libraries were prepared using the NEBNext and NEXTFlex kits, 19 libraries using NEBNext and 6 using NEXTFlex. All libraries were sequenced on NextSeq 500, and the results were evaluated as a function of the number of small non-coding RNA (sncRNA) detected, quality parameters of sequencing libraries, as well as technical features of sample preparation. Although the same amount of miRNA input was used for NEBNext and NEXTFlex libraries, the concentration of DNA in NEBNext libraries was significantly higher in comparison with NEXTFlex libraries. In high input (sperm count >28 million and more than 25 ng miRNA in library) NEXTFlex Small RNA-Seq kit detected more microRNAs. In low input, the NEBNext proved more effective. The tricks and traps to protocol optimization are presented, including an efficient and effector gel-based system for the removal of sequencing library adaptors.}, } @article {pmid34072052, year = {2021}, author = {Denisova, YI and Shandryuk, GA and Arinina, MP and Levin, IS and Zhigarev, VA and Gringolts, ML and Finkelshtein, ES and Malkin, AY and Kudryavtsev, YV}, title = {Multiblock Copolymers of Norbornene and Cyclododecene: Chain Structure and Properties.}, journal = {Polymers}, volume = {13}, number = {11}, pages = {}, pmid = {34072052}, issn = {2073-4360}, support = {17-73-10450//Russian Science Foundation/ ; }, abstract = {We investigate the structure-property relations of the multiblock copolymers of norbornene with cyclododecene synthesized via the macromolecular cross-metathesis reaction between amorphous polynorbornene and semicrystalline polydodecenamer in the presence of the first-generation Grubbs catalyst. By adjusting the reaction time, catalyst amount, and composition of the initial system, we obtain a set of statistical multiblock copolymers that differ in the composition and average length of norbornene and dodecenylene unit sequences. Structural, thermal, and mechanical characterization of the copolymers with NMR, XRD, DSC (including thermal fractionation by successive self-nucleation and annealing), and rotational rheology allows us to relate the reaction conditions to the average length of crystallizable unit sequences, thicknesses of corresponding lamellas, and temperatures of their melting. We demonstrate that isolated dodecenylene units can be incorporated into crystalline lamellas so that even nearly random copolymers should retain crystallinity. Weak high-temperature endotherms observed in the multiblock copolymers of norbornene with cyclododecene and other cycloolefins could indicate that the corresponding systems are microphase-separated in the melt state.}, } @article {pmid34050022, year = {2021}, author = {Zhang, X and Witt, KE and Bañuelos, MM and Ko, A and Yuan, K and Xu, S and Nielsen, R and Huerta-Sanchez, E}, title = {The history and evolution of the Denisovan-EPAS1 haplotype in Tibetans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {22}, pages = {}, pmid = {34050022}, issn = {1091-6490}, support = {R35 GM119856/GM/NIGMS NIH HHS/United States ; R35 GM128946/GM/NIGMS NIH HHS/United States ; T32 GM128596/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/genetics ; Altitude ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; *Evolution, Molecular ; *Haplotypes ; Humans ; Tibet ; }, abstract = {Recent studies suggest that admixture with archaic hominins played an important role in facilitating biological adaptations to new environments. For example, interbreeding with Denisovans facilitated the adaptation to high-altitude environments on the Tibetan Plateau. Specifically, the EPAS1 gene, a transcription factor that regulates the response to hypoxia, exhibits strong signatures of both positive selection and introgression from Denisovans in Tibetan individuals. Interestingly, despite being geographically closer to the Denisova Cave, East Asian populations do not harbor as much Denisovan ancestry as populations from Melanesia. Recently, two studies have suggested two independent waves of Denisovan admixture into East Asians, one of which is shared with South Asians and Oceanians. Here, we leverage data from EPAS1 in 78 Tibetan individuals to interrogate which of these two introgression events introduced the EPAS1 beneficial sequence into the ancestral population of Tibetans, and we use the distribution of introgressed segment lengths at this locus to infer the timing of the introgression and selection event. We find that the introgression event unique to East Asians most likely introduced the beneficial haplotype into the ancestral population of Tibetans around 48,700 (16,000-59,500) y ago, and selection started around 9,000 (2,500-42,000) y ago. Our estimates suggest that one of the most convincing examples of adaptive introgression is in fact selection acting on standing archaic variation.}, } @article {pmid34045664, year = {2022}, author = {Denisova, E and Westphal, D and Surowy, HM and Meier, F and Hutter, B and Reifenberger, J and Rütten, A and Schulz, A and Sergon, M and Ziemer, M and Brors, B and Betz, RC and Redler, S}, title = {Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies.}, journal = {Cancer gene therapy}, volume = {29}, number = {6}, pages = {697-708}, pmid = {34045664}, issn = {1476-5500}, mesh = {*Eccrine Porocarcinoma ; Humans ; Mutation ; *Sweat Gland Neoplasms ; Tumor Suppressor Protein p53/genetics ; Exome Sequencing ; }, abstract = {Malignant sweat gland tumours are rare, with the most common form being Eccrine porocarcinoma (EP). To investigate the mutational landscape of EP, we performed whole-exome sequencing (WES) on 14 formalin-fixed paraffin-embedded samples of matched primary EP and healthy surrounding tissue. Mutational profiling revealed a high overall median mutation rate. This was attributed to signatures of mutational processes related to ultraviolet (UV) exposure, APOBEC enzyme dysregulation, and defective homologous double-strand break repair. All of these processes cause genomic instability and are implicated in carcinogenesis. Recurrent driving somatic alterations were detected in the EP candidate drivers TP53, FAT2, CACNA1S, and KMT2D. The analyses also identified copy number alterations and recurrent gains and losses in several chromosomal regions including that containing BRCA2, as well as deleterious alterations in multiple HRR components. In accordance with this reduced or even a complete loss of BRCA2 protein expression was detected in 50% of the investigated EP tumours. Our results implicate crucial oncogenic driver pathways and suggest that defective homologous double-strand break repair and the p53 pathway are involved in EP aetiology. Targeting of the p53 axis and PARP inhibition, and/or immunotherapy may represent promising treatment strategies.}, } @article {pmid34028527, year = {2021}, author = {Ahlquist, KD and Bañuelos, MM and Funk, A and Lai, J and Rong, S and Villanea, FA and Witt, KE}, title = {Our Tangled Family Tree: New Genomic Methods Offer Insight into the Legacy of Archaic Admixture.}, journal = {Genome biology and evolution}, volume = {13}, number = {7}, pages = {}, pmid = {34028527}, issn = {1759-6653}, support = {T32 GM007601/GM/NIGMS NIH HHS/United States ; R35 GM139628/GM/NIGMS NIH HHS/United States ; T32 GM128596/GM/NIGMS NIH HHS/United States ; R35 GM128946/GM/NIGMS NIH HHS/United States ; R01 GM127472/GM/NIGMS NIH HHS/United States ; R01 GM118652/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Genome, Human ; Genomics ; *Hominidae/genetics ; Humans ; *Neanderthals/genetics ; Pedigree ; }, abstract = {The archaic ancestry present in the human genome has captured the imagination of both scientists and the wider public in recent years. This excitement is the result of new studies pushing the envelope of what we can learn from the archaic genetic information that has survived for over 50,000 years in the human genome. Here, we review the most recent ten years of literature on the topic of archaic introgression, including the current state of knowledge on Neanderthal and Denisovan introgression, as well as introgression from other as-yet unidentified archaic populations. We focus this review on four topics: 1) a reimagining of human demographic history, including evidence for multiple admixture events between modern humans, Neanderthals, Denisovans, and other archaic populations; 2) state-of-the-art methods for detecting archaic ancestry in population-level genomic data; 3) how these novel methods can detect archaic introgression in modern African populations; and 4) the functional consequences of archaic gene variants, including how those variants were co-opted into novel function in modern human populations. The goal of this review is to provide a simple-to-access reference for the relevant methods and novel data, which has changed our understanding of the relationship between our species and its siblings. This body of literature reveals the large degree to which the genetic legacy of these extinct hominins has been integrated into the human populations of today.}, } @article {pmid33992907, year = {2021}, author = {Kerner, G and Patin, E and Quintana-Murci, L}, title = {New insights into human immunity from ancient genomics.}, journal = {Current opinion in immunology}, volume = {72}, number = {}, pages = {116-125}, pmid = {33992907}, issn = {1879-0372}, mesh = {Animals ; COVID-19/epidemiology/genetics/*immunology ; Evolution, Molecular ; Genetic Predisposition to Disease ; Genetics, Population ; Genomics ; Hominidae ; Humans ; Immunity/*genetics ; SARS-CoV-2/*physiology ; }, abstract = {Population genetic studies have clearly indicated that immunity and host defense are among the functions most frequently subject to natural selection, and increased our understanding of the biological relevance of the corresponding genes and their contribution to variable immune traits and diseases. Herein, we will focus on some recently studied forms of human adaptation to infectious agents, including hybridization with now-extinct hominins, such as Neanderthals and Denisovans, and admixture between modern human populations. These studies, which are partly enabled by the technological advances in the sequencing of DNA from ancient remains, provide new insight into the sources of immune response variation in contemporary humans, such as the recently reported link between Neanderthal heritage and susceptibility to severe COVID-19 disease. Furthermore, ancient DNA analyses, in both humans and pathogens, allow to measure the action of natural selection on immune genes across time and to reconstruct the impact of past epidemics on the evolution of human immunity.}, } @article {pmid33934123, year = {2021}, author = {Mualim, K and Theunert, C and Slatkin, M}, title = {Estimation of coalescence probabilities and population divergence times from SNP data.}, journal = {Heredity}, volume = {127}, number = {1}, pages = {1-9}, pmid = {33934123}, issn = {1365-2540}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Humans ; *Neanderthals/genetics ; Population Density ; Probability ; }, abstract = {We present a method called the G(A|B) method for estimating coalescence probabilities within population lineages from genome sequences when one individual is sampled from each population. Population divergence times can be estimated from these coalescence probabilities if additional assumptions about the history of population sizes are made. Our method is based on a method presented by Rasmussen et al. (2014) to test whether an archaic genome is from a population directly ancestral to a present-day population. The G(A|B) method does not require distinguishing ancestral from derived alleles or assumptions about demographic history before population divergence. We discuss the relationship of our method to two similar methods, one introduced by Green et al. (2010) and called the F(A|B) method and the other introduced by Schlebusch et al. (2017) and called the TT method. When our method is applied to individuals from three or more populations, it provides a test of whether the population history is treelike because coalescence probabilities are additive on a tree. We illustrate the use of our method by applying it to three high-coverage archaic genomes, two Neanderthals (Vindija and Altai) and a Denisovan.}, } @article {pmid33892510, year = {2021}, author = {Villanea, FA and Huerta-Sanchez, E and Fox, K}, title = {ABO Genetic Variation in Neanderthals and Denisovans.}, journal = {Molecular biology and evolution}, volume = {38}, number = {8}, pages = {3373-3382}, pmid = {33892510}, issn = {1537-1719}, support = {R35 GM128946/GM/NIGMS NIH HHS/United States ; }, mesh = {ABO Blood-Group System/*genetics ; Animals ; Genetic Variation ; Genome, Human ; Haplotypes ; Humans ; Neanderthals/*genetics ; }, abstract = {Variation at the ABO locus was one of the earliest sources of data in the study of human population identity and history, and to this day remains widely genotyped due to its importance in blood and tissue transfusions. Here, we look at ABO blood type variants in our archaic relatives: Neanderthals and Denisovans. Our goal is to understand the genetic landscape of the ABO gene in archaic humans, and how it relates to modern human ABO variation. We found two Neanderthal variants of the O allele in the Siberian Neanderthals (O1 and O2), one of these variants is shared with an European Neanderthal, who is a heterozygote for this O1 variant and a rare cis-AB variant. The Denisovan individual is heterozygous for two variants of the O1 allele, functionally similar to variants found widely in modern humans. Perhaps more surprisingly, the O2 allele variant found in Siberian Neanderthals can be found at low frequencies in modern Europeans and Southeast Asians, and the O1 allele variant found in Siberian and European Neanderthal is also found at very low frequency in modern East Asians. Our genetic distance analyses suggest both alleles survive in modern humans due to inbreeding with Neanderthals. We find that the sequence backgrounds of the surviving Neanderthal-like O alleles in modern humans retain a higher sequence divergence than other surviving Neanderthal genome fragments, supporting a view of balancing selection operating in the Neanderthal ABO alleles by retaining highly diverse haplotypes compared with portions of the genome evolving neutrally.}, } @article {pmid33885362, year = {2021}, author = {Weiss, CV and Harshman, L and Inoue, F and Fraser, HB and Petrov, DA and Ahituv, N and Gokhman, D}, title = {The cis-regulatory effects of modern human-specific variants.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33885362}, issn = {2050-084X}, support = {1U01MH116438/MH/NIMH NIH HHS/United States ; UM1 HG009408/HG/NHGRI NIH HHS/United States ; P01 HD084387/HD/NICHD NIH HHS/United States ; 1R01MH109907/MH/NIMH NIH HHS/United States ; R01 MH116438/MH/NIMH NIH HHS/United States ; R35 GM118165/GM/NIGMS NIH HHS/United States ; 1UM1HG009408/HG/NHGRI NIH HHS/United States ; F31 HG011568/HG/NHGRI NIH HHS/United States ; }, mesh = {Embryonic Stem Cells/*metabolism ; *Gene Expression Regulation ; Genome, Human ; Humans ; Osteoblasts/*metabolism ; *Polymorphism, Single Nucleotide ; Stem Cells/*metabolism ; Transcription Factors/*metabolism ; }, abstract = {The Neanderthal and Denisovan genomes enabled the discovery of sequences that differ between modern and archaic humans, the majority of which are noncoding. However, our understanding of the regulatory consequences of these differences remains limited, in part due to the decay of regulatory marks in ancient samples. Here, we used a massively parallel reporter assay in embryonic stem cells, neural progenitor cells, and bone osteoblasts to investigate the regulatory effects of the 14,042 single-nucleotide modern human-specific variants. Overall, 1791 (13%) of sequences containing these variants showed active regulatory activity, and 407 (23%) of these drove differential expression between human groups. Differentially active sequences were associated with divergent transcription factor binding motifs, and with genes enriched for vocal tract and brain anatomy and function. This work provides insight into the regulatory function of variants that emerged along the modern human lineage and the recent evolution of human gene expression.}, } @article {pmid33883706, year = {2020}, author = {}, title = {Podcast: Denisovan DNA in modern Europeans, and the birth of an unusual celestial object.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-020-01170-6}, pmid = {33883706}, issn = {1476-4687}, } @article {pmid33877744, year = {2021}, author = {Denisova, K}, title = {Genetic vulnerability of exposures to antenatal maternal treatments in 1- to 2-month-old infants.}, journal = {Infancy : the official journal of the International Society on Infant Studies}, volume = {26}, number = {3}, pages = {515-532}, pmid = {33877744}, issn = {1532-7078}, support = {R01 MH121605/MH/NIMH NIH HHS/United States ; R01MH121605/MH/NIMH NIH HHS/United States ; }, mesh = {*Autism Spectrum Disorder/genetics ; Female ; Humans ; Infant ; Magnetic Resonance Imaging ; Mothers ; Pregnancy ; Risk Factors ; Siblings ; }, abstract = {The growth and maturation of the nervous system are vulnerable during pregnancy. The impact of antenatal exposures to maternal treatments, in the context of genetic vulnerability of the fetus, on sensorimotor functioning in early infancy remains unexplored. Statistical features of head movements obtained from resting-state sleep fMRI scans are examined in 1- to 2-month-old infants, both those at high risk (HR) for autism spectrum disorder (ASD) due to a biological sibling with ASD and at low risk (LR) (N = 56). In utero exposures include maternal prescription medications (psychotropic Rx: N = 3HR ; N = 5LR vs. non-psychotropic Rx: N = 11HR ; N = 9LR vs. none: N = 11HR ; N = 16LR), psychiatric diagnoses (two or more Dx2 : N = 5HR ; N = 1LR ; one Dx1 : N = 4HR ; N = 5LR ; no Dx: N = 12HR ; N = 19LR), infections requiring antibiotics (infection: N = 5HR ; N = 8LR ; no infection: N = 20HR ; N = 22LR), or high fever (fever: N = 2HR ; N = 2LR ; no fever: N = 23HR ; N = 27LR). Movements with significantly higher variability are detected in infants exposed to psychotropics (e.g., opioid analgesics) and those whose mothers had fever, and this effect is significantly worse for infants at HR for ASD. Movements are significantly less variable in HR infants with non-psychotropic exposures (e.g., antibiotics). Heightened number of psychiatric or mental health conditions is associated with noisier movements in both risk groups. Genetic vulnerability due to in utero exposure to maternal treatments is an important future approach to be advanced in the field of early mind and brain development.}, } @article {pmid33854233, year = {2021}, author = {Choin, J and Mendoza-Revilla, J and Arauna, LR and Cuadros-Espinoza, S and Cassar, O and Larena, M and Ko, AM and Harmant, C and Laurent, R and Verdu, P and Laval, G and Boland, A and Olaso, R and Deleuze, JF and Valentin, F and Ko, YC and Jakobsson, M and Gessain, A and Excoffier, L and Stoneking, M and Patin, E and Quintana-Murci, L}, title = {Genomic insights into population history and biological adaptation in Oceania.}, journal = {Nature}, volume = {592}, number = {7855}, pages = {583-589}, pmid = {33854233}, issn = {1476-4687}, mesh = {Adaptation, Biological/*genetics ; Animals ; Australia ; *Biological Evolution ; Datasets as Topic ; Asia, Eastern ; Genetic Introgression ; *Genetics, Population ; Genome, Human/*genetics ; *Genomics ; History, Ancient ; Human Migration/*history ; Humans ; *Islands ; Native Hawaiian or Other Pacific Islander/*genetics ; Neanderthals/genetics ; Oceania ; Pacific Ocean ; Taiwan ; }, abstract = {The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes[1]. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region. We find that the ancestors of Papuan-related ('Near Oceanian') groups underwent a strong bottleneck before the settlement of the region, and separated around 20,000-40,000 years ago. We infer that the East Asian ancestors of Pacific populations may have diverged from Taiwanese Indigenous peoples before the Neolithic expansion, which is thought to have started from Taiwan around 5,000 years ago[2-4]. Additionally, this dispersal was not followed by an immediate, single admixture event with Near Oceanian populations, but involved recurrent episodes of genetic interactions. Our analyses reveal marked differences in the proportion and nature of Denisovan heritage among Pacific groups, suggesting that independent interbreeding with highly structured archaic populations occurred. Furthermore, whereas introgression of Neanderthal genetic information facilitated the adaptation of modern humans related to multiple phenotypes (for example, metabolism, pigmentation and neuronal development), Denisovan introgression was primarily beneficial for immune-related functions. Finally, we report evidence of selective sweeps and polygenic adaptation associated with pathogen exposure and lipid metabolism in the Pacific region, increasing our understanding of the mechanisms of biological adaptation to island environments.}, } @article {pmid36286785, year = {2021}, author = {Dmitrieva, OA and Mironova, OY and Sivakova, OA and Denisova, AR and Solnceva, TD and Fomin, VV}, title = {[The periprocedural myocardial infarction and probability of the developing of the contrast-induced acute kidneys injury in clinical practice. Case report].}, journal = {Terapevticheskii arkhiv}, volume = {93}, number = {4}, pages = {482-486}, doi = {10.26442/00403660.2021.04.200686}, pmid = {36286785}, issn = {0040-3660}, abstract = {Nowadays, taking into account the number of elderly patients with sеveral associated diseases requiring percutaneous transluminal balloon coronary angioplasty (PTCA), the risk of the development of unwanted complications is also growing. In this article we present the clinical case, where the PTCA had complications with myocardial infarction of the 4a type without contrast-induced acute kidney injury (contrast-induced nephropathy).}, } @article {pmid33825739, year = {2021}, author = {Gulaĭ, IS and Snegirev, AI and Denisova, NP and Dmitriev, AB}, title = {[Chronic spinal stimulation in treatment of lower limb critical ischaemia syndrome].}, journal = {Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery}, volume = {27}, number = {1}, pages = {128-135}, doi = {10.33529/ANGIO2020413}, pmid = {33825739}, issn = {1027-6661}, mesh = {*Arterial Occlusive Diseases ; Arteries ; Humans ; Ischemia/diagnosis/etiology/therapy ; Leg ; Lower Extremity ; *Peripheral Arterial Disease ; }, abstract = {Obliterating peripheral artery disease is a commonly occurring pathological condition, most often resulting from an atherosclerotic lesion of vessels with progressive narrowing of their lumens. The consequences of decompensation of chronic arterial insufficiency such as ischaemic pain, claudication, and trophic impairments are in some instances difficult to treat, despite using multicomponent medicamentous therapy and/or performing revascularizing interventions. This article describes a clinical case report regarding the use of spinal stimulation in a patient presenting with stage IV chronic lower limb ischaemia according to the Fontaine classification. This is accompanied and followed by depicting the dynamics of the laboratory, instrumental, and clinical parameters over a two-year follow-up period. In order to explain the choice of the intervention and the causes of the described picture, discussed are the existing theories of the mechanisms of action of spinal stimulation. To this is added a literature review of using this method in treatment of lower limb critical ischaemia when performing reconstructive angiosurgical treatment is unavailable. Mention is also made of the incidence and types of probable complications, as well as possibilities and limitations of the method.}, } @article {pmid33769498, year = {2021}, author = {Sjödin, P and McKenna, J and Jakobsson, M}, title = {Estimating divergence times from DNA sequences.}, journal = {Genetics}, volume = {217}, number = {4}, pages = {}, pmid = {33769498}, issn = {1943-2631}, mesh = {Animals ; DNA, Ancient ; Genetic Drift ; Humans ; *Mutation Rate ; Neanderthals/genetics ; *Polymorphism, Genetic ; Population/*genetics ; Time ; }, abstract = {The patterns of genetic variation within and among individuals and populations can be used to make inferences about the evolutionary forces that generated those patterns. Numerous population genetic approaches have been developed in order to infer evolutionary history. Here, we present the "Two-Two (TT)" and the "Two-Two-outgroup (TTo)" methods; two closely related approaches for estimating divergence time based in coalescent theory. They rely on sequence data from two haploid genomes (or a single diploid individual) from each of two populations. Under a simple population-divergence model, we derive the probabilities of the possible sample configurations. These probabilities form a set of equations that can be solved to obtain estimates of the model parameters, including population split times, directly from the sequence data. This transparent and computationally efficient approach to infer population divergence time makes it possible to estimate time scaled in generations (assuming a mutation rate), and not as a compound parameter of genetic drift. Using simulations under a range of demographic scenarios, we show that the method is relatively robust to migration and that the TTo method can alleviate biases that can appear from drastic ancestral population size changes. We illustrate the utility of the approaches with some examples, including estimating split times for pairs of human populations as well as providing further evidence for the complex relationship among Neandertals and Denisovans and their ancestors.}, } @article {pmid33759196, year = {2021}, author = {Shunatova, N and Denisova, S and Shchenkov, S}, title = {Ultrastructure of rhizoids in the marine bryozoan Dendrobeania fruticosa (Gymnolaemata: Cheilostomata).}, journal = {Journal of morphology}, volume = {282}, number = {6}, pages = {847-862}, doi = {10.1002/jmor.21351}, pmid = {33759196}, issn = {1097-4687}, mesh = {Animals ; *Bryozoa ; Epidermis ; Extracellular Matrix ; Torso ; }, abstract = {Bryozoans form colonies of iterated modules, termed zooids, and display varying degrees of polymorphism. Polymorphic colonies comprise autozooids (or feeding zooids) and heteromorphic zooids, among which the most common types are avicularia and kenozooids. Kenozooids differ in shape, size, and presumed function. Among this diversity, there are rhizoids, which serve to attach colonies to the substrate or to lift them above it. To date, only general data on anatomy of kenozooids at light microscopy level are available. Here, we present the first description of the ultrastructure of the holdfast-like rhizoids of the cheilostome bryozoan Dendrobeania fruticosa. The rhizoid wall is composed of a single-layered epidermis, which produces the ectocyst. The voluminous cavity is acoelomate: it has no special cellular lining, nor any signs of an extracellular matrix toward the epidermis. It is traversed by delicate branching funicular strands that originate from the pore plate. The only cells in contact with the epidermis are the cells of the funicular system and the storage cells. The pore plate between the rhizoid and autozooid includes a variable number of communication pores. Each pore is plugged with a rosette complex, which includes a cincture cell and four special cells extending through the pore. The limiting cells are absent, and the special cells are in direct contact with the funicular strands. Cell contacts between special cells are absent; moreover, there are spaces between their proximal lobes filled with a heterogeneous matrix similar to that in the lumen of the funicular strands. Such matrix is also found outside of the extracellular matrix surrounding the special cells. These findings allow us to suggest that nutrient transport most likely occurs between, rather than through, the special cells. However, further studies are needed to understand how the rosette complex functions.}, } @article {pmid33753899, year = {2021}, author = {Teixeira, JC and Jacobs, GS and Stringer, C and Tuke, J and Hudjashov, G and Purnomo, GA and Sudoyo, H and Cox, MP and Tobler, R and Turney, CSM and Cooper, A and Helgen, KM}, title = {Widespread Denisovan ancestry in Island Southeast Asia but no evidence of substantial super-archaic hominin admixture.}, journal = {Nature ecology & evolution}, volume = {5}, number = {5}, pages = {616-624}, pmid = {33753899}, issn = {2397-334X}, mesh = {Animals ; Asia, Southeastern ; Fossils ; *Hominidae/genetics ; Humans ; Islands ; *Neanderthals ; }, abstract = {The hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic 'super-archaic' species-Homo luzonensis and H. floresiensis-were present around the time anatomically modern humans arrived in the region >50,000 years ago. Intriguingly, contemporary human populations across ISEA carry distinct genomic traces of ancient interbreeding events with Denisovans-a separate hominin lineage that currently lacks a fossil record in ISEA. To query this apparent disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in >400 modern human genomes, including >200 from ISEA. Our results corroborate widespread Denisovan ancestry in ISEA populations, but fail to detect any substantial super-archaic admixture signals compatible with the endemic fossil record of ISEA. We discuss the implications of our findings for the understanding of hominin history in ISEA, including future research directions that might help to unlock more details about the prehistory of the enigmatic Denisovans.}, } @article {pmid33743527, year = {2021}, author = {Denisova, K and Barmettler, A}, title = {Evaluating the Thyroid Eye Disease Patient.}, journal = {International ophthalmology clinics}, volume = {61}, number = {2}, pages = {33-52}, doi = {10.1097/IIO.0000000000000351}, pmid = {33743527}, issn = {1536-9617}, mesh = {*Graves Ophthalmopathy/diagnosis/therapy ; Humans ; }, } @article {pmid33720649, year = {2021}, author = {Soldatsky, YL and Denisova, OA and Vitkovskaya, IP and Krugovskaya, NL}, title = {[Modern causes of tracheostomy in children].}, journal = {Vestnik otorinolaringologii}, volume = {86}, number = {1}, pages = {36-40}, doi = {10.17116/otorino20218601136}, pmid = {33720649}, issn = {0042-4668}, mesh = {*Airway Obstruction ; Child ; Humans ; Infant, Newborn ; Intubation, Intratracheal ; Respiration, Artificial ; Retrospective Studies ; *Tracheostomy/adverse effects ; }, abstract = {UNLABELLED: The purpose of work is to analyze the causes of tracheostomy in children hospitalized in a large multidisciplinary pediatric hospital.

MATERIAL AND METHODS: Retrospective analysis of case of children treated in a multidisciplinary urgent hospital - GBUZ «Morozovskaya CCCH of MDH», which in the period from 01.01.16 to 31.12.18 was made operation «tracheostomy» was conducted.

RESULTS: Tracheostomy was performed in 138 (0.064%) among 216 469 hospitalized children. Age at the time of tracheostomy ranged from 2 weeks to 17.5 years (on average 67.9±59.84 months, Me=47.5 months), and 36.2% of children had tracheostomy was done on the 1[st] year of life. 126 (91.3%) patients required prolonged tracheal intubation prior to tracheostomy placement; the duration of intubation ranged from 1 to 95 days (on average 19.9±13.42 days, Me=14 days). The main reasons of tracheostomy were the need for long-term mechanical ventilation/respiratory support; the need for constant sanitation of the lower respiratory tract with bulbar/pseudobulbar disorders; upper respiratory paths obstruction. The diseases that led to this condition can be grouped into 4 categories: CNS pathology - 76 (55.1%) patients; brain / spinal cord tumors - 36 (26.1%); neurodystrophy and stenosis of the upper respiratory tract of various etiology - 13 (9.4% each) patients. 68.1% of patients were found incurable and required palliative care. Mortality among patients with a known catamnesis was 39.1%, mainly due to progression of the underlying disease; the lethality associated with tracheal cannulation was 1.4%.

CONCLUSION: Currently, pediatric tracheostomy is moving into the category of predominantly planned surgical interventions. More than 2/3 of children requiring tracheostomy are patients in need of palliative care with severe pathology of the central nervous system; in which the main indications for surgery are the need for respiration support and regular tracheobronchial care..}, } @article {pmid33659800, year = {2020}, author = {Makarova, EN and Yakovleva, TV and Balyibina, NY and Baranov, KO and Denisova, EI and Dubinina, AD and Feofanova, NA and Bazhan, NM}, title = {Pharmacological effects of fibroblast growth factor 21 are sex-specific in mice with the lethal yellow (A[y]) mutation.}, journal = {Vavilovskii zhurnal genetiki i selektsii}, volume = {24}, number = {2}, pages = {200-208}, doi = {10.18699/VJ20.40-o}, pmid = {33659800}, issn = {2500-0462}, abstract = {Hypothalamic melanocortin 4 receptors (MC4R) regulate energy balance. Mutations in the MC4R gene are the most common cause of monogenic obesity in humans. Fibroblast growth factor 21 (FGF21) is a promising antiobesity agent, but its effects on melanocortin obesity are unknown. Sex is an important biological variable that must be considered when conducting preclinical studies; however, in laboratory animal models, the pharmacological effects of FGF21 are well documented only for male mice. We aimed at investigating whether FGF21 affects metabolism in male and female mice with the lethal yellow (A[y]) mutation, which results in MC4R blockage and obesity development. Obese C57Bl-A[y] male and female mice were administered subcutaneously for 10 days with vehicle or FGF21 (1 mg per 1 kg). Food intake (FI), body weight (BW), blood parameters, and gene expression in the liver, muscles, brown adipose tissue, subcutaneous and visceral white adipose tissues, and hypothalamus were measured. FGF21 action strongly depended on the sex of the animals. In the males, FGF21 decreased BW and insulin blood levels without affecting FI. In the females, FGF21 increased FI and liver weight, but did not affect BW. In control A[y]-mice, expression of genes involved in lipid and glucose metabolism (Ppargc1a, Cpt1, Pck1, G6p, Slc2a2) in the liver and genes involved in lipogenesis (Pparg, Lpl, Slc2a4) in visceral adipose tissue was higher in females than in males, and FGF21 administration inhibited the expression of these genes in females. FGF21 administration decreased hypothalamic POMC mRNA only in males. Thus, the pharmacological effect of FGF21 were significantly different in male and female A[y]-mice; unlike males, females were resistant to catabolic effects of FGF21.}, } @article {pmid33580755, year = {2021}, author = {Gusev, EI and Blokhin, VE and Vartanov, SA and Martynov, MY and Katunina, EA and Alesenko, AV and Denisova, IA and Pavlova, EN and Polterovich, VM and Kucheryanu, VG and Shupik, MA and Nodel, MR and Kalinkin, AL and Sokolov, SA and Chubarova, TV and Shakleina, MV and Pronina, TS and Ugryumov, MV}, title = {[Development of early diagnosis of Parkinson's disease and comprehensive economic analysis of the effect of its implementation].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {121}, number = {1}, pages = {9-20}, doi = {10.17116/jnevro20211210119}, pmid = {33580755}, issn = {1997-7298}, mesh = {Animals ; Biomarkers ; Early Diagnosis ; Humans ; *Parkinson Disease/diagnosis ; Positron-Emission Tomography ; Prodromal Symptoms ; }, abstract = {The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility» analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.}, } @article {pmid33574182, year = {2021}, author = {Trujillo, CA and Rice, ES and Schaefer, NK and Chaim, IA and Wheeler, EC and Madrigal, AA and Buchanan, J and Preissl, S and Wang, A and Negraes, PD and Szeto, RA and Herai, RH and Huseynov, A and Ferraz, MSA and Borges, FS and Kihara, AH and Byrne, A and Marin, M and Vollmers, C and Brooks, AN and Lautz, JD and Semendeferi, K and Shapiro, B and Yeo, GW and Smith, SEP and Green, RE and Muotri, AR}, title = {Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6530}, pages = {}, pmid = {33574182}, issn = {1095-9203}, support = {R01 HL137223/HL/NHLBI NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; R01 MH121487/MH/NIMH NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; R01 MH113545/MH/NIMH NIH HHS/United States ; K01 AA026911/AA/NIAAA NIH HHS/United States ; U19 MH107367/MH/NIMH NIH HHS/United States ; T32 HG008345/HG/NHGRI NIH HHS/United States ; U41 HG009889/HG/NHGRI NIH HHS/United States ; }, mesh = {Alleles ; Alternative Splicing ; Amino Acid Substitution ; Animals ; Binding Sites ; Biological Evolution ; CRISPR-Cas Systems ; Cell Proliferation ; Cerebral Cortex/cytology/*growth & development/*physiology ; Gene Expression Regulation, Developmental ; Genetic Variation ; Genome ; Genome, Human ; Haplotypes ; Hominidae/genetics ; Humans ; Induced Pluripotent Stem Cells ; Neanderthals/*genetics ; Nerve Net/physiology ; Nerve Tissue Proteins/genetics/metabolism ; Neuro-Oncological Ventral Antigen ; Neurons/*physiology ; Organoids ; RNA-Binding Proteins/*genetics/*metabolism ; Synapses/physiology ; }, abstract = {The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (NOVA1) plays a key role in neural development and function. NOVA1 also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of NOVA1 Moreover, levels of synaptic markers and synaptic protein coassociations correlated with altered electrophysiological properties in organoids expressing the archaic variant. Our results suggest that the human-specific substitution in NOVA1, which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species' evolution.}, } @article {pmid33568824, year = {2021}, author = {Bergström, A and Stringer, C and Hajdinjak, M and Scerri, EML and Skoglund, P}, title = {Origins of modern human ancestry.}, journal = {Nature}, volume = {590}, number = {7845}, pages = {229-237}, pmid = {33568824}, issn = {1476-4687}, support = {/ERC_/European Research Council/International ; /WT_/Wellcome Trust/United Kingdom ; 217223/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Africa/ethnology ; Animals ; Fossils ; Gene Flow/genetics ; History, Ancient ; Human Migration/*history ; Humans ; Neanderthals/genetics ; *Pedigree ; }, abstract = {New finds in the palaeoanthropological and genomic records have changed our view of the origins of modern human ancestry. Here we review our current understanding of how the ancestry of modern humans around the globe can be traced into the deep past, and which ancestors it passes through during our journey back in time. We identify three key phases that are surrounded by major questions, and which will be at the frontiers of future research. The most recent phase comprises the worldwide expansion of modern humans between 40 and 60 thousand years ago (ka) and their last known contacts with archaic groups such as Neanderthals and Denisovans. The second phase is associated with a broadly construed African origin of modern human diversity between 60 and 300 ka. The oldest phase comprises the complex separation of modern human ancestors from archaic human groups from 0.3 to 1 million years ago. We argue that no specific point in time can currently be identified at which modern human ancestry was confined to a limited birthplace, and that patterns of the first appearance of anatomical or behavioural traits that are used to define Homo sapiens are consistent with a range of evolutionary histories.}, } @article {pmid33556445, year = {2021}, author = {Reinscheid, RK and Mafessoni, F and Lüttjohann, A and Jüngling, K and Pape, HC and Schulz, S}, title = {Neandertal introgression and accumulation of hypomorphic mutations in the neuropeptide S (NPS) system promote attenuated functionality.}, journal = {Peptides}, volume = {138}, number = {}, pages = {170506}, doi = {10.1016/j.peptides.2021.170506}, pmid = {33556445}, issn = {1873-5169}, mesh = {Animals ; *Biological Evolution ; Genetic Introgression/*genetics ; Hominidae/genetics ; Humans ; Mutation/genetics ; Neanderthals/genetics ; Neuropeptides/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, G-Protein-Coupled/*genetics ; *Selection, Genetic ; }, abstract = {The neuropeptide S (NPS) system plays an important role in fear and fear memory processing but has also been associated with allergic and inflammatory diseases. Genes for NPS and its receptor NPSR1 are found in all tetrapods. Compared to non-human primates, several non-synonymous single-nucleotide polymorphisms (SNPs) occur in both human genes that collectively result in functional attenuation, suggesting adaptive mechanisms in a human context. To investigate historic and geographic origins of these hypomorphic mutations and explore genetic signs of selection, we analyzed ancient genomes and worldwide genotype frequencies of four prototypic SNPs in the NPS system. Neandertal and Denisovan genomes contain exclusively ancestral alleles for NPSR1 while all derived alleles occur in ancient genomes of anatomically modern humans, indicating that they arose in modern Homo sapiens. Worldwide genotype frequencies for three hypomorphic NPSR1 SNPs show significant regional homogeneity but follow a gradient towards increasing derived allele frequencies that supports an out-of-Africa scenario. Increased density of high-frequency polymorphisms around the three NPSR1 loci suggests weak or possibly balancing selection. A hypomorphic mutation in the NPS precursor, however, was detected at high frequency in Eurasian Neandertal genomes and shows genetic signatures indicating that it was introgressed into the human gene pool, particularly in Southern Europe, by interbreeding with Neandertals. We discuss potential evolutionary scenarios including behavior and immune-based natural selection.}, } @article {pmid33547071, year = {2021}, author = {Bonfante, B and Faux, P and Navarro, N and Mendoza-Revilla, J and Dubied, M and Montillot, C and Wentworth, E and Poloni, L and Varón-González, C and Jones, P and Xiong, Z and Fuentes-Guajardo, M and Palmal, S and Chacón-Duque, JC and Hurtado, M and Villegas, V and Granja, V and Jaramillo, C and Arias, W and Barquera, R and Everardo-Martínez, P and Sánchez-Quinto, M and Gómez-Valdés, J and Villamil-Ramírez, H and Silva de Cerqueira, CC and Hünemeier, T and Ramallo, V and Liu, F and Weinberg, SM and Shaffer, JR and Stergiakouli, E and Howe, LJ and Hysi, PG and Spector, TD and Gonzalez-José, R and Schüler-Faccini, L and Bortolini, MC and Acuña-Alonzo, V and Canizales-Quinteros, S and Gallo, C and Poletti, G and Bedoya, G and Rothhammer, F and Thauvin-Robinet, C and Faivre, L and Costedoat, C and Balding, D and Cox, T and Kayser, M and Duplomb, L and Yalcin, B and Cotney, J and Adhikari, K and Ruiz-Linares, A}, title = {A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation.}, journal = {Science advances}, volume = {7}, number = {6}, pages = {}, pmid = {33547071}, issn = {2375-2548}, support = {R00 DE024194/DE/NIDCR NIH HHS/United States ; R01 DE016148/DE/NIDCR NIH HHS/United States ; R01 DE027023/DE/NIDCR NIH HHS/United States ; U01 DE020078/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; *Face/anatomy & histology ; Genome-Wide Association Study ; Genotype ; Hispanic or Latino/genetics ; Humans ; Mice ; Phenotype ; *Polymorphism, Single Nucleotide ; *Vesicular Transport Proteins/genetics ; }, abstract = {To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.}, } @article {pmid33459549, year = {2020}, author = {Kondratieva, EA and Kondratev, SA and Denisova, AA and Ivanova, NE and Kondratiev, AN}, title = {[Results of treatment with intravenous amantadine sulfate (PK-Merz) patients with chronic disorders of consciousness].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {120}, number = {12}, pages = {102-108}, doi = {10.17116/jnevro2020120121102}, pmid = {33459549}, issn = {1997-7298}, mesh = {*Amantadine ; *Consciousness ; Consciousness Disorders ; Humans ; Persistent Vegetative State ; Wakefulness ; }, abstract = {The article presents literature review of the recent publications devoted to the drugs with dopaminergic, antiglutamatergic and GABA-ergic effects in the treatment of patients with vegetative state/areactive wakefulness syndrome (VS/AWS). The authors analyzed their own results of the effects of intravenous form of amantadine sulfate (PK Merz) in 142 VS/AWS patients caused by different etiological factors. Depending on the dominant neurological symptoms, patients were divided into three main groups: areactive type of course (group 1 - 61 patients), predominance of primitive limbic reactions (group 2 - 35 patients) and predominance of extrapyramidal symptoms (group 3 - 46 patients). Therapy results were evaluated one month later by CRS-R scale, which showed that the most distinct positive dynamics was observed in group 3.}, } @article {pmid33417716, year = {2021}, author = {Greer, C and Bhakta, H and Ghanem, L and Refai, F and Linn, E and Avella, M}, title = {Deleterious variants in genes regulating mammalian reproduction in Neanderthals, Denisovans and extant humans.}, journal = {Human reproduction (Oxford, England)}, volume = {36}, number = {3}, pages = {734-755}, doi = {10.1093/humrep/deaa347}, pmid = {33417716}, issn = {1460-2350}, mesh = {Animals ; Europe ; Genome, Human ; *Hominidae/genetics ; Humans ; Male ; *Neanderthals/genetics ; Nuclear Proteins ; Reproduction/genetics ; Trans-Activators ; }, abstract = {STUDY QUESTION: Were Neanderthals and Denisovans (referred here also as extinct hominidae) carrying deleterious variants in genes regulating reproduction?

SUMMARY ANSWER: The majority of extinct hominidae analyzed here, presented a considerable number of deleterious variants per individual in proteins regulating different aspects of reproduction, including gonad and uterine function, and gametogenesis.

WHAT IS KNOWN ALREADY: Neanderthals, Denisovans and extant humans were interfertile and hybridized while occupying geographically overlapping areas in Europe and Asia. This is evidenced by the small archaic genome component (average ∼2%) present in non-African extant humans.

STUDY DESIGN, SIZE, DURATION: The genome of eight extinct hominidae, together with five human genome databases, plus 44 mothers and 48 fathers (fertile controls), were screened to look for deleterious variants in 1734 protein-coding genes regulating reproduction.

Ancient DNA from six Neanderthals and two Denisovans dated between ∼82 000 and 43 000 calibrated years was retrieved from the public European Nucleotide Archive. The hominins analyzed include Altai, Vindija 33.15, 33.19, 33.25 and 33.26, El Sidron 1253, Denisova 3 and 11. Their DNA was analyzed using the CLC Genomics Workbench 12, by mapping overlapping paired-end reads (Illumina, FASTQ files) to the human genome assembly GRCh37 (hg19) (Vindija 33.19, 33.25, 33.26, Denisova 3 and Denisova 11) or by analyzing BAM files (Altai, El Sidron 1253 and Vindija 33.15) (human genome reference, GRCh37 (hg19)). Non-synonymous reproductive variants were classified as deleterious or tolerated (PolyPhen-2 and SIFT analyses) and were compared to deleterious variants obtained from extant human genome databases (Genome Aggregation Database (GnomAD), 1000 Genomes, the Haplotype Map (HapMap), Single Nucleotide Polymorphism Database (dbSNPs)) across different populations. A genetic intersection between extant or extinct DNA variants and other genetic disorders was evaluated by annotating the obtained variants with the Clinical Variant (ClinVar) database.

Among the eight extinct hominidae analyzed, a total of 9650 non-synonymous variants (only coverage ≥20 reads included; frameshift mutations were excluded) in 1734 reproductive protein-coding genes were found, 24% of which were classified as deleterious. The majority (73%) of the deleterious alleles present in extant humans that are shared between extant humans and extinct hominidae were found to be rare (<1%) in extant human populations. A set of 8044 variants were found uniquely in extinct hominidae. At the single-gene level, no extinct individual was found to be homozygous for deleterious variants in genes necessary for gamete recognition and fusion, and no higher chance of embryo-lethality (calculated by Mendelian Genetics) was found upon simulated mating between extant human and extinct hominidae compared to extant human-extant human. However, three of the eight extinct hominidae were found to be homozygous for 48-69 deleterious variants in 55 genes controlling ovarian and uterine functions, or oogenesis (AKAP1, BUB1B, CCDC141, CDC73, DUSP6, ESR1, ESR2, PATL2, PSMC3IP, SEMA3A, WT1 and WNT4). Moreover, we report the distribution of nine Neanderthal variants in genes associated with a human fertility phenotype found in extant human populations, one of which has been associated with polycystic ovarian syndrome and primary congenital glaucoma.

While analyzing archaic DNA, stringent filtering criteria were adopted to screen for deleterious variants in Neanderthals and Denisovans, which could result in missing a number of variants. Such restraints preserve the potential for detection of additional deleterious variants in reproductive proteins in extinct hominidae.

This study provides a comprehensive overview of putatively deleterious variants in extant human populations and extinct individuals occurring in 1734 protein-coding genes controlling reproduction and provides the fundaments for future functional studies of extinct variants in human reproduction.

This study was supported by the Department of Biological Science and by the Office of Research and Sponsored Programs at the University of Tulsa (Faculty Research Grant and Faculty Research Summer Fellowship) to M.A. and the University of Tulsa, Tulsa Undergraduate Research Challenge (TURC) program to E.L.; no conflict of interest to declare.

TRIAL REGISTRATION NUMBER: N/A.}, } @article {pmid33407590, year = {2021}, author = {Alexeeva, E and Horneff, G and Dvoryakovskaya, T and Denisova, R and Nikishina, I and Zholobova, E and Malievskiy, V and Santalova, G and Stadler, E and Balykova, L and Spivakovskiy, Y and Kriulin, I and Alshevskaya, A and Moskalev, A}, title = {Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial.}, journal = {Pediatric rheumatology online journal}, volume = {19}, number = {1}, pages = {5}, pmid = {33407590}, issn = {1546-0096}, mesh = {Adolescent ; Antirheumatic Agents/*administration & dosage/therapeutic use ; Arthritis, Juvenile/*drug therapy ; Child ; Child, Preschool ; Double-Blind Method ; Drug Therapy, Combination ; Etanercept/*administration & dosage/therapeutic use ; Female ; Humans ; Male ; Methotrexate/*administration & dosage/therapeutic use ; Remission Induction/methods ; }, abstract = {BACKGROUND: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease.

METHODS: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit.

RESULTS: By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/-IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14-32) and 32 (24-40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients.

CONCLUSIONS: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.}, } @article {pmid33343925, year = {2020}, author = {Kist, NC and Lambert, B and Campbell, S and Katzourakis, A and Lunn, D and Lemey, P and Iversen, AKN}, title = {HIV-1 p24Gag adaptation to modern and archaic HLA-allele frequency differences in ethnic groups contributes to viral subtype diversification.}, journal = {Virus evolution}, volume = {6}, number = {2}, pages = {veaa085}, pmid = {33343925}, issn = {2057-1577}, abstract = {Pathogen-driven selection and past interbreeding with archaic human lineages have resulted in differences in human leukocyte antigen (HLA)-allele frequencies between modern human populations. Whether or not this variation affects pathogen subtype diversification is unknown. Here we show a strong positive correlation between ethnic diversity in African countries and both human immunodeficiency virus (HIV)-1 p24gag and subtype diversity. We demonstrate that ethnic HLA-allele differences between populations have influenced HIV-1 subtype diversification as the virus adapted to escape common antiviral immune responses. The evolution of HIV Subtype B (HIV-B), which does not appear to be indigenous to Africa, is strongly affected by immune responses associated with Eurasian HLA variants acquired through adaptive introgression from Neanderthals and Denisovans. Furthermore, we show that the increasing and disproportionate number of HIV-infections among African Americans in the USA drive HIV-B evolution towards an Africa-centric HIV-1 state. Similar adaptation of other pathogens to HLA variants common in affected populations is likely.}, } @article {pmid33341120, year = {2020}, author = {Árnason, Ú and Hallström, B}, title = {The reversal of human phylogeny: Homo left Africa as erectus, came back as sapiens sapiens.}, journal = {Hereditas}, volume = {157}, number = {1}, pages = {51}, pmid = {33341120}, issn = {1601-5223}, support = {2018//Kungliga Fysiografiska Sällskapet i Lund (SE)/ ; 2018//Erik Philip Sörensens Foundation (SE)/ ; }, mesh = {Africa ; Animals ; *Biological Evolution ; Cytogenetic Analysis ; DNA, Mitochondrial ; Environment ; Evolution, Molecular ; Gene-Environment Interaction ; *Genetics, Population ; Hominidae/*classification/*genetics ; *Human Genetics ; Humans ; *Phylogeny ; }, abstract = {BACKGROUND: The molecular out of Africa hypothesis, OOAH, has been considered as an established fact amid population geneticists for some 25-30 years despite the early concern with it among phylogeneticists with experience beyond that of Homo. The palaeontological support for the hypothesis is also questionable, a circumstance that in the light of expanding Eurasian palaeontological knowledge has become accentuated through the last decades.

RESULTS: The direction of evolution in the phylogenetic tree of modern humans (Homo sapiens sapiens, Hss) was established inter alia by applying progressive phylogenetic analysis to an mtDNA sampling that included a Eurasian, Lund, and the African Mbuti, San and Yoruba. The examination identified the African populations as paraphyletic, thereby compromising the OOAH. The finding, which was consistent with the out of Eurasia hypothesis, OOEH, was corroborated by the mtDNA introgression from Hss into Hsnn (Neanderthals) that demonstrated the temporal and physical Eurasian coexistence of the two lineages. The results are consistent with the palaeontologically established presence of H. erectus in Eurasia, a Eurasian divergence between H. sapiens and H. antecessor ≈ 850,000 YBP, an Hs divergence between Hss and Hsn (Neanderthals + Denisovans) ≈ 800,000 YBP, an mtDNA introgression from Hss into Hsnn* ≈ 500,000 YBP and an Eurasian divergence among the ancestors of extant Hss ≈ 250,000 YBP at the exodus of Mbuti/San into Africa.

CONCLUSIONS: The present study showed that Eurasia was not the receiver but the donor in Hss evolution. The findings that Homo left Africa as erectus and returned as sapiens sapiens constitute a change in the understanding of Hs evolution to one that conforms to the extensive Eurasian record of Hs palaeontology and archaeology.}, } @article {pmid33215809, year = {2021}, author = {Bentzon, AK and Panteleev, A and Mitsura, V and Borodulina, E and Skrahina, A and Denisova, E and Tetradov, S and Podlasin, R and Riekstina, V and Kancauskiene, Z and Paduto, D and Mocroft, A and Trofimova, T and Miller, R and Post, F and Grezesczuk, A and Lundgren, JD and Inglot, M and Podlekareva, D and Bolokadze, N and Kirk, O and , }, title = {Healthcare delivery for HIV-positive people with tuberculosis in Europe.}, journal = {HIV medicine}, volume = {22}, number = {4}, pages = {283-293}, pmid = {33215809}, issn = {1468-1293}, support = {D43 TW007124/TW/FIC NIH HHS/United States ; MR/T001127/1/MRC_/Medical Research Council/United Kingdom ; RP-2016-07-012/DH_/Department of Health/United Kingdom ; }, mesh = {Antitubercular Agents/therapeutic use ; Delivery of Health Care ; Europe/epidemiology ; *HIV Infections/complications/drug therapy ; Humans ; *Tuberculosis/diagnosis/drug therapy ; }, abstract = {BACKGROUND: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE).

OBJECTIVES: To verify the differences in TB and HIV services in EE vs. WE.

METHODS: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey.

RESULTS: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged.

CONCLUSION: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites.}, } @article {pmid33183249, year = {2020}, author = {Cook, S and Kudryavtsev, AV and Bobrova, N and Saburova, L and Denisova, D and Malyutina, S and Lewis, G and Leon, DA}, title = {Prevalence of symptoms, ever having received a diagnosis and treatment of depression and anxiety, and associations with health service use amongst the general population in two Russian cities.}, journal = {BMC psychiatry}, volume = {20}, number = {1}, pages = {537}, pmid = {33183249}, issn = {1471-244X}, support = {100217/WT_/Wellcome Trust/United Kingdom ; N/A//UiT The Arctic University of Norway/ ; N/A//Norwegian Institute of Public Health/ ; N/A//Norwegian Ministry of Health and Social Affairs/ ; }, mesh = {Adult ; Aged ; *Anxiety/diagnosis/epidemiology/therapy ; Cities ; Cross-Sectional Studies ; *Depression/diagnosis/drug therapy/epidemiology ; Female ; Health Services ; Humans ; Male ; Middle Aged ; Prevalence ; Russia/epidemiology ; }, abstract = {BACKGROUND: Little is known about the burden of common mental disorders in Russia despite high levels of suicide and alcohol-related mortality. Here we investigated levels of symptoms, self-reports of ever having received a diagnosis and treatment of anxiety and depression in two Russian cities.

METHODS: The study population was men and women aged 35-69 years old participating in cross-sectional population-based studies in the cities of Arkhangelsk and Novosibirsk (2015-18). Participants completed an interview which included the PHQ-9 and GAD-7 scales, questions on whether participants had ever received a diagnosis of depression or anxiety, and health service use in the past year. Participants also reported current medication use and medications were coded in line with the WHO anatomical therapeutic classification (ATC). Depression was defined as PHQ-9 ≥ 10 and Anxiety as GAD-7 ≥ 10.

RESULTS: Age-standardised prevalence of PHQ-9 ≥ 10 was 10.7% in women and 5.4% in men (GAD-7 ≥ 10 6.2% in women; 3.0% in men). Among those with PHQ-9 ≥ 10 17% reported ever having been diagnosed with depression (equivalent finding for anxiety 29%). Only 1.5% of those with PHQ-9 ≥ 10 reported using anti-depressants and 0.6% of those with GAD-7 ≥ 10 reported using anxiolytics. No men with PHQ-9 ≥ 10 and/or GAD-7 ≥ 10 reported use of anti-depressants or anxiolytics. Use of health services increased with increasing severity of both depression and anxiety.

CONCLUSION: There was a large gap between symptoms and reporting of past diagnosis and treatment of common mental disorders in two Russian cities. Interventions aimed at improving mental health literacy and reducing stigma could be of benefit in closing this substantial treatment gap.}, } @article {pmid33183137, year = {2020}, author = {Aston, S and Denisova, K and Hurlbert, A and Olkkonen, M and Pearce, B and Rudd, M and Werner, A and Xiao, B}, title = {Exploring the Determinants of Color Perception Using #Thedress and Its Variants: The Role of Spatio-Chromatic Context, Chromatic Illumination, and Material-Light Interaction.}, journal = {Perception}, volume = {49}, number = {11}, pages = {1235-1251}, pmid = {33183137}, issn = {1468-4233}, support = {R01 MH121605/MH/NIMH NIH HHS/United States ; }, mesh = {Color ; *Color Perception ; Humans ; Light ; Lighting ; *Vision, Entoptic ; }, abstract = {The colors that people see depend not only on the surface properties of objects but also on how these properties interact with light as well as on how light reflected from objects interacts with an individual's visual system. Because individual visual systems vary, the same visual stimulus may elicit different perceptions from different individuals. #thedress phenomenon drove home this point: different individuals viewed the same image and reported it to be widely different colors: blue and black versus white and gold. This phenomenon inspired a collection of demonstrations presented at the Vision Sciences Society 2015 Meeting which showed how spatial and temporal manipulations of light spectra affect people's perceptions of material colors and illustrated the variability in individual color perception. The demonstrations also explored the effects of temporal alterations in metameric lights, including Maxwell's Spot, an entoptic phenomenon. Crucially, the demonstrations established that #thedress phenomenon occurs not only for images of the dress but also for the real dress under real light sources of different spectral composition and spatial configurations.}, } @article {pmid33180850, year = {2020}, author = {Vorobieva, NV and Makunin, AI and Druzhkova, AS and Kusliy, MA and Trifonov, VA and Popova, KO and Polosmak, NV and Molodin, VI and Vasiliev, SK and Shunkov, MV and Graphodatsky, AS}, title = {High genetic diversity of ancient horses from the Ukok Plateau.}, journal = {PloS one}, volume = {15}, number = {11}, pages = {e0241997}, pmid = {33180850}, issn = {1932-6203}, mesh = {Animals ; Animals, Domestic/*genetics ; Animals, Wild/*genetics ; DNA, Ancient/analysis ; Evolution, Molecular ; Extinction, Biological ; Fossils/history ; Genome, Mitochondrial ; Haplotypes ; High-Throughput Nucleotide Sequencing/veterinary ; History, Ancient ; Horses ; Mitochondria/*genetics ; Phylogeny ; Russia ; Whole Genome Sequencing/*veterinary ; }, abstract = {A growing number of researchers studying horse domestication come to a conclusion that this process happened in multiple locations and involved multiple wild maternal lines. The most promising approach to address this problem involves mitochondrial haplotype comparison of wild and domestic horses from various locations coupled with studies of possible migration routes of the ancient shepherds. Here, we sequenced complete mitochondrial genomes of six horses from burials of the Ukok plateau (Russia, Altai Mountains) dated from 2.7 to 1.4 thousand years before present and a single late Pleistocene wild horse from the neighboring region (Denisova cave). Sequencing data indicates that the wild horse belongs to an extinct pre-domestication lineage. Integration of the domestic horse data with known Eurasian haplotypes of a similar age revealed two distinct groups: the first one widely distributed in Europe and presumably imported to Altai, and the second one specific for Altai Mountains and surrounding area.}, } @article {pmid33168070, year = {2020}, author = {Nesterenko, MA and Starunov, VV and Shchenkov, SV and Maslova, AR and Denisova, SA and Granovich, AI and Dobrovolskij, AA and Khalturin, KV}, title = {Molecular signatures of the rediae, cercariae and adult stages in the complex life cycles of parasitic flatworms (Digenea: Psilostomatidae).}, journal = {Parasites & vectors}, volume = {13}, number = {1}, pages = {559}, pmid = {33168070}, issn = {1756-3305}, support = {МК-2105.2017.4//Council on grants of the President of the Russian Federation/ ; 19-34-90111//RFBR/ ; }, mesh = {Animals ; Cercaria/genetics ; Computational Biology ; Gene Ontology ; *Life Cycle Stages ; Snails/parasitology ; *Transcriptome ; Trematoda/*genetics/*growth & development ; }, abstract = {BACKGROUND: Parasitic flatworms (Trematoda: Digenea) represent one of the most remarkable examples of drastic morphological diversity among the stages within a life cycle. Which genes are responsible for extreme differences in anatomy, physiology, behavior, and ecology among the stages? Here we report a comparative transcriptomic analysis of parthenogenetic and amphimictic generations in two evolutionary informative species of Digenea belonging to the family Psilostomatidae.

METHODS: In this study the transcriptomes of rediae, cercariae and adult worm stages of Psilotrema simillimum and Sphaeridiotrema pseudoglobulus, were sequenced and analyzed. High-quality transcriptomes were generated, and the reference sets of protein-coding genes were used for differential expression analysis in order to identify stage-specific genes. Comparative analysis of gene sets, their expression dynamics and Gene Ontology enrichment analysis were performed for three life stages within each species and between the two species.

RESULTS: Reference transcriptomes for P. simillimum and S. pseudoglobulus include 21,433 and 46,424 sequences, respectively. Among 14,051 orthologous groups (OGs), 1354 are common and specific for two analyzed psilostomatid species, whereas 13 and 43 OGs were unique for P. simillimum and S. pseudoglobulus, respectively. In contrast to P. simillimum, where more than 60% of analyzed genes were active in the redia, cercaria and adult worm stages, in S. pseudoglobulus less than 40% of genes had such a ubiquitous expression pattern. In general, 7805 (36.41%) and 30,622 (65.96%) of genes were preferentially expressed in one of the analyzed stages of P. simillimum and S. pseudoglobulus, respectively. In both species 12 clusters of co-expressed genes were identified, and more than a half of the genes belonging to the reference sets were included into these clusters. Functional specialization of the life cycle stages was clearly supported by Gene Ontology enrichment analysis.

CONCLUSIONS: During the life cycles of the two species studied, most of the genes change their expression levels considerably, consequently the molecular signature of a stage is not only a unique set of expressed genes, but also the specific levels of their expression. Our results indicate unexpectedly high level of plasticity in gene regulation between closely related species. Transcriptomes of P. simillimum and S. pseudoglobulus provide high quality reference resource for future evolutionary studies and comparative analyses.}, } @article {pmid33149716, year = {2020}, author = {Mahesh, S and Denisova, T and Gerasimova, L and Pakhmutova, N and Mallappa, M and Vithoulkas, G}, title = {Multimorbidity After Surgical Menopause Treated with Individualized Classical Homeopathy: A Case Report.}, journal = {Clinical medicine insights. Case reports}, volume = {13}, number = {}, pages = {1179547620965560}, pmid = {33149716}, issn = {1179-5476}, abstract = {Classical homeopathy was shown to be beneficial in climacteric syndrome in many studies, but the clinical effect is unclear. To inspect if individualized classical homeopathy has a role in treating complaints after surgical menopause through real world case, we present a case of a 54-year-old Russian woman treated with individualized classical homeopathy for multimorbid conditions after surgical menopause examined for changes from homeopathic treatment. We assessed changes in climacteric symptoms, changes in comorbidities, and the general well-being of the patient. The woman had severe climacteric syndrome, pelvic inflammatory disease, dyslipidemia, obesity, hepatic steatosis, pancreatic lipomatosis, gall bladder disease, and mild subclinical hypothyroidism to begin with. She was treated with individualized classical homeopathy and followed up for 31 months. She was relieved of the vasomotor symptoms and psychological disturbances of climacteric syndrome, her weight reduced, the ultrasound scan showed absence of lipomatosis/gall bladder disease/hepatic steatosis. Blood tests showed reduction of thyroid stimulating hormone and a balance in the lipid status. Individualized classical homeopathy may have a role in the climacteric syndrome and comorbidities after surgical menopause. The efficacy of homeopathic therapy in climacteric problems must be scientifically investigated further.}, } @article {pmid33133486, year = {2020}, author = {Chernyshev, VM and Denisova, EA and Eremin, DB and Ananikov, VP}, title = {The key role of R-NHC coupling (R = C, H, heteroatom) and M-NHC bond cleavage in the evolution of M/NHC complexes and formation of catalytically active species.}, journal = {Chemical science}, volume = {11}, number = {27}, pages = {6957-6977}, pmid = {33133486}, issn = {2041-6520}, abstract = {Complexes of metals with N-heterocyclic carbene ligands (M/NHC) are typically considered the systems of choice in homogeneous catalysis due to their stable metal-ligand framework. However, it becomes obvious that even metal species with a strong M-NHC bond can undergo evolution in catalytic systems, and processes of M-NHC bond cleavage are common for different metals and NHC ligands. This review is focused on the main types of the M-NHC bond cleavage reactions and their impact on activity and stability of M/NHC catalytic systems. For the first time, we consider these processes in terms of NHC-connected and NHC-disconnected active species derived from M/NHC precatalysts and classify them as fundamentally different types of catalysts. Problems of rational catalyst design and sustainability issues are discussed in the context of the two different types of M/NHC catalysis mechanisms.}, } @article {pmid33122381, year = {2020}, author = {Zhang, D and Xia, H and Chen, F and Li, B and Slon, V and Cheng, T and Yang, R and Jacobs, Z and Dai, Q and Massilani, D and Shen, X and Wang, J and Feng, X and Cao, P and Yang, MA and Yao, J and Yang, J and Madsen, DB and Han, Y and Ping, W and Liu, F and Perreault, C and Chen, X and Meyer, M and Kelso, J and Pääbo, S and Fu, Q}, title = {Denisovan DNA in Late Pleistocene sediments from Baishiya Karst Cave on the Tibetan Plateau.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6516}, pages = {584-587}, doi = {10.1126/science.abb6320}, pmid = {33122381}, issn = {1095-9203}, mesh = {Animals ; *Caves ; DNA, Ancient/*isolation & purification ; DNA, Mitochondrial/genetics ; Geologic Sediments/*chemistry ; Hominidae/*classification/*genetics ; Humans ; Phylogeny ; Tibet ; }, abstract = {A late Middle Pleistocene mandible from Baishiya Karst Cave (BKC) on the Tibetan Plateau has been inferred to be from a Denisovan, an Asian hominin related to Neanderthals, on the basis of an amino acid substitution in its collagen. Here we describe the stratigraphy, chronology, and mitochondrial DNA extracted from the sediments in BKC. We recover Denisovan mitochondrial DNA from sediments deposited ~100 thousand and ~60 thousand years ago (ka) and possibly as recently as ~45 ka. The long-term occupation of BKC by Denisovans suggests that they may have adapted to life at high altitudes and may have contributed such adaptations to modern humans on the Tibetan Plateau.}, } @article {pmid33122380, year = {2020}, author = {Massilani, D and Skov, L and Hajdinjak, M and Gunchinsuren, B and Tseveendorj, D and Yi, S and Lee, J and Nagel, S and Nickel, B and Devièse, T and Higham, T and Meyer, M and Kelso, J and Peter, BM and Pääbo, S}, title = {Denisovan ancestry and population history of early East Asians.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6516}, pages = {579-583}, doi = {10.1126/science.abc1166}, pmid = {33122380}, issn = {1095-9203}, support = {324139/ERC_/European Research Council/International ; 694707/ERC_/European Research Council/International ; }, mesh = {Animals ; Asian People/*genetics ; DNA, Ancient ; *Evolution, Molecular ; Female ; Hominidae/*genetics ; Humans ; Mongolia ; Population ; Skull ; }, abstract = {We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in northeastern Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.}, } @article {pmid33122362, year = {2020}, author = {Gibbons, A}, title = {Denisovan DNA found in cave on Tibetan Plateau.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6516}, pages = {512-513}, doi = {10.1126/science.370.6516.512}, pmid = {33122362}, issn = {1095-9203}, mesh = {Altitude ; Animals ; Caves ; Cold Temperature ; DNA, Ancient/*isolation & purification ; DNA, Mitochondrial/*isolation & purification ; Geologic Sediments/*chemistry ; Hominidae/*genetics ; Humans ; Tibet ; }, } @article {pmid37588361, year = {2020}, author = {Sánchez Goñi, MF}, title = {Regional impacts of climate change and its relevance to human evolution.}, journal = {Evolutionary human sciences}, volume = {2}, number = {}, pages = {e55}, pmid = {37588361}, issn = {2513-843X}, abstract = {The traditional concept of long and gradual, glacial-interglacial climate changes during the Quaternary has been challenged since the 1980s. High temporal resolution analysis of marine, terrestrial and ice geological archives has identified rapid, millennial- to centennial-scale, and large-amplitude climatic cycles throughout the last few million years. These changes were global but have had contrasting regional impacts on the terrestrial and marine ecosystems, with in some cases strong changes in the high latitudes of both hemispheres but muted changes elsewhere. Such a regionalization has produced environmental barriers and corridors that have probably triggered niche contractions/expansions of hominin populations living in Eurasia and Africa. This article reviews the long- and short-timescale ecosystem changes that have punctuated the last few million years, paying particular attention to the environments of the last 650,000 years, which have witnessed key events in the evolution of our lineage in Africa and Eurasia. This review highlights, for the first time, a contemporaneity between the split between Denisovan and Neanderthals, at ~650-400 ka, and the strong Eurasian ice-sheet expansion down to the Black Sea. This ice expansion could form an ice barrier between Europe and Asia that may have triggered the genetic drift between these two populations.}, } @article {pmid33077870, year = {2021}, author = {Yang, S and Varghese, AM and Sood, N and Chiattone, C and Akinola, NO and Huang, X and Gale, RP}, title = {Ethnic and geographic diversity of chronic lymphocytic leukaemia.}, journal = {Leukemia}, volume = {35}, number = {2}, pages = {433-439}, pmid = {33077870}, issn = {1476-5551}, mesh = {Aged ; Asian/genetics/statistics & numerical data ; Ethnicity/*genetics/*statistics & numerical data ; Asia, Eastern/epidemiology ; Female ; *Genetic Predisposition to Disease ; *Genetic Variation ; *Genetics, Population ; Genome, Human ; Geography ; Global Health ; Humans ; Incidence ; Leukemia, Lymphocytic, Chronic, B-Cell/*epidemiology/genetics/pathology ; Male ; Middle Aged ; Risk Factors ; White People/genetics/statistics & numerical data ; }, abstract = {East Asians, Asian Indians and Amerindians have a five to ten-fold lower age-adjusted incidence rate (AAIR) of chronic lymphocytic leukaemia (CLL) compared with persons of predominately European descent. The data we review suggest a genetic rather than environmental basis for this discordance. All these populations arose from a common African Black ancestor but different clades have different admixture with archaic hominins including Neanderthals, Denisovans and Homo erectus, which may explain different CLL incidences. There are also some differences in clinical laboratory and molecular co-variates of CLL between these populations. Because the true age-adjusted incidence rate in African Blacks is unknown it is not possible to determine whether modern Europeans acquired susceptibility to CLL or the other populations lost susceptibility and/or developed resistance to developing CLL. We also found other B-cell lymphomas and T- and NK-cell cancers had different incidences in the populations we studied. These data provide clues to determining the cause(s) of CLL.}, } @article {pmid33039881, year = {2020}, author = {Pan, L and Dumoncel, J and Mazurier, A and Zanolli, C}, title = {Hominin diversity in East Asia during the Middle Pleistocene: A premolar endostructural perspective.}, journal = {Journal of human evolution}, volume = {148}, number = {}, pages = {102888}, doi = {10.1016/j.jhevol.2020.102888}, pmid = {33039881}, issn = {1095-8606}, mesh = {Animals ; Bicuspid ; Asia, Eastern ; Fossils ; *Hominidae ; Humans ; *Neanderthals ; }, abstract = {Following the recent studies of East Asian mid-Middle to early Late Pleistocene hominin material, a large spectrum of morphological diversity has been recognized and the coexistence of archaic ('Homo erectus-like') and derived ('modern-like') dental morphological patterns has been highlighted. In fact, for most of these Chinese fossils, generally categorized as 'archaic Homo sapiens' or 'post-H. erectus Homo', the taxonomic attribution is a matter of contention. With the help of μCT techniques and a deformation-based 3D geometric morphometric approach, we focused on the morphological variation in the enamel-dentine junction (EDJ) of 18 upper and lower premolars from Chinese Middle Pleistocene hominins. We then compared our results with a number of fossil and modern human groups, including Early Pleistocene H. erectus from Sangiran; late Early Pleistocene hominins from Tighenif, Algeria; classic Neanderthals; and modern humans. Our results highlight an evolutionary/chronological trend of crown base reduction, elevation of EDJ topography, and EDJ surface simplification in the hominin groups studied here. Moreover, this study brings insights to the taxonomy/phylogeny of 6 late Middle Pleistocene specimens whose evolutionary placement has been debated for decades. Among these specimens, Changyang premolars show features that can be aligned with the Asian H. erectus hypodigm, whereas Panxian Dadong and Tongzi premolars are more similar to Late Pleistocene Homo. Compared with early to mid-Middle Pleistocene hominins in East Asia, late Middle Pleistocene hominins evince an enlarged morphological variation. A persistence of archaic morphotypes and possible admixture among populations during the late Middle Pleistocene are discussed.}, } @article {pmid32973032, year = {2020}, author = {Petr, M and Hajdinjak, M and Fu, Q and Essel, E and Rougier, H and Crevecoeur, I and Semal, P and Golovanova, LV and Doronichev, VB and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Shunkov, MV and Kozlikin, MB and Derevianko, AP and Vernot, B and Meyer, M and Kelso, J}, title = {The evolutionary history of Neanderthal and Denisovan Y chromosomes.}, journal = {Science (New York, N.Y.)}, volume = {369}, number = {6511}, pages = {1653-1656}, doi = {10.1126/science.abb6460}, pmid = {32973032}, issn = {1095-9203}, support = {694707/ERC_/European Research Council/International ; }, mesh = {Animals ; Chromosomes, Human, Y/genetics ; DNA, Ancient ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Humans ; *Life History Traits ; Male ; Neanderthals/classification/*genetics ; Phylogeny ; Y Chromosome/*genetics ; }, abstract = {Ancient DNA has provided new insights into many aspects of human history. However, we lack comprehensive studies of the Y chromosomes of Denisovans and Neanderthals because the majority of specimens that have been sequenced to sufficient coverage are female. Sequencing Y chromosomes from two Denisovans and three Neanderthals shows that the Y chromosomes of Denisovans split around 700 thousand years ago from a lineage shared by Neanderthals and modern human Y chromosomes, which diverged from each other around 370 thousand years ago. The phylogenetic relationships of archaic and modern human Y chromosomes differ from the population relationships inferred from the autosomal genomes and mirror mitochondrial DNA phylogenies, indicating replacement of both the mitochondrial and Y chromosomal gene pools in late Neanderthals. This replacement is plausible if the low effective population size of Neanderthals resulted in an increased genetic load in Neanderthals relative to modern humans.}, } @article {pmid32954276, year = {2020}, author = {Merisaari, J and Denisova, OV and Doroszko, M and Le Joncour, V and Johansson, P and Leenders, WPJ and Kastrinsky, DB and Zaware, N and Narla, G and Laakkonen, P and Nelander, S and Ohlmeyer, M and Westermarck, J}, title = {Monotherapy efficacy of blood-brain barrier permeable small molecule reactivators of protein phosphatase 2A in glioblastoma.}, journal = {Brain communications}, volume = {2}, number = {1}, pages = {fcaa002}, pmid = {32954276}, issn = {2632-1297}, abstract = {Glioblastoma is a fatal disease in which most targeted therapies have clinically failed. However, pharmacological reactivation of tumour suppressors has not been thoroughly studied as yet as a glioblastoma therapeutic strategy. Tumour suppressor protein phosphatase 2A is inhibited by non-genetic mechanisms in glioblastoma, and thus, it would be potentially amendable for therapeutic reactivation. Here, we demonstrate that small molecule activators of protein phosphatase 2A, NZ-8-061 and DBK-1154, effectively cross the in vitro model of blood-brain barrier, and in vivo partition to mouse brain tissue after oral dosing. In vitro, small molecule activators of protein phosphatase 2A exhibit robust cell-killing activity against five established glioblastoma cell lines, and nine patient-derived primary glioma cell lines. Collectively, these cell lines have heterogeneous genetic background, kinase inhibitor resistance profile and stemness properties; and they represent different clinical glioblastoma subtypes. Moreover, small molecule activators of protein phosphatase 2A were found to be superior to a range of kinase inhibitors in their capacity to kill patient-derived primary glioma cells. Oral dosing of either of the small molecule activators of protein phosphatase 2A significantly reduced growth of infiltrative intracranial glioblastoma tumours. DBK-1154, with both higher degree of brain/blood distribution, and more potent in vitro activity against all tested glioblastoma cell lines, also significantly increased survival of mice bearing orthotopic glioblastoma xenografts. In summary, this report presents a proof-of-principle data for blood-brain barrier-permeable tumour suppressor reactivation therapy for glioblastoma cells of heterogenous molecular background. These results also provide the first indications that protein phosphatase 2A reactivation might be able to challenge the current paradigm in glioblastoma therapies which has been strongly focused on targeting specific genetically altered cancer drivers with highly specific inhibitors. Based on demonstrated role for protein phosphatase 2A inhibition in glioblastoma cell drug resistance, small molecule activators of protein phosphatase 2A may prove to be beneficial in future glioblastoma combination therapies.}, } @article {pmid32881095, year = {2020}, author = {Eremin, DB and Boiko, DA and Kostyukovich, AY and Burykina, JV and Denisova, EA and Anania, M and Martens, J and Berden, G and Oomens, J and Roithová, J and Ananikov, VP}, title = {Mechanistic Study of Pd/NHC-Catalyzed Sonogashira Reaction: Discovery of NHC-Ethynyl Coupling Process.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {26}, number = {67}, pages = {15672-15681}, doi = {10.1002/chem.202003533}, pmid = {32881095}, issn = {1521-3765}, support = {17-13-01526//Russian Science Foundation/ ; }, abstract = {The product of a revealed transformation-NHC-ethynyl coupling-was observed as a catalyst transformation pathway in the Sonogashira cross-coupling, catalyzed by Pd/NHC complexes. The 2-ethynylated azolium salt was isolated in individual form and fully characterized, including X-ray analysis. A number of possible intermediates of this transformation with common formulae (NHC)n Pd(C2 Ph) (n=1,2) were observed and subjected to collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) experiments to elucidate their structure. Measured bond dissociation energies (BDEs) and IRMPD spectra were in an excellent agreement with quantum calculations for coupling product π-complexes with Pd[0] . Molecular dynamics simulations confirmed the observed multiple CID fragmentation pathways. An unconventional methodology to study catalyst evolution suggests the reported transformation to be considered in the development of new catalytic systems for alkyne functionalization reactions.}, } @article {pmid32839541, year = {2020}, author = {Telis, N and Aguilar, R and Harris, K}, title = {Selection against archaic hominin genetic variation in regulatory regions.}, journal = {Nature ecology & evolution}, volume = {4}, number = {11}, pages = {1558-1566}, pmid = {32839541}, issn = {2397-334X}, support = {R35 GM133428/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Hominidae/genetics ; Humans ; *Neanderthals/genetics ; Regulatory Sequences, Nucleic Acid ; Selection, Genetic ; }, abstract = {Traces of Neandertal and Denisovan DNA persist in the modern human gene pool, but have been systematically purged by natural selection from genes and other functionally important regions. This implies that many archaic alleles harmed the fitness of hybrid individuals, but the nature of this harm is poorly understood. Here, we show that enhancers contain less Neandertal and Denisovan variation than expected given the background selection they experience, suggesting that selection acted to purge these regions of archaic alleles that disrupted their gene regulatory functions. We infer that selection acted mainly on young archaic variation that arose in Neandertals or Denisovans shortly before their contact with humans; enhancers are not depleted of older variants found in both archaic species. Some types of enhancer appear to have tolerated introgression better than others; compared with tissue-specific enhancers, pleiotropic enhancers show stronger depletion of archaic single-nucleotide polymorphisms. To some extent, evolutionary constraint is predictive of introgression depletion, but certain tissues' enhancers are more depleted of Neandertal and Denisovan alleles than expected given their comparative tolerance to new mutations. Foetal brain and muscle are the tissues whose enhancers show the strongest depletion of archaic alleles, but only brain enhancers show evidence of unusually stringent purifying selection. We conclude that epistatic incompatibilities between human and archaic alleles are needed to explain the degree of archaic variant depletion from foetal muscle enhancers, perhaps due to divergent selection for higher muscle mass in archaic hominins compared with humans.}, } @article {pmid32783351, year = {2021}, author = {Quartier, P and Alexeeva, E and Constantin, T and Chasnyk, V and Wulffraat, N and Palmblad, K and Wouters, C and I Brunner, H and Marzan, K and Schneider, R and Horneff, G and Martini, A and Anton, J and Wei, X and Slade, A and Ruperto, N and Abrams, K and , }, title = {Tapering Canakinumab Monotherapy in Patients With Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results From a Phase IIIb/IV Open-Label, Randomized Study.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {73}, number = {2}, pages = {336-346}, pmid = {32783351}, issn = {2326-5205}, mesh = {Adolescent ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Antirheumatic Agents/*administration & dosage/therapeutic use ; Arthritis, Juvenile/*drug therapy/physiopathology ; Child ; Child, Preschool ; Deprescriptions ; Drug Tapering/*methods ; Female ; Glucocorticoids/therapeutic use ; Humans ; Male ; Methotrexate/therapeutic use ; Remission Induction ; }, abstract = {OBJECTIVE: To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA).

METHODS: The study was designed as a 2-part phase IIIb/IV open-label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study.

RESULTS: In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified.

CONCLUSION: Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin-1 inhibition appears necessary to maintain this response.}, } @article {pmid32763953, year = {2020}, author = {Shchur, V and Svedberg, J and Medina, P and Corbett-Detig, R and Nielsen, R}, title = {On the Distribution of Tract Lengths During Adaptive Introgression.}, journal = {G3 (Bethesda, Md.)}, volume = {10}, number = {10}, pages = {3663-3673}, pmid = {32763953}, issn = {2160-1836}, support = {R35 GM128932/GM/NIGMS NIH HHS/United States ; R01 GM116044/GM/NIGMS NIH HHS/United States ; T32 HG008345/HG/NHGRI NIH HHS/United States ; }, mesh = {Alleles ; Gene Frequency ; *Genetic Drift ; Genetics, Population ; Linkage Disequilibrium ; *Selection, Genetic ; }, abstract = {Admixture is increasingly being recognized as an important factor in evolutionary genetics. The distribution of genomic admixture tracts, and the resulting effects on admixture linkage disequilibrium, can be used to date the timing of admixture between species or populations. However, the theory used for such prediction assumes selective neutrality despite the fact that many famous examples of admixture involve natural selection acting for or against admixture. In this paper, we investigate the effects of positive selection on the distribution of tract lengths. We develop a theoretical framework that relies on approximating the trajectory of the selected allele using a logistic function. By numerically calculating the expected allele trajectory, we also show that the approach can be extended to cases where the logistic approximation is poor due to the effects of genetic drift. Using simulations, we show that the model is highly accurate under most scenarios. We use the model to show that positive selection on average will tend to increase the admixture tract length. However, perhaps counter-intuitively, conditional on the allele frequency at the time of sampling, positive selection will actually produce shorter expected tract lengths. We discuss the consequences of our results in interpreting the timing of the introgression of EPAS1 from Denisovans into the ancestors of Tibetans.}, } @article {pmid32760067, year = {2020}, author = {Hubisz, MJ and Williams, AL and Siepel, A}, title = {Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph.}, journal = {PLoS genetics}, volume = {16}, number = {8}, pages = {e1008895}, pmid = {32760067}, issn = {1553-7404}, support = {R35 GM127070/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Evolution, Molecular ; *Gene Flow ; Human Migration ; Humans ; *Models, Genetic ; Neanderthals/*genetics ; Population/*genetics ; *Recombination, Genetic ; }, abstract = {The sequencing of Neanderthal and Denisovan genomes has yielded many new insights about interbreeding events between extinct hominins and the ancestors of modern humans. While much attention has been paid to the relatively recent gene flow from Neanderthals and Denisovans into modern humans, other instances of introgression leave more subtle genomic evidence and have received less attention. Here, we present a major extension of the ARGweaver algorithm, called ARGweaver-D, which can infer local genetic relationships under a user-defined demographic model that includes population splits and migration events. This Bayesian algorithm probabilistically samples ancestral recombination graphs (ARGs) that specify not only tree topologies and branch lengths along the genome, but also indicate migrant lineages. The sampled ARGs can therefore be parsed to produce probabilities of introgression along the genome. We show that this method is well powered to detect the archaic migration into modern humans, even with only a few samples. We then show that the method can also detect introgressed regions stemming from older migration events, or from unsampled populations. We apply it to human, Neanderthal, and Denisovan genomes, looking for signatures of older proposed migration events, including ancient humans into Neanderthal, and unknown archaic hominins into Denisovans. We identify 3% of the Neanderthal genome that is putatively introgressed from ancient humans, and estimate that the gene flow occurred between 200-300kya. We find no convincing evidence that negative selection acted against these regions. Finally, we predict that 1% of the Denisovan genome was introgressed from an unsequenced, but highly diverged, archaic hominin ancestor. About 15% of these "super-archaic" regions-comprising at least about 4Mb-were, in turn, introgressed into modern humans and continue to exist in the genomes of people alive today.}, } @article {pmid32750315, year = {2020}, author = {Course, MM and Gudsnuk, K and Smukowski, SN and Winston, K and Desai, N and Ross, JP and Sulovari, A and Bourassa, CV and Spiegelman, D and Couthouis, J and Yu, CE and Tsuang, DW and Jayadev, S and Kay, MA and Gitler, AD and Dupre, N and Eichler, EE and Dion, PA and Rouleau, GA and Valdmanis, PN}, title = {Evolution of a Human-Specific Tandem Repeat Associated with ALS.}, journal = {American journal of human genetics}, volume = {107}, number = {3}, pages = {445-460}, pmid = {32750315}, issn = {1537-6605}, support = {T32 GM007454/GM/NIGMS NIH HHS/United States ; U24 AG041689/AG/NIA NIH HHS/United States ; R01 DK078424/DK/NIDDK NIH HHS/United States ; P30 AG066509/AG/NIA NIH HHS/United States ; P50 AG005136/AG/NIA NIH HHS/United States ; R01 HG010169/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Aged ; Alzheimer Disease/genetics/pathology ; Amyotrophic Lateral Sclerosis/*genetics/pathology ; DNA Repeat Expansion/genetics ; *Evolution, Molecular ; Female ; Gene Expression Regulation/genetics ; Humans ; Male ; Minisatellite Repeats/genetics ; Phenotype ; Species Specificity ; Tandem Repeat Sequences/*genetics ; }, abstract = {Tandem repeats are proposed to contribute to human-specific traits, and more than 40 tandem repeat expansions are known to cause neurological disease. Here, we characterize a human-specific 69 bp variable number tandem repeat (VNTR) in the last intron of WDR7, which exhibits striking variability in both copy number and nucleotide composition, as revealed by long-read sequencing. In addition, greater repeat copy number is significantly enriched in three independent cohorts of individuals with sporadic amyotrophic lateral sclerosis (ALS). Each unit of the repeat forms a stem-loop structure with the potential to produce microRNAs, and the repeat RNA can aggregate when expressed in cells. We leveraged its remarkable sequence variability to align the repeat in 288 samples and uncover its mechanism of expansion. We found that the repeat expands in the 3'-5' direction, in groups of repeat units divisible by two. The expansion patterns we observed were consistent with duplication events, and a replication error called template switching. We also observed that the VNTR is expanded in both Denisovan and Neanderthal genomes but is fixed at one copy or fewer in non-human primates. Evaluating the repeat in 1000 Genomes Project samples reveals that some repeat segments are solely present or absent in certain geographic populations. The large size of the repeat unit in this VNTR, along with our multiplexed sequencing strategy, provides an unprecedented opportunity to study mechanisms of repeat expansion, and a framework for evaluating the roles of VNTRs in human evolution and disease.}, } @article {pmid32745133, year = {2020}, author = {Örd, T and Puurand, T and Örd, D and Annilo, T and Möls, M and Remm, M and Örd, T}, title = {A human-specific VNTR in the TRIB3 promoter causes gene expression variation between individuals.}, journal = {PLoS genetics}, volume = {16}, number = {8}, pages = {e1008981}, pmid = {32745133}, issn = {1553-7404}, support = {HHSN268201000029C/HL/NHLBI NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Cell Cycle Proteins/*genetics ; Estonia/epidemiology ; Female ; Gene Expression Regulation/genetics ; *Genetic Heterogeneity ; *Genetics, Population ; Genotype ; Humans ; Male ; Minisatellite Repeats/*genetics ; Promoter Regions, Genetic ; Protein Serine-Threonine Kinases/*antagonists & inhibitors/genetics ; RNA-Seq ; Repressor Proteins/*genetics ; Whole Genome Sequencing ; }, abstract = {Tribbles homolog 3 (TRIB3) is pseudokinase involved in intracellular regulatory processes and has been implicated in several diseases. In this article, we report that human TRIB3 promoter contains a 33-bp variable number tandem repeat (VNTR) and characterize the heterogeneity and function of this genetic element. Analysis of human populations around the world uncovered the existence of alleles ranging from 1 to 5 copies of the repeat, with 2-, 3- and 5-copy alleles being the most common but displaying considerable geographical differences in frequency. The repeated sequence overlaps a C/EBP-ATF transcriptional regulatory element and is highly conserved, but not repeated, in various mammalian species, including great apes. The repeat is however evident in Neanderthal and Denisovan genomes. Reporter plasmid experiments in human cell culture reveal that an increased copy number of the TRIB3 promoter 33-bp repeat results in increased transcriptional activity. In line with this, analysis of whole genome sequencing and RNA-Seq data from human cohorts demonstrates that the copy number of TRIB3 promoter 33-bp repeats is positively correlated with TRIB3 mRNA expression level in many tissues throughout the body. Moreover, the copy number of the TRIB3 33-bp repeat appears to be linked to known TRIB3 eQTL SNPs as well as TRIB3 SNPs reported in genetic association studies. Taken together, the results indicate that the promoter 33-bp VNTR constitutes a causal variant for TRIB3 expression variation between individuals and could underlie the results of SNP-based genetic studies.}, } @article {pmid32690317, year = {2020}, author = {Montinaro, F and Capelli, C}, title = {A Worldwide Map of Human Structural Variants.}, journal = {Trends in genetics : TIG}, volume = {36}, number = {10}, pages = {722-725}, doi = {10.1016/j.tig.2020.07.002}, pmid = {32690317}, issn = {0168-9525}, mesh = {Genomics ; Humans ; *Neanderthals/genetics ; }, abstract = {Genomic variation extends from single nucleotide variants to large chromosomal rearrangements, but the extent of structural variation in Homo sapiens is still unclear. Almarri et al. provide a worldwide catalogue of structural variants present in human populations. Most of the reported variation is novel, with some variants being inherited from Neanderthals and Denisovans. Drift and selection shaped the distribution of these variants with some suggested to have functional implications.}, } @article {pmid32615344, year = {2020}, author = {Yan, SM and McCoy, RC}, title = {Archaic hominin genomics provides a window into gene expression evolution.}, journal = {Current opinion in genetics & development}, volume = {62}, number = {}, pages = {44-49}, pmid = {32615344}, issn = {1879-0380}, support = {R35 GM133747/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anthropology, Physical ; DNA/analysis/*genetics ; *Evolution, Molecular ; Fossils ; *Gene Expression Regulation ; *Genetic Variation ; Genomics/*methods ; Hominidae ; Humans ; Neanderthals ; }, abstract = {Differences in gene expression are thought to account for most phenotypic differences within and between species. Consequently, gene expression is a powerful lens through which to study divergence between modern humans and our closest evolutionary relatives, the Neanderthals and Denisovans. Such insights complement biological knowledge gleaned from the fossil record, while also revealing general features of the mode and tempo of regulatory evolution. Because of the degradation of ancient RNA, gene expression profiles of archaic hominins must be studied by indirect means. As such, conclusions drawn from these studies are often laden with assumptions about the genetic architecture of gene expression, the complexity of which is increasingly apparent. Despite these challenges, rapid technical and conceptual advances in the fields of ancient genomics, functional genomics, statistical genomics, and genome engineering are revolutionizing understanding of hominin gene expression evolution.}, } @article {pmid32603726, year = {2021}, author = {Agrawal, R and Testi, I and Bodaghi, B and Barisani-Asenbauer, T and McCluskey, P and Agarwal, A and Kempen, JH and Gupta, A and Smith, JR and de Smet, MD and Yuen, YS and Mahajan, S and Kon, OM and Nguyen, QD and Pavesio, C and Gupta, V and , }, title = {Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis.}, journal = {Ophthalmology}, volume = {128}, number = {2}, pages = {277-287}, doi = {10.1016/j.ophtha.2020.06.052}, pmid = {32603726}, issn = {1549-4713}, support = {MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Algorithms ; Antitubercular Agents/*therapeutic use ; Chemotherapy, Adjuvant ; Delphi Technique ; Eye Infections, Bacterial/diagnosis/*drug therapy/microbiology ; Glucocorticoids/therapeutic use ; Humans ; Interferon-gamma Release Tests ; Panuveitis/diagnosis/*drug therapy/microbiology ; Radiography, Thoracic ; Retinal Vasculitis/*drug therapy/microbiology ; Retrospective Studies ; Surveys and Questionnaires ; Tomography, X-Ray Computed ; Tuberculosis, Ocular/diagnosis/*drug therapy/microbiology ; Uveitis, Anterior/diagnosis/*drug therapy/microbiology ; Uveitis, Intermediate/*drug therapy/microbiology ; }, abstract = {TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU).

CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition.

METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process.

RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive.

DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.}, } @article {pmid32580520, year = {2020}, author = {Filippenkov, IB and Stavchansky, VV and Denisova, AE and Yuzhakov, VV and Sevan'kaeva, LE and Sudarkina, OY and Dmitrieva, VG and Gubsky, LV and Myasoedov, NF and Limborska, SA and Dergunova, LV}, title = {Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats.}, journal = {Genes}, volume = {11}, number = {6}, pages = {}, pmid = {32580520}, issn = {2073-4425}, mesh = {Adrenocorticotropic Hormone/*analogs & derivatives/pharmacology ; Animals ; Brain/drug effects/pathology ; Brain Ischemia/*drug therapy/genetics/pathology ; Disease Models, Animal ; Humans ; Infarction, Middle Cerebral Artery/*drug therapy/genetics/pathology ; Peptide Fragments/*pharmacology ; RNA-Seq ; Rats ; Reperfusion Injury/*drug therapy/genetics/pathology ; Transcriptome/drug effects/genetics ; }, abstract = {Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7)PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia-reperfusion on the brain transcriptome in rats. Here, using RNA-Seq analysis, we investigated the protective properties of the Semax peptide at the transcriptome level under tMCAO conditions. We have identified 394 differentially expressed genes (DEGs) (>1.5-fold change) in the brains of rats at 24 h after tMCAO treated with Semax relative to saline. Following tMCAO, we found that Semax suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission. In contrast, ischaemia-reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes. Therefore, the neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia-reperfusion conditions.}, } @article {pmid32574964, year = {2020}, author = {Mathov, Y and Batyrev, D and Meshorer, E and Carmel, L}, title = {Harnessing epigenetics to study human evolution.}, journal = {Current opinion in genetics & development}, volume = {62}, number = {}, pages = {23-29}, doi = {10.1016/j.gde.2020.05.023}, pmid = {32574964}, issn = {1879-0380}, mesh = {*DNA Methylation ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Genetic Variation ; *Genome, Human ; Humans ; }, abstract = {Recent advances in ancient DNA extraction and high-throughput sequencing technologies enabled the high-quality sequencing of archaic genomes, including the Neanderthal and the Denisovan. While comparisons with modern humans revealed both archaic-specific and human-specific sequence changes, in the absence of gene expression information, understanding the functional implications of such genetic variations remains a major challenge. To study gene regulation in archaic humans, epigenetic research comes to our aid. DNA methylation, which is highly correlated with transcription, can be directly measured in modern samples, as well as reconstructed in ancient samples. This puts DNA methylation as a natural basis for comparative epigenetics between modern humans, archaic humans and nonhuman primates.}, } @article {pmid32571487, year = {2020}, author = {Kim, J and Perkins, GB and Coates, PT}, title = {Evolutionary immunology: how your ancestry can affect your kidney transplant.}, journal = {Kidney international}, volume = {98}, number = {1}, pages = {45-47}, doi = {10.1016/j.kint.2020.01.020}, pmid = {32571487}, issn = {1523-1755}, mesh = {Alleles ; Animals ; Biological Evolution ; Humans ; *Kidney Transplantation ; Mice ; Phosphorylation ; Tumor Necrosis Factor alpha-Induced Protein 3 ; }, } @article {pmid32556248, year = {2020}, author = {Khan, N and de Manuel, M and Peyregne, S and Do, R and Prufer, K and Marques-Bonet, T and Varki, N and Gagneux, P and Varki, A}, title = {Multiple Genomic Events Altering Hominin SIGLEC Biology and Innate Immunity Predated the Common Ancestor of Humans and Archaic Hominins.}, journal = {Genome biology and evolution}, volume = {12}, number = {7}, pages = {1040-1050}, pmid = {32556248}, issn = {1759-6653}, support = {R01 GM032373/GM/NIGMS NIH HHS/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Expression ; Genome ; Hominidae/*genetics/immunology ; Humans ; Immunity, Innate/genetics ; Multigene Family ; Mutation ; Polymorphism, Genetic ; Selection, Genetic ; Sialic Acid Binding Ig-like Lectin 3/*genetics ; }, abstract = {Human-specific pseudogenization of the CMAH gene eliminated the mammalian sialic acid (Sia) Neu5Gc (generating an excess of its precursor Neu5Ac), thus changing ubiquitous cell surface "self-associated molecular patterns" that modulate innate immunity via engagement of CD33-related-Siglec receptors. The Alu-fusion-mediated loss-of-function of CMAH fixed ∼2-3 Ma, possibly contributing to the origins of the genus Homo. The mutation likely altered human self-associated molecular patterns, triggering multiple events, including emergence of human-adapted pathogens with strong preference for Neu5Ac recognition and/or presenting Neu5Ac-containing molecular mimics of human glycans, which can suppress immune responses via CD33-related-Siglec engagement. Human-specific alterations reported in some gene-encoding Sia-sensing proteins suggested a "hotspot" in hominin evolution. The availability of more hominid genomes including those of two extinct hominins now allows full reanalysis and evolutionary timing. Functional changes occur in 8/13 members of the human genomic cluster encoding CD33-related Siglecs, all predating the human common ancestor. Comparisons with great ape genomes indicate that these changes are unique to hominins. We found no evidence for strong selection after the Human-Neanderthal/Denisovan common ancestor, and these extinct hominin genomes include almost all major changes found in humans, indicating that these changes in hominin sialobiology predate the Neanderthal-human divergence ∼0.6 Ma. Multiple changes in this genomic cluster may also explain human-specific expression of CD33rSiglecs in unexpected locations such as amnion, placental trophoblast, pancreatic islets, ovarian fibroblasts, microglia, Natural Killer(NK) cells, and epithelia. Taken together, our data suggest that innate immune interactions with pathogens markedly altered hominin Siglec biology between 0.6 and 2 Ma, potentially affecting human evolution.}, } @article {pmid32546518, year = {2020}, author = {Mafessoni, F and Grote, S and de Filippo, C and Slon, V and Kolobova, KA and Viola, B and Markin, SV and Chintalapati, M and Peyrégne, S and Skov, L and Skoglund, P and Krivoshapkin, AI and Derevianko, AP and Meyer, M and Kelso, J and Peter, B and Prüfer, K and Pääbo, S}, title = {A high-coverage Neandertal genome from Chagyrskaya Cave.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {26}, pages = {15132-15136}, pmid = {32546518}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Female ; Fossils ; Gene Expression Regulation ; Genetic Variation ; *Genome ; Humans ; Inbreeding ; Neanderthals/*genetics ; Population Density ; Russia ; }, abstract = {We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We show that this Neandertal was a female and that she was more related to Neandertals in western Eurasia [Prüfer et al., Science 358, 655-658 (2017); Hajdinjak et al., Nature 555, 652-656 (2018)] than to Neandertals who lived earlier in Denisova Cave [Prüfer et al., Nature 505, 43-49 (2014)], which is located about 100 km away. About 12.9% of the Chagyrskaya genome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with the fact that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains, and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more amino-acid-changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.}, } @article {pmid32531199, year = {2020}, author = {Almarri, MA and Bergström, A and Prado-Martinez, J and Yang, F and Fu, B and Dunham, AS and Chen, Y and Hurles, ME and Tyler-Smith, C and Xue, Y}, title = {Population Structure, Stratification, and Introgression of Human Structural Variation.}, journal = {Cell}, volume = {182}, number = {1}, pages = {189-199.e15}, pmid = {32531199}, issn = {1097-4172}, support = {FC001595/CRUK_/Cancer Research UK/United Kingdom ; FC001595/MRC_/Medical Research Council/United Kingdom ; FC001595/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Alleles ; Databases, Genetic ; Gene Dosage ; Gene Duplication ; Gene Frequency/genetics ; Genetic Variation ; *Genetics, Population ; Genome, Human ; *Genomic Structural Variation ; Humans ; }, abstract = {Structural variants contribute substantially to genetic diversity and are important evolutionarily and medically, but they are still understudied. Here we present a comprehensive analysis of structural variation in the Human Genome Diversity panel, a high-coverage dataset of 911 samples from 54 diverse worldwide populations. We identify, in total, 126,018 variants, 78% of which were not identified in previous global sequencing projects. Some reach high frequency and are private to continental groups or even individual populations, including regionally restricted runaway duplications and putatively introgressed variants from archaic hominins. By de novo assembly of 25 genomes using linked-read sequencing, we discover 1,643 breakpoint-resolved unique insertions, in aggregate accounting for 1.9 Mb of sequence absent from the GRCh38 reference. Our results illustrate the limitation of a single human reference and the need for high-quality genomes from diverse populations to fully discover and understand human genetic variation.}, } @article {pmid32494067, year = {2020}, author = {Skov, L and Coll Macià, M and Sveinbjörnsson, G and Mafessoni, F and Lucotte, EA and Einarsdóttir, MS and Jonsson, H and Halldorsson, B and Gudbjartsson, DF and Helgason, A and Schierup, MH and Stefansson, K}, title = {The nature of Neanderthal introgression revealed by 27,566 Icelandic genomes.}, journal = {Nature}, volume = {582}, number = {7810}, pages = {78-83}, pmid = {32494067}, issn = {1476-4687}, mesh = {Animals ; Female ; Genetic Association Studies ; Genetic Introgression/*genetics ; Genome, Human/*genetics ; *Genomics ; Haploidy ; Humans ; Iceland ; Male ; *Mutation ; Neanderthals/*genetics ; Phenotype ; Phylogeny ; }, abstract = {Human evolutionary history is rich with the interbreeding of divergent populations. Most humans outside of Africa trace about 2% of their genomes to admixture from Neanderthals, which occurred 50-60 thousand years ago[1]. Here we examine the effect of this event using 14.4 million putative archaic chromosome fragments that were detected in fully phased whole-genome sequences from 27,566 Icelanders, corresponding to a range of 56,388-112,709 unique archaic fragments that cover 38.0-48.2% of the callable genome. On the basis of the similarity with known archaic genomes, we assign 84.5% of fragments to an Altai or Vindija Neanderthal origin and 3.3% to Denisovan origin; 12.2% of fragments are of unknown origin. We find that Icelanders have more Denisovan-like fragments than expected through incomplete lineage sorting. This is best explained by Denisovan gene flow, either into ancestors of the introgressing Neanderthals or directly into humans. A within-individual, paired comparison of archaic fragments with syntenic non-archaic fragments revealed that, although the overall rate of mutation was similar in humans and Neanderthals during the 500 thousand years that their lineages were separate, there were differences in the relative frequencies of mutation types-perhaps due to different generation intervals for males and females. Finally, we assessed 271 phenotypes, report 5 associations driven by variants in archaic fragments and show that the majority of previously reported associations are better explained by non-archaic variants.}, } @article {pmid32487809, year = {2020}, author = {Denisova, K and Barmettler, A}, title = {Oculoplastic considerations for refractive procedures.}, journal = {Current opinion in ophthalmology}, volume = {31}, number = {4}, pages = {241-246}, doi = {10.1097/ICU.0000000000000667}, pmid = {32487809}, issn = {1531-7021}, mesh = {Astigmatism/surgery ; Blepharoptosis/etiology/*physiopathology ; Dry Eye Syndromes/etiology/*physiopathology ; Humans ; Keratomileusis, Laser In Situ ; Keratoplasty, Penetrating ; Orbital Diseases/etiology/*physiopathology ; Postoperative Period ; Refraction, Ocular/physiology ; Refractive Errors/*physiopathology ; *Refractive Surgical Procedures ; }, abstract = {PURPOSE OF REVIEW: Refractive surgery is one of the most popular elective procedures performed in the world. Given that dry eye is a common complaint following keratorefractive surgery, evaluation, and treatment of periocular conditions that further predispose the patient to dry eye symptoms is an important part of the presurgical assessment. Periocular conditions and surgeries can also affect the ocular surface and keratometry, and should be addressed. For example, ptosis, orbital fat herniation, ectropion, and eyelid masses have been shown to induce corneal topography changes and astigmatism. The oculoplastic considerations for refractive surgery include both the contribution of eyelid position on dry eye, ocular surface damage, refractive error, and outcomes, as well as the timing of oculoplastic surgery in relation to the refractive surgery. In this review, the recently published literature on eyelid and orbital surgery in relation to keratorefractive surgery is reviewed to elucidate the relationship of periocular factors with refractive surgery outcomes and complications. To improve keratorefractive surgery outcomes, a literature review is presented, discussing evaluation, management, and timing of management of oculoplastics conditions.

RECENT FINDINGS: Dry eye syndrome is a well known complication of keratorefractive procedures. This is exacerbated with concurrent eyelid or orbital disorders, such as ectropion, lagophthalmos, and thyroid eye disease. In addition to impacting dry eye and ocular surface damage, eyelid surgeries can also affect corneal topography and refraction. Studies have found that patients with ptosis have topographic corneal aberrations from the eyelid exerting pressure on the cornea, while ptosis repair and blepharoplasty patients may undergo an astigmatic change postoperatively. Finally, the corneal flap created in laser-assisted in situ keratomileusis may be at risk for displacement or damage postoperatively with this risk changing, depending on method of flap creation, and time elapsed since keratorefractive surgery.

SUMMARY: Eyelid and orbital conditions that predispose to dry eye syndrome and refractive changes should be evaluated and optimized prior to keratorefractive surgery. Patients electing to have oculoplastic surgery, like ptosis repair, should be fully healed prior to any refractive surgery to allow both refractive changes and eyelid positions to stabilize prior to the refractive surgery.}, } @article {pmid32453742, year = {2020}, author = {Natri, HM and Bobowik, KS and Kusuma, P and Crenna Darusallam, C and Jacobs, GS and Hudjashov, G and Lansing, JS and Sudoyo, H and Banovich, NE and Cox, MP and Gallego Romero, I}, title = {Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago.}, journal = {PLoS genetics}, volume = {16}, number = {5}, pages = {e1008749}, pmid = {32453742}, issn = {1553-7404}, mesh = {CpG Islands ; *DNA Methylation ; Environment ; Epigenesis, Genetic/physiology ; Ethnicity/*genetics/statistics & numerical data ; Gene Expression Profiling/statistics & numerical data ; *Gene-Environment Interaction ; Genetics, Population ; Genome-Wide Association Study/statistics & numerical data ; Genomics/methods ; Humans ; Indonesia/epidemiology ; Islands/epidemiology ; Pacific Islands/epidemiology ; Pedigree ; Phenotype ; Polymorphism, Single Nucleotide ; RNA-Seq ; *Transcriptome ; }, abstract = {Indonesia is the world's fourth most populous country, host to striking levels of human diversity, regional patterns of admixture, and varying degrees of introgression from both Neanderthals and Denisovans. However, it has been largely excluded from the human genomics sequencing boom of the last decade. To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide CpG methylation and gene expression measurements in over 100 individuals from three locations that capture the major genomic and geographical axes of diversity across the Indonesian archipelago. Investigating between- and within-island differences, we find up to 10.55% of tested genes are differentially expressed between the islands of Sumba and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.80% of genes correlating with nearby promoter CpG methylation, and many of these genes being differentially expressed between islands. Genes identified in our differential expression and methylation analyses are enriched in pathways involved in immunity, highlighting Indonesia's tropical role as a source of infectious disease diversity and the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-island variation in DNA methylation and gene expression, likely driven by fine-scale environmental differences across sampling sites. Together, these results strongly suggest complex relationships between DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the environment. This has implications for the application of genomic medicine, both in critically understudied Indonesia and globally, and will allow a better understanding of the interacting roles of genomic and environmental factors shaping molecular and complex phenotypes.}, } @article {pmid32436183, year = {2020}, author = {Ricci, C and Kakularam, KR and Marzocchi, C and Capecchi, G and Riolo, G and Boschin, F and Kuhn, H and Castagna, MG and Cantara, S}, title = {Thr92Ala polymorphism in the type 2 deiodinase gene: an evolutionary perspective.}, journal = {Journal of endocrinological investigation}, volume = {43}, number = {12}, pages = {1749-1757}, doi = {10.1007/s40618-020-01287-5}, pmid = {32436183}, issn = {1720-8386}, support = {KU 961-14/1//German Research Council/ ; }, mesh = {Alanine/genetics ; Alleles ; Amino Acid Substitution/genetics ; Animals ; *Evolution, Molecular ; Gene Frequency ; Genetics, Population ; Geography ; History, Ancient ; Humans ; Iodide Peroxidase/*genetics ; Neanderthals/genetics ; *Polymorphism, Single Nucleotide ; Threonine/genetics ; }, abstract = {PURPOSE: In the past, a role of thyroid hormones in human evolution has been hypothesized. T3, the metabolically active form, derives from extrathyroidal conversion of T4 by deionidase 2 (D2) enzyme encoded by DIO2 gene. In thyroid-deficient patients, decreased levels of free T3 have been associated with the polymorphism rs225014 A/G in DIO2, which causes the substitution of Threonine with Alanine (p.Thr92Ala) at protein level.

METHODS: We compared DNA and protein sequences of D2 from archaic human subspecies with those of contemporary humans.

RESULTS: Neanderthals and Denisovans displayed only the G allele at the rs225014 polymorphism, which encodes for an Alanine on the amino acid level. These data suggest that these hominines were homozygous for the Ala amino acid. These arcaic humans often lived in condition of iodine deficiency and thus, defective mechanisms of T3 biosynthesis could be life threatining. A reduced D2 activity is likely to cause decreased T3 levels, which could be critical for those individuals. Neanderthals and Denisovans were hunters/gatherers, and their diet was mainly based on the consumption of meat, with a low intake of carbohydrates. The need for circulating T3 is reduced at such alimentary conditions. On the basis of our genome comparisons the A allele, corresponding to Threonine and associated with higher levels of circulating T3 in thyroid-deficient patients, appeared for the first time during evolution in Anatomically Modern Humans during the Upper Pleistocene and has been conserved during the Neolithic age. With the advent of agriculture and herding, individuals carrying A allele might have a higher probability for surviving and reproducing. Thus, the variant was positively selected during the evolution.

CONCLUSION: Here we present an evolutionary perspective for p.Thr92Ala variant of D2 from Neanderthals to Anatomically Modern Humans.}, } @article {pmid32375623, year = {2020}, author = {Larina, VN and Akhmatova, FD and Arakelov, SE and Mokhov, AE and Doronina, IM and Denisova, NN}, title = {[Modern strategies for cardiac rehabilitation after myocardial infarction and percutaneous coronary intervention].}, journal = {Kardiologiia}, volume = {60}, number = {3}, pages = {111-118}, doi = {10.18087/cardio.2020.3.n546}, pmid = {32375623}, issn = {0022-9040}, mesh = {*Cardiac Rehabilitation ; Exercise ; Exercise Therapy ; Humans ; *Myocardial Infarction ; *Percutaneous Coronary Intervention ; }, abstract = {Modern cardiac rehabilitation represents a structured, multicomponent program, which includes physical activity, education of the patient, modification of the health behavior, and psychological and social support. In EU countries, only 44.8% of patients with ischemic heart disease receive a recommendation to participate in any form of rehabilitation, and only 36.5% of all patients presently have an access to any rehabilitation program. Systematic analysis of programs for prevention of cardiovascular diseases and for rehabilitation in patients with myocardial infarction (MI) and percutaneous coronary intervention showed that complex programs can still reduce all-cause and cardiovascular mortality and frequency of recurrent MI and stroke. These programs include key components of cardiac rehabilitation, reduction of six or more risk factors, and effective control by drug therapy.}, } @article {pmid32369667, year = {2020}, author = {Denisova, SA and Shchenkov, SV}, title = {Fine structure of the nervous system of Cercaria parvicaudata Stunkard & Shaw, 1931 (Digenea, Renicolidae).}, journal = {Journal of morphology}, volume = {281}, number = {7}, pages = {765-777}, doi = {10.1002/jmor.21137}, pmid = {32369667}, issn = {1097-4687}, mesh = {Animals ; Cercaria/*anatomy & histology/ultrastructure ; Ganglia, Invertebrate/ultrastructure ; Nervous System/*anatomy & histology/ultrastructure ; Neurons/ultrastructure ; Neuropil Threads/ultrastructure ; Synapses/ultrastructure ; }, abstract = {The biology of free-living and parasitic Platyhelminthes is diverse. Taking into account the widespread prevalence of parasitic flatworms, Digenea is the least studied group regarding the fine structure of nervous system especially of the cercarial life stage. Here, we present a description of the fine structure of central nervous system (CNS) and two types of uniciliate sensory papillae of xiphidiocercaria Cercaria parvicaudata (Microphalloidea, Renicolidae). The present study documents that C. parvicaudata has a complex nervous system that includes a well-developed ganglion with a cortex of perikarya and glia-like sheaths, myelin-like structures within one of the dorsal nerve cords and four types of polarized synapses between neurites. Different types of neurons in the CNS could not be distinguished on ultrastructural level due to high similarity in their fine structure. Shared polarized synapses with high electron density of presynaptic components are numerous in the neuropile and nerve cords of this larva. Within the larval body, we detected specialized "support" processes that relate to different tissues. Some "support" processes are also closely related to the nervous system of C. parvicaudata, where they are considered as glia-like structures. In this case, the fine structure of glia-like "support" cells of C. parvicaudata differs from those described as glia-like cells in adult flatworms. We suggest a wide prevalence of glia-like cells among cercariae, as well as the fact that glia-like structures in digenean nervous systems can develop from various nonneuronal tissues.}, } @article {pmid32368616, year = {2020}, author = {Hammill, JA and Kwiecien, JM and Dvorkin-Gheva, A and Lau, VWC and Baker, C and Wu, Y and Bezverbnaya, K and Aarts, C and Heslen, CW and Denisova, GF and Derocher, H and Milne, K and Nelson, BH and Bramson, JL}, title = {A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity.}, journal = {Molecular therapy oncolytics}, volume = {17}, number = {}, pages = {278-292}, pmid = {32368616}, issn = {2372-7705}, abstract = {Tumor-targeted chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR-T cells) have demonstrated striking clinical success, but their use has been associated with a constellation of toxicities. A better understanding of the pathogenesis of these toxicities is required to improve the safety profile of CAR-T cells. Herein, we describe a xenograft model of off-tumor CAR-T cell-associated toxicity. Human CAR-T cells targeted against HER2 using a small-protein binding domain induced acute, dose-dependent toxicities in mice. The inclusion of a CD28 or 4-1BB co-stimulatory domain in the CAR was required to produce toxicity; however, co-stimulation through CD28 was most toxic on a per-cell basis. CAR-T cell activation in the lungs and heart was associated with a systemic cytokine storm. The severity of observed toxicities was dependent upon the peripheral blood mononuclear cell (PBMC) donor used as a T cell source and paralleled the CD4[+]-to-CD8[+] T cell ratio in the adoptive transfer product. CD4[+] CAR-T cells were determined to be the primary contributors to CAR-T cell-associated toxicity. However, donor-specific differences persisted after infusion of a purified CD4[+] CAR-T cell product, indicating a role for additional variables. This work highlights the contributions of CAR-T cell-intrinsic variables to the pathogenesis of off-tumor toxicity.}, } @article {pmid32350419, year = {2019}, author = {}, title = {The mysterious Denisovans have at last come in from the cold.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-019-01310-7}, pmid = {32350419}, issn = {1476-4687}, } @article {pmid32330268, year = {2020}, author = {Lodewijk, GA and Fernandes, DP and Vretzakis, I and Savage, JE and Jacobs, FMJ}, title = {Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels.}, journal = {Molecular biology and evolution}, volume = {37}, number = {9}, pages = {2531-2548}, pmid = {32330268}, issn = {1537-1719}, mesh = {Animals ; *Biological Evolution ; Genome, Human ; Genomic Structural Variation ; Humans ; Multigene Family ; Neanderthals/*genetics ; Receptor, Notch2/*genetics/metabolism ; }, abstract = {Ever since the availability of genomes from Neanderthals, Denisovans, and ancient humans, the field of evolutionary genomics has been searching for protein-coding variants that may hold clues to how our species evolved over the last ∼600,000 years. In this study, we identify such variants in the human-specific NOTCH2NL gene family, which were recently identified as possible contributors to the evolutionary expansion of the human brain. We find evidence for the existence of unique protein-coding NOTCH2NL variants in Neanderthals and Denisovans which could affect their ability to activate Notch signaling. Furthermore, in the Neanderthal and Denisovan genomes, we find unusual NOTCH2NL configurations, not found in any of the modern human genomes analyzed. Finally, genetic analysis of archaic and modern humans reveals ongoing adaptive evolution of modern human NOTCH2NL genes, identifying three structural variants acting complementary to drive our genome to produce a lower dosage of NOTCH2NL protein. Because copy-number variations of the 1q21.1 locus, encompassing NOTCH2NL genes, are associated with severe neurological disorders, this seemingly contradicting drive toward low levels of NOTCH2NL protein indicates that the optimal dosage of NOTCH2NL may have not yet been settled in the human population.}, } @article {pmid32299352, year = {2020}, author = {Moriano, J and Boeckx, C}, title = {Modern human changes in regulatory regions implicated in cortical development.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {304}, pmid = {32299352}, issn = {1471-2164}, support = {FFI2016-78034-C2-1-P//SpanishMinistry of Economy and Competitiveness/FEDER/ ; PIRG-GA-2009-256413//Marie Curie International Reintegration Grant/ ; Evolinguistics: JP17H06379//MEXT/JSPS/ ; -//Fundació Bosch i Gimpera (ES)/ ; 2017-SGR-341//Generalitat de Catalunya (ES)/ ; }, mesh = {Animals ; Cerebral Cortex/*growth & development ; Chromatin/genetics/metabolism ; *Enhancer Elements, Genetic ; Gene Expression Regulation, Developmental ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Hominidae/*genetics ; Humans ; Neanderthals/*genetics ; Neurogenesis/*genetics ; Polymorphism, Single Nucleotide ; *Promoter Regions, Genetic ; Species Specificity ; Wnt Signaling Pathway/genetics ; }, abstract = {BACKGROUND: Recent paleogenomic studies have highlighted a very small set of proteins carrying modern human-specific missense changes in comparison to our closest extinct relatives. Despite being frequently alluded to as highly relevant, species-specific differences in regulatory regions remain understudied. Here, we integrate data from paleogenomics, chromatin modification and physical interaction, and single-cell gene expression of neural progenitor cells to identify derived regulatory changes in the modern human lineage in comparison to Neanderthals/Denisovans. We report a set of genes whose enhancers and/or promoters harbor modern human single nucleotide changes and are active at early stages of cortical development.

RESULTS: We identified 212 genes controlled by regulatory regions harboring modern human changes where Neanderthals/Denisovans carry the ancestral allele. These regulatory regions significantly overlap with putative modern human positively-selected regions and schizophrenia-related genetic loci. Among the 212 genes, we identified a substantial proportion of genes related to transcriptional regulation and, specifically, an enrichment for the SETD1A histone methyltransferase complex, known to regulate WNT signaling for the generation and proliferation of intermediate progenitor cells.

CONCLUSIONS: This study complements previous research focused on protein-coding changes distinguishing our species from Neanderthals/Denisovans and highlights chromatin regulation as a functional category so far overlooked in modern human evolution studies. We present a set of candidates that will help to illuminate the investigation of modern human-specific ontogenetic trajectories.}, } @article {pmid32296179, year = {2020}, author = {Grün, R and Pike, A and McDermott, F and Eggins, S and Mortimer, G and Aubert, M and Kinsley, L and Joannes-Boyau, R and Rumsey, M and Denys, C and Brink, J and Clark, T and Stringer, C}, title = {Dating the skull from Broken Hill, Zambia, and its position in human evolution.}, journal = {Nature}, volume = {580}, number = {7803}, pages = {372-375}, pmid = {32296179}, issn = {1476-4687}, mesh = {Animals ; *Biological Evolution ; Fossils ; *Hominidae ; *Skull ; Time Factors ; }, abstract = {The cranium from Broken Hill (Kabwe) was recovered from cave deposits in 1921, during metal ore mining in what is now Zambia[1]. It is one of the best-preserved skulls of a fossil hominin, and was initially designated as the type specimen of Homo rhodesiensis, but recently it has often been included in the taxon Homo heidelbergensis[2-4]. However, the original site has since been completely quarried away, and-although the cranium is often estimated to be around 500 thousand years old[5-7]-its unsystematic recovery impedes its accurate dating and placement in human evolution. Here we carried out analyses directly on the skull and found a best age estimate of 299 ± 25 thousand years (mean ± 2σ). The result suggests that later Middle Pleistocene Africa contained multiple contemporaneous hominin lineages (that is, Homo sapiens[8,9], H. heidelbergensis/H. rhodesiensis and Homo naledi[10,11]), similar to Eurasia, where Homo neanderthalensis, the Denisovans, Homo floresiensis, Homo luzonensis and perhaps also Homo heidelbergensis and Homo erectus[12] were found contemporaneously. The age estimate also raises further questions about the mode of evolution of H. sapiens in Africa and whether H. heidelbergensis/H. rhodesiensis was a direct ancestor of our species[13,14].}, } @article {pmid32285198, year = {2020}, author = {Barreiro, LB and Quintana-Murci, L}, title = {Evolutionary and population (epi)genetics of immunity to infection.}, journal = {Human genetics}, volume = {139}, number = {6-7}, pages = {723-732}, pmid = {32285198}, issn = {1432-1203}, support = {ANR-10-LABX-69-01//ANR/ ; R01 GM115656/GM/NIGMS NIH HHS/United States ; R01-GM115656/GM/NIGMS NIH HHS/United States ; R01-GM134376/GM/NIGMS NIH HHS/United States ; R01 GM134376/GM/NIGMS NIH HHS/United States ; ANR-10- LABX-62-IBEID//ANR/ ; }, mesh = {Animals ; *Biological Evolution ; *Epigenesis, Genetic ; *Genetic Variation ; *Genetics, Population ; *Genome, Human ; Humans ; Infections/epidemiology/genetics/*immunology ; Selection, Genetic ; }, abstract = {Immune response is one of the functions that have been more strongly targeted by natural selection during human evolution. The evolutionary genetic dissection of the immune system has greatly helped to distinguish genes and functions that are essential, redundant or advantageous for human survival. It is also becoming increasingly clear that admixture between early Eurasians with now-extinct hominins such as Neanderthals or Denisovans, or admixture between modern human populations, can be beneficial for human adaptation to pathogen pressures. In this review, we discuss how the integration of population genetics with functional genomics in diverse human populations can inform about the changes in immune functions related to major lifestyle transitions (e.g., from hunting and gathering to farming), the action of natural selection to the evolution of the immune system, and the history of past epidemics. We also highlight the need of expanding the characterization of the immune system to a larger array of human populations-particularly neglected human groups historically exposed to different pathogen pressures-to fully capture the relative contribution of genetic, epigenetic, and environmental factors to immune response variation in humans.}, } @article {pmid32269345, year = {2020}, author = {Welker, F and Ramos-Madrigal, J and Gutenbrunner, P and Mackie, M and Tiwary, S and Rakownikow Jersie-Christensen, R and Chiva, C and Dickinson, MR and Kuhlwilm, M and de Manuel, M and Gelabert, P and Martinón-Torres, M and Margvelashvili, A and Arsuaga, JL and Carbonell, E and Marques-Bonet, T and Penkman, K and Sabidó, E and Cox, J and Olsen, JV and Lordkipanidze, D and Racimo, F and Lalueza-Fox, C and Bermúdez de Castro, JM and Willerslev, E and Cappellini, E}, title = {The dental proteome of Homo antecessor.}, journal = {Nature}, volume = {580}, number = {7802}, pages = {235-238}, pmid = {32269345}, issn = {1476-4687}, support = {/WT_/Wellcome Trust/United Kingdom ; U01 MH106874/MH/NIMH NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Dental Enamel/*chemistry/*metabolism ; *Fossils ; Georgia (Republic) ; *Hominidae ; Humans ; Male ; Molar/chemistry/metabolism ; Neanderthals ; Phosphoproteins/analysis/chemistry/metabolism ; Phosphorylation ; Phylogeny ; Proteome/*analysis/chemistry/*metabolism ; Spain ; }, abstract = {The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated[1-5]. For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge[6-8]. Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)[9,10] and Homo erectus from Dmanisi (Georgia)[1], two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo.}, } @article {pmid32264696, year = {2020}, author = {Kurmukov, A and Mussabaeva, A and Denisova, Y and Moyer, D and Jahanshad, N and Thompson, PM and Gutman, BA}, title = {Optimizing Connectivity-Driven Brain Parcellation Using Ensemble Clustering.}, journal = {Brain connectivity}, volume = {10}, number = {4}, pages = {183-194}, pmid = {32264696}, issn = {2158-0022}, support = {R01 MH116147/MH/NIMH NIH HHS/United States ; U01 AG024904/AG/NIA NIH HHS/United States ; U54 EB020403/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Atlases as Topic ; Brain/*anatomy & histology/diagnostic imaging ; Connectome ; Diffusion Magnetic Resonance Imaging/*methods/standards ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Image Processing, Computer-Assisted/methods ; Male ; Nerve Net/*anatomy & histology/diagnostic imaging ; Neuroimaging/*methods/standards ; Young Adult ; }, abstract = {This work addresses the problem of constructing a unified, topologically optimal connectivity-based brain atlas. The proposed approach aggregates an ensemble partition from individual parcellations without label agreement, providing a balance between sufficiently flexible individual parcellations and intuitive representation of the average topological structure of the connectome. The methods exploit a previously proposed dense connectivity representation, first performing graph-based hierarchical parcellation of individual brains, and subsequently aggregating the individual parcellations into a consensus parcellation. The search for consensus-based on the hard ensemble (HE) algorithm-approximately minimizes the sum of cluster membership distances, effectively estimating a pseudo-Karcher mean of individual parcellations. Computational stability, graph structure preservation, and biological relevance of the simplified representation resulting from the proposed parcellation are assessed on the Human Connectome Project data set. These aspects are assessed using (1) edge weight distribution divergence with respect to the dense connectome representation, (2) interhemispheric symmetry, (3) network characteristics' stability and agreement with respect to individually and anatomically parcellated networks, and (4) performance of the simplified connectome in a biological sex classification task. Ensemble parcellation was found to be highly stable with respect to subject sampling, outperforming anatomical atlases and other connectome-based parcellations in classification as well as preserving global connectome properties. The HE-based parcellation also showed a degree of symmetry comparable with anatomical atlases and a high degree of spatial contiguity without using explicit priors.}, } @article {pmid32250731, year = {2020}, author = {Agrawal, R and Testi, I and Mahajan, S and Yuen, YS and Agarwal, A and Rousselot, A and Raje, D and Gunasekeran, DV and Kon, OM and Barisani-Asenbauer, T and Kempen, JH and Gupta, A and Jabs, DA and Smith, JR and Bodaghi, B and Zierhut, M and DeSmet, M and Cluskey, PM and Agarwal, M and Agarwal, M and Aggarwal, K and Agrawal, M and Al-Dhibi, H and Androudi, S and Asyari, F and Balasundaram, MB and Murthy, KB and Baglivo, E and Banker, A and Bansal, R and Basu, S and Behera, D and Biswas, J and Carreño, E and Caspers, L and Chee, SP and Chhabra, R and Cimino, L and Del Rio, LEC and Cunningham, ET and Curi, ALL and Das, D and Denisova, E and Denniston, AK and Errera, MH and Fonollosa, A and George, A and Goldstein, DA and Crosier, YG and Gurbaxani, A and Invernizzi, A and Isa, HM and Md Islam, S and Jones, N and Katoch, D and Khairallah, M and Khosla, A and Kramer, M and Kumar, A and Kumar, A and Nora, RD and Lee, R and Lowder, C and Luthra, S and Mahendradas, P and Makhoul, D and Mazumdar, S and Mehta, S and Miserocchi, E and Mochizuki, M and Mohamed, OS and Muccioli, C and Munk, MR and Murthy, S and Narain, S and Nascimento, H and Neri, P and Nguyen, M and Okada, AA and Ozdal, P and Palestine, A and Pichi, F and Rathinam, SR and Schlaen, A and Sehgal, S and Sen, HN and Sharma, A and Sharma, K and Shoughy, SS and Singh, N and Singh, R and Soheilian, M and Sridharan, S and Thorne, JE and Tappeiner, C and Teoh, S and Tognon, MS and Tugal-Tutkun, I and Tyagi, M and Uy, H and Santos, DVV and Valentincic, NV and Westcott, M and Yanai, R and Alvarez, BY and Zahedur, R and Nguyen, QD and Pavesio, C and Gupta, V}, title = {The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings.}, journal = {Ocular immunology and inflammation}, volume = {28}, number = {sup1}, pages = {85-95}, doi = {10.1080/09273948.2020.1716025}, pmid = {32250731}, issn = {1744-5078}, abstract = {An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.}, } @article {pmid32234956, year = {2020}, author = {Taskent, O and Lin, YL and Patramanis, I and Pavlidis, P and Gokcumen, O}, title = {Analysis of Haplotypic Variation and Deletion Polymorphisms Point to Multiple Archaic Introgression Events, Including from Altai Neanderthal Lineage.}, journal = {Genetics}, volume = {215}, number = {2}, pages = {497-509}, pmid = {32234956}, issn = {1943-2631}, mesh = {Animals ; *Genetics, Population ; Genome, Human ; *Haplotypes ; Hominidae ; Humans ; Neanderthals/*genetics ; *Phenotype ; *Polymorphism, Genetic ; Russia ; *Selection, Genetic ; }, abstract = {The time, extent, and genomic effect of the introgressions from archaic humans into ancestors of extant human populations remain some of the most exciting venues of population genetics research in the past decade. Several studies have shown population-specific signatures of introgression events from Neanderthals, Denisovans, and potentially other unknown hominin populations in different human groups. Moreover, it was shown that these introgression events may have contributed to phenotypic variation in extant humans, with biomedical and evolutionary consequences. In this study, we present a comprehensive analysis of the unusually divergent haplotypes in the Eurasian genomes and show that they can be traced back to multiple introgression events. In parallel, we document hundreds of deletion polymorphisms shared with Neanderthals. A locus-specific analysis of one such shared deletion suggests the existence of a direct introgression event from the Altai Neanderthal lineage into the ancestors of extant East Asian populations. Overall, our study is in agreement with the emergent notion that various Neanderthal populations contributed to extant human genetic variation in a population-specific manner.}, } @article {pmid32201812, year = {2020}, author = {Mitoudi Vagourdi, E and Zhang, W and Denisova, K and Lemmens, P and Halasyamani, PS and Johnsson, M}, title = {Synthesis and Characterization of Two New Second Harmonic Generation Active Iodates: K3Sc(IO3)6 and KSc(IO3)3Cl.}, journal = {ACS omega}, volume = {5}, number = {10}, pages = {5235-5240}, pmid = {32201812}, issn = {2470-1343}, abstract = {Transparent single crystals of two new iodates K3Sc(IO3)6 and KSc(IO3)3Cl have been synthesized hydrothermally. Single-crystal X-ray diffraction was used to determine their crystal structures. Both compounds crystallize in non-centrosymmetric space groups. The compound K3Sc(IO3)6 crystallizes in the orthorhombic space group Fdd2. The crystal structure is made up of [ScO6] octahedra, [IO3] trigonal pyramids, and [KO8] distorted cubes. The compound KSc(IO3)3Cl crystallizes in the trigonal space group R3. The building blocks are [ScO6] octahedra, [KO12] polyhedra, and [IO3] trigonal pyramids. The Cl[-] ions act as counter ions and reside in tunnels in the crystal structure. The second harmonic generation (SHG) measurements at room temperature, using 1064 nm radiation, on polycrystalline samples show that the SHG intensities of K3Sc(IO3)6 and KSc(IO3)3Cl are around 2.8 and 2.5 times that of KH2PO4 (KDP), respectively. In addition, K3Sc(IO3)6 and KSc(IO3)3Cl are phase-matchable at the fundamental wavelength of 1064 nm. The large anharmonicity in the optical response of both compounds is further supported by an anomalous temperature dependence of optical phonon frequencies as well as their enlarged intensities in Raman scattering. The latter corresponds to a very large electronic polarizability.}, } @article {pmid32193295, year = {2020}, author = {Bergström, A and McCarthy, SA and Hui, R and Almarri, MA and Ayub, Q and Danecek, P and Chen, Y and Felkel, S and Hallast, P and Kamm, J and Blanché, H and Deleuze, JF and Cann, H and Mallick, S and Reich, D and Sandhu, MS and Skoglund, P and Scally, A and Xue, Y and Durbin, R and Tyler-Smith, C}, title = {Insights into human genetic variation and population history from 929 diverse genomes.}, journal = {Science (New York, N.Y.)}, volume = {367}, number = {6484}, pages = {}, pmid = {32193295}, issn = {1095-9203}, support = {/ERC_/European Research Council/International ; /HHMI/Howard Hughes Medical Institute/United States ; 206194/WT_/Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; //Medical Research Council,/International ; FC001595/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FC001595/CRUK_/Cancer Research UK/United Kingdom ; FC001595/MRC_/Medical Research Council/United Kingdom ; 207492/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Africa ; Americas ; Animals ; Asia ; DNA Copy Number Variations ; *Genetic Variation ; *Genetics, Population ; *Genome, Human ; Haplotypes ; Hominidae/genetics ; Humans ; INDEL Mutation ; Neanderthals/genetics ; Oceania ; Phylogeny ; Polymorphism, Single Nucleotide ; Population Density ; Racial Groups/genetics ; *Whole Genome Sequencing ; }, abstract = {Genome sequences from diverse human groups are needed to understand the structure of genetic variation in our species and the history of, and relationships between, different populations. We present 929 high-coverage genome sequences from 54 diverse human populations, 26 of which are physically phased using linked-read sequencing. Analyses of these genomes reveal an excess of previously undocumented common genetic variation private to southern Africa, central Africa, Oceania, and the Americas, but an absence of such variants fixed between major geographical regions. We also find deep and gradual population separations within Africa, contrasting population size histories between hunter-gatherer and agriculturalist groups in the past 10,000 years, and a contrast between single Neanderthal but multiple Denisovan source populations contributing to present-day human populations.}, } @article {pmid32151667, year = {2020}, author = {Stark, MS and Denisova, E and Kays, TA and Heidenreich, B and Rachakonda, S and Requena, C and Sturm, RA and Soyer, HP and Nagore, E and Kumar, R}, title = {Mutation Signatures in Melanocytic Nevi Reveal Characteristics of Defective DNA Repair.}, journal = {The Journal of investigative dermatology}, volume = {140}, number = {10}, pages = {2093-2096.e2}, doi = {10.1016/j.jid.2020.02.021}, pmid = {32151667}, issn = {1523-1747}, mesh = {DNA Copy Number Variations ; *DNA Repair ; Humans ; *Mutation ; Nevus, Pigmented/*genetics ; Polymorphism, Single Nucleotide ; Exome Sequencing ; }, } @article {pmid32132541, year = {2020}, author = {Gokhman, D and Nissim-Rafinia, M and Agranat-Tamir, L and Housman, G and García-Pérez, R and Lizano, E and Cheronet, O and Mallick, S and Nieves-Colón, MA and Li, H and Alpaslan-Roodenberg, S and Novak, M and Gu, H and Osinski, JM and Ferrando-Bernal, M and Gelabert, P and Lipende, I and Mjungu, D and Kondova, I and Bontrop, R and Kullmer, O and Weber, G and Shahar, T and Dvir-Ginzberg, M and Faerman, M and Quillen, EE and Meissner, A and Lahav, Y and Kandel, L and Liebergall, M and Prada, ME and Vidal, JM and Gronostajski, RM and Stone, AC and Yakir, B and Lalueza-Fox, C and Pinhasi, R and Reich, D and Marques-Bonet, T and Meshorer, E and Carmel, L}, title = {Differential DNA methylation of vocal and facial anatomy genes in modern humans.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {1189}, pmid = {32132541}, issn = {2041-1723}, support = {P51 OD011133/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Cells, Cultured ; Child ; Chondrocytes ; *DNA Methylation ; *DNA, Ancient ; Evolution, Molecular ; Face/*anatomy & histology ; Female ; Gene Regulatory Networks ; Genetic Speciation ; Humans ; Larynx/anatomy & histology ; Male ; Middle Aged ; Neanderthals/genetics ; Pan troglodytes/genetics ; *Phenotype ; Phonation/*genetics ; Primary Cell Culture ; Tongue/anatomy & histology ; Vocal Cords/anatomy & histology ; Vocalization, Animal ; }, abstract = {Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and experimentally measured DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that likely emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes associated with face and vocal tract anatomy went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-associated genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract.}, } @article {pmid32128408, year = {2020}, author = {Rogers, AR and Harris, NS and Achenbach, AA}, title = {Neanderthal-Denisovan ancestors interbred with a distantly related hominin.}, journal = {Science advances}, volume = {6}, number = {8}, pages = {eaay5483}, pmid = {32128408}, issn = {2375-2548}, mesh = {Animals ; Confidence Intervals ; *Consanguinity ; Gene Flow ; Genetics, Population ; Hominidae/*genetics ; Models, Genetic ; Neanderthals/*genetics ; Phylogeny ; }, abstract = {Previous research has shown that modern Eurasians interbred with their Neanderthal and Denisovan predecessors. We show here that hundreds of thousands of years earlier, the ancestors of Neanderthals and Denisovans interbred with their own Eurasian predecessors-members of a "superarchaic" population that separated from other humans about 2 million years ago. The superarchaic population was large, with an effective size between 20 and 50 thousand individuals. We confirm previous findings that (i) Denisovans also interbred with superarchaics, (ii) Neanderthals and Denisovans separated early in the middle Pleistocene, (iii) their ancestors endured a bottleneck of population size, and (iv) the Neanderthal population was large at first but then declined in size. We provide qualified support for the view that (v) Neanderthals interbred with the ancestors of modern humans.}, } @article {pmid32119213, year = {2020}, author = {Denisova, OA and Gudina, TV and Bukina, IA and Lekhanova, OL and Bukin, DA}, title = {[The medical pedagogical prevention of deviant behavior in adolescents from disadvantaged family in conditions of rural school].}, journal = {Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsiny}, volume = {28}, number = {1}, pages = {74-82}, doi = {10.32687/0869-866X-2020-28-1-74-82}, pmid = {32119213}, issn = {0869-866X}, mesh = {Adolescent ; Child ; Humans ; Prevalence ; *Rural Population ; Schools ; *Substance-Related Disorders ; *Vulnerable Populations ; }, abstract = {The article considers medical and pedagogical prevention of deviant behavior of adolescents from dysfunctional families in conditions of rural school, related to the need of strengthening targeted joint interaction of medical and pedagogical institutions. The description and results of testing of diagnostic tools used to establish severity of deviant behavior of children in a selected group is discussed. The interaction of medical and educational institutions in preventing deviant behavior of adolescents from dysfunctional families in rural school is of key importance for combating prevalence of drug addiction, tobacco smoking, alcohol abuse and psychoactive substances consumption, and contributing to physical and mental health promotion of younger generation, development of healthy lifestyle. The study was organized to cover cognitive, behavioral, affective and value-motivational components. The qualitative characteristics of levels of severity of deviant behavior of adolescents from dysfunctional families were developed and proposed for practice application.}, } @article {pmid32115264, year = {2021}, author = {Agrawal, R and Testi, I and Mahajan, S and Yuen, YS and Agarwal, A and Kon, OM and Barisani-Asenbauer, T and Kempen, JH and Gupta, A and Jabs, DA and Smith, JR and Nguyen, QD and Pavesio, C and Gupta, V and , }, title = {Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis.}, journal = {Ophthalmology}, volume = {128}, number = {2}, pages = {266-276}, doi = {10.1016/j.ophtha.2020.01.008}, pmid = {32115264}, issn = {1549-4713}, support = {MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Antitubercular Agents/*therapeutic use ; Chemotherapy, Adjuvant ; Delphi Technique ; Drug Therapy, Combination ; Eye Infections, Bacterial/diagnosis/*drug therapy/microbiology ; Glucocorticoids/therapeutic use ; Humans ; Multifocal Choroiditis/diagnosis/*drug therapy/microbiology ; Radiography, Thoracic ; Retrospective Studies ; Surveys and Questionnaires ; Tomography, X-Ray Computed ; Tuberculin Test ; Tuberculosis, Ocular/diagnosis/*drug therapy/microbiology ; }, abstract = {TOPIC: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis.

CLINICAL RELEVANCE: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU.

METHODS: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process.

RESULTS: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis.

DISCUSSION: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.}, } @article {pmid32095519, year = {2020}, author = {Durvasula, A and Sankararaman, S}, title = {Recovering signals of ghost archaic introgression in African populations.}, journal = {Science advances}, volume = {6}, number = {7}, pages = {eaax5097}, pmid = {32095519}, issn = {2375-2548}, support = {R35 GM125055/GM/NIGMS NIH HHS/United States ; R00 GM111744/GM/NIGMS NIH HHS/United States ; }, mesh = {Black People/*genetics ; Ethnicity/genetics ; Gene Frequency ; *Genetics, Population ; Humans ; Phylogeny ; }, abstract = {While introgression from Neanderthals and Denisovans has been documented in modern humans outside Africa, the contribution of archaic hominins to the genetic variation of present-day Africans remains poorly understood. We provide complementary lines of evidence for archaic introgression into four West African populations. Our analyses of site frequency spectra indicate that these populations derive 2 to 19% of their genetic ancestry from an archaic population that diverged before the split of Neanderthals and modern humans. Using a method that can identify segments of archaic ancestry without the need for reference archaic genomes, we built genome-wide maps of archaic ancestry in the Yoruba and the Mende populations. Analyses of these maps reveal segments of archaic ancestry at high frequency in these populations that represent potential targets of adaptive introgression. Our results reveal the substantial contribution of archaic ancestry in shaping the gene pool of present-day West African populations.}, } @article {pmid32067025, year = {2020}, author = {Shlyakhtina, AV and Avdeev, M and Lyskov, NV and Abrantes, JCC and Gomes, E and Denisova, KN and Kolbanev, IV and Chernyak, SA and Volkova, OS and Vasiliev, AN}, title = {Structure, conductivity and magnetism of orthorhombic and fluorite polymorphs in MoO3-Ln2O3 (Ln = Gd, Dy, Ho) systems.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {49}, number = {9}, pages = {2833-2842}, doi = {10.1039/c9dt04724g}, pmid = {32067025}, issn = {1477-9234}, abstract = {Phase-pure orthorhombic compositions at a Ln/Mo ratio ∼ 5.2-5.7 (Ln = Gd, Dy, Ho) have been obtained for the first time by prolonged (40-160 h) heat treatment of mechanically activated 5Ln2O3 + 2MoO3 (Ln = Gd, Dy, Ho) oxide mixtures at 1200 °C. Although the starting Ln : Mo ratio was 5 : 1 (Ln10Mo2O21 (Ln = Dy, Ho)), it changed slightly in the final product due to the volatility of molybdenum oxide at 1200 °C (40-160 h) (ICP-MS analysis). Brief high-temperature firing (1600 °C, 3 h) of 5Ln2O3 + 2MoO3 (Ln = Gd, Dy, Ho) oxide mixtures leads to the formation of phase-pure fluorites with compositions close to Ln10Mo2O21 (Ln = Gd, Dy, Ho). Gd10Mo2O21 molybdate seems to undergo an order-disorder (orthorhombic-fluorite) phase transition in the range of 1200-1600 °C. For the first time, using the neutron diffraction method, it was shown that low-temperature phases with a Ln/Mo ratio ∼ 5.2-5.7 (Ln = Gd, Dy, Ho) have an orthorhombic structure rather than a tetragonal structure. Proton contribution to the total conductivity of Ln10Mo2O21 (Ln = Gd, Dy, Ho) fluorites and gadolinium and dysprosium orthorhombic phases in a wet atmosphere was observed for the first time. In both orthorhombic and fluorite phases, the total conductivity in wet air decreases with decreasing lanthanide ionic radii. In a wide temperature range, the compounds under study exhibit paramagnetic behaviour. However, the orthorhombic phases of Dy and Ho compounds reach the antiferromagnetic state at 2.4 K and 2.6 K, respectively.}, } @article {pmid32032517, year = {2020}, author = {Gokhman, D and Mishol, N and de Manuel, M and de Juan, D and Shuqrun, J and Meshorer, E and Marques-Bonet, T and Rak, Y and Carmel, L}, title = {Reconstructing Denisovan Anatomy Using DNA Methylation Maps.}, journal = {Cell}, volume = {180}, number = {3}, pages = {601}, doi = {10.1016/j.cell.2020.01.020}, pmid = {32032517}, issn = {1097-4172}, } @article {pmid34692055, year = {2020}, author = {, and He, Y and Lou, H and Cui, C and Deng, L and Gao, Y and Zheng, W and Guo, Y and Wang, X and Ning, Z and Li, J and Li, B and Bai, C and , and , and , and , and , and Liu, S and Wu, T and Xu, S and Qi, X and Su, B}, title = {De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation.}, journal = {National science review}, volume = {7}, number = {2}, pages = {391-402}, pmid = {34692055}, issn = {2053-714X}, abstract = {Structural variants (SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome (ZF1), with a contig N50 length of 24.57 mega-base pairs (Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps (0.25 Mb in total length) in the reference human genome (GRCh38). Markedly, we detected 17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid (Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1 (1.32%-1.53%) compared to other East Asian genomes (0.70%-0.98%), reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence-a 662-bp intronic insertion in the SCUBE2 gene-is enriched and associated with better lung function (the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.}, } @article {pmid32004458, year = {2020}, author = {Chen, L and Wolf, AB and Fu, W and Li, L and Akey, JM}, title = {Identifying and Interpreting Apparent Neanderthal Ancestry in African Individuals.}, journal = {Cell}, volume = {180}, number = {4}, pages = {677-687.e16}, doi = {10.1016/j.cell.2020.01.012}, pmid = {32004458}, issn = {1097-4172}, support = {R01 GM110068/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Black People/*genetics ; *Evolution, Molecular ; Gene Flow ; Human Migration ; Humans ; Models, Genetic ; Neanderthals/*genetics ; Pedigree ; Polymorphism, Genetic ; }, abstract = {Admixture has played a prominent role in shaping patterns of human genomic variation, including gene flow with now-extinct hominins like Neanderthals and Denisovans. Here, we describe a novel probabilistic method called IBDmix to identify introgressed hominin sequences, which, unlike existing approaches, does not use a modern reference population. We applied IBDmix to 2,504 individuals from geographically diverse populations to identify and analyze Neanderthal sequences segregating in modern humans. Strikingly, we find that African individuals carry a stronger signal of Neanderthal ancestry than previously thought. We show that this can be explained by genuine Neanderthal ancestry due to migrations back to Africa, predominately from ancestral Europeans, and gene flow into Neanderthals from an early dispersing group of humans out of Africa. Our results refine our understanding of Neanderthal ancestry in African and non-African populations and demonstrate that remnants of Neanderthal genomes survive in every modern human population studied to date.}, } @article {pmid31987110, year = {2020}, author = {Rudnev, S and Burns, JS and Williams, PL and Lee, MM and Korrick, SA and Denisova, T and Dikov, Y and Kozupitsa, G and Hauser, R and Sergeyev, O}, title = {Comparison of bioimpedance body composition in young adults in the Russian Children's Study.}, journal = {Clinical nutrition ESPEN}, volume = {35}, number = {}, pages = {153-161}, pmid = {31987110}, issn = {2405-4577}, support = {P30 ES000002/ES/NIEHS NIH HHS/United States ; R01 ES014370/ES/NIEHS NIH HHS/United States ; }, mesh = {Absorptiometry, Photon ; Adipose Tissue ; Adolescent ; Anthropometry ; *Body Composition ; Body Mass Index ; Child ; Cross-Sectional Studies ; *Electric Impedance ; Humans ; Male ; Russia ; Young Adult ; }, abstract = {BACKGROUND & AIMS: Body mass index is a simple anthropometric measure (kg/m[2]) used as an indirect estimate of body fat in individuals, and in assessments of population health and comparisons between populations. Bioelectrical impedance analysis (BIA) is often used to provide additional information on body fat and fat-free mass, and has been used to generate body composition reference data in national health surveys. However, BIA measurements are known to be device-specific and there are few published studies comparing results from different BIA instruments. Therefore, we compared the performance of two BIA instruments in the Russian Children's Study (RCS) of male growth, pubertal development and maturation.

METHODS: Paired BIA measurements were obtained using the Tanita BC-418MA (Tanita Corp., Tokyo, Japan) and ABC-01 'Medas' (Medas Ltd, Moscow, Russia) BIA instruments. Cross-sectional data on 236 RCS subjects aged 18-22 years were used for the BIA comparison and the development of a conversion formula between measured resistances; follow-up data (n = 96) were used for validation of the conversion formula.

RESULTS: Whole-body resistances were highly correlated (Spearman rho = 0.95), but fat mass (FM) estimates were significantly higher with the Medas than the Tanita device (median difference 3.3 kg, 95% CI: 2.9, 3.6 kg) with large limits of agreement (LoA) for the FM difference (-2.0, 8.6 kg). A conversion formula between the resistances (Res) was obtained: Medas Res = 0.882 × Tanita Res+26.2 (r[2] = 0.91, SEE = 17.6 Ohm). After applying the conversion formula to Tanita data and application of the Medas assessment algorithm, the 'converted' Tanita FM estimates closely matched the Medas original estimates (median difference -0.1 kg, 95% CI: -0.3, 0.2 kg), with relatively small LoA for the FM difference (-2.3 to 2.1 kg), suggesting potential interchangeability of the ABC-01 'Medas' and Tanita BC-418MA data at the group level.

CONCLUSIONS: Our results support the importance of cross-calibration of BIA instruments for population comparisons and proper data interpretation in clinical and epidemiological studies.}, } @article {pmid36659062, year = {2020}, author = {Zhang, D and Xia, H and Cheng, T and Chen, F}, title = {New portraits of the Denisovans.}, journal = {Science bulletin}, volume = {65}, number = {1}, pages = {1-3}, doi = {10.1016/j.scib.2019.10.013}, pmid = {36659062}, issn = {2095-9281}, } @article {pmid31935281, year = {2020}, author = {Gouy, A and Excoffier, L}, title = {Polygenic Patterns of Adaptive Introgression in Modern Humans Are Mainly Shaped by Response to Pathogens.}, journal = {Molecular biology and evolution}, volume = {37}, number = {5}, pages = {1420-1433}, doi = {10.1093/molbev/msz306}, pmid = {31935281}, issn = {1537-1719}, mesh = {Adaptation, Biological/*genetics ; *Genetic Introgression ; Host-Pathogen Interactions/*genetics ; Humans ; Melanesia ; *Multifactorial Inheritance ; *Selection, Genetic ; }, abstract = {Anatomically modern humans carry many introgressed variants from other hominins in their genomes. Some of them affect their phenotype and can thus be negatively or positively selected. Several individual genes have been proposed to be the subject of adaptive introgression, but the possibility of polygenic adaptive introgression has not been extensively investigated yet. In this study, we analyze archaic introgression maps with refined functional enrichment methods to find signals of polygenic adaptation of introgressed variants. We first apply a method to detect sets of connected genes (subnetworks) within biological pathways that present higher-than-expected levels of archaic introgression. We then introduce and apply a new statistical test to distinguish between epistatic and independent selection in gene sets of present-day humans. We identify several known targets of adaptive introgression, and we show that they belong to larger networks of introgressed genes. After correction for genetic linkage, we find that signals of polygenic adaptation are mostly explained by independent and potentially sequential selection episodes. However, we also find some gene sets where introgressed variants present significant signals of epistatic selection. Our results confirm that archaic introgression has facilitated local adaptation, especially in immunity related and metabolic functions and highlight its involvement in a coordinated response to pathogens out of Africa.}, } @article {pmid31878873, year = {2019}, author = {Bücking, R and Cox, MP and Hudjashov, G and Saag, L and Sudoyo, H and Stoneking, M}, title = {Archaic mitochondrial DNA inserts in modern day nuclear genomes.}, journal = {BMC genomics}, volume = {20}, number = {1}, pages = {1017}, pmid = {31878873}, issn = {1471-2164}, mesh = {Animals ; Cell Nucleus/*genetics ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; Genomics/*methods ; Hominidae/genetics ; Neanderthals/genetics ; Phylogeny ; }, abstract = {BACKGROUND: Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Saharan Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs).

RESULTS: We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin, present in 15 analysed genomes; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male.

CONCLUSIONS: Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.}, } @article {pmid31848254, year = {2020}, author = {Scott, GR and Irish, JD and Martinón-Torres, M}, title = {A more comprehensive view of the Denisovan 3-rooted lower second molar from Xiahe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {1}, pages = {37-38}, pmid = {31848254}, issn = {1091-6490}, mesh = {Asian People ; *Fossils ; Humans ; Molar/anatomy & histology ; *Tooth ; }, } @article {pmid31821096, year = {2020}, author = {Agrawal, R and Agarwal, A and Jabs, DA and Kee, A and Testi, I and Mahajan, S and McCluskey, PJ and Gupta, A and Palestine, A and Denniston, A and Banker, A and Invernizzi, A and Fonollosa, A and Sharma, A and Kumar, A and Curi, A and Okada, A and Schlaen, A and Heiligenhaus, A and Kumar, A and Gurbaxani, A and Bodaghi, B and Islam Shah, B and Lowder, C and Tappeiner, C and Muccioli, C and Vasconcelos-Santos, DV and Goldstein, D and Behra, D and Das, D and Makhoul, D and Baglivo, E and Denisova, E and Miserocchi, E and Carreno, E and Asyari, F and Pichi, F and Sen, HN and Uy, H and Nascimento, H and Tugal-Tutkun, I and Arevalo, JF and Davis, J and Thorne, J and Hisae Yamamoto, J and Smith, J and Garweg, JG and Biswas, J and Babu, K and Aggarwal, K and Cimino, L and Kuffova, L and Agarwal, M and Zierhut, M and Agarwal, M and De Smet, M and Tognon, MS and Errera, MH and Munk, M and Westcott, M and Soheilian, M and Accorinti, M and Khairallah, M and Nguyen, M and Kon, OM and Mahendradas, P and Yang, P and Neri, P and Ozdal, P and Amer, R and Lee, R and Distia Nora, R and Chhabra, R and Belfort, R and Mehta, S and Shoughy, S and Luthra, S and Mohamed, SO and Chee, SP and Basu, S and Teoh, S and Ganesh, S and Barisani-Asenbauer, T and Guex-Crosier, Y and Ozyazgan, Y and Akova, Y and Habot-Wilner, Z and Kempen, J and Nguyen, QD and Pavesio, C and Gupta, V and , }, title = {Standardization of Nomenclature for Ocular Tuberculosis - Results of Collaborative Ocular Tuberculosis Study (COTS) Workshop.}, journal = {Ocular immunology and inflammation}, volume = {28}, number = {sup1}, pages = {74-84}, doi = {10.1080/09273948.2019.1653933}, pmid = {31821096}, issn = {1744-5078}, support = {ETM/351/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {Purpose: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).Methods: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.Results: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes.Conclusion: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity.}, } @article {pmid31809748, year = {2019}, author = {Wall, JD and Ratan, A and Stawiski, E and , }, title = {Identification of African-Specific Admixture between Modern and Archaic Humans.}, journal = {American journal of human genetics}, volume = {105}, number = {6}, pages = {1254-1261}, pmid = {31809748}, issn = {1537-6605}, support = {P30 CA044579/CA/NCI NIH HHS/United States ; R01 GM115433/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Black People/*genetics ; *Fossils ; Gene Pool ; *Genetics, Population ; *Genome, Human ; Hominidae/*genetics ; Humans ; Neanderthals/*genetics ; }, abstract = {Recent work has demonstrated that two archaic human groups (Neanderthals and Denisovans) interbred with modern humans and contributed to the contemporary human gene pool. These findings relied on the availability of high-coverage genomes from both Neanderthals and Denisovans. Here we search for evidence of archaic admixture from a worldwide panel of 1,667 individuals using an approach that does not require the presence of an archaic human reference genome. We find no evidence for archaic admixture in the Andaman Islands, as previously claimed, or on the island of Flores, where Homo floresiensis fossils have been found. However, we do find evidence for at least one archaic admixture event in sub-Saharan Africa, with the strongest signal in Khoesan and Pygmy individuals from Southern and Central Africa. The locations of these putative archaic admixture tracts are weighted against functional regions of the genome, consistent with the long-term effects of purifying selection against introgressed genetic material.}, } @article {pmid31793960, year = {2019}, author = {Buzlukov, AL and Arapova, IY and Baklanova, YV and Medvedeva, NI and Denisova, TA and Savina, AA and Lazoryak, BI and Khaikina, EG and Bardet, M}, title = {Coexistence of three types of sodium motion in double molybdate Na9Sc(MoO4)6: [23]Na and [45]Sc NMR data and ab initio calculations.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {22}, number = {1}, pages = {144-154}, doi = {10.1039/c9cp05249f}, pmid = {31793960}, issn = {1463-9084}, abstract = {The rechargeable Na-ion batteries attract much attention as an alternative to the widely used but expensive Li-ion batteries. The search for materials with high sodium diffusion is important for the development of solid state electrolytes. We present the results of experimental and ab initio studies of the Na-ion diffusion mechanism in Na9Sc(MoO4)6. The ion conductivity reaches the value of 3.6 × 10-2 S cm-1 at T ∼ 850 K. The 23Na and 45Sc NMR data reveal the coexistence of three different types of Na-ion motion in the temperature range from 300 to 750 K. They are activated at different temperatures and are characterized by substantially different dynamics parameters. These features are confirmed by ab initio calculations of activation barriers for sodium diffusion along various paths.}, } @article {pmid31793531, year = {2019}, author = {Bulynko, SA and Denisova, OA and Kovalets, ES and Kislyakov, AN and Polunin, MM and Soldatsky, YL and Bogomilsky, MR}, title = {[Two cases of bilateral lymphangiomatous palatine tonsil polyps in children].}, journal = {Vestnik otorinolaringologii}, volume = {84}, number = {5}, pages = {73-75}, doi = {10.17116/otorino20198405173}, pmid = {31793531}, issn = {0042-4668}, mesh = {Child ; Humans ; Palatine Tonsil ; *Polyps ; Tonsillar Neoplasms ; }, abstract = {Lymphangiomatous polyps of palatine tonsils are a rare condition, which is diagnosed with patomorphological study. About cases in total are reported in the literature, mostly with one-sided lesions. We managed to find only two reports of lymphangiomatous polyps of palatine tonsils in the available literature. The patients were children in both cases. We report our two cases of children with lymphangiomatous polyps of palatine tonsils.}, } @article {pmid31784916, year = {2019}, author = {Evseeva, NV and Tkachenko, OV and Denisova, AY and Burygin, GL and Veselov, DS and Matora, LY and Shchyogolev, SY}, title = {Functioning of plant-bacterial associations under osmotic stress in vitro.}, journal = {World journal of microbiology & biotechnology}, volume = {35}, number = {12}, pages = {195}, pmid = {31784916}, issn = {1573-0972}, support = {19-016-00116//Russian Foundation for basic research/ ; }, mesh = {Azospirillum brasilense/physiology ; Chlorophyll A ; Colony Count, Microbial ; Droughts ; Host Microbial Interactions/*physiology ; Malonates ; Ochrobactrum/physiology ; *Osmotic Pressure ; *Plant Development ; Plant Leaves ; Plant Roots/microbiology ; Plant Shoots ; Rhizosphere ; Solanum tuberosum/*microbiology ; Stress, Physiological/*physiology ; }, abstract = {The search for effective plant-growth-promoting strains of rhizospheric bacteria that would ensure the resistance of plant-microbial associations to environmental stressors is essential for the design of environmentally friendly agrobiotechnologies. We investigated the interaction of potato (cv. Nevsky) microplants with the plant-growth-promoting bacteria Azospirillum brasilense Sp245 and Ochrobactrum cytisi IPA7.2 under osmotic stress in vitro. The bacteria improved the physiological and biochemical variables of the microplants, significantly increasing shoot length and root number (1.3-fold, on average). Inoculation also led a more effective recovery of the plants after stress. During repair, inoculation contributed to a decreased leaf content of malonic dialdehyde. With A. brasilense Sp245, the decrease was 1.75-fold; with O. cytisi IPA7.2, it was 1.4-fold. During repair, the shoot length, node number, and root number of the inoculated plants were greater than the control values by an average of 1.3-fold with A. brasilense Sp245 and by an average of 1.6-fold with O. cytisi IPA7.2. O. cytisi IPA7.2, previously isolated from the potato rhizosphere, protected the physiological and biochemical processes in the plants under stress and repair better than did A. brasilense Sp245. Specifically, root weight increased fivefold during repair, as compared to the noninoculated plants, while chlorophyll a content remained at the level found in the nonstressed controls. The results indicate that these bacteria can be used as components of biofertilizers. A. brasilense Sp245 has favorable prospects for use in temperate latitudes, whereas O. cytisi IPA7.2 can be successfully used in saline and drought-stressed environments.}, } @article {pmid31783664, year = {2019}, author = {Bazhan, N and Jakovleva, T and Feofanova, N and Denisova, E and Dubinina, A and Sitnikova, N and Makarova, E}, title = {Sex Differences in Liver, Adipose Tissue, and Muscle Transcriptional Response to Fasting and Refeeding in Mice.}, journal = {Cells}, volume = {8}, number = {12}, pages = {}, pmid = {31783664}, issn = {2073-4409}, mesh = {Adipose Tissue/*metabolism ; Animals ; Carnitine O-Palmitoyltransferase/metabolism ; Fasting/*metabolism ; Fatty Acid Synthase, Type I/metabolism ; Fatty Acids/metabolism ; Female ; Fibroblast Growth Factors/metabolism ; Liver/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; PPAR alpha/metabolism ; Quadriceps Muscle/*metabolism ; Refeeding Syndrome/*metabolism ; *Sex Characteristics ; Uncoupling Protein 3/metabolism ; }, abstract = {Fasting is often used for obesity correction but the "refeeding syndrome" limits its efficiency, and molecular mechanisms underlying metabolic response to different food availability are under investigation. Sex was shown to affect hormonal and metabolic reactions to fasting/refeeding. The aim of this study was to evaluate hormonal and transcriptional responses to fasting and refeeding in male and female C57Bl/6J mice. Sex asymmetry was observed both at the hormonal and transcriptional levels. Fasting (24 h) induced increase in hepatic Fgf21 gene expression, which was associated with elevation of plasma FGF21 and adiponectin levels, and the upregulation of expression of hepatic (Pparα, Cpt1α) and muscle (Cpt1β, Ucp3) genes involved in fatty acid oxidation. These changes were more pronounced in females. Refeeding (6 h) evoked hyperinsulinemia and increased hepatic expression of gene related to lipogenesis (Fasn) only in males and hyperleptinemia and increase in Fgf21 gene expression in muscles and adipose tissues only in females. The results suggest that in mice, one of the molecular mechanisms underlying sex asymmetry in hepatic Pparα, Cpt1α, muscle Cpt1β, and Ucp3 expression during fasting is hepatic Fgf21 expression, and the reason for sex asymmetry in hepatic Fasn expression during refeeding is male-specific hyperinsulinemia.}, } @article {pmid31725722, year = {2019}, author = {V Barroso, G and Puzović, N and Dutheil, JY}, title = {Inference of recombination maps from a single pair of genomes and its application to ancient samples.}, journal = {PLoS genetics}, volume = {15}, number = {11}, pages = {e1008449}, pmid = {31725722}, issn = {1553-7404}, mesh = {Animals ; Chromosome Mapping ; Genetic Variation/genetics ; Genome, Human/*genetics ; Hominidae/*genetics ; Humans ; Markov Chains ; *Metagenomics ; Neanderthals/genetics ; Paleontology/trends ; Phylogeny ; Recombination, Genetic/*genetics ; }, abstract = {Understanding the causes and consequences of recombination landscape evolution is a fundamental goal in genetics that requires recombination maps from across the tree of life. Such maps can be obtained from population genomic datasets, but require large sample sizes. Alternative methods are therefore necessary to research organisms where such datasets cannot be generated easily, such as non-model or ancient species. Here we extend the sequentially Markovian coalescent model to jointly infer demography and the spatial variation in recombination rate. Using extensive simulations and sequence data from humans, fruit-flies and a fungal pathogen, we demonstrate that iSMC accurately infers recombination maps under a wide range of scenarios-remarkably, even from a single pair of unphased genomes. We exploit this possibility and reconstruct the recombination maps of ancient hominins. We report that the ancient and modern maps are correlated in a manner that reflects the established phylogeny of Neanderthals, Denisovans, and modern human populations.}, } @article {pmid31724235, year = {2019}, author = {Eremin, DB and Denisova, EA and Yu Kostyukovich, A and Martens, J and Berden, G and Oomens, J and Khrustalev, VN and Chernyshev, VM and Ananikov, VP}, title = {Ionic Pd/NHC Catalytic System Enables Recoverable Homogeneous Catalysis: Mechanistic Study and Application in the Mizoroki-Heck Reaction.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {25}, number = {72}, pages = {16439}, doi = {10.1002/chem.201904825}, pmid = {31724235}, issn = {1521-3765}, abstract = {Invited for the cover of this issue are Valentine P. Ananikov and co-workers. The image depicts the dynamic behaviour of a Pd/NHC catalytic system with easy transition from molecular to ionic complex. Read the full text of the article at 10.1002/chem.201903221.}, } @article {pmid31703240, year = {2020}, author = {Denisova, EI and Kozhevnikova, VV and Bazhan, NM and Makarova, EN}, title = {Sex-specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring.}, journal = {FEBS open bio}, volume = {10}, number = {1}, pages = {96-106}, pmid = {31703240}, issn = {2211-5463}, mesh = {Animals ; Female ; Fetus/*drug effects/*metabolism ; Hyperglycemia/prevention & control ; Leptin/administration & dosage/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy ; Phenotype ; Placenta/*drug effects/*metabolism ; Pregnancy ; Recombinant Proteins/administration & dosage/metabolism ; *Sex Characteristics ; }, abstract = {Obesity during pregnancy has been shown to increase the risk of metabolic diseases in the offspring. However, the factors within the maternal milieu which affect offspring phenotypes and the underlying mechanisms remain unknown. The adipocyte hormone leptin plays a key role in regulating energy homeostasis and is known to participate in sex-specific developmental programming. To examine the action of leptin on fetal growth, placental gene expression and postnatal offspring metabolism, we injected C57BL mice with leptin or saline on gestational day 12 and then measured body weights (BWs) of offspring fed on a standard or obesogenic diet, as well as mRNA expression levels of insulin-like growth factors and glucose and amino acid transporters. Male and female offspring born to leptin-treated mothers exhibited growth retardation before and a growth surge after weaning. Mature male offspring, but not female offspring, exhibited increased BWs on a standard diet. Leptin administration prevented the development of hyperglycaemia in the obese offspring of both sexes. The placentas of the male and female foetuses differed in size and gene expression, and leptin injection decreased the fetal weights of both sexes, the placental weights of the male foetuses and placental gene expression of the GLUT1 glucose transporter in female foetuses. The data suggest that mid-pregnancy is an ontogenetic window for the sex-specific programming effects of leptin, and these effects may be exerted via fetal sex-specific placental responses to leptin administration.}, } @article {pmid31702050, year = {2020}, author = {Gokcumen, O}, title = {Archaic hominin introgression into modern human genomes.}, journal = {American journal of physical anthropology}, volume = {171 Suppl 70}, number = {}, pages = {60-73}, doi = {10.1002/ajpa.23951}, pmid = {31702050}, issn = {1096-8644}, support = {1714867//United States National Science Foundation/International ; }, mesh = {Animals ; DNA/genetics ; *Gene Flow ; *Genetic Introgression ; *Genome, Human ; Hominidae/*genetics ; Humans ; Neanderthals/genetics ; }, abstract = {Ancient genomes from multiple Neanderthal and the Denisovan individuals, along with DNA sequence data from diverse contemporary human populations strongly support the prevalence of gene flow among different hominins. Recent studies now provide evidence for multiple gene flow events that leave genetic signatures in extant and ancient human populations. These events include older gene flow from an unknown hominin in Africa predating out-of-Africa migrations, and in the last 50,000-100,000 years, multiple gene flow events from Neanderthals into ancestral Eurasian human populations, and at least three distinct introgression events from a lineage close to Denisovans into ancestors of extant Southeast Asian and Oceanic populations. Some of these introgression events may have happened as late as 20,000 years before present and reshaped the way in which we think about human evolution. In this review, I aim to answer anthropologically relevant questions with regard to recent research on ancient hominin introgression in the human lineage. How have genomic data from archaic hominins changed our view of human evolution? Is there any doubt about whether introgression from ancient hominins to the ancestors of present-day humans occurred? What is the current view of human evolutionary history from the genomics perspective? What is the impact of introgression on human phenotypes?}, } @article {pmid31686394, year = {2020}, author = {Denisova, O and Chernogoryuk, G and Baranovskaya, N and Rikhvanov, L and Shefer, N and Chernjavskaya, G and Palchikova, I and Kalacheva, T}, title = {Trace Elements in the Lung Tissue Affected by Sarcoidosis.}, journal = {Biological trace element research}, volume = {196}, number = {1}, pages = {66-73}, doi = {10.1007/s12011-019-01915-z}, pmid = {31686394}, issn = {1559-0720}, mesh = {Adult ; Female ; Humans ; Inflammation/*chemically induced/pathology ; Lung/*chemistry/pathology ; Male ; Middle Aged ; Neutron Activation Analysis ; Sarcoidosis/*chemically induced/pathology ; Trace Elements/*analysis ; }, abstract = {In the lungs of 76 patients with verified sarcoidosis, 28 chemical elements were identified with neutron activation analysis. High levels of Ca, Fe, Cr, Co, Cs, Eu, Lu, Th, Hf, Au, and U and low level of Na compared to the control samples were determined in sarcoidosis. There were no significant differences in the content of Zn, Rb, La, Sm, Sr, Nd, As, Br, Ag, Tb, Sc, Ta, Sb, Ba, and Yb. Spearman correlation analysis shows multiple positive associations, with the maximum being in pairs as follows: Fe-Cr, Eu-La, Ce-Lu, Hf-Cr, Sc-Zn, Fe-Hf, Ce-Co, and Sb-Cr. These studies support the hypothesis that sarcoidosis is a response of the organism in the form of granulomatous inflammation when exposed to heavy metals and rare earth elements in the environment. We assume that the role of calcium and iron is to separate granulomas from the tissues of the body.}, } @article {pmid31624180, year = {2019}, author = {Hsieh, P and Vollger, MR and Dang, V and Porubsky, D and Baker, C and Cantsilieris, S and Hoekzema, K and Lewis, AP and Munson, KM and Sorensen, M and Kronenberg, ZN and Murali, S and Nelson, BJ and Chiatante, G and Maggiolini, FAM and Blanché, H and Underwood, JG and Antonacci, F and Deleuze, JF and Eichler, EE}, title = {Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes.}, journal = {Science (New York, N.Y.)}, volume = {366}, number = {6463}, pages = {}, pmid = {31624180}, issn = {1095-9203}, support = {/HHMI_/Howard Hughes Medical Institute/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Chromosome Duplication ; Chromosomes, Human, Pair 16/genetics ; Chromosomes, Human, Pair 8/genetics ; DNA Copy Number Variations ; Evolution, Molecular ; *Genetic Introgression ; Genome, Human ; Haplotypes ; Hominidae/genetics ; Humans ; Melanesia ; Models, Genetic ; Neanderthals/genetics ; Polymorphism, Genetic ; Selection, Genetic ; Whole Genome Sequencing ; }, abstract = {Copy number variants (CNVs) are subject to stronger selective pressure than single-nucleotide variants, but their roles in archaic introgression and adaptation have not been systematically investigated. We show that stratified CNVs are significantly associated with signatures of positive selection in Melanesians and provide evidence for adaptive introgression of large CNVs at chromosomes 16p11.2 and 8p21.3 from Denisovans and Neanderthals, respectively. Using long-read sequence data, we reconstruct the structure and complex evolutionary history of these polymorphisms and show that both encode positively selected genes absent from most human populations. Our results collectively suggest that large CNVs originating in archaic hominins and introgressed into modern humans have played an important role in local population adaptation and represent an insufficiently studied source of large-scale genetic variation.}, } @article {pmid31604218, year = {2019}, author = {Price, M}, title = {Face of the mysterious Denisovans emerges.}, journal = {Science (New York, N.Y.)}, volume = {365}, number = {6459}, pages = {1232}, doi = {10.1126/science.365.6459.1232}, pmid = {31604218}, issn = {1095-9203}, mesh = {Animals ; Asia ; *Biological Evolution ; DNA Methylation ; Epigenesis, Genetic ; Extinction, Biological ; Hominidae/*classification ; Neanderthals ; }, } @article {pmid31591491, year = {2019}, author = {Colbran, LL and Gamazon, ER and Zhou, D and Evans, P and Cox, NJ and Capra, JA}, title = {Inferred divergent gene regulation in archaic hominins reveals potential phenotypic differences.}, journal = {Nature ecology & evolution}, volume = {3}, number = {11}, pages = {1598-1606}, pmid = {31591491}, issn = {2397-334X}, support = {R01 MH113362/MH/NIMH NIH HHS/United States ; R35 GM127087/GM/NIGMS NIH HHS/United States ; R35 HG010718/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Female ; Genome, Human ; Haplotypes ; *Hominidae ; Humans ; *Neanderthals ; Phenotype ; }, abstract = {Sequencing DNA derived from archaic bones has enabled genetic comparison of Neanderthals and anatomically modern humans (AMHs), and revealed that they interbred. However, interpreting what genetic differences imply about their phenotypic differences remains challenging. Here, we introduce an approach for identifying divergent gene regulation between archaic hominins, such as Neanderthals, and AMH sequences, and find 766 genes that are likely to have been divergently regulated (DR) by Neanderthal haplotypes that do not remain in AMHs. DR genes include many involved in phenotypes known to differ between Neanderthals and AMHs, such as the structure of the rib cage and supraorbital ridge development. They are also enriched for genes associated with spontaneous abortion, polycystic ovary syndrome, myocardial infarction and melanoma. Phenotypes associated with modern human variation in these genes' regulation in ~23,000 biobank patients further support their involvement in immune and cardiovascular phenotypes. Comparing DR genes between two Neanderthals and a Denisovan revealed divergence in the immune system and in genes associated with skeletal and dental morphology that are consistent with the archaeological record. These results establish differences in gene regulatory architecture between AMHs and archaic hominins, and provide an avenue for exploring phenotypic differences between archaic groups from genomic information alone.}, } @article {pmid31564255, year = {2019}, author = {Shchenkov, SV and Denisova, SA and Kremnev, GA and Dobrovolskij, AA}, title = {Five new morphological types of virgulate and microcotylous xiphidiocercariae based on morphological and molecular phylogenetic analyses.}, journal = {Journal of helminthology}, volume = {94}, number = {}, pages = {e94}, doi = {10.1017/S0022149X19000853}, pmid = {31564255}, issn = {1475-2697}, mesh = {Animals ; Biological Evolution ; Cercaria/classification/genetics/*growth & development/*isolation & purification ; Female ; Male ; *Phylogeny ; }, abstract = {The phylogenetic position of most xiphidiocercariae from subgroups Cercariae virgulae and Cercariae microcotylae remains unknown or unclear, even at the family level. In this paper, we studied the morphology and molecular phylogeny of 15 microcotylous and virgulate cercariae (11 new and four previously described ones). Based on morphological and molecular data, we suggested five distinct morphological types of xiphidiocercariae, which are a practical alternative to Cercariae virgulae and Cercariae microcotylae subgroups. Four of these types correspond to actual digenean taxa (Microphallidae, Lecithodendriidae, Pleurogenidae and Prosthogonimidae), while the fifth is represented by Cercaria nigrospora Wergun, 1957, which we classified on the basis of molecular data for the first time. We reassessed the relative importance of morphological characters used for the classification of virgulate and microcotylous cercariae, and discussed the main evolutionary trends within xiphidiocercariae. Now stylet cercariae can be reliably placed into several sub-taxa of Microphalloidea on the basis of their morphological features.}, } @article {pmid31560950, year = {2019}, author = {Mata, X and Renaud, G and Mollereau, C}, title = {The repertoire of family A-peptide GPCRs in archaic hominins.}, journal = {Peptides}, volume = {122}, number = {}, pages = {170154}, doi = {10.1016/j.peptides.2019.170154}, pmid = {31560950}, issn = {1873-5169}, mesh = {Animals ; Diabetic Nephropathies/*genetics/pathology ; *Evolution, Molecular ; Genome, Human/genetics ; Haplotypes/genetics ; Hominidae/genetics ; Humans ; Neanderthals/genetics ; Obesity/*genetics/pathology ; Peptides/genetics ; Platelet Aggregation/genetics ; Receptors, G-Protein-Coupled/*genetics ; Risk Factors ; }, abstract = {Given the importance of G-protein coupled receptors in the regulation of many physiological functions, deciphering the relationships between genotype and phenotype in past and present hominin GPCRs is of main interest to understand the evolutionary process that contributed to the present-day variability in human traits and health. Here, we carefully examined the publicly available genomic and protein sequence databases of the archaic hominins (Neanderthal and Denisova) to draw up the catalog of coding variations in GPCRs for peptide ligands, in comparison with living humans. We then searched in the literature the functional changes, phenotypes and risk of disease possibly associated with the detected variants. Our survey suggests that Neanderthal and Denisovan hominins were likely prone to lower risk of obesity, to enhanced platelet aggregation in response to thrombin, to better response to infection, to less anxiety and aggressiveness and to favorable sociability. While some archaic variants were likely advantageous in the past, they might be responsible for maladaptive disorders today in the context of modern life and/or specific regional distribution. For example, an archaic haplotype in the neuromedin receptor 2 is susceptible to confer risk of diabetic nephropathy in type 1 diabetes in present-day Europeans. Paying attention to the pharmacological properties of some of the archaic variants described in this study may be helpful to understand the variability of therapeutic efficacy between individuals or ethnic groups.}, } @article {pmid31558742, year = {2019}, author = {Morley, MW and Goldberg, P and Uliyanov, VA and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Jacobs, Z and Roberts, RG}, title = {Hominin and animal activities in the microstratigraphic record from Denisova Cave (Altai Mountains, Russia).}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {13785}, pmid = {31558742}, issn = {2045-2322}, mesh = {Animals ; Archaeology ; *Caves ; Cold Climate ; DNA, Ancient/isolation & purification ; *Fossils ; History, Ancient ; *Hominidae/genetics ; Humans ; Neanderthals/genetics ; Paleontology ; Siberia ; }, abstract = {Denisova Cave in southern Siberia uniquely contains evidence of occupation by a recently discovered group of archaic hominins, the Denisovans, starting from the middle of the Middle Pleistocene. Artefacts, ancient DNA and a range of animal and plant remains have been recovered from the sedimentary deposits, along with a few fragmentary fossils of Denisovans, Neanderthals and a first-generation Neanderthal-Denisovan offspring. The deposits also contain microscopic traces of hominin and animal activities that can provide insights into the use of the cave over the last 300,000 years. Here we report the results of a micromorphological study of intact sediment blocks collected from the Pleistocene deposits in the Main and East Chambers of Denisova Cave. The presence of charcoal attests to the use of fire by hominins, but other evidence of their activities preserved in the microstratigraphic record are few. The ubiquitous occurrence of coprolites, which we attribute primarily to hyenas, indicates that the site was visited for much of its depositional history by cave-dwelling carnivores. Microscopic traces of post-depositional diagenesis, bioturbation and incipient cryoturbation are observed in only a few regions of the deposit examined here. Micromorphology can help identify areas of sedimentary deposit that are most conducive to ancient DNA preservation and could be usefully integrated with DNA analyses of sediments at archaeological sites to illuminate features of their human and environmental history that are invisible to the naked eye.}, } @article {pmid31551547, year = {2019}, author = {Callaway, E}, title = {First portrait of mysterious Denisovans drawn from DNA.}, journal = {Nature}, volume = {573}, number = {7775}, pages = {475-476}, pmid = {31551547}, issn = {1476-4687}, mesh = {Animals ; DNA ; DNA Methylation ; Fossils ; Hominidae/*genetics ; Neanderthals/*genetics ; }, } @article {pmid31539495, year = {2019}, author = {Gokhman, D and Mishol, N and de Manuel, M and de Juan, D and Shuqrun, J and Meshorer, E and Marques-Bonet, T and Rak, Y and Carmel, L}, title = {Reconstructing Denisovan Anatomy Using DNA Methylation Maps.}, journal = {Cell}, volume = {179}, number = {1}, pages = {180-192.e10}, doi = {10.1016/j.cell.2019.08.035}, pmid = {31539495}, issn = {1097-4172}, mesh = {Animals ; Base Sequence ; DNA Methylation/*genetics ; Databases, Genetic ; Extinction, Biological ; Fossils ; Genome, Human/genetics ; Humans ; Neanderthals/*anatomy & histology/*genetics ; Pan troglodytes/*anatomy & histology/*genetics ; *Phenotype ; Polymorphism, Single Nucleotide/genetics ; Skeleton ; Skull ; }, abstract = {Denisovans are an extinct group of humans whose morphology remains unknown. Here, we present a method for reconstructing skeletal morphology using DNA methylation patterns. Our method is based on linking unidirectional methylation changes to loss-of-function phenotypes. We tested performance by reconstructing Neanderthal and chimpanzee skeletal morphologies and obtained >85% precision in identifying divergent traits. We then applied this method to the Denisovan and offer a putative morphological profile. We suggest that Denisovans likely shared with Neanderthals traits such as an elongated face and a wide pelvis. We also identify Denisovan-derived changes, such as an increased dental arch and lateral cranial expansion. Our predictions match the only morphologically informative Denisovan bone to date, as well as the Xuchang skull, which was suggested by some to be a Denisovan. We conclude that DNA methylation can be used to reconstruct anatomical features, including some that do not survive in the fossil record.}, } @article {pmid31534238, year = {2019}, author = {Zammit, NW and Siggs, OM and Gray, PE and Horikawa, K and Langley, DB and Walters, SN and Daley, SR and Loetsch, C and Warren, J and Yap, JY and Cultrone, D and Russell, A and Malle, EK and Villanueva, JE and Cowley, MJ and Gayevskiy, V and Dinger, ME and Brink, R and Zahra, D and Chaudhri, G and Karupiah, G and Whittle, B and Roots, C and Bertram, E and Yamada, M and Jeelall, Y and Enders, A and Clifton, BE and Mabbitt, PD and Jackson, CJ and Watson, SR and Jenne, CN and Lanier, LL and Wiltshire, T and Spitzer, MH and Nolan, GP and Schmitz, F and Aderem, A and Porebski, BT and Buckle, AM and Abbott, DW and Ziegler, JB and Craig, ME and Benitez-Aguirre, P and Teo, J and Tangye, SG and King, C and Wong, M and Cox, MP and Phung, W and Tang, J and Sandoval, W and Wertz, IE and Christ, D and Goodnow, CC and Grey, ST}, title = {Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity.}, journal = {Nature immunology}, volume = {20}, number = {10}, pages = {1299-1310}, pmid = {31534238}, issn = {1529-2916}, support = {R01 AI052127/AI/NIAID NIH HHS/United States ; U54 AI054523/AI/NIAID NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Extinction, Biological ; Humans ; Immunity ; Inflammation ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation, Missense/genetics ; Phosphorylation ; Poxviridae/*physiology ; Poxviridae Infections/*immunology ; Protein Domains/*genetics ; Tumor Necrosis Factor alpha-Induced Protein 3/*genetics ; }, abstract = {Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of anatomically modern humans, extinct Denisovan hominins and mice revealed a TNFAIP3 allelic series with alterations in the encoded immune response inhibitor A20. Each TNFAIP3 allele encoded substitutions at non-catalytic residues of the ubiquitin protease OTU domain that diminished IκB kinase-dependent phosphorylation and activation of A20. Two TNFAIP3 alleles encoding A20 proteins with partial phosphorylation deficits seemed to be beneficial by increasing immunity without causing spontaneous inflammatory disease: A20 T108A;I207L, originating in Denisovans and introgressed in modern humans throughout Oceania, and A20 I325N, from an N-ethyl-N-nitrosourea (ENU)-mutagenized mouse strain. By contrast, a rare human TNFAIP3 allele encoding an A20 protein with 95% loss of phosphorylation, C243Y, caused spontaneous inflammatory disease in humans and mice. Analysis of the partial-phosphorylation A20 I325N allele in mice revealed diminished tolerance of bacterial lipopolysaccharide and poxvirus inoculation as tradeoffs for enhanced immunity.}, } @article {pmid31517046, year = {2019}, author = {Bennett, EA and Crevecoeur, I and Viola, B and Derevianko, AP and Shunkov, MV and Grange, T and Maureille, B and Geigl, EM}, title = {Morphology of the Denisovan phalanx closer to modern humans than to Neanderthals.}, journal = {Science advances}, volume = {5}, number = {9}, pages = {eaaw3950}, pmid = {31517046}, issn = {2375-2548}, mesh = {Animals ; Finger Phalanges/*anatomy & histology ; *Genome, Human ; Humans ; Molar/*anatomy & histology ; *Neanderthals/anatomy & histology/genetics ; Species Specificity ; }, abstract = {A fully sequenced high-quality genome has revealed in 2010 the existence of a human population in Asia, the Denisovans, related to and contemporaneous with Neanderthals. Only five skeletal remains are known from Denisovans, mostly molars; the proximal fragment of a fifth finger phalanx used to generate the genome, however, was too incomplete to yield useful morphological information. Here, we demonstrate through ancient DNA analysis that a distal fragment of a fifth finger phalanx from the Denisova Cave is the larger, missing part of this phalanx. Our morphometric analysis shows that its dimensions and shape are within the variability of Homo sapiens and distinct from the Neanderthal fifth finger phalanges. Thus, unlike Denisovan molars, which display archaic characteristics not found in modern humans, the only morphologically informative Denisovan postcranial bone identified to date is suggested here to be plesiomorphic and shared between Denisovans and modern humans.}, } @article {pmid31506618, year = {2019}, author = {Callaway, E}, title = {Lost Denisovan bone reveals surprisingly human-like finger.}, journal = {Nature}, volume = {573}, number = {7773}, pages = {175-176}, pmid = {31506618}, issn = {1476-4687}, mesh = {Animals ; Archaeology ; Fingers ; *Hominidae ; Humans ; *Neanderthals ; }, } @article {pmid31477933, year = {2019}, author = {Speidel, L and Forest, M and Shi, S and Myers, SR}, title = {A method for genome-wide genealogy estimation for thousands of samples.}, journal = {Nature genetics}, volume = {51}, number = {9}, pages = {1321-1329}, pmid = {31477933}, issn = {1546-1718}, support = {098387/Z/12/Z//Wellcome Trust (Wellcome)/International ; 098387/WT_/Wellcome Trust/United Kingdom ; 203141/WT_/Wellcome Trust/United Kingdom ; 212284/WT_/Wellcome Trust/United Kingdom ; 220457/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 203141/Z/16/Z//Wellcome Trust (Wellcome)/International ; 212284/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; 212284/Z/18/Z//Wellcome Trust (Wellcome)/International ; }, mesh = {Animals ; *Evolution, Molecular ; *Genetics, Population ; *Genome, Human ; Genome-Wide Association Study/*methods ; Haplotypes ; Humans ; Mutation ; Neanderthals ; *Pedigree ; Polymorphism, Single Nucleotide ; Population Density ; *Selection, Genetic ; }, abstract = {Knowledge of genome-wide genealogies for thousands of individuals would simplify most evolutionary analyses for humans and other species, but has remained computationally infeasible. We have developed a method, Relate, scaling to >10,000 sequences while simultaneously estimating branch lengths, mutational ages and variable historical population sizes, as well as allowing for data errors. Application to 1,000 Genomes Project haplotypes produces joint genealogical histories for 26 human populations. Highly diverged lineages are present in all groups, but most frequent in Africa. Outside Africa, these mainly reflect ancient introgression from groups related to Neanderthals and Denisovans, while African signals instead reflect unknown events unique to that continent. Our approach allows more powerful inferences of natural selection than has previously been possible. We identify multiple regions under strong positive selection, and multi-allelic traits including hair color, body mass index and blood pressure, showing strong evidence of directional selection, varying among human groups.}, } @article {pmid31475413, year = {2020}, author = {Garduño-Alanís, A and Malyutina, S and Pajak, A and Stepaniak, U and Kubinova, R and Denisova, D and Pikhart, H and Peasey, A and Bobak, M and Stefler, D}, title = {Association between soft drink, fruit juice consumption and obesity in Eastern Europe: cross-sectional and longitudinal analysis of the HAPIEE study.}, journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association}, volume = {33}, number = {1}, pages = {66-77}, pmid = {31475413}, issn = {1365-277X}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AG023522/AG/NIA NIH HHS/United States ; WT064947/WT_/Wellcome Trust/United Kingdom ; WT081081/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Body Mass Index ; Carbonated Beverages/adverse effects/*statistics & numerical data ; Cross-Sectional Studies ; Czech Republic/epidemiology ; Diet Surveys ; Drinking Behavior ; Female ; Follow-Up Studies ; Fruit and Vegetable Juices/adverse effects/*statistics & numerical data ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Obesity/*epidemiology/etiology ; Poland/epidemiology ; Prospective Studies ; Russia/epidemiology ; }, abstract = {BACKGROUND: Fruit juice and soft drink consumption have been shown to be related to obesity. However, this relationship has not been explored in Eastern Europe. The present study aimed to assess the cross-sectional and longitudinal relationships between fruit juice, soft drink consumption and body mass index (BMI) in Eastern European cohorts.

METHODS: Data from the Health, Alcohol and Psychosocial factors in Eastern Europe population-based prospective cohort study, based in Russia, Poland and the Czech Republic, were used. Intakes of sugar-sweetened beverage (SSB), artificially-sweetened beverage (ASB) and fruit juice were estimated from a food frequency questionnaire. Participant BMI values were assessed at baseline (n = 26 634) and after a 3-year follow-up (data available only for Russia, n = 5205).

RESULTS: Soft drink consumption was generally low, particularly in Russia. Compared to never drinkers of SSB, participants who drank SSB every day had a significantly higher BMI in the Czech [β-coefficient = 0.28; 95% confidence interval (CI) = 0.02-0.54], Russian (β-coefficient = 1.38; 95% CI = 0.62-2.15) and Polish (β-coefficient = 0.83; 95% CI = 0.29-1.37) cohorts. Occasional or daily ASB consumption was also positively associated with BMI in all three cohorts. Results for daily fruit juice intake were inconsistent, with a positive association amongst Russians (β-coefficient = 0.75; 95% CI = 0.28-1.21) but a negative trend in the Czech Republic (β-coefficient = -0.42; 95% CI = -0.86 to 0.02). Russians participants who drank SSB or ASB had an increased BMI after follow-up.

CONCLUSIONS: Our findings support previous studies suggesting that soft drink consumption (including SSBs and ASBs) is positively related to BMI, whereas our results for fruit juice were less consistent. Policies regarding these beverages should be considered in Eastern Europe to lower the risk of obesity.}, } @article {pmid33951887, year = {2019}, author = {Caldararo, N}, title = {Probability, Populations, Phylogenetics, and Hominin Speciation.}, journal = {Human biology}, volume = {90}, number = {2}, pages = {129-155}, doi = {10.13110/humanbiology.90.2.04}, pmid = {33951887}, issn = {1534-6617}, abstract = {A number of recent articles have appeared on the hominin Denisova fossil remains. Many of them focus on attempts to produce DNA sequences from the extracted samples. Often these project mitochondrial DNA (mtDNA) sequences from the fossils of a number of Neandertals and the Denisovans in an attempt to understand the evolution of Middle Pleistocene human ancestors. These articles introduce a number of problems in the interpretation of speciation in hominins. One concerns the degradation of the ancient DNA and its interpretation as authentic genetic information. Another problem concerns the ideas of "species" versus "population" and the use of these ideas in building evolutionary diagrams to indicate ancestry and extinction. A third issue concerns the theory of haplotypes in the mtDNA. Given the severe constraints on mutations in the mtDNA genome to maintain functionality and the purifying processes to reduce such mutations in the ovaries, putative geographic and historical variations seem contradictory. Local diversity and variations in supposed "macrohaplotypes" are explained as back migrations or back mutations, which dilutes the robust nature of the theory. A central issue involves what human variation means, how much population variation there has been in the past, and whether this variation distinguishes hominid speciation or is simply a process of anagenesis. This brings up the question of how much can be interpreted from the analysis of DNA. Some businesses today claim to be able to use DNA analysis to discover past ethnic identities, and a new niche in restaurants is producing "DNA" menus. Perhaps some caution is in order.}, } @article {pmid31461192, year = {2019}, author = {Eremin, DB and Denisova, EA and Yu Kostyukovich, A and Martens, J and Berden, G and Oomens, J and Khrustalev, VN and Chernyshev, VM and Ananikov, VP}, title = {Ionic Pd/NHC Catalytic System Enables Recoverable Homogeneous Catalysis: Mechanistic Study and Application in the Mizoroki-Heck Reaction.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {25}, number = {72}, pages = {16564-16572}, doi = {10.1002/chem.201903221}, pmid = {31461192}, issn = {1521-3765}, support = {19-13-00460//Russian Science Foundation/ ; }, abstract = {N-Heterocyclic carbene (NHC) ligands are ubiquitously utilized in catalysis. A common catalyst design model assumes strong M-NHC binding in this metal-ligand framework. In contrast to this common assumption, we demonstrate here that lability and controlled cleavage of the M-NHC bond (rather than its stabilization) could be more important for high-performance catalysis at low catalyst concentrations. The present study reveals a dynamic stabilization mechanism with labile metal-NHC binding and [PdX3 ][-] [NHC-R][+] ion pair formation. Access to reactive anionic palladium intermediates formed by dissociation of the NHC ligands and plausible stabilization of the molecular catalyst in solution by interaction with the [NHC-R][+] azolium ion is of particular importance for an efficient and recyclable catalyst. These ionic Pd/NHC complexes allowed for the first time the recycling of the complex in a well-defined form with isolation at each cycle. Computational investigation of the reaction mechanism confirms a facile formation of NHC-free anionic Pd in polar media through either Ph-NHC coupling or reversible H-NHC coupling. The present study formulates novel ideas for M/NHC catalyst design.}, } @article {pmid31448903, year = {2019}, author = {Denisova, EA and Eremin, DB and Gordeev, EG and Tsedilin, AM and Ananikov, VP}, title = {Addressing Reversibility of R-NHC Coupling on Palladium: Is Nano-to-Molecular Transition Possible for the Pd/NHC System?.}, journal = {Inorganic chemistry}, volume = {58}, number = {18}, pages = {12218-12227}, doi = {10.1021/acs.inorgchem.9b01630}, pmid = {31448903}, issn = {1520-510X}, abstract = {It has recently been shown that palladium-catalyzed reactions with N-heterocyclic carbene (NHC) ligands involve R-NHC coupling accompanied by transformation of the molecular catalytic system into the nanoscale catalytic system. An important question appeared in this regard is whether such a change in the catalytic system is irreversible. More specifically, is the reverse nano-to-molecular transformation possible? In view of the paramount significance of this question to the area of catalyst design, we studied the capability of 2-substituted azolium salts to undergo the breakage of C-C bond and exchange substituents on the carbene carbon with corresponding aryl halides in the presence of Pd nanoparticles. The study provides important experimental evidence of possibility of the reversible R-NHC coupling. The observed behavior indicates that the nanosized metal species are capable of reverse transition to molecular species. Such an option, known for phosphine ligands, was previously unexplored for NHC ligands. The present study for the first time demonstrates bidirectional dynamic transitions between the molecular and nanostructured states in Pd/NHC systems. As a unique feature, surprisingly small activation barriers (<18 kcal/mol) and noticeable thermodynamic driving force (-5 to -7 kcal/mol) were calculated for C-C bond oxidative addition to Pd(0) centers in the studied system. The first example of NHC-mediated Pd leaching from metal nanoparticles to solution was observed and formation of Pd/NHC complex in solution was detected by ESI-MS.}, } @article {pmid31409814, year = {2019}, author = {Zwyns, N and Paine, CH and Tsedendorj, B and Talamo, S and Fitzsimmons, KE and Gantumur, A and Guunii, L and Davakhuu, O and Flas, D and Dogandžić, T and Doerschner, N and Welker, F and Gillam, JC and Noyer, JB and Bakhtiary, RS and Allshouse, AF and Smith, KN and Khatsenovich, AM and Rybin, EP and Byambaa, G and Hublin, JJ}, title = {The Northern Route for Human dispersal in Central and Northeast Asia: New evidence from the site of Tolbor-16, Mongolia.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {11759}, pmid = {31409814}, issn = {2045-2322}, mesh = {Animals ; Asia ; Fossils ; *Human Migration ; Humans ; Mongolia ; Neanderthals/*genetics ; }, abstract = {The fossil record suggests that at least two major human dispersals occurred across the Eurasian steppe during the Late Pleistocene. Neanderthals and Modern Humans moved eastward into Central Asia, a region intermittently occupied by the enigmatic Denisovans. Genetic data indicates that the Denisovans interbred with Neanderthals near the Altai Mountains (South Siberia) but where and when they met H. sapiens is yet to be determined. Here we present archaeological evidence that document the timing and environmental context of a third long-distance population movement in Central Asia, during a temperate climatic event around 45,000 years ago. The early occurrence of the Initial Upper Palaeolithic, a techno-complex whose sudden appearance coincides with the first occurrence of H. sapiens in the Eurasian steppes, establishes an essential archaeological link between the Siberian Altai and Northwestern China . Such connection between regions provides empirical ground to discuss contacts between local and exogenous populations in Central and Northeast Asia during the Late Pleistocene.}, } @article {pmid31386798, year = {2020}, author = {Mikaeeli, S and Susan-Resiga, D and Girard, E and Ben Djoudi Ouadda, A and Day, R and Prost, S and Seidah, NG}, title = {Functional analysis of natural PCSK9 mutants in modern and archaic humans.}, journal = {The FEBS journal}, volume = {287}, number = {3}, pages = {515-528}, doi = {10.1111/febs.15036}, pmid = {31386798}, issn = {1742-4658}, support = {148363//CIHR/Canada ; }, mesh = {Animals ; Binding Sites ; DNA Methylation ; Humans ; *Loss of Function Mutation ; Neanderthals/*genetics ; Proprotein Convertase 9/chemistry/*genetics/metabolism ; Protein Binding ; Receptors, LDL/metabolism ; }, abstract = {PCSK9 is the last member of the proprotein convertases (PCs) family and its gene is mutated in ~ 2% to 3% of individuals with familial hypercholesterolemia (FH). This protein enhances the degradation of the low-density lipoprotein receptor (LDLR) and hence increases the levels of circulating LDL-cholesterol (LDLc). Studies of the underlying mechanism(s) regulating the activity of different mutations in the PCSK9 gene are ongoing as they enhance our understanding of the biology and clinical relevance of PCSK9 and its partners. In an attempt to unravel the regulation of PCSK9 transcription and possibly identify mutation 'hot spot' regions with alterations in CpG methylation, we present for the first time the complete methylome profile of the PCSK9 gene in modern and archaic humanoids. Our data showed that the genomes of modern humans and archaic PCSK9 exhibit a similar methylation pattern. Next, we defined the mechanistic consequences of three PCSK9 natural mutations (PCSK9-R96L, -R105W, and -P174S) and one archaic Denisovan mutation (PCSK9-H449L) using various complementary cellular and in vitro binding assays. Our results showed that the PCSK9-H449L is a loss-of-function (LOF) mutation, likely due to its lower binding affinity to the LDLR. Similarly, PCSK9-R96L and -R105W are LOF mutations, even though they have been identified in FH patients. The PCSK9-R105W mutation leads to a significantly lower autocatalytic processing of proPCSK9. PCSK9-P174S resulted in a LOF in both extracellular and intracellular pathways. In conclusion, our extensive analyses revealed that all studied mutations result in PCSK9 LOF, via various mechanisms, leading to lower levels of LDLc.}, } @article {pmid31372716, year = {2019}, author = {Derenko, M and Denisova, G and Malyarchuk, B and Hovhannisyan, A and Khachatryan, Z and Hrechdakian, P and Litvinov, A and Yepiskoposyan, L}, title = {Insights into matrilineal genetic structure, differentiation and ancestry of Armenians based on complete mitogenome data.}, journal = {Molecular genetics and genomics : MGG}, volume = {294}, number = {6}, pages = {1547-1559}, pmid = {31372716}, issn = {1617-4623}, support = {The state assignment theme for the IBPN FEB RAS (0290-2018-0024)//the Ministry of Science and Higher Education of Russia/ ; 18T-1F186//State Committee of Science/ ; NT-18/TB//State Committee of Science/ ; hubio-4562//Armenian National Science and Education Fund/ ; }, mesh = {Armenia ; Asia, Central ; Asia, Western ; DNA, Mitochondrial/chemistry ; Europe ; Genetic Variation ; *Genome, Mitochondrial ; Haplotypes ; Humans ; Phylogeny ; Phylogeography ; }, abstract = {Distinctive peculiarities of Armenians such as their millennia-long genetic isolation and strong national identity attract a keen interest while studying the demographic history of the West Asia. Here, to examine their fine-scale matrilineal genetic structure, ancestry and relationships with neighboring populations, we analyzed 536 complete mitogenomes (141 of which are novel) from 8 geographically different Armenian populations, covering the whole stretch of historical Armenia. The observed patterns highlight a remarkable degree of matrilineal genetic heterogeneity and weak population structuring of Armenians. Moreover, our phylogeographic analysis reveals common ancestries for some mtDNA lineages shared by West Asians, Transcaucasians, Europeans, Central Asians and Armenians. About third of the mtDNA subhaplogroups found in Armenian gene pool might be considered as Armenian-specific, as these are virtually absent elsewhere in Europe, West Asia and Transcaucasia. Coalescence ages of most of these lineages do not exceed 3.1 kya and coincide well with the population size growth started around 1.8-2.8 kya detectable only in the Bayesian Skyline Plots based on the Armenian-specific mtDNA haplotypes.}, } @article {pmid31300536, year = {2019}, author = {Teixeira, JC and Cooper, A}, title = {Using hominin introgression to trace modern human dispersals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {31}, pages = {15327-15332}, pmid = {31300536}, issn = {1091-6490}, mesh = {Africa ; Animals ; Asia, Southeastern ; DNA/genetics ; Geography ; Hominidae/*physiology ; *Human Migration ; Humans ; Population Dynamics ; }, abstract = {The dispersal of anatomically modern human populations out of Africa and across much of the rest of the world around 55 to 50 thousand years before present (ka) is recorded genetically by the multiple hominin groups they met and interbred with along the way, including the Neandertals and Denisovans. The signatures of these introgression events remain preserved in the genomes of modern-day populations, and provide a powerful record of the sequence and timing of these early migrations, with Asia proving a particularly complex area. At least 3 different hominin groups appear to have been involved in Asia, of which only the Denisovans are currently known. Several interbreeding events are inferred to have taken place east of Wallace's Line, consistent with archaeological evidence of widespread and early hominin presence in the area. However, archaeological and fossil evidence indicates archaic hominins had not spread as far as the Sahul continent (New Guinea, Australia, and Tasmania), where recent genetic evidence remains enigmatic.}, } @article {pmid31285349, year = {2019}, author = {Bailey, SE and Hublin, JJ and Antón, SC}, title = {Rare dental trait provides morphological evidence of archaic introgression in Asian fossil record.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {30}, pages = {14806-14807}, pmid = {31285349}, issn = {1091-6490}, mesh = {Animals ; Asian People/genetics ; *Evolution, Molecular ; Fossils/*anatomy & histology ; Hominidae/*anatomy & histology/genetics ; Humans ; Mandible/anatomy & histology ; Molar/*anatomy & histology ; }, abstract = {The recently described Denisovan hemimandible from Xiahe, China [F. Chen et al., (2019) Nature 569, 409-412], possesses an unusual dental feature: a 3-rooted lower second molar. A survey of the clinical and bioarchaeological literature demonstrates that the 3-rooted lower molar is rare (less than 3.5% occurrence) in non-Asian Homo sapiens In contrast, its presence in Asian-derived populations can exceed 40% in China and the New World. It has long been thought that the prevalence of 3-rooted lower molars in Asia is a relatively late acquisition occurring well after the origin and dispersal of H. sapiens However, the presence of a 3-rooted lower second molar in this 160,000-y-old fossil hominin suggests greater antiquity for the trait. Importantly, it also provides morphological evidence of a strong link between archaic and recent Asian H. sapiens populations. This link provides compelling evidence that modern Asian lineages acquired the 3-rooted lower molar via introgression from Denisovans.}, } @article {pmid31278514, year = {2019}, author = {Brzozowska, MM and Havula, E and Allen, RB and Cox, MP}, title = {Genetics, adaptation to environmental changes and archaic admixture in the pathogenesis of diabetes mellitus in Indigenous Australians.}, journal = {Reviews in endocrine & metabolic disorders}, volume = {20}, number = {3}, pages = {321-332}, pmid = {31278514}, issn = {1573-2606}, mesh = {Australia ; Diabetes Mellitus, Type 2/*genetics/*pathology ; Genome-Wide Association Study ; Humans ; Indigenous Peoples ; Obesity/genetics/pathology ; }, abstract = {Indigenous Australians are particularly affected by type 2 diabetes mellitus (T2D) due to both their genetic susceptibility and a range of environmental and lifestyle risk factors. Recent genetic studies link predisposition to some diseases, including T2D, to alleles acquired from archaic hominins, such as Neanderthals and Denisovans, which persist in the genomes of modern humans today. Indo-Pacific human populations, including Indigenous Australians, remain extremely underrepresented in genomic research with a paucity of data examining the impact of Denisovan or Neanderthal lineages on human phenotypes in Oceania. The few genetic studies undertaken emphasize the uniqueness and antiquity of Indigenous Australian genomes, with possibly the largest proportion of Denisovan ancestry of any population in the world. In this review, we focus on the potential contributions of ancient genes/pathways to modern human phenotypes, while also highlighting the evolutionary roles of genetic adaptation to dietary and environmental changes associated with an adopted Western lifestyle. We discuss the role of genetic and epigenetic factors in the pathogenesis of T2D in understudied Indigenous Australians, including the potential impact of archaic gene lineages on this disease. Finally, we propose that greater understanding of the underlying genetic predisposition may contribute to the clinical efficacy of diabetes management in Indigenous Australians. We suggest that improved identification of T2D risk variants in Oceania is needed. Such studies promise to clarify how genetic and phenotypic differences vary between populations and, crucially, provide novel targets for personalised medical therapies in currently marginalized groups.}, } @article {pmid31233688, year = {2019}, author = {Kobelkova, IV and Martinchik, AN and Keshabyants, EE and Denisova, NN and Peskova, EV and Vybornaya, KV and Sokolov, AI and Lavrinenko, SV and Nikityuk, DB}, title = {[An analysis of the diet of members of the Russian national men's water polo team during the sports training camps].}, journal = {Voprosy pitaniia}, volume = {88}, number = {2}, pages = {50-57}, doi = {10.24411/0042-8833-2019-10017}, pmid = {31233688}, issn = {0042-8833}, support = {theme 0529-2017-0053//Russian Academy of Science/ ; }, mesh = {Adult ; *Athletes ; Dietary Carbohydrates/*administration & dosage ; Dietary Fats/*administration & dosage ; *Energy Intake ; *Energy Metabolism ; Humans ; Male ; *Nutritional Status ; *Water Sports ; }, abstract = {Increasing the adaptive capacity of professional athletes depends on proper nutrition, especially in training and competitions' period. In this regard, it is relevant to study the actual nutrition and assess its compliance with the energy expenditure of athletes. The aim - to study the actual nutrition and energy expenditure of athletes from male water polo national team of the Russian Federation in the competitive period. Material and methods. In March 2018, 15 highly skilled sportsmen-men engaged in water polo were examined; qualification - 11 masters of sports, 4 candidates for the master of sports; Slavic ethnos. The average age was 23.1±0.6 years. The actual nutrition was studied by a 24-hour food record method and by the frequency method. The anthropometric examination was carried out according to a unified method using standard medical scales, a medical height meter and a rubberized measuring tape. Measurement of energy expenditure and heart rate at rest and under load was performed on a bicycle ergometer using an wireless ergospirometer and a chest pulse meter. Results and discussion. The determination of daily energy expenditure in athletes of the men's Russian national water polo team showed that the average value was 4350±129 kcal. А peculiar feature of the diet of water polo players is its high caloric value (5165±539 kcal/day), caused by energy expenditure during physical exertion and additional thermogenesis in conditions of long training in water. Excessive (1.5 times in comparison with the recommended values) consumption of fats, including saturated fatty acids by 1.3 times, added sugar and added salt is a risk factor of cardiovascular diseases, diseases of digestive organs, endocrine system, including type 2 diabetes. Low values of consumption of vegetables and fruits, dairy products, fish products and high levels of sugar and confectionery have been established. Conclusion. The imbalance of diets on two basic nutrients (fats, carbohydrates) has been revealed. The data obtained were the basis for the formation of individual recommendations on nutrition for each athlete, taking into account athletes' metabolic parameters and the level of physical activity. It is necessary to continue studies of anthropometric indices in dynamics for the most adequate assessment of the compliance of actual nutrition with energy consumption, and further correction of the diet in order to improve athletes' performance.}, } @article {pmid31228375, year = {2019}, author = {Denisova, OA and Livzan, MA and Denisov, AP and Kun, OA}, title = {[Clinical aspect of diagnostics of gastroesophageal reflux disease in elderly patients.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {32}, number = {1-2}, pages = {108-111}, pmid = {31228375}, issn = {1561-9125}, mesh = {Aged ; Cross-Sectional Studies ; *Gastroesophageal Reflux/complications/diagnosis ; Heartburn ; Humans ; *Quality of Life ; Surveys and Questionnaires ; }, abstract = {Insufficient knowledge age peculiarities of gastroesophageal reflux disease (GERD) in the elderly against the background of its prevalence determine the high demand for studies on the topic. In an open study cohort by cross-sectional analysis was conducted clinical features GERD patients older age groups. By continuous sampling of 90 patients taken away: the main group - 45 persons 60-86, comparison group - 45 persons 25-59 years. Found that for GERD in patients older than 60 years has its own characteristics. Maximum observed incidence of GERD in the range of 60-69 years (57%) with a further reduction. More typical is a decrease in the frequency of heartburn (p<0,05) with increasing retrosternal pain (p<0,001) and dysphagia (p<0,05) and coughing (p<0,001) with simultaneous increase in the number of complaints from various organs and systems. In this case, deterioration of health associated with a statistically significant reduction in quality of life parameters when compared with the young. When survey by questionnaire SF-36 in elderly patients reported a more marked reduction of scales that characterize the physical and psychological health of the component against high polymorbidity. Identified features of the flow of GERD in the elderly, may be useful for streamlining diagnosis and therapy.}, } @article {pmid31177447, year = {2019}, author = {Zotova, TY and Lapaev, NN and Azova, MM and Blagonravov, ML and Gigani, OO and Ait Aissa, A and Denisova, AP}, title = {Distribution of Polymorphisms of the Renin-Angiotensin System Genes (ACE, AGT, and AGTR1), ITGB3, and FTO in Pregnant Patients with Hypertensive Disorders.}, journal = {Bulletin of experimental biology and medicine}, volume = {167}, number = {1}, pages = {74-78}, doi = {10.1007/s10517-019-04464-6}, pmid = {31177447}, issn = {1573-8221}, mesh = {Adult ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics ; Angiotensinogen/*genetics ; Female ; Humans ; Hypertension, Pregnancy-Induced/*genetics ; Integrin beta3/*genetics ; Peptidyl-Dipeptidase A/*genetics ; Polymorphism, Genetic/genetics ; Pregnancy ; Prospective Studies ; Receptor, Angiotensin, Type 1/*genetics ; Renin-Angiotensin System/*genetics/*physiology ; }, abstract = {The study included pregnant women aged 23-41 years with preeclampsia and gestation-associated arterial hypertension at weeks 27-40 and patients with essential arterial hypertension developing under conditions of the metabolic syndrome and without it. Frequency analysis of polymorphisms of the renin-angiotensin system genes (ACE, AGT, and AGTR1), ITGB3, FTO and their associations confirmed the syndrome nature of hypertensive disorders in pregnancy. The presence allele T of AGT gene and/or allele C of AGTR1 gene in the genotype of patients with preeclampsia was associated with higher BP and pressure load over 24 h. Allele D of ACE gene was also essential for BP parameters (pressure load) in patients with preeclampsia and gestation-associated arterial hypertension. Due to high genetic heterogeneity of the preeclampsia syndrome and genetic differences in the incidence of the studied gene polymorphisms in preeclampsia and gestation-associated arterial hypertension, no direct associations between these gestation disorders and polymorphic markers of the renin-angiotensin system genes can be established. However, polymorphisms of the renin-angiotensin system genes are essential for the 24-h dynamics of BP and pressure load under conditions of hypertensive disorders in pregnancy.}, } @article {pmid31164119, year = {2019}, author = {Shebanits, K and Günther, T and Johansson, ACV and Maqbool, K and Feuk, L and Jakobsson, M and Larhammar, D}, title = {Copy number determination of the gene for the human pancreatic polypeptide receptor NPY4R using read depth analysis and droplet digital PCR.}, journal = {BMC biotechnology}, volume = {19}, number = {1}, pages = {31}, pmid = {31164119}, issn = {1472-6750}, mesh = {DNA Copy Number Variations/*genetics ; *Gene Dosage ; Genome, Human/genetics ; Genomics/methods ; Humans ; Polymerase Chain Reaction/*methods ; Receptors, Neuropeptide Y/*genetics ; Reproducibility of Results ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Copy number variation (CNV) plays an important role in human genetic diversity and has been associated with multiple complex disorders. Here we investigate a CNV on chromosome 10q11.22 that spans NPY4R, the gene for the appetite-regulating pancreatic polypeptide receptor Y4. This genomic region has been challenging to map due to multiple repeated elements and its precise organization has not yet been resolved. Previous studies using microarrays were interpreted to show that the most common copy number was 2 per genome.

RESULTS: We have investigated 18 individuals from the 1000 Genomes project using the well-established method of read depth analysis and the new droplet digital PCR (ddPCR) method. We find that the most common copy number for NPY4R is 4. The estimated number of copies ranged from three to seven based on read depth analyses with Control-FREEC and CNVnator, and from four to seven based on ddPCR. We suggest that the difference between our results and those published previously can be explained by methodological differences such as reference gene choice, data normalization and method reliability. Three high-quality archaic human genomes (two Neanderthal and one Denisova) display four copies of the NPY4R gene indicating that a duplication occurred prior to the human-Neanderthal/Denisova split.

CONCLUSIONS: We conclude that ddPCR is a sensitive and reliable method for CNV determination, that it can be used for read depth calibration in CNV studies based on already available whole-genome sequencing data, and that further investigation of NPY4R copy number variation and its consequences are necessary due to the role of Y4 receptor in food intake regulation.}, } @article {pmid31163991, year = {2019}, author = {Santander, C and Montinaro, F and Capelli, C}, title = {Searching for archaic contribution in Africa.}, journal = {Annals of human biology}, volume = {46}, number = {2}, pages = {129-139}, doi = {10.1080/03014460.2019.1624823}, pmid = {31163991}, issn = {1464-5033}, mesh = {Africa ; Animals ; Black People/*genetics ; DNA, Ancient/*analysis ; Genome, Human ; Hominidae/*genetics ; Humans ; *Hybridization, Genetic ; }, abstract = {Context: Africa's role in the narrative of human evolution is indisputably emphasised in the emergence of Homo sapiens. However, once humans dispersed beyond Africa, the history of those who stayed remains vastly under-studied, lacking the proper attention the birthplace of both modern and archaic humans deserves. The sequencing of Neanderthal and Denisovan genomes has elucidated evidence of admixture between archaic and modern humans outside of Africa, but has not aided efforts in answering whether archaic admixture happened within Africa. Objectives: This article reviews the state of research for archaic introgression in African populations and discusses recent insights into this topic. Methods: Gathering published sources and recently released preprints, this review reports on the different methods developed for detecting archaic introgression. Particularly it discusses how relevant these are when implemented on African populations and what findings these studies have shown so far. Results: Methods for detecting archaic introgression have been predominantly developed and implemented on non-African populations. Recent preprints present new methods considering African populations. While a number of studies using these methods suggest archaic introgression in Africa, without an African archaic genome to validate these results, such findings remain as putative archaic introgression. Conclusion: In light of the caveats with implementing current archaic introgression detection methods in Africa, we recommend future studies to concentrate on unravelling the complicated demographic history of Africa through means of ancient DNA where possible and through more focused efforts to sequence modern DNA from more representative populations across the African continent.}, } @article {pmid31136573, year = {2019}, author = {Durvasula, A and Sankararaman, S}, title = {A statistical model for reference-free inference of archaic local ancestry.}, journal = {PLoS genetics}, volume = {15}, number = {5}, pages = {e1008175}, pmid = {31136573}, issn = {1553-7404}, support = {R00 GM111744/GM/NIGMS NIH HHS/United States ; R35 GM125055/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Genetics, Population/*methods ; Genome, Human/genetics ; Genomics/*methods ; Hominidae/*genetics ; Humans ; Models, Statistical ; Neanderthals/genetics ; }, abstract = {Statistical analyses of genomic data from diverse human populations have demonstrated that archaic hominins, such as Neanderthals and Denisovans, interbred or admixed with the ancestors of present-day humans. Central to these analyses are methods for inferring archaic ancestry along the genomes of present-day individuals (archaic local ancestry). Methods for archaic local ancestry inference rely on the availability of reference genomes from the ancestral archaic populations for accurate inference. However, several instances of archaic admixture lack reference archaic genomes, making it difficult to characterize these events. We present a statistical method that combines diverse population genetic summary statistics to infer archaic local ancestry without access to an archaic reference genome. We validate the accuracy and robustness of our method in simulations. When applied to genomes of European individuals, our method recovers segments that are substantially enriched for Neanderthal ancestry, even though our method did not have access to any Neanderthal reference genomes.}, } @article {pmid31133435, year = {2019}, author = {Denisova, K}, title = {Failure to attune to language predicts autism in high risk infants.}, journal = {Brain and language}, volume = {194}, number = {}, pages = {109-120}, doi = {10.1016/j.bandl.2019.04.002}, pmid = {31133435}, issn = {1090-2155}, mesh = {Autism Spectrum Disorder/diagnostic imaging/*physiopathology ; Head Movements ; Humans ; Infant ; *Language Development ; Magnetic Resonance Imaging ; Sleep ; Speech Perception ; }, abstract = {Young humans are typically sensitive to evolutionarily important aspects of information in the surrounding environment in a way that makes us thrive. Seeking to probe the putative disruptions of this process in infancy, I examined the statistical character of head movements in 52 9-10 mo-old infants, half at high familial risk (HR) for Autism Spectrum Disorders (ASD), who underwent an fMRI scan while listening to words spoken with alternating stress patterns on syllables. Relative to low risk (LR) infants, HR infants, in particular those showing the least rapid receptive language progress, had significantly lower noise-to-signal levels and increased symmetry. A comparison of patterns during a native language and a sleep scan revealed the most atypical ordering of signatures on the 3 tasks in a subset of HR infants, suggesting that the biological mechanism of language development is least acquisitive in those HR infants who go on to develop ASD in toddlerhood.}, } @article {pmid31114607, year = {2019}, author = {Liu, C and Everall, I and Pantelis, C and Bousman, C}, title = {Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {389}, pmid = {31114607}, issn = {1664-8021}, abstract = {Schizophrenia is a psychiatric disorder with a worldwide prevalence of ∼1%. The high heritability and reduced fertility among schizophrenia patients have raised an evolutionary paradox: why has negative selection not eliminated schizophrenia associated alleles during evolution? To address this question, we examined evolutionary markers, known as modern-human-specific (MD) sites and archaic-human-specific sites, using existing genome-wide association study (GWAS) data from 34,241 individuals with schizophrenia and 45,604 healthy controls included in the Psychiatric Genomics Consortium (PGC). By testing the distribution of schizophrenia single nucleotide polymorphisms (SNPs) with risk and protective effects in the human-specific sites, we observed a negative selection of risk alleles for schizophrenia in modern humans relative to archaic humans (e.g., Neanderthal and Denisovans). Such findings indicate that risk alleles of schizophrenia have been gradually removed from the modern human genome due to negative selection pressure. This novel evidence contributes to our understanding of the genetic origins of schizophrenia.}, } @article {pmid31102945, year = {2019}, author = {Denisova, K}, title = {Age attenuates noise and increases symmetry of head movements during sleep resting-state fMRI in healthy neonates, infants, and toddlers.}, journal = {Infant behavior & development}, volume = {57}, number = {}, pages = {101317}, doi = {10.1016/j.infbeh.2019.03.008}, pmid = {31102945}, issn = {1934-8800}, mesh = {Age Factors ; Brain/*diagnostic imaging/*physiology ; Child, Preschool ; Cross-Sectional Studies ; Female ; Head Movements/*physiology ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging/*methods ; Male ; Noise ; Rest/*physiology ; Sleep/*physiology ; }, abstract = {Newborns produce spontaneous movements during sleep that are functionally important for their future development. This nuance has been previously studied using animal models and more recently using movement data from sleep resting-state fMRI (rs-fMRI) scans. Age-related trajectory of statistical features of spontaneous movements of the head is under-examined. This study quantitatively mapped a developmental trajectory of spontaneous head movements during an rs-fMRI scan acquired during natural sleep in 91 datasets from healthy children from ∼birth to 3 years old, using the Open Science Infancy Research upcycling protocol. The youngest participants studied, 2-3 week-old neonates, showed increased noise-to-signal levels as well as lower symmetry features of their movements; noise-to-signal levels were attenuated and symmetry was increased in the older infants and toddlers (all Spearman's rank-order correlations, P < 0.05). Thus, statistical features of spontaneous head movements become more symmetrical and less noisy from birth to ∼3 years in children. Because spontaneous movements during sleep in early life may trigger new neuronal activity in the cortex, the key outstanding question for in vivo, non-invasive neuroimaging studies in young children is not "How can we correct head movement better?" but rather: How can we represent all important sources of neuronal activity that shape functional connections in the still-developing human central nervous system?}, } @article {pmid31090374, year = {2019}, author = {Kovalkova, NA and Ragino, YI and Scherbakova, LV and Hudyakovа, AD and Denisova, DV and Voevoda, MI}, title = {Relationships of arterial hypertension and reduced renal function in a population 25-45 years.}, journal = {Terapevticheskii arkhiv}, volume = {91}, number = {1}, pages = {64-70}, doi = {10.26442/00403660.2019.01.000032}, pmid = {31090374}, issn = {0040-3660}, mesh = {Adult ; Blood Pressure/physiology ; Blood Pressure Determination ; Creatinine/*blood ; Cross-Sectional Studies ; Female ; Glomerular Filtration Rate/*physiology ; Humans ; Hypertension/epidemiology/*physiopathology ; Kidney/*physiopathology ; Male ; Middle Aged ; Risk Factors ; Russia/epidemiology ; }, abstract = {AIM: To study relationships of reduced renal function with hypertension and other cardiometabolic risk factors in persons aged 25-45 years.

MATERIALS AND METHODS: A cross-sectional population study of one of the typical district of Novosibirsk (Russia) was performed during 2013-2016 years. The study included 468 men and 606 women aged 25-45 years. Blood pressure (BP), waist circumference (WC), blood lipids, glucose, creatinine were measured. Glomerular filtration rate (GFR) was calculated with the formula CKD-EPI. Hypertension was registered if blood pressure (BP) was ≥140/90 mm Hg, reduced kidney function - at GFR<90 ml/min/1.73 cm2.

RESULTS: Prevalence of hypertension among men was 28%, among women - 9%. The proportion of people with GFR<90 ml/min/1.73 cm2 among men was 9.8%, among women - 34%. Among all examined people GFRs <60 ml/min/1.73 cm2 was revealed in 0.3% only. The association of hypertension with reduced renal function was determined only in men. Based on results of multivariate linear regression analysis, a significant negative association of GFR with age was determined, there was no association of GFR with systolic BP (SBP) in either men or women. In men, inverse relationships of GFR with low-density lipoprotein cholesterol (LDL-С), triglycerides (TG), direct - with WC were determined. Significant inverse association of GFR with diastolic BP (DBP) was revealed only after exception of TG from the regression model. In women, GFR's inverse relationship with LDL-С and DBP was observed, and the direct - with WC. In stepwise analysis the validity of all associations was confirmed after exception of the association of GFR with WC in men.

CONCLUSION: In a population of 25-45 years a reduced GFR was associated with increased DBP; levels of LDL-С, TG showed negative association with GFR; in men increased TG levels were more important in reducing GFR than elevated DBP.}, } @article {pmid31084661, year = {2019}, author = {Denisova, SA and Shchenkov, SV}, title = {New data on the nervous system of Cercaria parvicaudata Stunkard & Shaw, 1931 (Trematoda: Renicolidae): revisiting old hypotheses.}, journal = {Journal of helminthology}, volume = {94}, number = {}, pages = {e52}, doi = {10.1017/S0022149X1900035X}, pmid = {31084661}, issn = {1475-2697}, mesh = {Animals ; Cercaria/*anatomy & histology ; Microscopy, Electron, Scanning ; Nervous System/*anatomy & histology/ultrastructure ; Sensory Receptor Cells/*ultrastructure ; Silver Nitrate ; Specimen Handling ; Staining and Labeling ; }, abstract = {Data on the interposition of the immunoreactive nerve cords in Cercaria parvicaudata Stunkard & Shaw, 1931 (Trematoda: Renicolidae) and its chaetotaxy were obtained. The nervous system of C. parvicaudata was described using immunostaining of 5-hydroxytryptamine and FMRFamide immunoreactive nerve elements. The morphology and distribution of sensory receptors were analysed using scanning electron microscopy and the silver nitrate impregnation technique. Our integrated approach to the study of the nervous system revealed a clear colocalization of surface papillae with nerve cords and commissures in C. parvicaudata. The structure of the nervous system in C. parvicaudata differs partly from the classical model that defines the entire nomenclature of chaetotaxy.}, } @article {pmid31068377, year = {2019}, author = {Vangenot, C and Gagneux, P and de Groot, NG and Baumeyer, A and Mouterde, M and Crouau-Roy, B and Darlu, P and Sanchez-Mazas, A and Sabbagh, A and Poloni, ES}, title = {Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes.}, journal = {G3 (Bethesda, Md.)}, volume = {9}, number = {7}, pages = {2199-2224}, pmid = {31068377}, issn = {2160-1836}, mesh = {Alleles ; Animals ; Arylamine N-Acetyltransferase/*genetics ; *Genetic Variation ; Genome ; Genomics/methods ; Haplotypes ; Hominidae ; Humans ; Multigene Family ; Pan troglodytes/*genetics ; Polymorphism, Genetic ; Species Specificity ; }, abstract = {Among the many genes involved in the metabolism of therapeutic drugs, human arylamine N-acetyltransferases (NATs) genes have been extensively studied, due to their medical importance both in pharmacogenetics and disease epidemiology. One member of this small gene family, NAT2, is established as the locus of the classic human acetylation polymorphism in drug metabolism. Current hypotheses hold that selective processes favoring haplotypes conferring lower NAT2 activity have been operating in modern humans' recent history as an adaptation to local chemical and dietary environments. To shed new light on such hypotheses, we investigated the genetic diversity of the three members of the NAT gene family in seven hominid species, including modern humans, Neanderthals and Denisovans. Little polymorphism sharing was found among hominids, yet all species displayed high NAT diversity, but distributed in an opposite fashion in chimpanzees and bonobos (Pan genus) compared to modern humans, with higher diversity in Pan species at NAT1 and lower at NAT2, while the reverse is observed in humans. This pattern was also reflected in the results returned by selective neutrality tests, which suggest, in agreement with the predicted functional impact of mutations detected in non-human primates, stronger directional selection, presumably purifying selection, at NAT1 in modern humans, and at NAT2 in chimpanzees. Overall, the results point to the evolution of divergent functions of these highly homologous genes in the different primate species, possibly related to their specific chemical/dietary environment (exposome) and we hypothesize that this is likely linked to the emergence of controlled fire use in the human lineage.}, } @article {pmid31048468, year = {2019}, author = {Gibbons, A}, title = {Ancient jaw gives elusive Denisovans a face.}, journal = {Science (New York, N.Y.)}, volume = {364}, number = {6439}, pages = {418-419}, doi = {10.1126/science.364.6439.418}, pmid = {31048468}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Collagen/chemistry/isolation & purification ; Face ; *Fossils ; *Hominidae ; Humans ; Jaw/*chemistry ; Sequence Analysis, Protein/*methods ; Tibet ; }, } @article {pmid31043746, year = {2019}, author = {Chen, F and Welker, F and Shen, CC and Bailey, SE and Bergmann, I and Davis, S and Xia, H and Wang, H and Fischer, R and Freidline, SE and Yu, TL and Skinner, MM and Stelzer, S and Dong, G and Fu, Q and Dong, G and Wang, J and Zhang, D and Hublin, JJ}, title = {A late Middle Pleistocene Denisovan mandible from the Tibetan Plateau.}, journal = {Nature}, volume = {569}, number = {7756}, pages = {409-412}, pmid = {31043746}, issn = {1476-4687}, mesh = {Altitude ; Animals ; Caves ; *Fossils ; Hominidae/*anatomy & histology/classification ; Human Migration ; Humans ; Mandible/*anatomy & histology ; Phylogeny ; Tibet ; Tooth/anatomy & histology ; }, abstract = {Denisovans are members of a hominin group who are currently only known directly from fragmentary fossils, the genomes of which have been studied from a single site, Denisova Cave[1-3] in Siberia. They are also known indirectly from their genetic legacy through gene flow into several low-altitude East Asian populations[4,5] and high-altitude modern Tibetans[6]. The lack of morphologically informative Denisovan fossils hinders our ability to connect geographically and temporally dispersed fossil hominins from Asia and to understand in a coherent manner their relation to recent Asian populations. This includes understanding the genetic adaptation of humans to the high-altitude Tibetan Plateau[7,8], which was inherited from the Denisovans. Here we report a Denisovan mandible, identified by ancient protein analysis[9,10], found on the Tibetan Plateau in Baishiya Karst Cave, Xiahe, Gansu, China. We determine the mandible to be at least 160 thousand years old through U-series dating of an adhering carbonate matrix. The Xiahe specimen provides direct evidence of the Denisovans outside the Altai Mountains and its analysis unique insights into Denisovan mandibular and dental morphology. Our results indicate that archaic hominins occupied the Tibetan Plateau in the Middle Pleistocene epoch and successfully adapted to high-altitude hypoxic environments long before the regional arrival of modern Homo sapiens.}, } @article {pmid31043736, year = {2019}, author = {Warren, M}, title = {Biggest Denisovan fossil yet spills ancient human's secrets.}, journal = {Nature}, volume = {569}, number = {7754}, pages = {16-17}, pmid = {31043736}, issn = {1476-4687}, } @article {pmid30990461, year = {2019}, author = {Jones, M and Denisova, A and Mitchell, S and Owen, T}, title = {Acceptability of a Plasticity-Focused Serious Game Intervention for Posttraumatic Stress Disorder: User Requirements Analysis.}, journal = {JMIR serious games}, volume = {7}, number = {2}, pages = {e11909}, pmid = {30990461}, issn = {2291-9279}, abstract = {BACKGROUND: Trauma-focused cognitive behavioral therapy (TF-CBT) is a first-line treatment for posttraumatic stress disorder (PTSD). Despite a solid evidence base, TF-CBT response and attrition rates vary considerably. Plasticity-focused interventions, including the use of serious games, have the potential to improve TF-CBT response and treatment retention.

OBJECTIVE: The aim of this study was to assess the acceptability of a mobile phone-delivered plasticity-focused serious game to improve response to TF-CBT for PTSD, and carry out a user requirements analysis should the development of a prototype be warranted.

METHODS: We conducted 2 one-to-one interviews (n=2), one focus group involving service users who had received a diagnosis of PTSD (n=3) and one focus group involving psychological trauma service clinicians (n=4).

RESULTS: We found that the concept of a plasticity-focused mobile phone intervention for PTSD is acceptable to patients and clinicians. Service users and clinicians both believed that the usage should be guided by a therapist, and both contributed useful inputs regarding the audiovisual aspects of the proposed serious game. It was accepted that the game would not be suitable for all patients and that clinicians would need to appropriately prescribe the usage of the game.

CONCLUSIONS: The findings highlight the acceptability of the proposed serious game and clarify the user requirements for such an intervention. It is the intention of the authors to carry out a user experience evaluation using a prototype serious game in a clinical population.}, } @article {pmid30990150, year = {2019}, author = {Ragino, YI and Shcherbakova, LV and Denisova, DV and Kuzminykh, NA and Yachmeneva, MP and Voevoda, MI}, title = {[Blood lipids and angina pectoris (by epidemiological cardiological Rose questionnaire) in the population of 25-45 years of Novosibirsk].}, journal = {Kardiologiia}, volume = {59}, number = {3S}, pages = {30-35}, doi = {10.18087/cardio.2600}, pmid = {30990150}, issn = {0022-9040}, mesh = {Adult ; *Angina Pectoris ; Cholesterol, HDL ; Cholesterol, LDL ; Cross-Sectional Studies ; Female ; Humans ; Lipids ; Male ; Middle Aged ; Risk Factors ; Surveys and Questionnaires ; Triglycerides ; }, abstract = {UNLABELLED: The aim of the study was to investigate the prevalence of angina pectoris (AP) according to the standardized epidemiological questionnaire of Rose in the population of 25-45 years of Novosibirsk and to identify its association with some lipid and non-lipid risk factors for coronary heart disease (CHD).

MATERIAL AND METHODS: Cross-sectional survey of the population aged 25-45 in Novosibirsk was carried out. The study included 1439 people (656 men and 783 women). Within the framework of the complex survey program, the standardized epidemiological questionnaire of Rose (WHO, 1984) was used. Blood levels of total cholesterol (total C), triglycerides (TG), low and high density lipoprotein cholesterol (LDL-C, HDL-C) were determinate by biochemical methods.

RESULTS: For all lipid indicators, significant differences were found between men and women. The levels of total C, TG and LDL-C were significantly higher, and the level of HDL-C was lower in men, than in women. According to the Rose questionnaire, out of 1439 people included in the study, 12 patients (0.8%) had AP (75% women). In persons with AP, blood levels of TG were 1.8 times higher, and the levels of HDL-C in blood was 1.2 times lower compared to persons without AP. Univariate analysis of associations of AP with CHD risk factors showed that the chance of developing angina pectoris in the population of 25-45 years was significantly increased in individuals with high blood TG levels (OR 3,515, DI 1,106-11,168, p = 0.039) and low HDL-C (OR 1,203, DI 1,054-1,372, p = 0.006). A natural, although statistically not significant (OR 3,165, p=0,055, due to the small number of groups with AP) increasing in the chance of developing AP in hypertension was detected.

CONCLUSION: In the young population of 25-45 years in Novosibirsk, elevated blood levels of TG, reduced levels of HDL-C, and hypertension were associated with AP, according to Rosecardiological questionnaire, which underlines the importance of conducting screening surveys of the young population to improve effective prevention and treatment of diseases.}, } @article {pmid30990136, year = {2019}, author = {Kuznetsov, AA and Tsvetkova, EE and Denisova, DV and Ragino, YI and Voevoda, MI}, title = {[Central Aortic Pressure: Reference and Diagnostic Values].}, journal = {Kardiologiia}, volume = {59}, number = {3}, pages = {11-17}, doi = {10.18087/cardio.2019.3.10235}, pmid = {30990136}, issn = {0022-9040}, mesh = {Adult ; *Arterial Pressure ; Blood Pressure ; Blood Pressure Determination ; Female ; Humans ; *Hypertension ; Male ; Radial Artery ; Reference Values ; }, abstract = {OBJECTIVE: Practical application of central aortic pressure (CAP) parameters is limited by the absence of generally recognized reference and threshold diagnostic indices. The purpose of this work is to establish their values in the general population of Novosibirsk. Materials and Methods. A total of 327 people were examined: 155 men and 172 women aged 25-44 years from a representative sample from the general population of Novosibirsk. Applanation tonometry of the radial artery was performed by the SphygmoCor system. The reference values of CAP parameters were obtained by a nonparametric method according to the Clinical and Laboratory Standards Institute (CLSI) recommendations (95 % percentile interval with 2.5 % and 97.5 % cut-off points and their 90 % confidence intervals). Diagnostic thresholds and categories of CAP were determined as mean values depending on the categories of brachial arterial pressure (BP) and on the basis of risk estimates, as well as sensitivity and specificity values for left ventricular hypertrophy similar to risk and sensitivity and specificity values of threshold levels (categories) of brachial BP.

RESULTS: The reference values of the parameters of the CAP were: 18-43 mm Hg for pulse pressure; 5-24 mm Hg for the amplification of pulse pressure; - 8.8-40 % for the augmentation index. Diagnostic categories of CAP were determined to be: optimal - less than 110 / 80, normal - 110 / 80-114 / 84, high normal - 115 / 85-124 / 89, hypertension - more than 125 / 90 mm Hg.

CONCLUSION: The reference values, diagnostic thresholds and categories of parameters of CAP in the general population of Novosibirsk aged 25-44 years have been determined. It is expedient to further study them.}, } @article {pmid30981557, year = {2019}, author = {Jacobs, GS and Hudjashov, G and Saag, L and Kusuma, P and Darusallam, CC and Lawson, DJ and Mondal, M and Pagani, L and Ricaut, FX and Stoneking, M and Metspalu, M and Sudoyo, H and Lansing, JS and Cox, MP}, title = {Multiple Deeply Divergent Denisovan Ancestries in Papuans.}, journal = {Cell}, volume = {177}, number = {4}, pages = {1010-1021.e32}, doi = {10.1016/j.cell.2019.02.035}, pmid = {30981557}, issn = {1097-4172}, mesh = {Animals ; Asian People/genetics ; Biological Evolution ; Gene Flow ; Genetic Introgression/*genetics ; Genetic Variation/genetics ; Genome, Human/genetics ; Haplotypes/*genetics ; Hominidae/*genetics ; Humans ; Indonesia ; Neanderthals/genetics ; Oceania ; }, abstract = {Genome sequences are known for two archaic hominins-Neanderthals and Denisovans-which interbred with anatomically modern humans as they dispersed out of Africa. We identified high-confidence archaic haplotypes in 161 new genomes spanning 14 island groups in Island Southeast Asia and New Guinea and found large stretches of DNA that are inconsistent with a single introgressing Denisovan origin. Instead, modern Papuans carry hundreds of gene variants from two deeply divergent Denisovan lineages that separated over 350 thousand years ago. Spatial and temporal structure among these lineages suggest that introgression from one of these Denisovan groups predominantly took place east of the Wallace line and continued until near the end of the Pleistocene. A third Denisovan lineage occurs in modern East Asians. This regional mosaic suggests considerable complexity in archaic contact, with modern humans interbreeding with multiple Denisovan groups that were geographically isolated from each other over deep evolutionary time.}, } @article {pmid30948532, year = {2019}, author = {Gibbons, A}, title = {Moderns said to mate with late-surviving Denisovans.}, journal = {Science (New York, N.Y.)}, volume = {364}, number = {6435}, pages = {12-13}, doi = {10.1126/science.364.6435.12}, pmid = {30948532}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; *Extinction, Biological ; *Hominidae ; Neanderthals ; New Guinea ; }, } @article {pmid30942856, year = {2019}, author = {Harris, DN and Ruczinski, I and Yanek, LR and Becker, LC and Becker, DM and Guio, H and Cui, T and Chilton, FH and Mathias, RA and O'Connor, TD}, title = {Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World.}, journal = {Genome biology and evolution}, volume = {11}, number = {5}, pages = {1417-1430}, pmid = {30942856}, issn = {1759-6653}, support = {R01 AT008621/AT/NCCIH NIH HHS/United States ; R01 HL087698/HL/NHLBI NIH HHS/United States ; R01 HL112064/HL/NHLBI NIH HHS/United States ; U01 HL072518/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Fatty Acid Desaturases/*genetics/metabolism ; Fatty Acids, Unsaturated/*metabolism ; Hominidae/*genetics/metabolism ; Humans ; Indians, North American/genetics ; Selection, Genetic ; Siberia ; }, abstract = {The metabolic conversion of dietary omega-3 and omega-6 18 carbon (18C) to long chain (>20 carbon) polyunsaturated fatty acids (LC-PUFAs) is vital for human life. The rate-limiting steps of this process are catalyzed by fatty acid desaturase (FADS) 1 and 2. Therefore, understanding the evolutionary history of the FADS genes is essential to our understanding of hominin evolution. The FADS genes have two haplogroups, ancestral and derived, with the derived haplogroup being associated with more efficient LC-PUFA biosynthesis than the ancestral haplogroup. In addition, there is a complex global distribution of these haplogroups that is suggestive of Neanderthal introgression. We confirm that Native American ancestry is nearly fixed for the ancestral haplogroup, and replicate a positive selection signal in Native Americans. This positive selection potentially continued after the founding of the Americas, although simulations suggest that the timing is dependent on the allele frequency of the ancestral Beringian population. We also find that the Neanderthal FADS haplotype is more closely related to the derived haplogroup and the Denisovan clusters closer to the ancestral haplogroup. Furthermore, the derived haplogroup has a time to the most recent common ancestor of 688,474 years before present. These results support an ancient polymorphism, as opposed to Neanderthal introgression, forming in the FADS region during the Pleistocene with possibly differential selection pressures on both haplogroups. The near fixation of the ancestral haplogroup in Native American ancestry calls for future studies to explore the potential health risk of associated low LC-PUFA levels in these populations.}, } @article {pmid30889271, year = {2019}, author = {Vyas, DN and Mulligan, CJ}, title = {Analyses of Neanderthal introgression suggest that Levantine and southern Arabian populations have a shared population history.}, journal = {American journal of physical anthropology}, volume = {169}, number = {2}, pages = {227-239}, doi = {10.1002/ajpa.23818}, pmid = {30889271}, issn = {1096-8644}, support = {BCS-1258965//National Science Foundation/International ; }, mesh = {Animals ; Arabia ; Gene Flow/genetics ; Gene Frequency/genetics ; *Genetics, Population ; History, Ancient ; Human Migration/*history ; Humans ; Middle East ; Neanderthals/*genetics ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {OBJECTIVES: Modern humans are thought to have interbred with Neanderthals in the Near East soon after modern humans dispersed out of Africa. This introgression event likely took place in either the Levant or southern Arabia depending on the dispersal route out of Africa that was followed. In this study, we compare Neanderthal introgression in contemporary Levantine and southern Arabian populations to investigate Neanderthal introgression and to study Near Eastern population history.

MATERIALS AND METHODS: We analyzed genotyping data on >400,000 autosomal SNPs from seven Levantine and five southern Arabian populations and compared these data to those from populations from around the world including Neanderthal and Denisovan genomes. We used f4 and D statistics to estimate and compare levels of Neanderthal introgression between Levantine, southern Arabian, and comparative global populations. We also identified 1,581 putative Neanderthal-introgressed SNPs within our dataset and analyzed their allele frequencies as a means to compare introgression patterns in Levantine and southern Arabian genomes.

RESULTS: We find that Levantine and southern Arabian populations have similar levels of Neanderthal introgression to each other but lower levels than other non-Africans. Furthermore, we find that introgressed SNPs have very similar allele frequencies in the Levant and southern Arabia, which indicates that Neanderthal introgression is similarly distributed in Levantine and southern Arabian genomes.

DISCUSSION: We infer that the ancestors of contemporary Levantine and southern Arabian populations received Neanderthal introgression prior to separating from each other and that there has been extensive gene flow between these populations.}, } @article {pmid30885783, year = {2019}, author = {Alexeeva, E and Dvoryakovskaya, T and Denisova, R and Sleptsova, T and Isaeva, K and Chomahidze, A and Fetisova, A and Mamutova, A and Alshevskaya, A and Gladkikh, V and Moskalev, A}, title = {Dynamics of concomitant therapy in children with juvenile idiopathic arthritis treated with etanercept and methotrexate.}, journal = {Pediatrics and neonatology}, volume = {60}, number = {5}, pages = {549-555}, doi = {10.1016/j.pedneo.2019.02.003}, pmid = {30885783}, issn = {2212-1692}, mesh = {Adolescent ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antirheumatic Agents/*therapeutic use ; Arthritis, Juvenile/*drug therapy ; Child ; Child, Preschool ; Drug Therapy, Combination ; Etanercept/administration & dosage/*therapeutic use ; Female ; Humans ; Infant ; Male ; Methotrexate/administration & dosage/*therapeutic use ; }, abstract = {BACKGROUND: Both the steroid- and NSAID-sparing effects of biologics in juvenile idiopathic arthritis (JIA) treatment are key aspects of the dynamics of patient's condition. The proper selection of biologics enables maximum treatment effectiveness and reduction of the dosage of concomitant therapy. Our aim was to study the dynamics of concomitant therapy during etanercept (ETA) and methotrexate (MTX) treatment in patients with JIA.

METHODS: This analysis included 215 JIA patients (63.3% females) showing sufficient response to main therapy. One hundred patients received MTX as main therapy, 24 received ETA monotherapy, and 91 received ETA þ MTX combination therapy. The dynamics of concomitant therapy were analyzed after 1 month, every 3 months during the first year, and every 6 months during the long-term follow-up (up to 5 years).

RESULTS: At the baseline, 24 (11.2%) patients received concomitant oral glucocorticoids (orGCs) and NSAIDs; the remaining 191 (88.8%) patients were treated with concomitant NSAIDs only. Within 1-year treatment, NSAIDs were discontinued in 162 (75.3%) patients. There were no significant differences in the dynamics of withdrawal of NSAIDs in patients who received and did not receive concomitant MTX. However, the percentage of treatment discontinuation in the MTX group was significantly lower compared to the other two groups (p < 0.001). Oral GCs were discontinued completely in 4 children (16.7%), and the dose of oral GCs was reduced in another 4 patients (16.7%). By the end of the follow-up period, 44 of 115 patients (38.3%) treated with ETA in combination with any concomitant therapy could switch to ETA monotherapy.

CONCLUSION: Therapy with ETA makes it possible to reduce the dosage or completely discontinue most concomitant medications (orGCs, NSAIDs, MTX) in a significant percentage of patients. This reduces the risk of development of NSAID- and GC-induced pathological conditions, while the effectiveness of therapy of the underlying condition remains high.}, } @article {pmid30854422, year = {2019}, author = {Rogers, J and Raveendran, M and Harris, RA and Mailund, T and Leppälä, K and Athanasiadis, G and Schierup, MH and Cheng, J and Munch, K and Walker, JA and Konkel, MK and Jordan, V and Steely, CJ and Beckstrom, TO and Bergey, C and Burrell, A and Schrempf, D and Noll, A and Kothe, M and Kopp, GH and Liu, Y and Murali, S and Billis, K and Martin, FJ and Muffato, M and Cox, L and Else, J and Disotell, T and Muzny, DM and Phillips-Conroy, J and Aken, B and Eichler, EE and Marques-Bonet, T and Kosiol, C and Batzer, MA and Hahn, MW and Tung, J and Zinner, D and Roos, C and Jolly, CJ and Gibbs, RA and Worley, KC and , }, title = {The comparative genomics and complex population history of Papio baboons.}, journal = {Science advances}, volume = {5}, number = {1}, pages = {eaau6947}, pmid = {30854422}, issn = {2375-2548}, support = {P51 OD011133/OD/NIH HHS/United States ; R01 GM059290/GM/NIGMS NIH HHS/United States ; R35 GM118335/GM/NIGMS NIH HHS/United States ; W 1225/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Female ; Gene Flow ; Genomics/*methods ; Haplotypes/genetics ; Humans ; Hybridization, Genetic ; Male ; Papio/*genetics ; Phylogeny ; Polymorphism, Genetic ; Whole Genome Sequencing ; }, abstract = {Recent studies suggest that closely related species can accumulate substantial genetic and phenotypic differences despite ongoing gene flow, thus challenging traditional ideas regarding the genetics of speciation. Baboons (genus Papio) are Old World monkeys consisting of six readily distinguishable species. Baboon species hybridize in the wild, and prior data imply a complex history of differentiation and introgression. We produced a reference genome assembly for the olive baboon (Papio anubis) and whole-genome sequence data for all six extant species. We document multiple episodes of admixture and introgression during the radiation of Papio baboons, thus demonstrating their value as a model of complex evolutionary divergence, hybridization, and reticulation. These results help inform our understanding of similar cases, including modern humans, Neanderthals, Denisovans, and other ancient hominins.}, } @article {pmid30853019, year = {2019}, author = {Kovalkova, NA and Ragino, YI and Hudyakovа, AD and Denisova, DV and Voevoda, MI}, title = {[Not Available].}, journal = {Kardiologiia}, volume = {59}, number = {2}, pages = {32-37}, doi = {10.18087/cardio.2019.2.10228}, pmid = {30853019}, issn = {0022-9040}, mesh = {Adult ; Blood Pressure ; Cross-Sectional Studies ; Female ; Humans ; *Hypertension ; Male ; Middle Aged ; Prevalence ; Russia ; Siberia ; }, abstract = {PURPOSE: to study blood pressure levels and the prevalence of hypertension in persons aged 25-45 years in Novosibirsk.

MATERIALS AND METHODS: A cross-sectional population study in one of typical areas of Novosibirsk was performed in 2013-2016. The study included 479 men and 612 women aged 25-45 years. Arterial hypertension was defined as blood pressure (BP) ≥140 / 90 mmHg according to Russian recommendations (2004). For analysis two age groups were distinguished: 25-34 years and 35-45 years.

RESULTS: Mean values of systolic and diastolic BP were significantly lower in women than in men in age groups. In men and women, the analyzed indicators were significantly higher in the older than in the younger age group. Mean values of pulse pressure in men were significantly higher than in women in both age groups, there were no differences in the analyzed index between age groups in either men or women. Optimal BP was more often recorded among women than among men in both age groups. The proportion of persons with normal BP among men was grate than among women in both age groups. In the age group 35-45 years compared with the younger group, in men there was a decrease in incidence of category with BP<140 / 90 mmHg, an increase of the proportion of persons with hypertension grades 1 and 2, the appearance of persons with grade 3 hypertension; in women - an increase of the proportion of individuals with normal, high-normal BP, and with grade 1 hypertension, appearance of individuals with grades 2 and 3 hypertension. Frequency of BP categories ≥140 / 90 mmHg in age group 25-34 years among men was 17.6 %, among women 3.1 % (p<0.0001); in age group 35-45 years among men - 34.7 %, among women - 12.5 % (p<0.0001).

CONCLUSIONS: Prevalence of hypertension in men was 28 %, in women - 9 %. Favorable tendencies of BP indicators in both sexes were revealed over a 30-year period, while gender differences did not change.}, } @article {pmid30777361, year = {2019}, author = {Martinón-Torres, M and Bermúdez de Castro, JM and Martínez de Pinillos, M and Modesto-Mata, M and Xing, S and Martín-Francés, L and García-Campos, C and Wu, X and Liu, W}, title = {New permanent teeth from Gran Dolina-TD6 (Sierra de Atapuerca). The bearing of Homo antecessor on the evolutionary scenario of Early and Middle Pleistocene Europe.}, journal = {Journal of human evolution}, volume = {127}, number = {}, pages = {93-117}, doi = {10.1016/j.jhevol.2018.12.001}, pmid = {30777361}, issn = {1095-8606}, mesh = {Animals ; Anthropology, Physical ; *Biological Evolution ; Fossils/*anatomy & histology ; Hominidae/*anatomy & histology/classification ; Spain ; Tooth/*anatomy & histology ; }, abstract = {Here we analyze the unpublished hominin dental remains recovered from the late Early Pleistocene Gran Dolina-TD6.2 level of the Sierra de Atapuerca (northern Spain), as well as provide a reassessment of the whole TD6.2 hominin dental sample. Comparative descriptions of the outer enamel surface (OES) and the enamel-dentine junction (EDJ) are provided. Overall, the data presented here support the taxonomic validity of Homo antecessor, since this species presents a unique mosaic of traits. Homo antecessor displays several primitive features for the genus Homo as well as some traits exclusively shared with Early and Middle Pleistocene Eurasian hominins. Some of these Eurasian traits were retained by the Middle Pleistocene hominins of Europe, and subsequently became the typical condition of the Neanderthal lineage. Although other skeletal parts present resemblances with Homo sapiens, TD6.2 teeth do not show any synapomorphy with modern humans. In addition, TD6.2 teeth can be well differentiated from those of Asian Homo erectus. The dental evidence is compatible with previous hypothesis about H. antecessor belonging to the basal population from which H. sapiens, Homo neanderthalensis, and Denisovans emerged. Future findings and additional research may help to elucidate the precise phylogenetic link among them.}, } @article {pmid30773169, year = {2019}, author = {Buttura, RV and Ramalho, J and Lima, THA and Donadi, EA and Veiga-Castelli, LC and Mendes-Junior, CT and Castelli, EC}, title = {HLA-F displays highly divergent and frequent haplotype lineages associated with different mRNA expression levels.}, journal = {Human immunology}, volume = {80}, number = {2}, pages = {112-119}, doi = {10.1016/j.humimm.2018.10.016}, pmid = {30773169}, issn = {1879-1166}, mesh = {Animals ; Brazil ; Gene Expression Regulation ; Gene Frequency ; Genetics, Population ; Haplotypes ; High-Throughput Nucleotide Sequencing ; Histocompatibility Antigens Class I/*genetics ; Humans ; Linkage Disequilibrium ; Neanderthals/genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/*genetics ; }, abstract = {HLA-F is one of the most conserved loci among the HLA gene family. The exact function of HLA-F is still under investigation. HLA-F might present tolerogenic features, participate in the stabilization of HLA molecules in open conformation, and also participate in the recycling of HLA molecules. Here we evaluate the variability and haplotype structure of the HLA-F distal promoter segment (from -1893 to -943) and how this segment is correlated with the coding region. Variability at the promoter segment was surveyed in 196 Brazilian samples using second-generation sequencing. The HLA-F promoter region presents two major haplotype lineages. Most of the variable sites are in perfect linkage and associated with a single promoter haplotype, here named F[∗]distal-C. This haplotype is associated with F[∗]01:01:02 alleles, while alleles from the F[∗]01:01:01 or F[∗]01:03 groups present closely related promoter sequences. F[∗]distal-C is quite frequent in Brazil and in worldwide populations, with frequencies ranging from 8.41% at the Iberian Population in Spain to 34.34% in Vietnam. F[∗]distal-C is also present in Neanderthal and Denisovan samples. In silico analyses demonstrated that F[∗]distal-C presents a different transcription factor binding profile compared with other HLA-F promoters. Moreover, individuals carrying this haplotype present higher HLA-F mRNA expression levels. Functional studies are required to define the exact mechanism underlying this higher HLA-F mRNA expression level associated with F[∗]distal-C and F[∗]01:01:02 alleles.}, } @article {pmid30772945, year = {2019}, author = {James, WPT and Johnson, RJ and Speakman, JR and Wallace, DC and Frühbeck, G and Iversen, PO and Stover, PJ}, title = {Nutrition and its role in human evolution.}, journal = {Journal of internal medicine}, volume = {285}, number = {5}, pages = {533-549}, doi = {10.1111/joim.12878}, pmid = {30772945}, issn = {1365-2796}, mesh = {Animals ; *Biological Evolution ; DNA, Mitochondrial/genetics ; Emigration and Immigration ; Hominidae/genetics/*physiology ; Humans ; Mutation ; *Nutritional Physiological Phenomena ; }, abstract = {Our understanding of human evolution has improved rapidly over recent decades, facilitated by large-scale cataloguing of genomic variability amongst both modern and archaic humans. It seems clear that the evolution of the ancestors of chimpanzees and hominins separated 7-9 million years ago with some migration out of Africa by the earlier hominins; Homo sapiens slowly emerged as climate change resulted in drier, less forested African conditions. The African populations expanded and evolved in many different conditions with slow mutation and selection rates in the human genome, but with much more rapid mutation occurring in mitochondrial DNA. We now have evidence stretching back 300 000 years of humans in their current form, but there are clearly four very different large African language groups that correlate with population DNA differences. Then, about 50 000-100 000 years ago a small subset of modern humans also migrated out of Africa resulting in a persistent signature of more limited genetic diversity amongst non-African populations. Hybridization with archaic hominins occurred around this time such that all non-African modern humans possess some Neanderthal ancestry and Melanesian populations additionally possess some Denisovan ancestry. Human populations both within and outside Africa also adapted to diverse aspects of their local environment including altitude, climate, UV exposure, diet and pathogens, in some cases leaving clear signatures of patterns of genetic variation. Notable examples include haemoglobin changes conferring resistance to malaria, other immune changes and the skin adaptations favouring the synthesis of vitamin D. As humans migrated across Eurasia, further major mitochondrial changes occurred with some interbreeding with ancient hominins and the development of alcohol intolerance. More recently, an ability to retain lactase persistence into adulthood has evolved rapidly under the environmental stimulus of pastoralism with the ability to husband lactating ruminants. Increased amylase copy numbers seem to relate to the availability of starchy foods, whereas the capacity to desaturase and elongate monounsaturated fatty acids in different societies seems to be influenced by whether there is a lack of supply of readily available dietary sources of long-chain polyunsaturated fatty acids. The process of human evolution includes genetic drift and adaptation to local environments, in part through changes in mitochondrial and nuclear DNA. These genetic changes may underlie susceptibilities to some modern human pathologies including folate-responsive neural tube defects, diabetes, other age-related pathologies and mental health disorders.}, } @article {pmid30763487, year = {2018}, author = {Denisova, EI and Korolev, AA and Nikitenko, EI and Kirpichenkova, EV and Fetisov, RN and Kozlov, VV and Onishchenko, GG}, title = {[Hygienic assessment of indoles in the diet of medical students].}, journal = {Voprosy pitaniia}, volume = {87}, number = {6}, pages = {22-27}, doi = {10.24411/0042-8833-2018-10063}, pmid = {30763487}, issn = {0042-8833}, mesh = {Adult ; *Brassicaceae ; *Diet ; Female ; Humans ; Indoles/*administration & dosage ; Male ; Moscow ; Neoplasms/ethnology/prevention & control ; Retrospective Studies ; *Students, Medical ; *Surveys and Questionnaires ; *Vegetables ; }, abstract = {A number of studies have shown the relationship between the regular consumption of cruciferous vegetables and the risk of malignant tumors in certain localizations, the activation of mechanisms of alimentary adaptation of the organism under conditions of alien loads, by inducing enzymes of the biotransformation system of xenobiotics. The cruciferous vegetables are distinguished by the presence of minor components, such as indole-3-carbinol, formed during the hydrolysis of glucosinolates. The aim of the investigation was a retrospective study of the content of indoles in students' diet with subsequent quantitative analysis in different comparison groups. The study involved 250 students from a medical university aged 21 to 27 years. To assess the actual nutrition, the developed questionnaires were used, which included the most common products in the Moscow region, sources of indole glucosinolates. It was found that 44% of the respondents didn't include cruciferous vegetables in the diet, and of those who consumed sources of indoles (56% of respondents), only about half received them in the recommended amount. It should also be noted that as in men, in women the most commonly used in the diet product as a source of indoles was cabbage, it was included in the diet of 68% of the respondents who used cruciferous vegetables, rarely pekin cabbage was used (16.3%) and broccoli (16.3%). Cauliflower, radishes, Kale and horseradish was included in the diet of 7.8-14.9% of the students. Less often turnip was consumed - only by 2.1% of the students. No significant differences in the consumption of indoles in the student with deficient, normal or overweight was revealed. Also, there was no correlation between excess weight and the consumption of various indoles sources. The obtained results testify to the extremely low level of alimentary intake of indole-3-carbinol.}, } @article {pmid30745996, year = {2019}, author = {Gringolts, ML and Denisova, YI and Finkelshtein, ES and Kudryavtsev, YV}, title = {Olefin metathesis in multiblock copolymer synthesis.}, journal = {Beilstein journal of organic chemistry}, volume = {15}, number = {}, pages = {218-235}, pmid = {30745996}, issn = {1860-5397}, abstract = {Multiblock copolymers constitute a basis for an emerging class of nanomaterials that combine various functional properties with durability and enhanced mechanical characteristics. Our mini-review addresses synthetic approaches to the design of multiblock copolymers from unsaturated monomers and polymers using olefin metathesis reactions and other ways of chemical modification across double C=C bonds. The main techniques, actively developed during the last decade and discussed here, are the coupling of end-functionalized blocks, sequential ring-opening metathesis polymerization, and cross metathesis between unsaturated polymers, or macromolecular cross metathesis. The last topic attracts special interest due to its relative simplicity and broad opportunities to tailor the structure and hence the properties of the copolymer products. Whenever possible, we analyze the structure-property relations for multiblock copolymers and point to their possible practical applications.}, } @article {pmid30721182, year = {2018}, author = {Bulynko, SA and Denisova, OA and Soldatsky, YL and Severin, TV and Cherednichenko, AS}, title = {[The observation of two cases of isolated parapharyngeal abscess in a single child].}, journal = {Vestnik otorinolaringologii}, volume = {83}, number = {6}, pages = {44-45}, doi = {10.17116/otorino20188306144}, pmid = {30721182}, issn = {0042-4668}, mesh = {Child ; Child, Preschool ; Humans ; *Pharyngeal Diseases/diagnosis ; *Retropharyngeal Abscess/diagnosis ; Retrospective Studies ; }, abstract = {This article reports a rare observation of the simultaneous appearance of two isolated parapharyngeal abscesses in a 3 year-old child.}, } @article {pmid30700881, year = {2019}, author = {Dennell, R}, title = {Dating of hominin discoveries at Denisova.}, journal = {Nature}, volume = {565}, number = {7741}, pages = {571-572}, doi = {10.1038/d41586-019-00264-0}, pmid = {30700881}, issn = {1476-4687}, mesh = {Animals ; Archaeology ; Caves ; *Fossils ; *Hominidae ; }, } @article {pmid30700871, year = {2019}, author = {Douka, K and Slon, V and Jacobs, Z and Ramsey, CB and Shunkov, MV and Derevianko, AP and Mafessoni, F and Kozlikin, MB and Li, B and Grün, R and Comeskey, D and Devièse, T and Brown, S and Viola, B and Kinsley, L and Buckley, M and Meyer, M and Roberts, RG and Pääbo, S and Kelso, J and Higham, T}, title = {Age estimates for hominin fossils and the onset of the Upper Palaeolithic at Denisova Cave.}, journal = {Nature}, volume = {565}, number = {7741}, pages = {640-644}, doi = {10.1038/s41586-018-0870-z}, pmid = {30700871}, issn = {1476-4687}, mesh = {Animals ; Bayes Theorem ; *Caves ; DNA, Mitochondrial/genetics ; Deer ; Femur/chemistry ; *Fossils ; Geologic Sediments/chemistry ; History, Ancient ; *Hominidae/genetics ; Humans ; Neanderthals/genetics ; Oxygen Isotopes ; *Radiometric Dating ; Siberia ; Time Factors ; Tooth/chemistry ; }, abstract = {Denisova Cave in the Siberian Altai (Russia) is a key site for understanding the complex relationships between hominin groups that inhabited Eurasia in the Middle and Late Pleistocene epoch. DNA sequenced from human remains found at this site has revealed the presence of a hitherto unknown hominin group, the Denisovans[1,2], and high-coverage genomes from both Neanderthal and Denisovan fossils provide evidence for admixture between these two populations[3]. Determining the age of these fossils is important if we are to understand the nature of hominin interaction, and aspects of their cultural and subsistence adaptations. Here we present 50 radiocarbon determinations from the late Middle and Upper Palaeolithic layers of the site. We also report three direct dates for hominin fragments and obtain a mitochondrial DNA sequence for one of them. We apply a Bayesian age modelling approach that combines chronometric (radiocarbon, uranium series and optical ages), stratigraphic and genetic data to calculate probabilistically the age of the human fossils at the site. Our modelled estimate for the age of the oldest Denisovan fossil suggests that this group was present at the site as early as 195,000 years ago (at 95.4% probability). All Neanderthal fossils-as well as Denisova 11, the daughter of a Neanderthal and a Denisovan[4]-date to between 80,000 and 140,000 years ago. The youngest Denisovan dates to 52,000-76,000 years ago. Direct radiocarbon dating of Upper Palaeolithic tooth pendants and bone points yielded the earliest evidence for the production of these artefacts in northern Eurasia, between 43,000 and 49,000 calibrated years before present (taken as AD 1950). On the basis of current archaeological evidence, it may be assumed that these artefacts are associated with the Denisovan population. It is not currently possible to determine whether anatomically modern humans were involved in their production, as modern-human fossil and genetic evidence of such antiquity has not yet been identified in the Altai region.}, } @article {pmid30700870, year = {2019}, author = {Jacobs, Z and Li, B and Shunkov, MV and Kozlikin, MB and Bolikhovskaya, NS and Agadjanian, AK and Uliyanov, VA and Vasiliev, SK and O'Gorman, K and Derevianko, AP and Roberts, RG}, title = {Timing of archaic hominin occupation of Denisova Cave in southern Siberia.}, journal = {Nature}, volume = {565}, number = {7741}, pages = {594-599}, doi = {10.1038/s41586-018-0843-2}, pmid = {30700870}, issn = {1476-4687}, mesh = {Animals ; *Caves ; Geologic Sediments/chemistry ; History, Ancient ; *Hominidae ; Siberia ; Time Factors ; }, abstract = {The Altai region of Siberia was inhabited for parts of the Pleistocene by at least two groups of archaic hominins-Denisovans and Neanderthals. Denisova Cave, uniquely, contains stratified deposits that preserve skeletal and genetic evidence of both hominins, artefacts made from stone and other materials, and a range of animal and plant remains. The previous site chronology is based largely on radiocarbon ages for fragments of bone and charcoal that are up to 50,000 years old; older ages of equivocal reliability have been estimated from thermoluminescence and palaeomagnetic analyses of sediments, and genetic analyses of hominin DNA. Here we describe the stratigraphic sequences in Denisova Cave, establish a chronology for the Pleistocene deposits and associated remains from optical dating of the cave sediments, and reconstruct the environmental context of hominin occupation of the site from around 300,000 to 20,000 years ago.}, } @article {pmid30672457, year = {2019}, author = {Henry, JP}, title = {[Genetics and origin of Homo sapiens].}, journal = {Medecine sciences : M/S}, volume = {35}, number = {1}, pages = {39-45}, doi = {10.1051/medsci/2018311}, pmid = {30672457}, issn = {1958-5381}, mesh = {Africa ; Animals ; Asia ; Biological Evolution ; DNA/analysis/chemistry ; Europe ; *Evolution, Molecular ; *Genome, Human ; Hominidae/*genetics ; Human Genome Project ; Humans ; Neanderthals/genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Selection, Genetic ; Sequence Homology ; }, abstract = {Usually, paleoanthropology studies remains and artefacts. However, more recently, genetics offer new avenues. Information on humanisation mechanisms has been obtained from comparison with primate or archaic Homo DNA sequences. Likewise, the 1 000 Genomes Project has characterized the geographic spectrum of human genetic variation offering a basis for a genomic study of Homo sapiens phylogeny. From these studies, a model, Out of Africa, was derived. His origin is Africa, where he lived 200 000 years ago. A small fraction of the population left Africa between 50 and 100 000 years ago that have populated the rest of the world, to Europe, coastal Asia to Australia and mainland Asia to Behring Land Bridge and America. The model is supported by the decrease of genetic diversity with the distance to Eastern Africa (serial founder effect). In Europe and Asia, Homo sapiens met archaic Homo neanderthalis and H denisova. The presence of 1-3% neanderthalis sequences in modern Homo ADN indicates admixtures between these groups. Some archaic sequences are on positive selection pressure, thus suggesting that the extinct hominins might have facilitated the adaptation of H sapiens to new environments.}, } @article {pmid30651539, year = {2019}, author = {Mondal, M and Bertranpetit, J and Lao, O}, title = {Approximate Bayesian computation with deep learning supports a third archaic introgression in Asia and Oceania.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {246}, pmid = {30651539}, issn = {2041-1723}, abstract = {Since anatomically modern humans dispersed Out of Africa, the evolutionary history of Eurasian populations has been marked by introgressions from presently extinct hominins. Some of these introgressions have been identified using sequenced ancient genomes (Neanderthal and Denisova). Other introgressions have been proposed for still unidentified groups using the genetic diversity present in current human populations. We built a demographic model based on deep learning in an Approximate Bayesian Computation framework to infer the evolutionary history of Eurasian populations including past introgression events in Out of Africa populations fitting the current genetic evidence. In addition to the reported Neanderthal and Denisovan introgressions, our results support a third introgression in all Asian and Oceanian populations from an archaic population. This population is either related to the Neanderthal-Denisova clade or diverged early from the Denisova lineage. We propose the use of deep learning methods for clarifying situations with high complexity in evolutionary genomics.}, } @article {pmid30592887, year = {2018}, author = {Kirpichenkova, EV and Korolev, AA and Onishchenko, GG and Nikitenko, EI and Lipatov, DV and Kuz'min, AG and Dyskin, YA and Denisova, EL and Fetisov, RN}, title = {[Study of lutein and zeaxanthin content in the diet with the assessment of the relationship between the level of alimentary intake of non-vitamin carotenoids and the density of the macular region of the retina at a young age].}, journal = {Voprosy pitaniia}, volume = {87}, number = {5}, pages = {20-26}, doi = {10.24411/0042-8833-2018-10049}, pmid = {30592887}, issn = {0042-8833}, mesh = {Adult ; *Carotenoids/administration & dosage/analysis ; *Diet ; *Eating ; Female ; Food Analysis ; Humans ; *Lutein/administration & dosage/analysis ; *Macula Lutea/diagnostic imaging/metabolism ; Male ; Retrospective Studies ; *Tomography, Optical Coherence ; *Zeaxanthins/administration & dosage/analysis ; }, abstract = {Lutein and zeaxanthin are carotenoid pigments that affect the function of the visual analyzer. They selectively accumulate in the yellow spot of the retina, form macular pigment and determine the density of the retina macula. Lutein and zeaxanthin slow down the progression of age-related macular degeneration, a leading cause of senior-age blindness. The main food sources of non-vitamin carotenoids are green leafy vegetables, zucchini, pumpkin, green peas, broccoli. The aim of the study is a retrospective assessment of the levels and sources of alimentary intake of lutein and zeaxanthin in young people and research of the effect of lutein and zeaxanthin in the diet on macula density. A specially designed questionnaire was used to quantify the content of lutein and zeaxanthin in the diet, reflecting the amount of consumption of the main sources of these carotenoids on the day preceding the survey. A non-invasive non-contact method of optical coherence tomography of the retina was used to determine the density of the macula. The study involved 96 students of Sechenov University at the age of 21-27 years. The study found that only 6.25% of the respondents had daily intake of lutein and zeaxanthin of 6 mg or more, 8.33% had 4.6-5.9 mg, 8.33% had 3.0-4.5 mg, in 18.75% - 1.5-2.9 mg, in 45.83% <1.4 mg. 12.5% of respondents didn't include sources of lutein and zeaxanthin in the diet. The more common sources of lutein and zeaxanthin in the diet were eggs and fresh tomatoes. Retinal density indices corresponded to the age standards in the majority of the examined. In 8.3% surveyed the thickness of the retina was decreased, and 4.2% had higher thickness of the retina in comparison with the standards. Significant differences in the Central subfield thickness in men and women were revealed. There was no dependence of the levels of lutein and zeaxanthin coming from food sources on the retina thickness indicators.}, } @article {pmid30592878, year = {2018}, author = {Martinchik, AN and Baeva, VS and Peskova, EV and Kudryavtseva, KV and Denisova, NN and Lavrinenko, SV and Kambarov, AO and Badtieva, VA and Nikityuk, DB}, title = {[Actual liquid consumption by highly qualified athletes in the mode of the training process].}, journal = {Voprosy pitaniia}, volume = {87}, number = {3}, pages = {36-44}, doi = {10.24411/0042-8833-2018-10029}, pmid = {30592878}, issn = {0042-8833}, mesh = {Adult ; *Athletes ; *Body Weight ; *Drinking Water ; *Energy Drinks ; *Energy Intake ; Humans ; Male ; *Nutrition Surveys ; }, abstract = {The purpose of the study was to evaluate the actual intake of fluids by athletes of various sports during the day with one and two training sessions before, during and after workout. The dietary intake, including consumption of various types of liquid foods and beverages, was evaluated by the method of 24-hour recall in 280 athletes of high qualification (candidates for masters and masters of sports) of both gender of various sports during the training period. It has been established that the main drink of rehydration was drinking bottled water. Bottled water was consumed on average by 86% of athletes. It was consumed by 95-96% of sportsmen from the group of single combats and power kinds, whereas in other groups the share of water consumers was less - 67-79%. In second place in terms of percentage of consuming was tea. Consumption of sports drinks was observed only during training by athletes from the group of cyclic sports (31%) and single combat (11%). Calculating the per capita fluid intake of athletes who had 2 workouts a day showed that athletes from the martial arts group consumed the largest volumes of fluid in the mode of both training sessions as compared to representatives of other sports. Athletes of other sports consumed on average less liquid in the 2nd training mode compared to the 1st one. The total fluid intake during two training sessions was maximum in the group of martial arts and was minimum in the group of complex coordination sports. It should be specially noted a small proportion of athletes who consumed specialized sports drinks - only 17% of athletes and more than half of them - cyclical sportsmen. Consumption of liquid food outside training has been observed in 76% of athletes. The mean volume of consumed liquid products varied by the user from 382 and 437 ml in complex coordination and game sports up to 504-553 ml in other sports. The daily fluid intake was maximum (2326 ml) in athletes engaged in martial arts, minimum (1009 ml) - in athletes of complex coordination sports.}, } @article {pmid30566634, year = {2019}, author = {Reher, D and Key, FM and Andrés, AM and Kelso, J}, title = {Immune Gene Diversity in Archaic and Present-day Humans.}, journal = {Genome biology and evolution}, volume = {11}, number = {1}, pages = {232-241}, pmid = {30566634}, issn = {1759-6653}, mesh = {Animals ; Genetic Variation ; Humans ; Immunity, Innate/*genetics ; *Major Histocompatibility Complex ; Neanderthals/*genetics/immunology ; }, abstract = {Genome-wide analyses of two Neandertals and a Denisovan have shown that these archaic humans had lower genetic heterozygosity than present-day people. A similar reduction in genetic diversity of protein-coding genes (gene diversity) was found in exome sequences of three Neandertals. Reduced gene diversity, particularly in genes involved in immunity, may have important functional consequences. In fact, it has been suggested that reduced diversity in immune genes may have contributed to Neandertal extinction. We therefore explored gene diversity in different human groups, and at different time points on the Neandertal lineage, with a particular focus on the diversity of genes involved in innate immunity and genes of the Major Histocompatibility Complex (MHC).We find that the two Neandertals and a Denisovan have similar gene diversity, all significantly lower than any present-day human. This is true across gene categories, with no gene set showing an excess decrease in diversity compared with the genome-wide average. Innate immune-related genes show a similar reduction in diversity to other genes, both in present-day and archaic humans. There is also no observable decrease in gene diversity over time in Neandertals, suggesting that there may have been no ongoing reduction in gene diversity in later Neandertals, although this needs confirmation with a larger sample size. In both archaic and present-day humans, genes with the highest levels of diversity are enriched for MHC-related functions. In fact, in archaic humans the MHC genes show evidence of having retained more diversity than genes involved only in the innate immune system.}, } @article {pmid30552618, year = {2018}, author = {Starshinova, A and Zinchenko, Y and Filatov, M and Denisova, N and Istomina, E and Landa, S and Burdakov, V and Churilov, L and Sapozhnikova, N and Pavlova, M and Stepanenko, T and Mayevskaya, V and Yablonskiy, P}, title = {Specific features of immune complexes in patients with sarcoidosis and pulmonary tuberculosis.}, journal = {Immunologic research}, volume = {66}, number = {6}, pages = {737-743}, pmid = {30552618}, issn = {1559-0755}, mesh = {Antigen-Antibody Complex/*immunology ; Diagnosis, Differential ; Humans ; Immunologic Tests/methods ; Lung/immunology ; Prospective Studies ; Sarcoidosis, Pulmonary/*diagnosis/*immunology ; Tuberculosis, Pulmonary/*diagnosis/*immunology ; }, abstract = {Clinical and radiological features of tuberculosis and sarcoidosis are quite overlapping, and therefore, a diagnostic dilemma often persists. There are no commonly accepted criteria for the diagnosis of sarcoidosis due to the lack of data on the etiology of the disease. The exclusion of tuberculosis in every patient with suspected sarcoidosis is a mandatory stage of diagnosis, especially in countries with a high burden of tuberculosis. A prospective study was conducted with two groups of patients: group I (n = 50)-patients with pulmonary sarcoidosis established according to standard criteria; group II (n = 28)-patients with pulmonary tuberculosis with bacterial excretion. The control group (n = 24) was presented by healthy subjects. The examination complex included x-ray, bacteriological, immunological (Mantoux test with 2 TE, TB.SPOT test), and histological methods. All patients and healthy subjects were assessed for immune complexes with the use of the dynamic light scattering (DLS) method and adding of "healthy lung tissue extract" antigens and specific tuberculosis antigens ESAT-6 and SFP-10 in vitro. Significant differences were found in determining specific immune complexes in patients with pulmonary sarcoidosis and pulmonary tuberculosis. Registration of specific immune complex formation with "healthy lung tissue extract" in 100% cases may indicate the autoimmune nature of sarcoidosis. The absence of the immune complex formation in response to ESAT-6/SFP-10 antigens can be used for the differential diagnosis of two diseases. The diagnostic significance of the DLS method was 100% for sarcoidosis and 92.2% for tuberculosis. The data obtained in the study allows not only understanding the etiology of sarcoidosis, but also obtaining new criteria for the differential diagnosis of tuberculosis and pulmonary sarcoidosis.}, } @article {pmid30546947, year = {2019}, author = {Pol, JG and Acuna, SA and Yadollahi, B and Tang, N and Stephenson, KB and Atherton, MJ and Hanwell, D and El-Warrak, A and Goldstein, A and Moloo, B and Turner, PV and Lopez, R and LaFrance, S and Evelegh, C and Denisova, G and Parsons, R and Millar, J and Stoll, G and Martin, CG and Pomoransky, J and Breitbach, CJ and Bramson, JL and Bell, JC and Wan, Y and Stojdl, DF and Lichty, BD and McCart, JA}, title = {Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials.}, journal = {Oncoimmunology}, volume = {8}, number = {1}, pages = {e1512329}, pmid = {30546947}, issn = {2162-4011}, abstract = {Multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. We evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (NHP) (Macaca fascicularis). Primates received a replication-deficient adenoviral prime, boosted by the oncolytic Maraba MG1 rhabdovirus. Both vectors expressed the human MAGE-A3. No severe adverse events were observed. Boosting with MG1-MAGEA3 induced an expansion of hMAGE-A3-specific CD4[+] and CD8[+] T-cells with the latter peaking at remarkable levels and persisting for several months. T-cells reacting against epitopes fully conserved between simian and human MAGE-A3 were identified. Humoral immunity was demonstrated by the detection of circulating MAGE-A3 antibodies. These preclinical data establish the capacity for the Ad:MG1 vaccination to engage multiple effector immune cell populations without causing significant toxicity in outbred NHPs. Clinical investigations utilizing this program for the treatment of MAGE-A3-positive solid malignancies are underway (NCT02285816, NCT02879760).}, } @article {pmid30545758, year = {2019}, author = {Banerjee, N and Polushina, T and Bettella, F and Steen, VM and Andreassen, OA and Le Hellard, S}, title = {Analysis of differentially methylated regions in great apes and extinct hominids provides support for the evolutionary hypothesis of schizophrenia.}, journal = {Schizophrenia research}, volume = {206}, number = {}, pages = {209-216}, doi = {10.1016/j.schres.2018.11.025}, pmid = {30545758}, issn = {1573-2509}, mesh = {Animals ; *Biological Evolution ; DNA Methylation/*genetics ; Epigenesis, Genetic/*genetics ; Genetic Predisposition to Disease/*genetics ; *Genome-Wide Association Study ; Gorilla gorilla ; Hominidae/*genetics ; Humans ; Neanderthals ; Pan troglodytes ; Polymorphism, Single Nucleotide ; Pongo ; Schizophrenia/*genetics ; }, abstract = {INTRODUCTION: The persistence of schizophrenia in human populations separated by geography and time led to the evolutionary hypothesis that proposes schizophrenia as a by-product of the higher cognitive abilities of modern humans. To explore this hypothesis, we used here an evolutionary epigenetics approach building on differentially methylated regions (DMRs) of the genome.

METHODS: We implemented a polygenic enrichment testing pipeline using the summary statistics of genome-wide association studies (GWAS) of schizophrenia and 12 other phenotypes. We investigated the enrichment of association of these traits across genomic regions with variable methylation between modern humans and great apes (orangutans, chimpanzees and gorillas; great ape DMRs) and between modern humans and recently extinct hominids (Neanderthals and Denisovans; hominid DMRs).

RESULTS: Regions that are hypo-methylated in humans compared to great apes show enrichment of association with schizophrenia only if the major histocompatibility complex (MHC) region is included. With the MHC region removed from the analysis, only a modest enrichment for SNPs of low effect persists. The INRICH pipeline confirms this finding after rigorous permutation and bootstrapping procedures.

CONCLUSION: The analyses of regions with differential methylation changes in humans and great apes do not provide compelling evidence of enrichment of association with schizophrenia, in contrast to our previous findings on more recent methylation differences between modern humans, Neanderthals and Denisovans. Our results further support the evolutionary hypothesis of schizophrenia and indicate that the origin of some of the genetic susceptibility factors of schizophrenia may lie in recent human evolution.}, } @article {pmid30538215, year = {2018}, author = {Denisova, TG and Gerasimova, LI and Pakhmutova, NL and Mahesh, S and Vithoulkas, G}, title = {Individualized Homeopathic Therapy in a Case of Obesity, Dysfunctional Uterine Bleeding, and Autonomic Dystonia.}, journal = {The American journal of case reports}, volume = {19}, number = {}, pages = {1474-1479}, pmid = {30538215}, issn = {1941-5923}, mesh = {Adult ; Dystonia/complications/*therapy ; Female ; *Homeopathy ; Humans ; Metrorrhagia/complications/*therapy ; Obesity/complications/*therapy ; }, abstract = {BACKGROUND Obesity is one of the leading causes of morbidity and mortality globally and challenging to treat because of the multifactorial etiology and presentation. Individualized homeopathy takes into account factors that led to a patient's health condition and hence may have a role in the treatment of obesity and related co-morbidities; co-morbidities that may arising from the same etiology may respond as a whole to homeopathy treatment. CASE REPORT A 39-year-old Russian female who developed multiple problems after severe emotional stress was treated with individualized classical homeopathic therapy. Obesity, dysfunctional uterine bleeding, and dysautonomia were pathologies that showed improvement. CONCLUSIONS The response in this patient's case, supports the need for further investigation on the relevance of individualized homeopathy in these related conditions.}, } @article {pmid30450552, year = {2019}, author = {Safronova, EI and Dydykin, SS and Grigorevskiy, ED and Tverye, EA and Kolchenko, SI and Piskunova, NN and Denisova, AV and Titova, GP and Parshin, VD and Romanova, OA and Panteleyev, AA}, title = {Experimental animal model for assessment of tracheal epithelium regeneration.}, journal = {The Laryngoscope}, volume = {129}, number = {6}, pages = {E213-E219}, doi = {10.1002/lary.27480}, pmid = {30450552}, issn = {1531-4995}, mesh = {Animals ; Disease Models, Animal ; Epithelium/*pathology ; Rabbits ; Regeneration/*physiology ; Respiratory Mucosa/*pathology ; Tissue Engineering/*methods ; *Tissue Scaffolds ; Trachea/injuries/pathology/*surgery ; Tracheal Diseases/pathology/*surgery ; }, abstract = {OBJECTIVES/HYPOTHESIS: To develop an experimental model in rabbits for assessment of tracheal epithelium regeneration through application of either natural or artificial polymer scaffolds.

STUDY DESIGN: First, we identified the size of full-thickness mucosal defect, which does not allow self-healing (a "critical defect"), thus representing an adequate experimental model for regenerative therapy of tracheal epithelium damage. Then, two methods of polymer scaffold fixation at the site of the epithelium defect were compared: suturing and fixation with a stent. This was done through: 1) formation of a full-thickness anterolateral mucosal defect by tracheal mucosa excision; and 2) fixation of the scaffold at the site of the tracheal epithelium defect using sutures (through a tracheal wall "window") or a vascular stent (through a small tracheal incision).

RESULTS: The dimension of a critical anterolateral mucosal defect of the trachea for rabbits was found to be 1.5 cm in length and more than 50% of the tracheal circumference. Fixation of the scaffold with a stent proved to be more efficient due to a uniform distribution of the pressure over the entire surface of the scaffold, whereas the suturing of the scaffold provided unsatisfactory results. In addition, fixation of the scaffold by suturing required formation of a large "window" in the tracheal wall. Thus, using the stent appeared to be technically less complicated and much less traumatic as compared to suturing.

CONCLUSION: We present an experimental in vivo animal model of tracheal epithelium injury and recovery. It can be effectively used with certain further modifications as a basis for routine testing of bioengineered constructs.

LEVEL OF EVIDENCE: NA Laryngoscope, 129:E213-E219, 2019.}, } @article {pmid30362431, year = {2018}, author = {Malinova, LI and Furman, NV and Dolotovskaya, PV and Chernousova, LA and Denisova, TP}, title = {[ADP-Induced Recalcified Blood Clotting Time as a Marker of Rethrombosis Risk and Effectiveness of Antiplatelet Therapy in Acute Coronary Syndrome].}, journal = {Kardiologiia}, volume = {58}, number = {6}, pages = {5-12}, pmid = {30362431}, issn = {0022-9040}, mesh = {Acute Coronary Syndrome/*blood/complications/*drug therapy ; Adenosine Diphosphate/blood ; Adult ; Aspirin/therapeutic use ; Biomarkers ; Humans ; Male ; Platelet Aggregation Inhibitors/adverse effects/*therapeutic use ; Recurrence ; Risk Factors ; Thrombosis/etiology/*prevention & control ; *Whole Blood Coagulation Time ; }, abstract = {PURPOSE: to assess the possibility of the use of ADP induced blood-clotting time measurement in clinical practice prognostication of the course of acute coronary syndrome (ACS) and assessment of effectiveness of antiplatelet therapy (APT).

MATERIALS AND METHODS: We enrolled in the study 163 male patients admitted to the coronary unit for acute coronary syndrome (ACS) and 38 male practically healthy volunteers (PHV). ADP induced blood-clotting time (ADP BCT) was measured as time (sec) between addition of ADP (10 μcmol) to recalcificated sample of citrate blood and clot formation. In healthy volunteers ADP BCT was determined before and 45 minutes after oral administration of acetylsalicylic acid (ASA, 250 mg). Risk of cardiovascular death was calculated using the GRACE score. Platelet function tests were performed by optical aggregometry. Follow-up period for patients with ACS was 24 months. The primary end point (PEP) was the composite of cardiovascular death and rehospitalization.

RESULTS: In ACS patients ADP BCT was significantly lower than in PHV: 134.8 (109.9; 161.3) vs 85.7 (60.5; 108.7) sec, p=0.015. In PHV ASA increased ADP BCT - 103.2 (95.1; 130.7) vs 133.1 (102.8; 154.3) sec, p=0.041. ADP BCT correlated with age in both PHV and patients (R= -0.431, p.}, } @article {pmid32598648, year = {2018}, author = {Mustafina, SV and Ovsyannikova, AK and Voevoda, MI and Denisova, DV and Sherbakova, LV and Rymar, OD}, title = {[The prevalence of components of metabolic syndrome in the patients with diabetes melitus type 2 and mody diabetes in young people of Novosibirsk].}, journal = {Terapevticheskii arkhiv}, volume = {90}, number = {10}, pages = {55-59}, doi = {10.26442/terarkh201890104-59}, pmid = {32598648}, issn = {0040-3660}, abstract = {AIM: To estimate the prevalence of type 2 diabetes mellitus (DM2) and MODY diabetes as well as the prevalence of metabolic syndrome (MS) components for these types of diabetes in the young population of the city of Novosibirsk.

MATERIALS AND METHODS: In 2013-2017 years a population survey was conducted of a random representative sample of the population of 25-45 years of both sexes, residents of one of the typical districts of Novosibirsk. WHO criteria (1999-2013) were used for the diagnosis of diabetes: fasting blood glucose ≥7.0 mmol / l after an 8-hour fasting. Also group with DM2 included persons with a fasting blood glucose level.}, } @article {pmid30289977, year = {2019}, author = {Johannessen, TC and Hasan-Olive, MM and Zhu, H and Denisova, O and Grudic, A and Latif, MA and Saed, H and Varughese, JK and Røsland, GV and Yang, N and Sundstrøm, T and Nordal, A and Tronstad, KJ and Wang, J and Lund-Johansen, M and Simonsen, A and Janji, B and Westermarck, J and Bjerkvig, R and Prestegarden, L}, title = {Thioridazine inhibits autophagy and sensitizes glioblastoma cells to temozolomide.}, journal = {International journal of cancer}, volume = {144}, number = {7}, pages = {1735-1745}, doi = {10.1002/ijc.31912}, pmid = {30289977}, issn = {1097-0215}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/pharmacology ; Autophagosomes/drug effects ; Autophagy/*drug effects ; Brain Neoplasms/*drug therapy/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Resistance, Neoplasm/drug effects ; Drug Synergism ; Glioblastoma/*drug therapy/genetics ; Humans ; Lysosomes/drug effects ; Mice ; Synthetic Lethal Mutations ; Temozolomide/*administration & dosage/therapeutic use ; Thioridazine/*administration & dosage/pharmacology ; Xenograft Model Antitumor Assays ; }, abstract = {Glioblastoma multiforme (GBM) has a poor prognosis with an overall survival of 14-15 months after surgery, radiation and chemotherapy using temozolomide (TMZ). A major problem is that the tumors acquire resistance to therapy. In an effort to improve the therapeutic efficacy of TMZ, we performed a genome-wide RNA interference (RNAi) synthetic lethality screen to establish a functional gene signature for TMZ sensitivity in human GBM cells. We then queried the Connectivity Map database to search for drugs that would induce corresponding changes in gene expression. By this approach we identified several potential pharmacological sensitizers to TMZ, where the most potent drug was the established antipsychotic agent Thioridazine, which significantly improved TMZ sensitivity while not demonstrating any significant toxicity alone. Mechanistically, we show that the specific chemosensitizing effect of Thioridazine is mediated by impairing autophagy, thereby preventing adaptive metabolic alterations associated with TMZ resistance. Moreover, we demonstrate that Thioridazine inhibits late-stage autophagy by impairing fusion between autophagosomes and lysosomes. Finally, Thioridazine in combination with TMZ significantly inhibits brain tumor growth in vivo, demonstrating the potential clinical benefits of compounds targeting the autophagy-lysosome pathway. Our study emphasizes the feasibility of exploiting drug repurposing for the design of novel therapeutic strategies for GBM.}, } @article {pmid30278065, year = {2018}, author = {Hoover, KC}, title = {Intragenus (Homo) variation in a chemokine receptor gene (CCR5).}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0204989}, pmid = {30278065}, issn = {1932-6203}, mesh = {Animals ; Gene Expression Regulation ; *Genetic Variation ; Hominidae/*genetics ; Humans ; Receptors, CCR5/*genetics ; Species Specificity ; }, abstract = {Humans have a comparatively higher rate of more polymorphisms in regulatory regions of the primate CCR5 gene, an immune system gene with both general and specific functions. This has been interpreted as allowing flexibility and diversity of gene expression in response to varying disease loads. A broad expression repertoire is useful to humans-the only globally distributed primate-due to our unique adaptive pattern that increased pathogen exposure and disease loads (e.g., sedentism, subsistence practices). The main objective of the study was to determine if the previously observed human pattern of increased variation extended to other members of our genus, Homo. The data for this study are mined from the published genomes of extinct hominins (four Neandertals and two Denisovans), an ancient human (Ust'-Ishim), and modern humans (1000 Genomes). An average of 15 polymorphisms per individual were found in human populations (with a total of 262 polymorphisms). There were 94 polymorphisms identified across extinct Homo (an average of 13 per individual) with 41 previously observed in modern humans and 53 novel polymorphisms (32 in Denisova and 21 in Neandertal). Neither the frequency nor distribution of polymorphisms across gene regions exhibit significant differences within the genus Homo. Thus, humans are not unique with regards to the increased frequency of regulatory polymorphisms and the evolution of variation patterns across CCR5 gene appears to have originated within the genus. A broader evolutionary perspective on regulatory flexibility may be that it provided an advantage during the transition to confrontational foraging (and later hunting) that altered human-environment interaction as well as during migration to Eurasia and encounters with novel pathogens.}, } @article {pmid30226838, year = {2018}, author = {Skov, L and Hui, R and Shchur, V and Hobolth, A and Scally, A and Schierup, MH and Durbin, R}, title = {Detecting archaic introgression using an unadmixed outgroup.}, journal = {PLoS genetics}, volume = {14}, number = {9}, pages = {e1007641}, pmid = {30226838}, issn = {1553-7404}, support = {207492/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; WT207492/WT_/Wellcome Trust/United Kingdom ; WT206194/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Asian People/genetics ; Black People/genetics ; Fossils ; Genome, Human/*genetics ; Hominidae/*genetics ; Humans ; Hybridization, Genetic/*genetics ; Native Hawaiian or Other Pacific Islander/genetics ; Neanderthals/*genetics ; Phylogeny ; White People/genetics ; }, abstract = {Human populations outside of Africa have experienced at least two bouts of introgression from archaic humans, from Neanderthals and Denisovans. In Papuans there is prior evidence of both these introgressions. Here we present a new approach to detect segments of individual genomes of archaic origin without using an archaic reference genome. The approach is based on a hidden Markov model that identifies genomic regions with a high density of single nucleotide variants (SNVs) not seen in unadmixed populations. We show using simulations that this provides a powerful approach to identifying segments of archaic introgression with a low rate of false detection, given data from a suitable outgroup population is available, without the archaic introgression but containing a majority of the variation that arose since initial separation from the archaic lineage. Furthermore our approach is able to infer admixture proportions and the times both of admixture and of initial divergence between the human and archaic populations. We apply the model to detect archaic introgression in 89 Papuans and show how the identified segments can be assigned to likely Neanderthal or Denisovan origin. We report more Denisovan admixture than previous studies and find a shift in size distribution of fragments of Neanderthal and Denisovan origin that is compatible with a difference in admixture time. Furthermore, we identify small amounts of Denisova ancestry in South East Asians and South Asians.}, } @article {pmid30209350, year = {2018}, author = {Clyde, D}, title = {The girl with Neanderthal and Denisovan parents.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {668-669}, doi = {10.1038/s41576-018-0054-6}, pmid = {30209350}, issn = {1471-0064}, mesh = {Fathers ; Female ; Genome ; Humans ; Male ; Mothers ; Neanderthals/*genetics ; Parents ; }, } @article {pmid30185153, year = {2018}, author = {Dergunova, LV and Filippenkov, IB and Stavchansky, VV and Denisova, AE and Yuzhakov, VV and Mozerov, SA and Gubsky, LV and Limborska, SA}, title = {Genome-wide transcriptome analysis using RNA-Seq reveals a large number of differentially expressed genes in a transient MCAO rat model.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {655}, pmid = {30185153}, issn = {1471-2164}, support = {16-14-00077//Russian Science Foundation/ ; }, mesh = {Animals ; Brain/diagnostic imaging/metabolism ; Disease Models, Animal ; *Gene Expression Profiling ; Infarction, Middle Cerebral Artery/complications/diagnostic imaging/*genetics/pathology ; Magnetic Resonance Imaging ; Rats ; Reperfusion Injury/complications ; *Sequence Analysis, RNA ; Signal Transduction/genetics ; }, abstract = {BACKGROUND: The transient middle cerebral artery occlusion (tMCAO) model is used for studying the molecular mechanisms of ischemic damage and neuroprotection. Numerous studies have demonstrated the role of individual genes and associated signaling pathways in the pathogenesis of ischemic stroke. Here, the tMCAO model was used to investigate the genome-wide response of the transcriptome of rat brain tissues to the damaging effect of ischemia and subsequent reperfusion.

RESULTS: Magnetic resonance imaging and histological examination showed that the model of focal ischemia based on endovascular occlusion of the right middle cerebral artery for 90 min using a monofilament, followed by restoration of the blood flow, led to reproducible localization of ischemic damage in the subcortical structures of the brain. High-throughput RNA sequencing (RNA-Seq) revealed the presence of differentially expressed genes (DEGs) in subcortical structures of rat brains resulting from hemisphere damage by ischemia after tMCAO, as well as in the corresponding parts of the brains of sham-operated animals. Real-time reverse transcription polymerase chain reaction expression analysis of 20 genes confirmed the RNA-Seq results. We identified 469 and 1939 genes that exhibited changes in expression of > 1.5-fold at 4.5 and 24 h after tMCAO, respectively. Interestingly, we found 2741 and 752 DEGs under ischemia-reperfusion and sham-operation conditions at 24 h vs. 4.5 h after tMCAO, respectively. The activation of a large number of genes involved in inflammatory, immune and stress responses, apoptosis, ribosome function, DNA replication and other processes was observed in ischemia-reperfusion conditions. Simultaneously, massive down-regulation of the mRNA levels of genes involved in the functioning of neurotransmitter systems was recorded. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that dozens of signaling pathways were associated with DEGs in ischemia-reperfusion conditions.

CONCLUSIONS: The data obtained revealed a global profile of gene expression in the rat brain sub-cortex under tMCAO conditions that can be used to identify potential therapeutic targets in the development of new strategies for the prevention and treatment of ischemic stroke.}, } @article {pmid30149747, year = {2019}, author = {Alexeeva, E and Dvoryakovskaya, T and Denisova, R and Sleptsova, T and Isaeva, K and Chomahidze, A and Fetisova, A and Mamutova, A and Alshevskaya, A and Gladkikh, V and Moskalev, A}, title = {Comparative analysis of the etanercept efficacy in children with juvenile idiopathic arthritis under the age of 4 years and children of older age groups using the propensity score matching method.}, journal = {Modern rheumatology}, volume = {29}, number = {5}, pages = {848-855}, doi = {10.1080/14397595.2018.1516329}, pmid = {30149747}, issn = {1439-7609}, mesh = {Adolescent ; Age Factors ; Aged ; Antirheumatic Agents/*therapeutic use ; Arthritis, Juvenile/*drug therapy ; Child ; Child, Preschool ; Etanercept/*therapeutic use ; Female ; Humans ; Male ; Propensity Score ; }, abstract = {Objective: The aim of this study was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the data with those for older age groups. Methods: Three groups comprising 34 patients each (total of 102 patients) were selected using the propensity score matching (PSM) method. The study group (patients under the age of 4 years; the Junior group (JNR)) was compared with patients of the older age groups, adjusted for criteria such as gender, JIA category, JIA severity, and either age at disease onset (the Reference by Age of disease Onset (RAO) group) or disease duration (the Reference by Disease Duration (RDD) group). Results: All three groups showed a good response to ETA therapy. During the follow-up period, only 4 (3.9%) patients failed to reach American College of Rheumatology (ACR) Pediatric criteria improvement at ACR50 level. In the JNR group, 82.4% of patients achieved ACR90 within a median time of 3 months (IQR, 3-6 months), which was a better result compared to the other two groups: 61.8% (RAO group) and 58.8% (RDD group) of patients achieved ACR90 within 6 (Interquartile Range (IQR), 3-9) months (p = .028). Three (9%) patients in the JNR group and none of the RDD and RAO groups discontinued treatment because of clinical remission (p = .045). Conclusion: An analysis of the ETA efficacy in different age groups comparable in terms of the diagnosis and disease severity demonstrated a higher efficacy of earlier ETA therapy in children of the same age at disease onset. In children at the early stage of arthritis (≤ 2.5 years long), ETA was more efficient in those with an earlier disease onset.}, } @article {pmid30147753, year = {2018}, author = {Guichard, E and Peona, V and Malagoli Tagliazucchi, G and Abitante, L and Jagoda, E and Musella, M and Ricci, M and Rubio-Roldán, A and Sarno, S and Luiselli, D and Pettener, D and Taccioli, C and Pagani, L and Garcia-Perez, JL and Boattini, A}, title = {Impact of non-LTR retrotransposons in the differentiation and evolution of anatomically modern humans.}, journal = {Mobile DNA}, volume = {9}, number = {}, pages = {28}, pmid = {30147753}, issn = {1759-8753}, support = {/WT_/Wellcome Trust/United Kingdom ; 295733/ERC_/European Research Council/International ; }, abstract = {BACKGROUND: Transposable elements are biologically important components of eukaryote genomes. In particular, non-LTR retrotransposons (N-LTRrs) played a key role in shaping the human genome throughout evolution. In this study, we compared retrotransposon insertions differentially present in the genomes of Anatomically Modern Humans, Neanderthals, Denisovans and Chimpanzees, in order to assess the possible impact of retrotransposition in the differentiation of the human lineage.

RESULTS: We first identified species-specific N-LTRrs and established their distribution in present day human populations. These analyses shortlisted a group of N-LTRr insertions that were found exclusively in Anatomically Modern Humans. These insertions are associated with an increase in the number of transcriptional/splicing variants of those genes they inserted in. The analysis of the functionality of genes containing human-specific N-LTRr insertions reflects changes that occurred during human evolution. In particular, the expression of genes containing the most recent N-LTRr insertions is enriched in the brain, especially in undifferentiated neurons, and these genes associate in networks related to neuron maturation and migration. Additionally, we identified candidate N-LTRr insertions that have likely produced new functional variants exclusive to modern humans, whose genomic loci show traces of positive selection.

CONCLUSIONS: Our results strongly suggest that N-LTRr impacted our differentiation as a species, most likely inducing an increase in neural complexity, and have been a constant source of genomic variability all throughout the evolution of the human lineage.}, } @article {pmid30135579, year = {2018}, author = {Slon, V and Mafessoni, F and Vernot, B and de Filippo, C and Grote, S and Viola, B and Hajdinjak, M and Peyrégne, S and Nagel, S and Brown, S and Douka, K and Higham, T and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Kelso, J and Meyer, M and Prüfer, K and Pääbo, S}, title = {The genome of the offspring of a Neanderthal mother and a Denisovan father.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {113-116}, pmid = {30135579}, issn = {1476-4687}, support = {324139/ERC_/European Research Council/International ; 694707/ERC_/European Research Council/International ; 715069/ERC_/European Research Council/International ; }, mesh = {Alleles ; Animals ; Fathers ; Female ; Gene Flow/genetics ; Genome ; Genomics ; History, Ancient ; Hominidae/*genetics ; Humans ; Hybridization, Genetic/*genetics ; Male ; Mothers ; Neanderthals/*genetics ; Time Factors ; }, abstract = {Neanderthals and Denisovans are extinct groups of hominins that separated from each other more than 390,000 years ago[1,2]. Here we present the genome of 'Denisova 11', a bone fragment from Denisova Cave (Russia)[3] and show that it comes from an individual who had a Neanderthal mother and a Denisovan father. The father, whose genome bears traces of Neanderthal ancestry, came from a population related to a later Denisovan found in the cave[4-6]. The mother came from a population more closely related to Neanderthals who lived later in Europe[2,7] than to an earlier Neanderthal found in Denisova Cave[8], suggesting that migrations of Neanderthals between eastern and western Eurasia occurred sometime after 120,000 years ago. The finding of a first-generation Neanderthal-Denisovan offspring among the small number of archaic specimens sequenced to date suggests that mixing between Late Pleistocene hominin groups was common when they met.}, } @article {pmid30135540, year = {2018}, author = {Warren, M}, title = {Mum's a Neanderthal, Dad's a Denisovan: First discovery of an ancient-human hybrid.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {417-418}, doi = {10.1038/d41586-018-06004-0}, pmid = {30135540}, issn = {1476-4687}, } @article {pmid30121933, year = {2018}, author = {Zotova, TY and Blagonravov, ML and Lapaev, NN and Denisova, AP}, title = {Hemodynamic Allostasis of Pregnant Women against the Background of Preeclampsia.}, journal = {Bulletin of experimental biology and medicine}, volume = {165}, number = {4}, pages = {440-444}, doi = {10.1007/s10517-018-4189-4}, pmid = {30121933}, issn = {1573-8221}, mesh = {Adult ; Allostasis ; Blood Pressure/physiology ; Circadian Rhythm ; Female ; Heart Rate/physiology ; Hemodynamics/*physiology ; Humans ; Hypertension/physiopathology ; Pre-Eclampsia/*physiopathology ; Pregnancy ; Young Adult ; }, abstract = {We analyzed diurnal hemodynamic parameters (HR, systolic BP, and diastolic BP) recorded from two groups of edematous and preeclamptic pregnant women. The unidirectional character of changes in the control over the functional state of cardiovascular system was revealed except for the indices, which mark a pathological process: elevated diurnal BP in preeclampsia and diminished percentage of oscillation power in edematous patients. Uniformity of the regulatory changes in patients with and without arterial hypertension can be viewed as manifestation of allostasis developed by the cardiovascular system during pregnancy. In preeclampsia, the greater allostatic load was reflected by the changes in diurnal, daytime, and nighttime BP and in the circadian index calculated for HR, systolic BP, and diastolic BP. In edematous patients, elevation of allostatic load was indicated by the percentage of ultradian rhythms.}, } @article {pmid30076299, year = {2018}, author = {Helsen, CW and Hammill, JA and Lau, VWC and Mwawasi, KA and Afsahi, A and Bezverbnaya, K and Newhook, L and Hayes, DL and Aarts, C and Bojovic, B and Denisova, GF and Kwiecien, JM and Brain, I and Derocher, H and Milne, K and Nelson, BH and Bramson, JL}, title = {The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {3049}, pmid = {30076299}, issn = {2041-1723}, mesh = {Adoptive Transfer ; Animals ; CD28 Antigens/immunology ; Cell Line, Tumor ; Cytokines/blood/metabolism ; Cytotoxicity, Immunologic ; Female ; Genetic Engineering ; HEK293 Cells ; Humans ; Immunotherapy, Adoptive/methods ; Lentivirus/genetics ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred NOD ; Protein Engineering ; Receptor, ErbB-2/immunology ; Receptors, Antigen/genetics/*immunology ; Receptors, Chimeric Antigen/genetics/*immunology ; Recombinant Proteins/*immunology ; Single-Domain Antibodies ; T-Cell Antigen Receptor Specificity/genetics/*immunology ; T-Lymphocytes/*immunology ; T-Lymphocytes, Cytotoxic/immunology ; Vision, Ocular ; Xenograft Model Antitumor Assays ; }, abstract = {Engineering T cells with chimeric antigen receptors (CARs) is an effective method for directing T cells to attack tumors, but may cause adverse side effects such as the potentially lethal cytokine release syndrome. Here the authors show that the T cell antigen coupler (TAC), a chimeric receptor that co-opts the endogenous TCR, induces more efficient anti-tumor responses and reduced toxicity when compared with past-generation CARs. TAC-engineered T cells induce robust and antigen-specific cytokine production and cytotoxicity in vitro, and strong anti-tumor activity in a variety of xenograft models including solid and liquid tumors. In a solid tumor model, TAC-T cells outperform CD28-based CAR-T cells with increased anti-tumor efficacy, reduced toxicity, and faster tumor infiltration. Intratumoral TAC-T cells are enriched for Ki-67[+] CD8[+] T cells, demonstrating local expansion. These results indicate that TAC-T cells may have a superior therapeutic index relative to CAR-T cells.}, } @article {pmid30072539, year = {2018}, author = {Tucci, S and Vohr, SH and McCoy, RC and Vernot, B and Robinson, MR and Barbieri, C and Nelson, BJ and Fu, W and Purnomo, GA and Sudoyo, H and Eichler, EE and Barbujani, G and Visscher, PM and Akey, JM and Green, RE}, title = {Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {511-516}, pmid = {30072539}, issn = {1095-9203}, support = {/ERC_/European Research Council/International ; /HHMI/Howard Hughes Medical Institute/United States ; R01 GM110068/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Biological/*genetics ; Animals ; *Biological Evolution ; Body Height/*genetics ; Dwarfism/*genetics ; Gene Flow ; Genome, Human ; Humans ; Indonesia ; *Islands ; Neanderthals/genetics ; Population/*genetics ; *Selection, Genetic ; }, abstract = {Flores Island, Indonesia, was inhabited by the small-bodied hominin species Homo floresiensis, which has an unknown evolutionary relationship to modern humans. This island is also home to an extant human pygmy population. Here we describe genome-scale single-nucleotide polymorphism data and whole-genome sequences from a contemporary human pygmy population living on Flores near the cave where H. floresiensis was found. The genomes of Flores pygmies reveal a complex history of admixture with Denisovans and Neanderthals but no evidence for gene flow with other archaic hominins. Modern individuals bear the signatures of recent positive selection encompassing the FADS (fatty acid desaturase) gene cluster, likely related to diet, and polygenic selection acting on standing variation that contributed to their short-stature phenotype. Thus, multiple independent instances of hominin insular dwarfism occurred on Flores.}, } @article {pmid30064273, year = {2020}, author = {Morgunov, LY and Denisova, IA and Rozhkova, TI and Stakhovskaya, LV and Skvortsova, VI}, title = {Hypogonadism and its treatment following ischaemic stroke in men with type 2 diabetes mellitus.}, journal = {The aging male : the official journal of the International Society for the Study of the Aging Male}, volume = {23}, number = {1}, pages = {71-80}, doi = {10.1080/13685538.2018.1487932}, pmid = {30064273}, issn = {1473-0790}, mesh = {Aged ; Biomarkers/blood ; Diabetes Mellitus, Type 2/*complications ; Gonadal Steroid Hormones/blood ; Humans ; Hypogonadism/*drug therapy/epidemiology/*etiology ; Male ; Middle Aged ; Russia/epidemiology ; Stroke/*complications ; Testosterone/*analogs & derivatives/therapeutic use ; }, abstract = {Premature mortality in Russia is a major socio-economic problem, especially from acute cerebrovascular diseases which constitute 21.4% of the total mortality and is a considerable contributor to chronic disability. Risk of vascular catastrophe is higher in males than females, thought, in part, due to anti-atherosclerotic effects of oestrogens in females whilst an associated age-related deficiency of testosterone is observed in men. Clinical symptoms such as high blood pressure, changes in lipid profile, insulin resistance, obesity, and blood coagulation factors often accompany declining testosterone in males and reduced total testosterone is considered a cardiovascular risk factor. In the present study, the prevalence of hypogonadism in men who had suffered ischaemic stroke was evaluated along with the efficacy of testosterone undecanoate injections (TU) in patients with testosterone deficiency and type-2 diabetes (T2DM) in the acute phase of hemispheric ischaemic stroke. Hypogonadism was present in 66.3% of patients with ischaemic stroke, 50% with T2DM, and 26.3% without T2DM, respectively. TU treatment, at both the 2 and 5-year observation points, demonstrated significant improvements in biochemical, physical, and mental parameters. This supports that testosterone deficiency is a contributing factor in ischaemic events and that long-term testosterone therapy could play an important role in patient recovery.}, } @article {pmid30022013, year = {2018}, author = {Dolgova, O and Lao, O}, title = {Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes.}, journal = {Genes}, volume = {9}, number = {7}, pages = {}, pmid = {30022013}, issn = {2073-4425}, abstract = {The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered. It is currently known that AMH interbred with archaic hominins once they left the African continent. Current non-African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.}, } @article {pmid30010009, year = {2019}, author = {Denisova, K}, title = {Neurobiology, not artifacts: Challenges and guidelines for imaging the high risk infant.}, journal = {NeuroImage}, volume = {185}, number = {}, pages = {624-640}, doi = {10.1016/j.neuroimage.2018.07.023}, pmid = {30010009}, issn = {1095-9572}, mesh = {*Artifacts ; Autism Spectrum Disorder/*diagnostic imaging ; Female ; *Head Movements ; Humans ; Infant ; Magnetic Resonance Imaging/methods ; Male ; Neurobiology ; Neuroimaging/methods ; }, abstract = {The search for the brain-basis of atypical development in human infants is challenging because the process of imaging and the generation of the MR signal itself relies on assumptions that reflect biophysical properties of the brain tissue. These assumptions are not inviolate, have been questioned by recent empirical evidence from high risk infant-sibling studies, and to date remain largely underexamined at the between-group level. In particular, I consider recent work showing that infants at High vs. Low familial risk (HR vs. LR, respectively) for developing Autism Spectrum Disorders (ASD) have atypical patterns of head movements during an MR scan that are functionally important-they are linked to future learning trajectories in toddlerhood. Addressing head movement issues in neuroimaging analyses in infant research as well as understanding the causes of these movements from a developmental perspective requires acknowledging the complexity of this endeavor. For example, head movement signatures in infants can interact with experimental task conditions (such as listening to language compared to sleeping), autism risk, and age. How can new knowledge about newborns' individual, subject-specific behavioral differences which may impact MR signal acquisition and statistical inference ignite critical thinking for the field of infant brain imaging across the spectrum of typical and atypical development? Early behavioral differences between HR and LR infant cohorts that are often examples of "artifactual" confounds in MR work provide insight into nascent neurobiological differences, including biophysical tissue properties and hemodynamic response variability, in these and related populations at risk for atypical development. Are these neurobiological drivers of atypical development? This work identifies important knowledge gaps and suggests guidelines at the leading edge of baby imaging science to transform our understanding of atypical brain development in humans. The precise study of the neurobiological underpinnings of atypical development in humans calls for approaches including quantitative MRI (qMRI) pulse sequences, multi-modal imaging (including DTI, MRS, as well as MEG), and infant-specific HRF shapes when modeling BOLD signal.}, } @article {pmid30004998, year = {2021}, author = {Raevis, JJ and Denisova, K and Mechel, E and Shrier, EM}, title = {MOSAICISM AS A PROPOSED MECHANISM FOR ASYMMETRIC RETINAL TESSELLATIONS.}, journal = {Retinal cases & brief reports}, volume = {15}, number = {3}, pages = {214-217}, doi = {10.1097/ICB.0000000000000770}, pmid = {30004998}, issn = {1937-1578}, mesh = {Axial Length, Eye/pathology ; Female ; Fluorescein Angiography ; Humans ; Middle Aged ; *Mosaicism ; Retinal Diseases/*genetics/physiopathology ; Tomography, Optical Coherence ; Visual Acuity/physiology ; }, abstract = {BACKGROUND/PURPOSE: Report a case of markedly asymmetric retinal tessellations and propose mosaicism as a mechanism.

METHODS AND RESULTS: A 59-year-old pseudophakic woman presented with uncorrected 20/20 vision and was found to have markedly different retinal tessellation appearances in both eyes. The axial lengths were 25.66 mm and 25.88 mm in the right and left eyes, respectively, and no significant asymmetrical choroidal thinning was seen on optical coherence tomography or optical coherence tomography angiography. Fluorescein angiogram showed significant hyperfluorescence, representing the underlying choroid, which correlated with the tessellation patterns in the left eye. She had no other ocular or systemic findings such as stripes or whorled skin.

CONCLUSION: This is the first reported case of markedly asymmetric retinal tessellation patterns that are not due to asymmetric axial myopia or choroidal thinning. We propose that mosaicism is a possible mechanism causing this finding.}, } @article {pmid29995885, year = {2018}, author = {Zhao, G and Walsh, K and Long, J and Gui, W and Denisova, K}, title = {Reduced structural complexity of the right cerebellar cortex in male children with autism spectrum disorder.}, journal = {PloS one}, volume = {13}, number = {7}, pages = {e0196964}, pmid = {29995885}, issn = {1932-6203}, mesh = {Autism Spectrum Disorder/*diagnostic imaging/pathology/physiopathology ; Case-Control Studies ; Cerebellar Cortex/*diagnostic imaging/pathology/physiopathology ; Child ; Child Development/physiology ; Cognition/*physiology ; Fractals ; Gray Matter/*diagnostic imaging/pathology/physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; Sex Factors ; }, abstract = {The cerebellum contains 80% of all neurons in the human brain and contributes prominently to implicit learning and predictive processing across motor, sensory, and cognitive domains. As morphological features of the cerebellum in atypically developing individuals remain unexplored in-vivo, this is the first study to use high-resolution 3D fractal analysis to estimate fractal dimension (FD), a measure of structural complexity of an object, of the left and right cerebellar cortex (automatically segmented from Magnetic Resonance Images using FreeSurfer), in male children with Autism Spectrum Disorders (ASD) (N = 20; mean age: 8.8 years old, range: 7.13-10.27) and sex, age, verbal-IQ, and cerebellar volume-matched typically developing (TD) boys (N = 18; mean age: 8.9 years old, range: 6.47-10.52). We focus on an age range within the 'middle and late childhood' period of brain development, between 6 and 12 years. A Mann-Whitney U test revealed a significant reduction in the FD of the right cerebellar cortex in ASD relative to TD boys (P = 0.0063, Bonferroni-corrected), indicating flatter and less regular surface protrusions in ASD relative to TD males. Consistent with the prediction that the cerebellum participates in implicit learning, those ASD boys with a higher (vs. lower) PIQ>VIQ difference showed higher, more normative complexity values, closer to TD children, providing new insight on our understanding of the neurological basis of differences in verbal and performance cognitive abilities that often characterize individuals with ASD.}, } @article {pmid29960127, year = {2018}, author = {Lazaridis, I}, title = {The evolutionary history of human populations in Europe.}, journal = {Current opinion in genetics & development}, volume = {53}, number = {}, pages = {21-27}, doi = {10.1016/j.gde.2018.06.007}, pmid = {29960127}, issn = {1879-0380}, mesh = {Animals ; DNA, Ancient ; Europe ; *Genetics, Population ; Genome, Human/*genetics ; *Genomics ; Human Migration ; Humans ; Neanderthals/genetics ; White People/*genetics ; }, abstract = {I review the evolutionary history of human populations in Europe with an emphasis on what has been learned in recent years through the study of ancient DNA. Human populations in Europe ∼430-39kya (archaic Europeans) included Neandertals and their ancestors, who were genetically differentiated from other archaic Eurasians (such as the Denisovans of Siberia), as well as modern humans. Modern humans arrived to Europe by ∼45kya, and are first genetically attested by ∼39kya when they were still mixing with Neandertals. The first Europeans who were recognizably genetically related to modern ones appeared in the genetic record shortly thereafter at ∼37kya. At ∼15kya a largely homogeneous set of hunter-gatherers became dominant in most of Europe, but with some admixture from Siberian hunter-gatherers in the eastern part of the continent. These hunter-gatherers were joined by migrants from the Near East beginning at ∼8-9kya: Anatolian farmers settled most of mainland Europe, and migrants from the Caucasus reached eastern Europe, forming steppe populations. After ∼5kya there was migration from the steppe into mainland Europe and vice versa. Present-day Europeans (ignoring the long-distance migrations of the modern era) are largely the product of this Bronze Age collision of steppe pastoralists with Neolithic farmers.}, } @article {pmid29948329, year = {2018}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Litvinov, A and Rogalla, U and Skonieczna, K and Grzybowski, T and Pentelényi, K and Guba, Z and Zeke, T and Molnár, MJ}, title = {Whole mitochondrial genome diversity in two Hungarian populations.}, journal = {Molecular genetics and genomics : MGG}, volume = {293}, number = {5}, pages = {1255-1263}, pmid = {29948329}, issn = {1617-4623}, support = {16-34-00014//Russian Foundation for Basic Research/ ; ICRG-117//the Wenner-Gren Foundation/ ; }, mesh = {DNA, Mitochondrial/*genetics ; Ethnicity/*genetics ; *Genetic Variation ; *Genetics, Population ; *Genome, Mitochondrial ; *Haplotypes ; Humans ; Hungary ; Phylogeography ; }, abstract = {Complete mitochondrial genomics is an effective tool for studying the demographic history of human populations, but there is still a deficit of mitogenomic data in European populations. In this paper, we present results of study of variability of 80 complete mitochondrial genomes in two Hungarian populations from eastern part of Hungary (Szeged and Debrecen areas). The genetic diversity of Hungarian mitogenomes is remarkably high, reaching 99.9% in a combined sample. According to the analysis of molecular variance (AMOVA), European populations showed a low, but statistically significant level of between-population differentiation (Fst = 0.61%, p = 0), and two Hungarian populations demonstrate lack of between-population differences. Phylogeographic analysis allowed us to identify 71 different mtDNA sub-clades in Hungarians, sixteen of which are novel. Analysis of ancestry-informative mtDNA sub-clades revealed a complex genetic structure associated with the genetic impact of populations from different parts of Eurasia, though the contribution from European populations is the most pronounced. At least 8% of ancestry-informative haplotypes found in Hungarians demonstrate similarity with East and West Slavic populations (sub-clades H1c23a, H2a1c1, J2b1a6, T2b25a1, U4a2e, K1c1j, and I1a1c), while the influence of Siberian populations is not so noticeable (sub-clades A12a, C4a1a, and probably U4b1a4).}, } @article {pmid29927400, year = {2018}, author = {Rzaev, DA and Denisova, NP and Moisak, GI and Rogov, DY and Kulikova, EV}, title = {[Experience of the use of gasserian ganglion balloon compression in patients with trigeminal neuralgia associated with multiple sclerosis].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {118}, number = {5}, pages = {30-35}, doi = {10.17116/jnevro20181185130}, pmid = {29927400}, issn = {1997-7298}, mesh = {Aged ; Catheterization ; Female ; Humans ; Male ; Middle Aged ; *Multiple Sclerosis ; Recurrence ; Treatment Outcome ; Trigeminal Ganglion ; *Trigeminal Neuralgia ; }, abstract = {AIM: To evaluate the efficacy of gasserian ganglion balloon compression in patients with trigeminal neuralgia associated with multiple sclerosis (MS).

MATERIAL AND METHODS: Eight patients (3 men, 5 women), aged from 46 to 66 years (mean age 55 years), with trigeminal neuralgia associated with MS underwent surgery. An average duration of the pain syndrome was 8,4 years. Six patients had previous surgeries due to facial pain. Percutaneous balloon compression of gasserian ganglion was performed to all patients. Follow up period was from 2 to 24 months.

RESULTS: Six patients (75%) reported 100% of pain relief right after the surgery, 2 patients (25%) reported a significant decrease of pain (2-3 points on VAS). Pain recurrence occurred in 3 patients: in 4 months, in 12 months and in 6 months. All of them were operated repeatedly. After the surgery, hypoesthesia on the side of surgery was observed in all patients with a trend towards regression. There was no keratopathy or any complications.

CONCLUSION: Percutaneous balloon compression of gasserian ganglion is an effective and minimally invasive method which can be performed repeatedly in patients with trigeminal neuralgia associated with MS.}, } @article {pmid29914355, year = {2018}, author = {Cserhati, MF and Mooter, ME and Peterson, L and Wicks, B and Xiao, P and Pauley, M and Guda, C}, title = {Motifome comparison between modern human, Neanderthal and Denisovan.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {472}, pmid = {29914355}, issn = {1471-2164}, support = {P20 GM103427/GM/NIGMS NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; 2P20GM103427//Nebraska INBRE/ ; 5P30CA036727//CCSG award/ ; }, mesh = {Animals ; Endogenous Retroviruses/genetics ; *Fossils ; *Genome ; Humans ; Neanderthals/*genetics ; Nucleotide Motifs/*genetics ; Phenotype ; Promoter Regions, Genetic ; Trans-Activators ; }, abstract = {BACKGROUND: The availability of the genomes of two archaic humans, Neanderthal and Denisovan, and that of modern humans provides researchers an opportunity to investigate genetic differences between these three subspecies on a genome-wide scale. Here we describe an algorithm that predicts statistically significant motifs based on the difference between a given motif's actual and expected distributions. The algorithm was previously applied to plants but was modified for this work.

RESULTS: The result of applying the algorithm to the human, Neanderthal, and Denisovan genomes is a catalog of potential regulatory motifs in these three human subspecies. We examined the distributions of these motifs in genetic elements including human retroviruses, human accelerated regions, and human accelerated conserved noncoding sequences regions. Differences in these distributions could be the origin of differences in phenotype between the three subspecies. Twenty significant motifs common to all three genomes were found; thirty-three were found in endogenous retroviruses in Neanderthal and Denisovan. Ten of these motifs mapped to the 22 bp core of MiR-1304. The core of this genetic element regulates the ENAM and AMTN genes, which take part in odontogenesis and whose 3' UTRs contained significant motifs. The introns of 20 genes were found to contain a large number of significant motifs, which were also overrepresented in 49 human accelerated regions. These genes include NAV2, SorCS2, TRAPPC9, GRID1, PRDM16, CAMTA1, and ASIC which are all involved in neuroregulation. Further analysis of these genes using the GO database indicates that many are associated with neurodevelopment. Also, varying numbers of significant motifs were found to occur in regions of the Neanderthal and Denisovan genomes that are missing from the human genome, suggesting further functional differences between modern and archaic humans.

CONCLUSION: Although Neanderthal and Denisovan are now extinct, detailed examination of elements from their genomes can shed light on possible phenotypic and cognitive differences between these two archaic human subspecies and modern humans. Genetic similarities and differences between these three subspecies and other fossil hominids would also be of interest.}, } @article {pmid29894925, year = {2018}, author = {Dannemann, M and Racimo, F}, title = {Something old, something borrowed: admixture and adaptation in human evolution.}, journal = {Current opinion in genetics & development}, volume = {53}, number = {}, pages = {1-8}, doi = {10.1016/j.gde.2018.05.009}, pmid = {29894925}, issn = {1879-0380}, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Biological Evolution ; DNA, Ancient ; *Evolution, Molecular ; Genetics, Population ; Genome, Human/genetics ; Haplotypes ; Hominidae/*genetics ; Humans ; Neanderthals/genetics ; }, abstract = {The sequencing of ancient DNA from archaic humans-Neanderthals and Denisovans-has revealed that modern and archaic humans interbred at least twice during the Pleistocene. The field of human paleogenomics has now turned its attention towards understanding the nature of this genetic legacy in the gene pool of present-day humans. What exactly did modern humans obtain from interbreeding with Neanderthals and Denisovans? Was the introgressed genetic material beneficial, neutral or maladaptive? Can differences in phenotypes among present-day human populations be explained by archaic human introgression? These questions are of prime importance for our understanding of recent human evolution, but will require careful computational modeling and extensive functional assays before they can be answered in full. Here, we review the recent literature characterizing introgressed DNA and the likely biological consequences for their modern human carriers. We focus particularly on archaic human haplotypes that were beneficial to modern humans as they expanded across the globe, and on ways to understand how populations harboring these haplotypes evolved over time.}, } @article {pmid29747567, year = {2018}, author = {Banerjee, N and Polushina, T and Bettella, F and Giddaluru, S and Steen, VM and Andreassen, OA and Le Hellard, S}, title = {Recently evolved human-specific methylated regions are enriched in schizophrenia signals.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {63}, pmid = {29747567}, issn = {1471-2148}, support = {#2 T23273//Norges Forskningsråd/International ; SKGJ-MED-008//KG Jebsen Foundation/International ; }, mesh = {Adult ; Bipolar Disorder/genetics ; Body Height/genetics ; Body Mass Index ; DNA Methylation/*genetics ; *Evolution, Molecular ; Female ; Genetic Markers ; Genome-Wide Association Study ; Genotype ; Humans ; Major Histocompatibility Complex/genetics ; Male ; Molecular Sequence Annotation ; Multifactorial Inheritance ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Schizophrenia/*genetics ; }, abstract = {BACKGROUND: One explanation for the persistence of schizophrenia despite the reduced fertility of patients is that it is a by-product of recent human evolution. This hypothesis is supported by evidence suggesting that recently-evolved genomic regions in humans are involved in the genetic risk for schizophrenia. Using summary statistics from genome-wide association studies (GWAS) of schizophrenia and 11 other phenotypes, we tested for enrichment of association with GWAS traits in regions that have undergone methylation changes in the human lineage compared to Neanderthals and Denisovans, i.e. human-specific differentially methylated regions (DMRs). We used analytical tools that evaluate polygenic enrichment of a subset of genomic variants against all variants.

RESULTS: Schizophrenia was the only trait in which DMR SNPs showed clear enrichment of association that passed the genome-wide significance threshold. The enrichment was not observed for Neanderthal or Denisovan DMRs. The enrichment seen in human DMRs is comparable to that for genomic regions tagged by Neanderthal Selective Sweep markers, and stronger than that for Human Accelerated Regions. The enrichment survives multiple testing performed through permutation (n = 10,000) and bootstrapping (n = 5000) in INRICH (p < 0.01). Some enrichment of association with height was observed at the gene level.

CONCLUSIONS: Regions where DNA methylation modifications have changed during recent human evolution show enrichment of association with schizophrenia and possibly with height. Our study further supports the hypothesis that genetic variants conferring risk of schizophrenia co-occur in genomic regions that have changed as the human species evolved. Since methylation is an epigenetic mark, potentially mediated by environmental changes, our results also suggest that interaction with the environment might have contributed to that association.}, } @article {pmid29739306, year = {2018}, author = {Akkuratov, EE and Gelfand, MS and Khrameeva, EE}, title = {Neanderthal and Denisovan ancestry in Papuans: A functional study.}, journal = {Journal of bioinformatics and computational biology}, volume = {16}, number = {2}, pages = {1840011}, doi = {10.1142/S0219720018400115}, pmid = {29739306}, issn = {1757-6334}, mesh = {Alleles ; Animals ; Black People/genetics ; Bone Remodeling/genetics ; Cluster Analysis ; Genetics, Population ; *Genome, Human ; Hominidae/*genetics ; Humans ; Multigene Family ; Neanderthals/genetics ; Papua New Guinea ; Polymorphism, Single Nucleotide ; Transcription Factors/genetics ; }, abstract = {Sequencing of complete nuclear genomes of Neanderthal and Denisovan stimulated studies about their relationship with modern humans demonstrating, in particular, that DNA alleles from both Neanderthal and Denisovan genomes are present in genomes of modern humans. The Papuan genome is a unique object because it contains both Neanderthal and Denisovan alleles. Here, we have shown that the Papuan genomes contain different gene functional groups inherited from each of the ancient people. The Papuan genomes demonstrate a relative prevalence of Neanderthal alleles in genes responsible for the regulation of transcription and neurogenesis. The enrichment of specific functional groups with Denisovan alleles is less pronounced; these groups are responsible for bone and tissue remodeling. This analysis shows that introgression of alleles from Neanderthals and Denisovans to Papuans occurred independently and retention of these alleles may carry specific adaptive advantages.}, } @article {pmid29688213, year = {2018}, author = {Shkliaev, AE and Denisova, NI and Kulikov, IV}, title = {[Splenic artery aneurysm masked by postcholecystectomy syndrome].}, journal = {Angiologiia i sosudistaia khirurgiia = Angiology and vascular surgery}, volume = {24}, number = {1}, pages = {175-178}, pmid = {29688213}, issn = {1027-6661}, mesh = {*Aneurysm/diagnosis/physiopathology/surgery ; Angiography/methods ; Blood Vessel Prosthesis Implantation/*methods ; Diagnosis, Differential ; Endovascular Procedures/*methods ; Female ; Humans ; Middle Aged ; Postcholecystectomy Syndrome/*diagnosis ; *Splenic Artery/diagnostic imaging/pathology ; Tomography, Spiral Computed/methods ; Treatment Outcome ; }, abstract = {Visceral artery aneurysms appear to belong to uncommon and potentially lethal vascular diseases. They are usually revealed accidentally during an ultrasonographic examination, magnetic resonance imaging, or computed tomography. Described in the article is a clinical case report concerning a sacciform aneurysm of the splenic artery, detected in a 53-year-old woman presenting with postcholecystectomy syndrome and followed up for abdominalgia by therapeutists and gastroenterologists. Timely performed radiodiagnosis (including multispiral computed tomography and angiography of the abdominal vessels) made it possible not only to detect the aneurysm, having thus verified the volumetric formation previously found on ultrasonographic examination, but to take adequate measures aimed at preventing rupture of the aneurysm and consisting in endovascular occlusion of the aneurysmatic cavity with metal spirals. Lack of complete clarity in the understanding of the mechanisms of the origin of and no distinctly defined therapeutic-and-diagnostic algorithm for visceral artery aneurysms dictate the necessity to continue collecting and generalizing clinical case reports regarding this rarely encountered vascular pathology.}, } @article {pmid29667630, year = {2018}, author = {Bogomolov, DV and Fetisov, VA and Denisova, OP and Zbrueva, YV and Semenov, GG}, title = {[The principal and auxiliary immunohistochemical markers of intravital mechanical strangulation asphyxia].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {61}, number = {2}, pages = {11-13}, doi = {10.17116/sudmed201861211-13}, pmid = {29667630}, issn = {0039-4521}, mesh = {Adolescent ; Adult ; *Asphyxia/etiology/pathology ; Biomarkers/analysis ; *Cause of Death ; Child ; Diagnosis, Differential ; Fibrinogen/immunology ; Forensic Pathology/methods ; Humans ; Immunohistochemistry/*methods ; *Lung/immunology/pathology ; *Neck Injuries/immunology/pathology ; Proto-Oncogene Proteins c-kit/*analysis ; }, abstract = {UNLABELLED: The objective of the present study was the evaluation of the auxiliary methods for the diagnostics of the intravital formation of the constriction marks; the secondary objective was to determine the pace at which the death and asphyxia occur.

MATERIAL AND METHODS: The materials on which the study was based included 17 cases of mechanical strangulation asphyxia involving 13 men and 4 women at the age from 8 to 28 years. All cases of hanging were associated with different blood alcohol levels. Their characteristic feature was the formation of the obliquely ascending constriction marks. The group of comparison was comprised of three cases of death by drowning and one case of manual strangulation. The control group consisted of 10 patients who died from the acute form of coronary heart disease and 5 cases of death from traumatic shock. All the corpses were examined with the use of the traditional methods within the first 24 hours after death. The special laboratory studies were performed by means of the standard histological and immunohistochemical methods with the use of the polyclonal antibodies against total cytokeratin, fibrinogen, immunoglobulin-lambda, fibronectin, and CD-117 antigen. The histological preparations were stained by the method of Spielmeyer and with toluidine blue.

RESULTS: The results of the study give evidence of the possibility of diagnostics of mechanical strangulation asphyxia making use of the reaction with anti-fibrinogen antibodies in the stromal tissue of the constriction mark even in the absence of other intravital signs of death. Such diagnostics is also possible with the use of the CD-117 antigen in the pulmonary tissue. The expression of this antigen is characteristic of the cases of alveolar hypoxia. The possibility of application of other markers for the differential diagnostics of mechanical strangulation asphyxia from other causes of death is discussed.}, } @article {pmid29659494, year = {2018}, author = {Khabarova, EA and Denisova, NP and Dmitriev, AB and Slavin, KV and Verhagen Metman, L}, title = {Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson Disease with Prior Pallidotomy or Thalamotomy.}, journal = {Brain sciences}, volume = {8}, number = {4}, pages = {}, pmid = {29659494}, issn = {2076-3425}, abstract = {Objective. To evaluate the efficacy of deep brain stimulation of the subthalamic nucleus (STN DBS) in patients with Parkinson disease (PD) who previously underwent lesioning of the basal ganglia. Material and methods. The study included 22 patients who underwent STN DBS. Eleven patients had undergone prior unilateral pallidotomy (n = 6) or VL/VIM thalamotomy (n = 5) while the other 11 patients had not. The primary outcome was the change from baseline in the motor subscore of the Unified Parkinson Disease Rating Scale (UPDRS-III) 12 months after STN DBS. Secondary outcomes included change in motor response complications (UPDRS-IV) and change in levodopa equivalent daily dose (LEDD). Results. In the group with prior lesioning UPDRS-III improved by 45%, from 51.5 ± 9.0% (range, 35&ndash;65) to 26.5 ± 8.4 (range, 21&ndash;50) (p < 0.01) and UPDRS-IV by 75%, from 8.0 ± 2.01 (range, 5&ndash;11) to 2.1 ± 0.74 (range, 1&ndash;3) (p < 0.01). In the group without prior lesioning UPDRS-III improved by 61%, from 74.2% ± 7.32 (range, 63&ndash;82) to 29.3 ± 5.99 (range, 20&ndash;42) (p < 0.01) and UPDRS-IV by 77%, from 9.1 ± 2.46 (range, 5&ndash;12) to 2.0 ± 1.1 (range, 1&ndash;4) (p < 0.01). Comparing the two groups (with and without lesioning) no significant differences were found either in UPDRS-III (p > 0.05) or UPDRS-IV scores (p > 0.05) at 12 months post-DBS. The LEDD was reduced by 51.4%, from 1008.2 ± 346.4 to 490.0 ± 194.3 in those with prior surgery (p < 0.01) and by 55.0%, from 963.4 ± 96.2 to 433.3 ± 160.2 in those without (p < 0.01).UPDRS-III improved by 51.8%, from 53.7 ± 4.6 (range, 50&ndash;62) to 25.0 ± 3.8 (range, 21&ndash;31) in those with prior pallidotomy (p < 0.01), and by 37.5%, from 48.8 ± 12.6 (range, 35&ndash;65) to 29.8 ± 13.6 (range, 22&ndash;50) in those with prior thalamotomy (p < 0.01). This numerical difference in improvement was not statistically significant (p > 0.05). Conclusion. Our comparative study indicates that bilateral STN DBS is effective and can be used in patients with Parkinson disease with prior unilateral stereotactic destructive operations on subcortical structures. The results in our patient cohort are generally consistent with previously published reports of smaller series from multiple centers worldwide.}, } @article {pmid29658973, year = {2018}, author = {Viscardi, LH and Paixão-Côrtes, VR and Comas, D and Salzano, FM and Rovaris, D and Bau, CD and Amorim, CEG and Bortolini, MC}, title = {Searching for ancient balanced polymorphisms shared between Neanderthals and Modern Humans.}, journal = {Genetics and molecular biology}, volume = {41}, number = {1}, pages = {67-81}, pmid = {29658973}, issn = {1415-4757}, abstract = {Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of trans-SNP in two gene sets: one associated with the immune system (IMMS) and another one with behavioral system (BEHS). We identified a significant excess of trans-SNPs in IMMS (N=547), of which six of these located within genes previously associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but five genes in this system harbor potential signals for balancing selection and are associated with psychiatric or neurodevelopmental disorders. Our approach evidenced recent Homo trans-SNPs that have been previously implicated in psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire common to the immune and behavioral systems could have been maintained by balancing selection starting before the split between archaic and modern humans.}, } @article {pmid29615820, year = {2018}, author = {Otto, G}, title = {Human evolution: Archaic admixture with Denisovans.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {251}, pmid = {29615820}, issn = {1471-0064}, mesh = {Base Sequence ; Evolution, Molecular ; Humans ; Neanderthals/*genetics ; }, } @article {pmid29608725, year = {2018}, author = {Zehra, R and Abbasi, AA}, title = {Homo sapiens-Specific Binding Site Variants within Brain Exclusive Enhancers Are Subject to Accelerated Divergence across Human Population.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {956-966}, pmid = {29608725}, issn = {1759-6653}, mesh = {Animals ; Binding Sites/genetics ; Brain/metabolism ; Enhancer Elements, Genetic/*genetics ; *Evolution, Molecular ; Humans ; Primates/*genetics ; Species Specificity ; Transcription Factors/genetics ; }, abstract = {Empirical assessments of human accelerated noncoding DNA frgaments have delineated presence of many cis-regulatory elements. Enhancers make up an important category of such accelerated cis-regulatory elements that efficiently control the spatiotemporal expression of many developmental genes. Establishing plausible reasons for accelerated enhancer sequence divergence in Homo sapiens has been termed significant in various previously published studies. This acceleration by including closely related primates and archaic human data has the potential to open up evolutionary avenues for deducing present-day brain structure. This study relied on empirically confirmed brain exclusive enhancers to avoid any misjudgments about their regulatory status and categorized among them a subset of enhancers with an exceptionally accelerated rate of lineage specific divergence in humans. In this assorted set, 13 distinct transcription factor binding sites were located that possessed unique existence in humans. Three of 13 such sites belonging to transcription factors SOX2, RUNX1/3, and FOS/JUND possessed single nucleotide variants that made them unique to H. sapiens upon comparisons with Neandertal and Denisovan orthologous sequences. These variants modifying the binding sites in modern human lineage were further substantiated as single nucleotide polymorphisms via exploiting 1000 Genomes Project Phase3 data. Long range haplotype based tests laid out evidence of positive selection to be governing in African population on two of the modern human motif modifying alleles with strongest results for SOX2 binding site. In sum, our study acknowledges acceleration in noncoding regulatory landscape of the genome and highlights functional parts within it to have undergone accelerated divergence in present-day human population.}, } @article {pmid29570998, year = {2018}, author = {Vernot, B and Pääbo, S}, title = {The Predecessors Within . .}, journal = {Cell}, volume = {173}, number = {1}, pages = {6-7}, doi = {10.1016/j.cell.2018.03.023}, pmid = {29570998}, issn = {1097-4172}, mesh = {Asia ; *Family ; Humans ; }, abstract = {By examining the genomes of present-day people from Asia, researchers show that modern humans met and interbred with Denisovans, distant relatives to Neanderthals, on at least two occasions. As a result, people today carry DNA from two different Denisovan populations.}, } @article {pmid29551270, year = {2018}, author = {Browning, SR and Browning, BL and Zhou, Y and Tucci, S and Akey, JM}, title = {Analysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture.}, journal = {Cell}, volume = {173}, number = {1}, pages = {53-61.e9}, pmid = {29551270}, issn = {1097-4172}, support = {R01 GM110068/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asian People/genetics ; *Genome, Human ; Humans ; Neanderthals/genetics ; Selection, Genetic ; Exome Sequencing ; }, abstract = {Anatomically modern humans interbred with Neanderthals and with a related archaic population known as Denisovans. Genomes of several Neanderthals and one Denisovan have been sequenced, and these reference genomes have been used to detect introgressed genetic material in present-day human genomes. Segments of introgression also can be detected without use of reference genomes, and doing so can be advantageous for finding introgressed segments that are less closely related to the sequenced archaic genomes. We apply a new reference-free method for detecting archaic introgression to 5,639 whole-genome sequences from Eurasia and Oceania. We find Denisovan ancestry in populations from East and South Asia and Papuans. Denisovan ancestry comprises two components with differing similarity to the sequenced Altai Denisovan individual. This indicates that at least two distinct instances of Denisovan admixture into modern humans occurred, involving Denisovan populations that had different levels of relatedness to the sequenced Altai Denisovan. VIDEO ABSTRACT.}, } @article {pmid29477182, year = {2018}, author = {Warren, KA and Ritzman, TB and Humphreys, RA and Percival, CJ and Hallgrímsson, B and Ackermann, RR}, title = {Craniomandibular form and body size variation of first generation mouse hybrids: A model for hominin hybridization.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {57-74}, pmid = {29477182}, issn = {1095-8606}, support = {R01 DE019638/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Body Size/genetics ; Fossils/anatomy & histology ; Hominidae/*anatomy & histology/genetics/*physiology ; *Hybridization, Genetic ; Mandible/anatomy & histology ; Mice/*anatomy & histology/genetics/*physiology ; *Models, Animal ; Phenotype ; Skull/anatomy & histology ; }, abstract = {Hybridization occurs in a number of mammalian lineages, including among primate taxa. Analyses of ancient genomes have shown that hybridization between our lineage and other archaic hominins in Eurasia occurred numerous times in the past. However, we still have limited empirical data on what a hybrid skeleton looks like, or how to spot patterns of hybridization among fossils for which there are no genetic data. Here we use experimental mouse models to supplement previous studies of primates. We characterize size and shape variation in the cranium and mandible of three wild-derived inbred mouse strains and their first generation (F1) hybrids. The three parent taxa in our analysis represent lineages that diverged over approximately the same period as the human/Neanderthal/Denisovan lineages and their hybrids are variably successful in the wild. Comparisons of body size, as quantified by long bone measurements, are also presented to determine whether the identified phenotypic effects of hybridization are localized to the cranium or represent overall body size changes. The results indicate that hybrid cranial and mandibular sizes, as well as limb length, exceed that of the parent taxa in all cases. All three F1 hybrid crosses display similar patterns of size and form variation. These results are generally consistent with earlier studies on primates and other mammals, suggesting that the effects of hybridization may be similar across very different scenarios of hybridization, including different levels of hybrid fitness. This paper serves to supplement previous studies aimed at identifying F1 hybrids in the fossil record and to introduce further research that will explore hybrid morphologies using mice as a proxy for better understanding hybridization in the hominin fossil record.}, } @article {pmid29445326, year = {2018}, author = {Leacock, S and Syed, P and James, VM and Bode, A and Kawakami, K and Keramidas, A and Suster, M and Lynch, JW and Harvey, RJ}, title = {Structure/Function Studies of the α4 Subunit Reveal Evolutionary Loss of a GlyR Subtype Involved in Startle and Escape Responses.}, journal = {Frontiers in molecular neuroscience}, volume = {11}, number = {}, pages = {23}, pmid = {29445326}, issn = {1662-5099}, support = {MR/J004049/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Inhibitory glycine receptors (GlyRs) are pentameric ligand-gated anion channels with major roles in startle disease/hyperekplexia (GlyR α1), cortical neuronal migration/autism spectrum disorder (GlyR α2), and inflammatory pain sensitization/rhythmic breathing (GlyR α3). However, the role of the GlyR α4 subunit has remained enigmatic, because the corresponding human gene (GLRA4) is thought to be a pseudogene due to an in-frame stop codon at position 390 within the fourth membrane-spanning domain (M4). Despite this, a recent genetic study has implicated GLRA4 in intellectual disability, behavioral problems and craniofacial anomalies. Analyzing data from sequenced genomes, we found that GlyR α4 subunit genes are predicted to be intact and functional in the majority of vertebrate species-with the exception of humans. Cloning of human GlyR α4 cDNAs excluded alternative splicing and RNA editing as mechanisms for restoring a full-length GlyR α4 subunit. Moreover, artificial restoration of the missing conserved arginine (R390) in the human cDNA was not sufficient to restore GlyR α4 function. Further bioinformatic and mutagenesis analysis revealed an additional damaging substitution at K59 that ablates human GlyR α4 function, which is not present in other vertebrate GlyR α4 sequences. The substitutions K59 and X390 were also present in the genome of an ancient Denisovan individual, indicating that GLRA4 has been a pseudogene for at least 30,000-50,000 years. In artificial synapses, we found that both mouse and gorilla α4β GlyRs mediate synaptic currents with unusually slow decay kinetics. Lastly, to gain insights into the biological role of GlyR α4 function, we studied the duplicated genes glra4a and glra4b in zebrafish. While glra4b expression is restricted to the retina, using a novel tol2-GAL4FF gene trap line (SAIGFF16B), we found that the zebrafish GlyR α4a subunit gene (glra4a) is strongly expressed in spinal cord and hindbrain commissural neurones. Using gene knockdown and a dominant-negative GlyR α4a[R278Q] mutant, we found that GlyR α4a contributes to touch-evoked escape behaviors in zebrafish. Thus, although GlyR α4 is unlikely to be involved in human startle responses or disease states, this subtype may contribute to escape behaviors in other organisms.}, } @article {pmid29428968, year = {2018}, author = {Jiang, L and Peng, J and Huang, M and Liu, J and Wang, L and Ma, Q and Zhao, H and Yang, X and Ji, A and Li, C}, title = {Differentiation analysis for estimating individual ancestry from the Tibetan Plateau by an archaic altitude adaptation EPAS1 haplotype among East Asian populations.}, journal = {International journal of legal medicine}, volume = {132}, number = {6}, pages = {1527-1535}, pmid = {29428968}, issn = {1437-1596}, support = {2017YFC0803501//National Key Research and Development Program of China/ ; 2016JB039//basic research project/ ; 2017JB027//basic research project/ ; }, mesh = {Adaptation, Physiological ; Altitude ; Asian People/*genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; China ; Genotype ; *Haplotypes ; Humans ; *Polymorphism, Single Nucleotide ; Tibet/ethnology ; }, abstract = {Tibetans have adapted to the extreme environment of high altitude for hundreds of generations. A highly differentiated 5-SNP (Single Nucleotide Polymorphism) haplotype motif (AGGAA) on a hypoxic pathway gene, EPAS1, is observed in Tibetans and lowlanders. To evaluate the potential usage of the 5-SNP haplotype in ancestry inference for Tibetan or Tibetan-related populations, we analyzed this haplotype in 1053 individuals of 12 Chinese populations residing on the Tibetan Plateau, peripheral regions of Tibet, and plain regions. These data were integrated with the genotypes from the 1000 Genome populations and populations in a previously reported paper for population structure analyses. We found that populations representing highland and lowland groups have different dominant ancestry components. The core Denisovan haplotype (AGGAA) was observed at a frequency of 72.32% in the Tibetan Plateau, with a frequency range from 9.48 to 21.05% in the peripheral regions and < 2.5% in the plains area. From the individual perspective, 87.57% of the individuals from the Tibetan Plateau carried the archaic haplotype, while < 5% of the Chinese Han people carried the haplotype. Our findings indicate that the 5-SNP haplotype has a special distribution pattern in populations of Tibet and peripheral regions and could be integrated into AISNP (Ancestry Informative Single Nucleotide Polymorphism) panels to enhance ancestry resolution.}, } @article {pmid29422656, year = {2018}, author = {Rodríguez-Paredes, M and Bormann, F and Raddatz, G and Gutekunst, J and Lucena-Porcel, C and Köhler, F and Wurzer, E and Schmidt, K and Gallinat, S and Wenck, H and Röwert-Huber, J and Denisova, E and Feuerbach, L and Park, J and Brors, B and Herpel, E and Nindl, I and Hofmann, TG and Winnefeld, M and Lyko, F}, title = {Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {577}, pmid = {29422656}, issn = {2041-1723}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/*genetics ; Case-Control Studies ; Cell Differentiation ; DNA Methylation/*genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Keratinocytes ; Keratosis, Actinic/*genetics ; Male ; Middle Aged ; Skin Neoplasms/*genetics ; Young Adult ; }, abstract = {Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and usually progresses from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain partially understood. Here, we use Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status in healthy, AK and cSCC epidermis samples. Importantly, we show that AK methylation patterns already display classical features of cancer methylomes and are highly similar to cSCC profiles. Further analysis identifies typical features of stem cell methylomes, such as reduced DNA methylation age, non-CpG methylation, and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature is detected only in half of the samples, while the other half shows patterns more closely related to healthy epidermis. These findings suggest the existence of two subclasses of AK and cSCC emerging from distinct keratinocyte differentiation stages.}, } @article {pmid29383489, year = {2018}, author = {Yew, CW and Lu, D and Deng, L and Wong, LP and Ong, RT and Lu, Y and Wang, X and Yunus, Y and Aghakhanian, F and Mokhtar, SS and Hoque, MZ and Voo, CL and Abdul Rahman, T and Bhak, J and Phipps, ME and Xu, S and Teo, YY and Kumar, SV and Hoh, BP}, title = {Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia.}, journal = {Human genetics}, volume = {137}, number = {2}, pages = {161-173}, pmid = {29383489}, issn = {1432-1203}, support = {100-RM/BIOTEK 16/6/2 B (1/2011)//Kementerian Sains, Teknologi dan Inovasi (MY)/ ; [100-RMI/GOV 16/6/2 (19/2011]//Kementerian Sains, Teknologi dan Inovasi (MY)/ ; 100-RM/BIOTEK 16/6/2 B (1/2011)//Kementerian Sains, Teknologi dan Inovasi (MY)/ ; 100-RM/BIOTEK 16/6/2 B (1/2011)//Kementerian Sains, Teknologi dan Inovasi (MY)/ ; FRGS/1/2015/ST03/UCSI/01/1//Ministry of Higher Education, Malaysia (MY)/ ; NRF-RF-2010-05//National Foundation for Cancer Research (US)/ ; NRF-RF-2010-05//National Foundation for Cancer Research (US)/ ; NRF-RF-2010-05//National Research Foundation Singapore (SG)/ ; 91331204//National Natural Science Foundation of China (CN)/ ; 31525014//National Natural Science Foundation of China (CN)/ ; 91731303//National Natural Science Foundation of China (CN)/ ; 31771388//National Natural Science Foundation of China (CN)/ ; 31501011//National Natural Science Foundation of China (CN)/ ; 31711530221//National Institutes of Natural Sciences (JP)/ ; 10040231//Industry Strategic Development Program/ ; (1.150014.01)//Ulsan National Institute of Science and Technology (KR)/ ; }, mesh = {Asia, Southeastern ; Borneo ; DNA, Mitochondrial/*genetics ; Gene Flow/genetics ; Genetic Variation/*genetics ; *Genetics, Population ; Genome, Human/*genetics ; Genomics ; Human Migration ; Humans ; Malaysia ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.}, } @article {pmid29320204, year = {2018}, author = {Shipilovskikh, SA and Vaganov, VY and Denisova, EI and Rubtsov, AE and Malkov, AV}, title = {Dehydration of Amides to Nitriles under Conditions of a Catalytic Appel Reaction.}, journal = {Organic letters}, volume = {20}, number = {3}, pages = {728-731}, doi = {10.1021/acs.orglett.7b03862}, pmid = {29320204}, issn = {1523-7052}, abstract = {A highly expedient protocol for a catalytic Appel-type dehydration of amides to nitriles has been developed that employs oxalyl chloride and triethylamine along with triphenylphosphine oxide as a catalyst. The reactions are usually complete in less than 10 min with only a 1 mol % catalyst loading. The reaction scope includes aromatic, heteroaromatic, and aliphatic amides, including derivatives of α-hydroxy and α-amino acids.}, } @article {pmid29285967, year = {2017}, author = {Berens, AJ and Cooper, TL and Lachance, J}, title = {The Genomic Health of Ancient Hominins.}, journal = {Human biology}, volume = {89}, number = {1}, pages = {7-19}, doi = {10.13110/humanbiology.89.1.01}, pmid = {29285967}, issn = {1534-6617}, mesh = {Animals ; DNA Primers ; DNA, Mitochondrial/classification/genetics ; Evolution, Molecular ; Gene Library ; Genetic Association Studies ; Genetic Predisposition to Disease/classification/*genetics/history ; Genetic Variation/*genetics ; Genomics ; Geography/classification/history ; History, Ancient ; Hominidae/*genetics ; Humans ; Neanderthals/genetics ; Phylogeny ; }, abstract = {The genomes of ancient humans, Neandertals, and Denisovans contain many alleles that influence disease risks. Using genotypes at 3,180 disease-associated loci, we estimated the disease burden of 147 ancient genomes. After correcting for missing data, genetic risk scores (GRS) were generated for nine disease categories and the set of all combined diseases. We used these genetic risk scores to examine the effects of different types of subsistence, geography, and sample age on the number of risk alleles in each ancient genome. On a broad scale, hereditary disease risks are similar for ancient hominins and modern-day humans, and the GRS percentiles of ancient individuals span the full range of what is observed in present-day individuals. In addition, there is evidence that ancient pastoralists may have had healthier genomes than hunter-gatherers and agriculturalists. We also observed a temporal trend whereby genomes from the recent past are more likely to be healthier than genomes from the deep past. This calls into question the idea that modern lifestyles have caused genetic load to increase over time. Focusing on individual genomes, we found that the overall genomic health of the Altai Neandertal is worse than 97% of present-day humans and that Ötzi, the Tyrolean Iceman, had a genetic predisposition for gastrointestinal and cardiovascular diseases. As demonstrated by this work, ancient genomes afford us new opportunities to diagnose past human health, which has previously been limited by the quality and completeness of remains.}, } @article {pmid29246791, year = {2018}, author = {Belousov, AB and Nishimune, H and Denisova, JV and Fontes, JD}, title = {A potential role for neuronal connexin 36 in the pathogenesis of amyotrophic lateral sclerosis.}, journal = {Neuroscience letters}, volume = {666}, number = {}, pages = {1-4}, pmid = {29246791}, issn = {1872-7972}, support = {P30 AG035982/AG/NIA NIH HHS/United States ; R01 NS078214/NS/NINDS NIH HHS/United States ; R01 AG051470/AG/NIA NIH HHS/United States ; UL1 TR000001/TR/NCATS NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*metabolism/*pathology ; Animals ; Connexins/*metabolism ; Disease Models, Animal ; Gap Junctions/metabolism ; Humans ; Mice ; Motor Neurons/metabolism ; Spinal Cord/metabolism ; Superoxide Dismutase-1/metabolism ; }, abstract = {Neuronal gap junctional protein connexin 36 (Cx36) contributes to neuronal death following a range of acute brain insults such as ischemia, traumatic brain injury and epilepsy. Whether Cx36 contributes to neuronal death and pathological outcomes in chronic neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), is not known. We show here that the expression of Cx36 is significantly decreased in lumbar segments of the spinal cord of both human ALS subjects and SOD1[G93A] mice as compared to healthy human and wild-type mouse controls, respectively. In purified neuronal cultures prepared from the spinal cord of wild-type mice, knockdown of Cx36 reduces neuronal death caused by overexpression of the mutant human SOD1-G93A protein. Taken together, these data suggest a possible contribution of Cx36 to ALS pathogenesis. A perspective for the use of blockers of Cx36 gap junction channels for ALS therapy is discussed.}, } @article {pmid29217544, year = {2017}, author = {Bae, CJ and Douka, K and Petraglia, MD}, title = {On the origin of modern humans: Asian perspectives.}, journal = {Science (New York, N.Y.)}, volume = {358}, number = {6368}, pages = {}, doi = {10.1126/science.aai9067}, pmid = {29217544}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Africa ; Asia ; *Biological Evolution ; *Fossils ; *Human Migration ; Humans ; }, abstract = {The traditional "out of Africa" model, which posits a dispersal of modern Homo sapiens across Eurasia as a single wave at ~60,000 years ago and the subsequent replacement of all indigenous populations, is in need of revision. Recent discoveries from archaeology, hominin paleontology, geochronology, genetics, and paleoenvironmental studies have contributed to a better understanding of the Late Pleistocene record in Asia. Important findings highlighted here include growing evidence for multiple dispersals predating 60,000 years ago in regions such as southern and eastern Asia. Modern humans moving into Asia met Neandertals, Denisovans, mid-Pleistocene Homo, and possibly H. floresiensis, with some degree of interbreeding occurring. These early human dispersals, which left at least some genetic traces in modern populations, indicate that later replacements were not wholesale.}, } @article {pmid29215085, year = {2018}, author = {Derenko, M and Denisova, G and Malyarchuk, B and Dambueva, I and Bazarov, B}, title = {Mitogenomic diversity and differentiation of the Buryats.}, journal = {Journal of human genetics}, volume = {63}, number = {1}, pages = {71-81}, pmid = {29215085}, issn = {1435-232X}, mesh = {Asian People/*ethnology/*genetics ; DNA, Mitochondrial/*genetics ; Female ; *Genome, Mitochondrial ; Humans ; Male ; *Phylogeny ; Siberia/ethnology ; }, abstract = {In this paper we present a results of first comprehensive study of the complete mitogenomes in the Buryats with regard to their belonging to the main regional (eastern and western Buryats); tribal (Khori, Ekhirid, Bulagad, and Khongodor), and ethno-territorial (Aginsk, Alar, Balagansk, Barguzin, Ida, Khorinsk, Kuda, Selenga, Verkholensk, Olkhon, Tunka, and Shenehen Buryats) groups. The analysis of molecular variation performed using regional, tribal, and ethno-territorial divisions of the Buryats showed lack of genetic differentiation at all levels. Nonetheless, the complete mitogenome analysis revealed a very high level of genetic diversity in the Buryats which is the highest among Siberian populations and comparable to that in populations of eastern and western Asia. The AMOVA and MDS analyses results imply to a strong genetic similarity between the Buryats and eastern Asian populations of Chinese and Japanese, suggesting their origin on the basis of common maternal ancestry components. Several new Buryat-specific branches of haplogroup G (G2a2a, G2a1i, G2a5a) display signals of dispersals dating to 2.6-6.6 kya with a possible origin in eastern Asia, thus testifying Bronze Age and Neolithic arrival of ancestral eastern Asian component to the South Siberia region.}, } @article {pmid29175608, year = {2018}, author = {Walter Costa, MB and Höner Zu Siederdissen, C and Tulpan, D and Stadler, PF and Nowick, K}, title = {Temporal ordering of substitutions in RNA evolution: Uncovering the structural evolution of the Human Accelerated Region 1.}, journal = {Journal of theoretical biology}, volume = {438}, number = {}, pages = {143-150}, doi = {10.1016/j.jtbi.2017.11.015}, pmid = {29175608}, issn = {1095-8541}, mesh = {*Evolution, Molecular ; Humans ; Models, Biological ; Mutation/genetics ; Nucleic Acid Conformation ; Probability ; RNA, Untranslated/*chemistry/*genetics ; Time Factors ; }, abstract = {The Human Accelerated Region 1 (HAR1) is the most rapidly evolving region in the human genome. It is part of two overlapping long non-coding RNAs, has a length of only 118 nucleotides and features 18 human specific changes compared to an ancestral sequence that is extremely well conserved across non-human primates. The human HAR1 forms a stable secondary structure that is strikingly different from the one in chimpanzee as well as other closely related species, again emphasizing its human-specific evolutionary history. This suggests that positive selection has acted to stabilize human-specific features in the ensemble of HAR1 secondary structures. To investigate the evolutionary history of the human HAR1 structure, we developed a computational model that evaluates the relative likelihood of evolutionary trajectories as a probabilistic version of a Hamiltonian path problem. The model predicts that the most likely last step in turning the ancestral primate HAR1 into the human HAR1 was exactly the substitution that distinguishes the modern human HAR1 sequence from that of Denisovan, an archaic human, providing independent support for our model. The MutationOrder software is available for download and can be applied to other instances of RNA structure evolution.}, } @article {pmid29171471, year = {2017}, author = {Kovalkova, NA and Ragino, YI and Travnikova, NY and Denisova, DV and Shcherbakova, LV and Voevoda, MI}, title = {[Associations between metabolic syndrome and reduced lung function in young people].}, journal = {Terapevticheskii arkhiv}, volume = {89}, number = {10}, pages = {54-61}, doi = {10.17116/terarkh2017891054-61}, pmid = {29171471}, issn = {0040-3660}, mesh = {Adult ; Blood Glucose/analysis ; *Blood Pressure Determination/methods/statistics & numerical data ; Body Mass Index ; Cardiovascular Diseases/*epidemiology ; Cholesterol/blood ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Female ; Humans ; Male ; *Metabolic Syndrome/blood/diagnosis/epidemiology/physiopathology ; Prevalence ; Respiratory Function Tests/methods/statistics & numerical data ; *Respiratory Insufficiency/diagnosis/epidemiology/physiopathology ; Risk Factors ; Siberia/epidemiology ; Statistics as Topic ; Triglycerides/blood ; *Waist Circumference ; }, abstract = {AIM: To reveal possible associations between metabolic syndrome (MS) and reduced lung function.

SUBJECTS AND METHODS: In 2013-016, a cross-sectional survey was conducted in 908 Novosibirsk dwellers, which included spirometry to evaluate external respiratory function (ERF). For the detection of MS, the investigators used the 2009 All-Russian Research Society of Cardiologists criteria: waist circumference (WC) > 80 cm for women and >94 cm for men in combination with two of the following criteria: blood pressure (BP) ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, high-density lipoproteins (HDL) cholesterol <1.0 mmol/l for men and <1.2 mmol/l for women, low-density lipoprotein (LDL) cholesterol >3.0 mmol/l, and glucose ≥6.1 mmol/l.

RESULTS: The mean values of WC were significantly greater with a forced expiratory volume in one second (FEV1) <80% than those with a FEV1 of ≥80% in both men (p=0.002) and women (p=0.050); in women, the mean values of WS were higher than those with a FEV1/forced vital capacity (FVC) <70% than those with a FEV1/FVC of ≥70% (p=0.047); the mean systolic and diastolic BP levels were significantly more with reductions in FEV1 and FVC, and the level of HDL cholesterol was significantly lower than that with a FEV1 of < 80% in men only. Significant correlations were found between FEV1 and all components of MS in men, between the majority of components of MS and FVC in men, between WC, BP, and FEV1/FVC in men and women, between plasma glucose levels and FEV1/FVC in women. Linear regression analysis revealed significant inverse correlations of FEV1 with TG, glucose, BP; those of FVC with TG, glucose; at the same time a positive association with HDL cholesterol in men, and only a negative correlation of FEV1/FVC with WC.

CONCLUSION: The revealed associations between MS and reduced lung function can most likely be explained by the greater prevalence of both MS and its components (hypertension, hypertriglyceridemia, hyperglycemia, LDL hypercholesterolemia) among Novosibirsk men. This is consistent with the assertion that the decline in ERF, particularly FEV1, may be a marker of future cardiovascular disease morbidity and mortality.}, } @article {pmid29165618, year = {2018}, author = {Novakowski, KE and Yap, NVL and Yin, C and Sakamoto, K and Heit, B and Golding, GB and Bowdish, DME}, title = {Human-Specific Mutations and Positively Selected Sites in MARCO Confer Functional Changes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {440-450}, pmid = {29165618}, issn = {1537-1719}, support = {R15 AI094436/AI/NIAID NIH HHS/United States ; MOP-123419//CIHR/Canada ; }, mesh = {Animals ; HEK293 Cells ; Humans ; Mutation ; Phagocytosis/*genetics ; Receptors, Immunologic/*genetics/metabolism ; *Selection, Genetic ; }, abstract = {Macrophage Receptor with COllagenous structure (MARCO) is a class A scavenger receptor that binds, phagocytoses, and modifies inflammatory responses to bacterial pathogens. Multiple candidate gene approach studies have shown that polymorphisms in MARCO are associated with susceptibility or resistance to Mycobacterium tuberculosis infection, but how these variants alter function is not known. To complement candidate gene approach studies, we previously used phylogenetic analyses to identify a residue, glutamine 452 (Q452), within the ligand-binding Scavenger Receptor Cysteine Rich domain as undergoing positive selection in humans. Herein, we show that Q452 is found in Denisovans, Neanderthals, and extant humans, but all other nonprimate, terrestrial, and aquatic mammals possess an aspartic acid (D452) residue. Further analysis of hominoid sequences of MARCO identified an additional human-specific mutation, phenylalanine 282 (F282), within the collagenous domain. We show that residue 282 is polymorphic in humans, but only 17% of individuals (rs6761637) possess the ancestral serine residue at position 282. We show that rs6761637 is in linkage disequilibrium with MARCO polymorphisms that have been previously linked to susceptibility to pulmonary tuberculosis. To assess the functional importance of sites Q452 and F282 in humans, we cloned the ancestral residues and loss-of-function mutations and investigated the role of these residues in binding and internalizing polystyrene microspheres and Escherichia coli. Herein, we show that the residues at sites 452 and 282 enhance receptor function.}, } @article {pmid29138326, year = {2017}, author = {Mafessoni, F and Prüfer, K}, title = {Better support for a small effective population size of Neandertals and a long shared history of Neandertals and Denisovans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {48}, pages = {E10256-E10257}, pmid = {29138326}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Fossils ; Hominidae ; *Neanderthals ; *Population Density ; }, } @article {pmid29072654, year = {2017}, author = {Soldatsky, YL and Denisova, OA and Bulynko, SA}, title = {[The specific features of the past medical history and etiology of pharyngeal abscess in the children].}, journal = {Vestnik otorinolaringologii}, volume = {82}, number = {5}, pages = {12-14}, doi = {10.17116/otorino201782512-14}, pmid = {29072654}, issn = {0042-4668}, mesh = {Adolescent ; Anti-Bacterial Agents/*therapeutic use ; Child ; Female ; Humans ; Male ; Medical History Taking ; Needs Assessment ; *Patient Care Management/methods/organization & administration/standards ; *Peritonsillar Abscess/diagnosis/etiology/prevention & control ; *Retropharyngeal Abscess/diagnosis/etiology/prevention & control ; Risk Factors ; Russia/epidemiology ; *Streptococcal Infections/complications/diagnosis/drug therapy/epidemiology ; *Streptococcus pyogenes/isolation & purification/pathogenicity ; Tonsillectomy/*methods ; *Tonsillitis/complications/diagnosis/epidemiology/therapy ; }, abstract = {The present study was undertaken for the purpose of elucidating the specific features of the past medical history and the etiological factors responsible for the development of tonsillogenic pharyngeal abscesses in the children. We performed the retrospective analysis of the medical histories of 291 children presenting with this condition who had been admitted for the treatment to the ENT Department of the Morozovskzya City Children's Clinical Hospital during the period from January till December 2015. The study has demonstrated the following most common shortcomings of the outpatient treatment of the patients suffering from chronic tonsillitis at the stage preceding formation of paratonsillar abscess: inadequate antibacterial therapy of acute chronic tonsillitis or its exacerbation and limited indications for tonsillectomy at the level of the outpatient treatment. The leading role in the etiology of tonsillogenic pharyngeal abscesses in the children is played by beta-hemolytic Streptococcus of group A. It is concluded that the medical history suggesting past paratonsillar abscess is the absolute indication for the subsequent tonsillectomy in the children of any age.}, } @article {pmid29053564, year = {2018}, author = {Yazdanyar, A and Rizzuti, AE and Mechel, E and Denisova, K and Lazzaro, DR}, title = {Gout Keratitis: A Case of Peripheral Ulcerative Keratitis Secondary to Gout With a Review of the Literature.}, journal = {Cornea}, volume = {37}, number = {3}, pages = {379-381}, doi = {10.1097/ICO.0000000000001415}, pmid = {29053564}, issn = {1536-4798}, mesh = {Adult ; Corneal Stroma/pathology ; Corneal Ulcer/*etiology/metabolism/pathology ; Gout/*complications ; Humans ; Male ; Uric Acid/metabolism ; }, abstract = {PURPOSE: To report a case of peripheral ulcerative keratitis secondary to gout.

METHODS: A 41-year-old man with a history of severe gout disease presented with pain and redness of the right eye. Physical examination revealed 2 areas of peripheral corneal thinning with overlying epithelial defects. Adjacent to these areas, reflective crystals were identified in the corneal stroma. Anterior segment optical coherence tomography demonstrated stromal corneal deposits.

RESULTS: Systemic workup was negative aside from an elevated serum uric acid level. The patient was administered oral prednisone, allopurinol, and colchicine. At his 2-month follow-up visit, the patient was asymptomatic and his corneal thinning had significantly improved.

CONCLUSIONS: Gout is the most common type of inflammatory arthritis in adults with rising incidence and prevalence. Ocular findings in gout are common, but patients are usually asymptomatic. Monosodium urate crystal deposition has been reported to occur in various parts of the eye, with and without ocular inflammation. Crystal deposition in the cornea is extremely rare and may be a cause of peripheral ulcerative keratitis.}, } @article {pmid28989973, year = {2017}, author = {Vashee, S and Stockwell, TB and Alperovich, N and Denisova, EA and Gibson, DG and Cady, KC and Miller, K and Kannan, K and Malouli, D and Crawford, LB and Voorhies, AA and Bruening, E and Caposio, P and Früh, K}, title = {Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination.}, journal = {mSphere}, volume = {2}, number = {5}, pages = {}, pmid = {28989973}, issn = {2379-5042}, support = {R41 AI106090/AI/NIAID NIH HHS/United States ; }, abstract = {Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full-length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes.}, } @article {pmid28980560, year = {2017}, author = {Saakyan, SV and Katargina, LA and Krichevskaya, GI and Myakoshina, EB and Denisova, EV}, title = {[Specific immunoglobulins G and M in blood serum in retinoblastoma and 'pseudoretinoblastoma'].}, journal = {Vestnik oftalmologii}, volume = {133}, number = {4}, pages = {12-16}, doi = {10.17116/oftalma2017133412-16}, pmid = {28980560}, issn = {0042-465X}, mesh = {Antibodies, Bacterial/*blood ; Antibodies, Viral/*blood ; Child, Preschool ; *Cytomegalovirus Retinitis/diagnosis/etiology ; Diagnosis, Differential ; Eye Abnormalities/*diagnosis ; Female ; Humans ; Immunoglobulin G/*blood ; Immunoglobulin M/*blood ; Infant ; Infant, Newborn ; Male ; Neonatal Screening ; Pregnancy ; Prenatal Exposure Delayed Effects/*diagnosis/microbiology ; Retina/abnormalities/microbiology ; *Retinal Neoplasms/diagnosis/immunology/microbiology/pathology ; *Retinoblastoma/diagnosis/immunology/microbiology/pathology ; }, abstract = {UNLABELLED: Perinatal inflammatory retinal diseases and intrauterine retinal maldevelopments are mistaken for retinoblastoma as often as in 8-16% of cases.

AIM: To analyze the infectious status in children with retinoblastoma and pseudoretinoblastoma at different ages.

MATERIAL AND METHODS: A total of 47 retinoblastoma suspects aged 4-69 months were enrolled. Pseudoretinoblastoma (inflammatory retinal diseases and intrauterine maldevelopments of the retina) was detected in 14 children (group 1), retinoblastoma - in 33 children (group 2). In each group, two subgroups were identified: 'a' - children under 12 months of age (1a - 5 patients, 2a - 10 patients) and 'b'- children over 12 months of age (1b - 9 patients, 2b - 23 patients). Their blood sera were examined for antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, toxoplasma, toxocara, chlamydia, and mycoplasma (enzyme-linked immunosorbent assay).

RESULTS: According to serological screening, all patients from group 1a (children under 12 months of age with pseudoretinoblastoma), in contrast to other groups, were infected perinatally with cytomegalovirus infection. All 47 patients were seronegative to toxoplasma. Toxocara infection was identified in children over 12 months of age: in 3 out of 9 patients with pseudoretinoblastoma and in 2 out of 23 patients with retinoblastoma (p>0.05). Markers of Epstein-Barr viral activity were detected only in 3 retinoblastoma children over 12 months of age.

CONCLUSION: The results suggest that cytomegalovirus infection plays the leading role in the development of perinatal eye pathology, which, in infants, is clinically similar to retinoblastoma. In children over 12 months of age we found no serological signs that could be regarded as specific of either retinoblastoma, or pseudoretinoblastoma. The only thing worth paying attention to is the activation of Epstein-Barr virus infection in children over 12 months of age with retinoblastoma.}, } @article {pmid28950836, year = {2017}, author = {Xu, D and Jaber, Y and Pavlidis, P and Gokcumen, O}, title = {VCFtoTree: a user-friendly tool to construct locus-specific alignments and phylogenies from thousands of anthropologically relevant genome sequences.}, journal = {BMC bioinformatics}, volume = {18}, number = {1}, pages = {426}, pmid = {28950836}, issn = {1471-2105}, mesh = {Algorithms ; Animals ; Base Sequence ; *Genetic Loci ; *Genome, Human ; Humans ; INDEL Mutation/genetics ; *Phylogeny ; Primates ; Sequence Alignment/*methods ; Sequence Analysis, DNA ; *Software ; User-Computer Interface ; }, abstract = {BACKGROUND: Constructing alignments and phylogenies for a given locus from large genome sequencing studies with relevant outgroups allow novel evolutionary and anthropological insights. However, no user-friendly tool has been developed to integrate thousands of recently available and anthropologically relevant genome sequences to construct complete sequence alignments and phylogenies.

RESULTS: Here, we provide VCFtoTree, a user friendly tool with a graphical user interface that directly accesses online databases to download, parse and analyze genome variation data for regions of interest. Our pipeline combines popular sequence datasets and tree building algorithms with custom data parsing to generate accurate alignments and phylogenies using all the individuals from the 1000 Genomes Project, Neanderthal and Denisovan genomes, as well as reference genomes of Chimpanzee and Rhesus Macaque. It can also be applied to other phased human genomes, as well as genomes from other species. The output of our pipeline includes an alignment in FASTA format and a tree file in newick format.

CONCLUSION: VCFtoTree fulfills the increasing demand for constructing alignments and phylogenies for a given loci from thousands of available genomes. Our software provides a user friendly interface for a wider audience without prerequisite knowledge in programming. VCFtoTree can be accessed from https://github.com/duoduoo/VCFtoTree_3.0.0 .}, } @article {pmid28902892, year = {2017}, author = {Zanolli, C and Hourset, M and Esclassan, R and Mollereau, C}, title = {Neanderthal and Denisova tooth protein variants in present-day humans.}, journal = {PloS one}, volume = {12}, number = {9}, pages = {e0183802}, pmid = {28902892}, issn = {1932-6203}, mesh = {Animals ; Dental Enamel/anatomy & histology/metabolism ; Dental Enamel Proteins/*genetics/metabolism ; Fossils ; Gene Frequency ; Genome, Human ; Geography ; *Hominidae/genetics/metabolism ; Humans ; *Neanderthals/genetics/metabolism ; Organ Size ; Phylogeny ; *Polymorphism, Genetic ; Selection, Genetic ; Sequence Homology, Amino Acid ; Tooth/anatomy & histology/chemistry/*metabolism ; }, abstract = {Environment parameters, diet and genetic factors interact to shape tooth morphostructure. In the human lineage, archaic and modern hominins show differences in dental traits, including enamel thickness, but variability also exists among living populations. Several polymorphisms, in particular in the non-collagenous extracellular matrix proteins of the tooth hard tissues, like enamelin, are involved in dental structure variation and defects and may be associated with dental disorders or susceptibility to caries. To gain insights into the relationships between tooth protein polymorphisms and dental structural morphology and defects, we searched for non-synonymous polymorphisms in tooth proteins from Neanderthal and Denisova hominins. The objective was to identify archaic-specific missense variants that may explain the dental morphostructural variability between extinct and modern humans, and to explore their putative impact on present-day dental phenotypes. Thirteen non-collagenous extracellular matrix proteins specific to hard dental tissues have been selected, searched in the publicly available sequence databases of Neanderthal and Denisova individuals and compared with modern human genome data. A total of 16 non-synonymous polymorphisms were identified in 6 proteins (ameloblastin, amelotin, cementum protein 1, dentin matrix acidic phosphoprotein 1, enamelin and matrix Gla protein). Most of them are encoded by dentin and enamel genes located on chromosome 4, previously reported to show signs of archaic introgression within Africa. Among the variants shared with modern humans, two are ancestral (common with apes) and one is the derived enamelin major variant, T648I (rs7671281), associated with a thinner enamel and specific to the Homo lineage. All the others are specific to Neanderthals and Denisova, and are found at a very low frequency in modern Africans or East and South Asians, suggesting that they may be related to particular dental traits or disease susceptibility in these populations. This modern regional distribution of archaic dental polymorphisms may reflect persistence of archaic variants in some populations and may contribute in part to the geographic dental variations described in modern humans.}, } @article {pmid28900155, year = {2017}, author = {Denisova, K and Zhao, G}, title = {Inflexible neurobiological signatures precede atypical development in infants at high risk for autism.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {11285}, pmid = {28900155}, issn = {2045-2322}, mesh = {Age Factors ; Autism Spectrum Disorder/diagnosis/*etiology/*psychology ; Brain Mapping ; Child ; Child, Preschool ; Disease Susceptibility ; Female ; Humans ; Infant ; Learning ; Magnetic Resonance Imaging ; Male ; Neuroimaging ; Neuropsychological Tests ; Phenotype ; Risk Assessment ; Risk Factors ; }, abstract = {Variability in neurobiological signatures is ubiquitous in early life but the link to adverse developmental milestones in humans is unknown. We examined how levels of signal and noise in movement signatures during the 1st year of life constrain early development in 71 healthy typically developing infants, either at High or Low familial Risk (HR or LR, respectively) for developing Autism Spectrum Disorders (ASD). Delays in early learning developmental trajectories in HR infants (validated in an analysis of 1,445 infants from representative infant-sibling studies) were predicted by worse stochastic patterns in their spontaneous head movements as early as 1-2 months after birth, relative to HR infants who showed more rapid developmental progress, as well as relative to all LR infants. While LR 1-2 mo-old infants' movements were significantly different during a language listening task compared to during sleep, HR infants' movements were more similar during both conditions, a striking lack of diversity that reveals context-inflexible experience of ambient information. Contrary to expectation, it is not the level of variability per se that is particularly detrimental in early life. Rather, inflexible sensorimotor systems and/or atypical transition between behavioral states may interfere with the establishment of capacity to extract structure and important cues from sensory input at birth, preceding and contributing to an atypical brain developmental trajectory in toddlerhood.}, } @article {pmid28860198, year = {2017}, author = {Hawks, J}, title = {Neanderthals and Denisovans as biological invaders.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {37}, pages = {9761-9763}, pmid = {28860198}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Fossils ; *Hominidae ; Humans ; *Neanderthals ; }, } @article {pmid28855259, year = {2017}, author = {Gardner, EJ and Lam, VK and Harris, DN and Chuang, NT and Scott, EC and Pittard, WS and Mills, RE and , and Devine, SE}, title = {The Mobile Element Locator Tool (MELT): population-scale mobile element discovery and biology.}, journal = {Genome research}, volume = {27}, number = {11}, pages = {1916-1929}, pmid = {28855259}, issn = {1549-5469}, support = {R01 HG002898/HG/NHGRI NIH HHS/United States ; R01 HG006849/HG/NHGRI NIH HHS/United States ; R01 GM059290/GM/NIGMS NIH HHS/United States ; R01 CA166661/CA/NCI NIH HHS/United States ; F31 HG009223/HG/NHGRI NIH HHS/United States ; T32 DK067872/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Computational Biology/*methods ; *DNA Transposable Elements ; Databases, Genetic ; Evolution, Molecular ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Neanderthals/*genetics ; Pan troglodytes/*genetics ; Polymorphism, Single Nucleotide ; Software ; Whole Genome Sequencing/methods ; }, abstract = {Mobile element insertions (MEIs) represent ∼25% of all structural variants in human genomes. Moreover, when they disrupt genes, MEIs can influence human traits and diseases. Therefore, MEIs should be fully discovered along with other forms of genetic variation in whole genome sequencing (WGS) projects involving population genetics, human diseases, and clinical genomics. Here, we describe the Mobile Element Locator Tool (MELT), which was developed as part of the 1000 Genomes Project to perform MEI discovery on a population scale. Using both Illumina WGS data and simulations, we demonstrate that MELT outperforms existing MEI discovery tools in terms of speed, scalability, specificity, and sensitivity, while also detecting a broader spectrum of MEI-associated features. Several run modes were developed to perform MEI discovery on local and cloud systems. In addition to using MELT to discover MEIs in modern humans as part of the 1000 Genomes Project, we also used it to discover MEIs in chimpanzees and ancient (Neanderthal and Denisovan) hominids. We detected diverse patterns of MEI stratification across these populations that likely were caused by (1) diverse rates of MEI production from source elements, (2) diverse patterns of MEI inheritance, and (3) the introgression of ancient MEIs into modern human genomes. Overall, our study provides the most comprehensive map of MEIs to date spanning chimpanzees, ancient hominids, and modern humans and reveals new aspects of MEI biology in these lineages. We also demonstrate that MELT is a robust platform for MEI discovery and analysis in a variety of experimental settings.}, } @article {pmid28854687, year = {2017}, author = {Jinam, TA and Phipps, ME and Aghakhanian, F and Majumder, PP and Datar, F and Stoneking, M and Sawai, H and Nishida, N and Tokunaga, K and Kawamura, S and Omoto, K and Saitou, N}, title = {Discerning the Origins of the Negritos, First Sundaland People: Deep Divergence and Archaic Admixture.}, journal = {Genome biology and evolution}, volume = {9}, number = {8}, pages = {2013-2022}, pmid = {28854687}, issn = {1759-6653}, mesh = {Asian People/genetics ; *Genetics, Population ; *Genome, Human ; Genome-Wide Association Study ; Humans ; Malaysia ; Philippines ; *Phylogeny ; *Polymorphism, Single Nucleotide ; }, abstract = {Human presence in Southeast Asia dates back to at least 40,000 years ago, when the current islands formed a continental shelf called Sundaland. In the Philippine Islands, Peninsular Malaysia, and Andaman Islands, there exist indigenous groups collectively called Negritos whose ancestry can be traced to the "First Sundaland People." To understand the relationship between these Negrito groups and their demographic histories, we generated genome-wide single nucleotide polymorphism data in the Philippine Negritos and compared them with existing data from other populations. Phylogenetic tree analyses show that Negritos are basal to other East and Southeast Asians, and that they diverged from West Eurasians at least 38,000 years ago. We also found relatively high traces of Denisovan admixture in the Philippine Negritos, but not in the Malaysian and Andamanese groups, suggesting independent introgression and/or parallel losses involving Denisovan introgressed regions. Shared genetic loci between all three Negrito groups could be related to skin pigmentation, height, facial morphology and malarial resistance. These results show the unique status of Negrito groups as descended from the First Sundaland People.}, } @article {pmid28854627, year = {2017}, author = {Sharbrough, J and Havird, JC and Noe, GR and Warren, JM and Sloan, DB}, title = {The Mitonuclear Dimension of Neanderthal and Denisovan Ancestry in Modern Human Genomes.}, journal = {Genome biology and evolution}, volume = {9}, number = {6}, pages = {1567-1581}, pmid = {28854627}, issn = {1759-6653}, mesh = {Alleles ; Animals ; Cell Nucleus/chemistry/*genetics ; DNA, Mitochondrial/chemistry/*genetics ; *Evolution, Molecular ; Gene Flow ; *Genome, Human ; Hominidae/classification/*genetics ; Humans ; Neanderthals/classification/*genetics ; Nucleic Acid Conformation ; Polymorphism, Genetic ; Reproductive Isolation ; }, abstract = {Some human populations interbred with Neanderthals and Denisovans, resulting in substantial contributions to modern-human genomes. Therefore, it is now possible to use genomic data to investigate mechanisms that shaped historical gene flow between humans and our closest hominin relatives. More generally, in eukaryotes, mitonuclear interactions have been argued to play a disproportionate role in generating reproductive isolation. There is no evidence of mtDNA introgression into modern human populations, which means that all introgressed nuclear alleles from archaic hominins must function on a modern-human mitochondrial background. Therefore, mitonuclear interactions are also potentially relevant to hominin evolution. We performed a detailed accounting of mtDNA divergence among hominin lineages and used population-genomic data to test the hypothesis that mitonuclear incompatibilities have preferentially restricted the introgression of nuclear genes with mitochondrial functions. We found a small but significant underrepresentation of introgressed Neanderthal alleles at such nuclear loci. Structural analyses of mitochondrial enzyme complexes revealed that these effects are unlikely to be mediated by physically interacting sites in mitochondrial and nuclear gene products. We did not detect any underrepresentation of introgressed Denisovan alleles at mitochondrial-targeted loci, but this may reflect reduced power because locus-specific estimates of Denisovan introgression are more conservative. Overall, we conclude that genes involved in mitochondrial function may have been subject to distinct selection pressures during the history of introgression from archaic hominins but that mitonuclear incompatibilities have had, at most, a small role in shaping genome-wide introgression patterns, perhaps because of limited functional divergence in mtDNA and interacting nuclear genes.}, } @article {pmid28794033, year = {2017}, author = {Chen, Z and Ho, WCS and Boon, SS and Law, PTY and Chan, MCW and DeSalle, R and Burk, RD and Chan, PKS}, title = {Ancient Evolution and Dispersion of Human Papillomavirus 58 Variants.}, journal = {Journal of virology}, volume = {91}, number = {21}, pages = {}, pmid = {28794033}, issn = {1098-5514}, support = {U01 CA078527/CA/NCI NIH HHS/United States ; }, mesh = {Capsid Proteins/genetics ; *Evolution, Molecular ; *Genetic Variation ; Genome, Viral ; Humans ; Papillomaviridae/*classification/*genetics ; Papillomavirus Infections/*virology ; Phylogeny ; Selection, Genetic ; }, abstract = {Human papillomavirus 58 (HPV58) is found in 10 to 18% of cervical cancers in East Asia but is rather uncommon elsewhere. The distribution and oncogenic potential of HPV58 variants appear to be heterogeneous, since the E7 T20I/G63S variant is more prevalent in East Asia and confers a 7- to 9-fold-higher risk of cervical precancer and cancer. However, the underlying genomic mechanisms that explain the geographic and carcinogenic diversity of HPV58 variants are still poorly understood. In this study, we used a combination of phylogenetic analyses and bioinformatics to investigate the deep evolutionary history of HPV58 complete genome variants. The initial splitting of HPV58 variants was estimated to occur 478,600 years ago (95% highest posterior density [HPD], 391,000 to 569,600 years ago). This divergence time is well within the era of speciation between Homo sapiens and Neanderthals/Denisovans and around three times longer than the modern Homo sapiens divergence times. The expansion of present-day variants in Eurasia could be the consequence of viral transmission from Neanderthals/Denisovans to non-African modern human populations through gene flow. A whole-genome sequence signature analysis identified 3 amino acid changes, 16 synonymous nucleotide changes, and a 12-bp insertion strongly associated with the E7 T20I/G63S variant that represents the A3 sublineage and carries higher carcinogenetic potential. Compared with the capsid proteins, the oncogenes E7 and E6 had increased substitution rates indicative of higher selection pressure. These data provide a comprehensive evolutionary history and genomic basis of HPV58 variants to assist further investigation of carcinogenic association and the development of diagnostic and therapeutic strategies.IMPORTANCE Papillomaviruses (PVs) are an ancient and heterogeneous group of double-stranded DNA viruses that preferentially infect the cutaneous and mucocutaneous epithelia of vertebrates. Persistent infection by specific oncogenic human papillomaviruses (HPVs), including HPV58, has been established as the primary cause of cervical cancer. In this work, we reveal the complex evolutionary history of HPV58 variants that explains the heterogeneity of oncogenic potential and geographic distribution. Our data suggest that HPV58 variants may have coevolved with archaic hominins and dispersed across the planet through host interbreeding and gene flow. Certain genes and codons of HPV58 variants representing higher carcinogenic potential and/or that are under positive selection may have important implications for viral host specificity, pathogenesis, and disease prevention.}, } @article {pmid28784789, year = {2017}, author = {Rogers, AR and Bohlender, RJ and Huff, CD}, title = {Early history of Neanderthals and Denisovans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {37}, pages = {9859-9863}, pmid = {28784789}, issn = {1091-6490}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R25 CA057730/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Evolution, Molecular ; Fossils ; Gene Flow/*genetics ; Genome, Human/genetics ; Hominidae/*classification/*genetics ; Humans ; Neanderthals/classification/*genetics ; *Pedigree ; Phylogeny ; }, abstract = {Extensive DNA sequence data have made it possible to reconstruct human evolutionary history in unprecedented detail. We introduce a method to study the past several hundred thousand years. Our results show that (i) the Neanderthal-Denisovan lineage declined to a small size just after separating from the modern lineage, (ii) Neanderthals and Denisovans separated soon thereafter, and (iii) the subsequent Neanderthal population was large and deeply subdivided. They also (iv) support previous estimates of gene flow from Neanderthals into modern Eurasians. These results suggest an archaic human diaspora early in the Middle Pleistocene.}, } @article {pmid28747750, year = {2017}, author = {Lettre, G}, title = {The osteoarthritis and height GDF5 locus yields its secrets.}, journal = {Nature genetics}, volume = {49}, number = {8}, pages = {1165-1166}, pmid = {28747750}, issn = {1546-1718}, mesh = {*Growth Differentiation Factor 5 ; Humans ; *Osteoarthritis ; }, abstract = {A new study reports molecular characterization of the GDF5 locus, which is associated with osteoarthritis risk and adult height in humans. This study provides evidence of positive selection for short stature at GDF5 in modern humans, as well as in archaic Neandertals and Denisovans.}, } @article {pmid28726833, year = {2017}, author = {Clarkson, C and Jacobs, Z and Marwick, B and Fullagar, R and Wallis, L and Smith, M and Roberts, RG and Hayes, E and Lowe, K and Carah, X and Florin, SA and McNeil, J and Cox, D and Arnold, LJ and Hua, Q and Huntley, J and Brand, HEA and Manne, T and Fairbairn, A and Shulmeister, J and Lyle, L and Salinas, M and Page, M and Connell, K and Park, G and Norman, K and Murphy, T and Pardoe, C}, title = {Human occupation of northern Australia by 65,000 years ago.}, journal = {Nature}, volume = {547}, number = {7663}, pages = {306-310}, pmid = {28726833}, issn = {1476-4687}, mesh = {Africa/ethnology ; Animals ; Australia ; Diet/history ; Fossils ; Geologic Sediments/analysis ; History, Ancient ; Human Migration/*history ; Humans ; Neanderthals ; }, abstract = {The time of arrival of people in Australia is an unresolved question. It is relevant to debates about when modern humans first dispersed out of Africa and when their descendants incorporated genetic material from Neanderthals, Denisovans and possibly other hominins. Humans have also been implicated in the extinction of Australia's megafauna. Here we report the results of new excavations conducted at Madjedbebe, a rock shelter in northern Australia. Artefacts in primary depositional context are concentrated in three dense bands, with the stratigraphic integrity of the deposit demonstrated by artefact refits and by optical dating and other analyses of the sediments. Human occupation began around 65,000 years ago, with a distinctive stone tool assemblage including grinding stones, ground ochres, reflective additives and ground-edge hatchet heads. This evidence sets a new minimum age for the arrival of humans in Australia, the dispersal of modern humans out of Africa, and the subsequent interactions of modern humans with Neanderthals and Denisovans.}, } @article {pmid28720580, year = {2017}, author = {Peyrégne, S and Boyle, MJ and Dannemann, M and Prüfer, K}, title = {Detecting ancient positive selection in humans using extended lineage sorting.}, journal = {Genome research}, volume = {27}, number = {9}, pages = {1563-1572}, pmid = {28720580}, issn = {1549-5469}, support = {694707/ERC_/European Research Council/International ; }, mesh = {Animals ; *Evolution, Molecular ; *Genetics, Population ; Genome, Human/genetics ; Hominidae/*genetics ; Humans ; Neanderthals/genetics ; Selection, Genetic/*genetics ; }, abstract = {Natural selection that affected modern humans early in their evolution has likely shaped some of the traits that set present-day humans apart from their closest extinct and living relatives. The ability to detect ancient natural selection in the human genome could provide insights into the molecular basis for these human-specific traits. Here, we introduce a method for detecting ancient selective sweeps by scanning for extended genomic regions where our closest extinct relatives, Neandertals and Denisovans, fall outside of the present-day human variation. Regions that are unusually long indicate the presence of lineages that reached fixation in the human population faster than expected under neutral evolution. Using simulations, we show that the method is able to detect ancient events of positive selection and that it can differentiate those from background selection. Applying our method to the 1000 Genomes data set, we find evidence for ancient selective sweeps favoring regulatory changes and present a list of genomic regions that are predicted to underlie positively selected human specific traits.}, } @article {pmid28695206, year = {2017}, author = {Slon, V and Viola, B and Renaud, G and Gansauge, MT and Benazzi, S and Sawyer, S and Hublin, JJ and Shunkov, MV and Derevianko, AP and Kelso, J and Prüfer, K and Meyer, M and Pääbo, S}, title = {A fourth Denisovan individual.}, journal = {Science advances}, volume = {3}, number = {7}, pages = {e1700186}, pmid = {28695206}, issn = {2375-2548}, support = {694707/ERC_/European Research Council/International ; }, abstract = {The presence of Neandertals in Europe and Western Eurasia before the arrival of anatomically modern humans is well supported by archaeological and paleontological data. In contrast, fossil evidence for Denisovans, a sister group of Neandertals recently identified on the basis of DNA sequences, is limited to three specimens, all of which originate from Denisova Cave in the Altai Mountains (Siberia, Russia). We report the retrieval of DNA from a deciduous lower second molar (Denisova 2), discovered in a deep stratigraphic layer in Denisova Cave, and show that this tooth comes from a female Denisovan individual. On the basis of the number of "missing substitutions" in the mitochondrial DNA determined from the specimen, we find that Denisova 2 is substantially older than two of the other Denisovans, reinforcing the view that Denisovans were likely to have been present in the vicinity of Denisova Cave over an extended time period. We show that the level of nuclear DNA sequence diversity found among Denisovans is within the lower range of that of present-day human populations.}, } @article {pmid28675384, year = {2017}, author = {Posth, C and Wißing, C and Kitagawa, K and Pagani, L and van Holstein, L and Racimo, F and Wehrberger, K and Conard, NJ and Kind, CJ and Bocherens, H and Krause, J}, title = {Deeply divergent archaic mitochondrial genome provides lower time boundary for African gene flow into Neanderthals.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {16046}, pmid = {28675384}, issn = {2041-1723}, mesh = {Animals ; Black People/*genetics ; DNA, Mitochondrial/*genetics ; *Evolution, Molecular ; Femur ; *Gene Flow ; Genome, Human/genetics ; *Genome, Mitochondrial ; Germany ; Hominidae/*genetics ; Humans ; Neanderthals/*genetics ; Time Factors ; }, abstract = {Ancient DNA is revealing new insights into the genetic relationship between Pleistocene hominins and modern humans. Nuclear DNA indicated Neanderthals as a sister group of Denisovans after diverging from modern humans. However, the closer affinity of the Neanderthal mitochondrial DNA (mtDNA) to modern humans than Denisovans has recently been suggested as the result of gene flow from an African source into Neanderthals before 100,000 years ago. Here we report the complete mtDNA of an archaic femur from the Hohlenstein-Stadel (HST) cave in southwestern Germany. HST carries the deepest divergent mtDNA lineage that splits from other Neanderthals ∼270,000 years ago, providing a lower boundary for the time of the putative mtDNA introgression event. We demonstrate that a complete Neanderthal mtDNA replacement is feasible over this time interval even with minimal hominin introgression. The highly divergent HST branch is indicative of greater mtDNA diversity during the Middle Pleistocene than in later periods.}, } @article {pmid28671685, year = {2017}, author = {Capellini, TD and Chen, H and Cao, J and Doxey, AC and Kiapour, AM and Schoor, M and Kingsley, DM}, title = {Ancient selection for derived alleles at a GDF5 enhancer influencing human growth and osteoarthritis risk.}, journal = {Nature genetics}, volume = {49}, number = {8}, pages = {1202-1210}, pmid = {28671685}, issn = {1546-1718}, support = {P30 AR066261/AR/NIAMS NIH HHS/United States ; R01 AR042236/AR/NIAMS NIH HHS/United States ; R37 AR042236/AR/NIAMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Chromosomes, Artificial, Bacterial ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Growth Differentiation Factor 5/*genetics ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Transgenic ; Osteoarthritis/*genetics ; *Selection, Genetic ; }, abstract = {Variants in GDF5 are associated with human arthritis and decreased height, but the causal mutations are still unknown. We surveyed the Gdf5 locus for regulatory regions in transgenic mice and fine-mapped separate enhancers controlling expression in joints versus growing ends of long bones. A large downstream regulatory region contains a novel growth enhancer (GROW1), which is required for normal Gdf5 expression at ends of developing bones and for normal bone lengths in vivo. Human GROW1 contains a common base-pair change that decreases enhancer activity and colocalizes with peaks of positive selection in humans. The derived allele is rare in Africa but common in Eurasia and is found in Neandertals and Denisovans. Our results suggest that an ancient regulatory variant in GROW1 has been repeatedly selected in northern environments and that past selection on growth phenotypes explains the high frequency of a GDF5 haplotype that also increases arthritis susceptibility in many human populations.}, } @article {pmid28669760, year = {2017}, author = {Margaryan, A and Derenko, M and Hovhannisyan, H and Malyarchuk, B and Heller, R and Khachatryan, Z and Avetisyan, P and Badalyan, R and Bobokhyan, A and Melikyan, V and Sargsyan, G and Piliposyan, A and Simonyan, H and Mkrtchyan, R and Denisova, G and Yepiskoposyan, L and Willerslev, E and Allentoft, ME}, title = {Eight Millennia of Matrilineal Genetic Continuity in the South Caucasus.}, journal = {Current biology : CB}, volume = {27}, number = {13}, pages = {2023-2028.e7}, doi = {10.1016/j.cub.2017.05.087}, pmid = {28669760}, issn = {1879-0445}, mesh = {Archaeology ; Armenia ; Azerbaijan ; Bayes Theorem ; DNA, Ancient/analysis ; *Gene Pool ; *Genetic Variation ; *Genome, Human ; *Genome, Mitochondrial ; Human Migration ; Humans ; }, abstract = {The South Caucasus, situated between the Black and Caspian Seas, geographically links Europe with the Near East and has served as a crossroad for human migrations for many millennia [1-7]. Despite a vast archaeological record showing distinct cultural turnovers, the demographic events that shaped the human populations of this region is not known [8, 9]. To shed light on the maternal genetic history of the region, we analyzed the complete mitochondrial genomes of 52 ancient skeletons from present-day Armenia and Artsakh spanning 7,800 years and combined this dataset with 206 mitochondrial genomes of modern Armenians. We also included previously published data of seven neighboring populations (n = 482). Coalescence-based analyses suggest that the population size in this region rapidly increased after the Last Glacial Maximum ca. 18 kya. We find that the lowest genetic distance in this dataset is between modern Armenians and the ancient individuals, as also reflected in both network analyses and discriminant analysis of principal components. We used approximate Bayesian computation to test five different demographic scenarios explaining the formation of the modern Armenian gene pool. Despite well documented cultural shifts in the South Caucasus across this time period, our results strongly favor a genetic continuity model in the maternal gene pool. This has implications for interpreting prehistoric migration dynamics and cultural shifts in this part of the world.}, } @article {pmid28655834, year = {2017}, author = {Easton, JD and Aunes, M and Albers, GW and Amarenco, P and Bokelund-Singh, S and Denison, H and Evans, SR and Held, P and Jahreskog, M and Jonasson, J and Minematsu, K and Molina, CA and Wang, Y and Wong, KSL and Johnston, SC and , }, title = {Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).}, journal = {Circulation}, volume = {136}, number = {10}, pages = {907-916}, doi = {10.1161/CIRCULATIONAHA.117.028566}, pmid = {28655834}, issn = {1524-4539}, mesh = {Adenosine/administration & dosage/adverse effects/*analogs & derivatives ; Aged ; Aspirin/administration & dosage/*adverse effects ; Female ; Hemorrhage/*chemically induced ; Humans ; Ischemic Attack, Transient/*complications/drug therapy ; Male ; Purinergic P2Y Receptor Antagonists/administration & dosage/*adverse effects ; Risk ; Stroke/*complications/drug therapy ; Ticagrelor ; Treatment Outcome ; }, abstract = {BACKGROUND: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH).

METHODS: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population.

RESULTS: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor.

CONCLUSIONS: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs.

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.}, } @article {pmid28615036, year = {2017}, author = {Alexeeva, EI and Namazova-Baranova, LS and Bzarova, TM and Valieva, SI and Denisova, RV and Sleptsova, TV and Isaeva, KB and Chomahidze, AM and Taibulatov, NI and Fetisova, AN and Karaseva, AV and Baranov, AA}, title = {Predictors of the response to etanercept in patients with juvenile idiopathic arthritis without systemic manifestations within 12 months: results of an open-label, prospective study conducted at the National Scientific and Practical Center of Children's Health, Russia.}, journal = {Pediatric rheumatology online journal}, volume = {15}, number = {1}, pages = {51}, pmid = {28615036}, issn = {1546-0096}, mesh = {Age of Onset ; Antirheumatic Agents/administration & dosage/adverse effects ; *Arthritis, Juvenile/diagnosis/drug therapy/epidemiology ; C-Reactive Protein/analysis ; Child ; Child, Preschool ; Drug Monitoring/methods ; *Etanercept/administration & dosage/adverse effects ; Female ; Humans ; Male ; Outcome and Process Assessment, Health Care ; Patient Acuity ; Range of Motion, Articular/drug effects ; Russia/epidemiology ; Severity of Illness Index ; }, abstract = {BACKGROUND: The aim of this study was to investigate the efficacy of etanercept treatment and to identify predictors of response to therapy within 12 months in patients with juvenile idiopathic arthritis (JIA) without systemic manifestations.

METHODS: A total of 197 juvenile patients were enrolled in this study. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the Wallace criteria, and the Juvenile Arthritis Disease Activity Score 71 (JADAS-71). Univariate and multivariate logistic regression analyses were performed to identify potential baseline factors associated with treatment response in different JIA categories.

RESULTS: One year after treatment initiation, 179 (90.9%) patients achieved ACRPedi30; 177 (89.8%) patients achieved ACRPedi50; 168 (85.3%) patients achieved ACRPedi70; and 135 (68.5%) patients achieved ACRPedi90 response. A total of 132 (67.0%) and 92 (46.7%) patients achieved inactive disease according to the Wallace criteria and the JADAS-71 cut-off point, respectively. Excellent response (achieving ACRPedi90 and clinically inactive disease according both to the Wallace criteria and the JADAS71 cut-off point) was associated with persistent oligoarticular JIA category, shorter disease duration before the start of etanercept, a lower number of DMARDs used before the introduction of etanercept, a lower number of joints with limited motion, and lower C-reactive protein at baseline. Poor response (failure to achieve ACR 70 or active disease according to both the Wallace criteria and JADAS71 even when ACR 70 was achieved) was associated with the polyarticular or enthesitis-related JIA categories, higher disease duration before the start of etanercept, and older age at disease onset.

CONCLUSION: Almost half (45.7%) of the patients who initiated etanercept treatment achieved an excellent response (inactive disease and ACRPedi90) after 1 year. What may be novel is our finding that the response to etanercept therapy was strongly associated with the JIA category. The response to etanercept therapy was also associated with the disease duration before the start of etanercept treatment.}, } @article {pmid28572766, year = {2017}, author = {Guo, S and Lai, C and Wu, C and Cen, G and , }, title = {Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images.}, journal = {Frontiers in aging neuroscience}, volume = {9}, number = {}, pages = {146}, pmid = {28572766}, issn = {1663-4365}, support = {K23 NS083711/NS/NINDS NIH HHS/United States ; P30 AG010129/AG/NIA NIH HHS/United States ; P50 AG005142/AG/NIA NIH HHS/United States ; }, abstract = {Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI-cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI-NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI-NC comparison. The best performances obtained by the SVM classifier using the essential features were 5-40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.}, } @article {pmid28514400, year = {2017}, author = {Denisova, OA and Livzan, MA and Denisov, AP}, title = {[Comparative characteristics of patients with gastroesophageal reflux disease in the age aspect].}, journal = {Terapevticheskii arkhiv}, volume = {89}, number = {4}, pages = {53-56}, doi = {10.17116/terarkh201789453-56}, pmid = {28514400}, issn = {0040-3660}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Esophageal pH Monitoring ; *Esophagitis, Peptic/etiology ; *Gastroesophageal Reflux/complications/diagnosis ; Humans ; Middle Aged ; Young Adult ; }, abstract = {AIM: To compare the characteristics of patients with gastroesophageal reflux disease (GERD) by age groups, a wide range of clinical signs, including life-of-quality (QOL) indicators, and instrumental findings.

SUBJECTS AND METHODS: A total of 110 patients aged 18 to 86 years with GERD were examined in accordance with the standard protocol. Two groups with equal numbers of patents were formed. A study group included elderly and senile patients and a control group consisted of young and adult ones.

RESULTS: The elderly patients with GERD were observed to have a number of age-related clinical features and age-unrelated symptoms. The scores in the scales characterizing the physical health component and those in the general health and vital activity scales were markedly decreased in patients older than 60 years of age. No age-related statistically significant differences were found in the esophageal, gastric, and duodenal mucosae. Daily pH-metry in the elderly showed indirect evidence for esophageal hypomotor dyskinesia in the predominance of alkaline refluxes.

CONCLUSION: The cohort of elderly patients with GERD was ascertained to have statistically significant clinical characteristics, and QOL and pH-metry indicators, which will be able to improve methods for diagnosis and early prevention in this age group.}, } @article {pmid28464262, year = {2017}, author = {Reales, G and Rovaris, DL and Jacovas, VC and Hünemeier, T and Sandoval, JR and Salazar-Granara, A and Demarchi, DA and Tarazona-Santos, E and Felkl, AB and Serafini, MA and Salzano, FM and Bisso-Machado, R and Comas, D and Paixão-Côrtes, VR and Bortolini, MC}, title = {A tale of agriculturalists and hunter-gatherers: Exploring the thrifty genotype hypothesis in native South Americans.}, journal = {American journal of physical anthropology}, volume = {163}, number = {3}, pages = {591-601}, doi = {10.1002/ajpa.23233}, pmid = {28464262}, issn = {1096-8644}, mesh = {Agriculture/*history ; Anthropology, Physical ; Apolipoproteins E/genetics ; CD36 Antigens/genetics ; Genotype ; History, Ancient ; Humans ; Indians, South American/*genetics/*history ; Polymorphism, Single Nucleotide/*genetics ; RNA-Binding Proteins/genetics ; }, abstract = {OBJECTIVES: To determine genetic differences between agriculturalist and hunter-gatherer southern Native American populations for selected metabolism-related markers and to test whether Neel's thrifty genotype hypothesis (TGH) could explain the genetic patterns observed in these populations.

MATERIALS AND METHODS: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36 rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701). Additionally, APOE genotypes from 39 individuals were obtained from the literature. AMOVA, main effects, and gene-gene interaction tests were performed.

RESULTS: We observed differences in allele distribution patterns between agriculturalists and hunter-gatherers for some markers. For instance, between-groups component of genetic variance (FCT) for APOE rs429358 showed strong differences in allelic distributions between hunter-gatherers and agriculturalists (p = 0.00196). Gene-gene interaction analysis indicated that the APOE E4/CD36 TT and APOE E4/IGF2BP2 A carrier combinations occur at a higher frequency in hunter-gatherers, but this combination is not replicated in archaic (Neanderthal and Denisovan) and ancient (Anzick, Saqqaq, Ust-Ishim, Mal'ta) hunter-gatherer individuals.

DISCUSSION: A complex scenario explains the observed frequencies of the tested markers in hunter-gatherers. Different factors, such as pleotropic alleles, rainforest selective pressures, and population dynamics, may be collectively shaping the observed genetic patterns. We conclude that although TGH seems a plausible hypothesis to explain part of the data, other factors may be important in our tested populations.}, } @article {pmid28450384, year = {2017}, author = {Slon, V and Hopfe, C and Weiß, CL and Mafessoni, F and de la Rasilla, M and Lalueza-Fox, C and Rosas, A and Soressi, M and Knul, MV and Miller, R and Stewart, JR and Derevianko, AP and Jacobs, Z and Li, B and Roberts, RG and Shunkov, MV and de Lumley, H and Perrenoud, C and Gušić, I and Kućan, Ž and Rudan, P and Aximu-Petri, A and Essel, E and Nagel, S and Nickel, B and Schmidt, A and Prüfer, K and Kelso, J and Burbano, HA and Pääbo, S and Meyer, M}, title = {Neandertal and Denisovan DNA from Pleistocene sediments.}, journal = {Science (New York, N.Y.)}, volume = {356}, number = {6338}, pages = {605-608}, doi = {10.1126/science.aam9695}, pmid = {28450384}, issn = {1095-9203}, mesh = {Animals ; Caves ; DNA, Ancient/analysis/*isolation & purification ; DNA, Mitochondrial/analysis/*isolation & purification ; Europe ; Fossils ; Geologic Sediments/chemistry ; Hominidae/*classification/*genetics ; Sequence Analysis, DNA ; }, abstract = {Although a rich record of Pleistocene human-associated archaeological assemblages exists, the scarcity of hominin fossils often impedes the understanding of which hominins occupied a site. Using targeted enrichment of mitochondrial DNA, we show that cave sediments represent a rich source of ancient mammalian DNA that often includes traces of hominin DNA, even at sites and in layers where no hominin remains have been discovered. By automation-assisted screening of numerous sediment samples, we detected Neandertal DNA in eight archaeological layers from four caves in Eurasia. In Denisova Cave, we retrieved Denisovan DNA in a Middle Pleistocene layer near the bottom of the stratigraphy. Our work opens the possibility of detecting the presence of hominin groups at sites and in areas where no skeletal remains are found.}, } @article {pmid28448578, year = {2017}, author = {Hu, H and Petousi, N and Glusman, G and Yu, Y and Bohlender, R and Tashi, T and Downie, JM and Roach, JC and Cole, AM and Lorenzo, FR and Rogers, AR and Brunkow, ME and Cavalleri, G and Hood, L and Alpatty, SM and Prchal, JT and Jorde, LB and Robbins, PA and Simonson, TS and Huff, CD}, title = {Evolutionary history of Tibetans inferred from whole-genome sequencing.}, journal = {PLoS genetics}, volume = {13}, number = {4}, pages = {e1006675}, pmid = {28448578}, issn = {1553-7404}, support = {R35 GM118335/GM/NIGMS NIH HHS/United States ; 089457/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; R01 GM104390/GM/NIGMS NIH HHS/United States ; P50 GM076547/GM/NIGMS NIH HHS/United States ; R01 GM059290/GM/NIGMS NIH HHS/United States ; I01 CX001372/CX/CSRD VA/United States ; R00 HL118215/HL/NHLBI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; P30 CA016672/CA/NCI NIH HHS/United States ; R25 CA057730/CA/NCI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Altitude ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cytochrome P-450 Enzyme System/genetics ; Female ; *Genome, Human ; Haplotypes ; High-Throughput Nucleotide Sequencing ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases/genetics ; Male ; Molecular Sequence Annotation ; Proteins/genetics ; Receptors, Calcitriol/genetics ; Selection, Genetic/*genetics ; Tibet ; }, abstract = {The indigenous people of the Tibetan Plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude. Recent studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high altitude-adaptation and originated in an archaic Denisovan-related population. We sequenced the whole-genomes of 27 Tibetans and conducted analyses to infer a detailed history of demography and natural selection of this population. We detected evidence of population structure between the ancestral Han and Tibetan subpopulations as early as 44 to 58 thousand years ago, but with high rates of gene flow until approximately 9 thousand years ago. The CMS test ranked EPAS1 and EGLN1 as the top two positive selection candidates, and in addition identified PTGIS, VDR, and KCTD12 as new candidate genes. The advantageous Tibetan EPAS1 haplotype shared many variants with the Denisovan genome, with an ancient gene tree divergence between the Tibetan and Denisovan haplotypes of about 1 million years ago. With the exception of EPAS1, we observed no evidence of positive selection on Denisovan-like haplotypes.}, } @article {pmid28444387, year = {2017}, author = {Jégou, B and Sankararaman, S and Rolland, AD and Reich, D and Chalmel, F}, title = {Meiotic Genes Are Enriched in Regions of Reduced Archaic Ancestry.}, journal = {Molecular biology and evolution}, volume = {34}, number = {8}, pages = {1974-1980}, pmid = {28444387}, issn = {1537-1719}, support = {R00 GM111744/GM/NIGMS NIH HHS/United States ; R01 GM100233/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Alleles ; Animals ; Databases, Genetic ; Evolution, Molecular ; Gene Expression Regulation, Developmental/genetics ; Genome, Human/genetics ; Genomics ; Hominidae/*genetics ; Humans ; Male ; Meiosis/*genetics ; Neanderthals/*genetics ; Selection, Genetic ; Testis ; }, abstract = {About 1-6% of the genetic ancestry of modern humans today originates from admixture with archaic humans. It has recently been shown that autosomal genomic regions with a reduced proportion of Neanderthal and Denisovan ancestries (NA and DA) are significantly enriched in genes that are more expressed in testis than in other tissues. To determine whether a cellular segregation pattern would exist, we combined maps of archaic introgression with a cross-analysis of three transcriptomic datasets deciphering the transcriptional landscape of human gonadal cell types. We reveal that the regions deficient in both NA and DA contain a significant enrichment of genes transcribed in meiotic germ cells. The interbreeding of anatomically modern humans with archaic humans may have introduced archaic-derived alleles that contributed to genetic incompatibilities affecting meiosis that were subsequently purged by natural selection.}, } @article {pmid28434540, year = {2017}, author = {Ao, H and Liu, CR and Roberts, AP and Zhang, P and Xu, X}, title = {An updated age for the Xujiayao hominin from the Nihewan Basin, North China: Implications for Middle Pleistocene human evolution in East Asia.}, journal = {Journal of human evolution}, volume = {106}, number = {}, pages = {54-65}, doi = {10.1016/j.jhevol.2017.01.014}, pmid = {28434540}, issn = {1095-8606}, mesh = {Animals ; China ; *Electron Spin Resonance Spectroscopy ; *Fossils ; *Hominidae ; Humans ; Molar ; Neanderthals ; Time Factors ; }, abstract = {The Xujiayao site in the Nihewan Basin (North China) is one of the most important Paleolithic sites in East Asia. Twenty Homo fossils, which were previously assigned to an archaic Homo sapiens group, have been excavated along with more than 30,000 lithic artifacts and ∼5000 mammalian fossil specimens. Dating of the Xujiayao hominin has been pursued since its excavation in the 1970s, but its age has remained controversial because of limitations of the dating techniques that have been applied to available materials. Here, we report new ages for the Xujiayao hominin based on combined electron spin resonance (ESR) dating of quartz in the sediments and high-resolution magnetostratigraphy of the fluvio-lacustrine sequence. The magnetostratigraphy suggests that the upper Matuyama and Brunhes polarity chrons are recorded at Xujiayao. The ESR dating results indicate a pooled average age of 260-370 ka for the Homo-bearing layer, which is consistent with its position within the middle Brunhes normal polarity chron indicated by magnetostratigraphy. This age estimate makes the Xujiayao hominin among the oldest mid-Pleistocene hominins with derived Neanderthal traits in East Asia. This age is consistent with the time when early Denisovans, a sister group of Neanderthals, appeared and colonized eastern Eurasia. Our updated age and the Neanderthal-like traits of the Xujiayao Homo fossils, particularly the Denisovan-like molar teeth, make it possible that the Xujiayao hominin could represent an early Denisovan.}, } @article {pmid28410231, year = {2017}, author = {Heidenreich, B and Denisova, E and Rachakonda, S and Sanmartin, O and Dereani, T and Hosen, I and Nagore, E and Kumar, R}, title = {Genetic alterations in seborrheic keratoses.}, journal = {Oncotarget}, volume = {8}, number = {22}, pages = {36639-36649}, pmid = {28410231}, issn = {1949-2553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Biomarkers ; DNA Mutational Analysis ; Female ; Gene Expression ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; *Genetic Variation ; Genotype ; Humans ; Keratosis, Seborrheic/*genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Single Nucleotide ; Exome Sequencing ; }, abstract = {Seborrheic keratoses are common benign epidermal lesions that are associated with increased age and sun-exposure. Those lesions despite harboring multiple somatic alterations in contrast to malignant tumors appear to be genetically stable. In order to investigate and characterize the presence of recurrent mutations, we performed exome sequencing on DNA from one seborrheic keratosis lesion and corresponding blood cells from the same patients with follow up investigation of alterations identified by exome sequencing in 24 additional lesions from as many patients. In addition we investigated alterations in all lesions at specific genes loci that included FGFR3, PIK3CA, HRAS, BRAF, CDKN2A and TERT and DHPH3 promoters. The exome sequencing data indicated three mutations per Mb of the targeted sequence. The mutational pattern depicted typical UV signature with majority of alterations being C>T and CC>TT base changes at dipyrimidinic sites. The FGFR3 mutations were the most frequent, detected in 12 of 25 (48%) lesions, followed by the PIK3CA (32%), TERT promoter (24%) and DPH3 promoter mutations (24%). TERT promoter mutations associated with increased age and were present mainly in the lesions excised from head and neck. Three lesions also carried alterations in CDKN2A. FGFR3, TERT and DPH3 expression did not correlate with mutations in the respective genes and promoters; however, increased FGFR3 transcript levels were associated with increased FOXN1 levels, a suggested positive feedback loop that stalls malignant progression. Thus, in this study we report overall mutation rate through exome sequencing and show the most frequent mutations seborrheic keratosis.}, } @article {pmid28408228, year = {2017}, author = {Kharitonova, MI and Denisova, AO and Andronova, VL and Kayushin, AL and Konstantinova, ID and Kotovskaya, SK and Galegov, GA and Charushin, VN and Miroshnikov, AI}, title = {New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their activity against herpes simplex virus type 1.}, journal = {Bioorganic & medicinal chemistry letters}, volume = {27}, number = {11}, pages = {2484-2487}, doi = {10.1016/j.bmcl.2017.03.100}, pmid = {28408228}, issn = {1464-3405}, mesh = {Acyclovir/pharmacology ; Antiviral Agents/*chemical synthesis/pharmacology ; Benzimidazoles/*chemistry ; Cidofovir ; Cytosine/analogs & derivatives/pharmacology ; Drug Resistance, Viral/drug effects ; Foscarnet/pharmacology ; Herpesvirus 1, Human/drug effects ; Humans ; Nucleosides/*chemistry/pharmacology ; Organophosphonates/pharmacology ; }, abstract = {Using the enzymatic transglycosylation reaction β-d-ribo- and 2'-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient.}, } @article {pmid28346564, year = {2017}, author = {Hu, Y and Malyutina, S and Pikhart, H and Peasey, A and Holmes, MV and Hubacek, J and Denisova, D and Nikitin, Y and Bobak, M}, title = {The Relationship between Body Mass Index and 10-Year Trajectories of Physical Functioning in Middle-Aged and Older Russians: Prospective Results of the Russian HAPIEE Study.}, journal = {The journal of nutrition, health & aging}, volume = {21}, number = {4}, pages = {381-388}, pmid = {28346564}, issn = {1760-4788}, support = {081081/Z/06/Z//Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Aging/*physiology ; Body Height ; Body Mass Index ; Body Weight ; Cohort Studies ; Data Collection ; Female ; *Health Status ; Humans ; Male ; Middle Aged ; Obesity/epidemiology/*pathology ; Physical Fitness/*physiology ; Prospective Studies ; Risk Factors ; Russia/epidemiology ; }, abstract = {OBJECTIVE: To investigate the associations of overweight and obesity with longitudinal decline in physical functioning (PF) among middle-aged and older Russians.

DESIGN: Prospective cohort study.

SETTING: Four rounds of data collection in the Russian Health, Alcohol and Psychosocial factors In Eastern Europe study with up to 10 years of follow-up.

PARTICIPANTS: 9,222 men and women aged 45-69 years randomly selected from the population of two districts of Novosibirsk, Russia.

MEASUREMENTS: PF score (range 0-100) was measured by the Physical Functioning Subscale (PF-10) of the 36-item Short Form Health Survey (SF-36) at baseline and three subsequent occasions. Body mass index (BMI), derived from objectively measured body height and weight at baseline, was classified into normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obesity class I (BMI 30.0-34.9), and obesity class II+ (BMI≥35.0).

RESULTS: The mean annual decline in the PF score during the follow-up was -1.92 (95% confidence interval -2.17; -1.68) in men and -1.91 (-2.13; -1.68) in women. At baseline, compared with normal weight, obesity classes I and II+ (but not overweight) were associated with significantly lower PF in both sexes. In prospective analyses, the decline in PF was faster in overweight men (difference from normal weight subjects -0.38 [-0.63; -0.14]), class I obese men and women (-0.49 [-0.82; -0.17] and -0.44 [-0.73; -0.15] respectively) and class II+ obese men and women (-1.13 [-1.73; -0.53] and -0.43 [-0.77; -0.09] respectively). Adjustment for physical activity and other covariates did not materially change the results.

CONCLUSIONS: PF decreased more rapidly in obese men and women than among those with normal weight. The adverse effect of high BMI on PF trajectories appeared to be more pronounced in men than in women, making more extremely obese Russian men an important target population to prevent/slow down the process of decline in PF.}, } @article {pmid28282561, year = {2017}, author = {Baklanova, YV and Lipina, OA and Maksimova, LG and Tyutyunnik, AP and Leonidov, II and Denisova, TA and Zubkov, VG}, title = {Nd[3+], Ho[3+]-codoped garnet-related Li7La3Hf2O12 phosphor with NIR luminescence.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {180}, number = {}, pages = {105-109}, doi = {10.1016/j.saa.2017.03.007}, pmid = {28282561}, issn = {1873-3557}, abstract = {Simultaneous emission lines around 1.05μm, 1.3μm, 1.8μm, 2.1μm and 2.7μm have been observed in Li7La3-xNdxHf2O12:Ho[3+] (x=0.00-0.15) under 808nm laser diode excitation. Near-infrared luminescence due to holmium ions with residual concentration in the Li7La3Hf2O12 host has been studied. The intensity of 2.1 and 2.7μm lines associated with [5]I7→[5]I8 and [5]I6→[5]I7 transitions in Ho[3+] depends on the neodymium codopant concentration. This result indicates that Nd[3+] ions can be potentially used as sensitizers for Ho[3+] ions to stimulate the intense near-infrared emission in this system. Possible energy transfer mechanisms between lanthanide ions have been briefly discussed.}, } @article {pmid28264524, year = {2017}, author = {Denisova, AV and Tibbelin, J and Emanuelsson, R and Ottosson, H}, title = {A Computational Investigation of the Substituent Effects on Geometric, Electronic, and Optical Properties of Siloles and 1,4-Disilacyclohexa-2,5-dienes.}, journal = {Molecules (Basel, Switzerland)}, volume = {22}, number = {3}, pages = {}, pmid = {28264524}, issn = {1420-3049}, mesh = {Electrons ; Models, Molecular ; Organosilicon Compounds/*chemistry ; Quantum Theory ; Silanes/*chemistry ; }, abstract = {Thirty two differently substituted siloles 1a-1p and 1,4-disilacyclohexa-2,5-dienes 2a-2p were investigated by quantum chemical calculations using the PBE0 hybrid density functional theory (DFT) method. The substituents included σ-electron donating and withdrawing, as well as π-electron donating and withdrawing groups, and their effects when placed at the Si atom(s) or at the C atoms were examined. Focus was placed on geometries, frontier orbital energies and the energies of the first allowed electronic excitations. We analyzed the variation in energies between the orbitals which correspond to HOMO and LUMO for the two parent species, here represented as ΔεHL, motivated by the fact that the first allowed transitions involve excitation between these orbitals. Even though ΔεHL and the excitation energies are lower for siloles than for 1,4-disilacyclohexa-2,5-dienes the latter display significantly larger variations with substitution. The ΔεHL of the siloles vary within 4.57-5.35 eV (ΔΔεHL = 0.78 eV) while for the 1,4-disilacyclohexa-2,5-dienes the range is 5.49-7.15 eV (ΔΔεHL = 1.66 eV). The excitation energy of the first allowed transitions display a moderate variation for siloles (3.60-4.41 eV) whereas the variation for 1,4-disilacyclohexa-2,5-dienes is nearly doubled (4.69-6.21 eV). Cyclobutadisiloles combine the characteristics of siloles and 1,4-disilacyclohexa-2,5-diene by having even lower excitation energies than siloles yet also extensive variation in excitation energies to substitution of 1,4-disilacyclohexa-2,5-dienes (3.47-4.77 eV, variation of 1.30 eV).}, } @article {pmid28255958, year = {2017}, author = {Ho, NT and Kim, PS and Kutzner, A and Heese, K}, title = {Cognitive Functions: Human vs. Animal - 4:1 Advantage |-FAM72-SRGAP2-|.}, journal = {Journal of molecular neuroscience : MN}, volume = {61}, number = {4}, pages = {603-606}, pmid = {28255958}, issn = {1559-1166}, mesh = {Animals ; *Cognition ; *Evolution, Molecular ; GTPase-Activating Proteins/*genetics ; Genetic Markers ; Hominidae/classification/*genetics/physiology ; Humans ; Phylogeny ; }, abstract = {With the advent of computational genomics, an intensive search is underway for unique biomarkers for Homo sapiens that could be used to differentiate taxa within the Hominoidea, in particular to distinguish Homo from the apes (Pan, Gorilla, Pongo, and Hylobates) and species or subspecies within the genus Homo (H. sapiens, H. heidelbergensis, H. neanderthalensis, H. erectus, and the Denisovans). Here, we suggest that the |-FAM72-SRGAP2-| (family with sequence similarity 72/SLIT-ROBO Rho GTPase activating protein 2) gene pair is a unique molecular biomarker for the genus Homo that could also help to place Australopithecus at its most appropriate place within the phylogenetic tree and may explain the distinctive higher brain cognitive functions of humans.}, } @article {pmid28252610, year = {2017}, author = {Bogomolov, DV and Putintsev, VA and Zbrueva, YV and Denisova, OP}, title = {[Certain immunohistochemical markers of the intravitality of strangulation mechanical asphyxia].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {60}, number = {1}, pages = {8-10}, doi = {10.17116/sudmed20176018-10}, pmid = {28252610}, issn = {0039-4521}, mesh = {*Asphyxia/diagnosis/etiology/pathology ; Biomarkers/analysis ; Fibrinogen/*analysis ; Forensic Pathology/methods ; Humans ; Immunohistochemistry ; *Lung/metabolism/pathology ; Neck/pathology ; *Neck Injuries/etiology/pathology ; *Skin/metabolism/pathology ; *Suicide ; }, abstract = {Thus article was designed to report the results of the investigations into specific histological features of the skin and soft tissue samples taken from the strangulation areas on the neck and from the lungs of the persons who had committed suicide by hanging. The studies revealed the well apparent expression of fibrinogen in the derma and the subdermal cellolocutaneous layer of the skin subjected to intravital strangulation. Similar changes were absent in lung alveoli.}, } @article {pmid28239784, year = {2017}, author = {Bugaeva, LI and Denisova, TD and Sergeeva, SA and Morozova, YA and Kharlamov, IV}, title = {Effects of Afobazole on Postnatal Development of Rat Offspring.}, journal = {Bulletin of experimental biology and medicine}, volume = {162}, number = {4}, pages = {441-444}, doi = {10.1007/s10517-017-3635-z}, pmid = {28239784}, issn = {1573-8221}, mesh = {Animals ; Animals, Newborn ; Anti-Anxiety Agents/*adverse effects ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Benzimidazoles/*adverse effects ; Female ; Maternal Exposure/*adverse effects ; Maze Learning/drug effects ; Memory/drug effects ; Morpholines/*adverse effects ; Motor Activity/drug effects ; Muscle Strength/drug effects ; Muscle, Skeletal/drug effects/growth & development ; Pregnancy ; Prenatal Exposure Delayed Effects/*etiology/physiopathology ; Rats ; Reflex, Pupillary/drug effects ; Sexual Maturation/drug effects ; Weight Gain/drug effects ; }, abstract = {Physical development, development of sensory and motor reflexes, behavioral and mnestic patterns were studied infantile and juvenile rat pups born by female rats receiving Afobazole during pregnancy. Physical development and development of sensory and motor reflexes in rats were completed without pathologies by the age of 2 months. During the infantile period, the rat pups demonstrated reduced body weight gain, delayed eye opening and pupillary response formation, decreased muscle force, and suppressed motor behavior. During the juvenile period, body weight gain and development of motor behavior were intensified. Females demonstrated later vagina opening and poorer mnestic responses. In males, the terms of sexual maturation were unchanged and processes of learning and memory retrieval were not impaired.}, } @article {pmid28239517, year = {2017}, author = {Denisova, K and Zhao, G and Wang, Z and Goh, S and Huo, Y and Peterson, BS}, title = {Cortical interactions during the resolution of information processing demands in autism spectrum disorders.}, journal = {Brain and behavior}, volume = {7}, number = {2}, pages = {e00596}, pmid = {28239517}, issn = {2162-3279}, support = {R01 MH089582/MH/NIMH NIH HHS/United States ; T32 MH016434/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Attention/*physiology ; Autism Spectrum Disorder/*physiopathology ; Brain/*physiopathology ; Child ; Female ; Functional Neuroimaging/*methods ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Psychomotor Performance/*physiology ; Space Perception/*physiology ; Visual Perception/*physiology ; Young Adult ; }, abstract = {INTRODUCTION: Our flexible and adaptive interactions with the environment are guided by our individual representation of the physical world, estimated through sensation and evaluation of available information against prior knowledge. When linking sensory evidence with higher-level expectations for action, the central nervous system (CNS) in typically developing (TD) individuals relies in part on distributed and interacting cortical regions to communicate neuronal signals flexibly across the brain. Increasing evidence suggests that the balance between levels of signal and noise during information processing may be disrupted in individuals with Autism Spectrum Disorders (ASD).

METHODS: Participants with and without ASD performed a visuospatial interference task while undergoing functional Magnetic Resonance Imaging (fMRI). We empirically estimated parameters characterizing participants' latencies and their subtle fluctuations (noise accumulation) over the 16-min scan. We modeled hemodynamic activation and used seed-based analyses of neural coupling to study dysfunction in interference-specific connectivity in a subset of ASD participants who were nonparametrically matched to TD participants on age, male-to-female ratio, and magnitude of movement during the scan.

RESULTS: Stochastic patterns of response fluctuations reveal significantly higher noise-to-signal levels and a more random and noisy structure in ASD versus TD participants, and in particular ASD adults who have the greatest clinical autistic deficits. While individuals with ASD show an overall weaker modulation of interference-specific functional connectivity relative to TD individuals, in particular between the seeds of Anterior Cingulate Cortex (ACC) and Inferior Parietal Sulcus (IPS) and the rest of the brain, we found that in ASD, higher uncertainty during the task is linked to increased interference-specific coupling between bilateral anterior insula and prefrontal cortex.

CONCLUSIONS: Subtle and informative differences in the structure of experiencing information exist between ASD and TD individuals. Our findings reveal in ASD an atypical capacity to apply previously perceived information in a manner optimal for adaptive functioning, plausibly revealing suboptimal message-passing across the CNS.}, } @article {pmid28233034, year = {2017}, author = {Tashi, T and Scott Reading, N and Wuren, T and Zhang, X and Moore, LG and Hu, H and Tang, F and Shestakova, A and Lorenzo, F and Burjanivova, T and Koul, P and Guchhait, P and Wittwer, CT and Julian, CG and Shah, B and Huff, CD and Gordeuk, VR and Prchal, JT and Ge, R}, title = {Gain-of-function EGLN1 prolyl hydroxylase (PHD2 D4E:C127S) in combination with EPAS1 (HIF-2α) polymorphism lowers hemoglobin concentration in Tibetan highlanders.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {95}, number = {6}, pages = {665-670}, pmid = {28233034}, issn = {1432-1440}, support = {P01 CA108671/CA/NCI NIH HHS/United States ; }, mesh = {Acclimatization/*genetics ; Adult ; Altitude ; Asian People/*genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Erythropoietin/blood ; Female ; Ferritins/blood ; Gene-Environment Interaction ; Haplotypes ; Hemoglobins/*analysis ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases/*genetics ; Male ; Polymorphism, Single Nucleotide ; Tibet ; }, abstract = {UNLABELLED: Tibetans have lived at high altitude for generations and are thought to be genetically adapted to hypoxic environments. Most are protected from hypoxia-induced polycythemia, and a haplotype of EPAS1, encoding hypoxia-inducible factor (HIF-2α), has been associated with lower hemoglobin levels. We earlier reported a Tibetan-specific EGLN1 haplotype encoding PHD2 which abrogates HIF augmentation in hypoxia. We genotyped 347 Tibetan individuals from varying altitudes for both the Tibetan-specific EGLN1 haplotype and 10 candidate SNPs in the EPAS1 haplotype and correlated their association with hemoglobin levels. The effect of the EGLN1 haplotype on hemoglobin exhibited age dependency at low altitude, while at higher altitudes, it showed a trend to lower hemoglobin levels in the presence of the Tibetan-selected EPAS1 rs142764723 C/C allele. The observed gene-environment and gene-gene interactions and the moderate effect of the EGLN1 and EPAS1 haplotypes on hemoglobin indicate that other modifiers exist. It remains to be determined whether a blunting of erythropoiesis or other physiological consequences of HIF downregulation are the primary drivers of these genetic adaptations among Tibetans.

KEY MESSAGE: Most Tibetans are protected from polycythemia while living in high altitude. An EGLN1 co-adapted haplotype, EGLN1 c.12C>G, c.380G>C is uniquely Tibetan. The Tibetan EPAS1 haplotype has introgressed from the Denisovan genome. While EGLN1 and EPAS1 genotypes lower Hb, this study indicates additional Hb modifiers.}, } @article {pmid33473722, year = {2017}, author = {Druzhkova, AS and Makunin, AI and Vorobieva, NV and Vasiliev, SK and Ovodov, ND and Shunkov, MV and Trifonov, VA and Graphodatsky, AS}, title = {Complete mitochondrial genome of an extinct Equus (Sussemionus) ovodovi specimen from Denisova cave (Altai, Russia).}, journal = {Mitochondrial DNA. Part B, Resources}, volume = {2}, number = {1}, pages = {79-81}, pmid = {33473722}, issn = {2380-2359}, abstract = {Sussemionus is an extinct subgenus of Equus first characterized and delineated in 2010. The almost complete mitochondrial genome is available only for a single specimen of Sussemionus - a 40,000 years old E. ovodovi from Proskuryakova cave (Khakassia, Russia). Our studies of ancient horses from Denisova cave (Altai, Russia) revealed mitochondrial DNA of this species in a 32,000 years old sample. Using alignments to multiple mitochondrial genomes of non-caballine equids, we recovered 100% complete mitochondrial genome of E. ovodovi for the first time. Phylogenetic analysis demonstrates close relationship between this individual and the one previously described in Khakassia.}, } @article {pmid28158547, year = {2016}, author = {Povysil, G and Hochreiter, S}, title = {IBD Sharing between Africans, Neandertals, and Denisovans.}, journal = {Genome biology and evolution}, volume = {8}, number = {12}, pages = {3406-3416}, pmid = {28158547}, issn = {1759-6653}, mesh = {Africa ; Animals ; Asian People/genetics ; Black People/genetics ; Breeding ; DNA/genetics ; *Evolution, Molecular ; *Gene Flow ; Genome ; Hominidae/*genetics ; Humans ; Neanderthals/genetics ; White People/genetics ; }, abstract = {Interbreeding between ancestors of humans and other hominins outside of Africa has been studied intensively, while their common history within Africa still lacks proper attention. However, shedding light on human evolution in this time period about which little is known, is essential for understanding subsequent events outside of Africa. We investigate the genetic relationships of humans, Neandertals, and Denisovans by identifying very short DNA segments in the 1000 Genomes Phase 3 data that these hominins share identical by descent (IBD). By focusing on low frequency and rare variants, we identify very short IBD segments with high confidence. These segments reveal events from a very distant past because shorter IBD segments are presumably older than longer ones. We extracted two types of very old IBD segments that are not only shared among humans, but also with Neandertals and/or Denisovans. The first type contains longer segments that are found primarily in Asians and Europeans where more segments are found in South Asians than in East Asians for both Neandertal and Denisovan. These longer segments indicate complex admixture events outside of Africa. The second type consists of shorter segments that are shared mainly by Africans and therefore may indicate events involving ancestors of humans and other ancient hominins within Africa. Our results from the autosomes are further supported by an analysis of chromosome X, on which segments that are shared by Africans and match the Neandertal and/or Denisovan genome were even more prominent. Our results indicate that interbreeding with other hominins was a common feature of human evolution starting already long before ancestors of modern humans left Africa.}, } @article {pmid28146472, year = {2017}, author = {Carus-Cadavieco, M and Gorbati, M and Ye, L and Bender, F and van der Veldt, S and Kosse, C and Börgers, C and Lee, SY and Ramakrishnan, C and Hu, Y and Denisova, N and Ramm, F and Volitaki, E and Burdakov, D and Deisseroth, K and Ponomarenko, A and Korotkova, T}, title = {Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking.}, journal = {Nature}, volume = {542}, number = {7640}, pages = {232-236}, pmid = {28146472}, issn = {1476-4687}, support = {R01 NS067199/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Eating/physiology/psychology ; Energy Metabolism/physiology ; Feeding Behavior/*physiology/psychology ; Gamma Rhythm/*physiology ; Hypothalamus/cytology/*physiology ; Learning ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/physiology ; Reward ; Somatostatin/metabolism ; }, abstract = {Both humans and animals seek primary rewards in the environment, even when such rewards do not correspond to current physiological needs. An example of this is a dissociation between food-seeking behaviour and metabolic needs, a notoriously difficult-to-treat symptom of eating disorders. Feeding relies on distinct cell groups in the hypothalamus, the activity of which also changes in anticipation of feeding onset. The hypothalamus receives strong descending inputs from the lateral septum, which is connected, in turn, with cortical networks, but cognitive regulation of feeding-related behaviours is not yet understood. Cortical cognitive processing involves gamma oscillations, which support memory, attention, cognitive flexibility and sensory responses. These functions contribute crucially to feeding behaviour by unknown neural mechanisms. Here we show that coordinated gamma (30-90 Hz) oscillations in the lateral hypothalamus and upstream brain regions organize food-seeking behaviour in mice. Gamma-rhythmic input to the lateral hypothalamus from somatostatin-positive lateral septum cells evokes food approach without affecting food intake. Inhibitory inputs from the lateral septum enable separate signalling by lateral hypothalamus neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. Upstream, medial prefrontal cortical projections provide gamma-rhythmic inputs to the lateral septum; these inputs are causally associated with improved performance in a food-rewarded learning task. Overall, our work identifies a top-down pathway that uses gamma synchronization to guide the activity of subcortical networks and to regulate feeding behaviour by dynamic reorganization of functional cell groups in the hypothalamus.}, } @article {pmid30615384, year = {2017}, author = {Kulyutsina, ER and Tatarchenko, IP and Levashova, OA and Denisova, AG and Drujinina, TA}, title = {[The interrelationship of indices of hemocysteine and genetic polymorphisms conditioning disorders of folates metabolism in healthy population].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {62}, number = {2}, pages = {82-87}, pmid = {30615384}, issn = {0869-2084}, mesh = {5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/*genetics ; Adult ; Alleles ; Female ; Ferredoxin-NADP Reductase/*genetics ; Folic Acid/genetics/metabolism ; Gene Frequency ; *Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Homocysteine/blood/genetics ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; Risk Factors ; }, abstract = {The study was carried out to investigate relationship of the level of homocysteine and genetic polymorphisms conditioning disorders of metabolism of folates in healthy population and of various age and gender groups. The study covered 168 donors: 98 males and 70 females. Two gender groups were singled out and in each of them age groups: 18-31, 32-45 and 46-60 years old. The analysis of concentration of homocysteine was implemented using immune chemiluminescence analysis. The polymerase chain reaction was applied for analyzing genetic polymorphisms associated with disorders of folate cycle by genes MTHFR (met hylentetrahydrofolatereductase) (polymorphisms MTHFR: 677 C>T and MTHFR: 1298 A>C), MTR (B12-dependent methionine-synthetase) (polymorphism MTR: 2756 A>G) and MTRR (methionine-synthetase-reductase) (polymorphism MTRR: 66 A>G). The level of homocysteine in blood of donors was reliably higher in male groups of 18-31 and 32-45 years old as against female groups comparable by age. The study established higher rate of occurrence of heterozygous genotypes bringing unfavorable types of polymorphisms of MTHFR and MTRR genes both in male and female groups. The study established higher rate of occurrence of unfavorable genotypes in examined patients in comparison with publications' data. The established statistically significant inverse correlation of concentration of homocysteine and genetic polymorphisms associated with disorders of folate cycle in individuals of young and middle age mainly males, permits to draw a conclusion about absence of their direct relationship. Therefore, implementation of genetic liability to increasing of homocysteine can occur under effect of external unfavorable factors.}, } @article {pmid28139571, year = {2016}, author = {Khabarova, EA and Denisova, NP and Rogov, DY and Dmitriev, AB}, title = {The preliminary results of subthalamic nucleus stimulation after destructive surgery in Parkinson's disease.}, journal = {Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko}, volume = {80}, number = {6}, pages = {36-41}, doi = {10.17116/neiro201680636-41}, pmid = {28139571}, issn = {0042-8817}, mesh = {Case-Control Studies ; Deep Brain Stimulation/*adverse effects ; Female ; Globus Pallidus/surgery ; Humans ; Male ; Middle Aged ; Motor Activity ; Neurosurgical Procedures/*adverse effects ; Parkinson Disease/surgery/*therapy ; Subthalamic Nucleus/*physiopathology ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate the efficacy of bilateral electrical stimulation (ES) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) after preceding pallidotomy or ventrolateral (VL) thalamotomy.

MATERIAL AND METHODS: The study included 9 patients with bilateral STN ES who had undergone previous unilateral destructive surgery on the subcortical structures: pallidotomy (5 patients) and VL thalamotomy (4). A control group consisted of 9 patients with STN ES, without prior destructive surgery. A clinical and neurological examination included quantitative assessment of motor disturbances using the Hoehn-Yahr scale and Unified Parkinson's disease rating scale (UPDRS). UPDRS was used to evaluate the motor activity (IIIrd part of the scale) and severity of drug-induced dyskinesia and motor fluctuations (IVth part of the scale).

RESULTS: In the group of STN ES with preceding destruction of the subcortical structures, an improvement in motor functions in the early period (6 months) was 45%, and severity of drug-induced complications was decreased by 75%. In a group of STN DBS without destruction, motor disturbances were improved by 61%, and drug-induced complications were decreased by 77%. Improvement in motor functions amounted to 51.9% in patients with preceding pallidotomy (GPi destruction) and 37.5% in a group with preceding VL thalamotomy. The equivalent dose of levodopa was reduced by 51.39%, from 1,008±346 to 490±194, in the study group and by 55.04%, from 963±96 to 433±160, in the control group.

CONCLUSION: Bilateral STN neurostimulation is effective after unilateral stereotaxic destruction of the subcortical structures in PD patients.}, } @article {pmid29874000, year = {2017}, author = {Bugaeva, LI and Denisova, TD and Mazanova, YA and Kharlamov, IV and Sergeeva, SA}, title = {[PHYSICAL AND BEHAVIORAL DEVELOPMENT OF THE OFFSPRING OF FEMALE RATS TREATED WITH AFOBAZOLE DURING PREGNANCY.].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {80}, number = {1}, pages = {28-31}, pmid = {29874000}, issn = {0869-2092}, mesh = {Animals ; Animals, Newborn ; Anti-Anxiety Agents/*pharmacology ; Behavior, Animal/*drug effects ; Benzimidazoles/*pharmacology ; Female ; Lactation/*drug effects/physiology ; Male ; Morpholines/*pharmacology ; Motor Activity/*drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects/diagnosis/pathology/physiopathology ; Sex Factors ; }, abstract = {It is experimentally established that afobazole produces no damaging action on the organogenesis and fetogenic processes registered in the postnatal period of rat offspring development. It was noted that, in rat babies in lactation age, the dynamics of body weight gain was lower on average by 7.4% (p < 0.05) in males and 17.0% (p < 0.001) in females; the rate of muscular force maturing was lower by 2.7% (p < 0.05); and the locomotive activity was lower (by 19.4% for ver- tical standings and by 50% for looking into floor holes, p < 0.05) compared to control values. For the same offspring passed to definitive food, the body weight gain and behavioral activity did not differ from control indicators, while the terms of sexual development were delayed in females and did not change in males. By two-month age, the physical development of rat offspring was completely created and met physiological standards.}, } @article {pmid28036300, year = {2017}, author = {Lanikova, L and Reading, NS and Hu, H and Tashi, T and Burjanivova, T and Shestakova, A and Siwakoti, B and Thakur, BK and Pun, CB and Sapkota, A and Abdelaziz, S and Feng, BJ and Huff, CD and Hashibe, M and Prchal, JT}, title = {Evolutionary selected Tibetan variants of HIF pathway and risk of lung cancer.}, journal = {Oncotarget}, volume = {8}, number = {7}, pages = {11739-11747}, pmid = {28036300}, issn = {1949-2553}, support = {P01 CA108671/CA/NCI NIH HHS/United States ; P30 CA042014/CA/NCI NIH HHS/United States ; }, mesh = {Acclimatization ; Aged ; Aged, 80 and over ; Female ; Humans ; Hypoxia/*genetics/*metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/*metabolism ; Lung Neoplasms/*genetics/*metabolism ; Male ; Middle Aged ; Tibet ; }, abstract = {Tibetans existed in high altitude for ~25 thousand years and have evolutionary selected unique haplotypes assumed to be beneficial to hypoxic adaptation. EGLN1/PHD2 and EPAS1/HIF-2α, both crucial components of hypoxia sensing, are the two best-established loci contributing to high altitude adaptation. The co-adapted Tibetan-specific haplotype encoding for PHD2:p.[D4E/C127S] promotes increased HIF degradation under hypoxic conditions. The Tibetan-specific 200 kb EPAS1 haplotype introgressed from an archaic human population related to Denisovans which underwent evolutionary decay; however, the functional variant(s) responsible for high-altitude adaptation at EPAS1/HIF-2α have not yet been identified. Since HIF modulates the behavior of cancer cells, we hypothesized that these Tibetan selected genomic variants may modify cancer risk predisposition. Here, we ascertained the frequencies of EGLN1D4E/C127S and EGLN1C127S variants and ten EPAS1/HIF-2α variants in lung cancer patients and controls in Nepal, whose population consists of people with Indo-Aryan origin and Tibetan-related Mongoloid origin. We observed a significant association between the selected Tibetan EGLN1/PHD2 haplotype and lung cancer (p=0.0012 for D4E, p=0.0002 for C127S), corresponding to a two-fold increase in lung cancer risk. We also observed a two-fold or greater increased risk for two of the ten EPAS1/HIF-2α variants, although the association was not significant after correcting for multiple comparisons (p=0.12). Although these data cannot address the role of these genetic variants on lung cancer initiation or progression, we conclude that some selected Tibetan variants are strongly associated with a modified risk of lung cancer.}, } @article {pmid28025273, year = {2017}, author = {Pimenoff, VN and de Oliveira, CM and Bravo, IG}, title = {Transmission between Archaic and Modern Human Ancestors during the Evolution of the Oncogenic Human Papillomavirus 16.}, journal = {Molecular biology and evolution}, volume = {34}, number = {1}, pages = {4-19}, pmid = {28025273}, issn = {1537-1719}, mesh = {Alleles ; Animals ; Biological Evolution ; Databases, Nucleic Acid ; Genetic Variation ; Hominidae/*genetics ; Human papillomavirus 16/*genetics ; Humans ; Male ; Neanderthals/genetics ; Oncogenes ; Papillomavirus Infections/*transmission/*virology ; Phylogeny ; Phylogeography ; }, abstract = {Every human suffers through life a number of papillomaviruses (PVs) infections, most of them asymptomatic. A notable exception are persistent infections by Human papillomavirus 16 (HPV16), the most oncogenic infectious agent for humans and responsible for most infection-driven anogenital cancers. Oncogenic potential is not homogeneous among HPV16 lineages, and genetic variation within HPV16 exhibits some geographic structure. However, an in-depth analysis of the HPV16 evolutionary history was still wanting. We have analyzed extant HPV16 diversity and compared the evolutionary and phylogeographical patterns of humans and of HPV16. We show that codivergence with modern humans explains at most 30% of the present viral geographical distribution. The most explanatory scenario suggests that ancestral HPV16 already infected ancestral human populations and that viral lineages co-diverged with the hosts in parallel with the split between archaic Neanderthal-Denisovans and ancestral modern human populations, generating the ancestral HPV16A and HPV16BCD viral lineages, respectively. We propose that after out-of-Africa migration of modern human ancestors, sexual transmission between human populations introduced HPV16A into modern human ancestor populations. We hypothesize that differential coevolution of HPV16 lineages with different but closely related ancestral human populations and subsequent host-switch events in parallel with introgression of archaic alleles into the genomes of modern human ancestors may be largely responsible for the present-day differential prevalence and association with cancers for HPV16 variants.}, } @article {pmid28007980, year = {2017}, author = {Racimo, F and Gokhman, D and Fumagalli, M and Ko, A and Hansen, T and Moltke, I and Albrechtsen, A and Carmel, L and Huerta-Sánchez, E and Nielsen, R}, title = {Archaic Adaptive Introgression in TBX15/WARS2.}, journal = {Molecular biology and evolution}, volume = {34}, number = {3}, pages = {509-524}, pmid = {28007980}, issn = {1537-1719}, support = {R01 HG003229/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptation, Biological/*genetics ; Adipose Tissue/physiology ; Alleles ; Animals ; DNA Methylation ; DNA, Ancient ; Greenland ; Haplotypes ; Humans ; Inuit/*genetics ; Models, Genetic ; Neanderthals ; Polymorphism, Single Nucleotide ; Selection, Genetic ; Sequence Analysis, DNA/methods ; T-Box Domain Proteins/*genetics ; }, abstract = {A recent study conducted the first genome-wide scan for selection in Inuit from Greenland using single nucleotide polymorphism chip data. Here, we report that selection in the region with the second most extreme signal of positive selection in Greenlandic Inuit favored a deeply divergent haplotype that is closely related to the sequence in the Denisovan genome, and was likely introgressed from an archaic population. The region contains two genes, WARS2 and TBX15, and has previously been associated with adipose tissue differentiation and body-fat distribution in humans. We show that the adaptively introgressed allele has been under selection in a much larger geographic region than just Greenland. Furthermore, it is associated with changes in expression of WARS2 and TBX15 in multiple tissues including the adrenal gland and subcutaneous adipose tissue, and with regional DNA methylation changes in TBX15.}, } @article {pmid27919236, year = {2016}, author = {Pajic, P and Lin, YL and Xu, D and Gokcumen, O}, title = {The psoriasis-associated deletion of late cornified envelope genes LCE3B and LCE3C has been maintained under balancing selection since Human Denisovan divergence.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {265}, pmid = {27919236}, issn = {1471-2148}, mesh = {Alleles ; Cornified Envelope Proline-Rich Proteins/*genetics ; *Evolution, Molecular ; *Gene Deletion ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide ; Psoriasis/*genetics ; Sequence Deletion ; }, abstract = {BACKGROUND: A common, 32kb deletion of LCE3B and LCE3C genes is strongly associated with psoriasis. We recently found that this deletion is ancient, predating Human-Denisovan divergence. However, it was not clear why negative selection has not removed this deletion from the population.

RESULTS: Here, we show that the haplotype block that harbors the deletion (i) retains high allele frequency among extant and ancient human populations; (ii) harbors unusually high nucleotide variation (π, P < 4.1 × 10[-3]); (iii) contains an excess of intermediate frequency variants (Tajima's D, P < 3.9 × 10[-3]); and (iv) has an unusually long time to coalescence to the most recent common ancestor (TSel, 0.1 quantile).

CONCLUSIONS: Our results are most parsimonious with the scenario where the LCE3BC deletion has evolved under balancing selection in humans. More broadly, this is consistent with the hypothesis that a balance between autoimmunity and natural vaccination through increased exposure to pathogens maintains this deletion in humans.}, } @article {pmid27916748, year = {2017}, author = {Noe, F and Polster, J and Geithe, C and Kotthoff, M and Schieberle, P and Krautwurst, D}, title = {OR2M3: A Highly Specific and Narrowly Tuned Human Odorant Receptor for the Sensitive Detection of Onion Key Food Odorant 3-Mercapto-2-methylpentan-1-ol.}, journal = {Chemical senses}, volume = {42}, number = {3}, pages = {195-210}, doi = {10.1093/chemse/bjw118}, pmid = {27916748}, issn = {1464-3553}, mesh = {Cells, Cultured ; Humans ; Molecular Structure ; Odorants/*analysis ; Onions/*chemistry ; Pentanols/*analysis/chemistry ; Receptors, Odorant/*metabolism ; *Smell ; Sulfhydryl Compounds/*analysis/chemistry ; }, abstract = {The detection of key food odorants appears to be an important capability of odorant receptors. Here, thiols occupy an outstanding position among the 230 known key food odorants because of their very low odor thresholds. Members of the homologous series of 3-mercapto-2-methylalkan-1-ols have been described as onion key food odorants or food constituents and are detected at logarithmically different thresholds. 3-Mercapto-2-methylpentan-1-ol being the only key food odorant within this series also has the lowest odor threshold. Most odorants typically activate combinations of odorant receptors, which may be narrowly or broadly tuned. Consequently, a specific receptor activation pattern will define an odor quality. In contrast, here we show that just 1 of the 391 human odorant receptors, OR2M3, responded exclusively to 3-mercapto-2-methylpentan-1-ol of the 190 key food odorants tested, with a half maximal effective concentration at submicromolar concentration. Moreover, neither the Denisovan OR2M3 nor the closest OR2M3 homologs from five species did respond to this compound. This outstanding specificity of extremely narrowly tuned human OR2M3 can explain both odor qualities and odor threshold trend within a homologous series of 3-mercapto-2-methylalkan-1-ols and suggests a modern human-specific, food-related function of OR2M3 in detecting a single onion key food odorant.}, } @article {pmid27869148, year = {2016}, author = {Torres, EB and Denisova, K}, title = {Motor noise is rich signal in autism research and pharmacological treatments.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {37422}, pmid = {27869148}, issn = {2045-2322}, mesh = {Adolescent ; Autistic Disorder/diagnosis/*drug therapy/*physiopathology ; Comorbidity ; Female ; Head Movements/drug effects ; Humans ; Intelligence ; Male ; Mental Health ; *Motor Activity/drug effects ; Noise ; Precision Medicine ; Psychotropic Drugs/pharmacology/therapeutic use ; Stochastic Processes ; }, abstract = {The human body is in constant motion, from every breath that we take, to every visibly purposeful action that we perform. Remaining completely still on command is a major achievement as involuntary fluctuations in our motions are difficult to keep under control. Here we examine the noise-to-signal ratio of micro-movements present in time-series of head motions extracted from resting-state functional magnetic resonance imaging scans in 1048 participants. These included individuals with autism spectrum disorders (ASD) and healthy-controls in shared data from the Autism Brain Imaging Data Exchange (ABIDE) and the Attention-Deficit Hyperactivity Disorder (ADHD-200) databases. We find excess noise and randomness in the ASD cases, suggesting an uncertain motor-feedback signal. A power-law emerged describing an orderly relation between the dispersion and shape of the probability distribution functions best describing the stochastic properties under consideration with respect to intelligence quotient (IQ-scores). In ASD, deleterious patterns of noise are consistently exacerbated with the presence of secondary (comorbid) neuropsychiatric diagnoses, lower verbal and performance intelligence, and autism severity. Importantly, such patterns in ASD are present whether or not the participant takes psychotropic medication. These data unambiguously establish specific noise-to-signal levels of head micro-movements as a biologically informed core feature of ASD.}, } @article {pmid27839976, year = {2016}, author = {Gittelman, RM and Schraiber, JG and Vernot, B and Mikacenic, C and Wurfel, MM and Akey, JM}, title = {Archaic Hominin Admixture Facilitated Adaptation to Out-of-Africa Environments.}, journal = {Current biology : CB}, volume = {26}, number = {24}, pages = {3375-3382}, pmid = {27839976}, issn = {1879-0445}, support = {R01 GM110068/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Biological Evolution ; DNA/*genetics ; Demography ; Gene Expression Regulation ; Genetic Variation ; *Genome, Human/genetics ; Haplotypes ; Humans ; Neanderthals ; Pigmentation ; }, abstract = {As modern humans dispersed from Africa throughout the world, they encountered and interbred with archaic hominins, including Neanderthals and Denisovans [1, 2]. Although genome-scale maps of introgressed sequences have been constructed [3-6], considerable gaps in knowledge remain about the functional, phenotypic, and evolutionary significance of archaic hominin DNA that persists in present-day individuals. Here, we describe a comprehensive set of analyses that identified 126 high-frequency archaic haplotypes as putative targets of adaptive introgression in geographically diverse populations. These loci are enriched for immune-related genes (such as OAS1/2/3, TLR1/6/10, and TNFAIP3) and also encompass genes (including OCA2 and BNC2) that influence skin pigmentation phenotypes. Furthermore, we leveraged existing and novel large-scale gene expression datasets to show many positively selected archaic haplotypes act as expression quantitative trait loci (eQTLs), suggesting that modulation of transcript abundance was a common mechanism facilitating adaptive introgression. Our results demonstrate that hybridization between modern and archaic hominins provided an important reservoir of advantageous alleles that enabled adaptation to out-of-Africa environments.}, } @article {pmid27633826, year = {2016}, author = {Birolo, C and Zannin, ME and Arsenyeva, S and Cimaz, R and Miserocchi, E and Dubko, M and Deslandre, CJ and Falcini, F and Alessio, M and La Torre, F and Denisova, E and Martini, G and Nikishina, I and Zulian, F}, title = {Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis.}, journal = {The Journal of rheumatology}, volume = {43}, number = {11}, pages = {2068-2073}, doi = {10.3899/jrheum.151389}, pmid = {27633826}, issn = {0315-162X}, mesh = {Abatacept/*therapeutic use ; Adolescent ; Antirheumatic Agents/*therapeutic use ; Arthritis, Juvenile/*drug therapy ; Child ; Child, Preschool ; Female ; Humans ; Immunosuppressive Agents/*therapeutic use ; Male ; Retreatment ; Treatment Outcome ; Uveitis/*drug therapy ; Young Adult ; }, abstract = {OBJECTIVE: Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)-associated uveitis refractory to anti-tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis.

METHODS: In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded.

RESULTS: Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile.

CONCLUSION: ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.}, } @article {pmid27801420, year = {2016}, author = {Voevoda, MI and Kovalkova, NA and Ragino, YI and Travnikova, NY and Denisova, DV}, title = {[Prevalence of metabolic syndrome in 25-45-year-old Novosibirsk dwellers].}, journal = {Terapevticheskii arkhiv}, volume = {88}, number = {10}, pages = {51-56}, doi = {10.17116/terarkh2016881051-56}, pmid = {27801420}, issn = {0040-3660}, mesh = {Adult ; Age Factors ; Anthropometry/methods ; Blood Glucose/*analysis ; *Blood Pressure Determination/methods/statistics & numerical data ; Cross-Sectional Studies ; Female ; Humans ; Lipoproteins, HDL/blood ; Lipoproteins, LDL/blood ; Male ; *Metabolic Syndrome/blood/diagnosis/epidemiology ; Prevalence ; Risk Factors ; Sex Factors ; Siberia/epidemiology ; Triglycerides/blood ; }, abstract = {AIM: To study the prevalence of metabolic syndrome (MS) and its components in a 25-45-year-old Novosibirsk population.

SUBJECTS AND METHODS: The Novosibirsk Research Institute of Internal and Preventive Medicine conducted a cross-sectional population-based survey in one of the typical districts of Novosibirsk in 2013-2015. The survey covered 346 men and 408 women. The criteria of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III, 2001), the International Diabetes Federation (IDF, 2005), the Joint Interim Statement (JIS, 2009), and the All-Russian Research Society of Cardiologists (ARRSC, 2009) were used to detect MS. According to the ARRSC criteria, MS was recorded if a waist circumference (WC) was >80 cm for women and >94 cm for men in conjunction with 2 of the following criteria: a blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, high-density lipoprotein (HDL) cholesterol <1.0 mmol/l for men and <1.2 mmol/l for women, low-density lipoprotein (LDL) cholesterol >3.0 mmol/l, and plasma glucose level ≥6.1 mmol/l.

RESULTS: According to the 2009 ARRSC criteria, the prevalence of abdominal obesity, hypertension, hypertriglyceridemia, HDL hypocholestrolemia, LDL hypercholesterolemia, and high plasma glucose level was 42.6, 33.5, 17.5, 24.3, 64.8, and 29%, respectively. The prevalence of MS in 25-45-year-old Novosibirsk people was 17% (19.9% in men and 14.5% in women) according to the 2001 NCEP-ATP III, 27% (29.5% in men and 24.5% in women) according to the 2005 IDF criteria, 30% (35.8% in men and 25% in women) according to the 2009 JIS criteria, and 29.3% (33.2% in men and 26% in women) according to the 2009 ARRSC criteria, this was higher among men than women. There was an increase in the prevalence of MS with age.

CONCLUSION: The highest prevalence of MS was 30 and 29.3% when using the 2009 JIS and the 2009 ARRSC criteria, respectively. Whatever the criterion was used, MS was more frequently recorded in men than women.}, } @article {pmid27154591, year = {2016}, author = {Kozela, M and Bobak, M and Besala, A and Micek, A and Kubinova, R and Malyutina, S and Denisova, D and Richards, M and Pikhart, H and Peasey, A and Marmot, M and Pająk, A}, title = {The association of depressive symptoms with cardiovascular and all-cause mortality in Central and Eastern Europe: Prospective results of the HAPIEE study.}, journal = {European journal of preventive cardiology}, volume = {23}, number = {17}, pages = {1839-1847}, pmid = {27154591}, issn = {2047-4881}, support = {G0100222/MRC_/Medical Research Council/United Kingdom ; G0701830/MRC_/Medical Research Council/United Kingdom ; G0902037/MRC_/Medical Research Council/United Kingdom ; WT081081/WT_/Wellcome Trust/United Kingdom ; G0601647/MRC_/Medical Research Council/United Kingdom ; G1000616/MRC_/Medical Research Council/United Kingdom ; R01 AG023522/AG/NIA NIH HHS/United States ; MC_UU_12019/3/MRC_/Medical Research Council/United Kingdom ; RG/07/008/23674/BHF_/British Heart Foundation/United Kingdom ; G19/35/MRC_/Medical Research Council/United Kingdom ; G8802774/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Cardiovascular Diseases/etiology/*mortality ; Cause of Death/trends ; Depressive Disorder/*complications/epidemiology ; Europe/epidemiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; *Registries ; *Risk Assessment ; Risk Factors ; Socioeconomic Factors ; Survival Rate/trends ; Time Factors ; }, abstract = {BACKGROUND: Studies in western populations have shown a positive association between depression and cardiovascular disease (CVD) and all-cause mortality. The association with depressive symptoms seems to be graded, rather than limited to the presence versus the absence of depression. Evidence from populations with potentially different patterns of confounders helps to address the consistency of these findings. The objective of the study was to investigate the association between depressive symptoms and all-cause and CVD mortality in populations of Central and Eastern Europe.

STUDY DESIGN: This was a prospective cohort study.

METHODS: A total of 24,542 participants aged 45-69 years, randomly selected from populations of Novosibirsk (Russia), Krakow (Poland) and six Czech towns, were included. Depressive symptoms, assessed by the 20-item Center for Epidemiologic Studies Depression (CES-D) scale, were used as both continuous and categorical variables. Data on deaths were obtained from local or national death registers. Associations between depression and mortality were assessed using Cox proportional hazards models.

RESULTS: Over a median of 7 years, 2091 deaths from all causes and 850 CVD deaths occurred in the cohorts. There was a graded association between CES-D score and mortality; the hazard ratio (HR) of CVD mortality for a 1 SD increase in CES-D was 1.20 (95% confidence interval (CI): 1.16-1.24) in men and 1.23 (95% CI: 1.12-1.35) in women; for all-cause mortality, the HRs were 1.13 (95% CI: 1.09-1.18) and 1.17 (95% CI: 1.10-1.25), respectively. The results were similar across countries.

CONCLUSIONS: Depressive symptoms predicted CVD and all-cause mortality independently of a wide range of potential confounders. The association followed a gradient and increased mortality risks were associated with scores below the cut-offs that are commonly used to define 'depression'.}, } @article {pmid27756828, year = {2017}, author = {Racimo, F and Marnetto, D and Huerta-Sánchez, E}, title = {Signatures of Archaic Adaptive Introgression in Present-Day Human Populations.}, journal = {Molecular biology and evolution}, volume = {34}, number = {2}, pages = {296-317}, pmid = {27756828}, issn = {1537-1719}, support = {R01 HG003229/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptation, Biological/*genetics ; Alleles ; Animals ; Biological Evolution ; Computer Simulation ; DNA, Ancient/*analysis ; Databases, Nucleic Acid ; Evolution, Molecular ; Gene Frequency ; Genetics, Population ; Haplotypes ; Humans ; Neanderthals ; Phylogeny ; Selection, Genetic ; Sequence Analysis, DNA/*methods ; }, abstract = {Comparisons of DNA from archaic and modern humans show that these groups interbred, and in some cases received an evolutionary advantage from doing so. This process-adaptive introgression-may lead to a faster rate of adaptation than is predicted from models with mutation and selection alone. Within the last couple of years, a series of studies have identified regions of the genome that are likely examples of adaptive introgression. In many cases, once a region was ascertained as being introgressed, commonly used statistics based on both haplotype as well as allele frequency information were employed to test for positive selection. Introgression by itself, however, changes both the haplotype structure and the distribution of allele frequencies, thus confounding traditional tests for detecting positive selection. Therefore, patterns generated by introgression alone may lead to false inferences of positive selection. Here we explore models involving both introgression and positive selection to investigate the behavior of various statistics under adaptive introgression. In particular, we find that the number and allelic frequencies of sites that are uniquely shared between archaic humans and specific present-day populations are particularly useful for detecting adaptive introgression. We then examine the 1000 Genomes dataset to characterize the landscape of uniquely shared archaic alleles in human populations. Finally, we identify regions that were likely subject to adaptive introgression and discuss some of the most promising candidate genes located in these regions.}, } @article {pmid27744216, year = {2016}, author = {Simons, YB and Sella, G}, title = {The impact of recent population history on the deleterious mutation load in humans and close evolutionary relatives.}, journal = {Current opinion in genetics & development}, volume = {41}, number = {}, pages = {150-158}, pmid = {27744216}, issn = {1879-0380}, support = {R01 GM115889/GM/NIGMS NIH HHS/United States ; }, mesh = {Africa ; Animals ; *Evolution, Molecular ; Genetic Variation ; *Genetics, Population ; Gorilla gorilla/genetics ; Humans ; Neanderthals/genetics ; Sequence Deletion/*genetics ; }, abstract = {Over the past decade, there has been both great interest and confusion about whether recent demographic events-notably the Out-of-Africa-bottleneck and recent population growth-have led to differences in mutation load among human populations. The confusion can be traced to the use of different summary statistics to measure load, which lead to apparently conflicting results. We argue, however, that when statistics more directly related to load are used, the results of different studies and data sets consistently reveal little or no difference in the load of non-synonymous mutations among human populations. Theory helps to understand why no such differences are seen, as well as to predict in what settings they are to be expected. In particular, as predicted by modeling, there is evidence for changes in the load of recessive loss of function mutations in founder and inbred human populations. Also as predicted, eastern subspecies of gorilla, Neanderthals and Denisovans, who are thought to have undergone reductions in population sizes that exceed the human Out-of-Africa bottleneck in duration and severity, show evidence for increased load of non-synonymous mutations (relative to western subspecies of gorillas and modern humans, respectively). A coherent picture is thus starting to emerge about the effects of demographic history on the mutation load in populations of humans and close evolutionary relatives.}, } @article {pmid27708712, year = {2016}, author = {Stankiewicz, P}, title = {One pedigree we all may have come from - did Adam and Eve have the chromosome 2 fusion?.}, journal = {Molecular cytogenetics}, volume = {9}, number = {}, pages = {72}, pmid = {27708712}, issn = {1755-8166}, abstract = {BACKGROUND: In contrast to Great Apes, who have 48 chromosomes, modern humans and likely Neandertals and Denisovans have and had, respectively, 46 chromosomes. The reduction in chromosome number was caused by the head-to-head fusion of two ancestral chromosomes to form human chromosome 2 (HSA2) and may have contributed to the reproductive barrier with Great Apes.

RESULTS: Next generation sequencing and molecular clock analyses estimated that this fusion arose prior to our last common ancestor with Neandertal and Denisovan hominins ~ 0.74 - 4.5 million years ago.

HYPOTHESES: I propose that, unlike recurrent Robertsonian translocations in humans, the HSA2 fusion was a single nonrecurrent event that spread through a small polygamous clan population bottleneck. Its heterozygous to homozygous conversion, fixation, and accumulation in the succeeding populations was likely facilitated by an evolutionary advantage through the genomic loss rather than deregulation of expression of the gene(s) flanking the HSA2 fusion site at 2q13.

CONCLUSIONS: The origin of HSA2 might have been a critical evolutionary event influencing higher cognitive functions in various early subspecies of hominins. Next generation sequencing of Homo heidelbergensis and Homo erectus genomes and complete reconstruction of DNA sequence of the orthologous subtelomeric chromosomes in Great Apes should enable more precise timing of HSA2 formation and better understanding of its evolutionary consequences.}, } @article {pmid27708336, year = {2016}, author = {Papadakis, R and Li, H and Bergman, J and Lundstedt, A and Jorner, K and Ayub, R and Haldar, S and Jahn, BO and Denisova, A and Zietz, B and Lindh, R and Sanyal, B and Grennberg, H and Leifer, K and Ottosson, H}, title = {Metal-free photochemical silylations and transfer hydrogenations of benzenoid hydrocarbons and graphene.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {12962}, pmid = {27708336}, issn = {2041-1723}, abstract = {The first hydrogenation step of benzene, which is endergonic in the electronic ground state (S0), becomes exergonic in the first triplet state (T1). This is in line with Baird's rule, which tells that benzene is antiaromatic and destabilized in its T1 state and also in its first singlet excited state (S1), opposite to S0, where it is aromatic and remarkably unreactive. Here we utilized this feature to show that benzene and several polycyclic aromatic hydrocarbons (PAHs) to various extents undergo metal-free photochemical (hydro)silylations and transfer-hydrogenations at mild conditions, with the highest yield for naphthalene (photosilylation: 21%). Quantum chemical computations reveal that T1-state benzene is excellent at H-atom abstraction, while cyclooctatetraene, aromatic in the T1 and S1 states according to Baird's rule, is unreactive. Remarkably, also CVD-graphene on SiO2 is efficiently transfer-photohydrogenated using formic acid/water mixtures together with white light or solar irradiation under metal-free conditions.}, } @article {pmid27695917, year = {2017}, author = {Yasukochi, Y and Ohashi, J}, title = {Elucidating the origin of HLA-B*73 allelic lineage: Did modern humans benefit by archaic introgression?.}, journal = {Immunogenetics}, volume = {69}, number = {1}, pages = {63-67}, pmid = {27695917}, issn = {1432-1211}, mesh = {Alleles ; Animals ; Asian People/genetics ; Black People/genetics ; Europe ; *Evolution, Molecular ; *Genome, Human ; HLA-B Antigens/*genetics ; Haplotypes/*genetics ; Hominidae/classification/*genetics ; Humans ; Neanderthals/genetics ; Pan troglodytes/genetics ; Phylogeny ; }, abstract = {A previous study reported that some of the human leukocyte antigen (HLA) alleles and haplotypes in present-day humans were acquired by admixture with archaic humans; specifically, an exceptionally diverged HLA-B*73 allele was proposed to be transmitted from Denisovans, although the DNA sequence of HLA-B*73 has not been detected in the Denisovan genome. Here, we argue against the hypothesis that HLA-B*73 introgressed from Denisovans into early modern humans. A phylogenetic analysis revealed that HLA-B*73:01 formed a monophyletic group with a chimpanzee MHC-B allele, strongly suggesting that the HLA-B*73 allelic lineage has been maintained in humans as well as in chimpanzees since the divergence of humans and chimpanzees. The global distribution of HLA-B*73 allele showed that the population frequency of HLA-B*73 in west Asia (0.24 %)-a possible site of admixture with Denisovans-is lower than that in Europe (0.72 %) and in south Asia (0.69 %). Furthermore, HLA-B*73 is not observed in Melanesia even though the Melanesian genome contains the highest proportion of Denisovan ancestry in present-day human populations. Single nucleotide polymorphisms in HLA-A*11-HLA-C*12:02 or HLA-A*11-C*15 haplotypes, one of which was assumed to be transmitted together with HLA-B*73 from Denisovans by the study of Abi-Rached and colleagues, were not differentiated from those in other HLA-A-C haplotypes in modern humans. These results do not support the introgression hypothesis. Thus, we conclude that it is highly likely that HLA-B*73 allelic lineage has been maintained in the direct ancestors of modern humans.}, } @article {pmid27671680, year = {2016}, author = {Kaur, A and Denisova, OV and Qiao, X and Jumppanen, M and Peuhu, E and Ahmed, SU and Raheem, O and Haapasalo, H and Eriksson, J and Chalmers, AJ and Laakkonen, P and Westermarck, J}, title = {PP2A Inhibitor PME-1 Drives Kinase Inhibitor Resistance in Glioma Cells.}, journal = {Cancer research}, volume = {76}, number = {23}, pages = {7001-7011}, doi = {10.1158/0008-5472.CAN-16-1134}, pmid = {27671680}, issn = {1538-7445}, support = {G0802755/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Glioma/*drug therapy/pathology ; Humans ; Mice ; Protein Kinase Inhibitors/*therapeutic use ; Protein Phosphatase 2/*metabolism ; Transfection ; }, abstract = {Glioblastoma multiforme lacks effective therapy options. Although deregulated kinase pathways are drivers of malignant progression in glioblastoma multiforme, glioma cells exhibit intrinsic resistance toward many kinase inhibitors, and the molecular basis of this resistance remains poorly understood. Here, we show that overexpression of the protein phosphatase 2A (PP2A) inhibitor protein PME-1 drives resistance of glioma cells to various multikinase inhibitors. The PME-1-elicited resistance was dependent on specific PP2A complexes and was mediated by a decrease in cytoplasmic HDAC4 activity. Importantly, both PME-1 and HDAC4 associated with human glioma progression, supporting clinical relevance of the identified mechanism. Synthetic lethality induced by both PME-1 and HDAC4 inhibition was dependent on the coexpression of proapoptotic protein BAD. Thus, PME-1-mediated PP2A inhibition is a novel mechanistic explanation for multikinase inhibitor resistance in glioma cells. Clinically, these results may inform patient stratification strategies for future clinical trials with selected kinase inhibitors in glioblastoma multiforme. Cancer Res; 76(23); 7001-11. ©2016 AACR.}, } @article {pmid27662059, year = {2016}, author = {Wall, JD and Yoshihara Caldeira Brandt, D}, title = {Archaic admixture in human history.}, journal = {Current opinion in genetics & development}, volume = {41}, number = {}, pages = {93-97}, doi = {10.1016/j.gde.2016.07.002}, pmid = {27662059}, issn = {1879-0380}, mesh = {Africa ; Animals ; DNA, Ancient/*analysis ; Genetics, Population/*history ; History, Ancient ; Hominidae/*genetics ; Humans ; Neanderthals/*genetics ; }, abstract = {Modern humans evolved in Southern or Eastern Africa, and spread from there across the rest of the world. As they expanded across Africa and Eurasia, they encountered other hominin groups. The extent to which modern and 'archaic' human groups interbred is an area of active research, and while we know that modern humans interbred with Neanderthals and Denisovans, there is not yet agreement on how many admixture events there were or on how much Neanderthal or Denisovan DNA can be found in contemporary genomes. Here we review what is known about archaic admixture in human history, with a focus on what has been discovered in the past 2 years.}, } @article {pmid27655273, year = {2016}, author = {Aarts, JM and Alink, GM and Scherjon, F and MacDonald, K and Smith, AC and Nijveen, H and Roebroeks, W}, title = {Fire Usage and Ancient Hominin Detoxification Genes: Protective Ancestral Variants Dominate While Additional Derived Risk Variants Appear in Modern Humans.}, journal = {PloS one}, volume = {11}, number = {9}, pages = {e0161102}, pmid = {27655273}, issn = {1932-6203}, abstract = {Studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. Fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. To investigate whether such genetic selection occurred, we investigated the alleles in Neanderthals, Denisovans and modern humans at gene polymorphisms well-known to be relevant from modern human epidemiological studies of habitual tobacco smoke exposure and mechanistic evidence. We compared these with the alleles in chimpanzees and gorillas. Neanderthal and Denisovan hominins predominantly possess gene variants conferring increased resistance to these toxic compounds. Surprisingly, we observed the same in chimpanzees and gorillas, implying that less efficient variants are derived and mainly evolved in modern humans. Less efficient variants are observable from the first early Upper Palaeolithic hunter-gatherers onwards. While not clarifying the deep history of fire use, our results highlight the long-term stability of the genes under consideration despite major changes in the hominin dietary niche. Specifically for detoxification gene variants characterised as deleterious by epidemiological studies, our results confirm the predominantly recent appearance reported for deleterious human gene variants, suggesting substantial impact of recent human population history, including pre-Holocene expansions.}, } @article {pmid27606907, year = {2016}, author = {Slatkin, M}, title = {Statistical methods for analyzing ancient DNA from hominins.}, journal = {Current opinion in genetics & development}, volume = {41}, number = {}, pages = {72-76}, pmid = {27606907}, issn = {1879-0380}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA, Ancient/*analysis ; DNA, Mitochondrial/*genetics ; Fossils ; Genetics, Population/*statistics & numerical data ; Genome/genetics ; Hominidae/*genetics ; Humans ; Neanderthals/genetics ; }, abstract = {In the past few years, the number of autosomal DNA sequences from human fossils has grown explosively and numerous partial or complete sequences are available from our closest relatives, Neanderthal and Denisovans. I review commonly used statistical methods applied to these sequences. These methods fall into three broad classes: methods for estimating levels of contamination, descriptive methods, and methods based on population genetic models. The latter two classes are largely methods developed for the analysis of present-day genomic data. When they are applied to ancient DNA (aDNA), they usually ignore the time dimension. A few methods, particularly those concerned with inferring something about selection or ancestor-descendant relationships, take explicit account of the ages of aDNA samples.}, } @article {pmid30592826, year = {2016}, author = {Bulavin, VV and Chaplyuk, AL and Kal'manov, AS and Solomka, AV and Denisova, MP and Blinov, VV}, title = {[Modern methods of diagnosis of chronic viral hepatitis used in the practice of the military-medical examination].}, journal = {Voenno-meditsinskii zhurnal}, volume = {337}, number = {9}, pages = {10-17}, pmid = {30592826}, issn = {0026-9050}, mesh = {Chronic Disease ; Female ; Hepatitis, Viral, Human/*classification/*diagnosis ; Humans ; Male ; Military Medicine/*methods ; }, abstract = {Modern methods of diagnosis of chronic viral hepatitis used in the practice of the military-medical examination. The article presents current views on the classification of chronic viral hepatitis. The characteristic of methodical diagnostic approaches is presented: The attention to the etiological pathology verification is paid. The results of study on clinical characteristics of patients with chronic viral hepatitis are used as the basis for the developed criteria for evaluating fitness for military service.}, } @article {pmid27569548, year = {2016}, author = {Lu, D and Lou, H and Yuan, K and Wang, X and Wang, Y and Zhang, C and Lu, Y and Yang, X and Deng, L and Zhou, Y and Feng, Q and Hu, Y and Ding, Q and Yang, Y and Li, S and Jin, L and Guan, Y and Su, B and Kang, L and Xu, S}, title = {Ancestral Origins and Genetic History of Tibetan Highlanders.}, journal = {American journal of human genetics}, volume = {99}, number = {3}, pages = {580-594}, pmid = {27569548}, issn = {1537-6605}, support = {K99 AA021802/AA/NIAAA NIH HHS/United States ; R00 AA021802/AA/NIAAA NIH HHS/United States ; }, mesh = {Altitude ; Animals ; Asian People/*genetics ; China/ethnology ; Ethnicity/genetics ; Gene Flow/*genetics ; Gene Pool ; Genetics, Population ; Genome, Human/*genetics ; Haplotypes/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Models, Genetic ; Neanderthals/genetics ; Oceania/ethnology ; *Phylogeny ; Selection, Genetic ; Tibet ; }, abstract = {The origin of Tibetans remains one of the most contentious puzzles in history, anthropology, and genetics. Analyses of deeply sequenced (30×-60×) genomes of 38 Tibetan highlanders and 39 Han Chinese lowlanders, together with available data on archaic and modern humans, allow us to comprehensively characterize the ancestral makeup of Tibetans and uncover their origins. Non-modern human sequences compose ∼6% of the Tibetan gene pool and form unique haplotypes in some genomic regions, where Denisovan-like, Neanderthal-like, ancient-Siberian-like, and unknown ancestries are entangled and elevated. The shared ancestry of Tibetan-enriched sequences dates back to ∼62,000-38,000 years ago, predating the Last Glacial Maximum (LGM) and representing early colonization of the plateau. Nonetheless, most of the Tibetan gene pool is of modern human origin and diverged from that of Han Chinese ∼15,000 to ∼9,000 years ago, which can be largely attributed to post-LGM arrivals. Analysis of ∼200 contemporary populations showed that Tibetans share ancestry with populations from East Asia (∼82%), Central Asia and Siberia (∼11%), South Asia (∼6%), and western Eurasia and Oceania (∼1%). Our results support that Tibetans arose from a mixture of multiple ancestral gene pools but that their origins are much more complicated and ancient than previously suspected. We provide compelling evidence of the co-existence of Paleolithic and Neolithic ancestries in the Tibetan gene pool, indicating a genetic continuity between pre-historical highland-foragers and present-day Tibetans. In particular, highly differentiated sequences harbored in highlanders' genomes were most likely inherited from pre-LGM settlers of multiple ancestral origins (SUNDer) and maintained in high frequency by natural selection.}, } @article {pmid27517578, year = {2016}, author = {Caldararo, N}, title = {Denisovans, Melanesians, Europeans, and Neandertals: The Confusion of DNA Assumptions and the Biological Species Concept.}, journal = {Journal of molecular evolution}, volume = {83}, number = {1-2}, pages = {78-87}, pmid = {27517578}, issn = {1432-1432}, mesh = {Animals ; Biological Evolution ; DNA/genetics ; DNA, Ancient/*analysis ; Fossils ; Hominidae/genetics ; Humans ; Neanderthals/*genetics ; Sequence Alignment/methods ; Sequence Analysis, DNA/methods ; }, abstract = {A number of recent articles have appeared on the Denisova fossil remains and attempts to produce DNA sequences from them. One of these recently appeared in Science by Vernot et al. (Science 352:235-239, 2016). We would like to advance an alternative interpretation of the data presented. One concerns the problem of contamination/degradation of the determined DNA sequenced. Just as the publication of the first Neandertal sequence included an interpretation that argued that Neandertals had not contributed any genes to modern humans, the Denisovan interpretation has considerable influence on ideas regarding human evolution. The new papers, however, confuse established ideas concerning the nature of species, as well as the use of terms like premodern, Archaic Homo, and Homo heidelbergensis. Examination of these problems presents a solution by means of reinterpreting the results. Given the claims for gene transfer among a number of Mid Pleistocene hominids, it may be time to reexamine the idea of anagenesis in hominid evolution.}, } @article {pmid27486223, year = {2016}, author = {Hubbard, TD and Murray, IA and Bisson, WH and Sullivan, AP and Sebastian, A and Perry, GH and Jablonski, NG and Perdew, GH}, title = {Divergent Ah Receptor Ligand Selectivity during Hominin Evolution.}, journal = {Molecular biology and evolution}, volume = {33}, number = {10}, pages = {2648-2658}, pmid = {27486223}, issn = {1537-1719}, support = {R01 ES004869/ES/NIEHS NIH HHS/United States ; R01 ES019964/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Benzo(a)pyrene ; Biological Evolution ; Cytochrome P-450 CYP1A1/genetics ; Cytochrome P-450 CYP1B1/genetics ; DNA/metabolism ; Evolution, Molecular ; Hominidae/*genetics ; Humans ; Ligands ; Neanderthals/*genetics ; Polycyclic Aromatic Hydrocarbons/metabolism ; Receptors, Aryl Hydrocarbon/*genetics ; }, abstract = {We have identified a fixed nonsynonymous sequence difference between humans (Val381; derived variant) and Neandertals (Ala381; ancestral variant) in the ligand-binding domain of the aryl hydrocarbon receptor (AHR) gene. In an exome sequence analysis of four Neandertal and Denisovan individuals compared with nine modern humans, there are only 90 total nucleotide sites genome-wide for which archaic hominins are fixed for the ancestral nonsynonymous variant and the modern humans are fixed for the derived variant. Of those sites, only 27, including Val381 in the AHR, also have no reported variability in the human dbSNP database, further suggesting that this highly conserved functional variant is a rare event. Functional analysis of the amino acid variant Ala381 within the AHR carried by Neandertals and nonhuman primates indicate enhanced polycyclic aromatic hydrocarbon (PAH) binding, DNA binding capacity, and AHR mediated transcriptional activity compared with the human AHR. Also relative to human AHR, the Neandertal AHR exhibited 150-1000 times greater sensitivity to induction of Cyp1a1 and Cyp1b1 expression by PAHs (e.g., benzo(a)pyrene). The resulting CYP1A1/CYP1B1 enzymes are responsible for PAH first pass metabolism, which can result in the generation of toxic intermediates and perhaps AHR-associated toxicities. In contrast, the human AHR retains the ancestral sensitivity observed in primates to nontoxic endogenous AHR ligands (e.g., indole, indoxyl sulfate). Our findings reveal that a functionally significant change in the AHR occurred uniquely in humans, relative to other primates, that would attenuate the response to many environmental pollutants, including chemicals present in smoke from fire use during cooking.}, } @article {pmid27486199, year = {2016}, author = {Söderholm, S and Kainov, DE and Öhman, T and Denisova, OV and Schepens, B and Kulesskiy, E and Imanishi, SY and Corthals, G and Hintsanen, P and Aittokallio, T and Saelens, X and Matikainen, S and Nyman, TA}, title = {Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages.}, journal = {Molecular & cellular proteomics : MCP}, volume = {15}, number = {10}, pages = {3203-3219}, pmid = {27486199}, issn = {1535-9484}, mesh = {Animals ; Computational Biology/methods ; Cyclin-Dependent Kinases/metabolism ; Gene Expression Regulation ; Host-Pathogen Interactions ; Humans ; Influenza A virus/*pathogenicity ; Influenza, Human/*metabolism ; Macrophages/metabolism/*virology ; Mice ; Phosphoproteins/*analysis ; Proteomics/*methods ; Signal Transduction ; }, abstract = {Influenza A viruses cause infections in the human respiratory tract and give rise to annual seasonal outbreaks, as well as more rarely dreaded pandemics. Influenza A viruses become quickly resistant to the virus-directed antiviral treatments, which are the current main treatment options. A promising alternative approach is to target host cell factors that are exploited by influenza viruses. To this end, we characterized the phosphoproteome of influenza A virus infected primary human macrophages to elucidate the intracellular signaling pathways and critical host factors activated upon influenza infection. We identified 1675 phosphoproteins, 4004 phosphopeptides and 4146 nonredundant phosphosites. The phosphorylation of 1113 proteins (66%) was regulated upon infection, highlighting the importance of such global phosphoproteomic profiling in primary cells. Notably, 285 of the identified phosphorylation sites have not been previously described in publicly available phosphorylation databases, despite many published large-scale phosphoproteome studies using human and mouse cell lines. Systematic bioinformatics analysis of the phosphoproteome data indicated that the phosphorylation of proteins involved in the ubiquitin/proteasome pathway (such as TRIM22 and TRIM25) and antiviral responses (such as MAVS) changed in infected macrophages. Proteins known to play roles in small GTPase-, mitogen-activated protein kinase-, and cyclin-dependent kinase- signaling were also regulated by phosphorylation upon infection. In particular, the influenza infection had a major influence on the phosphorylation profiles of a large number of cyclin-dependent kinase substrates. Functional studies using cyclin-dependent kinase inhibitors showed that the cyclin-dependent kinase activity is required for efficient viral replication and for activation of the host antiviral responses. In addition, we show that cyclin-dependent kinase inhibitors protect IAV-infected mice from death. In conclusion, we provide the first comprehensive phosphoproteome characterization of influenza A virus infection in primary human macrophages, and provide evidence that cyclin-dependent kinases represent potential therapeutic targets for more effective treatment of influenza infections.}, } @article {pmid27463216, year = {2016}, author = {Taylor, JS and Reimchen, TE}, title = {Opsin gene repertoires in northern archaic hominids.}, journal = {Genome}, volume = {59}, number = {8}, pages = {541-549}, doi = {10.1139/gen-2015-0164}, pmid = {27463216}, issn = {1480-3321}, mesh = {Animals ; Anthropology, Physical ; Base Sequence ; Evolution, Molecular ; Genome, Human ; Hominidae/*genetics ; Humans ; Methyl-CpG-Binding Protein 2/genetics ; Neanderthals/genetics ; Opsins/*genetics ; Phylogeny ; Vision, Ocular/genetics ; }, abstract = {The Neanderthals' northern distribution, hunting techniques, and orbit breadths suggest that they were more active in dim light than modern humans. We surveyed visual opsin genes from four Neanderthals and two other archaic hominids to see if they provided additional support for this hypothesis. This analysis was motivated by the observation that alleles responsible for anomalous trichromacy in humans are more common in northern latitudes, by data suggesting that these variants might enhance vision in mesopic conditions, and by the observation that dim light active species often have fewer opsin genes than diurnal relatives. We also looked for evidence of convergent amino acid substitutions in Neanderthal opsins and orthologs from crepuscular or nocturnal species. The Altai Neanderthal, the Denisovan, and the Ust'-Ishim early modern human had opsin genes that encoded proteins identical to orthologs in the human reference genome. Opsins from the Vindija Cave Neanderthals (three females) had many nonsynonymous substitutions, including several predicted to influence colour vision (e.g., stop codons). However, the functional implications of these observations were difficult to assess, given that "control" loci, where no substitutions were expected, differed from humans to the same extent. This left unresolved the test for colour vision deficiencies in Vindija Cave Neanderthals.}, } @article {pmid27429943, year = {2016}, author = {Ko, KH}, title = {Hominin interbreeding and the evolution of human variation.}, journal = {Journal of biological research (Thessalonike, Greece)}, volume = {23}, number = {}, pages = {17}, pmid = {27429943}, issn = {1790-045X}, abstract = {Mitochondrial Eve confirms the "out of Africa" theory, but the evidence also supports interbreeding between Homo sapiens and other hominins: Neanderthals, Denisovans, and Homo heidelbergensis. This article explains how interbreeding between early H. sapiens and archaic hominins occurred. The availability of edible insects in East Asia aided the spread of the unaggressive, highly cooperative Neanderthals, who interbred with H. sapiens in Asia, resulting in a higher admixture of Neanderthal DNA in East Asian populations. Geographical variation in degree of interbreeding between H. sapiens and Neanderthals likely contributed to neurological and behavioral differences in modern humans. Similarly, people with Denisovan genetic admixture were better able to dwell in mountainous regions, allowing their genetic legacy to cross the Himalayas and persist in Southeast Asian and Oceanian H. sapiens. In the Sub-Saharan region, unaffected by Denisovan or Neanderthal interbreeding, H. sapiens interbred with H. heidelbergensis, because high humidity militated against fire-making and allowed the survival of these non-fire-making hominins.}, } @article {pmid27423248, year = {2017}, author = {Miga, KH}, title = {Chromosome-Specific Centromere Sequences Provide an Estimate of the Ancestral Chromosome 2 Fusion Event in Hominin Genomes.}, journal = {The Journal of heredity}, volume = {108}, number = {1}, pages = {45-52}, doi = {10.1093/jhered/esw039}, pmid = {27423248}, issn = {1465-7333}, mesh = {Animals ; *Centromere ; Chromosomes, Human, Pair 2 ; *Chromosomes, Mammalian ; DNA, Satellite ; *Evolution, Molecular ; *Genome ; Genomics/methods ; Hominidae/*genetics ; Humans ; Pan troglodytes/genetics ; }, abstract = {Human chromosome 2 is a product of a telomere fusion of two ancestral chromosomes and loss/degeneration of one of the two original centromeres. Genomic signatures of this event are limited to inverted telomeric repeats at the precise site of chromosomal fusion and to the small amount of relic centromeric sequences that remain on 2q21.2. Unlike the site of fusion, which is enriched for sequences that are shared elsewhere in the human genome, the region of the nonfunctioning and degenerate ancestral centromere appears to share limited similarity with other sites in the human genome, thereby providing an opportunity to study this genomic arrangement in short, fragmented ancient DNA genomic datasets. Here, chromosome-assigned satellite DNAs are used to study shared centromere sequence organization in Denisovan and Neandertal genomes. By doing so, one is able to provide evidence for the presence of both active and degenerate centromeric satellite profiles on chromosome 2 in these archaic genomes, supporting the hypothesis that the chromosomal fusion event took place prior to our last common ancestor with Denisovan and Neandertal hominins and presenting a genomic reference for predicting karyotype in ancient genomic datasets.}, } @article {pmid27358932, year = {2016}, author = {Bogomolov, DV and Zbrueva, YV and Putintsev, VA and Denisova, OP}, title = {[Forensic medical diagnostics of intra-vitality of the strangulation mark by morphological methods].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {59}, number = {2}, pages = {40-43}, doi = {10.17116/sudmed201659240-43}, pmid = {27358932}, issn = {0039-4521}, mesh = {*Asphyxia/metabolism/pathology ; Forensic Pathology/methods ; Humans ; Immunohistochemistry ; }, abstract = {The objective of the present study WaS to overview the current domestic and foreign literature concerning the up-to-date methods employed for the expert evaluation of intra-vitality of the strangulation mark. The secondary objective was to propose the new approaches for addressing this problem. The methods of expert diagnostics with a view to determining the time of infliction of injuries as exemplified by mechanical asphyxia are discussed. It is concluded that immunohistochemical and morphometric studies provide the most promising tools for the evaluation of intra-vitality of the strangulation mark for the purpose of forensic medical expertise.}, } @article {pmid27337483, year = {2016}, author = {Abi-Rached, L and Raoult, D}, title = {Paleogenetics and Past Infections: the Two Faces of the Coin of Human Immune Evolution.}, journal = {Microbiology spectrum}, volume = {4}, number = {3}, pages = {}, doi = {10.1128/microbiolspec.PoH-0018-2015}, pmid = {27337483}, issn = {2165-0497}, mesh = {Communicable Diseases/*epidemiology/*immunology ; *Evolution, Molecular ; *Fossils ; Humans ; *Immune System ; Immunogenetics/*methods ; Paleopathology/*methods ; Selection, Genetic ; }, abstract = {With the advent of next-generation sequencing, paleogenetics has considerably expanded over the past few years and notably encompassed the characterization of the genomes of archaic humans who lived more than 30,000 years ago. These paleogenetics investigations have revealed that admixture between modern and archaic humans occurred, with Neanderthals having contributed to 1.5% to 2.1% of modern Eurasian genomes, and Denisovans to 3% to 6% of modern Melanesian genomes and to approximately 0.2% of modern Asian genomes. Although these contributions are modest, they played a major role in shaping immune gene families, such as the HLA class I genes, for which the archaic alleles now represent more than 50% of the alleles in Europe and Asia. Such a high frequency is consistent with these archaic HLA class I variants having been positively selected because of their protective effect against contagious and devastating epidemics, such as those due to the plague agent Yersinia pestis or to Mycobacterium tuberculosis, which is responsible for deadly tuberculosis. While the exact nature of the infectious agents that contributed to the selection of the archaic variants is unknown, we are entering an exciting period in which paleogenetics and paleomicrobiology data can be integrated to generate a clearer picture of how the immune system of modern populations was shaped and the role admixture and epidemics have played in such evolutions.}, } @article {pmid27298468, year = {2016}, author = {Stringer, C}, title = {The origin and evolution of Homo sapiens.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1698}, pages = {}, pmid = {27298468}, issn = {1471-2970}, mesh = {Africa ; Animals ; *Biological Evolution ; *Fossils ; *Hominidae ; Humans ; Neanderthals ; }, abstract = {If we restrict the use of Homo sapiens in the fossil record to specimens which share a significant number of derived features in the skeleton with extant H. sapiens, the origin of our species would be placed in the African late middle Pleistocene, based on fossils such as Omo Kibish 1, Herto 1 and 2, and the Levantine material from Skhul and Qafzeh. However, genetic data suggest that we and our sister species Homo neanderthalensis shared a last common ancestor in the middle Pleistocene approximately 400-700 ka, which is at least 200 000 years earlier than the species origin indicated from the fossils already mentioned. Thus, it is likely that the African fossil record will document early members of the sapiens lineage showing only some of the derived features of late members of the lineage. On that basis, I argue that human fossils such as those from Jebel Irhoud, Florisbad, Eliye Springs and Omo Kibish 2 do represent early members of the species, but variation across the African later middle Pleistocene/early Middle Stone Age fossils shows that there was not a simple linear progression towards later sapiens morphology, and there was chronological overlap between different 'archaic' and 'modern' morphs. Even in the late Pleistocene within and outside Africa, we find H. sapiens specimens which are clearly outside the range of Holocene members of the species, showing the complexity of recent human evolution. The impact on species recognition of late Pleistocene gene flow between the lineages of modern humans, Neanderthals and Denisovans is also discussed, and finally, I reconsider the nature of the middle Pleistocene ancestor of these lineages, based on recent morphological and genetic data.This article is part of the themed issue 'Major transitions in human evolution'.}, } @article {pmid27274045, year = {2016}, author = {Slatkin, M and Racimo, F}, title = {Ancient DNA and human history.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {23}, pages = {6380-6387}, pmid = {27274045}, issn = {1091-6490}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA Contamination ; *DNA, Ancient ; Fossils ; Genome ; Hominidae/*genetics ; Humans ; }, abstract = {We review studies of genomic data obtained by sequencing hominin fossils with particular emphasis on the unique information that ancient DNA (aDNA) can provide about the demographic history of humans and our closest relatives. We concentrate on nuclear genomic sequences that have been published in the past few years. In many cases, particularly in the Arctic, the Americas, and Europe, aDNA has revealed historical demographic patterns in a way that could not be resolved by analyzing present-day genomes alone. Ancient DNA from archaic hominins has revealed a rich history of admixture between early modern humans, Neanderthals, and Denisovans, and has allowed us to disentangle complex selective processes. Information from aDNA studies is nowhere near saturation, and we believe that future aDNA sequences will continue to change our understanding of hominin history.}, } @article {pmid27274044, year = {2016}, author = {Roebroeks, W and Soressi, M}, title = {Neandertals revised.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {23}, pages = {6372-6379}, pmid = {27274044}, issn = {1091-6490}, mesh = {Animals ; Anthropology, Physical ; Biological Evolution ; Life Style ; *Neanderthals ; }, abstract = {The last decade has seen a significant growth of our knowledge of the Neandertals, a population of Pleistocene hunter-gatherers who lived in (western) Eurasia between ∼400,000 and 40,000 y ago. Starting from a source population deep in the Middle Pleistocene, the hundreds of thousands of years of relative separation between African and Eurasian groups led to the emergence of different phenotypes in Late Pleistocene Europe and Africa. Both recently obtained genetic evidence and archeological data show that the biological and cultural gaps between these populations were probably smaller than previously thought. These data, reviewed here, falsify inferences to the effect that, compared with their near-modern contemporaries in Africa, Neandertals were outliers in terms of behavioral complexity. It is only around 40,000 y ago, tens of thousands of years after anatomically modern humans first left Africa and thousands of years after documented interbreeding between modern humans, Neandertals and Denisovans, that we see major changes in the archeological record, from western Eurasia to Southeast Asia, e.g., the emergence of representational imagery and the colonization of arctic areas and of greater Australia (Sahul).}, } @article {pmid27182564, year = {2016}, author = {Rabinovich, IM and Rabinovich, OF and Abramova, ES and Denisova, MA}, title = {[Clinical and pathogenetic aspects of various forms of cheilitis].}, journal = {Stomatologiia}, volume = {95}, number = {1}, pages = {67-72}, doi = {10.17116/stomat201695167-72}, pmid = {27182564}, issn = {0039-1735}, mesh = {Cheilitis/drug therapy/*etiology/*pathology ; Humans ; Microscopic Angioscopy/methods ; }, } @article {pmid27176232, year = {2016}, author = {Zhao, G and Denisova, K and Sehatpour, P and Long, J and Gui, W and Qiao, J and Javitt, DC and Wang, Z}, title = {Fractal Dimension Analysis of Subcortical Gray Matter Structures in Schizophrenia.}, journal = {PloS one}, volume = {11}, number = {5}, pages = {e0155415}, pmid = {27176232}, issn = {1932-6203}, support = {T32 MH016434/MH/NIMH NIH HHS/United States ; }, abstract = {A failure of adaptive inference-misinterpreting available sensory information for appropriate perception and action-is at the heart of clinical manifestations of schizophrenia, implicating key subcortical structures in the brain including the hippocampus. We used high-resolution, three-dimensional (3D) fractal geometry analysis to study subtle and potentially biologically relevant structural alterations (in the geometry of protrusions, gyri and indentations, sulci) in subcortical gray matter (GM) in patients with schizophrenia relative to healthy individuals. In particular, we focus on utilizing Fractal Dimension (FD), a compact shape descriptor that can be computed using inputs with irregular (i.e., not necessarily smooth) surfaces in order to quantify complexity (of geometrical properties and configurations of structures across spatial scales) of subcortical GM in this disorder. Probabilistic (entropy-based) information FD was computed based on the box-counting approach for each of the seven subcortical structures, bilaterally, as well as the brainstem from high-resolution magnetic resonance (MR) images in chronic patients with schizophrenia (n = 19) and age-matched healthy controls (n = 19) (age ranges: patients, 22.7-54.3 and healthy controls, 24.9-51.6 years old). We found a significant reduction of FD in the left hippocampus (median: 2.1460, range: 2.07-2.18 vs. median: 2.1730, range: 2.15-2.23, p<0.001; Cohen's effect size, U3 = 0.8158 (95% Confidence Intervals, CIs: 0.6316, 1.0)), the right hippocampus (median: 2.1430, range: 2.05-2.19 vs. median: 2.1760, range: 2.12-2.21, p = 0.004; U3 = 0.8421 (CIs: 0.5263, 1)), as well as left thalamus (median: 2.4230, range: 2.40-2.44, p = 0.005; U3 = 0.7895 (CIs: 0.5789, 0.9473)) in schizophrenia patients, relative to healthy individuals. Our findings provide in-vivo quantitative evidence for reduced surface complexity of hippocampus, with reduced FD indicating a less complex, less regular GM surface detected in schizophrenia.}, } @article {pmid27160892, year = {2016}, author = {Johnston, SC and Amarenco, P and Albers, GW and Denison, H and Easton, JD and Evans, SR and Held, P and Jonasson, J and Minematsu, K and Molina, CA and Wang, Y and Wong, KS and , }, title = {Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.}, journal = {The New England journal of medicine}, volume = {375}, number = {1}, pages = {35-43}, doi = {10.1056/NEJMoa1603060}, pmid = {27160892}, issn = {1533-4406}, mesh = {Adenosine/adverse effects/*analogs & derivatives/therapeutic use ; Aged ; Aspirin/adverse effects/*therapeutic use ; Double-Blind Method ; Female ; Hemorrhage/chemically induced ; Humans ; Ischemic Attack, Transient/*drug therapy ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/adverse effects/*therapeutic use ; Purinergic P2Y Receptor Antagonists/adverse effects/therapeutic use ; Stroke/*drug therapy ; Ticagrelor ; }, abstract = {BACKGROUND: Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.

METHODS: We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.

RESULTS: During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.

CONCLUSIONS: In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).}, } @article {pmid27114917, year = {2016}, author = {Pervaiz, N and Abbasi, AA}, title = {Molecular evolution of WDR62, a gene that regulates neocorticogenesis.}, journal = {Meta gene}, volume = {9}, number = {}, pages = {1-9}, pmid = {27114917}, issn = {2214-5400}, abstract = {Human brain evolution is characterized by dramatic expansion in cerebral cortex size. WDR62 (WD repeat domain 62) is one of the important gene in controlling human cortical development. Mutations in WDR62 lead to primary microcephaly, a neurodevelopmental disease characterized by three to four fold reduction in cerebral cortex size of affected individuals. This study analyzes comparative protein evolutionary rate to provide a useful insight into the molecular evolution of WDR62 and hence pinpointed human specific amino acid replacements. Comparative analysis of human WDR62 with two archaic humans (Neanderthals and Denisovans) and modern human populations revealed that five hominin specific amino acid residues (human specific amino acids shared with two archaic humans) might have been accumulated in the common ancestor of extinct archaic humans and modern humans about 550,000-765,000 years ago. Collectively, the data demonstrates an acceleration of WDR62 sequence evolution in hominin lineage and suggests that the ability of WDR62 protein to mediate the neurogenesis has been altered in the course of hominin evolution.}, } @article {pmid27070257, year = {2016}, author = {Denisova, NP and Rogov, DY and Rzaev, DA and Khabarova, EA and Dmitriev, AB}, title = {Spinal cord stimulation in the treatment of chronic pain syndromes.}, journal = {Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko}, volume = {80}, number = {2}, pages = {47-52}, doi = {10.17116/neiro201680247-52}, pmid = {27070257}, issn = {0042-8817}, mesh = {Adult ; Aged ; Aged, 80 and over ; Chronic Pain/*therapy ; Electric Stimulation Therapy/*methods ; Female ; Humans ; Male ; Middle Aged ; Neuralgia/*therapy ; *Spinal Cord ; Syndrome ; }, abstract = {AIM: The study objective was to estimate the efficacy of chronic epidural spinal cord stimulation in the treatment of patients with neuropathic pain syndrome.

MATERIAL AND METHODS: A system for chronic spinal cord stimulation (St. Jude) was implanted to 75 patients with neuropathic pain syndrome. Fifty three (70.7%) patients were diagnosed with failed back surgery syndrome (FBSS); 9 (12.0%) patients had complex regional pain syndrome type II; 4 (5.3%) patients had diabetic polyneuropathy of the lower limbs; 3 (4.0%) patients had idiopathic pelvic-perineal pain; 2 (2.7%) patients had spinal stroke pain; 2 (2.7%) patients had postherpetic intercostal neuralgia; 1 (1.3%) patient had stump pain; 1 (1.3%) patient had spinal cord injury pain. The treatment efficacy was evaluated using the visual analog scale (VAS) and DN4 questionnaire. The follow-up period ranged from 6 to 18 months.

RESULTS: 136 patients underwent test stimulation at the Center in 2014. A significant reduction in pain was observed in 75 (55.1%) patients. These patients underwent the second stage of surgery that included implantation of permanent electrodes and a generator. The mean VAS score was 6.5 (maximum: 10; minimum: 5) before surgery, 3.2 at discharge, and 3.1 after 3 and 6 months. The VAS score amounted to 3.6 after 12 months. Complications in the form of pain at the generator implantation site and the need for removal of the system occurred in 2 patients (2.6%), electrode migration was observed in 4 (5.3%) cases.

CONCLUSION: Chronic epidural spinal cord stimulation is an effective and safe technique for the treatment of drug-resistant chronic neurogenic pain syndromes.}, } @article {pmid27063929, year = {2016}, author = {Houldcroft, CJ and Underdown, SJ}, title = {Neanderthal genomics suggests a pleistocene time frame for the first epidemiologic transition.}, journal = {American journal of physical anthropology}, volume = {160}, number = {3}, pages = {379-388}, doi = {10.1002/ajpa.22985}, pmid = {27063929}, issn = {1096-8644}, mesh = {Animals ; Anthropology, Physical ; Communicable Diseases/*genetics/history/*immunology/microbiology ; Evolution, Molecular ; Fossils ; Genome/*genetics/*immunology ; Genomics ; History, Ancient ; Humans ; Neanderthals/*genetics/*immunology ; }, abstract = {High quality Altai Neanderthal and Denisovan genomes are revealing which regions of archaic hominin DNA have persisted in the modern human genome. A number of these regions are associated with response to infection and immunity, with a suggestion that derived Neanderthal alleles found in modern Europeans and East Asians may be associated with autoimmunity. As such Neanderthal genomes are an independent line of evidence of which infectious diseases Neanderthals were genetically adapted to. Sympathetically, human genome adaptive introgression is an independent line of evidence of which infectious diseases were important for AMH coming in to Eurasia and interacting with Neanderthals. The Neanderthals and Denisovans present interesting cases of hominin hunter-gatherers adapted to a Eurasian rather than African infectious disease package. Independent sources of DNA-based evidence allow a re-evaluation of the first epidemiologic transition and how infectious disease affected Pleistocene hominins. By combining skeletal, archaeological and genetic evidence from modern humans and extinct Eurasian hominins, we question whether the first epidemiologic transition in Eurasia featured a new package of infectious diseases or a change in the impact of existing pathogens. Coupled with pathogen genomics, this approach supports the view that many infectious diseases are pre-Neolithic, and the list continues to expand. The transfer of pathogens between hominin populations, including the expansion of pathogens from Africa, may also have played a role in the extinction of the Neanderthals and offers an important mechanism to understand hominin-hominin interactions well back beyond the current limits for aDNA extraction from fossils alone. Am J Phys Anthropol 160:379-388, 2016. © 2016 Wiley Periodicals, Inc.}, } @article {pmid27044111, year = {2016}, author = {Varki, A}, title = {Why are there no persisting hybrids of humans with Denisovans, Neanderthals, or anyone else?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {17}, pages = {E2354}, pmid = {27044111}, issn = {1091-6490}, support = {P01 HL107150/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Fossils ; *Hominidae ; Humans ; *Neanderthals ; }, } @article {pmid27032491, year = {2016}, author = {Sankararaman, S and Mallick, S and Patterson, N and Reich, D}, title = {The Combined Landscape of Denisovan and Neanderthal Ancestry in Present-Day Humans.}, journal = {Current biology : CB}, volume = {26}, number = {9}, pages = {1241-1247}, pmid = {27032491}, issn = {1879-0445}, support = {/HHMI/Howard Hughes Medical Institute/United States ; K99 GM111744/GM/NIGMS NIH HHS/United States ; R00 GM111744/GM/NIGMS NIH HHS/United States ; R01 GM100233/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Demography ; Genome, Human ; Humans ; Models, Genetic ; Neanderthals/*genetics ; Racial Groups/*genetics ; Time Factors ; }, abstract = {Some present-day humans derive up to ∼5% [1] of their ancestry from archaic Denisovans, an even larger proportion than the ∼2% from Neanderthals [2]. We developed methods that can disambiguate the locations of segments of Denisovan and Neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual Oceanians with high Denisovan ancestry [3]. In Oceanians, the average size of Denisovan fragments is larger than Neanderthal fragments, implying a more recent average date of Denisovan admixture in the history of these populations (p = 0.00004). We document more Denisovan ancestry in South Asia than is expected based on existing models of history, reflecting a previously undocumented mixture related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal ancestry, has been deleterious on a modern human genetic background, as reflected by its depletion near genes. Finally, the reduction of both archaic ancestries is especially pronounced on chromosome X and near genes more highly expressed in testes than other tissues (p = 1.2 × 10(-7) to 3.2 × 10(-7) for Denisovan and 2.2 × 10(-3) to 2.9 × 10(-3) for Neanderthal ancestry even after controlling for differences in level of selective constraint across gene classes). This suggests that reduced male fertility may be a general feature of mixtures of human populations diverged by >500,000 years.}, } @article {pmid27027286, year = {2016}, author = {Sutikna, T and Tocheri, MW and Morwood, MJ and Saptomo, EW and Jatmiko, and Awe, RD and Wasisto, S and Westaway, KE and Aubert, M and Li, B and Zhao, JX and Storey, M and Alloway, BV and Morley, MW and Meijer, HJ and van den Bergh, GD and Grün, R and Dosseto, A and Brumm, A and Jungers, WL and Roberts, RG}, title = {Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia.}, journal = {Nature}, volume = {532}, number = {7599}, pages = {366-369}, pmid = {27027286}, issn = {1476-4687}, mesh = {Aluminum Silicates ; Animals ; *Archaeology ; Australia ; Calibration ; Caves ; *Fossils ; Geologic Sediments/analysis ; Glass ; *Hominidae ; Humans ; Indonesia ; Potassium Compounds ; Quartz ; *Radiometric Dating ; Time Factors ; Uncertainty ; }, abstract = {Homo floresiensis, a primitive hominin species discovered in Late Pleistocene sediments at Liang Bua (Flores, Indonesia), has generated wide interest and scientific debate. A major reason this taxon is controversial is because the H. floresiensis-bearing deposits, which include associated stone artefacts and remains of other extinct endemic fauna, were dated to between about 95 and 12 thousand calendar years (kyr) ago. These ages suggested that H. floresiensis survived until long after modern humans reached Australia by ~50 kyr ago. Here we report new stratigraphic and chronological evidence from Liang Bua that does not support the ages inferred previously for the H. floresiensis holotype (LB1), ~18 thousand calibrated radiocarbon years before present (kyr cal. BP), or the time of last appearance of this species (about 17 or 13-11 kyr cal. BP). Instead, the skeletal remains of H. floresiensis and the deposits containing them are dated to between about 100 and 60 kyr ago, whereas stone artefacts attributable to this species range from about 190 to 50 kyr in age. Whether H. floresiensis survived after 50 kyr ago--potentially encountering modern humans on Flores or other hominins dispersing through southeast Asia, such as Denisovans--is an open question.}, } @article {pmid27020421, year = {2016}, author = {Brown, S and Higham, T and Slon, V and Pääbo, S and Meyer, M and Douka, K and Brock, F and Comeskey, D and Procopio, N and Shunkov, M and Derevianko, A and Buckley, M}, title = {Identification of a new hominin bone from Denisova Cave, Siberia using collagen fingerprinting and mitochondrial DNA analysis.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {23559}, pmid = {27020421}, issn = {2045-2322}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols ; Bone and Bones/*metabolism ; Collagen/analysis/*metabolism ; Cyclophosphamide ; DNA, Mitochondrial/chemistry/classification/*genetics ; Doxorubicin ; Evolution, Molecular ; *Fossils ; Hominidae ; Humans ; Phylogeny ; Podophyllotoxin ; Radiometric Dating ; Sequence Analysis, DNA ; Siberia ; Tandem Mass Spectrometry ; Time Factors ; Vincristine ; }, abstract = {DNA sequencing has revolutionised our understanding of archaic humans during the Middle and Upper Palaeolithic. Unfortunately, while many Palaeolithic sites contain large numbers of bones, the majority of these lack the diagnostic features necessary for traditional morphological identification. As a result the recovery of Pleistocene-age human remains is extremely rare. To circumvent this problem we have applied a method of collagen fingerprinting to more than 2000 fragmented bones from the site of Denisova Cave, Russia, in order to facilitate the discovery of human remains. As a result of our analysis a single hominin bone (Denisova 11) was identified, supported through in-depth peptide sequencing analysis, and found to carry mitochondrial DNA of the Neandertal type. Subsequent radiocarbon dating revealed the bone to be >50,000 years old. Here we demonstrate the huge potential collagen fingerprinting has for identifying hominin remains in highly fragmentary archaeological assemblages, improving the resources available for wider studies into human evolution.}, } @article {pmid26995655, year = {2016}, author = {Árnason, Ú}, title = {The Out of Africa hypothesis and the ancestry of recent humans: Cherchez la femme (et l'homme).}, journal = {Gene}, volume = {585}, number = {1}, pages = {9-12}, doi = {10.1016/j.gene.2016.03.018}, pmid = {26995655}, issn = {1879-0038}, mesh = {Africa ; Animals ; Asia ; *Biological Evolution ; China ; DNA, Mitochondrial/genetics ; Europe ; *Evolution, Molecular ; Female ; *Fossils ; Gene Flow ; Humans ; Male ; Neanderthals/*genetics ; Phylogeny ; }, abstract = {The Out of Africa hypothesis (OOAH) has been a mainstay in the discussion of human evolution since its presentation in the 1980's. However, recent advances in palaeontology and molecular genetics have made it possible to examine the hypothesis in a manner that was inconceivable at the time of its proposal. The palaeontological progress relates to early Homo finds in the Caucasus, Denisova finds in the Altai Mountains and Neanderthal finds in a wide range of localities from the Altai Mountains, the Caucasus, the Levant, Asia Minor, southern and Central Europe and the Iberian Peninsula. The Eurasian location of these finds and recognition of the principle of Last common ancestor (LCA) lend no support to OOAH. The same conclusion is drawn from genomic findings, which (a) have revealed the presence of Denisovan and Neanderthal nuclear DNA, primarily in the genomes of recent Eurasians and (b) have shown genomic introgression from early modern humans into Neanderthals in the Altai Mountains. Similarly, archaeological finds in Sulawesi and the discovery of ≈100,000years old human teeth in southern China constitute strong independent challenges to OOAH. The genomic and palaeogenomic results and the new palaeontological and archaeological discoveries suggest (a) that the ancestors of modern humans had their origin in a Eurasian (largely Asian) biogeographic region which may also have extended into NE Africa, and (b) that the founders of basal African lineages became separated, geographically and genetically, in the westernmost part of this region and spread from there to different parts of the African continent.}, } @article {pmid26989198, year = {2016}, author = {Vernot, B and Tucci, S and Kelso, J and Schraiber, JG and Wolf, AB and Gittelman, RM and Dannemann, M and Grote, S and McCoy, RC and Norton, H and Scheinfeldt, LB and Merriwether, DA and Koki, G and Friedlaender, JS and Wakefield, J and Pääbo, S and Akey, JM}, title = {Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals.}, journal = {Science (New York, N.Y.)}, volume = {352}, number = {6282}, pages = {235-239}, pmid = {26989198}, issn = {1095-9203}, support = {R01 GM110068/GM/NIGMS NIH HHS/United States ; 5R01GM110068/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA/*genetics ; Genetic Variation ; Genome, Human/*genetics ; Humans ; Melanesia ; Native Hawaiian or Other Pacific Islander/*genetics ; Neanderthals/*genetics ; Sequence Analysis, DNA ; }, abstract = {Although Neandertal sequences that persist in the genomes of modern humans have been identified in Eurasians, comparable studies in people whose ancestors hybridized with both Neandertals and Denisovans are lacking. We developed an approach to identify DNA inherited from multiple archaic hominin ancestors and applied it to whole-genome sequences from 1523 geographically diverse individuals, including 35 previously unknown Island Melanesian genomes. In aggregate, we recovered 1.34 gigabases and 303 megabases of the Neandertal and Denisovan genome, respectively. We use these maps of archaic sequences to show that Neandertal admixture occurred multiple times in different non-African populations, characterize genomic regions that are significantly depleted of archaic sequences, and identify signatures of adaptive introgression.}, } @article {pmid26979798, year = {2016}, author = {Carmody, RN and Dannemann, M and Briggs, AW and Nickel, B and Groopman, EE and Wrangham, RW and Kelso, J}, title = {Genetic Evidence of Human Adaptation to a Cooked Diet.}, journal = {Genome biology and evolution}, volume = {8}, number = {4}, pages = {1091-1103}, pmid = {26979798}, issn = {1759-6653}, support = {F32 DK101154/DK/NIDDK NIH HHS/United States ; F32DK101154/DK/NIDDK NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Animals ; *Biological Evolution ; *Cooking ; *Diet ; Energy Intake ; Energy Metabolism ; Feeding Behavior ; *Gene Expression Regulation ; Humans ; Liver/metabolism ; Male ; Meat/analysis ; Mice ; Mice, Inbred BALB C ; Neanderthals/genetics/physiology ; Nutrigenomics ; *Selection, Genetic ; Transcriptome ; }, abstract = {Humans have been argued to be biologically adapted to a cooked diet, but this hypothesis has not been tested at the molecular level. Here, we combine controlled feeding experiments in mice with comparative primate genomics to show that consumption of a cooked diet influences gene expression and that affected genes bear signals of positive selection in the human lineage. Liver gene expression profiles in mice fed standardized diets of meat or tuber were affected by food type and cooking, but not by caloric intake or consumer energy balance. Genes affected by cooking were highly correlated with genes known to be differentially expressed in liver between humans and other primates, and more genes in this overlap set show signals of positive selection in humans than would be expected by chance. Sequence changes in the genes under selection appear before the split between modern humans and two archaic human groups, Neandertals and Denisovans, supporting the idea that human adaptation to a cooked diet had begun by at least 275,000 years ago.}, } @article {pmid26978613, year = {2016}, author = {Kovalkova, NA and Denisova, DV and Polonskaya, YV and Kashtanova, EV}, title = {[The incidence of respiratory symptoms and their associations with serum cotinine levels as a marker of tobacco smoking in 25-45-year-old Novosibirsk dwellers].}, journal = {Terapevticheskii arkhiv}, volume = {88}, number = {1}, pages = {70-74}, doi = {10.17116/terarkh201688170-74}, pmid = {26978613}, issn = {0040-3660}, mesh = {Adult ; Cotinine/*blood ; *Cough/epidemiology/etiology ; Female ; Humans ; Incidence ; Male ; *Respiratory Sounds/etiology/physiopathology ; Respiratory System/drug effects/physiopathology ; Siberia/epidemiology ; *Smoking/adverse effects/blood/epidemiology/physiopathology ; Time Factors ; }, abstract = {AIM: To study the incidence of respiratory symptoms and to reveal their associations with serum cotinine levels (SCL) in 25-45-year-old Novosibirsk dwellers.

SUBJECTS AND METHODS: The WHO respiratory symptom questionnaire and the ECRHS screening questionnaire were used for a population-based survey conducted in Novosibirsk to identify respiratory symptoms; 545 people replied to the questions available in the questionnaires. SCL was determined by enzyme immunoassay on a random subsample of 182 examinees.

RESULTS: The incidence of respiratory symptoms was determined among the 25-45-year-old Novosibirsk dwellers: cough (27.7%), more than 3-month cough per year (22%), sputum discharge (25%), forced respiration/wheezing in the past year (22.6%), suffocation fits in the past year (5.3%), and cough/forced respiration/stertor bouts by breathing cold air (14.9%) or contacting animals, plants, or chemical agents (16.5%). There was a significant positive correlation between SCL and the presence of cough, more than 3-month cough per year, sputum discharge, forced respiration/wheezing in the past year (compared to the examinees who did not report these symptoms). The median SCL proved to be significantly higher in the people who complained of cough, more than 3-month cough per year, sputum discharge, and forced respiration/wheezing in the past year (compared to the examinees who did not report these symptoms). The people who had a SCL of more than 3 ng/ml were ascertained to be at higher risk of cough, more than 3-month cough per year, sputum discharge, and forced respiration/wheezing in the past year than those who had a SCL of less than 3 ng/ml.

CONCLUSION: The incidence of respiratory symptoms was determined among the 25-45-year-old Novosibirsk dwellers; SCL was found to be associated with the symptoms characteristic of bronchial obstructive diseases; the expediency of using the SCL threshold of 3 ng/ml as a marker of tobacco smoking was confirmed.}, } @article {pmid26976447, year = {2016}, author = {Meyer, M and Arsuaga, JL and de Filippo, C and Nagel, S and Aximu-Petri, A and Nickel, B and Martínez, I and Gracia, A and Bermúdez de Castro, JM and Carbonell, E and Viola, B and Kelso, J and Prüfer, K and Pääbo, S}, title = {Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins.}, journal = {Nature}, volume = {531}, number = {7595}, pages = {504-507}, pmid = {26976447}, issn = {1476-4687}, mesh = {Alleles ; Animals ; DNA, Mitochondrial/genetics ; Fossils ; Genome, Mitochondrial/genetics ; Hominidae/classification/*genetics ; Male ; Neanderthals/classification/genetics ; *Phylogeny ; Sequence Alignment ; Spain ; }, abstract = {A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago. An interesting question is how these Middle Pleistocene hominins were related to those who lived in the Late Pleistocene epoch, in particular to Neanderthals in western Eurasia and to Denisovans, a sister group of Neanderthals so far known only from southern Siberia. While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals. However, since the mitochondrial DNA does not reveal the full picture of relationships among populations, we have investigated DNA preservation in several individuals found at Sima de los Huesos. Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.}, } @article {pmid26966016, year = {2016}, author = {Ghirotto, S and Tassi, F and Barbujani, G and Pattini, L and Hayward, C and Vollenweider, P and Bochud, M and Rampoldi, L and Devuyst, O}, title = {The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human Evolution.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {27}, number = {10}, pages = {2983-2996}, pmid = {26966016}, issn = {1533-3450}, support = {295733/ERC_/European Research Council/International ; GGP14263/TI_/Telethon/Italy ; MC_PC_U127561128/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Evolution, Molecular ; Genetic Loci ; Genetic Markers ; Genetic Variation ; Humans ; Urinary Tract Infections/genetics ; Uromodulin/*genetics ; }, abstract = {Common variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD in the general population, increase UMOD expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. To determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead UMOD variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. The T allele of rs4293393, associated with CKD risk, has high frequency in most modern populations and was the one detected in primate genomes. In contrast, we identified only the derived, C allele in Denisovan and Neanderthal genomes. The distribution of the UMOD ancestral allele did not follow the ancestral susceptibility model observed for variants associated with salt-sensitive hypertension. Instead, the global frequencies of the UMOD alleles significantly correlated with pathogen diversity (bacteria, helminths) and prevalence of antibiotic-resistant urinary tract infections (UTIs). The inverse correlation found between urinary levels of uromodulin and markers of UTIs in the general population substantiates the link between UMOD variants and protection against UTIs. These data strongly suggest that the UMOD ancestral allele, driving higher urinary excretion of uromodulin, has been kept at a high frequency because of its protective effect against UTIs.}, } @article {pmid26912899, year = {2016}, author = {}, title = {Erratum for the Report "Ancient Ethiopian genome reveals extensive Eurasian admixture in Eastern Africa" (previously titled "Ancient Ethiopian genome reveals extensive Eurasian admixture throughout the African continent") by M. Gallego Llorente, E. R. Jones, A. Eriksson, V. Siska, K. W. Arthur, J. W. Arthur, M. C. Curtis, J. T. Stock, M. Coltorti, P. Pieruccini, S. Stretton, F. Brock, T. Higham, Y. Park, M. Hofreiter, D. G. Bradley, J. Bhak, R. Pinhasi, A. Manica.}, journal = {Science (New York, N.Y.)}, volume = {351}, number = {6275}, pages = {}, doi = {10.1126/science.aaf3945}, pmid = {26912899}, issn = {1095-9203}, abstract = {In the Report “Ancient Ethiopian genome reveals extensive Eurasian admixture in Eastern Africa,” the results were affected by a bioinformatics error. A script necessary to convert the input produced by samtools v0.1.19 to be compatible with PLINK was not run when merging the ancient genome, Mota, with the contemporary populations SNP panel, leading to homozygote positions to the human reference genome being dropped as missing data (the analysis of admixture with Neandertals and Denisovans was not affected). When those positions were included, 255,922 SNP out of 256,540 from the contemporary reference panel could be called in Mota. These changes are reflected in the corrected Fig. 2B, fig. S6, and table S5. Tables S6 and S7 have been removed from the corrected Supplementary Material, because there is no detectable Western Eurasian component in Yoruba and Mbuti. The conclusion of a migration into East Africa from Western Eurasia, and more precisely from a source genetically close to the early Neolithic farmers, is not affected. However, the geographic extent of the genetic impact of this migration was overestimated: The Western Eurasian backflow mostly affected East Africa and only a few Sub-Saharan populations; the Yoruba and Mbuti do not show higher levels of Western Eurasian ancestry compared to Mota. Hence, the title and abstract of the published paper did not accurately represent the geographical extent of the admixture, and both have been corrected accordingly. The authors acknowledge Pontus Skoglund and David Reich for detecting these problems.}, } @article {pmid26912479, year = {2016}, author = {Mozzi, A and Forni, D and Clerici, M and Pozzoli, U and Mascheretti, S and Guerini, FR and Riva, S and Bresolin, N and Cagliani, R and Sironi, M}, title = {The evolutionary history of genes involved in spoken and written language: beyond FOXP2.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {22157}, pmid = {26912479}, issn = {2045-2322}, mesh = {Animals ; *Evolution, Molecular ; Forkhead Transcription Factors/*genetics ; Humans ; Language Development Disorders/*genetics ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics ; Receptors, Immunologic/genetics ; Selection, Genetic ; Sequence Alignment ; }, abstract = {Humans possess a communication system based on spoken and written language. Other animals can learn vocalization by imitation, but this is not equivalent to human language. Many genes were described to be implicated in language impairment (LI) and developmental dyslexia (DD), but their evolutionary history has not been thoroughly analyzed. Herein we analyzed the evolution of ten genes involved in DD and LI. Results show that the evolutionary history of LI genes for mammals and aves was comparable in vocal-learner species and non-learners. For the human lineage, several sites showing evidence of positive selection were identified in KIAA0319 and were already present in Neanderthals and Denisovans, suggesting that any phenotypic change they entailed was shared with archaic hominins. Conversely, in FOXP2, ROBO1, ROBO2, and CNTNAP2 non-coding changes rose to high frequency after the separation from archaic hominins. These variants are promising candidates for association studies in LI and DD.}, } @article {pmid26911356, year = {2016}, author = {Malyarchuk, BA and Derenko, M and Denisova, G and Woźniak, M and Rogalla, U and Dambueva, I and Grzybowski, T}, title = {Y chromosome haplotype diversity in Mongolic-speaking populations and gene conversion at the duplicated STR DYS385a,b in haplogroup C3-M407.}, journal = {Journal of human genetics}, volume = {61}, number = {6}, pages = {491-496}, pmid = {26911356}, issn = {1435-232X}, mesh = {Alleles ; Asian People/*genetics ; China ; *Chromosomes, Human, Y ; Cluster Analysis ; Ethnicity/genetics ; Evolution, Molecular ; *Gene Conversion ; Gene Frequency ; Genetic Loci ; *Genetic Variation ; *Genetics, Population ; *Haplotypes ; Humans ; Male ; *Microsatellite Repeats ; Mutation ; Russia ; }, abstract = {Y chromosome microsatellite (Y-STR) diversity has been studied in different Mongolic-speaking populations from South Siberia, Mongolia, North-East China and East Europe. The results obtained indicate that the Mongolic-speaking populations clustered into two groups, with one group including populations from eastern part of South Siberia and Central Asia (the Buryats, Barghuts and Khamnigans) and the other group including populations from western part of Central Asia and East Europe (the Mongols and Kalmyks). High frequency of haplogroup C3-M407 (>50%) is present in the Buryats, Barghuts and Khamnigans, whereas in the Mongols and Kalmyks its frequency is much lower. In addition, two allelic combinations in DYS385a,b loci of C3-M407 haplotypes have been observed: the combination 11,18 (as well as 11,17 and 11,19) is frequent in different Mongolic-speaking populations, but the 11,11 branch is present mainly in the Kalmyks and Mongols. Results of locus-specific sequencing suggest that the action of gene conversion is a more likely explanation for origin of homoallelic 11,11 combination. Moreover, analysis of median networks of Y-STR haplotypes demonstrates that at least two gene conversion events can be revealed-one of them has probably occurred among the Mongols, and the other event occurred in the Barghuts. These two events give an average gene conversion rate range of 0.24-7.1 × 10(-3) per generation.}, } @article {pmid26898827, year = {2016}, author = {Gokhman, D and Meshorer, E and Carmel, L}, title = {Epigenetics: It's Getting Old. Past Meets Future in Paleoepigenetics.}, journal = {Trends in ecology & evolution}, volume = {31}, number = {4}, pages = {290-300}, doi = {10.1016/j.tree.2016.01.010}, pmid = {26898827}, issn = {1872-8383}, mesh = {Animals ; DNA/genetics ; DNA Methylation ; *Epigenesis, Genetic ; Hominidae/*genetics ; }, abstract = {Recent years have witnessed the rise of ancient DNA (aDNA) technology, allowing comparative genomics to be carried out at unprecedented time resolution. While it is relatively straightforward to use aDNA to identify recent genomic changes, it is much less clear how to utilize it to study changes in epigenetic regulation. Here we review recent works demonstrating that highly degraded aDNA still contains sufficient information to allow reconstruction of epigenetic signals, including DNA methylation and nucleosome positioning maps. We discuss challenges arising from the tissue specificity of epigenetics, and show how some of them might in fact turn into advantages. Finally, we introduce a method to infer methylation states in tissues that do not tend to be preserved over time.}, } @article {pmid26891221, year = {2016}, author = {Balistreri, G and Viiliäinen, J and Turunen, M and Diaz, R and Lyly, L and Pekkonen, P and Rantala, J and Ojala, K and Sarek, G and Teesalu, M and Denisova, O and Peltonen, K and Julkunen, I and Varjosalo, M and Kainov, D and Kallioniemi, O and Laiho, M and Taipale, J and Hautaniemi, S and Ojala, PM}, title = {Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication.}, journal = {PLoS pathogens}, volume = {12}, number = {2}, pages = {e1005424}, pmid = {26891221}, issn = {1553-7374}, mesh = {Cell Cycle Checkpoints/*genetics ; Cell Line, Tumor ; DNA Replication ; Gene Expression Regulation, Viral/*genetics ; Herpesvirus 8, Human/*genetics ; Humans ; RNA, Small Interfering/genetics ; Sarcoma, Kaposi/metabolism/virology ; Stress, Physiological/*genetics ; Virus Activation/physiology ; Virus Latency/genetics ; *Virus Replication/genetics ; }, abstract = {Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.}, } @article {pmid26888264, year = {2016}, author = {Hsieh, P and Woerner, AE and Wall, JD and Lachance, J and Tishkoff, SA and Gutenkunst, RN and Hammer, MF}, title = {Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies.}, journal = {Genome research}, volume = {26}, number = {3}, pages = {291-300}, pmid = {26888264}, issn = {1549-5469}, support = {8DP1ES022577-04/DP/NCCDPHP CDC HHS/United States ; R01 HG005226/HG/NHGRI NIH HHS/United States ; 1R01GM113657-01/GM/NIGMS NIH HHS/United States ; F32HG006648/HG/NHGRI NIH HHS/United States ; R01 GM113657/GM/NIGMS NIH HHS/United States ; F32 HG006648/HG/NHGRI NIH HHS/United States ; DP1 ES022577/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Black People/*genetics ; *Evolution, Molecular ; Gene Flow ; Gene Frequency ; Genetic Loci ; *Genetics, Population ; *Genome ; *Genome, Human ; *Genomics ; Haplotypes ; Humans ; Linkage Disequilibrium ; Pan paniscus/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {Comparisons of whole-genome sequences from ancient and contemporary samples have pointed to several instances of archaic admixture through interbreeding between the ancestors of modern non-Africans and now extinct hominids such as Neanderthals and Denisovans. One implication of these findings is that some adaptive features in contemporary humans may have entered the population via gene flow with archaic forms in Eurasia. Within Africa, fossil evidence suggests that anatomically modern humans (AMH) and various archaic forms coexisted for much of the last 200,000 yr; however, the absence of ancient DNA in Africa has limited our ability to make a direct comparison between archaic and modern human genomes. Here, we use statistical inference based on high coverage whole-genome data (greater than 60×) from contemporary African Pygmy hunter-gatherers as an alternative means to study the evolutionary history of the genus Homo. Using whole-genome simulations that consider demographic histories that include both isolation and gene flow with neighboring farming populations, our inference method rejects the hypothesis that the ancestors of AMH were genetically isolated in Africa, thus providing the first whole genome-level evidence of African archaic admixture. Our inferences also suggest a complex human evolutionary history in Africa, which involves at least a single admixture event from an unknown archaic population into the ancestors of AMH, likely within the last 30,000 yr.}, } @article {pmid26886800, year = {2016}, author = {Kuhlwilm, M and Gronau, I and Hubisz, MJ and de Filippo, C and Prado-Martinez, J and Kircher, M and Fu, Q and Burbano, HA and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Rudan, P and Brajkovic, D and Kucan, Ž and Gušic, I and Marques-Bonet, T and Andrés, AM and Viola, B and Pääbo, S and Meyer, M and Siepel, A and Castellano, S}, title = {Ancient gene flow from early modern humans into Eastern Neanderthals.}, journal = {Nature}, volume = {530}, number = {7591}, pages = {429-433}, pmid = {26886800}, issn = {1476-4687}, support = {R01 GM102192/GM/NIGMS NIH HHS/United States ; GM102192/GM/NIGMS NIH HHS/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; }, mesh = {Altitude ; Animals ; Bayes Theorem ; Chromosomes, Human, Pair 21/genetics ; Croatia/ethnology ; Gene Flow/*genetics ; Genome, Human/genetics ; Genomics ; Haplotypes/genetics ; Heterozygote ; Humans ; Hybridization, Genetic/genetics ; Neanderthals/*genetics ; Phylogeny ; Population Density ; Siberia ; Spain/ethnology ; Time Factors ; }, abstract = {It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.}, } @article {pmid26885854, year = {2016}, author = {Netea, MG and Joosten, LA}, title = {TLRs of Our Fathers.}, journal = {Immunity}, volume = {44}, number = {2}, pages = {218-220}, doi = {10.1016/j.immuni.2016.02.003}, pmid = {26885854}, issn = {1097-4180}, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Haplotypes ; Humans ; Immunity, Innate/*genetics ; Neanderthals/*genetics/*immunology ; Toll-Like Receptors/*genetics ; }, abstract = {Two new studies published in The American Journal of Human Genetics (Dannemann et al., 2016; Deschamps et al., 2016) show that introgression of innate immune genes from Neandertals and Denisovans contributed to the modern genome of European and Asian, but not African, populations, and this might partly explain differences in susceptibility to immune-mediated diseases.}, } @article {pmid26883865, year = {2016}, author = {Hackinger, S and Kraaijenbrink, T and Xue, Y and Mezzavilla, M and Asan, and van Driem, G and Jobling, MA and de Knijff, P and Tyler-Smith, C and Ayub, Q}, title = {Wide distribution and altitude correlation of an archaic high-altitude-adaptive EPAS1 haplotype in the Himalayas.}, journal = {Human genetics}, volume = {135}, number = {4}, pages = {393-402}, pmid = {26883865}, issn = {1432-1203}, support = {/WT_/Wellcome Trust/United Kingdom ; 087576/WT_/Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Altitude ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; *Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; }, abstract = {High-altitude adaptation in Tibetans is influenced by introgression of a 32.7-kb haplotype from the Denisovans, an extinct branch of archaic humans, lying within the endothelial PAS domain protein 1 (EPAS1), and has also been reported in Sherpa. We genotyped 19 variants in this genomic region in 1507 Eurasian individuals, including 1188 from Bhutan and Nepal residing at altitudes between 86 and 4550 m above sea level. Derived alleles for five SNPs characterizing the core Denisovan haplotype (AGGAA) were present at high frequency not only in Tibetans and Sherpa, but also among many populations from the Himalayas, showing a significant correlation with altitude (Spearman's correlation coefficient = 0.75, p value 3.9 × 10(-11)). Seven East- and South-Asian 1000 Genomes Project individuals shared the Denisovan haplotype extending beyond the 32-kb region, enabling us to refine the haplotype structure and identify a candidate regulatory variant (rs370299814) that might be interacting in an additive manner with the derived G allele of rs150877473, the variant previously associated with high-altitude adaptation in Tibetans. Denisovan-derived alleles were also observed at frequencies of 3-14% in the 1000 Genomes Project African samples. The closest African haplotype is, however, separated from the Asian high-altitude haplotype by 22 mutations whereas only three mutations, including rs150877473, separate the Asians from the Denisovan, consistent with distant shared ancestry for African and Asian haplotypes and Denisovan adaptive introgression.}, } @article {pmid26856178, year = {2015}, author = {Denisov, AP and Semenova, NV and Kun, OA and Denisova, OA}, title = {[COMPREHENSIVE ASSESSMENT OF HEALTH IN BABIES OF EARLY PRESCHOOL AGE].}, journal = {Gigiena i sanitariia}, volume = {94}, number = {8}, pages = {69-72}, pmid = {26856178}, issn = {0016-9900}, mesh = {Adolescent ; Adult ; Child ; *Child Health ; Child, Preschool ; Developmental Disabilities/*epidemiology/etiology ; Female ; *Health Status ; Humans ; Male ; Morbidity/trends ; Siberia/epidemiology ; Socioeconomic Factors ; Young Adult ; }, abstract = {Health of the children's population is one of the most important components of safety of the country. The incidence level in children of early age reflects an interaction of economic, ecological, social and hygienic and medico-organizational factors in society. The issue of the paper is the comprehensive assessment of health of children of the first three years of life upon indices of the morbidity rate, physical development, interrelation of given indices with the structure of the family and their social status. Indices of the physical development of boys in the all age groups exceeded the corresponding indices in girls (p < 0.05). There was also statistically significant and augmentation of indices of body weights of children along with the age (p < 0.05). The highest morbidity rate in children was established in the first year of life, the minimal one--in the third year. In the all age groups diseases of respiratory organs prevailed, at this their proportion in the total amount of diseases in the third year of life considerably exceeded the same in first and second years of life. The highest incidences of children took place in the families formed by juvenile and lonely women. Diseases of digestive organs in the second and third years of life in children from juvenile and lonely mothers were considerably enlarged on frequency (by 1,4-1,7 times), infectious and parasitic diseases (by 1,1-1,7 times) in comparison with children from full families. In the all studied types offamilies and age groups the state of health of children was worse, than in full families. There was substantiated the development of the multilevel system for the prophylaxis of losses of health in children at early preschool age.}, } @article {pmid26845858, year = {2015}, author = {Malyarchuk, BA and Derenko, MV and Denisova, GA}, title = {[Mitochondrial Genome Variability in the Wolverine (Gulo gulo)].}, journal = {Genetika}, volume = {51}, number = {11}, pages = {1291-1296}, pmid = {26845858}, issn = {0016-6758}, mesh = {Animals ; *Evolution, Molecular ; *Genome, Mitochondrial ; Mustelidae/*genetics ; *Phylogeny ; *Polymorphism, Genetic ; }, abstract = {The nucleotide sequence of an extended mitochondrial genome segment (11473 base pairs in size) was determined in the wolverine (Gulo gulo) from Magadan oblast. Phylogenetic and statistical analyses of mitochondrial DNA (mtDNA) sequences of mustelids showed that the separation of the Gulo phylogenetic branch occurred at the Miocene--early Pliocene (about 5.6 million years ago (MYA)), while the formation of the species G. gulo took place in the Middle Pleistocene (181 and 234 thousand years ago (KYA), according to the results of molecular dating based on the variability of the extended mtDNA segment and the mitochondrial cytochrome b gene, respectively). The molecular data were in agreement with the fossil records for wolverines.}, } @article {pmid31265485, year = {2016}, author = {Dannemann, M and Andrés, AM and Kelso, J}, title = {Erratum: Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors.}, journal = {American journal of human genetics}, volume = {98}, number = {2}, pages = {399}, doi = {10.1016/j.ajhg.2016.01.012}, pmid = {31265485}, issn = {1537-6605}, abstract = {[This corrects the article DOI: 10.1016/j.ajhg.2015.11.015.].}, } @article {pmid26791510, year = {2016}, author = {Gorgé, O and Bennett, EA and Massilani, D and Daligault, J and Pruvost, M and Geigl, EM and Grange, T}, title = {Analysis of Ancient DNA in Microbial Ecology.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1399}, number = {}, pages = {289-315}, doi = {10.1007/978-1-4939-3369-3_17}, pmid = {26791510}, issn = {1940-6029}, mesh = {Animals ; DNA, Bacterial/*genetics/isolation & purification ; Fossils ; Genome, Microbial/*genetics ; Genomics/methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Paleontology/*methods ; Soil Microbiology ; }, abstract = {The development of next-generation sequencing has led to a breakthrough in the analysis of ancient genomes, and the subsequent genomic analyses of the skeletal remains of ancient humans have revolutionized the knowledge of the evolution of our species, including the discovery of a new hominin, and demonstrated admixtures with more distantly related archaic populations such as Neandertals and Denisovans. Moreover, it has also yielded novel insights into the evolution of ancient pathogens. The analysis of ancient microbial genomes allows the study of their recent evolution, presently over the last several millennia. These spectacular results have been attained despite the degradation of DNA after the death of the host, which results in very short DNA molecules that become increasingly damaged, only low quantities of which remain. The low quantity of ancient DNA molecules renders their analysis difficult and prone to contamination with modern DNA molecules, in particular via contamination from the reagents used in DNA purification and downstream analysis steps. Finally, the rare ancient molecules are diluted in environmental DNA originating from the soil microorganisms that colonize bones and teeth. Thus, ancient skeletal remains can share DNA profiles with environmental samples and identifying ancient microbial genomes among the more recent, presently poorly characterized, environmental microbiome is particularly challenging. Here, we describe the methods developed and/or in use in our laboratory to produce reliable and reproducible paleogenomic results from ancient skeletal remains that can be used to identify the presence of ancient microbiota.}, } @article {pmid26748514, year = {2016}, author = {Dannemann, M and Andrés, AM and Kelso, J}, title = {Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors.}, journal = {American journal of human genetics}, volume = {98}, number = {1}, pages = {22-33}, pmid = {26748514}, issn = {1537-6605}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Cell Line ; *Haplotypes ; Humans ; Neanderthals/*genetics ; Polymorphism, Single Nucleotide ; Toll-Like Receptors/*genetics ; }, abstract = {Pathogens and the diseases they cause have been among the most important selective forces experienced by humans during their evolutionary history. Although adaptive alleles generally arise by mutation, introgression can also be a valuable source of beneficial alleles. Archaic humans, who lived in Europe and Western Asia for more than 200,000 years, were probably well adapted to this environment and its local pathogens. It is therefore conceivable that modern humans entering Europe and Western Asia who admixed with them obtained a substantial immune advantage from the introgression of archaic alleles. Here we document a cluster of three Toll-like receptors (TLR6-TLR1-TLR10) in modern humans that carries three distinct archaic haplotypes, indicating repeated introgression from archaic humans. Two of these haplotypes are most similar to the Neandertal genome, and the third haplotype is most similar to the Denisovan genome. The Toll-like receptors are key components of innate immunity and provide an important first line of immune defense against bacteria, fungi, and parasites. The unusually high allele frequencies and unexpected levels of population differentiation indicate that there has been local positive selection on multiple haplotypes at this locus. We show that the introgressed alleles have clear functional effects in modern humans; archaic-like alleles underlie differences in the expression of the TLR genes and are associated with increased [corrected] microbial resistance and increased allergic disease in large cohorts. This provides strong evidence for recurrent adaptive introgression at the TLR6-TLR1-TLR10 locus, resulting in differences in disease phenotypes in modern humans.}, } @article {pmid29889396, year = {2016}, author = {Reshetnikov, OV and Kurilovich, SA and Denisova, DV and Krotov, SA}, title = {PREVALENCE AND RISK FACTORS OF GERD IN ADOLESCENTS IN NOVOSIBIRSK: TEN-YEAR TRENDS.}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {9}, pages = {54-57}, pmid = {29889396}, issn = {1682-8658}, mesh = {Adolescent ; Antibodies, Bacterial/blood ; Female ; Gastroesophageal Reflux/blood/*epidemiology ; Helicobacter Infections/blood/*epidemiology ; *Helicobacter pylori ; Humans ; Immunoglobulin G/blood ; Male ; Prevalence ; Risk Factors ; Siberia/epidemiology ; }, abstract = {UNLABELLED: The aim of the study was the study of ten-year trends (1999-2009) of GERD symptoms and risk factors in schoolchildren in Novosibirsk from 14 to 17 years.

MATERIALS AND METHODS: The comparison of the results of the screenings performed at 1999 and 2009 was analyzed. Anthropometry, the survey to identify the symptoms of GERD and eating habits, smoking and alcohol consumption, determination of lgG and CagA antibodies to Helicobacterpylori were included at the program of screenings.

RESULTS: No significant dynamics of GER symptoms in adolescents, except weekly heartburn among boys. Among the factors associated with dyspepsia and GER, there have been some mixed changes: the frequency of smoking significantly reduced, but the proportion adolescents with excess body weight have increased. Violations of the regime and diet, and Helicobocrerpylori-infection has not changed significantly.

CONCLUSION: The frequency of GERD in adolescents remains high but does not reach the prevalence of GERD in adults.}, } @article {pmid29787668, year = {2016}, author = {Bugaeva, LI and Tyurenkov, IN and Denisova, TD and Morozova, YA}, title = {[INFLUENCE OF A NEW SUBSTANCE WITH ANTIDEPRESSANT ACTIVITY ON ORGANO- AND FETOGENESIS PROCESSES REGISTERED DURING ANTHENATAL PERIOD.].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {79}, number = {9}, pages = {25-28}, pmid = {29787668}, issn = {0869-2092}, mesh = {Animals ; Antidepressive Agents/*pharmacology ; Female ; Fetal Development/*drug effects ; Organogenesis/*drug effects ; Pregnancy ; Rats ; }, abstract = {Experiments on pregnant female rats showed that the beta-phenylglutaminic acid hydrochloride derivative neuroglutam (glutaron), exhibiting antidepressant and anxiolytic activity upon intragastric administration in doses of 26, 130 and 650 mg/kg to female rats from 6 to 16 days of pregnancy, does not impair organo- and fetogenesis processes (developments of fetus) registered during the anthenatal period, decreases fetal death, and activates the processes of prenatal development of the fetus bv 11.1% (p < 0.001), 8.3% (p < 0.001), and 2.8% (p < 0.05), respectively.}, } @article {pmid26719974, year = {2015}, author = {Arciero, E and Biagini, SA and Chen, Y and Xue, Y and Luiselli, D and Tyler-Smith, C and Pagani, L and Ayub, Q}, title = {Genes Regulated by Vitamin D in Bone Cells Are Positively Selected in East Asians.}, journal = {PloS one}, volume = {10}, number = {12}, pages = {e0146072}, pmid = {26719974}, issn = {1932-6203}, support = {/WT_/Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Asian People/*genetics ; Bone and Bones/*metabolism ; Core Binding Factor Alpha 1 Subunit/genetics ; DNA-Binding Proteins/genetics ; Gene Frequency/genetics ; Haplotypes/genetics ; Humans ; Low Density Lipoprotein Receptor-Related Protein-5/genetics ; Osteoporosis/genetics ; Polymorphism, Single Nucleotide/genetics ; Selection, Genetic/genetics ; Trans-Activators ; Vitamin D/*genetics ; }, abstract = {Vitamin D and folate are activated and degraded by sunlight, respectively, and the physiological processes they control are likely to have been targets of selection as humans expanded from Africa into Eurasia. We investigated signals of positive selection in gene sets involved in the metabolism, regulation and action of these two vitamins in worldwide populations sequenced by Phase I of the 1000 Genomes Project. Comparing allele frequency-spectrum-based summary statistics between these gene sets and matched control genes, we observed a selection signal specific to East Asians for a gene set associated with vitamin D action in bones. The selection signal was mainly driven by three genes CXXC finger protein 1 (CXXC1), low density lipoprotein receptor-related protein 5 (LRP5) and runt-related transcription factor 2 (RUNX2). Examination of population differentiation and haplotypes allowed us to identify several candidate causal regulatory variants in each gene. Four of these candidate variants (one each in CXXC1 and RUNX2 and two in LRP5) had a >70% derived allele frequency in East Asians, but were present at lower (20-60%) frequency in Europeans as well, suggesting that the adaptation might have been part of a common response to climatic and dietary changes as humans expanded out of Africa, with implications for their role in vitamin D-dependent bone mineralization and osteoporosis insurgence. We also observed haplotype sharing between East Asians, Finns and an extinct archaic human (Denisovan) sample at the CXXC1 locus, which is best explained by incomplete lineage sorting.}, } @article {pmid26696916, year = {2015}, author = {Irurtzun, A}, title = {The "Globularization Hypothesis" of the Language-ready Brain as a Developmental Frame for Prosodic Bootstrapping Theories of Language Acquisition.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {1817}, pmid = {26696916}, issn = {1664-1078}, abstract = {In recent research (Boeckx and Benítez-Burraco, 2014a,b) have advanced the hypothesis that our species-specific language-ready brain should be understood as the outcome of developmental changes that occurred in our species after the split from Neanderthals-Denisovans, which resulted in a more globular braincase configuration in comparison to our closest relatives, who had elongated endocasts. According to these authors, the development of a globular brain is an essential ingredient for the language faculty and in particular, it is the centrality occupied by the thalamus in a globular brain that allows its modulatory or regulatory role, essential for syntactico-semantic computations. Their hypothesis is that the syntactico-semantic capacities arise in humans as a consequence of a process of globularization, which significantly takes place postnatally (cf. Neubauer et al., 2010). In this paper, I show that Boeckx and Benítez-Burraco's hypothesis makes an interesting developmental prediction regarding the path of language acquisition: it teases apart the onset of phonological acquisition and the onset of syntactic acquisition (the latter starting significantly later, after globularization). I argue that this hypothesis provides a developmental rationale for the prosodic bootstrapping hypothesis of language acquisition (cf. i.a. Gleitman and Wanner, 1982; Mehler et al., 1988, et seq.; Gervain and Werker, 2013), which claim that prosodic cues are employed for syntactic parsing. The literature converges in the observation that a large amount of such prosodic cues (in particular, rhythmic cues) are already acquired before the completion of the globularization phase, which paves the way for the premises of the prosodic bootstrapping hypothesis, allowing babies to have a rich knowledge of the prosody of their target language before they can start parsing the primary linguistic data syntactically.}, } @article {pmid26693966, year = {2015}, author = {Gunbin, KV and Afonnikov, DA and Kolchanov, NA and Derevianko, AP and Rogaev, EI}, title = {The evolution of Homo sapiens denisova and Homo sapiens neanderthalensis miRNA targeting genes in the prenatal and postnatal brain.}, journal = {BMC genomics}, volume = {16 Suppl 13}, number = {Suppl 13}, pages = {S4}, pmid = {26693966}, issn = {1471-2164}, mesh = {Animals ; Brain/*embryology/growth & development/metabolism ; *Evolution, Molecular ; *Gene Expression Regulation ; Hominidae/*genetics ; Humans ; Infant, Newborn ; MicroRNAs/*genetics ; Pan troglodytes ; RNA, Messenger/*genetics ; }, abstract = {BACKGROUND: As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.

RESULTS: A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.

CONCLUSIONS: Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.}, } @article {pmid26673402, year = {2015}, author = {Hammill, JA and VanSeggelen, H and Helsen, CW and Denisova, GF and Evelegh, C and Tantalo, DG and Bassett, JD and Bramson, JL}, title = {Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors.}, journal = {Journal for immunotherapy of cancer}, volume = {3}, number = {}, pages = {55}, pmid = {26673402}, issn = {2051-1426}, abstract = {BACKGROUND: Adoptive cell transfer of tumor-specific T lymphocytes (T cells) is proving to be an effective strategy for treating established tumors in cancer patients. One method of generating these cells is accomplished through engineering bulk T cell populations to express chimeric antigen receptors (CARs), which are specific for tumor antigens. Traditionally, these CARs are targeted against tumor antigens using single-chain antibodies (scFv). Here we describe the use of a designed ankyrin repeat protein (DARPin) as the tumor-antigen targeting domain.

METHODS: We prepared second generation anti-HER2 CARs that were targeted to the tumor antigen by either a DARPin or scFv. The CARs were engineered into human and murine T cells. We then compared the ability of CARs to trigger cytokine production, degranulation and cytotoxicity.

RESULTS: The DARPin CARs displayed reduced surface expression relative to scFv CARs in murine cells but both CARs were expressed equally well on human T cells, suggesting that there may be a processing issue with the murine variants. In both the murine and human systems, the DARPin CARs were found to be highly functional, triggering cytokine and cytotoxic responses that were similar to those triggered by the scFv CARs.

CONCLUSIONS: These findings demonstrate the utility of DARPins as CAR-targeting agents and open up an avenue for the generation of CARs with novel antigen binding attributes.}, } @article {pmid26668361, year = {2015}, author = {Stringer, CB and Barnes, I}, title = {Deciphering the Denisovans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {15542-15543}, pmid = {26668361}, issn = {1091-6490}, mesh = {Animals ; Cell Nucleus/*genetics ; DNA, Mitochondrial/*chemistry ; Neanderthals/*genetics ; }, } @article {pmid26664599, year = {2015}, author = {Denisova, YI and Gringolts, ML and Peregudov, AS and Krentsel, LB and Litmanovich, EA and Litmanovich, AD and Finkelshtein, ESh and Kudryavtsev, YV}, title = {Cross-metathesis of polynorbornene with polyoctenamer: a kinetic study.}, journal = {Beilstein journal of organic chemistry}, volume = {11}, number = {}, pages = {1796-1808}, pmid = {26664599}, issn = {1860-5397}, abstract = {The cross-metathesis of polynorbornene and polyoctenamer in d-chloroform mediated by the 1(st) generation Grubbs' catalyst Cl2(PCy3)2Ru=CHPh is studied by monitoring the kinetics of carbene transformation and evolution of the dyad composition of polymer chains with in situ (1)H and ex situ (13)C NMR spectroscopy. The results are interpreted in terms of a simple kinetic two-stage model. At the first stage of the reaction all Ru-benzylidene carbenes are transformed into Ru-polyoctenamers within an hour, while the polymer molar mass is considerably decreased. The second stage actually including interpolymeric reactions proceeds much slower and takes one day or more to achieve a random copolymer of norbornene and cyclooctene. Its rate is limited by the interaction of polyoctenamer-bound carbenes with polynorbornene units, which is hampered, presumably due to steric reasons. Polynorbornene-bound carbenes are detected in very low concentrations throughout the whole process thus indicating their higher reactivity, as compared with the polyoctenamer-bound ones. Macroscopic homogeneity of the reacting media is proved by dynamic light scattering from solutions containing the polymer mixture and its components. In general, the studied process can be considered as a new way to unsaturated multiblock statistical copolymers. Their structure can be controlled by the amount of catalyst, mixture composition, and reaction time. It is remarkable that this goal can be achieved with a catalyst that is not suitable for ring-opening metathesis copolymerization of norbornene and cis-cyclooctene because of their substantially different monomer reactivities.}, } @article {pmid26634840, year = {2016}, author = {Denisova, MN and Makarova, EI and Pavlov, IN and Budaeva, VV and Sakovich, GV}, title = {Enzymatic Hydrolysis of Hydrotropic Pulps at Different Substrate Loadings.}, journal = {Applied biochemistry and biotechnology}, volume = {178}, number = {6}, pages = {1196-1206}, doi = {10.1007/s12010-015-1938-y}, pmid = {26634840}, issn = {1559-0291}, mesh = {Cellulase/*chemistry ; Cellulose/chemistry ; Hydrolysis ; Microscopy, Electron, Scanning ; Substrate Specificity ; }, abstract = {Enzymatic hydrolysis of cellulosic raw materials to produce nutrient broths for microbiological synthesis of ethanol and other valuable products is an important field of modern biotechnology. Biotechnological processing implies the selection of an effective pretreatment technique for raw materials. In this study, the hydrotropic treatment increased the reactivity of the obtained substrates toward enzymatic hydrolysis by 7.1 times for Miscanthus and by 7.3 times for oat hulls. The hydrotropic pulp from oat hulls was more reactive toward enzymatic hydrolysis compared to that from Miscanthus, despite that the substrates had similar compositions. As the initial substrate loadings were raised during enzymatic hydrolysis of the hydrotropic Miscanthus and oat hull pulps, the concentration of reducing sugars increased by 34 g/dm(3) and the yield of reducing sugars decreased by 31 %. The findings allow us to predict the efficiency of enzymatic hydrolysis of hydrotropic pulps from Miscanthus and oat hulls when scaling up the process by volume.}, } @article {pmid26630009, year = {2015}, author = {Sawyer, S and Renaud, G and Viola, B and Hublin, JJ and Gansauge, MT and Shunkov, MV and Derevianko, AP and Prüfer, K and Kelso, J and Pääbo, S}, title = {Nuclear and mitochondrial DNA sequences from two Denisovan individuals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {15696-15700}, pmid = {26630009}, issn = {1091-6490}, mesh = {Animals ; Base Sequence ; Cell Nucleus/*genetics ; DNA, Mitochondrial/*chemistry ; Evolution, Molecular ; Molecular Sequence Data ; Neanderthals/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans.}, } @article {pmid26601491, year = {2015}, author = {Malyarchuk, BA and Derenko, MV and Denisova, GA and Litvinov, AN}, title = {[Topological Conflicts in Phylogenetic Analysis of Different Regions of the Sable (Martes zibellina L.) Mitochondrial Genome].}, journal = {Genetika}, volume = {51}, number = {8}, pages = {915-923}, pmid = {26601491}, issn = {0016-6758}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Genome, Mitochondrial/*genetics ; Haplotypes/genetics ; Mustelidae/*genetics ; Mutation ; *Phylogeny ; RNA, Ribosomal/genetics ; }, abstract = {Phylogenetic analysis of different regions of the mitochondrial genome of the sable showed the presence of several topologies of phylogenetic trees, but the most statistically significant topology is A-BC, which was obtained as a result of the analysis of the mitochondrial genome as a whole, as well as of the individual CO1, ND4, and ND5 genes. Analysis of the intergroup divergence of the mtDNA haplotypes (Dxy) indicated that the maximum Dxy values between A and BC groups were accompanied by minimum differences between B and C groups only for six genes showing the A-BC topology (12S rRNA; CO1, CO2, ND4, ND5, and CYTB). It is assumed that the topological conflicts observed in the analysis of individual sable mtDNA genes are associated with the uneven distribution of mutations along the mitochondrial genome and the mitochondrial tree. This may be due to random causes, as well as the nonuniform effect of selection.}, } @article {pmid26596347, year = {2016}, author = {Racimo, F}, title = {Testing for Ancient Selection Using Cross-population Allele Frequency Differentiation.}, journal = {Genetics}, volume = {202}, number = {2}, pages = {733-750}, pmid = {26596347}, issn = {1943-2631}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; R01-GM40282/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; *Alleles ; Animals ; Asian People/genetics ; Computer Simulation ; Evolution, Molecular ; *Gene Frequency ; *Genetics, Population ; Genome-Wide Association Study ; Genomics/methods ; Humans ; *Models, Genetic ; Neanderthals/genetics ; ROC Curve ; *Selection, Genetic ; White People/genetics ; }, abstract = {A powerful way to detect selection in a population is by modeling local allele frequency changes in a particular region of the genome under scenarios of selection and neutrality and finding which model is most compatible with the data. A previous method based on a cross-population composite likelihood ratio (XP-CLR) uses an outgroup population to detect departures from neutrality that could be compatible with hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent selection and may miss selective events that happened a long time ago. To overcome this, we developed an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. Our method - called "3-population composite likelihood ratio" (3P-CLR) - outperforms XP-CLR when testing for selection that occurred before two populations split from each other and can distinguish between those events and events that occurred specifically in each of the populations after the split. We applied our new test to population genomic data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of Yoruba and Eurasians, but after their split from Neanderthals, and that could have led to the spread of modern-human-specific phenotypes. We also searched for sweep events that occurred in East Asians, Europeans, and the ancestors of both populations, after their split from Yoruba. In both cases, we are able to confirm a number of regions identified by previous methods and find several new candidates for selection in recent and ancient times. For some of these, we also find suggestive functional mutations that may have driven the selective events.}, } @article {pmid26567083, year = {2016}, author = {Vyas, DN and Kitchen, A and Miró-Herrans, AT and Pearson, LN and Al-Meeri, A and Mulligan, CJ}, title = {Bayesian analyses of Yemeni mitochondrial genomes suggest multiple migration events with Africa and Western Eurasia.}, journal = {American journal of physical anthropology}, volume = {159}, number = {3}, pages = {382-393}, doi = {10.1002/ajpa.22890}, pmid = {26567083}, issn = {1096-8644}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Africa ; Anthropology, Physical ; Asia, Western ; Bayes Theorem ; Europe ; Genome, Mitochondrial/*genetics ; Haplotypes ; History, Ancient ; *Human Migration ; Humans ; Phylogeny ; Yemen ; }, abstract = {OBJECTIVES: Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the first successful global dispersal. This initial migration may have passed through Yemen, a region that has experienced multiple migrations events with Africa and Eurasia throughout human history. We use Bayesian phylogenetics to determine how ancient and recent migrations have shaped Yemeni mitogenomic variation.

MATERIALS AND METHODS: We sequenced 113 mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as these groups have the oldest evolutionary history outside of Africa. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenomes in order to determine the age of Yemeni-specific clades.

RESULTS: As defined by Yemeni monophyly, Yemeni in situ evolution is limited to the Holocene or latest Pleistocene (ages of clades in subhaplogroups L3b1a1a, L3h2, L3x1, M1a1f, M1a5, N1a1a3, and N1a3 range from 2 to 14 kya) and is often situated within broader Horn of Africa/southern Arabia in situ evolution (L3h2, L3x1, M1a1f, M1a5, and N1a1a3 ages range from 7 to 29 kya). Five subhaplogroups show no monophyly and are candidates for Holocene migration into Yemen (L0a2a2a, L3d1a1a, L3i2, M1a1b, and N1b1a).

DISCUSSION: Yemeni mitogenomes are largely the product of Holocene migration, and subsequent in situ evolution, from Africa and western Eurasia. However, we hypothesize that recent population movements may obscure the genetic signature of more ancient migrations. Additional research, e.g., analyses of Yemeni nuclear genetic data, is needed to better reconstruct the complex population and migration histories associated with Out of Africa.}, } @article {pmid26525473, year = {2015}, author = {Soldatsky, YL and Denisova, OA and Mazur, EM}, title = {[Local anesthesia in the children undergoing the fibroendoscopic study of the nasal cavity, nasopharynx, and larynx: are topical anesthetics needed?].}, journal = {Vestnik otorinolaringologii}, volume = {80}, number = {5}, pages = {51-55}, doi = {10.17116/otorino201580551-55}, pmid = {26525473}, issn = {0042-4668}, mesh = {Adolescent ; Anesthesia, Local/methods/*standards ; *Anesthetics, Local/administration & dosage/adverse effects/pharmacology ; Child ; Child, Preschool ; Double-Blind Method ; Endoscopy/methods/*standards ; Female ; Humans ; Larynx/drug effects ; Male ; *Nasal Cavity/drug effects ; *Nasopharynx/drug effects ; }, abstract = {This prospective randomized study with double blind control was designed to evaluate the effectiveness of various anesthetic techniques employed prior to fibroendoscopy of the nose, nasopharynx, and larynx of the children. The study included 160 children at the age varying from 3 to 14 (mean 7.4±2.96) years randomly allocated to four statistically comparable groups matched for age and sex. The following preparations were used to treat the children prior to fibroendoscopy: physiological solution (group 1), a 0.05% xylometazoline solution (group 2), a 10% lidocaine solution (group 3), and a mixture of 0.05% xylometazoline and 10% lidocaine solutions (group 4). The evaluation of the tolerance to the pretreatment of the nasal cavity with lidocaine and lidocaine plus xylometazoline (groups 3 and 4) showed that it was significantly (p<0.05) worse than in groups 1 and 2. The subjective tolerance to fibroendoscopy as reported by the patients was on the average similar in the children of all four groups (p>0.05). The doctors found the tolerance of fibroendoscopy to be the worst following pretreatment with the physiological solution (group 1) and the best after pretreatment with a mixture of lidocaine and xylometazoline (group 4) (p=0.03). The children comprising groups 2 and 3 were not significantly different in terms of the tolerance to fibroendoscopy (p>0.05). It is concluded that the pretreatment of the nasal cavity of the children with a 10% lidocaine solution before fibroendoscopy has no advantage over the pretreatment with a 0.05% xylometazoline solution; at the same time, insuflation of lidocaine as an anesthetic induces more pronounced negative emotions compared with the application of 0.05% xylometazoline.}, } @article {pmid26455912, year = {2015}, author = {Bender, F and Gorbati, M and Cadavieco, MC and Denisova, N and Gao, X and Holman, C and Korotkova, T and Ponomarenko, A}, title = {Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {8521}, pmid = {26455912}, issn = {2041-1723}, mesh = {Animals ; GABAergic Neurons/physiology ; Hippocampus/*physiology ; *Locomotion ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; *Optogenetics ; Random Allocation ; Septum of Brain/*physiology ; Spatial Navigation ; *Theta Rhythm ; }, abstract = {Hippocampal theta oscillations support encoding of an animal's position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Combining optogenetic control of hippocampal theta oscillations with electrophysiological recordings in mice, we show that hippocampal theta oscillations regulate locomotion. In particular, we demonstrate that their regularity underlies more stable and slower running speeds during exploration. More regular theta oscillations are accompanied by more regular theta-rhythmic spiking output of pyramidal cells. Theta oscillations are coordinated between the hippocampus and its main subcortical output, the lateral septum (LS). Chemo- or optogenetic inhibition of this pathway reveals its necessity for the hippocampal regulation of running speed. Moreover, theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. These results suggest that changes in hippocampal theta synchronization are translated into rapid adjustment of running speed via the LS.}, } @article {pmid26454764, year = {2016}, author = {Weyer, S and Pääbo, S}, title = {Functional Analyses of Transcription Factor Binding Sites that Differ between Present-Day and Archaic Humans.}, journal = {Molecular biology and evolution}, volume = {33}, number = {2}, pages = {316-322}, pmid = {26454764}, issn = {1537-1719}, mesh = {Alleles ; *Binding Sites ; Cell Line ; *Evolution, Molecular ; *Genetic Variation ; Humans ; Polymorphism, Single Nucleotide ; Transcription Factors/*metabolism ; Transcriptional Activation ; }, abstract = {We analyze 25 previously identified transcription factor binding sites that carry DNA sequence changes that are present in all or nearly all present-day humans, yet occur in the ancestral state in Neandertals and Denisovans, the closest evolutionary relatives of humans. When the ancestral and derived forms of the transcription factor binding sites are tested using reporter constructs in 3 neuronal cell lines, the activity of 12 of the derived versions of transcription factor binding sites differ from the respective ancestral variants. This suggests that the majority of this class of evolutionary differences between modern humans and Neandertals may affect gene expression in at least some tissue or cell type.}, } @article {pmid26451479, year = {2015}, author = {Vattathil, S and Akey, JM}, title = {Small Amounts of Archaic Admixture Provide Big Insights into Human History.}, journal = {Cell}, volume = {163}, number = {2}, pages = {281-284}, doi = {10.1016/j.cell.2015.09.042}, pmid = {26451479}, issn = {1097-4172}, mesh = {Animals ; *Biological Evolution ; Genetics, Medical ; Genome, Human ; Hominidae/genetics ; Humans ; Neanderthals/classification/*genetics ; Selection, Genetic ; }, abstract = {Modern humans overlapped in time and space with other hominins, such as Neanderthals and Denisovans, and limited amounts of hybridization occurred. Here, we review recent work that has identified archaic hominin sequence that survives in modern human genomes and what these genomic excavations reveal about human evolutionary history.}, } @article {pmid26441731, year = {2015}, author = {Theofanopoulou, C}, title = {Brain asymmetry in the white matter making and globularity.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {1355}, pmid = {26441731}, issn = {1664-1078}, abstract = {Recent studies from the field of language genetics and evolutionary anthropology have put forward the hypothesis that the emergence of our species-specific brain is to be understood not in terms of size, but in light of developmental changes that gave rise to a more globular braincase configuration after the split from Neanderthals-Denisovans. On the grounds that (i) white matter myelination is delayed relative to other brain structures and, in humans, is protracted compared with other primates and that (ii) neural connectivity is linked genetically to our brain/skull morphology and language-ready brain, I argue that one significant evolutionary change in Homo sapiens' lineage is the interhemispheric connectivity mediated by the Corpus Callosum. The size, myelination and fiber caliber of the Corpus Callosum present an anterior-to-posterior increase, in a way that inter-hemispheric connectivity is more prominent in the sensory motor areas, whereas "high- order" areas are more intra-hemispherically connected. Building on evidence from language-processing studies that account for this asymmetry ('lateralization') in terms of brain rhythms, I present an evo-devo hypothesis according to which the myelination of the Corpus Callosum, Brain Asymmetry, and Globularity are conjectured to make up the angles of a co-evolutionary triangle that gave rise to our language-ready brain.}, } @article {pmid26416425, year = {2015}, author = {Denisova, E and Heidenreich, B and Nagore, E and Rachakonda, PS and Hosen, I and Akrap, I and Traves, V and García-Casado, Z and López-Guerrero, JA and Requena, C and Sanmartin, O and Serra-Guillén, C and Llombart, B and Guillén, C and Ferrando, J and Gimeno, E and Nordheim, A and Hemminki, K and Kumar, R}, title = {Frequent DPH3 promoter mutations in skin cancers.}, journal = {Oncotarget}, volume = {6}, number = {34}, pages = {35922-35930}, pmid = {26416425}, issn = {1949-2553}, mesh = {Amino Acid Sequence ; Base Sequence ; Carcinoma, Squamous Cell/*genetics/pathology ; Carrier Proteins/*genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; Melanoma/genetics/pathology ; Molecular Sequence Data ; Mutation ; Promoter Regions, Genetic ; Skin Neoplasms/*genetics/pathology ; }, abstract = {Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to -8/-9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined.}, } @article {pmid26415272, year = {2015}, author = {Denisova, EV and Nazarov, VE}, title = {[PRINCIPLES OF POSTOPERATIVE DRUG THERAPY OF COMPLICATED DUODENAL ULCERS].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {4}, pages = {89-93}, pmid = {26415272}, issn = {1682-8658}, mesh = {Adult ; Anti-Bacterial Agents/administration & dosage/therapeutic use ; Duodenal Ulcer/*complications/microbiology/*surgery ; Female ; Gastrointestinal Agents/administration & dosage/therapeutic use ; Gastrointestinal Motility/drug effects ; Helicobacter Infections/drug therapy/microbiology ; Humans ; Male ; Middle Aged ; Postoperative Complications/*drug therapy/etiology/microbiology ; *Precision Medicine ; Treatment Outcome ; Young Adult ; }, abstract = {The article highlights the principles of individualized drug therapy of complicated duodenal ulcers in the postoperative period, based on the removal of the pathophysiological changes that occurred after different types of medical or surgical benefits.}, } @article {pmid26399483, year = {2015}, author = {Rogers, RL}, title = {Chromosomal Rearrangements as Barriers to Genetic Homogenization between Archaic and Modern Humans.}, journal = {Molecular biology and evolution}, volume = {32}, number = {12}, pages = {3064-3078}, pmid = {26399483}, issn = {1537-1719}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; R01-GM40282/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; DNA Transposable Elements ; Evolution, Molecular ; Female ; Fossils ; Gene Flow/genetics ; *Gene Rearrangement ; Genetic Variation ; *Genome, Human ; Hominidae/*genetics ; Humans ; Male ; Neanderthals/*genetics ; Phylogeny ; Polymorphism, Genetic ; Recombination, Genetic/genetics ; Sequence Analysis, DNA ; Y Chromosome ; }, abstract = {Chromosomal rearrangements, which shuffle DNA throughout the genome, are an important source of divergence across taxa. Using a paired-end read approach with Illumina sequence data for archaic humans, I identify changes in genome structure that occurred recently in human evolution. Hundreds of rearrangements indicate genomic trafficking between the sex chromosomes and autosomes, raising the possibility of sex-specific changes. Additionally, genes adjacent to genome structure changes in Neanderthals are associated with testis-specific expression, consistent with evolutionary theory that new genes commonly form with expression in the testes. I identify one case of new-gene creation through transposition from the Y chromosome to chromosome 10 that combines the 5'-end of the testis-specific gene Fank1 with previously untranscribed sequence. This new transcript experienced copy number expansion in archaic genomes, indicating rapid genomic change. Among rearrangements identified in Neanderthals, 13% are transposition of selfish genetic elements, whereas 32% appear to be ectopic exchange between repeats. In Denisovan, the pattern is similar but numbers are significantly higher with 18% of rearrangements reflecting transposition and 40% ectopic exchange between distantly related repeats. There is an excess of divergent rearrangements relative to polymorphism in Denisovan, which might result from nonuniform rates of mutation, possibly reflecting a burst of transposable element activity in the lineage that led to Denisovan. Finally, loci containing genome structure changes show diminished rates of introgression from Neanderthals into modern humans, consistent with the hypothesis that rearrangements serve as barriers to gene flow during hybridization. Together, these results suggest that this previously unidentified source of genomic variation has important biological consequences in human evolution.}, } @article {pmid26387173, year = {2015}, author = {Denisova, OA and Livzan, MA}, title = {[THE POSSIBILITY OF USING ALGINATE TEST IN THE DIAGNOSIS GASTROESOPHAGEAL REFLUX DISEASE].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {5}, pages = {67-70}, pmid = {26387173}, issn = {1682-8658}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; *Alginates ; Endoscopy, Digestive System/*methods ; Female ; Gastroesophageal Reflux/*diagnosis/metabolism ; Glucuronic Acid ; Hexuronic Acids ; Humans ; Hydrogen-Ion Concentration ; Male ; Middle Aged ; }, abstract = {UNLABELLED: Currently, gastroesophageal reflux disease (GERD) in the elderly has become an issue of gastroenterology. To date, however, no reference criteria endoscopically negative forms of GERD, therefore, the most significant factor in diagnosis is the detection of gastroesophageal reflux.

PURPOSE: To estimate the information content of alginate test in the diagnosis of GERD in the age aspect.

MATERIALS AND METHODS: Core group--those aged 60-86 years, the comparative group 25-59 years. Two subgroups: the results of alginate test with a positive result and a negative result. Calculated the body mass index, endoscopic examination was performed daily pH--metry.

RESULTS: There is direct correlation between the test result and clinical and instrumental signs of GERD. Alginate test can be used as a screening method for the early diagnosis in patients with GERD different age groups.}, } @article {pmid26383930, year = {2015}, author = {Gibbons, A}, title = {HUMAN EVOLUTION. Cave was lasting home to Denisovans.}, journal = {Science (New York, N.Y.)}, volume = {349}, number = {6254}, pages = {1270-1271}, doi = {10.1126/science.349.6254.1270-b}, pmid = {26383930}, issn = {1095-9203}, mesh = {Animals ; Bone and Bones ; *Caves ; Child ; DNA/*genetics ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Female ; Fossils ; Genome, Human/*genetics ; Humans ; Sequence Analysis, DNA ; Siberia ; }, } @article {pmid26325393, year = {2016}, author = {Denisova, K and Feldman, J and Su, X and Singh, M}, title = {Investigating shape representation using sensitivity to part- and axis-based transformations.}, journal = {Vision research}, volume = {126}, number = {}, pages = {347-361}, pmid = {26325393}, issn = {1878-5646}, support = {R01 EY021494/EY/NEI NIH HHS/United States ; }, mesh = {*Discrimination, Psychological ; *Form Perception ; Humans ; Judgment ; Photic Stimulation/methods ; Psychometrics ; Rotation ; Sensory Thresholds ; *Visual Perception ; }, abstract = {Part- and axis-based approaches organize shape representations in terms of simple parts and their spatial relationships. Shape transformations that alter qualitative part structure have been shown to be more detectable than those that preserve it. We compared sensitivity to various transformations that change quantitative properties of parts and their spatial relationships, while preserving qualitative part structure. Shape transformations involving changes in length, width, curvature, orientation and location were applied to a small part attached to a larger base of a two-part shape. Increment thresholds were estimated for each transformation using a 2IFC procedure. Thresholds were converted into common units of shape difference to enable comparisons across transformations. Higher sensitivity was consistently found for transformations involving a parameter of a single part (length, width, curvature) than those involving spatial relations between two parts (relative orientation and location), suggesting a single-part superiority effect. Moreover, sensitivity to shifts in part location - a biomechanically implausible shape transformation - was consistently poorest. The influence of region-based geometry was investigated via stereoscopic manipulation of figure and ground. Sensitivity was compared across positive parts (protrusions) and negative parts (indentations) for transformations involving a change in orientation or location. For changes in part orientation (biomechanically plausible), sensitivity was better for positive than negative parts; whereas for changes in part location (biomechanically implausible), no systematic difference was observed.}, } @article {pmid26294746, year = {2015}, author = {Huerta-Sánchez, E and Casey, FP}, title = {Archaic inheritance: supporting high-altitude life in Tibet.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {119}, number = {10}, pages = {1129-1134}, doi = {10.1152/japplphysiol.00322.2015}, pmid = {26294746}, issn = {1522-1601}, mesh = {Adaptation, Physiological/*genetics ; *Altitude ; Animals ; Asian People/*genetics ; Demography/methods ; Genetic Association Studies/methods ; Humans ; Neanderthals/*genetics ; Tibet ; }, abstract = {The Tibetan Plateau, often called the roof of the world, sits at an average altitude exceeding 4,500 m. Because of its extreme altitude, the Plateau is one of the harshest human-inhabited environments in the world. This, however, did not impede human colonization, and the Tibetan people have made the Tibetan Plateau their home for many generations. Many studies have quantified their markedly different physiological response to altitude and proposed that Tibetans were genetically adapted. Recently, advances in sequencing technologies led to the discovery of a set of candidate genes which harbor mutations that are likely beneficial at high altitudes in Tibetans. Since then, other studies have further characterized this impressive adaptation. Here, in this minireview, we discuss the progress made since the discovery of the genes involved in Tibetans' adaptation to high altitude with a particular emphasis on describing the series of studies that led us to conclude that archaic human DNA likely contributed to this impressive adaptation.}, } @article {pmid26281203, year = {2015}, author = {Rekhtina, IG and Zakharova, EV and Stolyarevich, ES and Sinitsina, MN and Denisova, EN}, title = {[The concurrence of light-chain deposition disease, AL-amyloidosis, and cast nephropathy in a patient with multiple myeloma].}, journal = {Terapevticheskii arkhiv}, volume = {87}, number = {6}, pages = {98-101}, doi = {10.17116/terarkh201587698-101}, pmid = {26281203}, issn = {0040-3660}, mesh = {Amyloidosis/*complications/diagnosis ; Fatal Outcome ; Humans ; Immunoglobulin Light Chains/*metabolism ; Immunoglobulin Light-chain Amyloidosis ; Kidney Diseases/*complications/diagnosis ; Male ; Middle Aged ; Multiple Myeloma/*complications/diagnosis ; Paraproteinemias/*complications/diagnosis/metabolism ; }, abstract = {Despite of the fact that their clinical manifestations are similar, AL-amyloidosis (AL-A) and light chain deposition disease (LCDD) are individual nosological entities in view of considerable differences in their pathogenesis and pathomorphology. The paper describes a rare case of the concurrence of LCDD and AL-A in a patient with multiple myeloma. Clinically, there was dialysis-dependent renal failure, flail leg syndrome, myocardiopathy, and rhabdomyolysis. At the disease onset, his nephrobiopsy specimen could diagnose LCDD and myeloma or cast nephropathy. The disease was characterized by an aggressive course. Despite the administration of innovative agents, the patient had a short-term remission and died from disease progression. Autopsy additionally revealed amyloid deposition in the heart and kidney. The development of AL-A in the presence of prior LCDD may reflect the progression of the tumor and the appearance of an additional subclone of plasma cells that produce amyloidogenic light chains. The uncommonness of this case is that renal amyloid was found in the tubular casts and absent in the glomeruli, which may be considered as a special form--tubular AL-amyloidosis.}, } @article {pmid26249230, year = {2015}, author = {Sudmant, PH and Mallick, S and Nelson, BJ and Hormozdiari, F and Krumm, N and Huddleston, J and Coe, BP and Baker, C and Nordenfelt, S and Bamshad, M and Jorde, LB and Posukh, OL and Sahakyan, H and Watkins, WS and Yepiskoposyan, L and Abdullah, MS and Bravi, CM and Capelli, C and Hervig, T and Wee, JT and Tyler-Smith, C and van Driem, G and Romero, IG and Jha, AR and Karachanak-Yankova, S and Toncheva, D and Comas, D and Henn, B and Kivisild, T and Ruiz-Linares, A and Sajantila, A and Metspalu, E and Parik, J and Villems, R and Starikovskaya, EB and Ayodo, G and Beall, CM and Di Rienzo, A and Hammer, MF and Khusainova, R and Khusnutdinova, E and Klitz, W and Winkler, C and Labuda, D and Metspalu, M and Tishkoff, SA and Dryomov, S and Sukernik, R and Patterson, N and Reich, D and Eichler, EE}, title = {Global diversity, population stratification, and selection of human copy-number variation.}, journal = {Science (New York, N.Y.)}, volume = {349}, number = {6253}, pages = {aab3761}, pmid = {26249230}, issn = {1095-9203}, support = {5DP1ES022577 05/DP/NCCDPHP CDC HHS/United States ; 261213/ERC_/European Research Council/International ; 1R01DK104339-01/DK/NIDDK NIH HHS/United States ; R01 DK104339/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 HL119577/HL/NHLBI NIH HHS/United States ; 1R01GM113657-01/GM/NIGMS NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; 098051//Wellcome Trust/United Kingdom ; /ImNIH/Intramural NIH HHS/United States ; R01 GM113657/GM/NIGMS NIH HHS/United States ; T32 GM007266/GM/NIGMS NIH HHS/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; DP1 ES022577/ES/NIEHS NIH HHS/United States ; HHSN26120080001E//PHS HHS/International ; 2R01HG002385/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Black People/classification/genetics ; *DNA Copy Number Variations ; *Evolution, Molecular ; *Gene Duplication ; Genome, Human/*genetics ; Hominidae/genetics ; Humans ; Native Hawaiian or Other Pacific Islander/classification/genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Population/*genetics ; Selection, Genetic ; *Sequence Deletion ; }, abstract = {In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide-variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.}, } @article {pmid26206078, year = {2015}, author = {Kutzner, A and Pramanik, S and Kim, PS and Heese, K}, title = {All-or-(N)One - an epistemological characterization of the human tumorigenic neuronal paralogous FAM72 gene loci.}, journal = {Genomics}, volume = {106}, number = {5}, pages = {278-285}, doi = {10.1016/j.ygeno.2015.07.003}, pmid = {26206078}, issn = {1089-8646}, mesh = {Animals ; Carrier Proteins/*genetics ; Chromosomes, Human, Pair 1 ; Computer Simulation ; Genes ; Genetic Loci ; Genomics ; Hominidae/genetics ; Humans ; Membrane Proteins ; Neanderthals/genetics ; Neoplasm Proteins/*genetics ; Phylogeny ; Proteins ; Segmental Duplications, Genomic ; }, abstract = {FAM72 is a novel neuronal progenitor cell (NPC) self-renewal supporting protein expressed under physiological conditions at low levels in other tissues. Accumulating data indicate the potential pivotal tumourigenic effects of FAM72. Our in silico human genome-wide analysis (GWA) revealed that the FAM72 gene family consists of four human-specific paralogous members, all of which are located on chromosome (chr) 1. Unique asymmetric FAM72 segmental gene duplications are most likely to have occurred in conjunction with the paired genomic neighbour SRGAP2 (SLIT-ROBO Rho GTPase activating protein), as both genes have four paralogues in humans but only one vertebra-emerging orthologue in all other species. No species with two or three FAM72/SRGAP2 gene pairs could be identified, and the four exclusively human-defining ohnologues, with different mutation patterns in Homo neanderthalensis and Denisova hominin, may remain under epigenetic control through long non-coding (lnc) RNAs.}, } @article {pmid26202576, year = {2015}, author = {Nakaoka, H and Inoue, I}, title = {Distribution of HLA haplotypes across Japanese Archipelago: similarity, difference and admixture.}, journal = {Journal of human genetics}, volume = {60}, number = {11}, pages = {683-690}, pmid = {26202576}, issn = {1435-232X}, mesh = {Animals ; Asian People/*genetics ; Evolution, Molecular ; Gene Frequency ; Genetics, Population ; HLA Antigens/*genetics ; Haplotypes ; History, Ancient ; Hominidae/genetics/immunology ; Human Migration/history ; Humans ; Japan ; Linkage Disequilibrium ; Models, Genetic ; Neanderthals/genetics/immunology ; }, abstract = {The human leukocyte antigen (HLA) region is the most polymorphic region in the human genome. The polymorphic nature of the HLA region is thought to have been shaped from balancing selection. The complex migration events during the Out-of-Africa expansion have influenced geographic patterns of HLA allele frequencies and diversities across present-day human populations. Differences in the HLA allele frequency may contribute geographic differences in the susceptibility to many diseases, such as infectious, autoimmune and metabolic diseases. Here we briefly reviewed characteristics of frequency distribution of HLA alleles and haplotypes in Japanese population. A large part of HLA alleles and haplotypes that are common in Japanese are shared with neighboring Asian populations. The differentiations in HLA alleles and haplotypes across Japanese regional populations may provide clues to model for peopling of Japanese Archipelago and for design of genetic association studies. Finally, we introduce recent topics that new HLA alleles derived from ancient admixtures with Neanderthals and Denisovans are thought to have played an important role in the adaptation of modern humans to local pathogens during Out-of-Africa expansion.}, } @article {pmid26176239, year = {2015}, author = {Blank, M and Blank, O and Myasnikova, E and Denisova, D}, title = {Peculiarities of Anxiety Score Distribution in Adult Cancer Patients.}, journal = {Journal of psychosocial oncology}, volume = {33}, number = {5}, pages = {551-560}, doi = {10.1080/07347332.2015.1067280}, pmid = {26176239}, issn = {1540-7586}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Anxiety/*psychology ; Case-Control Studies ; Female ; Humans ; Male ; Neoplasms/drug therapy/*psychology ; Pregnancy ; Psychiatric Status Rating Scales ; Remission Induction ; }, abstract = {The goal of the present research is to investigate and analyze possible peculiarities of the psychological state of cancer patients undergoing treatment. Scores characterizing the trait and state anxiety were acquired using the Integrative Anxiety Test from four groups: adults with no appreciable disease, pregnant women, cancer patients examined during the specific antitumor treatment, and cancer patients brought into lasting clinical remission. Statistical analysis of the testing results revealed the bimodal type of the distribution of scores. The only statistically significant exception was the distribution of the state anxiety scores in cancer patients undergoing treatment that was clearly unimodal.}, } @article {pmid26156123, year = {2015}, author = {Fish, I and Boissinot, S}, title = {Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates.}, journal = {Immunogenetics}, volume = {67}, number = {9}, pages = {487-499}, pmid = {26156123}, issn = {1432-1211}, support = {P51 OD011133/OD/NIH HHS/United States ; P51 RR013986/RR/NCRR NIH HHS/United States ; }, mesh = {2',5'-Oligoadenylate Synthetase/*genetics ; Amino Acid Sequence ; Animals ; Base Sequence ; Disease Resistance/*genetics ; Evolution, Molecular ; Haplotypes/*genetics ; Macaca fascicularis/genetics/immunology ; Macaca mulatta/genetics/immunology ; Papio anubis/genetics/immunology ; Papio papio/genetics/immunology ; Polymorphism, Genetic/*genetics ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under long-term balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNA-binding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism.}, } @article {pmid26136701, year = {2015}, author = {Benítez-Burraco, A and Boeckx, C}, title = {Possible functional links among brain- and skull-related genes selected in modern humans.}, journal = {Frontiers in psychology}, volume = {6}, number = {}, pages = {794}, pmid = {26136701}, issn = {1664-1078}, abstract = {The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language.}, } @article {pmid26122933, year = {2015}, author = {VanSeggelen, H and Hammill, JA and Dvorkin-Gheva, A and Tantalo, DG and Kwiecien, JM and Denisova, GF and Rabinovich, B and Wan, Y and Bramson, JL}, title = {T Cells Engineered With Chimeric Antigen Receptors Targeting NKG2D Ligands Display Lethal Toxicity in Mice.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {23}, number = {10}, pages = {1600-1610}, pmid = {26122933}, issn = {1525-0024}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adoptive Transfer ; Animals ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cyclophosphamide/pharmacology ; Cytokines/metabolism ; *Cytotoxicity, Immunologic ; Disease Models, Animal ; Female ; Gene Expression ; Genetic Vectors/genetics ; Immunotherapy, Adoptive ; Ligands ; Mice ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Neoplasms/genetics/immunology/pathology/therapy ; Pneumonia/immunology/metabolism/pathology ; Receptors, Antigen, T-Cell/genetics/metabolism ; Receptors, Immunologic/genetics/metabolism ; *Recombinant Fusion Proteins ; Retroviridae/genetics ; T-Lymphocytes/immunology/metabolism ; Transplantation Conditioning ; }, abstract = {Ligands for the NKG2D receptor are overexpressed on tumors, making them interesting immunotherapy targets. To assess the tumoricidal properties of T cells directed to attack NKG2D ligands, we engineered murine T cells with two distinct NKG2D-based chimeric antigen receptors (CARs): (i) a fusion between the NKG2D receptor and the CD3ζ chain and (ii) a conventional second-generation CAR, where the extracellular domain of NKG2D was fused to CD28 and CD3ζ. To enhance the CAR surface expression, we also engineered T cells to coexpress DAP10. In vitro functionality and surface expression levels of all three CARs was greater in BALB/c T cells than C57BL/6 T cells, indicating strain-specific differences. Upon adoptive transfer of NKG2D-CAR-T cells into syngeneic animals, we observed significant clinical toxicity resulting in morbidity and mortality. The severity of these toxicities varied between the CAR configurations and paralleled their in vitro NKG2D surface expression. BALB/c mice were more sensitive to these toxicities than C57BL/6 mice, consistent with the higher in vitro functionality of BALB/c T cells. Treatment with cyclophosphamide prior to adoptive transfer exacerbated the toxicity. We conclude that while NKG2D ligands may be useful targets for immunotherapy, the pursuit of NKG2D-based CAR-T cell therapies should be undertaken with caution.}, } @article {pmid26104010, year = {2015}, author = {Qin, P and Stoneking, M}, title = {Denisovan Ancestry in East Eurasian and Native American Populations.}, journal = {Molecular biology and evolution}, volume = {32}, number = {10}, pages = {2665-2674}, doi = {10.1093/molbev/msv141}, pmid = {26104010}, issn = {1537-1719}, mesh = {Animals ; Consanguinity ; Gene Flow ; *Genealogy and Heraldry ; Geography ; Hominidae/genetics ; Humans ; Indians, North American/*genetics ; Models, Genetic ; Native Hawaiian or Other Pacific Islander/genetics ; Siberia ; }, abstract = {Although initial studies suggested that Denisovan ancestry was found only in modern human populations from island Southeast Asia and Oceania, more recent studies have suggested that Denisovan ancestry may be more widespread. However, the geographic extent of Denisovan ancestry has not been determined, and moreover the relationship between the Denisovan ancestry in Oceania and that elsewhere has not been studied. Here we analyze genome-wide single nucleotide polymorphism data from 2,493 individuals from 221 worldwide populations, and show that there is a widespread signal of a very low level of Denisovan ancestry across Eastern Eurasian and Native American (EE/NA) populations. We also verify a higher level of Denisovan ancestry in Oceania than that in EE/NA; the Denisovan ancestry in Oceania is correlated with the amount of New Guinea ancestry, but not the amount of Australian ancestry, indicating that recent gene flow from New Guinea likely accounts for signals of Denisovan ancestry across Oceania. However, Denisovan ancestry in EE/NA populations is equally correlated with their New Guinea or their Australian ancestry, suggesting a common source for the Denisovan ancestry in EE/NA and Oceanian populations. Our results suggest that Denisovan ancestry in EE/NA is derived either from common ancestry with, or gene flow from, the common ancestor of New Guineans and Australians, indicating a more complex history involving East Eurasians and Oceanians than previously suspected.}, } @article {pmid26081318, year = {2015}, author = {Katamanova, EV and Rukavishnikov, VS and Lakhman, OL and Shevchenko, OI and Denisova, IA}, title = {[Cognitive impairment in a toxic lesion of the brain].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {115}, number = {2}, pages = {11-15}, doi = {10.17116/jnevro20151152111-15}, pmid = {26081318}, issn = {1997-7298}, mesh = {Alcoholism/*complications/physiopathology ; Brain/*pathology ; Brain Diseases/*complications/diagnosis/physiopathology ; Cognition/*physiology ; Cognition Disorders/diagnosis/*etiology/physiopathology ; Electroencephalography ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Memory/*physiology ; Mercury Poisoning, Nervous System/*complications/physiopathology ; Middle Aged ; Neuropsychological Tests ; Severity of Illness Index ; Time Factors ; }, abstract = {OBJECTIVE: To identify features of cognitive impairment in patients with toxic (mercury or alcohol) encephalopathy.

MATERIAL AND METHODS: The study involved 36 patients with chronic mercury intoxication and 30 people with chronic alcoholism. A control group included 30 age-matched healthy men who were not exposed to toxic substances and alcohol abuse. All patients underwent neuropsychological examination, which involved a set of neuropsychological Luria rated memory status, praxis, gnosis and speeches. MMSE and FAB were used for the diagnosis of moderate cognitive impairment. Computer electroencephalography and cognitive evoked potentials method were used as well.

RESULTS AND CONCLUSION: The diffuse brain injury in toxic encephalopathy (alcohol and mercury) on EEG, and according to the results of neuropsychological testing was identified. Changes in analytical and synthetic thinking, audio-verbal, long-term, visual memory, reciprocal coordination, finger gnosis, impressive speech were observed in mercury encephalopathy. Functional failure of the frontal lobe and the premotor area of the left hemisphere were revealed in alcoholic encephalopathy.}, } @article {pmid26080582, year = {2015}, author = {Zavgorodnyaya, NG and Denisova, OO}, title = {[Surgical treatment for optic neuropathy in high myopia].}, journal = {Vestnik oftalmologii}, volume = {131}, number = {2}, pages = {45-49}, doi = {10.17116/oftalma2015131245-49}, pmid = {26080582}, issn = {0042-465X}, mesh = {Adult ; Collagen/therapeutic use ; Diagnostic Techniques, Ophthalmological ; Female ; Follow-Up Studies ; Humans ; Male ; *Myopia/complications/diagnosis ; *Optic Nerve Diseases/diagnosis/etiology/surgery ; Prostheses and Implants ; *Scleroplasty/instrumentation/methods ; Treatment Outcome ; }, abstract = {AIM: To improve the effectiveness of surgical treatment for optic neuropathy in high-degree myopia.

MATERIAL AND METHODS: A total of 54 patients (96 eyes) aged 18-30 with high myopia and signs of optic neuropathy were observed. The main group consisted of 20 patients (28 eyes) who underwent meridional scleral reinforcement with type I collagen-based implant placed over the posterior segment. The control group included 34 patients (68 eyes) who were given a 10-day vitamin and vascular therapy course. In most of the controls (21 patient, 21 eyes) indirect revascularization with ligation of the superficial temporal artery was performed. Ophthalmological examination was done before the beginning of the treatment and then at 1, 6, and 12 months. Results. At the end of the follow-up period best corrected visual acuity in the main group was 19.2% higher, on average, than baseline values, but remained unchanged in the controls. Light sensitivity of the retina in both group increased by 7% and 2% respectively. Electrically evoked phosphene thresholds decreased by 22.5% and 10.4% respectively. The main group also demonstrated a near-constant mean peripapillary nerve fiber layer (RNFL) thickness and a 16.4% higher than baseline blood flow velocity in the ophthalmic artery. In the control group the latter parameter showed no change.

CONCLUSIONS: Scleral reinforcement surgery in patients with high myopia complicated by optic neuropathy enables improvement of visual functions and regional blood flow as well as stabilization of RNFL thickness and volume, thus, preventing subsequent development of optic nerve atrophy.}, } @article {pmid26073780, year = {2015}, author = {Lou, H and Lu, Y and Lu, D and Fu, R and Wang, X and Feng, Q and Wu, S and Yang, Y and Li, S and Kang, L and Guan, Y and Hoh, BP and Chung, YJ and Jin, L and Su, B and Xu, S}, title = {A 3.4-kb Copy-Number Deletion near EPAS1 Is Significantly Enriched in High-Altitude Tibetans but Absent from the Denisovan Sequence.}, journal = {American journal of human genetics}, volume = {97}, number = {1}, pages = {54-66}, pmid = {26073780}, issn = {1537-6605}, mesh = {Adaptation, Biological/*genetics ; Algorithms ; *Altitude ; Animals ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; DNA Copy Number Variations/*genetics ; Ethnicity/*genetics ; *Evolution, Molecular ; Genetics, Population ; Hemoglobins/genetics/metabolism ; Hominidae/*genetics ; Humans ; Linkage Disequilibrium ; Microarray Analysis/methods ; Molecular Sequence Data ; Polymerase Chain Reaction/methods ; Sequence Analysis, DNA ; Tibet ; }, abstract = {Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a method developed in this study, we detected in microarray data a Tibetan-enriched deletion (TED) carried by 90% of Tibetans; 50% were homozygous for the deletion, whereas only 3% carried the TED and 0% carried the homozygous deletion in 2,792 worldwide samples (p < 10(-15)). We employed long PCR and Sanger sequencing technologies to determine the exact copy number and breakpoints of the TED in 70 additional Tibetan and 182 diverse samples. The TED had identical boundaries (chr2: 46,694,276-46,697,683; hg19) and was 80 kb downstream of EPAS1. Notably, the TED was in strong linkage disequilibrium (LD; r(2) = 0.8) with EPAS1 variants associated with reduced blood concentrations of hemoglobin. It was also in complete LD with the 5-SNP motif, which was suspected to be introgressed from Denisovans, but the deletion itself was absent from the Denisovan sequence. Correspondingly, we detected that footprints of positive selection for the TED occurred 12,803 (95% confidence interval = 12,075-14,725) years ago. We further whole-genome deep sequenced (>60×) seven Tibetans and verified the TED but failed to identify any other copy-number variations with comparable patterns, giving this TED top priority for further study. We speculate that the specific patterns of the TED resulted from its own functionality in HAA of Tibetans or LD with a functional variant of EPAS1.}, } @article {pmid26072518, year = {2015}, author = {Hoover, KC and Gokcumen, O and Qureshy, Z and Bruguera, E and Savangsuksa, A and Cobb, M and Matsunami, H}, title = {Global Survey of Variation in a Human Olfactory Receptor Gene Reveals Signatures of Non-Neutral Evolution.}, journal = {Chemical senses}, volume = {40}, number = {7}, pages = {481-488}, pmid = {26072518}, issn = {1464-3553}, support = {DC005782/DC/NIDCD NIH HHS/United States ; }, mesh = {Alleles ; Base Sequence ; DNA/genetics ; *Evolution, Molecular ; Genetic Variation/*genetics ; Humans ; Polymorphism, Single Nucleotide/genetics ; Receptors, Odorant/*genetics ; }, abstract = {Allelic variation at 4 loci in the human olfactory receptor gene OR7D4 is associated with perceptual variation in the sex steroid-derived odorants, androstenone, and androstadienone. Androstadienone has been linked with chemosensory identification whereas androstenone makes pork from uncastrated pigs distasteful ("boar taint"). In a sample of 2224 individuals from 43 populations, we identified 45 OR7D4 single nucleotide polymorphisms. Coalescent modeling of frequency-site-spectrum-based statistics identified significant deviation from neutrality in human OR7D4; individual populations with statistically significant deviations from neutrality include Gujarati, Beijing Han, Great Britain, Iberia, and Puerto Rico. Analysis of molecular variation values indicated statistically significant population differentiation driven mainly by the 4 alleles associated with androstenone perception variation; however, fixation values were low suggesting that genetic structure may not have played a strong role in creating these group divisions. We also studied OR7D4 in the genomes of extinct members of the human lineage: Altai Neandertal and Denisovan. No variants were identified in Altai but 2 were in Denisova, one of which is shared by modern humans and one of which is novel. A functional test of modern human and a synthesized mutant Denisova OR7D4 indicated no statistically significant difference in responses to androstenone between the 2 species. Our results suggest non-neutral evolution for an olfactory receptor gene.}, } @article {pmid26017008, year = {2015}, author = {Fontes, JD and Ramsey, J and Polk, JM and Koop, A and Denisova, JV and Belousov, AB}, title = {Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0125395}, pmid = {26017008}, issn = {1932-6203}, support = {P20 GM104936/GM/NIGMS NIH HHS/United States ; R21 NS076925/NS/NINDS NIH HHS/United States ; P30 AG035982/AG/NIA NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; UL1 TR000001/TR/NCATS NIH HHS/United States ; R21NS076925/NS/NINDS NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Cell Death/genetics/physiology ; Cell Survival/genetics/physiology ; Cells, Cultured ; Connexins/genetics/metabolism ; Gap Junctions/*metabolism ; Genetic Vectors/genetics ; HeLa Cells ; Humans ; Lentivirus/genetics ; Mice ; Mice, Knockout ; Receptors, N-Methyl-D-Aspartate/genetics/metabolism ; }, abstract = {Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed.}, } @article {pmid26000734, year = {2015}, author = {Kari, L and Hill, KA and Sayem, AS and Karamichalis, R and Bryans, N and Davis, K and Dattani, NS}, title = {Mapping the space of genomic signatures.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0119815}, pmid = {26000734}, issn = {1932-6203}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; *Models, Theoretical ; }, abstract = {We propose a computational method to measure and visualize interrelationships among any number of DNA sequences allowing, for example, the examination of hundreds or thousands of complete mitochondrial genomes. An "image distance" is computed for each pair of graphical representations of DNA sequences, and the distances are visualized as a Molecular Distance Map: Each point on the map represents a DNA sequence, and the spatial proximity between any two points reflects the degree of structural similarity between the corresponding sequences. The graphical representation of DNA sequences utilized, Chaos Game Representation (CGR), is genome- and species-specific and can thus act as a genomic signature. Consequently, Molecular Distance Maps could inform species identification, taxonomic classifications and, to a certain extent, evolutionary history. The image distance employed, Structural Dissimilarity Index (DSSIM), implicitly compares the occurrences of oligomers of length up to k (herein k = 9) in DNA sequences. We computed DSSIM distances for more than 5 million pairs of complete mitochondrial genomes, and used Multi-Dimensional Scaling (MDS) to obtain Molecular Distance Maps that visually display the sequence relatedness in various subsets, at different taxonomic levels. This general-purpose method does not require DNA sequence alignment and can thus be used to compare similar or vastly different DNA sequences, genomic or computer-generated, of the same or different lengths. We illustrate potential uses of this approach by applying it to several taxonomic subsets: phylum Vertebrata, (super)kingdom Protista, classes Amphibia-Insecta-Mammalia, class Amphibia, and order Primates. This analysis of an extensive dataset confirms that the oligomer composition of full mtDNA sequences can be a source of taxonomic information. This method also correctly finds the mtDNA sequences most closely related to that of the anatomically modern human (the Neanderthal, the Denisovan, and the chimp), and that the sequence most different from it in this dataset belongs to a cucumber.}, } @article {pmid25982166, year = {2015}, author = {Pääbo, S}, title = {The diverse origins of the human gene pool.}, journal = {Nature reviews. Genetics}, volume = {16}, number = {6}, pages = {313-314}, pmid = {25982166}, issn = {1471-0064}, mesh = {Animals ; *Evolution, Molecular ; Gene Flow ; *Genome, Human ; Humans ; Neanderthals/genetics ; Sequence Analysis, DNA ; }, abstract = {Analyses of the genomes of Neanderthals and Denisovans, the closest evolutionary relatives of present-day humans, suggest that our ancestors were part of a web of now-extinct populations linked by limited, but intermittent or sometimes perhaps even persistent, gene flow.}, } @article {pmid25956332, year = {2015}, author = {Solovyeva, EV and Myund, LA and Denisova, AS}, title = {Surface enhanced Raman scattering of new acridine based fluorophore adsorbed on silver electrode.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {149}, number = {}, pages = {196-200}, doi = {10.1016/j.saa.2015.04.092}, pmid = {25956332}, issn = {1873-3557}, abstract = {4,5-Bis(N,N-di(2-hydroxyethyl)iminomethyl)acridine (BHIA) is a new acridine based fluoroionophore and a highly-selective sensor for cadmium ion. The direct interaction of the aromatic nitrogen atom with a surface is impossible since there are bulky substituents in the 4,5-positions of the acridine fragment. Nevertheless BHIA molecule shows a reliable SERS spectrum while adsorbed on a silver electrode. The analysis of SERS spectra pH dependence reveals that BHIA species adsorbed on a surface can exist in both non-protonated and protonated forms. The adsorption of BHIA from alkaline solution is accompanied by carbonaceous species formation at the surface. The intensity of such "carbon bands" turned out to be related with the supporting electrolyte (KCl) concentration. Upon lowering the electrode potential the SERS spectra of BHIA do not undergo changes but the intensity of bands decreases. This indicates that the adsorption mechanism on the silver surface is realized via aromatic system of acridine fragment. In case of such an adsorption mechanism the chelate fragment of the BHIA molecule is capable of interaction with the solution components. Addition of Cd(2+) ions to a system containing BHIA adsorbed on a silver electrode in equilibrium with the solution leads to the formation of BHIA/Cd(2+) complex which desorption causes the loss of SERS signal.}, } @article {pmid25857197, year = {2015}, author = {Maliarchuk, BA and Derenko, MV and Denisova, GA}, title = {[Phylogenetic relationships among Asiatic salamanders of the genus Salamandrella based on variability of nuclear genes].}, journal = {Genetika}, volume = {51}, number = {1}, pages = {101-108}, pmid = {25857197}, issn = {0016-6758}, mesh = {Amphibian Proteins/*genetics ; Animals ; Cell Nucleus/genetics ; *Phylogeny ; Salamandridae/*genetics ; Siberia ; Species Specificity ; }, abstract = {Based on sequence variation of three nuclear genome genes (BDNF, POMC, and RAG1), the phylogenetic relationships among Asiatic salamanders of the genus Salamandrella, Siberian salamander (S. keyserlingii) and Schrenk salamander (S. schrenkii), were examined. Both species demonstrated high levels of heterozygosity determined by intraspecific polymorphism. Fixed interspecific differences were revealed at one nucleotide position of the RAG1 gene, and thus the level of interspecific divergence over the three genes constituted only 0.04%. Analysis of the RAG1 polymorphism across the whole range of S. keyserlingii showed that only one gene variant, encoding for modified RAG1 recombinase, had the highest distribution to the north of the Amur region (west and northeast of Siberia). It is possible that the changes in the RAG1 gene in Siberian salamander are of an adaptive nature. However, cases of interspecific hybridization were identified in Jewish autonomous oblast (JAO), which contains one of the range borders between the two Salamandrella species.}, } @article {pmid25831703, year = {2014}, author = {Musaeva, TS and Berdnikov, AP and Goncharenko, SI and Denisova, EA}, title = {[Efficiency of high-volume hemofiltration in patients with severe sepsis and intracranial hypertension].}, journal = {Anesteziologiia i reanimatologiia}, volume = {59}, number = {6}, pages = {48-51}, pmid = {25831703}, issn = {0201-7563}, mesh = {APACHE ; Carbon Dioxide/blood ; Hemodynamics/physiology ; Hemofiltration/adverse effects/*methods ; Humans ; Intracranial Hypertension/blood/etiology/physiopathology/*therapy ; Intracranial Pressure/physiology ; Oxygen/blood ; Retrospective Studies ; Sepsis/blood/complications/physiopathology/*therapy ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {We performed a retrospective study in 68 patients (144 procedures) with severe sepsis and intracranial hypertension measured by the pressure in the central retinal vein. The patients underwent high-volume hemofiltration (HV-HF) for extrarenal indications. Increased pressure in the central retinal vein was accompanied by critical points of cerebral perfusion pressure and the growth of neurological deficit with inhibition level of consciousness to coma 1. In this case, IHV-HF may be associated with the formation of the critical points of cerebral perfihsion and severe disorders of microcirculation and the lack of resolution of tissue hypoperfusion. In case of intracranial hypertension IHV-HF is not effective in the category of patients where there is a combination ΔpCO2 > 5.9 mm Hg level and GCS <10 points.}, } @article {pmid25816525, year = {2014}, author = {Karal'nik, BV and Ponomareva, TS and Deriabin, PN and Denisova, TG and Mel'nikova, NN and Tugambaev, TI and Atshabar, BB and Zakarian, SB}, title = {[Effect of immune modulation on immunogenic and protective activity of a live plague vaccine].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {6}, pages = {108-112}, pmid = {25816525}, issn = {0372-9311}, mesh = {Animals ; Antibodies, Bacterial/*biosynthesis ; Antigens, Bacterial/immunology ; Gene Expression ; Guinea Pigs ; Immunity, Cellular/drug effects ; Immunization ; Immunoglobulin G/*biosynthesis ; Immunologic Factors/*administration & dosage/immunology ; Injections, Intravenous ; Interleukin-1beta/*administration & dosage/immunology ; Piperazines/*administration & dosage/immunology ; Plague/blood/immunology/microbiology/*prevention & control ; Plague Vaccine/*administration & dosage/immunology ; Polymers/*administration & dosage ; Rabbits ; Receptors, Antigen, T-Cell/genetics/immunology ; Vaccines, Attenuated ; Yersinia pestis/immunology ; }, abstract = {AIM: Comparative evaluation of the effect of polyoxidonium and betaleukin on immunogenic and protective activity of a live plague vaccine in model animal experiments.

MATERIALS AND METHODS: Plague vaccine EV, polyoxidonium, betaleukin, erythrocytic antigenic diagnosticum for determination of F1 antibodies and immune reagents for detection of lymphocytes with F1 receptors (LFR) in adhesive test developed by the authors were used. The experiments were carried out in 12 rabbits and 169 guinea pigs.

RESULTS: Immune modulation accelerated the appearance and disappearance of LFR (early phase) and ensured a more rapid and intensive antibody formation (effector phase). Activation by betaleukin is more pronounced than by polyoxidonium. The more rapid and intensive was the development of early phase, the more effective was antibody response to the vaccine. Immune modulation in the experiment with guinea pigs significantly increased protective activity of the vaccine.

CONCLUSION: The use of immune modulators increased immunogenic (in both early and effector phases of antigen-specific response) and protective activity of the EV vaccine. A connection between the acceleration of the first phase of antigen-specific response and general intensity of effector phase of immune response to the EV vaccine was detected. ,}, } @article {pmid25711027, year = {2014}, author = {Maliarchuk, BA and Derenko, MV and Denisova, GA}, title = {[Episodes of adaptive evolution of mitochondrial genome in Asiatic salamanders (Amphibia, Caudata, Hynobiidae)].}, journal = {Genetika}, volume = {50}, number = {2}, pages = {189-196}, pmid = {25711027}, issn = {0016-6758}, mesh = {Adaptation, Biological/genetics ; Amino Acid Sequence ; Animals ; Base Sequence ; *Evolution, Molecular ; *Genetic Speciation ; Genome, Mitochondrial/*genetics ; Phylogeny ; Selection, Genetic/*genetics ; Urodela/genetics ; }, abstract = {To elucidate the effect of natural selection on the evolution of mitochondrial DNA (mtDNA) in Asiatic salamanders of the family Hynobiidae, nucleotide sequences of 12 protein-coding genes were analyzed. Using a mixed effects model of evolution, it was found that, in spite of the pronounced effect of negative selection on the mtDNA evolution in Hynobiidae (which is typical for the animals in general), two phylogenetic clusters, the West Asian one, represented by the genera Ranodon and Paradactylodon, and North Eurasian one, represented by the genus Salamandrella, were formed under the influence of episodic positive selection. Analysis of protein sequences encoded by the mitochondrial genome also supported the influence of positive selection on the evolution of Hynobiidae at some stages of their cladogenesis. It is suggested that the signatures of adaptive evolution detected in the mtDNA of Hynobiidae were determined by the complex and long-lasting history of their formation, accompanied by adaptation to the changing environment.}, } @article {pmid25588492, year = {2014}, author = {Soldatskiĭ, IuL and Denisova, OA and Ivanenko, AM}, title = {[The comparative effectiveness of framycetin included in combined therapy of adenoiditis in the children].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {5}, pages = {69-71}, pmid = {25588492}, issn = {0042-4668}, mesh = {Adolescent ; Anti-Infective Agents, Local/administration & dosage/*pharmacology ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Framycetin/administration & dosage/*pharmacology ; Humans ; Male ; Nasal Lavage ; Silver Proteins/administration & dosage/*pharmacology ; Tonsillitis/*drug therapy ; Treatment Outcome ; }, abstract = {The objective of the present study was to evaluate the effectiveness of framycetin included in combined therapy of adenoiditis in the children. The study involved 67 children at the mean age of 6.9±2.7 years. Group 1 was comprised of 35 children given framycetin as topical therapy, the patients of group 2 were treated by the endonasal administration of a 2% silver proteinate solution. It was shown that the use of framycetin as a component of combined therapy of adenoiditis enhances the effectiveness of the treatment and compliance to therapy in comparison with the same parameters in the case of the application of traditional topical antibacterial preparations.}, } @article {pmid25581429, year = {2015}, author = {Do, R and Balick, D and Li, H and Adzhubei, I and Sunyaev, S and Reich, D}, title = {No evidence that selection has been less effective at removing deleterious mutations in Europeans than in Africans.}, journal = {Nature genetics}, volume = {47}, number = {2}, pages = {126-131}, pmid = {25581429}, issn = {1546-1718}, support = {R01 GM078598/GM/NIGMS NIH HHS/United States ; R01MH101244/MH/NIMH NIH HHS/United States ; R01 GM100233/GM/NIGMS NIH HHS/United States ; R01 HG006399/HG/NHGRI NIH HHS/United States ; HG006399/HG/NHGRI NIH HHS/United States ; GM100233/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 GM105857/GM/NIGMS NIH HHS/United States ; R01GM078598/GM/NIGMS NIH HHS/United States ; R01 MH101244/MH/NIMH NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Animals ; Black People/*genetics ; Computer Simulation ; Gene Frequency ; Genetic Variation ; Genetics, Population ; Genome, Human/*genetics ; Humans ; Models, Genetic ; Mutation ; Neanderthals/*genetics ; Selection, Genetic/*physiology ; White People/*genetics ; }, abstract = {Non-African populations have experienced size reductions in the time since their split from West Africans, leading to the hypothesis that natural selection to remove weakly deleterious mutations has been less effective in the history of non-Africans. To test this hypothesis, we measured the per-genome accumulation of nonsynonymous substitutions across diverse pairs of populations. We find no evidence for a higher load of deleterious mutations in non-Africans. However, we detect significant differences among more divergent populations, as archaic Denisovans have accumulated nonsynonymous mutations faster than either modern humans or Neanderthals. To reconcile these findings with patterns that have been interpreted as evidence of the less effective removal of deleterious mutations in non-Africans than in West Africans, we use simulations to show that the observed patterns are not likely to reflect changes in the effectiveness of selection after the populations split but are instead likely to be driven by other population genetic factors.}, } @article {pmid25575941, year = {2015}, author = {Rogers, AR and Bohlender, RJ}, title = {Bias in estimators of archaic admixture.}, journal = {Theoretical population biology}, volume = {100C}, number = {}, pages = {63-78}, doi = {10.1016/j.tpb.2014.12.006}, pmid = {25575941}, issn = {1096-0325}, abstract = {This article evaluates bias in one class of methods used to estimate archaic admixture in modern humans. These methods study the pattern of allele sharing among modern and archaic genomes. They are sensitive to "ghost" admixture, which occurs when a population receives archaic DNA from sources not acknowledged by the statistical model. The effect of ghost admixture depends on two factors: branch-length bias and population-size bias. Branch-length bias occurs because a given amount of admixture has a larger effect if the two populations have been separated for a long time. Population-size bias occurs because differences in population size distort branch lengths in the gene genealogy. In the absence of ghost admixture, these effects are small. They become important, however, in the presence of ghost admixture. Estimators differ in the pattern of response. Increasing a given parameter may inflate one estimator but deflate another. For this reason, comparisons among estimators are informative. Using such comparisons, this article supports previous findings that the archaic population was small and that Europeans received little gene flow from archaic populations other than Neanderthals. It also identifies an inconsistency in estimates of archaic admixture into Melanesia.}, } @article {pmid25563409, year = {2015}, author = {Perry, GH and Kistler, L and Kelaita, MA and Sams, AJ}, title = {Insights into hominin phenotypic and dietary evolution from ancient DNA sequence data.}, journal = {Journal of human evolution}, volume = {79}, number = {}, pages = {55-63}, doi = {10.1016/j.jhevol.2014.10.018}, pmid = {25563409}, issn = {1095-8606}, mesh = {Animals ; Base Sequence ; *Biological Evolution ; DNA/analysis/genetics ; DNA Copy Number Variations ; Feeding Behavior/*physiology ; Fossils ; Genetic Variation ; Genomics ; Hominidae/*genetics/*physiology ; Humans ; Molecular Sequence Data ; Myosin Heavy Chains/genetics ; Neanderthals ; Paleontology ; Phenotype ; Receptors, G-Protein-Coupled/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Nuclear genome sequence data from Neandertals, Denisovans, and archaic anatomically modern humans can be used to complement our understanding of hominin evolutionary biology and ecology through i) direct inference of archaic hominin phenotypes, ii) indirect inference of those phenotypes by identifying the effects of previously-introgressed alleles still present among modern humans, or iii) determining the evolutionary timing of relevant hominin-specific genetic changes. Here we review and reanalyze published Neandertal and Denisovan genome sequence data to illustrate an example of the third approach. Specifically, we infer the timing of five human gene presence/absence changes that may be related to particular hominin-specific dietary changes and discuss these results in the context of our broader reconstructions of hominin evolutionary ecology. We show that pseudogenizing (gene loss) mutations in the TAS2R62 and TAS2R64 bitter taste receptor genes and the MYH16 masticatory myosin gene occurred after the hominin-chimpanzee divergence but before the divergence of the human and Neandertal/Denisovan lineages. The absence of a functional MYH16 protein may explain our relatively reduced jaw muscles; this gene loss may have followed the adoption of cooking behavior. In contrast, salivary amylase gene (AMY1) duplications were not observed in the Neandertal and Denisovan genomes, suggesting a relatively recent origin for the AMY1 copy number gains that are observed in modern humans. Thus, if earlier hominins were consuming large quantities of starch-rich underground storage organs, as previously hypothesized, then they were likely doing so without the digestive benefits of increased salivary amylase production. Our most surprising result was the observation of a heterozygous mutation in the first codon of the TAS2R38 bitter taste receptor gene in the Neandertal individual, which likely would have resulted in a non-functional protein and inter-individual PTC (phenylthiocarbamide) taste sensitivity variation, as also observed in both humans and chimpanzees.}, } @article {pmid25556237, year = {2015}, author = {Lin, YL and Pavlidis, P and Karakoc, E and Ajay, J and Gokcumen, O}, title = {The evolution and functional impact of human deletion variants shared with archaic hominin genomes.}, journal = {Molecular biology and evolution}, volume = {32}, number = {4}, pages = {1008-1019}, pmid = {25556237}, issn = {1537-1719}, mesh = {Alleles ; Animals ; *Evolution, Molecular ; Genetic Variation ; *Genome ; Hominidae/*genetics ; Humans ; *Sequence Deletion ; }, abstract = {Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins. However, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. We identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the Human-Neandertal divergence (ancient) and only approximately 9% of which have been introgressed from Neandertals (introgressed). Recurrence, incomplete lineage sorting between human and chimp lineages, and hominid-specific insertions constitute the remaining approximately 4% of allele sharing between humans and archaic hominins. We observed that ancient deletions correspond to more than 13% of all common (>5% allele frequency) deletion variation among modern humans. Our analyses indicate that the genomic landscapes of both ancient and introgressed deletion variants were primarily shaped by purifying selection, eliminating large and exonic variants. We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts. The affected genes are involved in metabolism of external and internal compounds, growth and sperm formation, as well as susceptibility to psoriasis and Crohn's disease. Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection. Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes.}, } @article {pmid27141645, year = {2015}, author = {Verikovsky, VA and Minakov, OE and Denisova, OI and Bondarenko, EV}, title = {[Results of Investigation of MRSA Susceptibility to Vancomycin in Clinical Units of Large Multifunctional Hospital and Recommendations on Optimization of Antibacterial Therapy of Staphylococcal Infection].}, journal = {Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]}, volume = {60}, number = {11-12}, pages = {35-38}, pmid = {27141645}, issn = {0235-2990}, mesh = {Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Cities ; Drug Resistance, Bacterial ; Hospital Bed Capacity, 500 and over/standards ; Hospitals, District/standards ; Humans ; Methicillin-Resistant Staphylococcus aureus/*drug effects/isolation & purification ; Microbial Sensitivity Tests/methods ; *Practice Guidelines as Topic ; Russia ; Staphylococcal Infections/*drug therapy/epidemiology/microbiology ; Vancomycin/administration & dosage/*therapeutic use ; }, abstract = {The frequency of MRSA and MRSE isolates in various units of the Voronezh Regional Hospital was investigated by the results of the local microbiological monitoring for 2014. The maximum position of MRSA was recorded in the ICU (38 to 75% of the strains). The MRSA strains were characterized by higher methicillin resistance, mainly from the cardiosurgical units (60 to 91% of the isolates). The use of the E-test for MRSA susceptibility to vancomycin allowed to estimate the validity of the use of various antibiotics active against MRSA in the treatment of inpatients and to reduce the risk of ineffective therapy.}, } @article {pmid27024918, year = {2015}, author = {Slepowa, OS and Svetlova, EV and Kovaleva, LA and Makarov, PV and Kugusheva, AE and Denisova, EV and Vahova, ES and Zaharova, GY and Kondrat'eva, YA and Andryushin, AE and Demkin, VV}, title = {[PCR study of the human herpes virus type 6 and other viruses of the herpes group in eye diseases].}, journal = {Voprosy virusologii}, volume = {60}, number = {6}, pages = {45-48}, pmid = {27024918}, issn = {0507-4088}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anterior Chamber/pathology/virology ; Aqueous Humor/virology ; Child ; Child, Preschool ; Cornea/pathology/virology ; Cytomegalovirus/genetics/isolation & purification ; DNA, Viral/*genetics ; Eye Diseases/*diagnosis/pathology/virology ; Female ; Herpesviridae Infections/*diagnosis/pathology/virology ; Herpesvirus 1, Human/genetics/isolation & purification ; Herpesvirus 2, Human/genetics/isolation & purification ; Herpesvirus 4, Human/genetics/isolation & purification ; Herpesvirus 6, Human/genetics/isolation & purification ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; }, abstract = {To study the role of the HHV-6 type in the development of eye diseases PCR tests of blood (152), cornea biopsies (61), and intraocular fluids (11) for HHV-6 and other viruses of the herpes group (HSV type 1 and 2, CMV, EBV) were conducted. It was found that the HHV-6, along with other representatives of the Herpesviridae, can be detected in patients with different clinical forms of ophthalmopathology (174 patients were surveyed). Viral DNA was detected in blood, cornea, and in the anterior chamber fluid. The obtained data allow that the HHV-6 to be suggested as a possible cause of the ophthalmic herpes along with the other viruses of this group. It makes finding the virus DNA an essential step towards setting the etiologic diagnosis of the ophthalmological patients.}, } @article {pmid25536760, year = {2014}, author = {Denisova, OI and Davydkin, NF and Kulikov, AG}, title = {[The pathogenetic prerequisites for the application of the general magnetic therapy in the children presenting with cerebral ischemia].}, journal = {Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury}, volume = {}, number = {5}, pages = {56-60}, pmid = {25536760}, issn = {0042-8787}, mesh = {Brain Ischemia/*etiology/physiopathology/*rehabilitation ; Cerebrovascular Circulation/physiology ; Child ; Humans ; Hypoxia, Brain/prevention & control ; *Magnetic Field Therapy ; Microcirculation/physiology ; }, abstract = {This article presents the analysis of the current literature and the original data of the authors providing the rationale for the use of magnetic therapy for the treatment of the children presenting with cerebral ischemia taking into consideration pathogenesis of this disease. It is demonstrated that the application of the general magnetic field decreases the tone of the cerebral vessels and improves blood flow to the brain which increases resistance to cerebral hypoxia. The results of investigations into the microcirculatory changes and liquor dynamics in conjunction with the ventriculometric measurements give evidence of the effectiveness of the combined treatment of cerebral ischemia making use of general magnetic therapy.}, } @article {pmid25509854, year = {2013}, author = {Maliarchuk, BA}, title = {[Mutation process in the protein-coding genes of human mitochondrial genome in context of evolution of the genus].}, journal = {Molekuliarnaia biologiia}, volume = {47}, number = {6}, pages = {927-933}, pmid = {25509854}, issn = {0026-8984}, mesh = {Animals ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Genome, Human/*genetics ; *Genome, Mitochondrial ; Humans ; Mutation/*genetics ; Neanderthals ; Polymorphism, Genetic ; }, abstract = {The human mitochondrial genome, although it has a small size, is characterized by high level of variation, non-uniformly distributed in groups of nucleotide positions that differ in the degree of variability. Considering the mutation process in human mtDNA relative to the mitochondrial genomes of the genus Homo-neandertals, denisova hominin and other primate species, it appears that more than half (56.5%) variable positions in the human mtDNA protein-coding genes are characterized by back (reverse) mutations to the pre-H. sapiens state of mitochondrial genome. It has been found that hypervariable nucleotide positions show a minimal proportion of specific to H. sapiens mutations, and, conversely, a high proportion of mutations (both nucleotide and amino acid substitutions), leading to the loss of Homo-specific variants of polymorphisms. Most often, polymorphisms specific to H. sapiens arise in result of single forward mutations and disappear mainly due to multiple back mutations, including those in the mutational "hotspots".}, } @article {pmid25487326, year = {2015}, author = {Sánchez-Quinto, F and Lalueza-Fox, C}, title = {Almost 20 years of Neanderthal palaeogenetics: adaptation, admixture, diversity, demography and extinction.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1660}, pages = {20130374}, pmid = {25487326}, issn = {1471-2970}, mesh = {Adaptation, Biological/*genetics ; Animals ; *Biological Evolution ; DNA, Mitochondrial/genetics ; *Extinction, Biological ; Fossils ; *Genetic Variation ; Genetics, Population ; Genomics/*methods/trends ; *Hybridization, Genetic ; Neanderthals/*genetics ; Population Dynamics ; }, abstract = {Nearly two decades since the first retrieval of Neanderthal DNA, recent advances in next-generation sequencing technologies have allowed the generation of high-coverage genomes from two archaic hominins, a Neanderthal and a Denisovan, as well as a complete mitochondrial genome from remains which probably represent early members of the Neanderthal lineage. This genomic information, coupled with diversity exome data from several Neanderthal specimens is shedding new light on evolutionary processes such as the genetic basis of Neanderthal and modern human-specific adaptations-including morphological and behavioural traits-as well as the extent and nature of the admixture events between them. An emerging picture is that Neanderthals had a long-term small population size, lived in small and isolated groups and probably practised inbreeding at times. Deleterious genetic effects associated with these demographic factors could have played a role in their extinction. The analysis of DNA from further remains making use of new large-scale hybridization-capture-based methods as well as of new approaches to discriminate contaminant DNA sequences will provide genetic information in spatial and temporal scales that could help clarify the Neanderthal's-and our very own-evolutionary history.}, } @article {pmid25447821, year = {2015}, author = {Adel, S and Kakularam, KR and Horn, T and Reddanna, P and Kuhn, H and Heydeck, D}, title = {Leukotriene signaling in the extinct human subspecies Homo denisovan and Homo neanderthalensis. Structural and functional comparison with Homo sapiens.}, journal = {Archives of biochemistry and biophysics}, volume = {565}, number = {}, pages = {17-24}, doi = {10.1016/j.abb.2014.10.012}, pmid = {25447821}, issn = {1096-0384}, mesh = {Animals ; Databases, Genetic ; Genome, Human/*physiology ; Humans ; Leukotrienes/*genetics/metabolism ; Lipoxygenases/*genetics/metabolism ; Neanderthals/*genetics/metabolism ; Signal Transduction/*genetics ; Species Specificity ; }, abstract = {Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies.}, } @article {pmid25403398, year = {2014}, author = {Bugayova, LI and Denisova, TD and Morozova, YA and Sergeeva, SA and Kharlamov, IV}, title = {Effect of afobazole administered to pregnant rats during organogenesis on prenatal development of fetuses.}, journal = {Bulletin of experimental biology and medicine}, volume = {158}, number = {1}, pages = {57-60}, doi = {10.1007/s10517-014-2691-x}, pmid = {25403398}, issn = {1573-8221}, mesh = {Animals ; Anti-Anxiety Agents/therapeutic use/*toxicity ; Benzimidazoles/therapeutic use/*toxicity ; Drug Evaluation, Preclinical ; Female ; Fetal Development/*drug effects ; Male ; Maternal-Fetal Exchange ; Morpholines/therapeutic use/*toxicity ; Organogenesis/*drug effects ; Pregnancy ; Pregnancy Complications/*drug therapy ; Rats ; }, abstract = {Experiments on pregnant rats have demonstrated the absence of damaging effect of Afobazole administered during the antenatal period on organogenesis in fetuses. Afobazole in a dose of 5 mg/kg given to pregnant rats on gestation days 6-16 reduced pre- and post-implantation fetal mortality and improved fertility; 20-day-old embryos had no developmental abnormalities and did not differ from controls by craniocaudal size, body weight, and skeleton ossification. Afobazole in a dose of 100 mg/kg reduced pre- and post-implantation fetal mortality, but had no effect on fertility. No congenital malformations were found in the fetuses, but they were characterized by lower craniocaudal size, body weight, and number of ossification foci in the sternum and spine.}, } @article {pmid25393762, year = {2014}, author = {Lesecque, Y and Glémin, S and Lartillot, N and Mouchiroud, D and Duret, L}, title = {The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.}, journal = {PLoS genetics}, volume = {10}, number = {11}, pages = {e1004790}, pmid = {25393762}, issn = {1553-7404}, mesh = {Animals ; Chromosomes/genetics ; *Crossing Over, Genetic ; DNA-Binding Proteins ; *Evolution, Molecular ; Gene Conversion ; Genome, Human ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Meiosis/genetics ; Pan troglodytes ; *Recombination, Genetic ; }, abstract = {Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan) to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC), which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.}, } @article {pmid25301575, year = {2014}, author = {Derenko, M and Malyarchuk, B and Denisova, G and Perkova, M and Litvinov, A and Grzybowski, T and Dambueva, I and Skonieczna, K and Rogalla, U and Tsybovsky, I and Zakharov, I}, title = {Western Eurasian ancestry in modern Siberians based on mitogenomic data.}, journal = {BMC evolutionary biology}, volume = {14}, number = {}, pages = {217}, pmid = {25301575}, issn = {1471-2148}, mesh = {Asian People/genetics ; DNA, Mitochondrial/*genetics ; Female ; *Gene Pool ; Genetics, Medical ; *Genetics, Population ; Humans ; Molecular Sequence Data ; Phylogeny ; Phylogeography ; Siberia ; White People/genetics ; }, abstract = {BACKGROUND: Although the genetic heritage of aboriginal Siberians is mostly of eastern Asian ancestry, a substantial western Eurasian component is observed in the majority of northern Asian populations. Traces of at least two migrations into southern Siberia, one from eastern Europe and the other from western Asia/the Caucasus have been detected previously in mitochondrial gene pools of modern Siberians.

RESULTS: We report here 166 new complete mitochondrial DNA (mtDNA) sequences that allow us to expand and re-analyze the available data sets of western Eurasian lineages found in northern Asian populations, define the phylogenetic status of Siberian-specific subclades and search for links between mtDNA haplotypes/subclades and events of human migrations. From a survey of 158 western Eurasian mtDNA genomes found in Siberia we estimate that nearly 40% of them most likely have western Asian and another 29% European ancestry. It is striking that 65 of northern Asian mitogenomes, i.e. ~41%, fall into 19 branches and subclades which can be considered as Siberian-specific being found so far only in Siberian populations. From the coalescence analysis it is evident that the sequence divergence of Siberian-specific subclades was relatively small, corresponding to only 0.6-9.5 kya (using the complete mtDNA rate) and 1-6 kya (coding region rate).

CONCLUSIONS: The phylogeographic analysis implies that the western Eurasian founders, giving rise to Siberian specific subclades, may trace their ancestry only to the early and mid-Holocene, though some of genetic lineages may trace their ancestry back to the end of Last Glacial Maximum (LGM). We have not found the modern northern Asians to have western Eurasian genetic components of sufficient antiquity to indicate traces of pre-LGM expansions.}, } @article {pmid25286439, year = {2014}, author = {Kelso, J and Prüfer, K}, title = {Ancient humans and the origin of modern humans.}, journal = {Current opinion in genetics & development}, volume = {29}, number = {}, pages = {133-138}, doi = {10.1016/j.gde.2014.09.004}, pmid = {25286439}, issn = {1879-0380}, mesh = {Africa ; Animals ; DNA/chemistry/classification/*genetics ; *Evolution, Molecular ; Genome, Human/*genetics ; Hominidae/*genetics ; Humans ; Oceania ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Recent advances in sequencing technologies and molecular methods have facilitated the sequencing of DNA from ancient human remains which has, in turn, provided unprecedented insight into human history. Within the past 4 years the genomes of Neandertals and Denisovans, as well as the genomes of at least two early modern humans, have been sequenced. These sequences showed that there have been several episodes of admixture between modern and archaic groups; including admixture from Neandertals into modern human populations outside of Africa, and admixture from Denisovans into modern human populations in Oceania. Recent results indicate that some of these introgressed regions may have been advantageous for modern humans as they expanded into new regions outside of Africa.}, } @article {pmid25277105, year = {2014}, author = {Schneider, E and El Hajj, N and Haaf, T}, title = {Epigenetic information from ancient DNA provides new insights into human evolution. Commentary on Gokhman D et al. (2014): Reconstructing the DNA methylation maps of the Neanderthal and the Denisovan. Science 344:523-527.}, journal = {Brain, behavior and evolution}, volume = {84}, number = {3}, pages = {169-171}, doi = {10.1159/000365650}, pmid = {25277105}, issn = {1421-9743}, mesh = {Animals ; *DNA Methylation ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Genome, Human ; Humans ; Neanderthals/*genetics ; }, } @article {pmid25269182, year = {2014}, author = {Cherniaevskaia, GM and Maksimenko, GV and Beloborodova, ÉI and Ustiuzhanina, EA and Denisova, OA}, title = {[Clinical and morphological peculiarities of the clinical course of duodenal ulcer in patients with bronchial asthma].}, journal = {Klinicheskaia meditsina}, volume = {92}, number = {2}, pages = {47-52}, pmid = {25269182}, issn = {0023-2149}, mesh = {Adolescent ; Adult ; Asthma/epidemiology/*pathology ; Comorbidity ; Duodenal Ulcer/epidemiology/etiology/*pathology ; Gastric Mucosa/microbiology/*pathology/physiopathology ; Helicobacter Infections/*complications/epidemiology/pathology ; Helicobacter pylori/*pathogenicity ; Humans ; Inflammation/epidemiology/microbiology/pathology ; Middle Aged ; Prospective Studies ; Young Adult ; }, abstract = {This work was aimed to study clinical features of H. pylori-associated duodenal ulcer (DU) and elucidate morphological features of gastric mucosa (GM) in patients with bronchial asthma (BA). Simultaneous prospective examination of 118 patients aged 18-64 yr included clinical and endoscopic study of the gastroduodenal region with the assessment of gastroenterological symptoms and morphological analysis of GM and duodenal biopsies by histological, histochemical, and morphometric methods. It was shown that GM inflammation in patients with DU and BA is associated not only with H. pylori infection but also with the phase of BA. Structural changes of GM in the patients with DU and BA, unlike those with DU without BA, were apparent not only in the antrum but also in the fundus. Growing density of eosinophil, neutrophil and mast cell infiltration of fundal and antral GM as well as increased total number of cells in the antrum reflects active immune-mediated inflammation in GM lamina propria. It is concluded that negative effect of uncontrolled BA on the clinical course of DU is not restricted to the association of DU exacerbation with the absence of BA control; it is also responsible for enhanced activity of gastritis. One of the possible factors determining combination of H. pylori-associated duodenal ulcer with BA is chronic hyperergic inflammation and marked structural changes in GM.}, } @article {pmid25265662, year = {2014}, author = {Denisova, OA and Cherniavskaia, GM and Beloborodova, ÉI and Topol'nitskiĭ, EB and Iakimenko, IuV and Chernogoriuk, GÉ and Beloborodova, EV and Strezh, IuA and Vil'danova, LR}, title = {[A case of thoracic actinomycosis].}, journal = {Klinicheskaia meditsina}, volume = {92}, number = {1}, pages = {59-61}, pmid = {25265662}, issn = {0023-2149}, mesh = {Actinomyces/*pathogenicity ; Actinomycosis/*diagnosis/drug therapy/pathology ; Amoxicillin-Potassium Clavulanate Combination/administration & dosage/pharmacology ; Anti-Bacterial Agents/administration & dosage/*pharmacology ; Humans ; Male ; Middle Aged ; Pneumonia, Bacterial/*diagnosis/drug therapy/pathology ; Respiratory Tract Infections/diagnosis/drug therapy/pathology ; Sulbactam/administration & dosage/pharmacology ; Treatment Outcome ; }, abstract = {A case of thoracic actinomycosis manifest as round shadow in the lung is described. Diagnosis was based on the presence of actinomycetes in a transthoracic lung biopsy sample. Treatment for 3 months resulted in recovery. No relapse was documented during 1 year follow-up period.}, } @article {pmid25257410, year = {2014}, author = {Pinchuk, TV and Fedulaev, YN and Khairetdinova, GA and Denisova, NN and Chura, OV and Logunova, IY}, title = {Anti-inflammatory effects of simvastatin in patients with chronic heart failure.}, journal = {Bulletin of experimental biology and medicine}, volume = {157}, number = {5}, pages = {552-554}, doi = {10.1007/s10517-014-2612-z}, pmid = {25257410}, issn = {1573-8221}, mesh = {Aged ; Anti-Inflammatory Agents/*therapeutic use ; Chronic Disease ; Female ; Heart Failure/*drug therapy ; Humans ; Inflammation Mediators/blood ; Male ; Middle Aged ; Simvastatin/*therapeutic use ; }, abstract = {Proinflammatory markers were evaluated in patients with chronic heart failure of ischemic origin and essential hypertension with preserved left-ventricular ejection fraction before and after a 6-month course of simvastatin therapy (20 mg/day). The study was carried out in 125 patients with diastolic dysfunction manifested as impaired relaxation and pseudonormalization. The main group received standard therapy for chronic heart failure and simvastatin, controls received only standard therapy. In addition, the results in the main group were compared in patients with different types of left-ventricular diastolic dysfunction. Simvastatin therapy significantly reduced the levels of C-reactive protein and IL-6.}, } @article {pmid25249249, year = {2015}, author = {Kang, L and Michalak, P}, title = {The evolution of cancer-related genes in hominoids.}, journal = {Journal of molecular evolution}, volume = {80}, number = {1}, pages = {37-41}, pmid = {25249249}, issn = {1432-1432}, mesh = {Animals ; Base Sequence ; *Evolution, Molecular ; *Genes, Tumor Suppressor ; Hominidae/*genetics ; Humans ; *Oncogenes ; Sequence Homology, Nucleic Acid ; }, abstract = {The evolution of cancer suppression is essential for the maintenance of multicellularity. The lack of correlation between body size and cancer risk across species, known as Peto's paradox, suggests that genetic variation in cancer resistance is sufficient to compensate for increases of cell numbers in bigger animals. To assess evolutionary dynamics of cancer-related genes, we analyzed Ka, Ks,and Ka/Ks values in 120 oncogenes and tumor suppressor genes (TSG) among seven hominoid species, including two extinct species, Neanderthal and Denisovan. Ka/Ks of tumor suppressor genes tended to be higher relative to that of oncogenes, consistent with relaxed purifying selection acting on the former. Ka/Ks values were positively correlated with TSG scores, but negatively correlated with oncogene scores, suggesting opposing selection pressures operating on the two groups of cancer-related genes. Additionally, we found 108 species-divergent substitutions that were prevalent germline genotypes in some species but in humans appeared only as somatic cancerous mutations. Better understanding the resistance to cancer may lead to new methods of cancer prevention in humans.}, } @article {pmid25190608, year = {2014}, author = {Ségurel, L and Quintana-Murci, L}, title = {Preserving immune diversity through ancient inheritance and admixture.}, journal = {Current opinion in immunology}, volume = {30}, number = {}, pages = {79-84}, doi = {10.1016/j.coi.2014.08.002}, pmid = {25190608}, issn = {1879-0372}, mesh = {Animals ; Evolution, Molecular ; Genome ; Genome-Wide Association Study ; Humans ; Models, Immunological ; Selection, Genetic/*immunology ; }, abstract = {The progress of genomic technologies is allowing researchers to scan the genomes of different species for the occurrence of natural selection at an unprecedented level of resolution. These studies show that genes involved in immune processes are preferential targets of different forms of selection, some of which act to preserve immune diversity over time. Recent work in humans shows that this can be achieved either by inheriting advantageous immune variation from distant ancestral species, through long-term balancing selection, or by acquiring novel selected alleles through admixture with extinct hominins such as Neanderthals or Denisovans. These studies collectively increase our knowledge of immune genes for which maintaining the functional diversity has conferred a strong selective advantage for host survival.}, } @article {pmid25172957, year = {2014}, author = {Racimo, F and Kuhlwilm, M and Slatkin, M}, title = {A test for ancient selective sweeps and an application to candidate sites in modern humans.}, journal = {Molecular biology and evolution}, volume = {31}, number = {12}, pages = {3344-3358}, pmid = {25172957}, issn = {1537-1719}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; R01-GM40282/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; *Evolution, Molecular ; Genome, Human ; Humans ; *Models, Genetic ; Neanderthals/genetics ; Polymorphism, Single Nucleotide ; Selection, Genetic ; }, abstract = {We introduce a new method to detect ancient selective sweeps centered on a candidate site. We explored different patterns produced by sweeps around a fixed beneficial mutation, and found that a particularly informative statistic measures the consistency between majority haplotypes near the mutation and genotypic data from a closely related population. We incorporated this statistic into an approximate Bayesian computation (ABC) method that tests for sweeps at a candidate site. We applied this method to simulated data and show that it has some power to detect sweeps that occurred more than 10,000 generations in the past. We also applied it to 1,000 Genomes and Complete Genomics data combined with high-coverage Denisovan and Neanderthal genomes to test for sweeps in modern humans since the separation from the Neanderthal-Denisovan ancestor. We tested sites at which humans are fixed for the derived (i.e., nonchimpanzee allele) whereas the Neanderthal and Denisovan genomes are homozygous for the ancestral allele. We observe only weak differences in statistics indicative of selection between functional categories. When we compare patterns of scaled diversity or use our ABC approach, we fail to find a significant difference in signals of classic selective sweeps between regions surrounding nonsynonymous and synonymous changes, but we detect a slight enrichment for reduced scaled diversity around splice site changes. We also present a list of candidate sites that show high probability of having undergone a classic sweep in the modern human lineage since the split from Neanderthals and Denisovans.}, } @article {pmid25142605, year = {2014}, author = {Lee, A and Huntley, D and Aiewsakun, P and Kanda, RK and Lynn, C and Tristem, M}, title = {Novel Denisovan and Neanderthal retroviruses.}, journal = {Journal of virology}, volume = {88}, number = {21}, pages = {12907-12909}, pmid = {25142605}, issn = {1098-5514}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Endogenous Retroviruses/classification/*genetics/*isolation & purification ; Female ; Fossils/*virology ; Genome ; Hominidae/*virology ; }, abstract = {Following the recent availability of high-coverage genomes for Denisovan and Neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported HERV-K(HML2) elements (HERV-K is human endogenous retrovirus K). These elements are absent from the human genome (hg38) and appear to be unique to archaic hominids. These findings provide further evidence supporting the recent activity of the HERV-K(HML2) group, which has been implicated in human disease. They will also provide insights into the evolution of archaic hominids.}, } @article {pmid25110108, year = {2014}, author = {Malyarchuk, B and Derenko, M and Denisova, G}, title = {A mitogenomic phylogeny and genetic history of sable (Martes zibellina).}, journal = {Gene}, volume = {550}, number = {1}, pages = {56-67}, doi = {10.1016/j.gene.2014.08.015}, pmid = {25110108}, issn = {1879-0038}, mesh = {Animals ; Asia ; Bayes Theorem ; Cytochromes b/genetics ; DNA, Mitochondrial/chemistry/classification/*genetics ; Europe ; Evolution, Molecular ; Genetic Variation ; Genetics, Population ; Genome, Mitochondrial/*genetics ; Geography ; Molecular Sequence Data ; Mustelidae/*genetics ; NADH Dehydrogenase/genetics ; *Phylogeny ; Selection, Genetic ; Sequence Analysis, DNA ; Time Factors ; }, abstract = {We assessed phylogeny of sable (Martes zibellina, Linnaeus, 1758) by sequence analysis of nearly complete, new mitochondrial genomes in 36 specimens from different localities in northern Eurasia (Primorye, Khabarovsk and Krasnoyarsk regions, the Kamchatka Peninsula, the Kuril Islands and the Urals). Phylogenetic analysis of mtDNA sequences demonstrates that two clades, A and BC, radiated about 200-300 thousandyears ago (kya) according to results of Bayesian molecular clock and RelTime analyses of different mitogenome alignments (nearly complete mtDNA sequences, protein-coding region, and synonymous sites), while the age estimates of clades A, B and C fall within the Late Pleistocene (~50-140 kya). Bayesian skyline plots (BSPs) of sable population size change based on analysis of nearly complete mtDNAs show an expansion around 40 kya in the warm Karganian time, without a decline of population size around the Last Glacial Maximum (21 kya). The BSPs based on synonymous clock rate indicate that M. zibellina experienced demographic expansions later, approximately 22 kya. The A2a clade that colonized Kamchatka ~23-50 kya (depending on the mutation rate used) survived the last glaciation there as demonstrated by the BSP analysis. In addition, we have found evidence of positive selection acting at ND4 and cytochrome b genes, thereby suggesting adaptive evolution of the A2a clade in Kamchatka.}, } @article {pmid25073341, year = {2014}, author = {Petrov, AG and Denisova, SV and Odintseva, OV and Raudina, SN}, title = {[Methodologic approaches to farmacologic economic analysis of actual inpatient treatment of occupational diseases].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {2}, pages = {42-45}, pmid = {25073341}, issn = {1026-9428}, mesh = {Hearing Loss, Sensorineural/drug therapy/economics ; *Hospitalization/economics/statistics & numerical data ; Humans ; Models, Statistical ; *Occupational Diseases/drug therapy/economics ; }, abstract = {To improve miners' health nowadays, effective application of available means and implication of economic management methods are necessary, as quality medical and pharmaceutic care for miners requires significant financial, material and working efforts both from the government and from every institution operating in health care.}, } @article {pmid25051667, year = {2014}, author = {Katamanova, EV and Shevchenko, OI and Lakhman, OL and Denisova, IA}, title = {[Cognitive disorders in patients with chronic mercury intoxication].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {4}, pages = {7-12}, pmid = {25051667}, issn = {1026-9428}, mesh = {Cognition Disorders/classification/etiology/*physiopathology ; Humans ; Male ; Mercury Poisoning, Nervous System/complications/*physiopathology ; Middle Aged ; Occupational Diseases/chemically induced/*physiopathology ; Occupational Exposure/*adverse effects ; Severity of Illness Index ; }, abstract = {To assess severity of cognitive disorders in chronic mercury intoxication, the authors performed claster and discrimination analysis of neuropsychologic and neurophysiologic research data from workers exposed to mercury during long length of service, from patients with early and marked stages of chronic mercurial intoxication. Cognitive disorders in chronic mercurial intoxication have three severity degrees, in the light degree disorders patients demonstrate lower amplitude of cognitive evoked potentials, poor long-term memory and associative thinking. Moderate cognitive disorders are characterized by decreased visual, long-term memory, concentration of attention, poor optic and spatial gnosis. Marked cognitive disorders with chronic mercurial intoxication present with more decreased long-term, short-term, picturesque memory, poor intellect, optic and spatial gnosis and associative thinking.}, } @article {pmid25043523, year = {2014}, author = {Jorner, K and Emanuelsson, R and Dahlstrand, C and Tong, H and Denisova, AV and Ottosson, H}, title = {Impact of ground- and excited-state aromaticity on cyclopentadiene and silole excitation energies and excited-state polarities.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {20}, number = {30}, pages = {9295-9303}, doi = {10.1002/chem.201402577}, pmid = {25043523}, issn = {1521-3765}, abstract = {A new qualitative model for estimating the properties of substituted cyclopentadienes and siloles in their lowest ππ* excited states is introduced and confirmed through quantum chemical calculations, and then applied to explain earlier reported experimental excitation energies. According to our model, which is based on excited-state aromaticity and antiaromaticity, siloles and cyclopentadienes are cross-hyperconjugated "aromatic chameleons" that adapt their electronic structures to conform to the various aromaticity rules in different electronic states (Hückel's rule in the π(2) electronic ground state (S0) and Baird's rule in the lowest ππ* excited singlet and triplet states (S1 and T1)). By using pen-and-paper arguments, one can explain polarity changes upon excitation of substituted cyclopentadienes and siloles, and one can tune their lowest excitation energies by combined considerations of ground- and excited-state aromaticity/antiaromaticity effects. Finally, the "aromatic chameleon" model can be extended to other monocyclic compound classes of potential use in organic electronics, thereby providing a unified view of the S0, T1, and S1 states of a range of different cyclic cross-π-conjugated and cross-hyperconjugated compound classes.}, } @article {pmid25043035, year = {2014}, author = {Huerta-Sánchez, E and Jin, X and Asan, and Bianba, Z and Peter, BM and Vinckenbosch, N and Liang, Y and Yi, X and He, M and Somel, M and Ni, P and Wang, B and Ou, X and Huasang, and Luosang, J and Cuo, ZX and Li, K and Gao, G and Yin, Y and Wang, W and Zhang, X and Xu, X and Yang, H and Li, Y and Wang, J and Wang, J and Nielsen, R}, title = {Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA.}, journal = {Nature}, volume = {512}, number = {7513}, pages = {194-197}, pmid = {25043035}, issn = {1476-4687}, support = {R01 HG003229/HG/NHGRI NIH HHS/United States ; R01HG003229-08S2/HG/NHGRI NIH HHS/United States ; R01HG003229/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; *Altitude ; Animals ; Asian People/genetics ; Basic Helix-Loop-Helix Transcription Factors/genetics ; DNA/*genetics ; Gene Frequency ; *Genetic Variation ; Haplotypes ; Hominidae/*genetics ; Humans ; Polymorphism, Single Nucleotide ; Tibet ; }, abstract = {As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.}, } @article {pmid25001002, year = {2014}, author = {Schwartz, JJ and Roach, DJ and Thomas, JH and Shendure, J}, title = {Primate evolution of the recombination regulator PRDM9.}, journal = {Nature communications}, volume = {5}, number = {}, pages = {4370}, pmid = {25001002}, issn = {2041-1723}, support = {R01 HG006283/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; HG006283/HG/NHGRI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *Evolution, Molecular ; Genetic Variation ; Histone-Lysine N-Methyltransferase/*genetics ; Molecular Sequence Data ; Primates/*genetics ; Selection, Genetic ; Sequence Analysis, DNA ; Zinc Fingers ; }, abstract = {The PRDM9 gene encodes a protein with a highly variable tandem-repeat zinc finger (ZF) DNA-binding domain that plays a key role in determining sequence-specific hotspots of meiotic recombination genome wide. Here we survey the diversity of the PRDM9 ZF domain by sequencing this region in 64 primates from 18 species, revealing 68 unique alleles across all groups. We report ubiquitous positive selection at nucleotide positions corresponding to DNA contact residues and the expansion of ZFs within clades, which confirms the rapid evolution of the ZF domain throughout the primate lineage. Alignment of Neandertal and Denisovan sequences suggests that PRDM9 in archaic hominins was closely related to present-day human alleles that are rare and specific to African populations. In the context of its role in reproduction, our results are consistent with variation in PRDM9 contributing to speciation events in primates.}, } @article {pmid24952670, year = {2014}, author = {Taylor, JS}, title = {Did Neanderthals and Denisovans have our de novo genes?.}, journal = {Journal of molecular evolution}, volume = {78}, number = {6}, pages = {321-323}, pmid = {24952670}, issn = {1432-1432}, mesh = {Alleles ; Animals ; Gene Duplication ; Neanderthals/*genetics ; Species Specificity ; }, } @article {pmid24845746, year = {2014}, author = {Denisova, K and Kibbe, MM and Cholewiak, SA and Kim, SH}, title = {Intra- and intermanual curvature aftereffect can be obtained via tool-touch.}, journal = {IEEE transactions on haptics}, volume = {7}, number = {1}, pages = {61-66}, doi = {10.1109/TOH.2013.63}, pmid = {24845746}, issn = {2329-4051}, mesh = {Adult ; Feedback, Sensory/*physiology ; Female ; Humans ; Male ; Space Perception/*physiology ; Touch Perception/*physiology ; }, abstract = {We examined the perception of virtual curved surfaces explored with a tool. We found a reliable curvature aftereffect, suggesting neural representation of the curvature in the absence of direct touch. Intermanual transfer of the aftereffect suggests that this representation is somewhat independent of the hand used to explore the surface.}, } @article {pmid24832686, year = {2014}, author = {Wong, LP and Lai, JK and Saw, WY and Ong, RT and Cheng, AY and Pillai, NE and Liu, X and Xu, W and Chen, P and Foo, JN and Tan, LW and Koo, SH and Soong, R and Wenk, MR and Lim, WY and Khor, CC and Little, P and Chia, KS and Teo, YY}, title = {Insights into the genetic structure and diversity of 38 South Asian Indians from deep whole-genome sequencing.}, journal = {PLoS genetics}, volume = {10}, number = {5}, pages = {e1004377}, pmid = {24832686}, issn = {1553-7404}, mesh = {*Genetic Variation ; *Genetics, Population ; *Genome, Human ; Haplotypes ; Humans ; India ; Polymorphism, Single Nucleotide ; }, abstract = {South Asia possesses a significant amount of genetic diversity due to considerable intergroup differences in culture and language. There have been numerous reports on the genetic structure of Asian Indians, although these have mostly relied on genotyping microarrays or targeted sequencing of the mitochondria and Y chromosomes. Asian Indians in Singapore are primarily descendants of immigrants from Dravidian-language-speaking states in south India, and 38 individuals from the general population underwent deep whole-genome sequencing with a target coverage of 30X as part of the Singapore Sequencing Indian Project (SSIP). The genetic structure and diversity of these samples were compared against samples from the Singapore Sequencing Malay Project and populations in Phase 1 of the 1,000 Genomes Project (1 KGP). SSIP samples exhibited greater intra-population genetic diversity and possessed higher heterozygous-to-homozygous genotype ratio than other Asian populations. When compared against a panel of well-defined Asian Indians, the genetic makeup of the SSIP samples was closely related to South Indians. However, even though the SSIP samples clustered distinctly from the Europeans in the global population structure analysis with autosomal SNPs, eight samples were assigned to mitochondrial haplogroups that were predominantly present in Europeans and possessed higher European admixture than the remaining samples. An analysis of the relative relatedness between SSIP with two archaic hominins (Denisovan, Neanderthal) identified higher ancient admixture in East Asian populations than in SSIP. The data resource for these samples is publicly available and is expected to serve as a valuable complement to the South Asian samples in Phase 3 of 1 KGP.}, } @article {pmid24786081, year = {2014}, author = {Gokhman, D and Lavi, E and Prüfer, K and Fraga, MF and Riancho, JA and Kelso, J and Pääbo, S and Meshorer, E and Carmel, L}, title = {Reconstructing the DNA methylation maps of the Neandertal and the Denisovan.}, journal = {Science (New York, N.Y.)}, volume = {344}, number = {6183}, pages = {523-527}, doi = {10.1126/science.1250368}, pmid = {24786081}, issn = {1095-9203}, mesh = {Animals ; *DNA Methylation ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Genome, Human ; Humans ; Neanderthals/*genetics ; }, abstract = {Ancient DNA sequencing has recently provided high-coverage archaic human genomes. However, the evolution of epigenetic regulation along the human lineage remains largely unexplored. We reconstructed the full DNA methylation maps of the Neandertal and the Denisovan by harnessing the natural degradation processes of methylated and unmethylated cytosines. Comparing these ancient methylation maps to those of present-day humans, we identified ~2000 differentially methylated regions (DMRs). Particularly, we found substantial methylation changes in the HOXD cluster that may explain anatomical differences between archaic and present-day humans. Additionally, we found that DMRs are significantly more likely to be associated with diseases. This study provides insight into the epigenetic landscape of our closest evolutionary relatives and opens a window to explore the epigenomes of extinct species.}, } @article {pmid24772099, year = {2014}, author = {Boeckx, C and Benítez-Burraco, A}, title = {The shape of the human language-ready brain.}, journal = {Frontiers in psychology}, volume = {5}, number = {}, pages = {282}, pmid = {24772099}, issn = {1664-1078}, abstract = {Our core hypothesis is that the emergence of our species-specific language-ready brain ought to be understood in light of the developmental changes expressed at the levels of brain morphology and neural connectivity that occurred in our species after the split from Neanderthals-Denisovans and that gave us a more globular braincase configuration. In addition to changes at the cortical level, we hypothesize that the anatomical shift that led to globularity also entailed significant changes at the subcortical level. We claim that the functional consequences of such changes must also be taken into account to gain a fuller understanding of our linguistic capacity. Here we focus on the thalamus, which we argue is central to language and human cognition, as it modulates fronto-parietal activity. With this new neurobiological perspective in place, we examine its possible molecular basis. We construct a candidate gene set whose members are involved in the development and connectivity of the thalamus, in the evolution of the human head, and are known to give rise to language-associated cognitive disorders. We submit that the new gene candidate set opens up new windows into our understanding of the genetic basis of our linguistic capacity. Thus, our hypothesis aims at generating new testing grounds concerning core aspects of language ontogeny and phylogeny.}, } @article {pmid24752266, year = {2014}, author = {Denisova, OV and Söderholm, S and Virtanen, S and Von Schantz, C and Bychkov, D and Vashchinkina, E and Desloovere, J and Tynell, J and Ikonen, N and Theisen, LL and Nyman, TA and Matikainen, S and Kallioniemi, O and Julkunen, I and Muller, CP and Saelens, X and Verkhusha, VV and Kainov, DE}, title = {Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.}, journal = {Antimicrobial agents and chemotherapy}, volume = {58}, number = {7}, pages = {3689-3696}, pmid = {24752266}, issn = {1098-6596}, mesh = {Cell Line ; Cytokines/metabolism ; Heterocyclic Compounds, 3-Ring/*pharmacology ; Host-Pathogen Interactions/drug effects ; Humans ; In Vitro Techniques ; *Influenza A Virus, H1N1 Subtype ; Influenza, Human/*prevention & control/virology ; Molecular Sequence Data ; Oncogene Protein v-akt/*antagonists & inhibitors ; Phosphoproteins/metabolism ; Protease Inhibitors/*pharmacology ; RNA, Small Interfering/genetics ; Transfection ; Viral Plaque Assay ; }, abstract = {The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.}, } @article {pmid24706482, year = {2014}, author = {Orlando, L}, title = {A 400,000-year-old mitochondrial genome questions phylogenetic relationships amongst archaic hominins: using the latest advances in ancient genomics, the mitochondrial genome sequence of a 400,000-year-old hominin has been deciphered.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {6}, pages = {598-605}, doi = {10.1002/bies.201400018}, pmid = {24706482}, issn = {1521-1878}, mesh = {Animals ; Base Sequence ; DNA Damage/genetics ; Genome, Mitochondrial/*genetics ; Genomics/*methods ; Hominidae/*genetics ; *Phylogeny ; Time Factors ; }, abstract = {By combining state-of-the-art approaches in ancient genomics, Meyer and co-workers have reconstructed the mitochondrial sequence of an archaic hominin that lived at Sierra de Atapuerca, Spain about 400,000 years ago. This achievement follows recent advances in molecular anthropology that delivered the genome sequence of younger archaic hominins, such as Neanderthals and Denisovans. Molecular phylogenetic reconstructions placed the Atapuercan as a sister group to Denisovans, although its morphology suggested closer affinities with Neanderthals. In addition to possibly challenging our interpretation of the fossil record, this study confirms that genomic information can be recovered from extremely damaged DNA molecules, even in the presence of significant levels of human contamination. Together with the recent characterization of a 700,000-year-old horse genome, this study opens the Middle Pleistocene to genomics, thereby extending the scope of ancient DNA to the last million years.}, } @article {pmid24667833, year = {2014}, author = {Sazzini, M and Schiavo, G and De Fanti, S and Martelli, PL and Casadio, R and Luiselli, D}, title = {Searching for signatures of cold adaptations in modern and archaic humans: hints from the brown adipose tissue genes.}, journal = {Heredity}, volume = {113}, number = {3}, pages = {259-267}, pmid = {24667833}, issn = {1365-2540}, mesh = {*Adaptation, Physiological/genetics ; *Adipose Tissue, Brown/metabolism ; Alleles ; Biological Evolution ; Climate ; Cold Temperature ; Fossils ; *Genome/genetics ; *Thermogenesis/genetics ; Humans ; }, abstract = {Adaptation to low temperatures has been reasonably developed in the human species during the colonization of the Eurasian landmass subsequent to Out of Africa migrations of anatomically modern humans. In addition to morphological and cultural changes, also metabolic ones are supposed to have favored human isolation from cold and body heat production and this can be hypothesized also for most Neandertal and at least for some Denisovan populations, which lived in geographical areas that strongly experienced the last glacial period. Modulation of non-shivering thermogenesis, for which adipocytes belonging to the brown adipose tissue are the most specialized cells, might have driven these metabolic adaptations. To perform an exploratory analysis aimed at looking into this hypothesis, variation at 28 genes involved in such functional pathway was investigated in modern populations from different climate zones, as well as in Neandertal and Denisovan genomes. Patterns of variation at the LEPR gene, strongly related to increased heat dissipation by mitochondria, appeared to have been shaped by positive selection in modern East Asians, but not in Europeans. Moreover, a single potentially cold-adapted LEPR allele, different from the supposed adaptive one identified in Homo sapiens, was found also in Neandertal and Denisovan genomes. These findings suggest that independent mechanisms for cold adaptations might have been developed in different non-African human groups, as well as that the evolution of possible enhanced thermal efficiency in Neandertals and in some Denisovan populations has plausibly entailed significant changes also in other functional pathways than in the examined one.}, } @article {pmid24599118, year = {2014}, author = {Mariotti, M and Smith, TF and Sudmant, PH and Goldberger, G}, title = {Pseudogenization of testis-specific Lfg5 predates human/Neanderthal divergence.}, journal = {Journal of human genetics}, volume = {59}, number = {5}, pages = {288-291}, pmid = {24599118}, issn = {1435-232X}, mesh = {Animals ; *Evolution, Molecular ; Exons ; Genomics ; Humans ; Introns ; Male ; Multigene Family ; Mutation ; Neanderthals/*genetics ; Organ Specificity/*genetics ; Phylogeny ; Testis/*metabolism ; }, abstract = {Recent reviews discussed the critical roles of apoptosis in human spermatogenesis and infertility. These reviews highlight the FasL-induced caspase cascade in apoptosis lending importance to our discovery of the pseudogene status of the Lfg5 gene in modern humans, Neanderthal and the Denisovan. This gene is a member of the ancient and highly conserved apoptosis Lifeguard family. This pseudogenization is the result of a premature stop codon at the 3'-end of exon 8 not found in any other ortholog. With the current exception of the domesticated bovine and buffalo, Lfg5's expression in mammals is testis-specific. A full analysis of this gene, its phylogenetic context and its recent hominin changes suggest its inactivation was likely under selection in human evolution.}, } @article {pmid24501955, year = {2013}, author = {Agafonova, EV and Malanicheva, TG and Denisova, SN}, title = {[Subpopulations and phagocytic activity of monocytes in chronic gastroduodenitis in children].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {5}, pages = {108-111}, pmid = {24501955}, issn = {1682-8658}, mesh = {Adolescent ; Candida/*immunology ; Candidiasis/*immunology ; Child ; Child, Preschool ; Duodenitis/*immunology ; Female ; Gastritis/*immunology ; Helicobacter Infections ; Helicobacter pylori/*immunology ; Humans ; Male ; Monocytes/*immunology ; Phagocytosis/*immunology ; }, abstract = {There was conducted a study of the phagocytic activity, immunophenotype and peripheral blood monocytes by flow cytometry in children with chronic gastroduodenitis associated with Helicobacter pylori, as well as the association of Helicobacter pylori with fungi of the genus Candida and markers of secondary immune deficiency. The differential changes in the structure of circulating profile of monocytes were revealed, that indicate the pathogenetic significance of these disorders in chronic gastroduodenitis with H. pylori etiology, as well as at association of Helicobacter pylori with fungi of the genus Candida. Violations of the phagocytic activity of monocytes in chronic gastroduodenitis in children are associated with depression of different stages of phagocytosis--capture functions, mobilization, killing, intracellular biocidity. A severe depression in phagocytic activity of monocytes occurs in CGD associated with Hp and fungi of the genus Candida.}, } @article {pmid24450152, year = {2013}, author = {Malyarchuk, BA and Denisova, GA and Derenko, MV}, title = {[Peculiarities of phosphoglycerate kinase-1 pseudogene evolution in Schrenck salamander (Salamandrella schrenckii Strauch, 1870)].}, journal = {Genetika}, volume = {49}, number = {7}, pages = {830-837}, doi = {10.7868/s0016675813070102}, pmid = {24450152}, issn = {0016-6758}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Molecular Sequence Data ; Phosphoglycerate Kinase/*genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Pseudogenes/*genetics ; Urodela/*genetics ; }, abstract = {Processed copies of genes generally evolve in neutral mode as pseudogenes, however, some of them might be important sources of new functional genes. The psiPGK1 pseudogene has been discovered in Schrenck salamander (Salamandrella schrenckii, Amphibia, Caudata, Hynobiidae) via polymerase chain reaction used to amplify the phosphoglycerate kinase 1 gene (PGK1). This pseudogene is an intronless copy of PGK1 gene absent of exon 6. Analysis of psiPGK1 pseudogene polymorphism has demonstrated that it lacks mutations, which results in shifts in the stop codons and reading frames, as well as that the interspecies variation of this pseudogene was inconsistent with the neutral model of evolution. In addition, the pattern of phylogeographic differentiation of the psiPGK1 variants mainly coincides with that observed in mitochondrial DNA. These observations allow it to be suggested that the psiPGK1 pseudogene is a new functional gene in the Schrenck salamander.}, } @article {pmid24392153, year = {2014}, author = {Hughes, GM and Teeling, EC and Higgins, DG}, title = {Loss of olfactory receptor function in hominin evolution.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e84714}, pmid = {24392153}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Databases, Nucleic Acid ; Evolution, Molecular ; Genome ; Genomics ; Hominidae/*genetics ; Humans ; Molecular Sequence Data ; Multigene Family ; Olfactory Receptor Neurons/*metabolism ; Phylogeny ; Receptors, Odorant/chemistry/classification/*genetics ; Sequence Alignment ; }, abstract = {The mammalian sense of smell is governed by the largest gene family, which encodes the olfactory receptors (ORs). The gain and loss of OR genes is typically correlated with adaptations to various ecological niches. Modern humans have 853 OR genes but 55% of these have lost their function. Here we show evidence of additional OR loss of function in the Neanderthal and Denisovan hominin genomes using comparative genomic methodologies. Ten Neanderthal and 8 Denisovan ORs show evidence of loss of function that differ from the reference modern human OR genome. Some of these losses are also present in a subset of modern humans, while some are unique to each lineage. Morphological changes in the cranium of Neanderthals suggest different sensory arrangements to that of modern humans. We identify differences in functional olfactory receptor genes among modern humans, Neanderthals and Denisovans, suggesting varied loss of function across all three taxa and we highlight the utility of using genomic information to elucidate the sensory niches of extinct species.}, } @article {pmid25929022, year = {2014}, author = {Pogozheva, AV and Sorokina, EY and Baturin, AK and Peskova, EV and Makurina, ON and Levin, LG and Soto, SKh and Aristarkhova, TA and Korosteleva, MM and Denisova, NN and Solntseva, TN and Aleshina, IV and Toboleva, MA and Redzyuk, LA and Polyakova, AV}, title = {[The role of the Consultative and Diagnostic Centre "Healthy Nutrition" in the diagnosis and nutritional prevention of non-communicable diseases].}, journal = {Voprosy pitaniia}, volume = {83}, number = {6}, pages = {52-57}, pmid = {25929022}, issn = {0042-8833}, mesh = {Body Mass Index ; Diabetes Mellitus, Type 2/blood/*diagnosis/genetics/*prevention & control ; Energy Intake ; Female ; Humans ; Male ; *Nutritional Status ; Obesity/blood/*diagnosis/genetics/*prevention & control ; Polymorphism, Genetic ; }, abstract = {In a consultative and diagnostic center "Healthy Nutrition" of Institute of Nutrition the nutritional status of 3500 patients (mean age 48.4 ± 0.3 years) liv- ing in the Moscow region, using a system Nutritest IP-3, including genomic analysis has been examined. In the analysis of dietary intake by an average review, increased energy intake due to excess intake of the total (44.2% energy) and saturated fat (13.6%) has been shown. 30.0% of patients were overweight and 34.1% were obese. Osteopenia was detected in 31.0% of men and 25.0% women, osteoporosis--20.9% and 30.3%, respectively. Analysis of the results of biochemical studies revealed increased cholesterol in 68.7% of patients, LDL cholesterol--at 63.9%, triglycerides-- at 22.5%, glucose--at 29.4%. The frequency of the occurrence of risk alleles of genes associated with the development of obesity and type 2 diabetes mellitus was: 47.8%--for the polymorphism rs9939609 (FTO gene), 8.3%--for polymorphism rs4994 (gene ADRB3), 60.2%--for the polymorphism rs659366 (gene UCP2), 36.6%--for the rs5219 polymorphism in the gene of ATP-dependent potassium channel.}, } @article {pmid25845144, year = {2014}, author = {Isaeva, NA and Torubarov, FS and Denisova, EA and Zvereva, ZF and Koronotova, MA}, title = {[Evaluating psychophysiologic adaptation state in operators of Bilibino nuclear power station].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {11}, pages = {16-20}, pmid = {25845144}, issn = {1026-9428}, mesh = {Adaptation, Physiological/*physiology ; Adaptation, Psychological/*physiology ; Adult ; Humans ; Middle Aged ; Neuropsychological Tests ; *Nuclear Power Plants ; Occupational Diseases/epidemiology/*physiopathology/psychology ; Occupational Exposure/analysis ; Psychophysiologic Disorders/epidemiology/*physiopathology/psychology ; Russia ; }, abstract = {The study revealed that 60% operators of Bilibino nuclear power station suffer from psychosomatic diseases, 41.7% of them are assigned to occupational group of workers, and major part of the examinees with psychosomatic diseases (45.82%) are aged 41-50, high integral level ofpsychophysiologic adaptation is revealed in 5 examinees (12.5%), medium integral level--in 12 examinees (30%). Lower integral level of psychophysiologic adaptation manifested in decrease in psychophysiologic and physiologic levels.}, } @article {pmid25816630, year = {2014}, author = {Shostak, NA and Muradiants, AA and Kondrashov, AA and Denisova, SN}, title = {[Clinical efficacy instant goat milk in the complex therapy and prevention of osteoporosis in patients with rheumatoid arthritis].}, journal = {Voprosy pitaniia}, volume = {83}, number = {5}, pages = {79-85}, pmid = {25816630}, issn = {0042-8833}, mesh = {Animals ; Arthritis, Rheumatoid/*blood/*prevention & control ; Calcifediol/blood ; Calcitriol/blood ; Calcium/blood ; Female ; *Goats ; Humans ; Male ; Middle Aged ; *Milk ; Osteoporosis, Postmenopausal/*blood/*prevention & control ; Phosphorus/blood ; }, abstract = {Osteoporosis (OP) in rheumatoid arthritis (RA) refers to a secondary immune-mediated metabolic osteopathy characterized by periarticular and systemic decreased bone mass, impaired bone strength and increased risk of fractures. According to some studies, adding milk in the diet helps to increase bone mineral density and to reduce the risk of osteoporosis and maintain normal levels of vitamin D. To study the state of mineral and bone metabolism in RA patients zeith osteopenic syndrome and to evaluate the effectiveness of treatment and prevention of OP by adding dry goat milk "Amalteya" in the diet. The study included 42 patients with a documented diagnosis of RA (ACR, 1987) - 23 men (mean age 59 years) and 19 postmenopausal women (mean age 62 years) with the presence of osteoporosis and osteopenia according to the dual-energy X-ray absorptiometry. 21 (50%) RA patients (main group) received standard antiosteoporotichesky (alendronate 70 mg/week + calcium 1000 mg/day + Vitamin D3 800 IU/day) therapy and milk powder Amalteya® (400 ml/day). The control group (21 patients with RA) received only standard antiosteoporotic therapy. Follow-up lasted for 6 months. The concentration of total calcium in the blood of RA patients was on average 2.33 mmol/l, ionized Ca - 1,18 mmol/l and inorganic P - 1,09 mmol/l, which corresponds to normal values. Vitamin D deficiency was found in 17,5% of patients, and failure - in 32,5% of patients with RA. After 6 months of the treatment it was found that b-CrossLaps levels tend to be reducing in both of the groups and with reduction of bone formation marker osteocalcin in the group not receiving goat milk. Also, due to the background of ongoing combinative therapy it was clear that concentrations of 1,25(OH)2D and 25(OH)D in the blood serum are increasing (by 18,5-28,2% at the main group and by 8,0-17,9% at the control group), however, inter-group differences was below the level of the reliable importance. It was strongly marked in the group who received goat's milk "Amalteya®". Reduced levels of vitamin D in the blood is typical for 50% of RA patients with osteopenic syndrome with normal values of calcium-phosphorus metabolism. Combination therapy and prevention of osteoporosis in patients with RA with an additional inclusion in the diet of the daily administration of 400 ml of goat's milk Amalthea® has a positive impact on bone metabolism.}, } @article {pmid25799827, year = {2014}, author = {Vizel', IIu and Shmelev, EI and Baranova, OP and Barlamov, PN and Borodina, GL and Denisova, OA and Dobin, VL and Kulbaisov, AM and Kupaev, VI and Listopadova, MV and Ovsiannikov, NV and Os'kin, DN and Petrov, DV and Solov'ev, KI and Shul'zhenko, LV and Vizel', AA}, title = {[Multicenter retrospective analysis of the patients with sarcoidosis with a 10 year interval in observations].}, journal = {Klinicheskaia meditsina}, volume = {92}, number = {6}, pages = {28-34}, pmid = {25799827}, issn = {0023-2149}, mesh = {Adult ; Antitubercular Agents/*therapeutic use ; Disease-Free Survival ; Female ; Glucocorticoids/*therapeutic use ; Humans ; Lung/diagnostic imaging ; Male ; Patient Acuity ; Prognosis ; Radiography ; Recurrence ; Respiratory Function Tests/methods ; Risk Factors ; Russia/epidemiology ; *Sarcoidosis/diagnosis/epidemiology/physiopathology/therapy ; }, abstract = {Comparison of the state of 83 patients with histologically confirmed sarcoidosis observed with a 10 year interval revealed remission in 47% of the cases. The main factors having negative effect on prognosis of the disease included extrapulmonary symptoms, the use ofcorticosteroids (at all stages, especially at stage I and in Lofgren syndrome) and antituberculosis drugs, positive TB test. Risk factors of relapses were stage II sarcoidosis, the use of systemic corticosteroids in patients with Lofgren syndrome and antituberculosis drugs, initially low FEV1/FVLC ratio and the number of lymphocytes in peripheral blood.}, } @article {pmid25734313, year = {2014}, author = {Mazur, EM and Soldatskiĭ, IL and Ivanenko, AM and Denisova, OA and Severin, TV}, title = {[Foreign bodies (disk batteries) in the nose].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {6}, pages = {64-65}, doi = {10.17116/otorino2014664-65}, pmid = {25734313}, issn = {0042-4668}, mesh = {Child, Preschool ; Electric Power Supplies/*adverse effects ; Female ; *Foreign Bodies ; Humans ; Male ; Nose/*injuries ; }, abstract = {This paper reports the results of analysis of the treatment of 8 children after the removal a disk battery from the nasal cavity. It was shown that the restoration of all the structures of the nasal cavity is possible if the foreign body remains in it during a short (up to 5 hours) time. The longer presence of such a body in the nasal cavity gives rise to post-traumatic defects, in the first place septal perforations and injuries to the inferior turbinated bone. In such cases, the foreign body must be immediately removed from the nasal cavity, and the child should be placed under thorough medical observation taking into consideration the long process of rejection of necrotic tissues and healing of the resulting defects.}, } @article {pmid24367647, year = {2013}, author = {Reno, PL and McLean, CY and Hines, JE and Capellini, TD and Bejerano, G and Kingsley, DM}, title = {A penile spine/vibrissa enhancer sequence is missing in modern and extinct humans but is retained in multiple primates with penile spines and sensory vibrissae.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e84258}, pmid = {24367647}, issn = {1932-6203}, support = {RR016483/RR/NCRR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; RR014491/RR/NCRR NIH HHS/United States ; U42 RR015087/RR/NCRR NIH HHS/United States ; C06 RR016483/RR/NCRR NIH HHS/United States ; C06 RR014491/RR/NCRR NIH HHS/United States ; P50 HG002568/HG/NHGRI NIH HHS/United States ; 5P50HG2568/HG/NHGRI NIH HHS/United States ; RR015087/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Enhancer Elements, Genetic/*genetics ; *Extinction, Biological ; Genome, Human/genetics ; Humans ; Male ; Molecular Sequence Data ; Penis/*metabolism ; Primates/*genetics ; Receptors, Androgen/*genetics ; Sequence Analysis ; Somatosensory Cortex/physiology ; Species Specificity ; Vibrissae/*metabolism/physiology ; }, abstract = {Previous studies show that humans have a large genomic deletion downstream of the Androgen Receptor gene that eliminates an ancestral mammalian regulatory enhancer that drives expression in developing penile spines and sensory vibrissae. Here we use a combination of large-scale sequence analysis and PCR amplification to demonstrate that the penile spine/vibrissa enhancer is missing in all humans surveyed and in the Neandertal and Denisovan genomes, but is present in DNA samples of chimpanzees and bonobos, as well as in multiple other great apes and primates that maintain some form of penile integumentary appendage and facial vibrissae. These results further strengthen the association between the presence of the penile spine/vibrissa enhancer and the presence of penile spines and macro- or micro- vibrissae in non-human primates as well as show that loss of the enhancer is both a distinctive and characteristic feature of the human lineage.}, } @article {pmid24352235, year = {2014}, author = {Prüfer, K and Racimo, F and Patterson, N and Jay, F and Sankararaman, S and Sawyer, S and Heinze, A and Renaud, G and Sudmant, PH and de Filippo, C and Li, H and Mallick, S and Dannemann, M and Fu, Q and Kircher, M and Kuhlwilm, M and Lachmann, M and Meyer, M and Ongyerth, M and Siebauer, M and Theunert, C and Tandon, A and Moorjani, P and Pickrell, J and Mullikin, JC and Vohr, SH and Green, RE and Hellmann, I and Johnson, PL and Blanche, H and Cann, H and Kitzman, JO and Shendure, J and Eichler, EE and Lein, ES and Bakken, TE and Golovanova, LV and Doronichev, VB and Shunkov, MV and Derevianko, AP and Viola, B and Slatkin, M and Reich, D and Kelso, J and Pääbo, S}, title = {The complete genome sequence of a Neanderthal from the Altai Mountains.}, journal = {Nature}, volume = {505}, number = {7481}, pages = {43-49}, pmid = {24352235}, issn = {1476-4687}, support = {R01-GM40282/GM/NIGMS NIH HHS/United States ; R01 GM100233/GM/NIGMS NIH HHS/United States ; R01 GM040282/GM/NIGMS NIH HHS/United States ; HG002385/HG/NHGRI NIH HHS/United States ; HG006283/HG/NHGRI NIH HHS/United States ; GM100233/GM/NIGMS NIH HHS/United States ; R01 HG006283/HG/NHGRI NIH HHS/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Africa ; Animals ; Caves ; DNA Copy Number Variations/genetics ; Female ; *Fossils ; Gene Flow/genetics ; Gene Frequency ; Genome/*genetics ; Heterozygote ; Humans ; Inbreeding ; Models, Genetic ; Neanderthals/classification/*genetics ; Phylogeny ; Population Density ; Siberia/ethnology ; Toe Phalanges/anatomy & histology ; }, abstract = {We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.}, } @article {pmid24349465, year = {2013}, author = {Kuhlwilm, M and Davierwala, A and Pääbo, S}, title = {Identification of putative target genes of the transcription factor RUNX2.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e83218}, pmid = {24349465}, issn = {1932-6203}, mesh = {Baculoviral IAP Repeat-Containing 3 Protein ; Core Binding Factor Alpha 1 Subunit/genetics/*metabolism ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation/*physiology ; Genes, Mitochondrial/physiology ; Genome, Mitochondrial/physiology ; HeLa Cells ; Hep G2 Cells ; Humans ; Inhibitor of Apoptosis Proteins/biosynthesis/genetics ; Osteogenesis/physiology ; Tooth/metabolism ; Ubiquitin-Protein Ligases ; }, abstract = {Comparisons of the genomes of Neandertals and Denisovans with present-day human genomes have suggested that the gene RUNX2, which encodes a transcription factor, may have been positively selected during early human evolution. Here, we overexpress RUNX2 in ten human cell lines and identify genes that are directly or indirectly affected by RUNX2 expression. We find a number of genes not previously known to be affected by RUNX2 expression, in particular BIRC3, genes encoded on the mitochondrial genome, and several genes involved in bone and tooth formation. These genes are likely to provide inroads into pathways affected by RUNX2 and potentially by the evolutionary changes that affected RUNX2 in modern humans.}, } @article {pmid24343584, year = {2014}, author = {Baklanova, YV and Denisova, TA and Maksimova, LG and Tyutyunnik, AP and Baklanova, IV and Shein, IR and Neder, RB and Tarakina, NV}, title = {Synthesis and characterisation of new MO(OH)2 (M = Zr, Hf) oxyhydroxides and related Li2MO3 salts.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {43}, number = {7}, pages = {2755-2763}, doi = {10.1039/c3dt52929k}, pmid = {24343584}, issn = {1477-9234}, abstract = {Two new solid MO(OH)2 (M = Zr, Hf) oxyhydroxides have been synthesised by an ion-exchange reaction from Li2MO3 (M = Zr, Hf) precursors obtained by a citrate combustion technique. The crystal structure of the oxyhydroxides has been solved by direct methods and refined using Rietveld full profile fitting based on X-ray powder diffraction data. Both oxyhydroxides crystallize in a P2(1)/c monoclinic unit cell and have a structure resembling that of the related salts. Detailed characterisation of the fine-structure features and chemical bonding in precursors and oxyhydroxide powders has been performed using vibrational spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, pair distribution function analysis and quantum-chemical modelling.}, } @article {pmid24336922, year = {2014}, author = {Ding, Q and Hu, Y and Xu, S and Wang, J and Jin, L}, title = {Neanderthal introgression at chromosome 3p21.31 was under positive natural selection in East Asians.}, journal = {Molecular biology and evolution}, volume = {31}, number = {3}, pages = {683-695}, doi = {10.1093/molbev/mst260}, pmid = {24336922}, issn = {1537-1719}, mesh = {Adaptation, Physiological/genetics ; Alleles ; Animals ; Asian People/*genetics ; Chromosomes, Human, Pair 3/*genetics ; Asia, Eastern ; Genetic Variation ; Geography ; Haplotypes/genetics ; Humans ; Linkage Disequilibrium/genetics ; Models, Genetic ; Neanderthals/*genetics ; Pan troglodytes/genetics ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Recombination, Genetic/genetics ; *Selection, Genetic ; Time Factors ; }, abstract = {Studies of the Neanderthal and Denisovan genomes demonstrate archaic hominin introgression in Eurasians. Here, we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans. We also detected a signal of strong positive selection in this region only in East Asians. Our data indicate that likely candidate targets of selection include rs12488302-T and its associated alleles--among which four are nonsynonymous, including rs35455589-G in HYAL2, a gene related to the cellular response to ultraviolet-B irradiation. Furthermore, suggestive evidence supports latitude-dependent selection, implicating a role of ultraviolet-B. Interestingly, the distribution of rs35455589-G suggests that this allele was lost during the exodus of ancestors of modern Eurasians from Africa and reintroduced to Eurasians from Neanderthals.}, } @article {pmid24311652, year = {2013}, author = {Gibbons, A}, title = {Human Evolution. Elusive Denisovans sighted in oldest human DNA.}, journal = {Science (New York, N.Y.)}, volume = {342}, number = {6163}, pages = {1156}, doi = {10.1126/science.342.6163.1156}, pmid = {24311652}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Bone and Bones ; *DNA, Mitochondrial ; *Fossils ; *Hominidae ; Humans ; Neanderthals ; Spain ; }, } @article {pmid24305051, year = {2014}, author = {Meyer, M and Fu, Q and Aximu-Petri, A and Glocke, I and Nickel, B and Arsuaga, JL and Martínez, I and Gracia, A and de Castro, JM and Carbonell, E and Pääbo, S}, title = {A mitochondrial genome sequence of a hominin from Sima de los Huesos.}, journal = {Nature}, volume = {505}, number = {7483}, pages = {403-406}, pmid = {24305051}, issn = {1476-4687}, mesh = {Animals ; Bayes Theorem ; Consensus Sequence/genetics ; Cytosine/metabolism ; DNA, Mitochondrial/genetics ; Deamination ; Femur/anatomy & histology/metabolism ; *Fossils ; Genome, Mitochondrial/*genetics ; Hominidae/anatomy & histology/*classification/*genetics ; Molecular Sequence Data ; Neanderthals/genetics ; *Phylogeny ; Spain ; }, abstract = {Excavations of a complex of caves in the Sierra de Atapuerca in northern Spain have unearthed hominin fossils that range in age from the early Pleistocene to the Holocene. One of these sites, the 'Sima de los Huesos' ('pit of bones'), has yielded the world's largest assemblage of Middle Pleistocene hominin fossils, consisting of at least 28 individuals dated to over 300,000 years ago. The skeletal remains share a number of morphological features with fossils classified as Homo heidelbergensis and also display distinct Neanderthal-derived traits. Here we determine an almost complete mitochondrial genome sequence of a hominin from Sima de los Huesos and show that it is closely related to the lineage leading to mitochondrial genomes of Denisovans, an eastern Eurasian sister group to Neanderthals. Our results pave the way for DNA research on hominins from the Middle Pleistocene.}, } @article {pmid24297219, year = {2013}, author = {Higham, C}, title = {Hunter-gatherers in southeast Asia: from prehistory to the present.}, journal = {Human biology}, volume = {85}, number = {1-3}, pages = {21-43}, doi = {10.3378/027.085.0302}, pmid = {24297219}, issn = {1534-6617}, mesh = {Agriculture ; Animals ; *Anthropology, Physical ; Appetitive Behavior ; Archaeology ; Asia, Southeastern ; Asian People/ethnology/*genetics ; *Biological Evolution ; Genetic Variation ; *Genetics, Population ; Geography ; Hominidae/*genetics ; Humans ; Phenotype ; Population Dynamics ; }, abstract = {Anatomically modern hunter-gatherers expanded from Africa into Southeast Asia at least 50,000 years ago, where they probably encountered and interacted with populations of Homo erectus and Homo floresiensis and the recently discovered Denisovans. Simulation studies suggest that these hunter-gatherers may well have followed a coastal route that ultimately led to the settlement of Sahul, while archaeology confirms that they also crossed significant seas and explored well into the interior. They also adapted to marked environmental changes that alternated between relatively cool and dry conditions and warmer, wetter interludes. During the former, the sea fell by up to 120 m below its present level, which opened up a vast low-lying area known as Sundaland. Three principal alignments can be identified: the first involved the occupation of rock shelters in upland regions, the second has identified settlement on broad riverine floodplains, and the last concentrated on the raised beaches formed from about five millennia ago when the sea level was elevated above its present position. This cultural sequence was dislocated about 4 kya when rice and millet farmers infiltrated the lowlands of Southeast Asia ultimately from the Yangtze River valley. It is suggested that this led to two forms of interaction. In the first, the indigenous hunter-gatherers integrated with intrusive Neolithic communities and, while losing their cultural identity, contributed their genes to the present population of Southeast Asia. In the second, hunter-gatherers withdrew to rainforest refugia and, through selective pressures inherent in such an environment, survived as the small-bodied, dark-skinned humans found to this day in the Philippines, Peninsular Malaysia and Thailand, and the Andaman Islands. Beyond the impact of expansive rice farmers in Melanesia and Australia, hunter-gatherers continued to dominate until they encountered European settlement.}, } @article {pmid24297218, year = {2013}, author = {Endicott, P}, title = {Introduction: revisiting the "negrito" hypothesis: a transdisciplinary approach to human prehistory in southeast Asia.}, journal = {Human biology}, volume = {85}, number = {1-3}, pages = {7-20}, doi = {10.3378/027.085.0301}, pmid = {24297218}, issn = {1534-6617}, mesh = {Animals ; *Anthropology, Physical ; Appetitive Behavior ; Asia, Southeastern ; Asian People/ethnology/*genetics ; *Biological Evolution ; Genetic Markers ; *Genetic Variation ; *Genetics, Population ; Hominidae/*genetics ; Humans ; Phenotype ; Population Dynamics ; }, abstract = {The "negrito" hypothesis predicts that a shared phenotype among various contemporary groups of hunter-gatherers in Southeast Asia--dark skin, short stature, tight curly hair--is due to common descent from a region-wide, pre-Neolithic substrate of humanity. The alternative is that their distinctive phenotype results from convergent evolution. The core issues of the negrito hypothesis are today more relevant than ever to studies of human evolution, including the out-of-Africa migration, admixture with Denisovans, and the effects of environment and ecology on life-history traits. Understanding the current distribution of the negrito phenotype dictates a wide-ranging remit for study, including the articulation of the relationship between foragers and farmers in the present, the development of settled agriculture in the mid-Holocene, and terminal Pleistocene population expansions. The consensus reached by the contributors to this special double issue of Human Biology is that there is not yet conclusive evidence either for or against the negrito hypothesis. Nevertheless, the process of revisiting the problem will benefit the knowledge of the human prehistory of Southeast Asia. Whether the term negrito accurately reflects the all-encompassing nature of the resulting inquiry is in itself questionable, but the publication of this double issue is testament to the enduring ability of this hypothesis to unite disparate academic disciplines in a common purpose.}, } @article {pmid24262833, year = {2013}, author = {Marchi, E and Kanapin, A and Byott, M and Magiorkinis, G and Belshaw, R}, title = {Neanderthal and Denisovan retroviruses in modern humans.}, journal = {Current biology : CB}, volume = {23}, number = {22}, pages = {R994-R995}, pmid = {24262833}, issn = {1879-0445}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/K010565/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Humans ; Neanderthals/*genetics ; Retroviridae/*genetics ; }, abstract = {In the June 5th 2012 issue of Current Biology, Agoni et al. reported finding 14 endogenous retrovirus (ERV) loci in the genome sequences of Neanderthal and/or Denisovan fossils (both ∼40,000 years old) that are not found in the human reference genome sequence. The authors concluded that these retroviruses were infecting the germline of these archaic hominins at or subsequent to their divergence from modern humans (∼400,000 years ago). However, in our search for unfixed ERVs in the modern human population, we have found most of these loci. We explain this apparent contradiction using population genetic theory and suggest that it illustrates an important phenomenon for the study of transposable elements such as ERVs.}, } @article {pmid24244704, year = {2013}, author = {Derenko, M and Malyarchuk, B and Bahmanimehr, A and Denisova, G and Perkova, M and Farjadian, S and Yepiskoposyan, L}, title = {Complete mitochondrial DNA diversity in Iranians.}, journal = {PloS one}, volume = {8}, number = {11}, pages = {e80673}, pmid = {24244704}, issn = {1932-6203}, mesh = {DNA, Mitochondrial/*genetics ; Gene Flow/genetics ; Genetics, Population ; Haplotypes ; Humans ; Iran ; Phylogeny ; White People ; }, abstract = {Due to its pivotal geographical location and proximity to transcontinental migratory routes, Iran has played a key role in subsequent migrations, both prehistoric and historic, between Africa, Asia and Europe. To shed light on the genetic structure of the Iranian population as well as on the expansion patterns and population movements which affected this region, the complete mitochondrial genomes of 352 Iranians were obtained. All Iranian populations studied here exhibit similarly high diversity values comparable to the other groups from the Caucasus, Anatolia and Europe. The results of AMOVA and MDS analyses did not associate any regional and/or linguistic group of populations in the Anatolia/Caucasus and Iran region pointing to close genetic positions of Persians and Qashqais to each other and to Armenians, and Azeris from Iran to Georgians. By reconstructing the complete mtDNA phylogeny of haplogroups R2, N3, U1, U3, U5a1g, U7, H13, HV2, HV12, M5a and C5c we have found a previously unexplored genetic connection between the studied Iranian populations and the Arabian Peninsula, India, Near East and Europe, likely the result of both ancient and recent gene flow. Our results for Persians and Qashqais point to a continuous increase of the population sizes from ∼24 kya to the present, although the phase between 14-24 kya is thought to be hyperarid according to the Gulf Oasis model. Since this would have affected hunter-gatherer ranges and mobility patterns and forced them to increasingly rely on coastal resources, this transition can explain the human expansion across the Persian Gulf region.}, } @article {pmid24174545, year = {2013}, author = {Hochreiter, S}, title = {HapFABIA: identification of very short segments of identity by descent characterized by rare variants in large sequencing data.}, journal = {Nucleic acids research}, volume = {41}, number = {22}, pages = {e202}, pmid = {24174545}, issn = {1362-4962}, mesh = {*Genetic Variation ; Genomics ; Genotyping Techniques ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Inheritance Patterns ; Sequence Analysis, DNA/*methods ; }, abstract = {Identity by descent (IBD) can be reliably detected for long shared DNA segments, which are found in related individuals. However, many studies contain cohorts of unrelated individuals that share only short IBD segments. New sequencing technologies facilitate identification of short IBD segments through rare variants, which convey more information on IBD than common variants. Current IBD detection methods, however, are not designed to use rare variants for the detection of short IBD segments. Short IBD segments reveal genetic structures at high resolution. Therefore, they can help to improve imputation and phasing, to increase genotyping accuracy for low-coverage sequencing and to increase the power of association studies. Since short IBD segments are further assumed to be old, they can shed light on the evolutionary history of humans. We propose HapFABIA, a computational method that applies biclustering to identify very short IBD segments characterized by rare variants. HapFABIA is designed to detect short IBD segments in genotype data that were obtained from next-generation sequencing, but can also be applied to DNA microarray data. Especially in next-generation sequencing data, HapFABIA exploits rare variants for IBD detection. HapFABIA significantly outperformed competing algorithms at detecting short IBD segments on artificial and simulated data with rare variants. HapFABIA identified 160 588 different short IBD segments characterized by rare variants with a median length of 23 kb (mean 24 kb) in data for chromosome 1 of the 1000 Genomes Project. These short IBD segments contain 752 000 single nucleotide variants (SNVs), which account for 39% of the rare variants and 23.5% of all variants. The vast majority-152 000 IBD segments-are shared by Africans, while only 19 000 and 11 000 are shared by Europeans and Asians, respectively. IBD segments that match the Denisova or the Neandertal genome are found significantly more often in Asians and Europeans but also, in some cases exclusively, in Africans. The lengths of IBD segments and their sharing between continental populations indicate that many short IBD segments from chromosome 1 existed before humans migrated out of Africa. Thus, rare variants that tag these short IBD segments predate human migration from Africa. The software package HapFABIA is available from Bioconductor. All data sets, result files and programs for data simulation, preprocessing and evaluation are supplied at http://www.bioinf.jku.at/research/short-IBD.}, } @article {pmid24136958, year = {2013}, author = {Cooper, A and Stringer, CB}, title = {Paleontology. Did the Denisovans cross Wallace's Line?.}, journal = {Science (New York, N.Y.)}, volume = {342}, number = {6156}, pages = {321-323}, doi = {10.1126/science.1244869}, pmid = {24136958}, issn = {1095-9203}, mesh = {Australia ; DNA/genetics ; Emigration and Immigration/*history ; *Gene Flow ; History, Ancient ; Humans ; New Guinea ; Phylogeography ; Population/*genetics ; Siberia ; }, } @article {pmid24132124, year = {2013}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Khoyt, S and Woźniak, M and Grzybowski, T and Zakharov, I}, title = {Y-chromosome diversity in the Kalmyks at the ethnical and tribal levels.}, journal = {Journal of human genetics}, volume = {58}, number = {12}, pages = {804-811}, doi = {10.1038/jhg.2013.108}, pmid = {24132124}, issn = {1435-232X}, mesh = {Asian People/*genetics ; Chromosomes, Human, Y/*genetics ; Ethnicity/*genetics ; Gene Flow/genetics ; Gene Frequency/genetics ; Genetics, Population ; Haplotypes ; Humans ; Male ; Microsatellite Repeats/genetics ; Polymorphism, Genetic/*genetics ; White People/*genetics ; }, abstract = {The Mongolic-speaking Kalmyks currently inhabiting the steppes of the Volga region have Central Asian ancestry and are organized into the tribal groups. The genetic relationships among these tribes and their origin have remained obscure. We analyzed 17 short tandem repeat and 44 binary polymorphisms of Y-chromosome in 426 individuals mainly from three major tribes of the Kalmyks (the Torguuds, Dörwöds and Khoshuuds). Among these tribes, the Dörwöds and Torguuds, as well as the Kalmyks collectively as an ethnic group, showed relatively close genetic affinities to each other and to the Mongols and Altaian Kazakhs, whereas the Khoshuuds were clearly separated from all of them, gathering with the Manchu, Tibetans or Evenks (depending on the algorithm used to calculate genetic distances). The genetic results also indicate that paternal gene flow from East Europeans to the Kalmyks is very little, despite their cohabitation in the North Caspian Steppe during the last 380 years. The occurrence of unique cluster of N1c-Tat haplotypes in the Khoshuuds, which dates to about 340 years and is likely to have East European ancestry, is considered as a result of interethnic contacts occurred soon after the appearance of the Kalmyk tribes in the Volga-Ural region.}, } @article {pmid28757862, year = {2013}, author = {Puppione, D and Whitelegge, JP}, title = {Proteogenomic Review of the Changes in Primate apoC-I during Evolution.}, journal = {Frontiers in biology}, volume = {8}, number = {5}, pages = {533-548}, pmid = {28757862}, issn = {1674-7984}, support = {R21 RR023132/RR/NCRR NIH HHS/United States ; }, abstract = {Apolipoprotein C-I has evolved more rapidly than any of the other soluble apolipoproteins. During the course of primate evolution, the gene for this apolipoprotein was duplicated. Prompted by our observation that the two resulting genes encode two distinct forms of apoC-I in great apes, we have reviewed both the genomic and proteomic data to examine what changes have occurred during the course of primate evolution. We have found data showing that one of the duplicated genes, known to be a pseudogene in humans, was also a pseudogene in Denisovans and Neandertals. Using genomic and proteomic data for primates, we will provide in this review evidence that the duplication took place after the divergence of New World monkeys from the human lineage and that the formation of the pseudogene took place after the divergence of the bonobos and chimpanzees from the human lineage.}, } @article {pmid24064255, year = {2014}, author = {Malyarchuk, B and Derenko, M and Mikhailova, E and Denisova, G}, title = {Phylogenetic relationships among Neoechinorhynchus species (Acanthocephala: Neoechinorhynchidae) from North-East Asia based on molecular data.}, journal = {Parasitology international}, volume = {63}, number = {1}, pages = {100-107}, doi = {10.1016/j.parint.2013.09.012}, pmid = {24064255}, issn = {1873-0329}, mesh = {Acanthocephala/*genetics ; Animals ; Asia/epidemiology ; DNA/genetics ; Demography ; Fish Diseases/epidemiology/parasitology ; Fishes ; *Genetic Variation ; Helminthiasis, Animal/epidemiology/parasitology ; *Phylogeny ; Species Specificity ; }, abstract = {Phylogenetic and statistical analyses of DNA sequences of two genes, cytochrome oxidase subunit 1 (cox 1) of the mitochondrial DNA and 18S subunit of the nuclear ribosomal RNA (18S rRNA), was used to characterize Neoechinorhynchus species from fishes collected in different localities of North-East Asia. It has been found that four species can be clearly recognized using molecular markers-Neoechinorhynchus tumidus, Neoechinorhynchus beringianus, Neoechinorhynchus simansularis and Neoechinorhynchus salmonis. 18S sequences ascribed to Neoechinorhynchus crassus specimens from North-East Asia were identical to those of N. tumidus, but differed substantially from North American N. crassus. We renamed North-East Asian N. crassus specimens to N. sp., although the possibility that they represent a subspecies of N. tumidus cannot be excluded, taking into account a relatively small distance between cox 1 sequences of North-East Asian specimens of N. crassus and N. tumidus. Maximum likelihood, maximum parsimony and Bayesian inference analyses were performed for phylogeny reconstruction. All the phylogenetic trees showed that North-East Asian species of Neoechinorhynchus analyzed in this study represent independent clades, with the only exception of N. tumidus and N. sp. for 18S data. Phylogenetic analysis has shown that the majority of species sampled (N. tumidus+N. sp., N. simansularis and N. beringianus) are probably very closely related, while N. salmonis occupies separate position in the trees, possibly indicating a North American origin of this species.}, } @article {pmid25486780, year = {2013}, author = {Maliarchuk, BA}, title = {[Mitochondrial DNA polymorphisms shared between modern humans and neanderthals: adaptive convergence or evidence for interspecific hybridization?].}, journal = {Genetika}, volume = {49}, number = {9}, pages = {1120-1123}, pmid = {25486780}, issn = {0016-6758}, mesh = {Animals ; *DNA, Mitochondrial ; *Genome, Human ; Genome, Mitochondrial ; Humans ; Hybridization, Genetic ; Neanderthals/*genetics ; Phylogeny ; *Polymorphism, Genetic ; Primates/genetics ; }, abstract = {An analysis of the variability of the nucleotide sequences in the mitochondrial genome of modern humans, neanderthals, Denisovans, and other primates has shown that there are shared polymorphisms at positions 2758 and 7146 between modern Homo sapiens (in phylogenetic cluster L2'3'4'5'6) and Homo neanderthalensis (in the group of European neanderthals younger than 48000 years). It is suggested that the convergence may be due to adaptive changes in the mitochondrial genomes of modern humans and neanderthals or interspecific hybridization associated with mtDNA recombination.}, } @article {pmid23980394, year = {2013}, author = {Ovchinnikov, IV}, title = {Hominin evolution and gene flow in the Pleistocene Africa.}, journal = {Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur}, volume = {70}, number = {2}, pages = {221-227}, doi = {10.1127/0003-5548/2013/0313}, pmid = {23980394}, issn = {0003-5548}, mesh = {Africa ; Animals ; Anthropology, Physical ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Fossils ; *Gene Flow ; Genome, Mitochondrial/genetics ; Hominidae/*genetics ; Humans ; Phylogeny ; }, abstract = {Africa demonstrates a complex process of the hominin evolution with a series of adaptive radiations during several millions of years that led to diverse morphological forms. Recently, Hammer et al. (2011) and Harvati et al. (2011) provided integrated morphological and genetic evidence of interbreeding between modern humans and unknown archaic hominins in Africa as recently as 35,000 years ago. However, a genetic evidence of hybridization between hominin lineages during the Lower and Middle Pleistocene epochs is unknown and the direct retrieval of DNA from extinct lineages of African hominins remains elusive. The availability of both nuclear and mitochondrial genome sequences from modern humans, Neanderthals, and Denisovans allows collecting nuclear DNA sequences of mitochondrial origin (numts) inserted into the nuclear genome of the ancestral hominin lineages and drawing conclusions about the hominin evolution in the remote past. The mtDNA and numt analysis uncovered a deep division of mtDNA lineages that existed in African hominins in the Middle Pleistocene. The first cluster included the human and Neanderthal-like mtDNA sequences while the second consisted of DNA sequences that are known today as mtAncestor-1, a nuclear fossil of the mtDNA, and the Denisova mtDNA isolated from a bone and a tooth found in southern Siberia. The two groups initially diverged 610,000-1,110,000 years ago. Approximately 220,000 years after the primary split, the Denisova - mtAncestor-1 mtDNA lineages mixed with the mtDNA pool of an ancestral population of Neanderthals and modern humans. This admixture after the profound division is demonstrated by the transposition of the Denisova-like mtDNA sequence into the nuclear genome of an ancestor of Neanderthals and modern humans. This finding suggests the matrilineal genetic structure among the Middle Pleistocene hominins as well as the existence of gene flow between African hominin lineages. Through paleogenomic analyses, it is impossible to exclude the theory that population structure and gene flow in African hominins influenced the admixture pattern observed in the nuclear genomes of non-Africans.}, } @article {pmid23959642, year = {2012}, author = {Setó-Salvia, N and Sánchez-Quinto, F and Carbonell, E and Lorenzo, C and Comas, D and Clarimón, J}, title = {Using the neanderthal and denisova genetic data to understand the common MAPT 17q21 inversion in modern humans.}, journal = {Human biology}, volume = {84}, number = {6}, pages = {633-640}, doi = {10.3378/027.084.0605}, pmid = {23959642}, issn = {1534-6617}, mesh = {Alleles ; Animals ; Biological Evolution ; *Chromosome Inversion ; Genome, Human ; Haplotypes ; Hominidae/*genetics ; Humans ; Linkage Disequilibrium ; Neanderthals/genetics ; Polymorphism, Genetic ; tau Proteins/*genetics ; }, abstract = {The polymorphic inversion on 17q21, that includes the MAPT gene, represents a unique locus in the human genome characterized by a large region with strong linkage disequilibrium. Two distinct haplotypes, H1 and H2, exist in modern humans, and H1 has been unequivocally related to several neurodegenerative disorders. Recent data indicate that recurrent inversions of this genomic region have occurred through primate evolution, with the H2 haplotype being the ancestral state. Neandertals harbored the H1 haplotype; however, until now, no data were available for the Denisova hominin. Neandertals and Denisovans are sister groups that share a common ancestor with modern humans. We analyzed the MAPT sequence and assessed the differences between modern humans, Neandertals, Denisovans, and great apes. Our analysis indicated that the Denisova hominin carried the H1 haplotype, and the Neandertal and Denisova common ancestor probably shared the same subhaplotype (H1j). We also found 68 intronic variants within the MAPT gene, 23 exclusive to Denisova hominin, 6 limited to Neandertals, and 24 exclusive to present-day humans. Our results reinforce previous data; this suggests that the 17q21 inversion arose within the modern human lineage. The data also indicate that archaic hominins that coexisted in Eurasia probably shared the same MAPT subhaplotype, and this can be found in almost 2% of chromosomes from European ancestry.}, } @article {pmid23951901, year = {2013}, author = {Agafonova, EV and Malanicheva, TG and Denisova, SN}, title = {[Defects of neutrophil function in chronic gastroduodenitis in children].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {1}, pages = {60-63}, pmid = {23951901}, issn = {1682-8658}, mesh = {Adolescent ; Candida albicans/isolation & purification ; Candidiasis/*blood/complications/microbiology/pathology ; Case-Control Studies ; Child ; Chronic Disease ; Data Interpretation, Statistical ; Duodenitis/*blood/complications/microbiology/pathology ; Gastritis/*blood/complications/microbiology/pathology ; Helicobacter Infections/*blood/complications/microbiology/pathology ; Helicobacter pylori/isolation & purification ; Humans ; Neutrophils/immunology/*physiology ; Phagocytosis/physiology ; }, abstract = {At present, chronic gastroduodenitis (CGD) occupies one ofthe leading places in the structure of diseases of the gastrointestinal tract in children. In the etiology of CGD, along with the leading pathogenic Helicobacterpylori (HP), the role of the fungal flora increased. The aim of the work was to evaluate the functional activity of neutrophils in children with the CGD, associated with HP and Candida albicans. Among 110 children in the age from 7 to 17 years with chronic gastroduodenitis, associated with Helicobacter pylory(HP), as well as the association of HP with Candida albicans and the markers of secondary immune insufficiency, a study of the phagocytic activity and immune phenotype of neutrophils by flow cytofluorimetry was conducted. Differentiated peculiarities of the phagocytic activity of neutrophils in association with bacterial pathogens (HP) and fungal flora were identified. The transformation of the immune phenotype was combined with a significant depression of the phagocytic and microbicidal functions, more pronounced with the association of HP and Candida albicans. Circulating mannano protein antigen of Candida albicans influenced on the surface of phenotype of neutrophils, increasing the expression of protopathic and HLADR-receptors, and decreasing the expression of adhesion receptors and cytolysis. Thus, in case of chronic gastroduodenitis in children, there was a considerable transformation of the phenotype of neutrophil with differentiated characteristics at the association with bacterial (HP) pathogens and fungal flora. The obtained data should be taken into account when carrying out medical activities, and the doctors should include in the composition of complex therapy of CGD, associated with Candida albicans, drugs, aimed at immunocorrection of the identified violations}, } @article {pmid23907779, year = {2013}, author = {Paixão-Côrtes, VR and Viscardi, LH and Salzano, FM and Cátira Bortolini, M and Hünemeier, T}, title = {The cognitive ability of extinct hominins: bringing down the hierarchy using genomic evidences.}, journal = {American journal of human biology : the official journal of the Human Biology Council}, volume = {25}, number = {5}, pages = {702-705}, doi = {10.1002/ajhb.22426}, pmid = {23907779}, issn = {1520-6300}, mesh = {Animals ; Biological Evolution ; *Cognition ; *Evolution, Molecular ; Genome, Human ; Hominidae/*genetics ; Humans ; Neanderthals/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The availability of the full genomes of Homo sapiens, Homo neanderthalensis, and Denisovans, as well as modern bioinformatic tools, are opening new possibilities for the understanding of the differences and similarities present in these taxa.

METHODS: We searched for cognitive genes, examined their status in the genomes of these three entities. All substitutions present among them were retrieved.

RESULTS: We found 93 nonsynonymous substitutions in 51 cognitive genes, in which the derived allele was present in archaic and modern humans and the ancestral allele in other nonhuman primates.

CONCLUSIONS: The general picture obtained is of similarity in cognitive genes between extinct and extant humans.}, } @article {pmid23906376, year = {2013}, author = {Hedrick, PW}, title = {Adaptive introgression in animals: examples and comparison to new mutation and standing variation as sources of adaptive variation.}, journal = {Molecular ecology}, volume = {22}, number = {18}, pages = {4606-4618}, doi = {10.1111/mec.12415}, pmid = {23906376}, issn = {1365-294X}, mesh = {Adaptation, Biological/*genetics ; Animals ; *Evolution, Molecular ; Genetic Variation ; Humans ; Models, Genetic ; Mutation ; *Selection, Genetic ; }, abstract = {Adaptive genetic variation has been thought to originate primarily from either new mutation or standing variation. Another potential source of adaptive variation is adaptive variants from other (donor) species that are introgressed into the (recipient) species, termed adaptive introgression. Here, the various attributes of these three potential sources of adaptive variation are compared. For example, the rate of adaptive change is generally thought to be faster from standing variation, slower from mutation and potentially intermediate from adaptive introgression. Additionally, the higher initial frequency of adaptive variation from standing variation and lower initial frequency from mutation might result in a higher probability of fixation of the adaptive variants for standing variation. Adaptive variation from introgression might have higher initial frequency than new adaptive mutations but lower than that from standing variation, again making the impact of adaptive introgression variation potentially intermediate. Adaptive introgressive variants might have multiple changes within a gene and affect multiple loci, an advantage also potentially found for adaptive standing variation but not for new adaptive mutants. The processes that might produce a common variant in two taxa, convergence, trans-species polymorphism from incomplete lineage sorting or from balancing selection and adaptive introgression, are also compared. Finally, potential examples of adaptive introgression in animals, including balancing selection for multiple alleles for major histocompatibility complex (MHC), S and csd genes, pesticide resistance in mice, black colour in wolves and white colour in coyotes, Neanderthal or Denisovan ancestry in humans, mimicry genes in Heliconius butterflies, beak traits in Darwin's finches, yellow skin in chickens and non-native ancestry in an endangered native salamander, are examined.}, } @article {pmid23889734, year = {2013}, author = {Bimbo, LM and Denisova, OV and Mäkilä, E and Kaasalainen, M and De Brabander, JK and Hirvonen, J and Salonen, J and Kakkola, L and Kainov, D and Santos, HA}, title = {Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles.}, journal = {ACS nano}, volume = {7}, number = {8}, pages = {6884-6893}, doi = {10.1021/nn402062f}, pmid = {23889734}, issn = {1936-086X}, support = {310892/ERC_/European Research Council/International ; }, mesh = {Amides/*administration & dosage ; Animals ; Dogs ; Drug Carriers ; Drug Delivery Systems ; Humans ; Influenza A virus/*drug effects ; Influenza, Human/*drug therapy ; Madin Darby Canine Kidney Cells ; Microscopy, Fluorescence ; Models, Chemical ; Nanoparticles/*chemistry ; Nanotechnology/*methods ; Particle Size ; Salicylates/*administration & dosage ; Silicon/*chemistry ; Solvents/chemistry ; }, abstract = {Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells.}, } @article {pmid23887633, year = {2013}, author = {Kakkola, L and Denisova, OV and Tynell, J and Viiliäinen, J and Ysenbaert, T and Matos, RC and Nagaraj, A and Ohman, T and Kuivanen, S and Paavilainen, H and Feng, L and Yadav, B and Julkunen, I and Vapalahti, O and Hukkanen, V and Stenman, J and Aittokallio, T and Verschuren, EW and Ojala, PM and Nyman, T and Saelens, X and Dzeyk, K and Kainov, DE}, title = {Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice.}, journal = {Cell death & disease}, volume = {4}, number = {7}, pages = {e742}, pmid = {23887633}, issn = {2041-4889}, mesh = {Aniline Compounds/*pharmacology ; Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cytokines/biosynthesis ; Disease Models, Animal ; Influenza A virus/physiology ; Macrophages/metabolism ; Mice ; Neoplasms/*drug therapy/pathology/virology ; Orthomyxoviridae Infections/metabolism/pathology ; Sulfonamides/*pharmacology ; }, abstract = {ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections.}, } @article {pmid23872234, year = {2013}, author = {Lowery, RK and Uribe, G and Jimenez, EB and Weiss, MA and Herrera, KJ and Regueiro, M and Herrera, RJ}, title = {Neanderthal and Denisova genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.}, journal = {Gene}, volume = {530}, number = {1}, pages = {83-94}, doi = {10.1016/j.gene.2013.06.005}, pmid = {23872234}, issn = {1879-0038}, mesh = {Africa South of the Sahara ; Animals ; DNA, Mitochondrial/genetics ; Europe ; Fossils ; Genetic Drift ; Genetics, Population ; Genome, Human ; Humans ; Neanderthals/*genetics ; Pan troglodytes/genetics ; *Phylogeny ; *Polymorphism, Genetic ; }, abstract = {Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations.}, } @article {pmid23840912, year = {2013}, author = {Mishra, S and Chauhan, N and Singhvi, AK}, title = {Continuity of microblade technology in the Indian Subcontinent since 45 ka: implications for the dispersal of modern humans.}, journal = {PloS one}, volume = {8}, number = {7}, pages = {e69280}, pmid = {23840912}, issn = {1932-6203}, mesh = {Africa ; Animals ; Archaeology ; Asia ; Australia ; Climate ; History, Ancient ; Hominidae ; *Human Migration ; Humans ; India ; Technology/history ; Tool Use Behavior ; }, abstract = {We extend the continuity of microblade technology in the Indian Subcontinent to 45 ka, on the basis of optical dating of microblade assemblages from the site of Mehtakheri, (22° 13' 44″ N Lat 76° 01' 36″ E Long) in Madhya Pradesh, India. Microblade technology in the Indian Subcontinent is continuously present from its first appearance until the Iron Age (~3 ka), making its association with modern humans undisputed. It has been suggested that microblade technology in the Indian Subcontinent was developed locally by modern humans after 35 ka. The dates reported here from Mehtakheri show this inference to be untenable and suggest alternatively that this technology arrived in the Indian Subcontinent with the earliest modern humans. It also shows that modern humans in Indian Subcontinent and SE Asia were associated with differing technologies and this calls into question the "southern dispersal" route of modern humans from Africa through India to SE Asia and then to Australia. We suggest that modern humans dispersed from Africa in two stages coinciding with the warmer interglacial conditions of MIS 5 and MIS 3. Competitive interactions between African modern humans and Indian archaics who shared an adaptation to tropical environments differed from that between modern humans and archaics like Neanderthals and Denisovans, who were adapted to temperate environments. Thus, while modern humans expanded into temperate regions during warmer climates, their expansion into tropical regions, like the Indian Subcontinent, in competition with similarly adapted populations, occurred during arid climates. Thus modern humans probably entered the Indian Subcontinent during the arid climate of MIS 4 coinciding with their disappearance from the Middle East and Northern Africa. The out of phase expansion of modern humans into tropical versus temperate regions has been one of the factors affecting the dispersal of modern humans from Africa during the period 200-40 ka.}, } @article {pmid23755774, year = {2013}, author = {Mandras, N and Roana, J and Allizond, V and Pasqualini, D and Crosasso, P and Burlando, M and Banche, G and Denisova, T and Berutti, E and Cuffini, AM}, title = {Antibacterial efficacy and drug-induced tooth discolouration of antibiotic combinations for endodontic regenerative procedures.}, journal = {International journal of immunopathology and pharmacology}, volume = {26}, number = {2}, pages = {557-563}, doi = {10.1177/039463201302600232}, pmid = {23755774}, issn = {0394-6320}, mesh = {Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/*adverse effects ; Ciprofloxacin/adverse effects ; Clarithromycin/adverse effects ; Dental Pulp Cavity/microbiology/*surgery ; Drug Therapy, Combination ; Female ; Fosfomycin/adverse effects ; Humans ; Male ; Metronidazole/adverse effects ; Middle Aged ; Minocycline/adverse effects ; Root Canal Irrigants/*adverse effects ; Root Canal Preparation/*adverse effects ; Therapeutic Irrigation/*adverse effects ; Tooth Discoloration/chemically induced/*prevention & control ; Tooth, Nonvital/microbiology/*surgery ; Young Adult ; }, abstract = {Elimination of microbial contamination from the root canal system is a precondition for successful root canal treatment. Teeth with immature root development, necrotic pulps and apical periodontitis present multiple challenges for successful treatment. Disinfection is achieved by irrigation followed by the placement of an intracanal medicament. A mixture of ciprofloxacin, metronidazole and minocycline (3-MIX S) has been shown to be very effective in eliminating endodontic pathogens in vitro and in vivo. Among the components of the mixture, minocycline can induce tooth discolouration after long-term oral use. Therefore, the elimination of minocycline from the above-mentioned combination has been suggested to prevent the occasion of this undesirable effect. The aim of this study was to investigate the potential antimicrobial efficacy of alternative antibiotic combinations [3-MIX C (clarithromycin); 3-MIX F (fosfomycin)] against bacteria from infected root canals. An additional objective was to evaluate their discolouration potential as possible alternatives to minocycline-based intracanal medicaments. Our in vitro results clearly demonstrated that 3-MIX C and 3-MIX F had a greater antimicrobial activity than 3-MIX S, underlying that clarithromycin still had a higher capacity to kill endodontic pathogens in vitro compared to fosfomycin. Both 3-MIX C and 3-MIX F were able to avoid the permanent staining effect of the crown.}, } @article {pmid23687020, year = {2013}, author = {Pennisi, E}, title = {Human evolution. More genomes from Denisova Cave show mixing of early human groups.}, journal = {Science (New York, N.Y.)}, volume = {340}, number = {6134}, pages = {799}, doi = {10.1126/science.340.6134.799}, pmid = {23687020}, issn = {1095-9203}, mesh = {Animals ; Anthropology ; *Biological Evolution ; *Caves ; DNA/genetics ; *Genome, Human ; Humans ; Neanderthals/*genetics ; Sequence Analysis, DNA/*methods ; Siberia ; Toe Phalanges ; }, } @article {pmid23677594, year = {2013}, author = {Dormitzer, PR and Suphaphiphat, P and Gibson, DG and Wentworth, DE and Stockwell, TB and Algire, MA and Alperovich, N and Barro, M and Brown, DM and Craig, S and Dattilo, BM and Denisova, EA and De Souza, I and Eickmann, M and Dugan, VG and Ferrari, A and Gomila, RC and Han, L and Judge, C and Mane, S and Matrosovich, M and Merryman, C and Palladino, G and Palmer, GA and Spencer, T and Strecker, T and Trusheim, H and Uhlendorff, J and Wen, Y and Yee, AC and Zaveri, J and Zhou, B and Becker, S and Donabedian, A and Mason, PW and Glass, JI and Rappuoli, R and Venter, JC}, title = {Synthetic generation of influenza vaccine viruses for rapid response to pandemics.}, journal = {Science translational medicine}, volume = {5}, number = {185}, pages = {185ra68}, doi = {10.1126/scitranslmed.3006368}, pmid = {23677594}, issn = {1946-6242}, support = {HHSN272200900007C//PHS HHS/United States ; HHSO100201000061C//PHS HHS/United States ; }, mesh = {Animals ; Cell Line ; Computer Simulation ; Dogs ; Genes, Synthetic ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Humans ; Influenza A Virus, H7N9 Subtype/immunology ; Influenza A virus/*immunology ; Influenza Vaccines/*immunology ; Influenza, Human/*immunology/*prevention & control/virology ; Madin Darby Canine Kidney Cells ; Neuraminidase/genetics ; Pandemics/*prevention & control ; Reassortant Viruses/immunology ; Reproducibility of Results ; Vaccines, Synthetic/*immunology ; Viral Load ; }, abstract = {During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.}, } @article {pmid23666864, year = {2013}, author = {Elhaik, E and Greenspan, E and Staats, S and Krahn, T and Tyler-Smith, C and Xue, Y and Tofanelli, S and Francalacci, P and Cucca, F and Pagani, L and Jin, L and Li, H and Schurr, TG and Greenspan, B and Spencer Wells, R and , }, title = {The GenoChip: a new tool for genetic anthropology.}, journal = {Genome biology and evolution}, volume = {5}, number = {5}, pages = {1021-1031}, pmid = {23666864}, issn = {1759-6653}, support = {/WT_/Wellcome Trust/United Kingdom ; T32 MH014592/MH/NIMH NIH HHS/United States ; 098051/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Anthropology, Cultural ; DNA, Mitochondrial/*genetics ; Genes, Y-Linked ; History, Ancient ; Human Genome Project ; Human Migration/history ; Humans ; *Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/*genetics ; }, abstract = {The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project's new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. The GenoChip includes ancestry informative markers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all known Y-chromosome and mtDNA haplogroups. The chip was carefully vetted to avoid inclusion of medically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs without any known health, medical, or phenotypic relevance, the GenoChip is a useful tool for genetic anthropology and population genetics.}, } @article {pmid23662523, year = {2012}, author = {Zabolotskikh, IB and Musaeva, TS and Denisova, EA}, title = {[Validity of APACHE II, APACHE III, SAPS 2, SAPS 3 and SOFA scales in obstetric patients with sepsis].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {6}, pages = {55-57}, pmid = {23662523}, issn = {0201-7563}, mesh = {*APACHE ; Adult ; Female ; Hospital Records/statistics & numerical data ; Humans ; *Organ Dysfunction Scores ; Pregnancy ; Pregnancy Complications, Infectious/*diagnosis ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; Sepsis/*diagnosis ; *Severity of Illness Index ; Young Adult ; }, abstract = {RESEARCH OBJECTIVE: to estimate efficiency of APACHE II, APACHE III, SAPS II, SAPS III, SOFA scales for obstetric patients with heavy sepsis.

MATERIALS AND METHODS: 186 medical cards retrospective analysis of pregnant women with pulmonary sepsis, 40 women with urosepsis and puerperas with abdominal sepsis--66 was performed. Middle age of women was 26.7 (22.4-34.5).

RESULTS: In population of puerperas with abdominal sepsis APACHE II, APACHE III, SAPS 2, SAPS 3, SOFA scales showed to good calibration, however, high resolution was observed only in APACHE III, SAPS 3 and SOFA (AUROC 0.95; 0.93; 0.92 respectively). APACHE III and SOFA scales provided qualitative prognosis in pregnant women with urosepsis; resolution ratio of these scales considerably exceeds APACHE II, SAPS 2 and SAPS 3 (AUROC 0.73; 0.74; 0.79 respectively). APACHE II scale is inapplicable because of a lack of calibration (X2 = 13.1; p < 0.01), and at other scales (APACHE III, SAPS 2, SAPS 3, SOFA) was observed the insufficient resolution (AUROC < 0.9) in pregnant women with pulmonary sepsis.

CONCLUSION: Prognostic possibilities assessment of score scales showed that APACHE III, SAPS 3 and SOFA scales can be used for a lethality prognosis for puerperas with abdominal sepsis, in population of pregnant women with urosepsis--only APACHE III and SOFA, and with pulmonary sepsis--SAPS 3 and APACHE III only in case of additional clinical information.}, } @article {pmid23657884, year = {2013}, author = {Contreras-Galindo, R and Kaplan, MH and He, S and Contreras-Galindo, AC and Gonzalez-Hernandez, MJ and Kappes, F and Dube, D and Chan, SM and Robinson, D and Meng, F and Dai, M and Gitlin, SD and Chinnaiyan, AM and Omenn, GS and Markovitz, DM}, title = {HIV infection reveals widespread expansion of novel centromeric human endogenous retroviruses.}, journal = {Genome research}, volume = {23}, number = {9}, pages = {1505-1513}, pmid = {23657884}, issn = {1549-5469}, support = {R01 AI062248/AI/NIAID NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; 1F31CA150523-01/CA/NCI NIH HHS/United States ; 5T32AI007528-13/AI/NIAID NIH HHS/United States ; UL1RR24986/RR/NCRR NIH HHS/United States ; T32 GM145304/GM/NIGMS NIH HHS/United States ; U54DA021519/DA/NIDA NIH HHS/United States ; F31 CA150523/CA/NCI NIH HHS/United States ; 3R01CA144043-03S1/CA/NCI NIH HHS/United States ; R01AI062248/AI/NIAID NIH HHS/United States ; P30 ES017885/ES/NIEHS NIH HHS/United States ; U54 DA021519/DA/NIDA NIH HHS/United States ; UL1 RR024986/RR/NCRR NIH HHS/United States ; P30U54ES017885/ES/NIEHS NIH HHS/United States ; R01 CA144043/CA/NCI NIH HHS/United States ; T32 GM007315/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Centromere/genetics/virology ; Chromosomes, Human/genetics/virology ; Endogenous Retroviruses/*genetics ; Evolution, Molecular ; *Genome, Human ; HIV Infections/*genetics ; Hominidae/genetics/virology ; Humans ; Proviruses/*genetics ; *Virus Integration ; tat Gene Products, Human Immunodeficiency Virus/genetics/metabolism ; }, abstract = {Human endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV-K (HML-2) family is the most recent group of these viruses to have inserted into the genome, and we have detected the activation of HERV-K (HML-2) proviruses in the blood of patients with HIV-1 infection. We report that HIV-1 infection activates expression of a novel HERV-K (HML-2) provirus, termed K111, present in multiple copies in the centromeres of chromosomes throughout the human genome yet not annotated in the most recent human genome assembly. Infection with HIV-1 or stimulation with the HIV-1 Tat protein leads to the activation of K111 proviruses. K111 is present as a single copy in the genome of the chimpanzee, yet K111 is not found in the genomes of other primates. Remarkably, K111 proviruses appear in the genomes of the extinct Neanderthal and Denisovan, while modern humans have at least 100 K111 proviruses spread across the centromeres of 15 chromosomes. Our studies suggest that the progenitor K111 integrated before the Homo-Pan divergence and expanded in copy number during the evolution of hominins, perhaps by recombination. The expansion of K111 provides sequence evidence suggesting that recombination between the centromeres of various chromosomes took place during the evolution of humans. K111 proviruses show significant sequence variations in each individual centromere, which may serve as markers in future efforts to annotate human centromere sequences. Further, this work is an example of the potential to discover previously unknown genomic sequences through the analysis of nucleic acids found in the blood of patients.}, } @article {pmid23553074, year = {2013}, author = {Khairat, R and Ball, M and Chang, CC and Bianucci, R and Nerlich, AG and Trautmann, M and Ismail, S and Shanab, GM and Karim, AM and Gad, YZ and Pusch, CM}, title = {First insights into the metagenome of Egyptian mummies using next-generation sequencing.}, journal = {Journal of applied genetics}, volume = {54}, number = {3}, pages = {309-325}, pmid = {23553074}, issn = {2190-3883}, mesh = {Base Sequence ; Biopsy ; Egypt, Ancient ; Embalming/history/*methods ; Gene Library ; History, Ancient ; Humans ; *Metagenome ; Molecular Sequence Data ; *Mummies ; Phylogeny ; Plasmodium falciparum/genetics ; Polymerase Chain Reaction/methods ; Sequence Analysis, DNA/methods ; Temperature ; Toxoplasma/genetics ; }, abstract = {We applied, for the first time, next-generation sequencing (NGS) technology on Egyptian mummies. Seven NGS datasets obtained from five randomly selected Third Intermediate to Graeco-Roman Egyptian mummies (806 BC-124AD) and two unearthed pre-contact Bolivian lowland skeletons were generated and characterised. The datasets were contrasted to three recently published NGS datasets obtained from cold-climate regions, i.e. the Saqqaq, the Denisova hominid and the Alpine Iceman. Analysis was done using one million reads of each newly generated or published dataset. Blastn and megablast results were analysed using MEGAN software. Distinct NGS results were replicated by specific and sensitive polymerase chain reaction (PCR) protocols in ancient DNA dedicated laboratories. Here, we provide unambiguous identification of authentic DNA in Egyptian mummies. The NGS datasets showed variable contents of endogenous DNA harboured in tissues. Three of five mummies displayed a human DNA proportion comparable to the human read count of the Saqqaq permafrost-preserved specimen. Furthermore, a metagenomic signature unique to mummies was displayed. By applying a "bacterial fingerprint", discrimination among mummies and other remains from warm areas outside Egypt was possible. Due to the absence of an adequate environment monitoring, a bacterial bloom was identified when analysing different biopsies from the same mummies taken after a lapse of time of 1.5 years. Plant kingdom representation in all mummy datasets was unique and could be partially associated with their use in embalming materials. Finally, NGS data showed the presence of Plasmodium falciparum and Toxoplasma gondii DNA sequences, indicating malaria and toxoplasmosis in these mummies. We demonstrate that endogenous ancient DNA can be extracted from mummies and serve as a proper template for the NGS technique, thus, opening new pathways of investigation for future genome sequencing of ancient Egyptian individuals.}, } @article {pmid23415986, year = {2013}, author = {Malyarchuk, B and Derenko, M and Denisova, G}, title = {Phylogeny and genetic history of the Siberian salamander (Salamandrella keyserlingii, Dybowski, 1870) inferred from complete mitochondrial genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {67}, number = {2}, pages = {348-357}, doi = {10.1016/j.ympev.2013.02.004}, pmid = {23415986}, issn = {1095-9513}, mesh = {Animals ; Genetics, Population ; *Genome, Mitochondrial ; Haplotypes ; *Phylogeny ; Russia ; Sequence Analysis, DNA ; Siberia ; *Urodela/classification/genetics ; }, abstract = {We assessed phylogeny of the Siberian salamander (Salamandrella keyserlingii, Dybowski, 1870), the most northern ectothermic, terrestrial vertebrate in Eurasia, by sequence analysis of complete mitochondrial genomes in 26 specimens from different localities (China, Khabarovsk region, Sakhalin, Yakutia, Magadan region, Chukotka, Kamchatka, Ural, European part of Russia). In addition, a complete mitochondrial genome of the Schrenck salamander, Salamandrella schrenckii, was determined for the first time. Bayesian phylogenetic analysis of the entire mtDNA genomes of S. keyserlingii demonstrates that two haplotype clades, AB and C, radiated about 1.4 million years ago (Mya). Bayesian skyline plots of population size change through time show an expansion around 250 thousand years ago (kya) and then a decline around the Last Glacial Maximum (25 kya) with subsequent restoration of population size. Climatic changes during the Quaternary period have dramatically affected the population genetic structure of the Siberian salamanders. In addition, complete mtDNA sequence analysis allowed us to recognize that the vast area of Northern Eurasia was colonized only by the Siberian salamander clade C1b during the last 150 kya. Meanwhile, we were unable to find evidence of molecular adaptation in this clade by analyzing the whole mitochondrial genomes of the Siberian salamanders.}, } @article {pmid23413113, year = {2012}, author = {Paixão-Côrtes, VR and Viscardi, LH and Salzano, FM and Hünemeier, T and Bortolini, MC}, title = {Homo sapiens, Homo neanderthalensis and the Denisova specimen: New insights on their evolutionary histories using whole-genome comparisons.}, journal = {Genetics and molecular biology}, volume = {35}, number = {4 (suppl)}, pages = {904-911}, pmid = {23413113}, issn = {1415-4757}, abstract = {After a brief review of the most recent findings in the study of human evolution, an extensive comparison of the complete genomes of our nearest relative, the chimpanzee (Pan troglodytes), of extant Homo sapiens, archaic Homo neanderthalensis and the Denisova specimen were made. The focus was on non-synonymous mutations, which consequently had an impact on protein levels and these changes were classified according to degree of effect. A total of 10,447 non-synonymous substitutions were found in which the derived allele is fixed or nearly fixed in humans as compared to chimpanzee. Their most frequent location was on chromosome 21. Their presence was then searched in the two archaic genomes. Mutations in 381 genes would imply radical amino acid changes, with a fraction of these related to olfaction and other important physiological processes. Eight new alleles were identified in the Neanderthal and/or Denisova genetic pools. Four others, possibly affecting cognition, occured both in the sapiens and two other archaic genomes. The selective sweep that gave rise to Homo sapiens could, therefore, have initiated before the modern/archaic human divergence.}, } @article {pmid23412349, year = {2012}, author = {Mota, NR and Araujo-Jnr, EV and Paixão-Côrtes, VR and Bortolini, MC and Bau, CH}, title = {Linking dopamine neurotransmission and neurogenesis: The evolutionary history of the NTAD (NCAM1-TTC12-ANKK1-DRD2) gene cluster.}, journal = {Genetics and molecular biology}, volume = {35}, number = {4 (suppl)}, pages = {912-918}, pmid = {23412349}, issn = {1415-4757}, abstract = {Genetic studies have long suggested the important role of the DRD2 gene in psychiatric disorders and behavior. Further research has shown a conjoined effect of genes in the Chr11q22-23 region, which includes the NCAM1, TTC12, ANKK1 and DRD2 genes, or NTAD cluster. Despite a growing need to unravel the role of this cluster, few studies have taken into account interspecies and evolutionary approaches. This study shows that behaviorally relevant SNPs from the NTAD cluster, such as rs1800497 (Taq1A) and rs6277, are ancient polymorphisms that date back to the common ancestor between modern humans and Neanderthals/Denisovans. Conserved synteny and neighborhood indicate the NTAD cluster seems to have been established at least 400 million years ago, when the first Sarcopterygians emerged. The NTAD genes are apparently co-regulated and this could be attributed to adaptive functional properties, including those that emerged when the central nervous system became more complex. Finally, our findings indicate that NTAD genes, which are related to neurogenesis and dopaminergic neurotransmission, should be approached as a unit in behavioral and psychiatric genetic studies.}, } @article {pmid23402178, year = {2012}, author = {Malanichevskaia, TG and Narykov, RKh and Denisova, SN}, title = {[Peculiarities of diet therapy in children with duodenal ulcers associated with the genus Candida].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {5}, pages = {87-90}, pmid = {23402178}, issn = {1682-8658}, mesh = {Adolescent ; Animals ; Biopsy ; *Candida ; Candidiasis/*diet therapy/microbiology/pathology ; Child ; Duodenal Ulcer/*diet therapy/microbiology/pathology ; Female ; Goats ; Humans ; Intestinal Mucosa/microbiology/pathology ; Male ; Milk ; }, abstract = {In children with relapsing DU in 50.8% cases there is a complicated disease course with Candida infection, as evidenced by the positive results of mycological examination of biopsy specimens of duodenal mucosa and detection of circulating Candida antigen in serum. The use in the complex therapy in children with DU associated with Candida species of instant New Zealand goat milk "Amalteya" leads to an overall therapeutic effect in 81.3% cases, which is manifested in the reduction of the duration of relapse 1.4 times prolongation of remission in 3 times and milder disease. Carried out in the dynamics fibrogastroduodenoscopy after treatment showed that 100% of the observed total endoscopic remission which is manifested in the disappearance of opalescent gray overlay on the bottom of the ulcer and ulcer epithelization.}, } @article {pmid23324662, year = {2013}, author = {Somel, M and Liu, X and Khaitovich, P}, title = {Human brain evolution: transcripts, metabolites and their regulators.}, journal = {Nature reviews. Neuroscience}, volume = {14}, number = {2}, pages = {112-127}, pmid = {23324662}, issn = {1471-0048}, mesh = {Animals ; *Biological Evolution ; Brain/anatomy & histology/*physiology ; Cognition/physiology ; Gene Expression Regulation/genetics/*physiology ; Humans ; Metabolomics ; Species Specificity ; Transcription, Genetic/genetics/*physiology ; Transcriptome/genetics ; }, abstract = {What evolutionary events led to the emergence of human cognition? Although the genetic differences separating modern humans from both non-human primates (for example, chimpanzees) and archaic hominins (Neanderthals and Denisovans) are known, linking human-specific mutations to the cognitive phenotype remains a challenge. One strategy is to focus on human-specific changes at the level of intermediate phenotypes, such as gene expression and metabolism, in conjunction with evolutionary changes in gene regulation involving transcription factors, microRNA and proximal regulatory elements. In this Review we show how this strategy has yielded some of the first hints about the mechanisms of human cognition.}, } @article {pmid23315957, year = {2013}, author = {Mendez, FL and Watkins, JC and Hammer, MF}, title = {Neandertal origin of genetic variation at the cluster of OAS immunity genes.}, journal = {Molecular biology and evolution}, volume = {30}, number = {4}, pages = {798-801}, doi = {10.1093/molbev/mst004}, pmid = {23315957}, issn = {1537-1719}, mesh = {2',5'-Oligoadenylate Synthetase/*genetics ; Animals ; Evolution, Molecular ; Genetic Loci/*immunology ; Genetic Speciation ; Gorilla gorilla/genetics ; Haplotypes ; Humans ; Linkage Disequilibrium ; Models, Genetic ; Multigene Family ; Neanderthals/*genetics ; Pan troglodytes/genetics ; Phylogeography ; *Polymorphism, Single Nucleotide ; }, abstract = {Analyses of ancient DNA from extinct humans reveal signals of at least two independent hybridization events in the history of non-African populations. To date, there are very few examples of specific genetic variants that have been rigorously identified as introgressive. Here, we survey DNA sequence variation in the OAS gene cluster on chromosome 12 and provide strong evidence that a haplotype extending for ~185 kb introgressed from Neandertals. This haplotype is nearly restricted to Eurasians and is estimated to have diverged from the Neandertal sequence ~125 kya. Despite the potential for novel functional variation, the observed frequency of this haplotype is consistent with neutral introgression. This is the second locus in the human genome, after STAT2, carrying distinct haplotypes that appear to have introgressed separately from both Neandertals and Denisova.}, } @article {pmid24933983, year = {2013}, author = {Reshetnikov, OV and Kurilovich, SA and Denisova, DV}, title = {[Symptoms of gastroesophageal reflux disease and associated factors in adolescents: population survey].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {12}, pages = {8-14}, pmid = {24933983}, issn = {1682-8658}, mesh = {Adolescent ; Antibodies, Bacterial/blood ; Female ; *Gastroesophageal Reflux/diagnosis/epidemiology/etiology ; Helicobacter Infections/complications/epidemiology/microbiology ; Helicobacter pylori/isolation & purification ; Humans ; Male ; *Population Surveillance ; Prevalence ; Risk Factors ; Sex Factors ; Siberia/epidemiology ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Gastroesophageal reflux (GER) is frequent among the general population affecting 10-20% of adults. However, there is a notable lack of epidemiological data describing prevalence of GER in children. The aims of the present study were to assess the prevalence of GER symptoms (GERS) in adolescents and to evaluate factors associated with GERS including markers of H. pylori infection.

METHODS: All school students in grades 9-11 in four randomly selected secondary schools in Novosibirsk participated (449 adolescents, 189 boys, 260 girls aged 14-17). They completed the Bowel Disease Questionnaire, life-style questionnaire, and sera were tested for antibodies against Helicobacter pylori infection.

RESULTS: Overall, 60% of adolescents experienced GERS (heartburn and/or acid regurgitation) over the previous year. GER symptoms on a monthly basis were reported by 22% of students, weekly GERS were reported by 9% of adolescents with the same frequency in both genders. GERS were related to family history of dyspepsia or GER, mother's lower educational attainment, overweight, unhealthy eating patterns, alcohol consumption, smoking, and H. pylori infection, as well as concomitant dyspepsia and irritable bowel syndrome. The majority of associations were more prominent in girls. Visiting a physician, endoscopic study, and school absenteeism were reported in the last year more frequently by adolescents with GERS vs those without GERS.

CONCLUSIONS: Gastroesophageal reflux symptoms are frequent among the adolescent population and result in frequent use of health care resources. Some precipitated factors found in this study are modifiable and may be corrected in adolescent population.}, } @article {pmid24933954, year = {2013}, author = {Malanicheva, TG and Ziatdinova, NV and Denisova, SN}, title = {[Prevalence and risk factors of gastroduodenal and biliary system diseases in infants and preschool children].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {8}, pages = {77-80}, pmid = {24933954}, issn = {1682-8658}, mesh = {Age Factors ; Bile Duct Diseases/*epidemiology ; Child ; Child, Preschool ; Duodenal Diseases/*epidemiology ; Female ; Humans ; Infant ; Male ; Prevalence ; Risk Factors ; Stomach Diseases/*epidemiology ; }, abstract = {To study the prevalence and risk factors of digestive diseases in children performed continuous screening questionnaire 786 children from 1.5 to 7 years. Were Revealed that 47.1 +/- 3.5% of children have symptoms of diseases of the gastrointestinal tract and biliary system. This symptoms occur in children aged 4 to 7 years in 2.3 times more frequently than in children from 1.5 to 3 years. In-depth study was revealed that the frequency of biliary dyskinesia (BD) was 33 +/- 3.3%, chronic gastritis (CG) and gastroduodenitis (CGD)--6.2 +/- 1.8%, chronic cholecystitis--4.2 +/- 1.4%, functional disorders of the stomach (FSD)--2.8 +/- 1.2%, and peptic duodenal ulcer (DU)--0.3 + 0.4%. In the structure of digestive diseases in children from 1.5 to 7 years on the 1st place are BD--70% on the 2nd--CG and CGD--14.7% on the 3rd chronic cholecystitis--8.9%, on the 4th FSD-5.9% and 5th place DU-0.5%. For dispensary observation in the children's clinic with digestive diseases consist of only 7.9 +/- 1.9% of children, which is 5.9 times lower than according to the active diagnostics data. The leading medical and social risk factors and their complex influence on the formation of digestive disorders in infants and preschool children.}, } @article {pmid24772875, year = {2013}, author = {Denisova, TL and Tiul'tiaeva, LA and Lipatova, TE and Bakulev, AL and Alipova, LN and Apanasevich, AV and Bezrodnaia, LA and Borisova, EA}, title = {[Tertiary syphilis of the pancreas and liver in 82-year-old patient: case study].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {7}, pages = {41-43}, pmid = {24772875}, issn = {1682-8658}, mesh = {Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage/therapeutic use ; Ceftriaxone/administration & dosage/therapeutic use ; Diagnosis, Differential ; *Diagnostic Errors ; Humans ; Liver Diseases/*diagnosis/drug therapy/pathology ; Liver Neoplasms/*diagnosis/secondary/surgery ; Male ; Pancreatic Diseases/*diagnosis/drug therapy/pathology ; Pancreatic Neoplasms/*diagnosis/pathology/surgery ; Syphilis/*diagnosis/drug therapy/pathology ; Syphilis Serodiagnosis ; Treatment Outcome ; }, abstract = {It has been described a clinical case of late diagnosis of syphilis of the pancreas and liver of elderly patients. Two years before that it was wrongly diagnosed with cancer of the pancreas with liver metastases, and the patient was operated on with the imposition of cholecystostomy. It was conducted appropriate therapy and reconstructive surgery after verification of the diagnosis of syphilis of the pancreas and liver.}, } @article {pmid24640735, year = {2013}, author = {Alekseeva, EI and Baranov, AA and Mitenko, EV and Bzarova, TM and Valieva, SI and Denisova, RV and Isaeva, KB and Chistiakova, EG and Sleptsova, TV and Taĭbulatov, NI and Zelikovich, EI and Kurilenkov, GV}, title = {[Efficiency and safety of human monoclonal antibodies to TNF-alpha in children with juvenile idiopathic arthritis in primary and secondary ineffectiveness of other biologicals].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {11}, pages = {73-82}, pmid = {24640735}, issn = {0869-6047}, mesh = {Adalimumab ; Adolescent ; Antibodies, Monoclonal, Humanized/*immunology/therapeutic use ; Antirheumatic Agents/therapeutic use ; Arthritis, Juvenile/*drug therapy ; Biological Factors/*therapeutic use ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Male ; Retrospective Studies ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors/immunology ; }, abstract = {PURPOSE: To evaluate the safety and efficiency of adalimumab in children with severe refractory JIA with primary inefficiency, partial effect or loss of the effectiveness of other biologicals.

PATIENTS AND METHODS: The article presents the results of the retrospective observational study of the efficacy and safety of adalimumab in 68 patients aged 10 (3, 17) years with various embodiments of JIA, with the primary inefficiency or partial or loss of the effectiveness of other biologicals. JIA diagnosis established on the basis of criteria ILAR (International League of Associations for Rheumatology).

RESULTS: Efficacy was assessed during 1 year in 68 and 2 years--in 56 patients . At the 24th week we observed the improvement by criteria AKR 30, 50.70 in 100, 91 and 74% of patients, respectively, and at the 52th week--in 100, 96 and 90%, respectively. Inactive disease status was recorded in 55.8, 66.1 and 98.2% of study participants after 6 months, 1 and 2 years, respectively. Remission was achieved in 55.8 and 96.4% of patients after 1 and 2 years of observation, respectively.

CONCLUSIONS: Adalimumab was effective and well tolerated by patients with primary inefficiency, partial and loss of efficiency of other biologicals. In clinical practice, patients with non-systemic JIA transition to the second TNF-alpha blocker can restore the biological effect of the first drug without increasing the frequency of infectious AEs.}, } @article {pmid23210182, year = {2012}, author = {Torubarov, FS and Isaeva, NA and Zvereva, ZF and Denisova, EA and Metliaeva, NA}, title = {[Contemporary legislation and importance of psychophysiologic examination in system of medical support for workers engaged into production with radiation and nuclear danger].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {10}, pages = {35-39}, pmid = {23210182}, issn = {1026-9428}, mesh = {*General Adaptation Syndrome/diagnosis/etiology/prevention & control ; Humans ; Mental Health/*legislation & jurisprudence ; Nuclear Energy/legislation & jurisprudence ; Nuclear Reactors/legislation & jurisprudence ; *Occupational Diseases/diagnosis/etiology/prevention & control ; *Occupational Exposure/adverse effects/legislation & jurisprudence/prevention & control ; Preventive Health Services/legislation & jurisprudence/methods ; Radiation Protection/legislation & jurisprudence/methods/standards ; *Radioactive Hazard Release/legislation & jurisprudence/prevention & control/psychology ; Russia ; Stress, Physiological/*radiation effects ; Work Capacity Evaluation ; }, abstract = {In accordance with contemporary legislation, the article covers materials on specification and approbation of concept model for psychophysiologic examination in medical establishments during medical examination of workers engaged into production with raidation and nuclear danger. The authors defined methodology, examination methods and designed an order of psychophysiologic examination. The psychophysiologic examination and purpose-oriented rehabilitation appeared efficient.}, } @article {pmid23124308, year = {2012}, author = {Disotell, TR}, title = {Archaic human genomics.}, journal = {American journal of physical anthropology}, volume = {149 Suppl 55}, number = {}, pages = {24-39}, doi = {10.1002/ajpa.22159}, pmid = {23124308}, issn = {1096-8644}, mesh = {Animals ; Anthropology, Physical ; DNA/*genetics ; DNA, Mitochondrial/genetics ; Europe ; *Evolution, Molecular ; Fossils ; Genetic Variation ; *Genome, Human ; Genomics ; Humans ; Neanderthals/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {For much of the 20th century, the predominant view of human evolutionary history was derived from the fossil record. Homo erectus was seen arising in Africa from an earlier member of the genus and then spreading throughout the Old World and into the Oceania. A regional continuity model of anagenetic change from H. erectus via various intermediate archaic species into the modern humans in each of the regions inhabited by H. erectus was labeled the multiregional model of human evolution (MRE). A contrasting model positing a single origin, in Africa, of anatomically modern H. sapiens with some populations later migrating out of Africa and replacing the local archaic populations throughout the world with complete replacement became known as the recent African origin (RAO) model. Proponents of both models used different interpretations of the fossil record to bolster their views for decades. In the 1980s, molecular genetic techniques began providing evidence from modern human variation that allowed not only the different models of modern human origins to be tested but also the exploration demographic history and the types of selection that different regions of the genome and even specific traits had undergone. The majority of researchers interpreted these data as strongly supporting the RAO model, especially analyses of mitochondrial DNA (mtDNA). Extrapolating backward from modern patterns of variation and using various calibration points and substitution rates, a consensus arose that saw modern humans evolving from an African population around 200,000 years ago. Much later, around 50,000 years ago, a subset of this population migrated out of Africa replacing Neanderthals in Europe and western Asia as well as archaics in eastern Asia and Oceania. mtDNA sequences from more than two-dozen Neanderthals and early modern humans re-enforced this consensus. In 2010, however, the complete draft genomes of Neanderthals and of heretofore unknown hominins from Siberia, called Denisovans, demonstrated gene flow between these archaic human species and modern Eurasians but not sub-Saharan Africans. Although the levels of gene flow may be very limited, this unexpected finding does not fit well with either the RAO model or MRE model. More thorough sampling of modern human diversity, additional fossil discoveries, and the sequencing of additional hominin fossils are necessary to throw light onto our origins and our history.}, } @article {pmid23112842, year = {2012}, author = {McIntosh, AM and Bennett, C and Dickson, D and Anestis, SF and Watts, DP and Webster, TH and Fontenot, MB and Bradley, BJ}, title = {The apolipoprotein E (APOE) gene appears functionally monomorphic in chimpanzees (Pan troglodytes).}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e47760}, pmid = {23112842}, issn = {1932-6203}, support = {RR016483/RR/NCRR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; RR014491/RR/NCRR NIH HHS/United States ; U42 RR015087/RR/NCRR NIH HHS/United States ; RR015087/RR/NCRR NIH HHS/United States ; C06 RR016483/RR/NCRR NIH HHS/United States ; C06 RR014491/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Apolipoproteins E/*genetics ; Genetic Variation ; Hominidae/genetics ; Humans ; Mutation ; Pan troglodytes/*genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis ; }, abstract = {BACKGROUND: The human apolipoprotein E (APOE) gene is polymorphic, with three primary alleles (E2, E3, E4) that differ at two key non-synonymous sites. These alleles are functionally different in how they bind to lipoproteins, and this genetic variation is associated with phenotypic variation for several medical traits, including cholesterol levels, cardiovascular health, Alzheimer's disease risk, and longevity. The relative frequencies of these alleles vary across human populations, and the evolution and maintenance of this diversity is much debated. Previous studies comparing human and chimpanzee APOE sequences found that the chimpanzee sequence is most similar to the human E4 allele, although the resulting chimpanzee protein might function like the protein coded for by the human E3 allele. However, these studies have used sequence data from a single chimpanzee and do not consider whether chimpanzees, like humans, show intra-specific and subspecific variation at this locus.

To examine potential intraspecific variation, we sequenced the APOE gene of 32 chimpanzees. This sample included 20 captive individuals representing the western subspecies (P. troglodytes verus) and 12 wild individuals representing the eastern subspecies (P. t. schweinfurthii). Variation in our resulting sequences was limited to one non-coding, intronic SNP, which showed fixed differences between the two subspecies. We also compared APOE sequences for all available ape genera and fossil hominins. The bonobo APOE protein is identical to that of the chimpanzee, and the Denisovan APOE exhibits all four human-specific, non-synonymous changes and appears functionally similar to the human E4 allele.

CONCLUSIONS: We found no coding variation within and between chimpanzee populations, suggesting that the maintenance of functionally diverse APOE polymorphisms is a unique feature of human evolution.}, } @article {pmid22946817, year = {2012}, author = {Bokma, F and van den Brink, V and Stadler, T}, title = {Unexpectedly many extinct hominins.}, journal = {Evolution; international journal of organic evolution}, volume = {66}, number = {9}, pages = {2969-2974}, doi = {10.1111/j.1558-5646.2012.01660.x}, pmid = {22946817}, issn = {1558-5646}, mesh = {Animals ; *Extinction, Biological ; *Genetic Speciation ; Hominidae/*genetics ; Humans ; Models, Genetic ; }, abstract = {Recent studies indicate that Neanderthal and Denisova hominins may have been separate species, while debate continues on the status of Homo floresiensis. The decade-long debate between "splitters," who recognize over 20 hominin species, and "lumpers," who maintain that all these fossils belong to just a few lineages, illustrates that we do not know how many extinct hominin species to expect. Here, we present probability distributions for the number of speciation events and the number of contemporary species along a branch of a phylogeny. With estimates of hominin speciation and extincton rates, we then show that the expected total number of extinct hominin species is 8, but may be as high as 27. We also show that it is highly unlikely that three very recent species disappeared due to natural, background extinction. This may indicate that human-like remains are too easily considered distinct species. Otherwise, the evidence suggesting that Neanderthal and the Denisova hominin represent distinct species implies a recent wave of extinctions, ostensibly driven by the only survivor, H. sapiens.}, } @article {pmid22936568, year = {2012}, author = {Meyer, M and Kircher, M and Gansauge, MT and Li, H and Racimo, F and Mallick, S and Schraiber, JG and Jay, F and Prüfer, K and de Filippo, C and Sudmant, PH and Alkan, C and Fu, Q and Do, R and Rohland, N and Tandon, A and Siebauer, M and Green, RE and Bryc, K and Briggs, AW and Stenzel, U and Dabney, J and Shendure, J and Kitzman, J and Hammer, MF and Shunkov, MV and Derevianko, AP and Patterson, N and Andrés, AM and Eichler, EE and Slatkin, M and Reich, D and Kelso, J and Pääbo, S}, title = {A high-coverage genome sequence from an archaic Denisovan individual.}, journal = {Science (New York, N.Y.)}, volume = {338}, number = {6104}, pages = {222-226}, pmid = {22936568}, issn = {1095-9203}, support = {R01-GM40282/GM/NIGMS NIH HHS/United States ; R01 GM100233/GM/NIGMS NIH HHS/United States ; R01 GM040282/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; GM100233/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Base Sequence ; Fossils ; Gene Flow ; Gene Library ; *Genetic Variation ; Genome, Human/*genetics ; *Heterozygote ; Humans ; Molecular Sequence Data ; Neanderthals/*genetics ; Sequence Analysis, DNA ; }, abstract = {We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.}, } @article {pmid22910914, year = {2012}, author = {Denisova, OV and Kakkola, L and Feng, L and Stenman, J and Nagaraj, A and Lampe, J and Yadav, B and Aittokallio, T and Kaukinen, P and Ahola, T and Kuivanen, S and Vapalahti, O and Kantele, A and Tynell, J and Julkunen, I and Kallio-Kokko, H and Paavilainen, H and Hukkanen, V and Elliott, RM and De Brabander, JK and Saelens, X and Kainov, DE}, title = {Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza a virus infection.}, journal = {The Journal of biological chemistry}, volume = {287}, number = {42}, pages = {35324-35332}, pmid = {22910914}, issn = {1083-351X}, support = {P01 CA095471/CA/NCI NIH HHS/United States ; R01 CA090349/CA/NCI NIH HHS/United States ; CA95471/CA/NCI NIH HHS/United States ; CA90349/CA/NCI NIH HHS/United States ; }, mesh = {Amides/*pharmacology ; Animals ; Antiviral Agents/*pharmacology ; Chlorocebus aethiops ; Deoxycytidine/*analogs & derivatives/pharmacology ; Dogs ; Humans ; Indoles ; Influenza A Virus, H3N2 Subtype/*drug effects/*physiology ; Influenza, Human/*drug therapy/metabolism ; Myeloid Cell Leukemia Sequence 1 Protein ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/metabolism ; Pyrroles/*pharmacology ; RNA, Viral/biosynthesis ; Salicylates/*pharmacology ; Vero Cells ; Virus Replication ; Gemcitabine ; }, abstract = {Influenza A viruses (IAVs) infect humans and cause significant morbidity and mortality. Different treatment options have been developed; however, these were insufficient during recent IAV outbreaks. Here, we conducted a targeted chemical screen in human nonmalignant cells to validate known and search for novel host-directed antivirals. The screen validated saliphenylhalamide (SaliPhe) and identified two novel anti-IAV agents, obatoclax and gemcitabine. Further experiments demonstrated that Mcl-1 (target of obatoclax) provides a novel host target for IAV treatment. Moreover, we showed that obatoclax and SaliPhe inhibited IAV uptake and gemcitabine suppressed viral RNA transcription and replication. These compounds possess broad spectrum antiviral activity, although their antiviral efficacies were virus-, cell type-, and species-specific. Altogether, our results suggest that phase II obatoclax, investigational SaliPhe, and FDA/EMEA-approved gemcitabine represent potent antiviral agents.}, } @article {pmid22883142, year = {2012}, author = {Mendez, FL and Watkins, JC and Hammer, MF}, title = {A haplotype at STAT2 Introgressed from neanderthals and serves as a candidate of positive selection in Papua New Guinea.}, journal = {American journal of human genetics}, volume = {91}, number = {2}, pages = {265-274}, pmid = {22883142}, issn = {1537-6605}, mesh = {Adaptation, Biological/genetics ; Animals ; Base Sequence ; Evolution, Molecular ; Gene Components ; *Genetics, Population ; Genotype ; Haplotypes/*genetics ; Humans ; Linkage Disequilibrium ; Molecular Sequence Data ; Mutation/genetics ; Neanderthals/*genetics ; Papua New Guinea ; *Phylogeny ; Receptor, ErbB-3/genetics ; STAT2 Transcription Factor/*genetics ; *Selection, Genetic ; Sequence Analysis, DNA ; }, abstract = {Signals of archaic admixture have been identified through comparisons of the draft Neanderthal and Denisova genomes with those of living humans. Studies of individual loci contributing to these genome-wide average signals are required for characterization of the introgression process and investigation of whether archaic variants conferred an adaptive advantage to the ancestors of contemporary human populations. However, no definitive case of adaptive introgression has yet been described. Here we provide a DNA sequence analysis of the innate immune gene STAT2 and show that a haplotype carried by many Eurasians (but not sub-Saharan Africans) has a sequence that closely matches that of the Neanderthal STAT2. This haplotype, referred to as N, was discovered through a resequencing survey of the entire coding region of STAT2 in a global sample of 90 individuals. Analyses of publicly available complete genome sequence data show that haplotype N shares a recent common ancestor with the Neanderthal sequence (~80 thousand years ago) and is found throughout Eurasia at an average frequency of ~5%. Interestingly, N is found in Melanesian populations at ~10-fold higher frequency (~54%) than in Eurasian populations. A neutrality test that controls for demography rejects the hypothesis that a variant of N rose to high frequency in Melanesia by genetic drift alone. Although we are not able to pinpoint the precise target of positive selection, we identify nonsynonymous mutations in ERBB3, ESYT1, and STAT2-all of which are part of the same 250 kb introgressive haplotype-as good candidates.}, } @article {pmid22810113, year = {2012}, author = {Malyarchuk, BA and Derenko, M and Denisova, G}, title = {On the Y-chromosome haplogroup C3c classification.}, journal = {Journal of human genetics}, volume = {57}, number = {10}, pages = {685-686}, doi = {10.1038/jhg.2012.93}, pmid = {22810113}, issn = {1435-232X}, mesh = {Chromosomes, Human, Y/*genetics ; Ethnicity/*genetics ; Europe, Eastern ; Asia, Eastern ; Genetic Markers ; Genetics, Population/*methods ; *Haplotypes ; Humans ; Male ; Minisatellite Repeats ; Mutation ; Phylogeny ; Polymorphism, Single Nucleotide ; Siberia ; }, abstract = {As there are ambiguities in classification of the Y-chromosome haplogroup C3c, relatively frequent in populations of Northern Asia, we analyzed all three haplogroup-defining markers M48, M77 and M86 in C3-M217-individuals from Siberia, Eastern Asia and Eastern Europe. We have found that haplogroup C3c is characterized by the derived state at M48, whereas mutations at both M77 and M86 define subhaplogroup C3c1. The branch defined by M48 alone would belong to subhaplogroup C3c*, characteristic for some populations of Central and Eastern Siberia, such as Koryaks, Evens, Evenks and Yukaghirs. Subhaplogroup C3c* individuals could be considered as remnants of the Neolithic population of Siberia, based on the age of C3c*-short tandem repeat variation amounting to 4.5 ± 2.4 thousand years.}, } @article {pmid22808780, year = {2012}, author = {Malanicheva, TG and Ziatdinova, NV and Denisova, SN}, title = {[Prevalence and risk factors of gastroduodenal and biliary system diseases in infants and preschool children].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {1}, pages = {55-58}, pmid = {22808780}, issn = {1682-8658}, mesh = {Age Factors ; *Biliary Tract Diseases/diagnosis/epidemiology/etiology ; Child ; Child, Preschool ; *Duodenal Diseases/diagnosis/epidemiology/etiology ; Humans ; Infant ; Mass Screening ; Prevalence ; Risk Factors ; Russia/epidemiology ; *Stomach Diseases/diagnosis/epidemiology/etiology ; }, abstract = {Gastroduodenal pathology, functional disorders and inflammatory diseases of the biliary tract take leading position among the diseases of the digestive system in children. Precisely these clinical forms are more intensive then other nosology. Continuous screening questionnaire of 786 children aged 1.5 to 7 years was carried out to study the prevalence and risk factors for diseases of the digestive system in children. Based on retrieved data was determined that 47,1 +/- 3,5% of children had symptoms of gastro-intestinal tract and biliary system diseases. They met 2.3 times more often in children aged 4 to 7 years, than in children from 1.5 to 3 years old. Immerced examination revealed that the incidence of dyskinesia of the biliary tract was 33 +/- 3,3%, chronic gastritis (CG) and gastroduodenitis (GDD)--6,2 +/- 1,8%, chronic cholecystitis--4,2 +/- 1,4%, functional disorders of the stomach (FGD)--2,8 +/- 1,2% and duodenal ulcer (DU)--0,3 +/- 0,4% of cases. In the structure of digestive diseases in children from 1.5 to 7 years in the first place were DBT--70%, the second--CGD and CG--14.7%--the third chronic cholecystitis--8.9%, the fourth--FGD--5.9% and in fifth place--DU-0.5% of cases. At the care record in the pediatric clinic with diseases of the digestive system were registered only 7,9 +/- 1,9% of children, which is 5.9 times lower accordinig to data of active diagnostic. The leading medical and social risk factors and their complex influence on the formation of digestive diseases in infants and preschool children.}, } @article {pmid22781494, year = {2012}, author = {Belousov, AB and Wang, Y and Song, JH and Denisova, JV and Berman, NE and Fontes, JD}, title = {Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.}, journal = {Neuroscience letters}, volume = {524}, number = {1}, pages = {16-19}, pmid = {22781494}, issn = {1872-7972}, support = {P30 HD002528/HD/NICHD NIH HHS/United States ; R01 NS064256/NS/NINDS NIH HHS/United States ; R21 NS076925/NS/NINDS NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Brain/metabolism/*pathology ; Brain Injuries/metabolism/*pathology ; Cell Death ; Cerebral Cortex/metabolism/pathology ; Connexins/*genetics ; Gap Junctions/drug effects/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/pathology/*physiology ; Receptors, Metabotropic Glutamate/antagonists & inhibitors ; }, abstract = {In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death.}, } @article {pmid22718477, year = {2012}, author = {Stringer, C}, title = {The status of Homo heidelbergensis (Schoetensack 1908).}, journal = {Evolutionary anthropology}, volume = {21}, number = {3}, pages = {101-107}, doi = {10.1002/evan.21311}, pmid = {22718477}, issn = {1520-6505}, mesh = {Animals ; *Anthropology, Physical ; DNA, Mitochondrial/analysis ; *Fossils ; Germany ; Hominidae/anatomy & histology/*classification/genetics ; Humans ; Mandible/anatomy & histology ; Neanderthals ; Phylogeny ; Skull/anatomy & histology ; }, abstract = {The species Homo heidelbergensis is central to many discussions about recent human evolution. For some workers, it was the last common ancestor for the subsequent species Homo sapiens and Homo neanderthalensis; others regard it as only a European form, giving rise to the Neanderthals. Following the impact of recent genomic studies indicating hybridization between modern humans and both Neanderthals and "Denisovans", the status of these as separate taxa is now under discussion. Accordingly, clarifying the status of Homo heidelbergensis is fundamental to the debate about modern human origins.}, } @article {pmid22702107, year = {2012}, author = {Bugaeva, LI and Denisova, TD and Spasov, AA}, title = {[Effect of ladasten on antenatal and postnatal development].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {75}, number = {4}, pages = {23-25}, pmid = {22702107}, issn = {0869-2092}, mesh = {Adamantane/administration & dosage/*analogs & derivatives ; Animals ; Female ; Fetal Development/*drug effects ; Pregnancy ; Rats ; Weight Gain/*drug effects ; }, abstract = {Positive effects of ladasten on both antenatal and postnatal development have been established in experiments on pregnant female rats. Under the action of this drug, the number of resorption events decreases and process of antenatal development of fetuses is activated. In the postnatal period, increased weight gain and accelerated physical development has been observed in the progeny of rats treated with ladasten.}, } @article {pmid22686063, year = {2012}, author = {Kul'bitskiĭ, BN and Larev, ZV and Fedulova, MV and Denisova, OP and Bogomolov, DV}, title = {[Pathology of the heart conducting system in the thanatogenesis of sudden death from alcoholic cardiomyopathy and coronary heart disease].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {55}, number = {2}, pages = {62-65}, pmid = {22686063}, issn = {0039-4521}, mesh = {Cardiomyopathy, Alcoholic/complications/*pathology ; Coronary Disease/complications/*pathology ; Death, Sudden/etiology/*pathology ; *Forensic Pathology ; Heart Conduction System/*pathology ; Humans ; Thanatology ; }, abstract = {The present literature review is focused on the contribution of various pathological changes in the heart conducting system to the tanatogenesis of sudden death from alcoholic cardiomyopathy and coronary heart disease viewed from the perspective of a forensic medical expert. The currently available data on the disorders in the heart conducting system in the subjects with these diseases are presented. Various aspects of pathology of the heart conducting system are considered in the modern and historical contexts. The prospects for the further investigations into the tanatogenic mechanisms of sudden death by reason of alcoholic cardiomyopathy and coronary heart disease are outlined.}, } @article {pmid22686058, year = {2012}, author = {Denisova, OP and Kul'bitskiĭ, BN and Putintsev, VA and Bogomolova, IN and Bogomolov, DV}, title = {[Characteristics of morphological manifestations of anaphylactic shock in response to the administration of pharmaceutical preparations encountered in the practice of forensic medical expert-histologist].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {55}, number = {2}, pages = {46-49}, pmid = {22686058}, issn = {0039-4521}, mesh = {Adult ; Anaphylaxis/chemically induced/*pathology ; *Drug-Related Side Effects and Adverse Reactions ; *Expert Testimony ; Fatal Outcome ; Female ; *Forensic Pathology ; *Forensic Toxicology ; Government Agencies ; *Histology ; Humans ; Male ; Pharmaceutical Preparations/administration & dosage/*classification ; Pregnancy ; Young Adult ; }, abstract = {The authors report the results of a forensic medical investigation of 6 cases of death associated with the administration of pharmaceutical products documented by forensic medical experts of the Russian Centre of Forensic Medical Expertise. The results of the study are compared with the clinical data and summarized using the methods of tanatogenetic analysis. The following main clinical variants of iatrogenic anaphylactic shock (IAS) are distinguished: bronchospastic IAS (n = 1), asphyxic IAS (n = 1), hemodynamic IAS (n = 3), and combined (bronchospastic plus hemodynamic) IAS (n = 1). The signs of all these variants are described allowing for their diagnostics and differentiation diagnostics. These data can be used for the purpose of forensic medical diagnostics and elucidation of the mechanisms of tanatogenesis.}, } @article {pmid22677281, year = {2012}, author = {Agoni, L and Golden, A and Guha, C and Lenz, J}, title = {Neandertal and Denisovan retroviruses.}, journal = {Current biology : CB}, volume = {22}, number = {11}, pages = {R437-8}, doi = {10.1016/j.cub.2012.04.049}, pmid = {22677281}, issn = {1879-0445}, support = {EB009040/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Humans ; Molecular Sequence Data ; Neanderthals/*genetics/virology ; Retroviridae/*genetics ; }, } @article {pmid22665810, year = {2012}, author = {Wang, X and Mitra, N and Secundino, I and Banda, K and Cruz, P and Padler-Karavani, V and Verhagen, A and Reid, C and Lari, M and Rizzi, E and Balsamo, C and Corti, G and De Bellis, G and Longo, L and , and Beggs, W and Caramelli, D and Tishkoff, SA and Hayakawa, T and Green, ED and Mullikin, JC and Nizet, V and Bui, J and Varki, A}, title = {Specific inactivation of two immunomodulatory SIGLEC genes during human evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {25}, pages = {9935-9940}, pmid = {22665810}, issn = {1091-6490}, support = {DP1 ES022577/ES/NIEHS NIH HHS/United States ; P01 HL107150/HL/NHLBI NIH HHS/United States ; R01 HD051796/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Deletion ; *Gene Silencing ; Humans ; Immune System ; Lectins/*genetics ; Primates ; Sialic Acid Binding Immunoglobulin-like Lectins ; }, abstract = {Sialic acid-recognizing Ig-like lectins (Siglecs) are signaling receptors that modulate immune responses, and are targeted for interactions by certain pathogens. We describe two primate Siglecs that were rendered nonfunctional by single genetic events during hominin evolution after our common ancestor with the chimpanzee. SIGLEC13 was deleted by an Alu-mediated recombination event, and a single base pair deletion disrupted the ORF of SIGLEC17. Siglec-13 is expressed on chimpanzee monocytes, innate immune cells that react to bacteria. The human SIGLEC17P pseudogene mRNA is still expressed at high levels in human natural killer cells, which bridge innate and adaptive immune responses. As both resulting pseudogenes are homozygous in all human populations, we resurrected the originally encoded proteins and examined their functions. Chimpanzee Siglec-13 and the resurrected human Siglec-17 recruit a signaling adapter and bind sialic acids. Expression of either Siglec in innate immune cells alters inflammatory cytokine secretion in response to Toll-like receptor-4 stimulation. Both Siglecs can also be engaged by two potentially lethal sialylated bacterial pathogens of newborns and infants, agents with a potential impact on reproductive fitness. Neanderthal and Denisovan genomes show human-like sequences at both loci, corroborating estimates that the initial pseudogenization events occurred in the common ancestral population of these hominins. Both loci also show limited polymorphic diversity, suggesting selection forces predating the origin of modern humans. Taken together, these data suggest that genetic elimination of Siglec-13 and/or Siglec-17 represents signatures of infectious and/or other inflammatory selective processes contributing to population restrictions during hominin origins.}, } @article {pmid22422974, year = {2012}, author = {Stewart, JR and Stringer, CB}, title = {Human evolution out of Africa: the role of refugia and climate change.}, journal = {Science (New York, N.Y.)}, volume = {335}, number = {6074}, pages = {1317-1321}, doi = {10.1126/science.1215627}, pmid = {22422974}, issn = {1095-9203}, mesh = {Adaptation, Biological ; Africa ; Animals ; Asia ; *Biological Evolution ; *Climate Change ; Demography ; Europe ; Extinction, Biological ; Fossils ; Genetic Speciation ; *Hominidae/anatomy & histology/genetics/physiology ; Humans ; Hybridization, Genetic ; Neanderthals/anatomy & histology/genetics/physiology ; Phylogeography ; Population Dynamics ; }, abstract = {Although an African origin of the modern human species is generally accepted, the evolutionary processes involved in the speciation, geographical spread, and eventual extinction of archaic humans outside of Africa are much debated. An additional complexity has been the recent evidence of limited interbreeding between modern humans and the Neandertals and Denisovans. Modern human migrations and interactions began during the buildup to the Last Glacial Maximum, starting about 100,000 years ago. By examining the history of other organisms through glacial cycles, valuable models for evolutionary biogeography can be formulated. According to one such model, the adoption of a new refugium by a subgroup of a species may lead to important evolutionary changes.}, } @article {pmid22412940, year = {2012}, author = {Burbano, HA and Green, RE and Maricic, T and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Kelso, J and Pollard, KS and Lachmann, M and Pääbo, S}, title = {Analysis of human accelerated DNA regions using archaic hominin genomes.}, journal = {PloS one}, volume = {7}, number = {3}, pages = {e32877}, pmid = {22412940}, issn = {1932-6203}, support = {R01 GM082901/GM/NIGMS NIH HHS/United States ; GM082901/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Biological/genetics ; Animals ; Cluster Analysis ; DNA/chemistry ; Evolution, Molecular ; *Genome ; *Genome, Human ; Hominidae/*genetics ; Humans ; Male ; Mutation ; Neanderthals/genetics ; }, abstract = {Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations.}, } @article {pmid22393781, year = {2011}, author = {Maliarchuk, BA}, title = {[Adaptive evolution of the Homo mitochondrial genome].}, journal = {Molekuliarnaia biologiia}, volume = {45}, number = {5}, pages = {845-850}, pmid = {22393781}, issn = {0026-8984}, mesh = {Adaptation, Biological/*genetics ; Amino Acid Sequence ; Amino Acid Substitution/*genetics ; Animals ; *Biological Evolution ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/*genetics/metabolism ; Genes, Mitochondrial ; *Genome, Mitochondrial ; Hominidae/*genetics ; Humans ; Molecular Sequence Data ; Neanderthals/*genetics ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {Adaptive evolution of 12 protein-coding mitochondrial genes in members of genus Homo (Denisova hominin (H. sp. Altai), Neandertals (H. neanderthalensis) and modern humans (H. sapiens)) has been evaluated by assessing the pattern of changes in the physicochemical properties of amino acid replacements during the primate evolution. It has been found that in the Homo molecular adaptation (positive destabilizing selection) become apparent in the form of 12 radical amino acid replacements accompanied by statistically significant (P < 0.001) changes of physicochemical properties that probably had the functional consequences. These replacements have occurred on the stage of a common ancestor of the Homo (in CO2 and CytB genes) as well as with the appearance of the common ancestor of Neandertals and modern humans (in CO1 and ND5 genes). Radical amino acid replacements were mainly revealed in the cytochrome c oxidase complex IV and cytochrome bc1 complex III, thus coinciding with general trend of increasing of non-synonymous changes in mtDNA genes coding subunits of complexes III and IV proteins in anthropoid primates.}, } @article {pmid22383531, year = {2012}, author = {Wang, X and Mitra, N and Cruz, P and Deng, L and , and Varki, N and Angata, T and Green, ED and Mullikin, J and Hayakawa, T and Varki, A}, title = {Evolution of siglec-11 and siglec-16 genes in hominins.}, journal = {Molecular biology and evolution}, volume = {29}, number = {8}, pages = {2073-2086}, pmid = {22383531}, issn = {1537-1719}, support = {P01 HL107150/HL/NHLBI NIH HHS/United States ; R01 GM032373/GM/NIGMS NIH HHS/United States ; P01HL107150/HL/NHLBI NIH HHS/United States ; R01GM32373/GM/NIGMS NIH HHS/United States ; }, mesh = {5' Untranslated Regions/genetics ; Adult ; Alleles ; Animals ; Base Sequence ; Binding Sites ; Brain/metabolism ; Cell Line ; *Evolution, Molecular ; Gene Conversion/genetics ; Gene Frequency/genetics ; Genetic Loci/genetics ; Genetics, Population ; Hominidae/*genetics ; Humans ; Ligands ; Mice ; Microglia/metabolism ; Molecular Sequence Data ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Pseudogenes/genetics ; Sequence Alignment ; Sialic Acid Binding Immunoglobulin-like Lectins/*genetics ; Transcription Factors ; }, abstract = {We previously reported a human-specific gene conversion of SIGLEC11 by an adjacent paralogous pseudogene (SIGLEC16P), generating a uniquely human form of the Siglec-11 protein, which is expressed in the human brain. Here, we show that Siglec-11 is expressed exclusively in microglia in all human brains studied-a finding of potential relevance to brain evolution, as microglia modulate neuronal survival, and Siglec-11 recruits SHP-1, a tyrosine phosphatase that modulates microglial biology. Following the recent finding of a functional SIGLEC16 allele in human populations, further analysis of the human SIGLEC11 and SIGLEC16/P sequences revealed an unusual series of gene conversion events between two loci. Two tandem and likely simultaneous gene conversions occurred from SIGLEC16P to SIGLEC11 with a potentially deleterious intervening short segment happening to be excluded. One of the conversion events also changed the 5' untranslated sequence, altering predicted transcription factor binding sites. Both of the gene conversions have been dated to ~1-1.2 Ma, after the emergence of the genus Homo, but prior to the emergence of the common ancestor of Denisovans and modern humans about 800,000 years ago, thus suggesting involvement in later stages of hominin brain evolution. In keeping with this, recombinant soluble Siglec-11 binds ligands in the human brain. We also address a second-round more recent gene conversion from SIGLEC11 to SIGLEC16, with the latter showing an allele frequency of ~0.1-0.3 in a worldwide population study. Initial pseudogenization of SIGLEC16 was estimated to occur at least 3 Ma, which thus preceded the gene conversion of SIGLEC11 by SIGLEC16P. As gene conversion usually disrupts the converted gene, the fact that ORFs of hSIGLEC11 and hSIGLEC16 have been maintained after an unusual series of very complex gene conversion events suggests that these events may have been subject to hominin-specific selection forces.}, } @article {pmid22363811, year = {2012}, author = {Derenko, M and Malyarchuk, B and Denisova, G and Perkova, M and Rogalla, U and Grzybowski, T and Khusnutdinova, E and Dambueva, I and Zakharov, I}, title = {Complete mitochondrial DNA analysis of eastern Eurasian haplogroups rarely found in populations of northern Asia and eastern Europe.}, journal = {PloS one}, volume = {7}, number = {2}, pages = {e32179}, pmid = {22363811}, issn = {1932-6203}, mesh = {Asia ; Asian People/*genetics ; DNA, Mitochondrial/*genetics ; Ethnicity/*genetics ; Europe ; Genetic Variation ; *Genetics, Population ; Haplotypes/*genetics ; Humans ; Molecular Sequence Data ; Phylogeny ; Phylogeography ; Principal Component Analysis ; White People/*genetics ; }, abstract = {With the aim of uncovering all of the most basal variation in the northern Asian mitochondrial DNA (mtDNA) haplogroups, we have analyzed mtDNA control region and coding region sequence variation in 98 Altaian Kazakhs from southern Siberia and 149 Barghuts from Inner Mongolia, China. Both populations exhibit the prevalence of eastern Eurasian lineages accounting for 91.9% in Barghuts and 60.2% in Altaian Kazakhs. The strong affinity of Altaian Kazakhs and populations of northern and central Asia has been revealed, reflecting both influences of central Asian inhabitants and essential genetic interaction with the Altai region indigenous populations. Statistical analyses data demonstrate a close positioning of all Mongolic-speaking populations (Mongolians, Buryats, Khamnigans, Kalmyks as well as Barghuts studied here) and Turkic-speaking Sojots, thus suggesting their origin from a common maternal ancestral gene pool. In order to achieve a thorough coverage of DNA lineages revealed in the northern Asian matrilineal gene pool, we have completely sequenced the mtDNA of 55 samples representing haplogroups R11b, B4, B5, F2, M9, M10, M11, M13, N9a and R9c1, which were pinpointed from a massive collection (over 5000 individuals) of northern and eastern Asian, as well as European control region mtDNA sequences. Applying the newly updated mtDNA tree to the previously reported northern Asian and eastern Asian mtDNA data sets has resolved the status of the poorly classified mtDNA types and allowed us to obtain the coalescence age estimates of the nodes of interest using different calibrated rates. Our findings confirm our previous conclusion that northern Asian maternal gene pool consists of predominantly post-LGM components of eastern Asian ancestry, though some genetic lineages may have a pre-LGM/LGM origin.}, } @article {pmid22343905, year = {2012}, author = {Xu, C and Schmidt, WU and Galinovic, I and Villringer, K and Hotter, B and Ostwaldt, AC and Denisova, N and Kellner, E and Kiselev, V and Fiebach, JB}, title = {The potential of microvessel density in prediction of infarct growth: a two-month experimental study in vessel size imaging.}, journal = {Cerebrovascular diseases (Basel, Switzerland)}, volume = {33}, number = {4}, pages = {303-309}, doi = {10.1159/000335302}, pmid = {22343905}, issn = {1421-9786}, mesh = {Aged ; Aged, 80 and over ; Blood Circulation Time ; Cerebral Infarction/*pathology ; Cohort Studies ; Data Interpretation, Statistical ; Diffusion Magnetic Resonance Imaging ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Angiography ; Male ; Microvessels/*pathology ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Reperfusion Injury/pathology ; Tissue Plasminogen Activator/therapeutic use ; }, abstract = {OBJECTIVES: Vessel size imaging is a novel technique to evaluate pathological changes of the microvessel density quantity Q and the mean vessel size index (VSI). As a follow-up study, we assessed these parameters for microscopic description of ischemic penumbra and their potentials in predicting lesion growth.

METHODS: Seventy-five patients with a perfusion-diffusion mismatch were examined within 24 h from symptom onset. We defined three regions of interest: the initial infarct (INF), the ischemic penumbra (IPE), and the healthy region (HEA) symmetric to the IPE. For 23 patients with a 6th-day follow-up, IPE regions were divided into areas of infarct growth and areas of oligemia.

RESULT: The median values of Q and VSI were: for INF 0.29 s(-1/3) and 15.8 μm, for IPE 0.33 s(-1/3) and 20.6 μm and for HEA 0.36 s(-1/3) and 17.4 μm. The Q in the IPE was significantly smaller than in HEA, and VSI was significantly larger. The Q with a threshold of 0.32 s(-1/3) predicted the final infarction with a sensitivity of 69% and a specificity of 64%.

CONCLUSIONS: The reduced Q and increased VSI in the IPE confirmed our previous pilot results. Although Q showed a trend to identify the severity of ischemia in an overall voxel population, its potential in predicting infarct growth needs to be further tested in a larger cohort including a clear status of reperfusion and recanalization.}, } @article {pmid22334930, year = {2011}, author = {Denisova, OA and Titarova, LS}, title = {[The atypical course of subperiosteal abscess of the orbital wall].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {5}, pages = {66-67}, pmid = {22334930}, issn = {0042-4668}, mesh = {Abscess/*pathology ; Anti-Bacterial Agents/administration & dosage ; Child ; Endoscopy/*methods ; Female ; Fibrinolytic Agents/administration & dosage ; Humans ; Leeching/methods ; *Maxillary Sinusitis/diagnostic imaging/etiology/physiopathology ; Nasal Bone/abnormalities ; *Nasal Obstruction/complications/congenital/diagnosis/physiopathology ; Orbit/*pathology ; *Orbital Diseases/diagnosis/etiology/physiopathology/therapy ; Punctures ; Radiography ; Rhinoplasty/*methods ; Treatment Outcome ; Turbinates/abnormalities ; }, abstract = {The authors describe a clinical case of malformation of intranasal structures of the lateral wall and the middle turbinated bone of the nose (bullous middle turbinated bone, lateral position of the middle turbinated bone, hypertrophy of ethmoidal bulla and uncinate process) in combination with expressed deformation of the nasal septum. These malformations were responsible for the development of acute hemisinusitis complicated by subperiosteal abscess of the superomedial orbital wall. Conjunctival chemosis was impossible to remove by traditional medicamental therapy and surgical intervention. Hirudotherapy produced the well-apparent anti-odematous, anti-inflammatory, anti-coagulative, and thrombolytic effects that resulted in reduced conjunctival oedema and marked positive dynamics of the state of the eyeball. Subcutaneous administration of anticoagulants was used to prevent thrombosis of orbital veins and cerebral venous sinuses.}, } @article {pmid22319157, year = {2012}, author = {Mendez, FL and Watkins, JC and Hammer, MF}, title = {Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations.}, journal = {Molecular biology and evolution}, volume = {29}, number = {6}, pages = {1513-1520}, doi = {10.1093/molbev/msr301}, pmid = {22319157}, issn = {1537-1719}, mesh = {2',5'-Oligoadenylate Synthetase/*genetics ; 5' Untranslated Regions/genetics ; Animals ; Asian People/genetics ; Black People/*genetics ; Chromosomes, Human, Pair 12/genetics ; Genetic Speciation ; Genotyping Techniques ; Haplotypes ; Hominidae/genetics ; Humans ; *Hybridization, Genetic ; Linkage Disequilibrium ; Melanesia ; Models, Genetic ; Native Hawaiian or Other Pacific Islander/genetics ; *Polymorphism, Genetic ; Sequence Analysis, DNA ; }, abstract = {Recent analysis of DNA extracted from two Eurasian forms of archaic human shows that more genetic variants are shared with humans currently living in Eurasia than with anatomically modern humans in sub-Saharan Africa. Although these genome-wide average measures of genetic similarity are consistent with the hypothesis of archaic admixture in Eurasia, analyses of individual loci exhibiting the signal of archaic introgression are needed to test alternative hypotheses and investigate the admixture process. Here, we provide a detailed sequence analysis of the innate immune gene OAS1, a locus with a divergent Melanesian haplotype that is very similar to the Denisova sequence from the Altai region of Siberia. We resequenced a 7-kb region encompassing the OAS1 gene in 88 individuals from six Old World populations (San, Biaka, Mandenka, French Basque, Han Chinese, and Papua New Guineans) and discovered previously unknown and ancient genetic variation. The 5' region of this gene has unusual patterns of diversity, including 1) higher levels of nucleotide diversity in Papuans than in sub-Saharan Africans, 2) very deep ancestry with an estimated time to the most recent common ancestor of >3 myr, and 3) a basal branching pattern with Papuan individuals on either side of the rooted network. A global geographic survey of >1,500 individuals showed that the divergent Papuan haplotype is nearly restricted to populations from eastern Indonesia and Melanesia. Polymorphic sites within this haplotype are shared with the draft Denisova genome over a span of ∼90 kb and are associated with an extended block of linkage disequilibrium, supporting the hypothesis that this haplotype introgressed from an archaic source that likely lived in Eurasia.}, } @article {pmid22238107, year = {2012}, author = {Wang, Y and Song, JH and Denisova, JV and Park, WM and Fontes, JD and Belousov, AB}, title = {Neuronal gap junction coupling is regulated by glutamate and plays critical role in cell death during neuronal injury.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {32}, number = {2}, pages = {713-725}, pmid = {22238107}, issn = {1529-2401}, support = {R01 NS064256/NS/NINDS NIH HHS/United States ; R01 NS064256-02/NS/NINDS NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; R01 NS064256-01A1/NS/NINDS NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Brain Ischemia/*pathology/physiopathology ; Cell Death/physiology ; Cells, Cultured ; Cerebral Cortex/cytology ; Connexins/genetics/physiology ; Gap Junctions/*physiology ; Glutamic Acid/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/pathology/*physiology ; }, abstract = {In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI), and epilepsy. The coupling of neurons by gap junctions (electrical synapses) increases during neuronal injury. We report here that the ischemic increase in neuronal gap junction coupling is regulated by glutamate via group II metabotropic glutamate receptors (mGluRs). Specifically, using electrotonic coupling, Western blots, and siRNA in the mouse somatosensory cortex in vivo and in vitro, we demonstrate that activation of group II mGluRs increases background levels of neuronal gap junction coupling and expression of connexin 36 (Cx36) (neuronal gap junction protein), and inactivation of group II mGluRs prevents the ischemia-mediated increases in the coupling and Cx36 expression. We also show that the regulation is via cAMP/PKA (cAMP-dependent protein kinase)-dependent signaling and posttranscriptional control of Cx36 expression and that other glutamate receptors are not involved in these regulatory mechanisms. Furthermore, using the analysis of neuronal death, we show that inactivation of group II mGluRs or genetic elimination of Cx36 both dramatically reduce ischemia-mediated neuronal death in vitro and in vivo. Similar results are obtained using in vitro models of TBI and epilepsy. Our results indicate that neuronal gap junction coupling is a critical component of glutamate-dependent neuronal death. They also suggest that causal link among group II mGluR function, neuronal gap junction coupling, and neuronal death has a universal character and operates in different types of neuronal injuries.}, } @article {pmid22224240, year = {2011}, author = {Morgunov, LIu and Denisova, IA and Rozhkova, TI and Stakhovskaia, LV and Skvortsova, VI}, title = {[Androgenic deficit and its treatment in stroke male patients with diabetes mellitus type II].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {111}, number = {8 Pt 2}, pages = {21-24}, pmid = {22224240}, issn = {1997-7298}, mesh = {Aged ; Androgens/*deficiency ; Diabetes Mellitus, Type 2/*metabolism ; *Hormone Replacement Therapy ; Humans ; Male ; Middle Aged ; Stroke/*metabolism ; Testosterone/administration & dosage/*analogs & derivatives ; }, abstract = {We have studied 154 men (mean age 61,4+/-4,1 years) with the first hemispheric ischemic stroke. Clinical and laboratory studies have revealed the androgenic deficit in 66,3%, with its frequency higher in patients with diabetes mellitus type II (50 and 26,3%, respectively). Forty-two men with diabetes mellitus type II and acquired androgenic deficit received replacing treatment with testosterone undecanoate in dose 1000 mg intramuscular. The treatment was started one week after the development of stroke, the next injections were given after 6 weeks and then every 12 weeks during 2 years. The control group included 30 males who did not receive androgens. After 2 years from the beginning of treatment, there were the decrease in clinical severity of androgenic deficit, the increase of total and free testosterone levels, and muscle power in the main group compared to the controls. Body mass index, glicated hemoglobin, cholesterol, triglycerides, low density lipoproteins have decreased as well. Secondary stroke has developed in 3 (7,1%) patients of the main group and in 5 (16,6%) controls; 12 (28,6%) patients returned to work in the main group compared to 2 (6,6%) in the control group. The treatment with androgens has a positive effect on risk factors of secondary ischemic stroke. It is an effective method for improvement of social adaptation of men survived after the stroke.}, } @article {pmid22192823, year = {2011}, author = {Lalueza-Fox, C and Gilbert, MT}, title = {Paleogenomics of archaic hominins.}, journal = {Current biology : CB}, volume = {21}, number = {24}, pages = {R1002-9}, doi = {10.1016/j.cub.2011.11.021}, pmid = {22192823}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Demography ; *Evolution, Molecular ; Fossils ; Gene Flow ; Genetic Variation ; Genome, Human ; Hominidae/anatomy & histology/*genetics/physiology ; Humans/anatomy & histology/genetics/physiology ; Neanderthals/anatomy & histology/*genetics/physiology ; Phylogeny ; Species Specificity ; }, abstract = {In order to understand the genetic basis for the evolutionary success of modern humans, it is necessary to compare their genetic makeup to that of closely related species. Unfortunately, our closest living relatives, the chimpanzees, are evolutionarily quite distant. With the advent of ancient DNA study and more recently paleogenomics - the study of the genomes of ancient organisms - it has become possible to compare human genomes to those of much more closely related groups. Our closest known relatives are the Neanderthals, which evolved and lived in Europe and Western Asia, from about 600,000 years ago until their disappearance around 30,000 years ago following the expansion of anatomically modern humans into their range. The closely related Denisovans are only known by virtue of their DNA, which has been extracted from bone fragments dating around 30,000 to 50,000 years ago found in a single Siberian cave. Analyses of Neanderthal and Denisovan nuclear and mitochondrial genomes have revealed surprising insights into these archaic humans as well as our own species. The genomes provide a preliminary catalogue of derived amino acids that are specific to all extant modern humans, thus offering insights into the functional differences between the three lineages. In addition, the genomes provide evidence of gene flow between the three lineages after anatomically modern humans left Africa, drastically changing our view of human evolution.}, } @article {pmid22099691, year = {2011}, author = {Wills, C}, title = {Genetic and phenotypic consequences of introgression between humans and Neanderthals.}, journal = {Advances in genetics}, volume = {76}, number = {}, pages = {27-54}, doi = {10.1016/B978-0-12-386481-9.00002-X}, pmid = {22099691}, issn = {0065-2660}, mesh = {Animals ; *Consanguinity ; DNA/genetics ; Genome, Human/genetics ; Humans ; Neanderthals/*genetics ; Phenotype ; White People/genetics ; }, abstract = {Strong evidence for introgression of Neanderthal genes into parts of the modern human gene pool has recently emerged. The evidence indicates that some populations of modern humans have received infusions of genes from two different groups of Neanderthals. One of these Neanderthal groups lived in the Middle East and Central Europe and the other group (the Denisovans) is known to have lived in Central Asia and was probably more widespread. This review examines two questions. First, how were these introgressions detected and what does the genetic evidence tell us about their nature and extent? We will see that an unknown but possibly large fraction of the entire Neanderthal gene complement may have survived in modern humans. Even though each modern European and Asian carries only a few percent of genes that can be traced back to Neanderthals, different individuals carry different subgroups of these introgressed genes. Second, what is the likelihood that this Neanderthal genetic legacy has had phenotypic effects on modern humans? We examine evidence for and against the possibility that some of the surviving fragments of Neanderthal genomes have been preserved by natural selection, and we explore the ways in which more evidence bearing on this question will become available in the future.}, } @article {pmid22042846, year = {2011}, author = {Skoglund, P and Jakobsson, M}, title = {Archaic human ancestry in East Asia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, number = {45}, pages = {18301-18306}, pmid = {22042846}, issn = {1091-6490}, mesh = {Asia ; *Fossils ; Genetic Drift ; Genotype ; History, Ancient ; Humans ; Principal Component Analysis ; }, abstract = {Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia ("Denisovans") and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome--a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova-related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed.}, } @article {pmid21944045, year = {2011}, author = {Reich, D and Patterson, N and Kircher, M and Delfin, F and Nandineni, MR and Pugach, I and Ko, AM and Ko, YC and Jinam, TA and Phipps, ME and Saitou, N and Wollstein, A and Kayser, M and Pääbo, S and Stoneking, M}, title = {Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania.}, journal = {American journal of human genetics}, volume = {89}, number = {4}, pages = {516-528}, pmid = {21944045}, issn = {1537-6605}, mesh = {Animals ; Asia, Southeastern ; Biological Evolution ; DNA, Mitochondrial/genetics ; *Gene Flow ; Genotype ; Geography ; Hominidae/*genetics ; Humans ; Models, Genetic ; Models, Statistical ; Native Hawaiian or Other Pacific Islander ; Oceania ; Pan troglodytes ; Polymorphism, Single Nucleotide ; }, abstract = {It has recently been shown that ancestors of New Guineans and Bougainville Islanders have inherited a proportion of their ancestry from Denisovans, an archaic hominin group from Siberia. However, only a sparse sampling of populations from Southeast Asia and Oceania were analyzed. Here, we quantify Denisova admixture in 33 additional populations from Asia and Oceania. Aboriginal Australians, Near Oceanians, Polynesians, Fijians, east Indonesians, and Mamanwa (a "Negrito" group from the Philippines) have all inherited genetic material from Denisovans, but mainland East Asians, western Indonesians, Jehai (a Negrito group from Malaysia), and Onge (a Negrito group from the Andaman Islands) have not. These results indicate that Denisova gene flow occurred into the common ancestors of New Guineans, Australians, and Mamanwa but not into the ancestors of the Jehai and Onge and suggest that relatives of present-day East Asians were not in Southeast Asia when the Denisova gene flow occurred. Our finding that descendants of the earliest inhabitants of Southeast Asia do not all harbor Denisova admixture is inconsistent with a history in which the Denisova interbreeding occurred in mainland Asia and then spread over Southeast Asia, leading to all its earliest modern human inhabitants. Instead, the data can be most parsimoniously explained if the Denisova gene flow occurred in Southeast Asia itself. Thus, archaic Denisovans must have lived over an extraordinarily broad geographic and ecological range, from Siberia to tropical Asia.}, } @article {pmid21897868, year = {2011}, author = {Vorobieva, NV and Sherbakov, DY and Druzhkova, AS and Stanyon, R and Tsybankov, AA and Vasil'ev, SK and Shunkov, MV and Trifonov, VA and Graphodatsky, AS}, title = {Genotyping of Capreolus pygargus fossil DNA from Denisova cave reveals phylogenetic relationships between ancient and modern populations.}, journal = {PloS one}, volume = {6}, number = {8}, pages = {e24045}, pmid = {21897868}, issn = {1932-6203}, mesh = {Animals ; DNA/*genetics/isolation & purification ; Deer/*genetics ; *Evolution, Molecular ; *Fossils ; Genetic Variation ; *Genotyping Techniques ; Geology ; Haplotypes ; *Phylogeny ; Sequence Analysis, DNA ; Siberia ; }, abstract = {BACKGROUND: The extant roe deer (Capreolus Gray, 1821) includes two species: the European roe deer (C. capreolus) and the Siberian roe deer (C. pygargus) that are distinguished by morphological and karyotypical differences. The Siberian roe deer occupies a vast area of Asia and is considerably less studied than the European roe deer. Modern systematics of the Siberian roe deer remain controversial with 4 morphological subspecies. Roe deer fossilized bones are quite abundant in Denisova cave (Altai Mountains, South Siberia), where dozens of both extant and extinct mammalian species from modern Holocene to Middle Pleistocene have been retrieved.

We analyzed a 629 bp fragment of the mitochondrial control region from ancient bones of 10 Holocene and four Pleistocene Siberian roe deer from Denisova cave as well as 37 modern specimen belonging to populations from Altai, Tian Shan (Kyrgyzstan), Yakutia, Novosibirsk region and the Russian Far East. Genealogical reconstructions indicated that most Holocene haplotypes were probably ancestral for modern roe deer populations of Western Siberia and Tian Shan. One of the Pleistocene haplotypes was possibly ancestral for modern Yakutian populations, and two extinct Pleistocene haplotypes were close to modern roe deer from Tian Shan and Yakutia. Most modern geographical populations (except for West Siberian Plains) are heterogeneous and there is some tentative evidence for structure. However, we did not find any distinct phylogenetic signal characterizing particular subspecies in either modern or ancient samples.

CONCLUSION/SIGNIFICANCE: Analysis of mitochondrial DNA from both ancient and modern samples of Siberian roe deer shed new light on understanding the evolutionary history of roe deer. Our data indicate that during the last 50,000 years multiple replacements of populations of the Siberian roe deer took place in the Altai Mountains correlating with climatic changes. The Siberian roe deer represent a complex and heterogeneous species with high migration rates and without evident subspecies structure. Low genetic diversity of the West Siberian Plain population indicates a recent bottleneck or founder effect.}, } @article {pmid21868647, year = {2011}, author = {Gibbons, A}, title = {Paleoanthropology. A Denisovan legacy in the immune system?.}, journal = {Science (New York, N.Y.)}, volume = {333}, number = {6046}, pages = {1086}, doi = {10.1126/science.333.6046.1086}, pmid = {21868647}, issn = {1095-9203}, mesh = {Alleles ; Animals ; Asian People/genetics ; Female ; *Fossils ; *Genes, MHC Class I ; HLA-B Antigens/*genetics ; HLA-C Antigens/*genetics ; Hominidae/*genetics/*immunology ; Humans ; White People/genetics ; }, } @article {pmid21868646, year = {2011}, author = {Gibbons, A}, title = {Paleoanthropology. Who were the Denisovans?.}, journal = {Science (New York, N.Y.)}, volume = {333}, number = {6046}, pages = {1084-1087}, doi = {10.1126/science.333.6046.1084}, pmid = {21868646}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Bone and Bones ; DNA/analysis/genetics ; DNA, Mitochondrial/*genetics ; Female ; *Fossils ; *Hominidae/classification/genetics ; Humans ; Molar/anatomy & histology ; Radiometric Dating ; Siberia ; Tool Use Behavior ; }, } @article {pmid21868630, year = {2011}, author = {Abi-Rached, L and Jobin, MJ and Kulkarni, S and McWhinnie, A and Dalva, K and Gragert, L and Babrzadeh, F and Gharizadeh, B and Luo, M and Plummer, FA and Kimani, J and Carrington, M and Middleton, D and Rajalingam, R and Beksac, M and Marsh, SG and Maiers, M and Guethlein, LA and Tavoularis, S and Little, AM and Green, RE and Norman, PJ and Parham, P}, title = {The shaping of modern human immune systems by multiregional admixture with archaic humans.}, journal = {Science (New York, N.Y.)}, volume = {334}, number = {6052}, pages = {89-94}, pmid = {21868630}, issn = {1095-9203}, support = {R01 AI031168/AI/NIAID NIH HHS/United States ; AI031168/AI/NIAID NIH HHS/United States ; RR000165/RR/NCRR NIH HHS/United States ; P51 RR000165/RR/NCRR NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Adaptation, Biological ; Alleles ; Animals ; Asian People/genetics ; Black People/genetics ; Evolution, Molecular ; *Genes, MHC Class I ; Genetic Variation ; HLA-A Antigens/*genetics/immunology/metabolism ; HLA-B Antigens/*genetics/immunology/metabolism ; HLA-C Antigens/*genetics/immunology ; Haplotypes ; Hominidae/*genetics/*immunology ; Humans ; *Hybridization, Genetic ; Killer Cells, Natural/immunology ; Ligands ; Linkage Disequilibrium ; Molecular Sequence Data ; Native Hawaiian or Other Pacific Islander/genetics ; Racial Groups/*genetics ; Receptors, KIR/immunology/metabolism ; Selection, Genetic ; White People/genetics ; }, abstract = {Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.}, } @article {pmid21850041, year = {2011}, author = {Stoneking, M and Krause, J}, title = {Learning about human population history from ancient and modern genomes.}, journal = {Nature reviews. Genetics}, volume = {12}, number = {9}, pages = {603-614}, pmid = {21850041}, issn = {1471-0064}, mesh = {Africa ; Animals ; Base Sequence ; Chromosome Mapping ; Fossils ; Genetic Association Studies/*methods ; *Genome, Human ; High-Throughput Nucleotide Sequencing ; Hominidae/*genetics ; Humans ; Molecular Sequence Data ; New Guinea ; Phylogeny ; Polymorphism, Single Nucleotide ; Population Groups/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {Genome-wide data, both from SNP arrays and from complete genome sequencing, are becoming increasingly abundant and are now even available from extinct hominins. These data are providing new insights into population history; in particular, when combined with model-based analytical approaches, genome-wide data allow direct testing of hypotheses about population history. For example, genome-wide data from both contemporary populations and extinct hominins strongly support a single dispersal of modern humans from Africa, followed by two archaic admixture events: one with Neanderthals somewhere outside Africa and a second with Denisovans that (so far) has only been detected in New Guinea. These new developments promise to reveal new stories about human population history, without having to resort to storytelling.}, } @article {pmid21807602, year = {2011}, author = {Zhang, G and Pei, Z and Ball, EV and Mort, M and Kehrer-Sawatzki, H and Cooper, DN}, title = {Cross-comparison of the genome sequences from human, chimpanzee, Neanderthal and a Denisovan hominin identifies novel potentially compensated mutations.}, journal = {Human genomics}, volume = {5}, number = {5}, pages = {453-484}, pmid = {21807602}, issn = {1479-7364}, mesh = {Animals ; Databases, Genetic ; *Genome ; Genome, Human ; Hominidae/*genetics ; Humans ; *Mutation ; Neanderthals/genetics ; Pan troglodytes/*genetics ; }, abstract = {The recent publication of the draft genome sequences of the Neanderthal and a ∼50,000-year-old archaic hominin from Denisova Cave in southern Siberia has ushered in a new age in molecular archaeology. We previously cross-compared the human, chimpanzee and Neanderthal genome sequences with respect to a set of disease-causing/disease-associated missense and regulatory mutations (Human Gene Mutation Database) and succeeded in identifying genetic variants which, although apparently pathogenic in humans, may represent a 'compensated' wild-type state in at least one of the other two species. Here, in an attempt to identify further 'potentially compensated mutations' (PCMs) of interest, we have compared our dataset of disease-causing/disease-associated mutations with their corresponding nucleotide positions in the Denisovan hominin, Neanderthal and chimpanzee genomes. Of the 15 human putatively disease-causing mutations that were found to be compensated in chimpanzee, Denisovan or Neanderthal, only a solitary F5 variant (Val1736Met) was specific to the Denisovan. In humans, this missense mutation is associated with activated protein C resistance and an increased risk of thromboembolism and recurrent miscarriage. It is unclear at this juncture whether this variant was indeed a PCM in the Denisovan or whether it could instead have been associated with disease in this ancient hominin.}, } @article {pmid21803765, year = {2011}, author = {Crisci, JL and Wong, A and Good, JM and Jensen, JD}, title = {On characterizing adaptive events unique to modern humans.}, journal = {Genome biology and evolution}, volume = {3}, number = {}, pages = {791-798}, pmid = {21803765}, issn = {1759-6653}, mesh = {Adaptation, Biological/genetics ; Amino Acid Substitution/*genetics ; Animals ; Biological Evolution ; Genome, Human/*genetics ; Hominidae/*genetics ; Humans ; Neanderthals/*genetics ; Pan troglodytes/genetics ; Selection, Genetic ; }, abstract = {Ever since the first draft of the human genome was completed in 2001, there has been increased interest in identifying genetic changes that are uniquely human, which could account for our distinct morphological and cognitive capabilities with respect to other apes. Recently, draft sequences of two extinct hominin genomes, a Neanderthal and Denisovan, have been released. These two genomes provide a much greater resolution to identify human-specific genetic differences than the chimpanzee, our closest extant relative. The Neanderthal genome paper presented a list of regions putatively targeted by positive selection around the time of the human-Neanderthal split. We here seek to characterize the evolutionary history of these candidate regions-examining evidence for selective sweeps in modern human populations as well as for accelerated adaptive evolution across apes. Results indicate that 3 of the top 20 candidate regions show evidence of selection in at least one modern human population (P < 5 × 10(5)). Additionally, four genes within the top 20 regions show accelerated amino acid substitutions across multiple apes (P < 0.01), suggesting importance across deeper evolutionary time. These results highlight the importance of evaluating evolutionary processes across both recent and ancient evolutionary timescales and intriguingly suggest a list of candidate genes that may have been uniquely important around the time of the human-Neanderthal split.}, } @article {pmid21796732, year = {2011}, author = {Sauter, D and Vogl, M and Kirchhoff, F}, title = {Ancient origin of a deletion in human BST2/Tetherin that confers protection against viral zoonoses.}, journal = {Human mutation}, volume = {32}, number = {11}, pages = {1243-1245}, doi = {10.1002/humu.21571}, pmid = {21796732}, issn = {1098-1004}, mesh = {Amino Acid Sequence ; Animals ; Antigens, CD/*genetics ; *Evolution, Molecular ; GPI-Linked Proteins/genetics ; Host-Pathogen Interactions ; Humans ; Molecular Sequence Data ; Neanderthals ; Primates ; *Sequence Deletion ; Simian Acquired Immunodeficiency Syndrome/genetics/transmission/virology ; Simian Immunodeficiency Virus/genetics/immunology/pathogenicity ; Zoonoses/*virology ; }, abstract = {Bone marrow stromal antigen 2 (BST2)/Tetherin is an antiviral factor that blocks the release of enveloped virions from infected cells. Recent data suggest that efficient BST2 antagonism was a prerequisite for the global spread of HIV/AIDS. Most simian immunodeficiency viruses (SIVs), including the direct precursors of HIV, use their Nef protein to antagonize BST2 of their respective host species. Human BST2, however, contains a five amino acid deletion in its cytoplasmic domain that confers resistance to Nef. Thus, this antiviral factor constitutes a major barrier to effective zoonotic transmissions of SIVs to humans. Here, we show that this protective deletion has already been present in Neanderthal and Denisovan BST2 and thus evolved at least 800,000 years ago. This ancient origin helps to explain why effectively spreading zoonotic transmissions of SIVs to humans have been rare, although SIVs are widespread in African nonhuman primates and humans must have been exposed to these viruses many times.}, } @article {pmid21786602, year = {2011}, author = {Baranov, AA and Alekseeva, EI and Valieva, SI and Bzarova, TM and Denisova, RV and Lisitsyn, AO and Chistiakova, EG and Sleptsova, TV and Mitenko, EV}, title = {[Biological therapy in pediatric rheumatology].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {6}, pages = {27-36}, pmid = {21786602}, issn = {0869-6047}, mesh = {Adolescent ; Antibodies, Monoclonal/pharmacokinetics/therapeutic use ; *Antirheumatic Agents/pharmacokinetics/therapeutic use ; *Arthritis, Juvenile/metabolism/physiopathology/therapy ; Biological Availability ; Biological Therapy/*methods ; Child ; Child, Preschool ; Etanercept ; Female ; Humans ; Immunoglobulin G/metabolism/therapeutic use ; *Immunosuppressive Agents/pharmacokinetics/therapeutic use ; Interleukin 1 Receptor Antagonist Protein/pharmacokinetics/therapeutic use ; Male ; Quality of Life ; Quality-Adjusted Life Years ; Receptors, Tumor Necrosis Factor/metabolism/therapeutic use ; Remission Induction ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {This article presents the unique experience of Research Centre of Children's Health in the treatment of 438 children with juvenile rheumatoid arthritis using biological preparations, viz. infliximab (270), adalimumab (55), ethanercept (25), rituximab (74), and tocilizumab (34). It is shown that differential biological therapy, unlike treatment with classical immunodepressants (methotrexate, cyclosporine, leflunomide, etc.), permits to achieve clinico-laboratory remission in 70% and markedly decrease activity of the disease in 20% of the patients within 1 year after the onset. It is concluded that treatment with gene-engineered drugs improves the quality of life of the children and their families, normal growth and development of the patients and affects prognosis of this formerly incurable chronic autoimmune disease.}, } @article {pmid21677663, year = {2011}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Maksimov, A and Wozniak, M and Grzybowski, T and Dambueva, I and Zakharov, I}, title = {Ancient links between Siberians and Native Americans revealed by subtyping the Y chromosome haplogroup Q1a.}, journal = {Journal of human genetics}, volume = {56}, number = {8}, pages = {583-588}, doi = {10.1038/jhg.2011.64}, pmid = {21677663}, issn = {1435-232X}, mesh = {Asia ; Asian People/genetics ; Chromosomes, Human, Y/*genetics ; Gene Frequency ; Genetic Variation ; Genetics, Population/*methods ; Haplotypes/*genetics ; Humans ; Indians, North American/ethnology/genetics ; Male ; Microsatellite Repeats/genetics ; Pedigree ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Siberia/ethnology ; }, abstract = {To investigate the structure of Y chromosome haplogroups R-M207 and Q-M242 in human populations of North Asia, we have performed high-resolution genotyping using both single nucleotide polymorphisms and short tandem repeat (STR)-based approaches of 121 M207- and M242-derived samples from 885 males of 16 ethnic groups of Siberia and East Asia. As a result, the following Y chromosome haplogroups were revealed: R1b1b1-M73 (2.0%), R1b1b2-M269 (0.7%), R2-M124 (1.1%), Q1a*-MEH2 (0.5%), Q1a2-M25 (0.1%), Q1a3*-M346 (9.2%) and Q1a3a-M3 (0.2%). Despite the low coalescence age of haplogroup Q1a3*-M346, which is estimated in South Siberia as about 4.5±1.5 thousand years ago (Ka), divergence time between these Q1a3*-M346 haplotypes and Amerindian-specific haplogroup Q1a3a-M3 is equal to 13.8±3.9 Ka, pointing to a relatively recent entry date to America. In addition, unique cluster of haplotypes belonging to Q1a*-MEH2 was found in Koryaks inhabiting the Sea of Okhotsk coast (at a frequency of 10.3%). Although the level of STR diversity associated with Q1a*-MEH2 is very low, this lineage appears to be closest to the extinct Palaeo-Eskimo individuals belonging to the Saqqaq culture arisen in the New World Arctic about 5.5 Ka. This finding suggests that Q1a*-MEH2 likely traces a population migration originating in Northeast Siberia across the Bering Strait.}, } @article {pmid21645926, year = {2011}, author = {Denisova, G and Jenkins, K and Evelegh, C and Bramson, J}, title = {Novel method for differentiation between Trastuzumab and host adaptive response.}, journal = {Molecular immunology}, volume = {48}, number = {15-16}, pages = {1882-1885}, doi = {10.1016/j.molimm.2011.05.016}, pmid = {21645926}, issn = {1872-9142}, mesh = {*Adaptive Immunity ; Antibodies, Monoclonal/*blood/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibody Affinity ; Antineoplastic Agents/blood/therapeutic use ; Autoantibodies/*blood/immunology ; Autoantigens/immunology ; Blotting, Western ; Breast Neoplasms/drug therapy/immunology ; Female ; Hematologic Tests/*methods ; Humans ; Mutation ; Receptor, ErbB-2/genetics/*immunology ; Recombinant Proteins/genetics/immunology ; Trastuzumab ; }, abstract = {Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF→SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated form of the human HER-2 ECD, we have a source of this protein to probe patient sera. Our method represents a proof of principle that mutated HER-2 which we constructed could be used to distinguish between a host response against HER-2 and the monoclonal antibody Herceptin targeting the same protein.}, } @article {pmid21542308, year = {2011}, author = {Denisova, GA and Malarchuk, BA and Derenko, MV and Kravtsova, OA}, title = {[Population structure of Volga Tatars inferred from the mitochondrial DNA diversity data].}, journal = {Genetika}, volume = {47}, number = {3}, pages = {387-393}, pmid = {21542308}, issn = {0016-6758}, mesh = {DNA, Mitochondrial/*genetics ; Ethnicity/*genetics ; Gene Frequency/genetics ; Genetic Variation ; Haplotypes/genetics ; Humans ; Polymorphism, Restriction Fragment Length/genetics ; Russia/ethnology ; }, abstract = {The data on mitochondrial DNA (mtDNA) variation in two populations of Volga Tatars, representing the population of Buinsk and Aznakaevo districts of the Republic of Tatarstan are presented. Comparative analysis of the data on mtDNA variation in the populations of Eastern Europe showed that Volga Tatars were characterized by low interpopulation differentiation (F(ST) = 0.33%), while the level of interethnic differentiation in Eastern Europe is 1.8%. Genetic similarity of Tatars from the eastern regions of Tatarstan to Bashkirs, as well as of Tatars from western regions to Chuvashes, with whom they share territorial borders, was revealed. Positive correlation between population genetic structure in Eastern Europe and linguistic affiliation of the ethnic groups studied was observed.}, } @article {pmid21508216, year = {2011}, author = {Park, WM and Wang, Y and Park, S and Denisova, JV and Fontes, JD and Belousov, AB}, title = {Interplay of chemical neurotransmitters regulates developmental increase in electrical synapses.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {31}, number = {16}, pages = {5909-5920}, pmid = {21508216}, issn = {1529-2401}, support = {R01 DA015088/DA/NIDA NIH HHS/United States ; R01 NS064256/NS/NINDS NIH HHS/United States ; P20 RR024214/RR/NCRR NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Analysis of Variance ; Animals ; Blotting, Western ; Cell Communication/physiology ; Cells, Cultured ; Cerebral Cortex/embryology/*metabolism ; Connexins/genetics/*metabolism ; Electrical Synapses/*metabolism ; Female ; Hypothalamus/embryology/*metabolism ; Male ; Mice ; Mice, Knockout ; Neurons/*metabolism ; Neurotransmitter Agents/*metabolism ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Synaptic Transmission/physiology ; }, abstract = {Coupling of neurons by electrical synapses (gap junctions) transiently increases in the mammalian CNS during development. We report here that the developmental increase in neuronal gap junction coupling and expression of connexin 36 (Cx36; neuronal gap junction protein) are regulated by an interplay between the activity of group II metabotropic glutamate receptors (mGluRs) and GABA(A) receptors. Specifically, using dye coupling, electrotonic coupling, Western blots and small interfering RNA in the rat and mouse hypothalamus and cortex in vivo and in vitro, we demonstrate that activation of group II mGluRs augments, and inactivation prevents, the developmental increase in neuronal gap junction coupling and Cx36 expression. However, changes in GABA(A) receptor activity have the opposite effects. The regulation by group II mGluRs is via cAMP/PKA-dependent signaling, and regulation by GABA(A) receptors is via Ca(2+)/PKC-dependent signaling. Furthermore, the receptor-mediated upregulation of Cx36 requires a neuron-restrictive silencer element in the Cx36 gene promoter, and the downregulation involves the 3'-untranslated region of the Cx36 mRNA, as shown using reverse-transcription quantitative real-time PCR and luciferase reporter activity analysis. In addition, the methyl thiazolyl tetrazolium analysis indicates that mechanisms for the developmental increase in neuronal gap junction coupling directly control the death/survival mechanisms in developing neurons. Together, the results suggest a multitiered strategy for chemical synapses in developmental regulation of electrical synapses.}, } @article {pmid21384257, year = {2011}, author = {Alexeeva, EI and Valieva, SI and Bzarova, TM and Semikina, EL and Isaeva, KB and Lisitsyn, AO and Denisova, RV and Chistyakova, EG}, title = {Efficacy and safety of repeat courses of rituximab treatment in patients with severe refractory juvenile idiopathic arthritis.}, journal = {Clinical rheumatology}, volume = {30}, number = {9}, pages = {1163-1172}, pmid = {21384257}, issn = {1434-9949}, mesh = {Adolescent ; Antibodies, Monoclonal, Murine-Derived/*therapeutic use ; Antirheumatic Agents/*therapeutic use ; Arthritis, Juvenile/*drug therapy/pathology/physiopathology ; B-Lymphocytes/drug effects ; Child ; Child, Preschool ; Drug Resistance, Multiple/drug effects ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents/*therapeutic use ; Joints/pathology/physiopathology ; Lymphocyte Depletion ; Male ; Remission Induction ; Rituximab ; Treatment Outcome ; }, abstract = {Treatment of severe juvenile idiopathic arthritis (JIA) represents a serious challenge. This study investigates the efficacy and safety of repeat courses of rituximab in patients with different forms of JIA refractory to infliximab and standard immunosuppressive therapy. Patients (n = 55; age 2.3-17.0 years) with severe polyarticular and systemic JIA (International League of Association for Rheumatology diagnostic criteria) received rituximab (one intravenous infusion/week for 4 weeks, 375 mg/m(2) per dose). Efficacy was assessed using the American College of Rheumatology Pediatric (ACR Pedi) criteria. The primary endpoint was an ACR Pedi 30 response at week 24. At week 24, ACR Pedi 30, 50, and 70 responses were achieved by 98%, 50%, and 40% of patients, respectively. By week 96, ACR Pedi 30, 50, and 70 responses were achieved by 98%, 93%, and 93% of 25 patients, respectively. Remission was recorded in 25%, 52%, 75%, and 98% of patients following the first (24 weeks), second (48 weeks), third (72 weeks), and fourth (96 weeks) courses of rituximab, respectively. Rituximab treatment significantly reduced the number of systemic manifestations at week 12 and also enabled 52% of patients to achieve remission of arthritis by week 48. This study supports the efficacy of rituximab in patients with severe forms of JIA, refractory to several prior agents.}, } @article {pmid21332627, year = {2011}, author = {Nowicki, M and Rychlik, I and Haller, H and Warren, ML and Suchower, L and Gause-Nilsson, I and , }, title = {Saxagliptin improves glycaemic control and is well tolerated in patients with type 2 diabetes mellitus and renal impairment.}, journal = {Diabetes, obesity & metabolism}, volume = {13}, number = {6}, pages = {523-532}, doi = {10.1111/j.1463-1326.2011.01382.x}, pmid = {21332627}, issn = {1463-1326}, mesh = {Adamantane/*analogs & derivatives/therapeutic use ; Aged ; Blood Glucose/drug effects ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Diabetic Nephropathies/blood/*drug therapy ; Dipeptides/*therapeutic use ; Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use ; Double-Blind Method ; Female ; Glycated Hemoglobin/*drug effects ; Humans ; Kidney Failure, Chronic/blood/*drug therapy ; Male ; Middle Aged ; Placebos ; Treatment Outcome ; }, abstract = {AIM: To evaluate the efficacy and safety of saxagliptin vs. placebo in patients with type 2 diabetes mellitus (T2DM) and renal impairment.

METHODS: In this multicentre, randomized, parallel-group, double-blind, placebo-controlled study, patients with glycated haemoglobin (HbA1c) 7-11% and creatinine clearance <50 ml/min were stratified by baseline renal impairment (moderate, severe or end-stage on haemodialysis), and randomized (1 : 1) to saxagliptin 2.5 mg once daily or placebo for 12 weeks. Oral antihyperglycaemic drugs and insulin therapy present at enrolment were continued throughout the study. The absolute change in HbA1c from baseline to week 12 (primary efficacy end-point) was analysed using an analysis of covariance model with last observation carried forward methodology.

RESULTS: A total of 170 patients were randomized and treated. The adjusted mean decrease from baseline to week 12 in HbA1c was statistically significantly greater in the saxagliptin group than in the placebo group; the difference between treatments was -0.42% (95% confidence interval: -0.71 to -0.12%, p = 0.007). Adjusted mean HbA1c decreases from baseline to week 12 were numerically greater with saxagliptin than with placebo in the subgroups of patients with moderate (-0.64 vs. -0.05%) and severe (-0.95 vs. -0.50%) renal impairment. HbA1c reductions were similar between saxagliptin and placebo in the subgroup with end-stage renal disease on haemodialysis (-0.84 vs. -0.87%). Saxagliptin was generally well tolerated; incidences of adverse events and hypoglycaemic events were similar to placebo.

CONCLUSIONS: Saxagliptin 2.5 mg once daily is a well-tolerated treatment option for patients with inadequately controlled T2DM and renal impairment.}, } @article {pmid21203537, year = {2010}, author = {Derenko, M and Malyarchuk, B and Grzybowski, T and Denisova, G and Rogalla, U and Perkova, M and Dambueva, I and Zakharov, I}, title = {Origin and post-glacial dispersal of mitochondrial DNA haplogroups C and D in northern Asia.}, journal = {PloS one}, volume = {5}, number = {12}, pages = {e15214}, pmid = {21203537}, issn = {1932-6203}, mesh = {Asia ; Asian People/genetics ; DNA, Mitochondrial/*genetics ; Emigration and Immigration ; Female ; Genetic Variation ; Genetics, Population ; Haplotypes ; Humans ; Phylogeny ; *Phylogeography ; Sequence Analysis, DNA ; }, abstract = {More than a half of the northern Asian pool of human mitochondrial DNA (mtDNA) is fragmented into a number of subclades of haplogroups C and D, two of the most frequent haplogroups throughout northern, eastern, central Asia and America. While there has been considerable recent progress in studying mitochondrial variation in eastern Asia and America at the complete genome resolution, little comparable data is available for regions such as southern Siberia--the area where most of northern Asian haplogroups, including C and D, likely diversified. This gap in our knowledge causes a serious barrier for progress in understanding the demographic pre-history of northern Eurasia in general. Here we describe the phylogeography of haplogroups C and D in the populations of northern and eastern Asia. We have analyzed 770 samples from haplogroups C and D (174 and 596, respectively) at high resolution, including 182 novel complete mtDNA sequences representing haplogroups C and D (83 and 99, respectively). The present-day variation of haplogroups C and D suggests that these mtDNA clades expanded before the Last Glacial Maximum (LGM), with their oldest lineages being present in the eastern Asia. Unlike in eastern Asia, most of the northern Asian variants of haplogroups C and D began the expansion after the LGM, thus pointing to post-glacial re-colonization of northern Asia. Our results show that both haplogroups were involved in migrations, from eastern Asia and southern Siberia to eastern and northeastern Europe, likely during the middle Holocene.}, } @article {pmid21179161, year = {2010}, author = {Reich, D and Green, RE and Kircher, M and Krause, J and Patterson, N and Durand, EY and Viola, B and Briggs, AW and Stenzel, U and Johnson, PL and Maricic, T and Good, JM and Marques-Bonet, T and Alkan, C and Fu, Q and Mallick, S and Li, H and Meyer, M and Eichler, EE and Stoneking, M and Richards, M and Talamo, S and Shunkov, MV and Derevianko, AP and Hublin, JJ and Kelso, J and Slatkin, M and Pääbo, S}, title = {Genetic history of an archaic hominin group from Denisova Cave in Siberia.}, journal = {Nature}, volume = {468}, number = {7327}, pages = {1053-1060}, pmid = {21179161}, issn = {1476-4687}, support = {R01 GM040282/GM/NIGMS NIH HHS/United States ; R01-GM40282/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asia ; DNA, Mitochondrial/genetics ; Europe ; Finger Phalanges/chemistry ; *Fossils ; *Gene Flow ; Genome/*genetics ; Hominidae/*classification/*genetics ; Humans ; Melanesia ; Molecular Sequence Data ; Phylogeny ; Siberia ; Tooth/anatomy & histology/chemistry ; }, abstract = {Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4-6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population 'Denisovans' and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.}, } @article {pmid21129766, year = {2011}, author = {Martinón-Torres, M and Dennell, R and Bermúdez de Castro, JM}, title = {The Denisova hominin need not be an out of Africa story.}, journal = {Journal of human evolution}, volume = {60}, number = {2}, pages = {251-255}, doi = {10.1016/j.jhevol.2010.10.005}, pmid = {21129766}, issn = {1095-8606}, mesh = {Africa ; *Animal Migration ; Animals ; DNA, Mitochondrial/genetics ; Fossils ; Hominidae/*genetics ; Siberia ; }, } @article {pmid21105351, year = {2010}, author = {Bogomil'skiĭ, MR and Garashchenko, TI and Denisova, OA}, title = {[Assessment of the effectiveness of sinuforte used for the combined treatment of rhinosinusitis and exudative otitis media in children].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {4}, pages = {74-77}, pmid = {21105351}, issn = {0042-4668}, mesh = {Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Combined Modality Therapy ; *Cyclamen ; Female ; Humans ; Male ; Otitis Media with Effusion/drug therapy/surgery/*therapy ; Phytotherapy ; Plant Extracts/*therapeutic use ; Rhinitis/drug therapy/surgery/*therapy ; Sinusitis/drug therapy/surgery/*therapy ; Treatment Outcome ; }, abstract = {The objective of the present study was to evaluate efficiency, safety, and tolerability of two single doses of sinuforte (INVAR, Russia) used in the combined treatment of rhinosinusitis (including that with concurrent exudative otitis media) in children at the age from 5 to 12 years. The data obtained suggest high efficiency of sinuforte in the treatment of mild and moderately severe acute rhinosinusitis and exudative otitis media. Inclusion of sinuforte in combined therapy of these conditions makes it possible to avoid drainage procedures and decreases duration of antibacterial treatment. Simultaneous acceleration of the recovery of functional activity of endonasal mucosa suggests pronounced anti-recurrent action of sinuforte.}, } @article {pmid21067548, year = {2010}, author = {Denisova, GF and Denisov, DA and Bramson, JL}, title = {Applying bioinformatics for antibody epitope prediction using affinity-selected mimotopes - relevance for vaccine design.}, journal = {Immunome research}, volume = {6 Suppl 2}, number = {Suppl 2}, pages = {S6}, pmid = {21067548}, issn = {1745-7580}, abstract = {To properly characterize protective polyclonal antibody responses, it is necessary to examine epitope specificity. Most antibody epitopes are conformational in nature and, thus, cannot be identified using synthetic linear peptides. Cyclic peptides can function as mimetics of conformational epitopes (termed mimotopes), thereby providing targets, which can be selected by immunoaffinity purification. However, the management of large collections of random cyclic peptides is cumbersome. Filamentous bacteriophage provides a useful scaffold for the expression of random peptides (termed phage display) facilitating both the production and manipulation of complex peptide libraries. Immunoaffinity selection of phage displaying random cyclic peptides is an effective strategy for isolating mimotopes with specificity for a given antiserum. Further epitope prediction based on mimotope sequence is not trivial since mimotopes generally display only small homologies with the target protein. Large numbers of unique mimotopes are required to provide sufficient sequence coverage to elucidate the target epitope. We have developed a method based on pattern recognition theory to deal with the complexity of large collections of conformational mimotopes. The analysis consists of two phases: 1) The learning phase where a large collection of epitope-specific mimotopes is analyzed to identify epitope specific "signs" and 2) The identification phase where immunoaffinity-selected mimotopes are interrogated for the presence of the epitope specific "signs" and assigned to specific epitopes. We are currently using computational methods to define epitope "signs" without the need for prior knowledge of specific mimotopes. This technology provides an important tool for characterizing the breadth of antibody specificities within polyclonal antisera.}, } @article {pmid20943940, year = {2010}, author = {Wang, Y and Denisova, JV and Kang, KS and Fontes, JD and Zhu, BT and Belousov, AB}, title = {Neuronal gap junctions are required for NMDA receptor-mediated excitotoxicity: implications in ischemic stroke.}, journal = {Journal of neurophysiology}, volume = {104}, number = {6}, pages = {3551-3556}, pmid = {20943940}, issn = {1522-1598}, support = {HD-002528/HD/NICHD NIH HHS/United States ; P20 RR-024214/RR/NCRR NIH HHS/United States ; R01 DA-015088/DA/NIDA NIH HHS/United States ; R01 NS-064256/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Blood-Brain Barrier ; Brain Ischemia/chemically induced/*physiopathology ; Cells, Cultured/drug effects/physiology ; Connexins/deficiency ; Dentate Gyrus/drug effects/pathology ; Dizocilpine Maleate/pharmacology/therapeutic use ; Excitatory Amino Acid Antagonists/pharmacology/therapeutic use ; Gap Junctions/drug effects/*physiology ; Male ; Mefloquine/pharmacology/therapeutic use ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; N-Methylaspartate/pharmacokinetics/*toxicity ; Nerve Degeneration/*chemically induced/prevention & control ; Neurons/*physiology ; Neurotoxins/pharmacokinetics/*toxicity ; Patch-Clamp Techniques ; Photochemistry ; Receptors, N-Methyl-D-Aspartate/drug effects/*physiology ; Rose Bengal/radiation effects/toxicity ; }, abstract = {N-methyl-D-aspartate receptors (NMDARs) play an important role in cell survival versus cell death decisions during neuronal development, ischemia, trauma, and epilepsy. Coupling of neurons by electrical synapses (gap junctions) is high or increases in neuronal networks during all these conditions. In the developing CNS, neuronal gap junctions are critical for two different types of NMDAR-dependent cell death. However, whether neuronal gap junctions play a role in NMDAR-dependent neuronal death in the mature CNS was not known. Using Fluoro-Jade B staining, we show that a single intraperitoneal administration of NMDA (100 mg/kg) to adult wild-type mice induces neurodegeneration in three forebrain regions, including rostral dentate gyrus. However, the NMDAR-mediated neuronal death is prevented by pharmacological blockade of neuronal gap junctions (with mefloquine, 30 mg/kg) and does not occur in mice lacking neuronal gap junction protein, connexin 36. Using Western blots, electrophysiology, calcium imaging, and gas chromatography-mass spectrometry in wild-type and connexin 36 knockout mice, we show that the reduced level of neuronal death in knockout animals is not caused by the reduced expression of NMDARs, activity of NMDARs, or permeability of the blood-brain barrier to NMDA. In wild-type animals, this neuronal death is not caused by upregulation of connexin 36 by NMDA. Finally, pharmacological and genetic inactivation of neuronal gap junctions in mice also dramatically reduces neuronal death caused by photothrombotic focal cerebral ischemia. The results indicate that neuronal gap junctions are required for NMDAR-dependent excitotoxicity and play a critical role in ischemic neuronal death.}, } @article {pmid20726964, year = {2010}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Wozniak, M and Grzybowski, T and Dambueva, I and Zakharov, I}, title = {Phylogeography of the Y-chromosome haplogroup C in northern Eurasia.}, journal = {Annals of human genetics}, volume = {74}, number = {6}, pages = {539-546}, doi = {10.1111/j.1469-1809.2010.00601.x}, pmid = {20726964}, issn = {1469-1809}, mesh = {Chromosomes, Human, Y/*genetics ; Ethnicity/genetics ; Europe, Eastern ; Asia, Eastern ; Genetic Variation ; *Haplotypes ; Humans ; Male ; Microsatellite Repeats ; *Phylogeography ; Polymorphism, Single Nucleotide ; Siberia ; }, abstract = {To reconstruct the phylogenetic structure of Y-chromosome haplogroup (hg) C in populations of northern Eurasia, we have analyzed the diversity of microsatellite (STR) loci in a total sample of 413 males from 18 ethnic groups of Siberia, Eastern Asia and Eastern Europe. Analysis of SNP markers revealed that all Y-chromosomes studied belong to hg C3 and its subhaplogroups C3c and C3d, although some populations (such as Mongols and Koryaks) demonstrate a relatively high input (more than 30%) of yet unidentified C3* haplotypes. Median joining network analysis of STR haplotypes demonstrates that Y-chromosome gene pools of populations studied are characterized by the presence of DNA clusters originating from a limited number of frequent founder haplotypes. These are subhaplogroup C3d characteristic for Mongolic-speaking populations, "star cluster" in C3* paragroup, and a set of DYS19 duplicated C3c Y-chromosomes. All these DNA clusters show relatively recent coalescent times (less than 3000 years), so it is probable that founder effects, including social selection resulting in high male fertility associated with a limited number of paternal lineages, may explain the observed distribution of hg C3 lineages.}, } @article {pmid20697660, year = {2010}, author = {Tarakina, NV and Neder, RB and Denisova, TA and Maksimova, LG and Baklanova, YV and Tyutyunnik, AP and Zubkov, VG}, title = {Defect crystal structure of new TiO(OH)2 hydroxide and related lithium salt Li2TiO3.}, journal = {Dalton transactions (Cambridge, England : 2003)}, volume = {39}, number = {35}, pages = {8168-8176}, doi = {10.1039/c0dt00354a}, pmid = {20697660}, issn = {1477-9234}, abstract = {Crystal structures of TiO(OH)(2) and Li(2)TiO(3) have been studied in detail and refined using X-ray powder diffraction data. Both compounds possess a high concentration of defects in the structure. The crystal structure of the Li(2)TiO(3) salt obtained at 700 degrees C reveals stacking faults of LiTi(2) metal layers, which leads to the appearance of short-range order in three possible space groups: C2/c, C2/m, P3(1)12. The possibility to stabilise this imperfect state increases the mobility of the Li(+) ions in the structure and allows the complete exchange of lithium by hydrogen in acid water solutions with formation of TiO(OH)(2). The crystal structure of TiO(OH)(2) belongs to the layered double hydroxide structure type with the 3R(1) sequence of oxygen layers and can be described as a stacking of charge-neutral metal oxyhydroxide slabs [(OH)(2)OTi(2)O(OH)(2)]. TiO(OH)(2) is the first layered double hydroxide structure formed by a cation with oxidation state +4 only.}, } @article {pmid20488990, year = {2010}, author = {Gibson, DG and Glass, JI and Lartigue, C and Noskov, VN and Chuang, RY and Algire, MA and Benders, GA and Montague, MG and Ma, L and Moodie, MM and Merryman, C and Vashee, S and Krishnakumar, R and Assad-Garcia, N and Andrews-Pfannkoch, C and Denisova, EA and Young, L and Qi, ZQ and Segall-Shapiro, TH and Calvey, CH and Parmar, PP and Hutchison, CA and Smith, HO and Venter, JC}, title = {Creation of a bacterial cell controlled by a chemically synthesized genome.}, journal = {Science (New York, N.Y.)}, volume = {329}, number = {5987}, pages = {52-56}, doi = {10.1126/science.1190719}, pmid = {20488990}, issn = {1095-9203}, mesh = {Bacterial Proteins/analysis ; Base Sequence ; *Bioengineering ; Cloning, Molecular ; DNA, Bacterial/chemical synthesis/genetics ; Escherichia coli/genetics ; Gene Deletion ; Genes, Bacterial ; *Genetic Engineering ; *Genome, Bacterial ; Molecular Sequence Data ; Mycoplasma capricolum/*genetics ; Mycoplasma mycoides/*genetics/growth & development/physiology/ultrastructure ; Phenotype ; Plasmids ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Saccharomyces cerevisiae/genetics ; Transformation, Bacterial ; }, abstract = {We report the design, synthesis, and assembly of the 1.08-mega-base pair Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and its transplantation into a M. capricolum recipient cell to create new M. mycoides cells that are controlled only by the synthetic chromosome. The only DNA in the cells is the designed synthetic DNA sequence, including "watermark" sequences and other designed gene deletions and polymorphisms, and mutations acquired during the building process. The new cells have expected phenotypic properties and are capable of continuous self-replication.}, } @article {pmid20457583, year = {2010}, author = {Malyarchuk, B and Derenko, M and Denisova, G and Kravtsova, O}, title = {Mitogenomic diversity in Tatars from the Volga-Ural region of Russia.}, journal = {Molecular biology and evolution}, volume = {27}, number = {10}, pages = {2220-2226}, doi = {10.1093/molbev/msq065}, pmid = {20457583}, issn = {1537-1719}, mesh = {Base Sequence ; DNA, Mitochondrial/*genetics ; Ethnicity/*genetics ; Evolution, Molecular ; *Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; Humans ; Models, Genetic ; Molecular Sequence Data ; *Phylogeny ; Polymorphism, Restriction Fragment Length ; Russia ; Sequence Analysis, DNA ; }, abstract = {To investigate diversity of mitochondrial gene pool of Tatars inhabiting the territory of the middle Volga River basin, 197 individuals from two populations representing Kazan Tatars and Mishars were subjected for analysis of mitochondrial DNA (mtDNA) control region variation. In addition, 73 mitochondrial genomes of individuals from Mishar population were sequenced completely. It was found that mitochondrial gene pool of the Volga Tatars consists of two parts, but western Eurasian component prevails considerably (84% on average) over eastern Asian one (16%). Eastern Asian mtDNAs detected in Tatars belonged to a heterogeneous set of haplogroups (A, C, D, G, M7, M10, N9a, Y, and Z), although only haplogroups A and D were revealed simultaneously in both populations. Complete mtDNA variation study revealed that the age of western Eurasian haplogroups (such as U4, HV0a, and H) is less than 18,000 years, thus suggesting re-expansion of eastern Europeans soon after the Last Glacial Maximum.}, } @article {pmid20336068, year = {2010}, author = {Krause, J and Fu, Q and Good, JM and Viola, B and Shunkov, MV and Derevianko, AP and Pääbo, S}, title = {The complete mitochondrial DNA genome of an unknown hominin from southern Siberia.}, journal = {Nature}, volume = {464}, number = {7290}, pages = {894-897}, pmid = {20336068}, issn = {1476-4687}, mesh = {Africa/ethnology ; Animals ; DNA, Mitochondrial/*genetics/isolation & purification ; Emigration and Immigration ; Extinction, Biological ; Finger Phalanges ; Genome, Mitochondrial/*genetics ; Hominidae/*classification/*genetics ; Humans ; Molecular Sequence Data ; *Phylogeny ; Sequence Alignment ; Siberia ; Time Factors ; }, abstract = {With the exception of Neanderthals, from which DNA sequences of numerous individuals have now been determined, the number and genetic relationships of other hominin lineages are largely unknown. Here we report a complete mitochondrial (mt) DNA sequence retrieved from a bone excavated in 2008 in Denisova Cave in the Altai Mountains in southern Siberia. It represents a hitherto unknown type of hominin mtDNA that shares a common ancestor with anatomically modern human and Neanderthal mtDNAs about 1.0 million years ago. This indicates that it derives from a hominin migration out of Africa distinct from that of the ancestors of Neanderthals and of modern humans. The stratigraphy of the cave where the bone was found suggests that the Denisova hominin lived close in time and space with Neanderthals as well as with modern humans.}, } @article {pmid20211840, year = {2010}, author = {Benders, GA and Noskov, VN and Denisova, EA and Lartigue, C and Gibson, DG and Assad-Garcia, N and Chuang, RY and Carrera, W and Moodie, M and Algire, MA and Phan, Q and Alperovich, N and Vashee, S and Merryman, C and Venter, JC and Smith, HO and Glass, JI and Hutchison, CA}, title = {Cloning whole bacterial genomes in yeast.}, journal = {Nucleic acids research}, volume = {38}, number = {8}, pages = {2558-2569}, pmid = {20211840}, issn = {1362-4962}, mesh = {Base Sequence ; Cloning, Molecular/*methods ; Diploidy ; Genetic Vectors/chemistry ; *Genome, Bacterial ; Molecular Sequence Data ; Mycoplasma/*genetics ; Mycoplasma genitalium/genetics ; Mycoplasma mycoides/genetics ; Mycoplasma pneumoniae/genetics ; Recombination, Genetic ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Most microbes have not been cultured, and many of those that are cultivatable are difficult, dangerous or expensive to propagate or are genetically intractable. Routine cloning of large genome fractions or whole genomes from these organisms would significantly enhance their discovery and genetic and functional characterization. Here we report the cloning of whole bacterial genomes in the yeast Saccharomyces cerevisiae as single-DNA molecules. We cloned the genomes of Mycoplasma genitalium (0.6 Mb), M. pneumoniae (0.8 Mb) and M. mycoides subspecies capri (1.1 Mb) as yeast circular centromeric plasmids. These genomes appear to be stably maintained in a host that has efficient, well-established methods for DNA manipulation.}, } @article {pmid21626818, year = {2010}, author = {Doronin, BM and Denisova, OA}, title = {[Disturbances of lipid metabolism in the period of age androgen deficit in middle-aged and elderly men with ischemic stroke].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {110}, number = {12 Pt 2}, pages = {52-54}, pmid = {21626818}, issn = {1997-7298}, mesh = {Aged ; Androgens/blood/deficiency ; Cholesterol/blood ; Humans ; Hyperlipidemias/*blood ; Intracranial Arteriosclerosis/*blood/*epidemiology ; Lipoproteins, LDL/blood ; Male ; Middle Aged ; Stroke/*blood ; Testosterone/blood/*deficiency ; Triglycerides/blood ; }, abstract = {Blood concentrations of total cholesterol, beta-lipoproteins, triglycerides and testosterone were studied in 73 men (mean age 65.9 +/- 8.6 years) with acute ischemic stroke. The concentrations of testosterone and triglycerides in men decrease with age and those of cholesterol and beta-lipoproteins do not depend on the age. In middle-aged patients, the negative correlations were found between concentrations of testosterone and beta-lipoproteins (r = -0.404; p < 0.05); testosterone and cholesterol (r = -0.273; p < 0.001). In elderly patients, there were negative correlations between concentrations of testosterone and triglycerides (r = -0.348; p < 0.05). In middle-aged and elderly patients, concentrations of triglycerides and testosterone were negatively correlated (r = -0.478; p < 0.001). The lower blood testosterone level was associated with the higher risk of the development of atherosclerotic lesions of major arteries that allowed to estimate risks of ischemic stroke in middle-aged and elderly men.}, } @article {pmid19882902, year = {2009}, author = {Baranova, EN and Sharipova, IN and Denisova, NM and Susekina, ME and Puzyrev, VF and Sarkisian, KA and Vorob'eva, MS and Burkov, AN and Ulanova, TI}, title = {[The capacities of current test systems to verify early HIV infection].}, journal = {Voprosy virusologii}, volume = {54}, number = {5}, pages = {37-40}, pmid = {19882902}, issn = {0507-4088}, mesh = {AIDS Serodiagnosis/*methods ; HIV Antibodies/blood ; HIV Core Protein p24/blood ; HIV Infections/blood/*diagnosis ; HIV-1/*immunology ; HIV-2/*immunology ; Humans ; Immunoblotting ; Immunoenzyme Techniques/*methods ; *Reagent Kits, Diagnostic ; Sensitivity and Specificity ; }, abstract = {The purpose of the present investigation was to comparatively evaluate the performance characteristics of the test systems designed to verify the positive results of screening survey for HIV infection, such as the solid-phase immunoassay DS-EIA-HIV-AB/AG-SPECTR (Diagnosticheskiye Sistemy (Diagnostic Systems) Research-and-Production Association, Nizhni Novgorod) and tests based on immune blotting (IB). The investigation examined 15 seroconversion panels produced by ZeptoMetrix (USA) and BBI (USA). The use of the DS-EIA-HIV-AB/AG-SPECTR test system determined 88 of the 167 seroconversion panels as HIV positive. The IB-based tests revealed only 45 of the 167 samples as positive. Consequently, the application of the DS-EIA-HIV-AB/AG-SPECTR test system is more effective than the IB-based tests in early HIV infection.}, } @article {pmid19795792, year = {2009}, author = {Zemlianskikh, NG and Denisova, ON}, title = {[Changes in erythrocyte membrane-cytoskeleton complex, induced by dimethyl sulfoxide, polyethylene glycol, and low temperature].}, journal = {Biofizika}, volume = {54}, number = {4}, pages = {693-703}, pmid = {19795792}, issn = {0006-3029}, mesh = {Animals ; Cryoprotective Agents/*chemistry/pharmacology ; Cytoskeleton/*chemistry/metabolism ; Dimethyl Sulfoxide/*chemistry/pharmacology ; Dogs ; Erythrocyte Membrane/*chemistry/metabolism ; Freezing ; Oxidation-Reduction/drug effects ; Polyethylene Glycols/*chemistry/pharmacology ; Surface-Active Agents/*chemistry/pharmacology ; }, abstract = {The effect of the cryoprotectants DMSO and PEG-1500 as well as freezing-thawing on the proteins of the canine erythrocyte membrane-cytoskeleton complex has been studied using the cross-linking reagent diamide. It was shown that the intensity of distortions in the protein network structure correlated to an increase in SH-group accessibility for the oxidation by this compound and accordingly, the enhancement of the formation of high-molecular-weight protein aggregates. The maximum level of diamide-induced aggregability was revealed upon freezing of erythrocytes in liquid nitrogen without the cryoprotectant. The electrophoretical analysis of the ghost proteins of erythrocytes incubated with cryoprotectants showed a significant increase in the aggregation level only in cells present in the polymer solution. After the freezing-thawing cycle, the diamide-induced protein aggregability in erythrocytes cryopreserved with PEG-1500 strongly increased, while if DMSO was used for cell protection, the level of aggregates was much less pronounced than in the control. One can suppose that the exocellular cryoprotectant PEG-1500, as distinct from the endocellular cryoprotectant DMSO, is unable to provide the preservation of the structure of the membrane-cytoskeleton protein complex at the acceptable level necessary for the maintenance of cell integrity after the return to the physiological conditions.}, } @article {pmid19705797, year = {2009}, author = {Stotskaia, TV and Mravian, SR and Vishniakova, MV and Vashchenko, AV and Stepanova, EA and Denisova, LB and Grigor'eva, NM}, title = {[Kawasaki disease in an adult European].}, journal = {Klinicheskaia meditsina}, volume = {87}, number = {7}, pages = {63-66}, pmid = {19705797}, issn = {0023-2149}, mesh = {Adult ; Humans ; Male ; Mucocutaneous Lymph Node Syndrome/*diagnosis/drug therapy ; White People ; }, abstract = {A case of Kawasaki disease is reported with manifestations of autoimmune vasculitis and predominant affection of coronary arteries. The relevant literature review describes major symptoms of this pathology and risk factors of its atypical forms. It is emphasized that rare occurrence of Kawasaki disease among non-mongoloid subjects should not make the general practitioner les suspicious of this condition.}, } @article {pmid19696314, year = {2009}, author = {Lartigue, C and Vashee, S and Algire, MA and Chuang, RY and Benders, GA and Ma, L and Noskov, VN and Denisova, EA and Gibson, DG and Assad-Garcia, N and Alperovich, N and Thomas, DW and Merryman, C and Hutchison, CA and Smith, HO and Venter, JC and Glass, JI}, title = {Creating bacterial strains from genomes that have been cloned and engineered in yeast.}, journal = {Science (New York, N.Y.)}, volume = {325}, number = {5948}, pages = {1693-1696}, doi = {10.1126/science.1173759}, pmid = {19696314}, issn = {1095-9203}, mesh = {Centromere ; *Cloning, Molecular ; DNA Methylation ; DNA Restriction Enzymes/genetics/metabolism ; Deoxyribonucleases, Type III Site-Specific/genetics ; *Gene Transfer Techniques ; *Genetic Engineering ; *Genome, Bacterial ; Mycoplasma capricolum/*genetics ; Mycoplasma mycoides/*genetics/growth & development/isolation & purification ; Plasmids ; Saccharomyces cerevisiae/*genetics ; Sequence Analysis, DNA ; Sequence Deletion ; Transformation, Bacterial ; }, abstract = {We recently reported the chemical synthesis, assembly, and cloning of a bacterial genome in yeast. To produce a synthetic cell, the genome must be transferred from yeast to a receptive cytoplasm. Here we describe methods to accomplish this. We cloned a Mycoplasma mycoides genome as a yeast centromeric plasmid and then transplanted it into Mycoplasma capricolum to produce a viable M. mycoides cell. While in yeast, the genome was altered by using yeast genetic systems and then transplanted to produce a new strain of M. mycoides. These methods allow the construction of strains that could not be produced with genetic tools available for this bacterium.}, } @article {pmid19566074, year = {2009}, author = {Denisova, EA and Kirichenko, LL and Rushkevich, OP}, title = {[Structural and functional changes in heart under medical therapy in mental workers having arterial hypertension].}, journal = {Meditsina truda i promyshlennaia ekologiia}, volume = {}, number = {5}, pages = {23-26}, pmid = {19566074}, issn = {1026-9428}, mesh = {Antihypertensive Agents/*therapeutic use ; Disease Progression ; Echocardiography ; Electrocardiography ; Female ; Follow-Up Studies ; Heart Ventricles/*diagnostic imaging/physiopathology ; Humans ; Hypertension/*drug therapy/etiology/physiopathology ; Male ; Middle Aged ; Occupational Diseases/*drug therapy/etiology/physiopathology ; Prognosis ; Stress, Psychological/*complications/physiopathology ; Ventricular Function, Left/*physiology ; }, abstract = {Aim of the study was to study main structural and functional parameters of heart, evaluate efficiency of treatment (Egiloc, Cardilopin, their combination) in arterial hypertension patients. Examinations including ECG, EchoCG were performed initially, in 3 and 6 months after the treatment start. The study covered 126 patients with arterial hypertension II degree, who received the medium-dose therapy, and 34 apparently healthy individuals.}, } @article {pmid19537091, year = {2009}, author = {Lideman, LF and Denisov, DA and Gibadulin, RA and Denisova, GF}, title = {[Autoimmune response in HIV-infected patients is directed against CD4 domain 4].}, journal = {Voprosy virusologii}, volume = {54}, number = {3}, pages = {12-16}, pmid = {19537091}, issn = {0507-4088}, mesh = {Alanine/genetics ; Algorithms ; Amino Acid Sequence ; Amino Acid Substitution ; *Autoimmunity ; CD4 Antigens/chemistry/genetics/*immunology ; Cell Line ; Epitope Mapping ; Epitopes, T-Lymphocyte/chemistry/genetics/*immunology ; HIV Infections/*immunology ; HIV-1/*immunology ; Humans ; Models, Molecular ; Peptide Library ; Protein Structure, Tertiary/genetics ; }, abstract = {Phage display epitope library technology and a novel computer algorithm have been used for the localization of CD4 epitopes specific for monoclonal antibody (mAb) T6 and autoimmune antibodies found in an HIV infected patient. Both predicted epitope clusters have been shown to overlap and to be localized within the domain 4 of CD4. They included Cys303, Glu304, Glu330, and Lys331 amino acids. Few amino acids predicted by the algorithm as the epitope residues and two residues that did not relate to the epitope were sequentially substituted for Ala. Further analysis of the mutated forms of sCD4 expressed in 293T cells transfected with the corresponding DNAs, supported the predicted localization of the mAb T6 epitope. The results demonstrate that the autoimmune response in HIV-infected patients is directed against domain D4 of sCD4.}, } @article {pmid19526099, year = {2008}, author = {Cheknyov, SB and Babayants, AA and Denisova, EA}, title = {Induction of interferon production by conformation-modified proteins of plasma gamma-globulin fraction.}, journal = {Bulletin of experimental biology and medicine}, volume = {146}, number = {5}, pages = {591-595}, doi = {10.1007/s10517-009-0349-x}, pmid = {19526099}, issn = {0007-4888}, mesh = {Cells, Cultured ; Copper/metabolism ; Gene Expression Regulation/*drug effects ; Humans ; Interferon-gamma/metabolism ; Interferons/*metabolism ; Leukocytes/*drug effects/*metabolism ; Protein Binding ; Protein Conformation ; Zinc/metabolism ; gamma-Globulins/*chemistry/metabolism/*pharmacology ; }, abstract = {Plasma gamma-globulin fraction proteins, copper and zinc cations, and metal-modified gamma-globulins induce the production of IFN by human leukocytes. Binding of zinc cations attenuates the realization of the IFN-inducing effects of human serum gamma-globulin, while binding of copper cations potentiated this effect. Activity of IFN and the dynamics of its production correspond to those in response to phytohemagglutinin stimulation. The pool of induced IFN contains acid-labile (up to 60%) and acid-stable (up to 40%) constituents. Anti-IFN-alpha antibodies do not modify activity of produced IFN. The results indicate the possibility of gamma-globulin conformation allowing stimulation or attenuation of the protein capacity to induce the production of IFN pool with predominant content of IFN-gamma.}, } @article {pmid19518411, year = {2009}, author = {Denisov, SI and Lyutyy, TV and Denisova, ES and Hänggi, P and Kantz, H}, title = {Directed transport in periodically rocked random sawtooth potentials.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {79}, number = {5 Pt 1}, pages = {051102}, doi = {10.1103/PhysRevE.79.051102}, pmid = {19518411}, issn = {1539-3755}, abstract = {We study directed transport of overdamped particles in a periodically rocked random sawtooth potential. Two transport regimes can be identified which are characterized by a nonzero value of the average velocity of particles and a zero value, respectively. The properties of directed transport in these regimes are investigated both analytically and numerically in terms of a random sawtooth potential and a periodically varying driving force. Precise conditions for the occurrence of transition between these two transport regimes are derived and analyzed in detail.}, } @article {pmid19514440, year = {2009}, author = {Denisova, EN and Sharipova, VR and Purlo, NV and Sukhanova, GA and Biriukova, LS}, title = {[Use of fractional plasma separation and adsorption (Prometheus technology) in the treatment of acute liver failure].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {2}, pages = {45-49}, pmid = {19514440}, issn = {0201-7563}, mesh = {Adolescent ; Adsorption ; Adult ; Aged ; Bilirubin/blood ; Extracorporeal Circulation/instrumentation/*methods ; Female ; Humans ; Liver Failure, Acute/blood/etiology/*therapy ; Male ; Middle Aged ; *Plasma ; Sorption Detoxification/instrumentation/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {This paper presents the results of treating 8 patients with acute liver failure, by using the separation and adsorption of fractional plasma (Prometheus technology). Twenty-five procedures lasting 5-6 hours were performed. Anticoagulation with heparin was made under guidance of coagulogram parameters. The results of testing blood parameters before and after a procedure and hemodynamic parameters are given. The investigations have demonstrated the effectiveness and safety of the procedure.}, } @article {pmid19390580, year = {2009}, author = {Denisova, G and Denisov, D and Evelegh, C and Weissgram, M and Beck, J and Foley, SR and Bramson, JL}, title = {Characterizing complex polysera produced by antigen-specific immunization through the use of affinity-selected mimotopes.}, journal = {PloS one}, volume = {4}, number = {4}, pages = {e5309}, pmid = {19390580}, issn = {1932-6203}, mesh = {Algorithms ; Animals ; Cell Proliferation ; Epitopes/*chemistry/*immunology ; Immune Sera/*immunology ; Immunization ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Peptide Library ; Rats ; Receptor, ErbB-2/metabolism ; }, abstract = {BACKGROUND: Antigen-based (as opposed to whole organism) vaccines are actively being pursued for numerous indications. Even though different formulations may produce similar levels of total antigen-specific antibody, the composition of the antibody response can be quite distinct resulting in different levels of therapeutic activity.

Using plasmid-based immunization against the proto-oncogene HER-2 as a model, we have demonstrated that affinity-selected epitope mimetics (mimotopes) can provide a defined signature of a polyclonal antibody response. Further, using novel computer algorithms that we have developed, these mimotopes can be used to predict epitope targets.

CONCLUSIONS/SIGNIFICANCE: By combining our novel strategy with existing methods of epitope prediction based on physical properties of an individual protein, we believe that this method offers a robust method for characterizing the breadth of epitope-specificity within a specific polyserum. This strategy is useful as a tool for monitoring immunity following vaccination and can also be used to define relevant epitopes for the creation of novel vaccines.}, } @article {pmid19297016, year = {2009}, author = {Denisova, LA and Maev, RG and Leontjev, VK and Denisov, AF and Grayson, GG and Rusanov, FS and Bakulin, EY and Gavrilov, DY and Grineva, TV}, title = {A study of the adhesion between dental cement and dentin using a nondestructive acoustic microscopy approach.}, journal = {Dental materials : official publication of the Academy of Dental Materials}, volume = {25}, number = {5}, pages = {557-565}, doi = {10.1016/j.dental.2008.10.011}, pmid = {19297016}, issn = {1879-0097}, mesh = {Adhesiveness ; *Dental Bonding ; Dental Stress Analysis ; Dentin/*diagnostic imaging ; *Dentin-Bonding Agents ; Glass Ionomer Cements ; Humans ; Materials Testing/methods ; *Microscopy, Acoustic ; Tensile Strength ; }, abstract = {OBJECTIVES: The goal of the present study was to investigate the potential for acoustic microscopy techniques to characterize the cement-dentin interface in restored teeth.

METHODS: Special flat-parallel specimens and whole extracted teeth with restorations were scanned using a high-frequency (50 MHz) focused ultrasonic transducer. Visual acoustic images (B- and C-scans) of the cement-dentin interface were obtained nondestructively, analyzed and compared with optical images taken after the samples were cut along the scanning axis. The shear bonding strength of a subsection of specimens was tested in a Lloyd material testing machine.

RESULTS: An essential distinction between the acoustical properties associated with good and failed bonding has been shown. In the case of failed adhesion, the ultrasound signal reflection from the cement-dentin interface is up to four to seven times higher in magnitude than in the case of good bonding. The comparison of the ultrasound imaging data with the data obtained using an optical microscope revealed a strong correspondence with the acoustical and optical results with respect to the presence, position and dimensions of the defects. The specimens showing higher ultrasound reflection from cement/dentin interface have also shown lower shear bonding strength.

SIGNIFICANCE: The results demonstrate that acoustic scanning with a high-frequency focused ultrasonic probe is a valuable method for nondestructive morpho-mechanical analysis of cement/dentin interface for either experimental models or whole restored teeth. An appropriately expanded approach can be widely used for the pre-clinical evaluation of dental materials. Further, this method may prove beneficial in the design of new diagnostic ultrasound devices and techniques for use within clinical dentistry.}, } @article {pmid19145899, year = {2008}, author = {Denisova, TP and Tiul'tiaeva, LA}, title = {[Peptic ulcer in industrial region: 25-year survey].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {4}, pages = {21-24}, pmid = {19145899}, issn = {1682-8658}, mesh = {Data Interpretation, Statistical ; Health Surveys ; Humans ; *Industry ; Kinetics ; Peptic Ulcer/*epidemiology/etiology/mortality ; Russia/epidemiology ; Severity of Illness Index ; Socioeconomic Factors ; }, abstract = {In the article the dynamics of gravity of the course of ulcer among the inhabitants of industrial region during the 25-summer period is analyzed, including the years of social stability, social stress and output from it. The index of the lethality of the patients with ulcer is used as the criterion of gravity. Temporary dependences and speed characteristics of studied statistical data underwent analysis. The interrelation of gravity of the course of ulcer with the social life of society is established.}, } @article {pmid20201400, year = {2009}, author = {Rachina, SA and Fokin, AA and Mishchenko, VV and Ishmukhametov, AA and Denisova, MN}, title = {[Comparative analysis of the use of antimicrobials with systemic action in outpatients in the Russian Federation, Ukraine and Kazakhstan].}, journal = {Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]}, volume = {54}, number = {7-8}, pages = {24-29}, pmid = {20201400}, issn = {0235-2990}, mesh = {*Ambulatory Care ; Anti-Bacterial Agents/*administration & dosage ; Drug Utilization/*statistics & numerical data ; Humans ; Kazakhstan ; Russia ; Ukraine ; }, } @article {pmid20201309, year = {2009}, author = {Baryshnikova, NV and Denisova, EV and Kornienko, EA and Lobach, SM and Loeva, IA and Parolova, NI and Ryzhikh, VA and Solonitsin, EG and Smirnova, AS and Starostin, BD and Suvorov, AN and Suvorova, MA and Tkachenko, EI and Uspenskiĭ, IuP}, title = {[Epidemiological research of Helicobacter pylori resistance to clarithromycin at inhabitants of Sankt of Petersburg with a stomach ulcer].}, journal = {Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology}, volume = {}, number = {5}, pages = {73-76}, pmid = {20201309}, issn = {1682-8658}, mesh = {Anti-Bacterial Agents/*administration & dosage ; Clarithromycin/*administration & dosage ; *Drug Resistance, Bacterial ; Female ; *Helicobacter Infections/drug therapy/epidemiology ; *Helicobacter pylori ; Humans ; Male ; Russia/epidemiology ; *Stomach Ulcer/drug therapy/epidemiology/microbiology ; Urban Population ; }, } @article {pmid19110593, year = {2008}, author = {Cheknyov, SB and Denisova, EA and Mongush, EM and Shukhovtseva, YV}, title = {The Results of Mancini's test depend on the presence bound metal cations in the test protein.}, journal = {Bulletin of experimental biology and medicine}, volume = {145}, number = {4}, pages = {457-459}, doi = {10.1007/s10517-008-0117-3}, pmid = {19110593}, issn = {0007-4888}, mesh = {Blood Chemical Analysis/*methods/standards ; Cations/chemistry/*metabolism/pharmacology ; Copper/chemistry/metabolism ; Humans ; Metals/chemistry/*metabolism/pharmacology ; Osmolar Concentration ; Protein Binding ; Serologic Tests/methods/standards ; Zinc/chemistry/metabolism ; gamma-Globulins/*analysis/*metabolism ; }, abstract = {Samples of human serum gamma-globulin with specifically bound copper or zinc cations were studied in Mancini's radial immunodiffusion test with human antibodies to IgG (H+L). The intensity of antibody binding to zinc-modified protein was 10-20% higher in comparison with the reference sample, while detection of gamma-globulin with bound copper by antibodies was 20-30% lower than in the corresponding reference sample. Comparison with the results of native gamma-globulin testing indicates limitations of Mancini's method as the quantitative assay for practical diagnosis, because under certain clinical conditions the traditional method can give over- and underestimated results.}, } @article {pmid19038455, year = {2009}, author = {Denisov, DA and Denisova, GF and Lelic, A and Loeb, MB and Bramson, JL}, title = {Deciphering epitope specificities within polyserum using affinity selection of random peptides and a novel algorithm based on pattern recognition theory.}, journal = {Molecular immunology}, volume = {46}, number = {3}, pages = {429-436}, doi = {10.1016/j.molimm.2008.10.013}, pmid = {19038455}, issn = {0161-5890}, support = {N01-AI-40066/AI/NIAID NIH HHS/United States ; }, mesh = {*Algorithms ; Amino Acid Sequence ; Chromatography, Affinity ; Computational Biology ; Epitopes/chemistry/*immunology ; Humans ; Immune Sera/*immunology ; Molecular Sequence Data ; *Pattern Recognition, Automated ; Peptides/chemistry/*immunology/*isolation & purification ; West Nile Fever/immunology ; West Nile virus/chemistry/immunology ; }, abstract = {While numerous strategies have been developed to map epitope specificities for monoclonal antibodies, few have been designed for elucidating epitope specificity within complex polysera. We have developed a novel algorithm based on pattern recognition theory that can be used to characterize the breadth of epitope specificities within a polyserum based on affinity selection of random peptides. To attribute these random peptides to a specific epitope, the sequences of the affinity-selected peptides were matched against a database of random peptides selected using well-described monoclonal antibodies. To test this novel algorithm, we employed polyserum from patients infected with West Nile virus and isolated 109 unique sequences which were recognized selectively by serum from West Nile virus-infected patients but not uninfected patients. Through application of our algorithm, it was possible to match 20% of the polyserum-selected peptides to the database of peptides isolated by affinity selection using monoclonal antibodies against the virus envelope protein. Statistical analysis demonstrated that the peptides selected with the polyserum could not be attributed to the peptide database by chance. This novel algorithm provides the basis for further development of methods to characterize the breadth of epitope recognition within a complex pool of antibodies.}, } @article {pmid18942387, year = {2008}, author = {Sidorenko, SV and Agapova, ED and Aleksandrova, IA and Bichul', OK and Vereshchagina, SA and Galeeva, EV and Denisova, OI and Eremina, LV and Ivanov, DV and Ivanova, TA and Ivanova, SF and Katosova, LK and Kirilin, DN and Kostina, GV and Kozlova, TA and Makeeva, NN and Marusina, NE and Monakhova, SI and Morozova, NA and Moskvitina, EN and Plakhoshchniuk, L and Rozanova, SM and Solov'eva, TD and Sukhoreva, MV and Sychev, IN and Tikhonov, IuG and Shumilova, MO and Furletova, NM and Shustrova, TA}, title = {[Cross and associated antibiotic resistance of gramnegative bacteria of the family Enterobacteriaceae resistant to the 3rd generation cephalosporins].}, journal = {Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]}, volume = {53}, number = {1-2}, pages = {10-18}, pmid = {18942387}, issn = {0235-2990}, mesh = {Anti-Bacterial Agents/*pharmacology ; Cephalosporins/*pharmacology ; Drug Resistance, Bacterial/*physiology ; Enterobacteriaceae/*enzymology/growth & development/*isolation & purification ; }, } @article {pmid18825996, year = {2008}, author = {Denisova, TV and Kazeev, KSh and Kolesnikov, SI and Val'kov, VF}, title = {[The stability of enzyme activity and the content of microflora of different soils of the South of Russia to influence of a variable magnetic field of industrial frequency].}, journal = {Radiatsionnaia biologiia, radioecologiia}, volume = {48}, number = {4}, pages = {481-486}, pmid = {18825996}, issn = {0869-8031}, mesh = {Bacteria/isolation & purification/metabolism/*radiation effects ; *Electromagnetic Fields ; Enzyme Stability ; Enzymes/metabolism/*radiation effects ; Fungi/isolation & purification/metabolism/*radiation effects ; Russia ; Soil/analysis ; *Soil Microbiology ; }, abstract = {In modelling experiments of the influence of variable magnetic field of industrial frequency (50 Hz) by induction of 1500 and 6000 mkTl during 5 days on microflora and on enzyme activity of soils the South of Russia of different genesis and properties is investigated.}, } @article {pmid18825995, year = {2008}, author = {Rogacheva, SM and Denisova, SA and Shul'gin, SV and Somov, AIu and Kuznetsov, PE}, title = {[Biological effects of electromagnetic radiation of extremely high frequencies combined with physiologically active compounds].}, journal = {Radiatsionnaia biologiia, radioecologiia}, volume = {48}, number = {4}, pages = {474-480}, pmid = {18825995}, issn = {0869-8031}, mesh = {Animals ; Antiprotozoal Agents/*pharmacology ; Cell Movement/drug effects/radiation effects ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Hydrogen Bonding/drug effects/radiation effects ; Metronidazole/*pharmacology ; *Microwaves ; Nicotine/*pharmacology ; Paramecium caudatum/*drug effects/*radiation effects ; Time Factors ; }, abstract = {The study of the action of the electromagnetic radiation (EMR) of low intensity (10 microW/cm2) in the range of frequencies 120-170 GHz at the test-reaction of Infusoria Paramecium caudatum was carried out. The resonant character of the effects was established. The EMR action at 156.6 and 161.3 GHz caused the increase of infusorians mobility, the action at frequencies 151.8, 155.7, 167.1 GHz caused the mobility reduction. Isolated and combined with EMR effects of nicotine (10(-4)-10(-15) mol/l) and antimicrobial drug metronidazole (10(-5), 10(-8), 10(-9) mol/l) were investigated. The radiation at the frequency 167.1 GHz was shown to reduce the effect of nicotine (10(-9) mol/l) and to enhance the effect of metronidazole (10(-9) mol/l). This phenomenon may be explained by different effects of the substances in low concentration at the water hydrogen bonds net structure.}, } @article {pmid18778753, year = {2008}, author = {Arumugam, H and Denisova, JV and Neve, RL and Corriveau, RA and Belousov, AB}, title = {Use of calcium imaging for analysis of neuronal gap junction coupling.}, journal = {Neuroscience letters}, volume = {445}, number = {1}, pages = {26-30}, pmid = {18778753}, issn = {0304-3940}, support = {P20 RR016816/RR/NCRR NIH HHS/United States ; R01 DA015088/DA/NIDA NIH HHS/United States ; R01 DA015088-05/DA/NIDA NIH HHS/United States ; P20RR16816/RR/NCRR NIH HHS/United States ; }, mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology ; Analysis of Variance ; Anesthetics/pharmacology ; Animals ; Bicuculline/pharmacology ; CREB-Binding Protein/metabolism/pharmacology ; Calcium/*metabolism ; Cells, Cultured ; Connexins/deficiency ; Diagnostic Imaging/*methods ; Embryo, Mammalian ; Excitatory Amino Acid Antagonists/pharmacology ; GABA Antagonists/pharmacology ; Gap Junctions/*metabolism ; Glycyrrhetinic Acid/pharmacology ; Halothane/pharmacology ; Hypothalamus, Middle/cytology ; Mice ; Mice, Knockout ; Neurons/drug effects/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/deficiency ; Valine/analogs & derivatives/pharmacology ; }, abstract = {We recently used Western blots for connexin 36 and neuronal dye coupling with neurobiotin to measure developmental decrease in neuronal gap junction coupling in cell cultures. To ask whether Ca2+ imaging also can be used to measure changes in the amount of neuronal gap junction coupling, we defined a Ca2+ coupling coefficient as the percentage of neurons with bicuculline-induced increases in intracellular Ca2+ that are suppressed by blocking gap junctions. We demonstrate in rat and mouse hypothalamic neuronal cultures that the Ca2+ coupling coefficient decreases during culture development, this decrease is prevented by manipulations that also prevent developmental decrease in neuronal gap junction coupling, and the coefficient is low in cultures lacking connexin 36. The results indicate that Ca2+ imaging is a useful tool to quantify the amount of neuronal gap junction coupling in cultures.}, } @article {pmid18760481, year = {2008}, author = {Denisova, GF and Denisov, DA and Yeung, J and Loeb, MB and Diamond, MS and Bramson, JL}, title = {A novel computer algorithm improves antibody epitope prediction using affinity-selected mimotopes: a case study using monoclonal antibodies against the West Nile virus E protein.}, journal = {Molecular immunology}, volume = {46}, number = {1}, pages = {125-134}, pmid = {18760481}, issn = {0161-5890}, support = {N01AI40066/AI/NIAID NIH HHS/United States ; U01 AI061373/AI/NIAID NIH HHS/United States ; U01 AI061373-04/AI/NIAID NIH HHS/United States ; AI-061373/AI/NIAID NIH HHS/United States ; }, mesh = {*Algorithms ; Amino Acid Sequence ; Antibodies, Monoclonal/*immunology ; Antibody Affinity/*immunology ; *Computers ; Epitopes/chemistry/*immunology ; Models, Molecular ; Molecular Sequence Data ; Structural Homology, Protein ; Viral Proteins/chemistry/*immunology ; West Nile virus/*immunology ; }, abstract = {Understanding antibody function is often enhanced by knowledge of the specific binding epitope. Here, we describe a computer algorithm that permits epitope prediction based on a collection of random peptide epitopes (mimotopes) isolated by antibody affinity purification. We applied this methodology to the prediction of epitopes for five monoclonal antibodies against the West Nile virus (WNV) E protein, two of which exhibit therapeutic activity in vivo. This strategy was validated by comparison of our results with existing F(ab)-E protein crystal structures and mutational analysis by yeast surface display. We demonstrate that by combining the results of the mimotope method with our data from mutational analysis, epitopes could be predicted with greater certainty. The two methods displayed great complementarity as the mutational analysis facilitated epitope prediction when the results with the mimotope method were equivocal and the mimotope method revealed a broader number of residues within the epitope than the mutational analysis. Our results demonstrate that the combination of these two prediction strategies provides a robust platform for epitope characterization.}, } @article {pmid18686374, year = {2007}, author = {Avakian, GN and Denisova, SV and Oleĭnikova, OM and Kurbanova, SA}, title = {[A role of circadian factors and melatonin in the development of epileptic paroxysms].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {107}, number = {9}, pages = {85-92}, pmid = {18686374}, issn = {1997-7298}, mesh = {Brain/*metabolism ; Circadian Rhythm/*physiology ; Disease Progression ; Epilepsy/*metabolism/*physiopathology ; Humans ; Melatonin/*metabolism ; Prognosis ; }, } @article {pmid18494287, year = {2008}, author = {Ivanov, SV and Zhabin, SN and Gorbacheva, OS and Barsukov, VS and Denisova, EIu}, title = {[Multifactor analysis of nodular goiter by the method of artificial neural network].}, journal = {Klinicheskaia meditsina}, volume = {86}, number = {4}, pages = {49-50}, pmid = {18494287}, issn = {0023-2149}, mesh = {Biopsy, Needle ; Diagnosis, Differential ; Follow-Up Studies ; Goiter, Nodular/*diagnosis/surgery ; Humans ; *Neural Networks, Computer ; Predictive Value of Tests ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {Study of 297 patients with preparative methods of nontoxic nodular goiter and cytological diagnose "adenomatosis" with the use of artificial neural network (ANN) were analyzed. Malignant pathology could be supposed with 95.5% accuracy when we applied experience of trained ANN. Clinical, instrumental and cytologic criteria, which make possible to prognosticate degree of malignant process in thyroid gland parenchyma, were determined. Painless elastic nodules with sonographically iso- o hyperechogenic structure, with clear outline and cytologically determined adenomatosis in combination with colloid can be interpreted as benign lesion of thyroid gland.}, } @article {pmid18454113, year = {2008}, author = {Denisova, LA and Maev, RG and Leont'ev, VK and Denisov, AF and Greĭson, GG and Rusanov, FS and Bakulin, EIu and Gavrilov, DIu and Grineva, TV}, title = {[Acoustic microscopy application for the evaluation of restorative materials bonding quality. Experimental investigation].}, journal = {Stomatologiia}, volume = {87}, number = {2}, pages = {15-24}, pmid = {18454113}, issn = {0039-1735}, mesh = {Dental Caries/*diagnostic imaging/therapy ; Dental Materials/*analysis ; Humans ; Microscopy, Acoustic/*methods ; *Models, Biological ; }, abstract = {Ultrasound transmission and reflection at the interface between restorative material and tooth tissue have been investigated using experimental flat-parallel models and whole extracted human teeth with restorations. It has been found that in the case of good bonding the ultrasound wave energy practically does not reflect at the cement/dentin interface and propagates into dentin layer. If any microscopic cavity had been formed between cement and dentin, the most part of the acoustic energy would be reflected from the interface between cement and gaseous or liquid contents of that cavity. The results acquired have been used for the interpretation of morphological peculiarities of the adhesive bonding area in visual images, non-destructively obtained in acoustic microscope ultrasound frequency - 50 MHz. The differences discovered could be used as a base for the design and development of new ultrasound methods for the restorative materials bonding evaluation as well as for secondary caries revealing.}, } @article {pmid18339829, year = {2008}, author = {Webb, E and Kuh, D and Peasey, A and Pajak, A and Malyutina, S and Kubinova, R and Topor-Madry, R and Denisova, D and Capkova, N and Marmot, M and Bobak, M}, title = {Childhood socioeconomic circumstances and adult height and leg length in central and eastern Europe.}, journal = {Journal of epidemiology and community health}, volume = {62}, number = {4}, pages = {351-357}, doi = {10.1136/jech.2006.056457}, pmid = {18339829}, issn = {1470-2738}, support = {R01 AG023522-01/AG/NIA NIH HHS/United States ; G19/35/MRC_/Medical Research Council/United Kingdom ; G0100222/MRC_/Medical Research Council/United Kingdom ; G8802774/MRC_/Medical Research Council/United Kingdom ; R01 AG023522/AG/NIA NIH HHS/United States ; R01 AG013196/AG/NIA NIH HHS/United States ; RG/07/008/23674/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Aged ; Anthropometry ; Body Height ; Child ; Educational Status ; Europe, Eastern/epidemiology ; Female ; Household Articles/statistics & numerical data ; Humans ; Leg/*growth & development ; Male ; Middle Aged ; Parents ; *Social Class ; Urban Health ; }, abstract = {BACKGROUND: Adult height and leg length have been shown to be positively associated with childhood socioeconomic circumstances in several studies in western populations. This study will determine whether similar associations are observable in settings with different social histories, and will assess whether adult leg length is more strongly associated than adult height.

METHODS: Random samples of men and women aged 45-69 years were taken from population registers in Novosibirsk (Russia), Krakow (Poland) and six towns of the Czech Republic, recruiting nearly 29,000 people. Participants completed a questionnaire that included questions regarding their mother's and father's education (not available in the Czech Republic) and ownership of several household items when they were 10 years old. Participants' standing and sitting heights were measured and from these an estimate of leg length was derived. Associations between indicators of childhood socioeconomic circumstances and anthropometric measures were analysed using linear regression.

RESULTS: Russian individuals were shorter and reported fewer household assets at the age of 10 years than Czech and Polish individuals. Parental education and household assets were strongly associated with each other and both were independently associated with height, leg length and trunk length. Height was associated with childhood circumstances more strongly than leg length. The associations of childhood circumstances with the leg/trunk ratio were weak and inconsistent.

CONCLUSION: In these urban populations in eastern Europe, adult height is associated with childhood conditions at least as strongly as leg length.}, } @article {pmid18322006, year = {2008}, author = {Liu, X and Popescu, IR and Denisova, JV and Neve, RL and Corriveau, RA and Belousov, AB}, title = {Regulation of cholinergic phenotype in developing neurons.}, journal = {Journal of neurophysiology}, volume = {99}, number = {5}, pages = {2443-2455}, pmid = {18322006}, issn = {0022-3077}, support = {R01 DA015088/DA/NIDA NIH HHS/United States ; R01 DA 015088/DA/NIDA NIH HHS/United States ; P20 RR 16816/RR/NCRR NIH HHS/United States ; }, mesh = {Acetylcholine/physiology ; Animals ; Calcium/metabolism ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein/physiology ; Cyclic AMP-Dependent Protein Kinases/physiology ; Dizocilpine Maleate/pharmacology ; Electrophysiology ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Postsynaptic Potentials/physiology ; Extracellular Signal-Regulated MAP Kinases/physiology ; Glutamic Acid/physiology ; Immunohistochemistry ; In Vitro Techniques ; Male ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinases/physiology ; NF-kappa B/physiology ; Neurons/drug effects/*physiology ; Parasympathetic Nervous System/*cytology/drug effects/*physiology ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholinergic/physiology ; Receptors, N-Methyl-D-Aspartate/genetics/physiology ; Synaptic Transmission/physiology ; Transfection ; }, abstract = {Specification of neurotransmitter phenotype is critical for neural circuit development and is influenced by intrinsic and extrinsic factors. Recent findings in rat hypothalamus in vitro suggest the role of neurotransmitter glutamate in the regulation of cholinergic phenotype. Here we extended our previous studies on the mechanisms of glutamate-dependent regulation of cholinergic phenotypic properties in hypothalamic neurons. Using immunocytochemistry, electrophysiology, and calcium imaging, we demonstrate that hypothalamic expression of choline acetyltransferase (the cholinergic marker) and responsiveness of neurons to acetylcholine (ACh) receptor agonists increase during chronic administration of an N-methyl-D-aspartate receptor (NMDAR) blocker, MK-801, in developing rats in vivo and genetic and pharmacological inactivation of NMDARs in mouse and rat developing neuronal cultures. In hypothalamic cultures, an inactivation of NMDA receptors also induces ACh-dependent synaptic activity, as do inactivations of PKA, ERK/MAPK, CREB, and NF-kappaB, which are known to be regulated by NMDA receptors. Interestingly, the increase in cholinergic properties in developing neurons that is induced by NMDAR blockade is prevented by the blockade of ACh receptors, suggesting that function of ACh receptor is required for the cholinergic up-regulation. Using dual recording of monosynaptic excitatory postsynaptic currents, we further demonstrate that chronic inactivation of ionotropic glutamate receptors induces the cholinergic phenotype in a subset of glutamatergic neurons. The phenotypic switch is partial as ACh and glutamate are coreleased. The results suggest that developing neurons may not only coexpress multiple transmitter phenotypes, but can also change the phenotypes following changes in signaling in neuronal circuits.}, } @article {pmid18318223, year = {2008}, author = {Filippov, AV and Ovsiankina, ES and Denisova, LS and Stakheeva, LB}, title = {[Comparative analysis of tuberculosis morbidity in children and adolescents from Moscow and the Penza Region].}, journal = {Problemy tuberkuleza i boleznei legkikh}, volume = {}, number = {1}, pages = {6-10}, pmid = {18318223}, issn = {1728-2993}, mesh = {Adolescent ; Catchment Area, Health ; Child ; Female ; Humans ; Incidence ; Male ; Mass Screening ; Prevalence ; Russia/epidemiology ; Tuberculosis, Pulmonary/*epidemiology ; }, abstract = {Tuberculosis morbidity was comparatively analyzed in the children and adolescents of Moscow and the Penza Region. The epidemiology of tuberculosis in the children and adolescents was established to be universal in the compared regions in the study period. This manifested itself as a stable tendency for higher morbidity rates (MR), increased incidence of destructive tuberculosis, inadequate use of the existing methods for active detection of tuberculosis in these age groups, and, among those who had fallen ill with this disease, an increase in the number of persons from the foci of tuberculous infection and persons with established contact with patients with tuberculosis. Along with a steady MR growth for tuberculosis among the children and adolescents, there has been a quantitative modification to the proportion of all epidemiologically hazardous forms of tuberculosis, such as the bacillary and destructive forms of pulmonary tuberculosis complicated by extrapulmonary tuberculosis. Hypodiagnosis of tuberculous pleurisy and extrapulmonary tuberculosis has been recently noted in the general health care network. The analysis also leads to the conclusion that the quality of mass tuberculin diagnosis remains poor. In both regions, general pediatricians are not adequately alert to tuberculosis, extrapulmonary tuberculosis in particular. With a rise in tuberculosis endemic, the incidence of tuberculosis in 18-21-year-old persons is 2-3 times greater than that in adolescents, which is associated with the greater activity of this population group and with the underdetection of the asymptomatic forms of tuberculosis in adolescents.}, } @article {pmid18279453, year = {2008}, author = {Kulagin, A and Lisukov, I and Denisova, V and Kruchkova, I and Sizikova, S and Gilevich, A and Pronkina, N and Kozhevnikov, V and Kozlov, V}, title = {Severe pancytopenia associated with a minor paroxysmal nocturnal haemoglobinuria clone and response to ciclosporin A in a heavily pretreated multiple myeloma patient.}, journal = {British journal of haematology}, volume = {141}, number = {1}, pages = {122-123}, doi = {10.1111/j.1365-2141.2008.07003.x}, pmid = {18279453}, issn = {1365-2141}, mesh = {Cyclosporine/*therapeutic use ; Hemoglobinuria, Paroxysmal/*drug therapy ; Humans ; Immunosuppressive Agents/*therapeutic use ; Male ; Middle Aged ; Multiple Myeloma/*drug therapy ; Pancytopenia/*drug therapy ; }, } @article {pmid18260893, year = {2007}, author = {Karpov, IuA and Deev, AD and , }, title = {[PRIVILEGIYA (Privilege) study - Prestarium in the treatment of arterial hypertension: antihypertensive effectiveness and safety in comparison with enalapril].}, journal = {Kardiologiia}, volume = {47}, number = {7}, pages = {35-40}, pmid = {18260893}, issn = {0022-9040}, mesh = {Adult ; Aged ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Antihypertensive Agents/administration & dosage/adverse effects/*therapeutic use ; Drug Administration Schedule ; Enalapril/administration & dosage/adverse effects/*therapeutic use ; Female ; Humans ; Hypertension/*drug therapy ; Male ; Middle Aged ; Perindopril/administration & dosage/adverse effects/*therapeutic use ; Russia ; Treatment Outcome ; }, } @article {pmid18260880, year = {2007}, author = {Denisova, DV and Nikitin, IuP and Zav'ialova, LG and Burakova, SV and Ivanova, MV}, title = {[Secular trends in blood lipid disorders among adolescents: population study in Novosibirsk (1989-2003)].}, journal = {Kardiologiia}, volume = {47}, number = {6}, pages = {62-67}, pmid = {18260880}, issn = {0022-9040}, mesh = {Adolescent ; Dyslipidemias/blood/*epidemiology ; Female ; Humans ; Lipids/*blood ; Male ; Morbidity/trends ; Population Surveillance/*methods ; Retrospective Studies ; Siberia/epidemiology ; }, abstract = {UNLABELLED: Hyperlipidemia is a known risk factor of coronary artery disease. The reduction of elevated serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in childhood may reduce cardiovascular morbidity and mortality in adulthood. Aim of the study was to assess prevalence and trends in lipid profile and lipid disorders in adolescent population in Novosibirsk (1989-2003).

METHODS: Four cross-sectional surveys of school children aged 14-17 years in 1989 (n=656), in 1994 (n=620), in 1999 (n=626) and in 2003 (n=667) were carried out. Total sample was 2569 (1214 males and 1355 females). Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) were measured by enzymatic methods. LDL-C was calculated with Friedwald's formula. Associations of blood lipids with age, sex, year of study, body mass index (kg/m2), blood pressure and main nutrients of diet were measured by GLM method. Prevalence of dyslipidemia was evaluated with NCEP-peds criteria. Diet was estimated using 24-hour dietary recall.

RESULTS: During the 15-year period (1989-2003) mean serum TC decreased from 175 to 162 mg/dl in males and from 191 to 175 mg/dl in females (p < 0.001). Average levels of LDL-C also fell significantly during this period, but no changes in HDL-C levels were found. Females had significantly higher mean TC and LDL-C than did males at all surveys (p < 0.001). According to NCFP-peds criteria prevalence of high TC (200 mg/dl und more) during the period (1989-2003) significantly decreased from 22% to 8% (p < 0.01) in males and from 32% to 17% (p < 0.05) in females. Frequencies of low HDL-C (< 40 mg/dl) also decreased in boys and girls (p < 0.05 for both gender groups). Significant regression coefficients for TC controlled by age, sex and year of study were revealed with body mass index, diastolic blood pressure and triceps skinfolds. Trends in diet during the period showed significant decrease of total energy and basic nutrient intakes (proteins, fats and carbohydrates).

CONCLUSION: During the period of socioeconomic reforms in Russia (1989-2003) the lipid profile and prevalence of atherogenic dislipidemias in adolescents of Novosibirsk significantly changed following the changes of body mass index and diet.}, } @article {pmid18218864, year = {2008}, author = {Gibson, DG and Benders, GA and Andrews-Pfannkoch, C and Denisova, EA and Baden-Tillson, H and Zaveri, J and Stockwell, TB and Brownley, A and Thomas, DW and Algire, MA and Merryman, C and Young, L and Noskov, VN and Glass, JI and Venter, JC and Hutchison, CA and Smith, HO}, title = {Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome.}, journal = {Science (New York, N.Y.)}, volume = {319}, number = {5867}, pages = {1215-1220}, doi = {10.1126/science.1151721}, pmid = {18218864}, issn = {1095-9203}, mesh = {Base Sequence ; Chromosomes, Artificial, Bacterial ; Chromosomes, Artificial, Yeast ; *Cloning, Molecular ; DNA, Bacterial/*chemical synthesis ; DNA, Recombinant ; Escherichia coli/genetics ; Genetic Vectors ; *Genome, Bacterial ; Genomics/*methods ; Mycoplasma genitalium/*genetics ; Oligodeoxyribonucleotides/chemical synthesis ; Plasmids ; Recombination, Genetic ; Saccharomyces cerevisiae/genetics ; Sequence Analysis, DNA ; Transformation, Genetic ; }, abstract = {We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments.}, } @article {pmid19555046, year = {2008}, author = {Denisova, EA and Kirichenko, LL and Struchkov, PV}, title = {[Structural functional state of cardiovascular system in hypertensive patients].}, journal = {Terapevticheskii arkhiv}, volume = {80}, number = {9}, pages = {84-86}, pmid = {19555046}, issn = {0040-3660}, mesh = {Humans ; *Hypertension/complications/pathology/physiopathology ; *Hypertrophy, Left Ventricular/etiology/pathology/physiopathology ; Myocardium/*pathology ; Prognosis ; *Vascular Diseases/etiology/pathology/physiopathology ; Vasodilation/physiology ; }, } @article {pmid18154131, year = {2007}, author = {Malinova, LI and Sergeeva, IuV and Simonenko, GV and Denisova, TP and Dovgalevskiĭ, PIa and Tuchin, VV}, title = {[Plasma dehydratation self-organization in patients with coronary heart].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {}, number = {10}, pages = {14-16}, pmid = {18154131}, issn = {0869-2084}, mesh = {Adult ; Aged ; Aged, 80 and over ; Coronary Disease/*diagnosis ; Female ; Humans ; Male ; Middle Aged ; *Plasma ; }, abstract = {The functional morphology of biological fluids is a basically new branch of science, which is based on the study of a result of phase change processes in the substrate under study. The paper shows the specific features of plasma spatial organization in patients with chronic and acute coronary heart disease (CHD). The findings may be used as an additional criterion for the differential diagnosis of the above forms of CHD and open up a new line in the diagnosis and risk stratification in CHD patients.}, } @article {pmid18019017, year = {2007}, author = {Silkov, AN and Gavrilenko, VA and Denisova, VV and Grishina, LV and Kozlov, VA and Sennikov, SV}, title = {Effects of recombinant IL-4delta2 on human peripheral blood mononuclears.}, journal = {Bulletin of experimental biology and medicine}, volume = {143}, number = {1}, pages = {72-74}, doi = {10.1007/s10517-007-0020-3}, pmid = {18019017}, issn = {0007-4888}, mesh = {Alternative Splicing ; Cell Proliferation/drug effects ; Humans ; Immunoglobulin E/biosynthesis/blood ; In Vitro Techniques ; Interleukin-4/genetics/*pharmacology ; Interleukin-6/biosynthesis/blood/genetics ; Leukocytes, Mononuclear/cytology/*drug effects/metabolism ; Recombinant Proteins/pharmacology ; }, abstract = {In human cells, expression of IL-4 gene involves alternative mRNA splicing. IL-4delta2 splice variant is an antagonist of full-length IL-4 protein and blocks its effect on the functional activity of immunocompetent cells. The effect of recombinant IL-4delta2 on cytokine-producing activity of human peripheral blood mononuclear cells is shown for the first time.}, } @article {pmid17970206, year = {2007}, author = {Denisova, VV and Kulagin, AD and Lisukov, IA and Kryuchkova, IV and Sizikova, SA and Sennikov, SV and Kozlov, VA}, title = {Cytokine-producing activity of bone marrow erythrokaryocytes and its regulation under normal conditions.}, journal = {Bulletin of experimental biology and medicine}, volume = {143}, number = {2}, pages = {218-221}, doi = {10.1007/s10517-007-0055-5}, pmid = {17970206}, issn = {0007-4888}, mesh = {Bone Marrow Cells/*metabolism ; Chemotactic Factors/metabolism ; Cytokines/*metabolism ; Erythrocytes/*metabolism ; Glycophorins/metabolism ; Granulocyte Colony-Stimulating Factor/metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Humans ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Interleukin-13/metabolism ; Interleukin-17/metabolism ; Interleukin-1beta/metabolism ; Interleukin-4/metabolism ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Macrophage Inflammatory Proteins/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {We showed that inhibition of cytokine production by bone marrow adherent cells and their soluble products is a mechanism of regulation of cytokine-producing activity of bone marrow erythrokaryocytes under normal conditions.}, } @article {pmid17970204, year = {2007}, author = {Cheknyov, SB and Babayeva, EE and Denisova, EA and Vorobyova, UA and Mongush, EM}, title = {Antigenic specificity of human serum gamma-globulin samples obtained under conditions of equimolar binding of copper and zinc cations.}, journal = {Bulletin of experimental biology and medicine}, volume = {143}, number = {2}, pages = {210-213}, doi = {10.1007/s10517-007-0053-7}, pmid = {17970204}, issn = {0007-4888}, mesh = {Copper/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Epitopes/chemistry/immunology/metabolism ; Humans ; Protein Binding ; Protein Conformation ; Spectrophotometry, Ultraviolet ; Zinc/*metabolism ; gamma-Globulins/chemistry/immunology/*metabolism ; }, abstract = {Samples of human serum gamma-globulin modified by equimolar binding of copper and zinc cations were obtained using the method of molecular ultrafiltration. Conformation characteristics of the protein were studied by UV spectrophotometry. Immunochemical study included radial immunodiffusion test, direct and sandwich enzyme immunoassays. Conformation changes in gamma-globulin caused by incorporation of solitary metal cations into the protein molecule modified presentation of antigenic determinants on the globule surface and their availability for recognition by specific antibodies. New antigenic determinants and new antigenic specificity of gamma-globulin are not formed under these conditions.}, } @article {pmid17930193, year = {2007}, author = {Denisov, SI and Kostur, M and Denisova, ES and Hänggi, P}, title = {Arrival time distribution for a driven system containing quenched dichotomous disorder.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {76}, number = {3 Pt 1}, pages = {031101}, doi = {10.1103/PhysRevE.76.031101}, pmid = {17930193}, issn = {1539-3755}, abstract = {We study the arrival time distribution of overdamped particles driven by a constant force in a piecewise linear random potential which generates the dichotomous random force. Our approach is based on the path integral representation of the probability density of the arrival time. We explicitly calculate the path integral for a special case of dichotomous disorder and use the corresponding characteristic function to derive prominent properties of the arrival time probability density. Specifically, we establish the scaling properties of the central moments, analyze the behavior of the probability density for short, long, and intermediate distances. In order to quantify the deviation of the arrival time distribution from a Gaussian shape, we evaluate the skewness and the kurtosis.}, } @article {pmid17929618, year = {2007}, author = {Denisova, DV and Nikitin, YP and Zavjalova, LG and Burakova, SV}, title = {Trends in cardiovascular risk factors of Siberian adolescents during socioeconomic reforms in Russia (1989-2003).}, journal = {Alaska medicine}, volume = {49}, number = {2 Suppl}, pages = {110-116}, pmid = {17929618}, issn = {0002-4538}, mesh = {Adolescent ; Age Factors ; Body Mass Index ; Cardiovascular Diseases/*epidemiology ; Cross-Sectional Studies ; Female ; Health Surveys ; Humans ; Male ; Motor Activity ; Nutritional Status ; *Politics ; Prevalence ; Risk Factors ; Russia/epidemiology ; Siberia/epidemiology ; Social Class ; }, abstract = {OBJECTIVE: Prevalence and trends of cardiovascular risk factors among adolescent population in Novosibirsk during the reforms in Russia (1989-2003).

STUDY DESIGN: Four cross-sectional surveys of representative samples of schoolchildren aged 14-17 since 1989 (total--2,569).

METHODS: Body mass index (BMI) was calculated (kg/m2), blood pressure was double measured with Korotkov's method, and serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were estimated with enzymatic methods. Low-density lipoprotein cholesterol (LDL-C) was calculated with Friedwald's formula. Self-report of smoking (1 cig/week and more) and physical inactivity (2 h/week and less) was obtained. Diet was estimated using 24-hour dietary recall.

RESULTS: Prevalence of high TC, high LDL-C and low HDL-C significantly decreased in both gender groups. Prevalence of arterial hypertension also decreased in boys and girls. Frequency of overweight decreased more in girls. Trends in diet showed significant decreasing of total energy and basic nutrient intakes. Cigarette smoking rate decreased in boys and increased in girls. Physical inactivity rate was high in boys and girls.

CONCLUSION: Obtained data indicate similar trends to reduction in classical CVD risk factors, energy intake and life style changes among Siberian adolescents during the period of socioeconomic reforms in Russia.}, } @article {pmid17924343, year = {2007}, author = {Derenko, M and Malyarchuk, B and Grzybowski, T and Denisova, G and Dambueva, I and Perkova, M and Dorzhu, C and Luzina, F and Lee, HK and Vanecek, T and Villems, R and Zakharov, I}, title = {Phylogeographic analysis of mitochondrial DNA in northern Asian populations.}, journal = {American journal of human genetics}, volume = {81}, number = {5}, pages = {1025-1041}, pmid = {17924343}, issn = {0002-9297}, mesh = {Asia ; Asian People/*genetics ; DNA, Mitochondrial/*genetics ; Genetic Variation ; *Geography ; Haplotypes ; Humans ; Molecular Sequence Data ; *Phylogeny ; Principal Component Analysis ; Sequence Analysis, DNA ; White People/genetics ; }, abstract = {To elucidate the human colonization process of northern Asia and human dispersals to the Americas, a diverse subset of 71 mitochondrial DNA (mtDNA) lineages was chosen for complete genome sequencing from the collection of 1,432 control-region sequences sampled from 18 autochthonous populations of northern, central, eastern, and southwestern Asia. On the basis of complete mtDNA sequencing, we have revised the classification of haplogroups A, D2, G1, M7, and I; identified six new subhaplogroups (I4, N1e, G1c, M7d, M7e, and J1b2a); and fully characterized haplogroups N1a and G1b, which were previously described only by the first hypervariable segment (HVS1) sequencing and coding-region restriction-fragment-length polymorphism analysis. Our findings indicate that the southern Siberian mtDNA pool harbors several lineages associated with the Late Upper Paleolithic and/or early Neolithic dispersals from both eastern Asia and southwestern Asia/southern Caucasus. Moreover, the phylogeography of the D2 lineages suggests that southern Siberia is likely to be a geographical source for the last postglacial maximum spread of this subhaplogroup to northern Siberia and that the expansion of the D2b branch occurred in Beringia ~7,000 years ago. In general, a detailed analysis of mtDNA gene pools of northern Asians provides the additional evidence to rule out the existence of a northern Asian route for the initial human colonization of Asia.}, } @article {pmid17886373, year = {2007}, author = {Mats, AN and Znamenskaia, LF and Fattiakhetdinova, ZA and Iashin, MM and Denisova, EV and Trofimova, IB}, title = {[Affinoleukin in combined treatment of psoriasis].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {4}, pages = {32-38}, pmid = {17886373}, issn = {0372-9311}, mesh = {Adolescent ; Adult ; Aged ; Anti-Inflammatory Agents/therapeutic use ; Biological Products/administration & dosage/chemistry/*therapeutic use ; Cell Count ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; Injections, Subcutaneous ; Killer Cells, Natural/immunology ; Leukocytes/chemistry ; Male ; Membrane Proteins/administration & dosage/chemistry/isolation & purification/therapeutic use ; Middle Aged ; Molecular Weight ; Monocytes/cytology ; Psoriasis/blood/*drug therapy ; Receptors, Antigen, T-Cell, gamma-delta ; T-Lymphocyte Subsets/immunology ; Treatment Outcome ; }, abstract = {Open randomized controlled clinical trials in which 161 patients were included showed that Affinoleukin (commercial drug which contains low molecular weight proteins obtained from extract of human leukocytes membranes) was effective in treatment of psoriasis. Affinoleukin, when added to regular treatment, accelerated the establishment of remission and its duration by restoration of impaired regulatory and defensive functions of T-lymphocytes, particularly, gamma deltaT- and NKT-cells as well as monocytes and NK-cells. Regular treatment led to marked positive effect in 45% of patients with severe psoriasis and psoriasis of intermediate severity. Addition of Affinoleukin in combined treatment increased proportion of patients with marked positive effect to 72%. Magnitude of Affinoleukin effect was directly related with its dose and severity of psoriasis. Course of Affinoleukin injections (up to 30 units in adults) is worthwhile to use as immunobiological component of combined treatment of exacerbations of severe psoriasis and psoriasis of intermediate severity.}, } @article {pmid17867504, year = {2007}, author = {Denisova, TV and Kazeev, KSh}, title = {[The influence of variable and constant magnetic fields on biota and biological activity of ordinary chernozem soils].}, journal = {Radiatsionnaia biologiia, radioecologiia}, volume = {47}, number = {3}, pages = {345-348}, pmid = {17867504}, issn = {0869-8031}, mesh = {Electromagnetic Fields/*adverse effects ; Radiation Monitoring/*methods ; Russia ; *Soil/analysis/standards ; *Soil Microbiology/standards ; }, abstract = {In model experiments on influence variable magnetic fields of industrial frequency (50 Hz) an induction of 1500 and of 6000 mkTl and the constant magnetic field an induction of 6000 mkTl and of 15000 mkTl during 5 days of exposure on biological properties of chernozem ordinary is shown, that the soil microflora is more sensitive to magnetic fields, than enzymes activity. Bacteria are more sensitive, than microscopic mushrooms. Dehydrogenase it is steady against influence of all variants. Constant magnetic field by the induction of 15000 mkTl rendered practically identical authentic overwhelming influence on catalase and saccharase activity - on 51 and 47% accordingly.}, } @article {pmid17706584, year = {2007}, author = {Denisova, OV and Chernov, AV and Koledachkina, TY and Matvienko, NI}, title = {A tag-based approach for high-throughput analysis of CCWGG methylation.}, journal = {Analytical biochemistry}, volume = {369}, number = {2}, pages = {154-160}, doi = {10.1016/j.ab.2007.06.048}, pmid = {17706584}, issn = {0003-2697}, mesh = {Animals ; Base Sequence ; *DNA Methylation ; DNA Primers/*genetics ; DNA-Cytosine Methylases/*genetics/metabolism ; Deoxyribonucleases, Type II Site-Specific/*genetics/metabolism ; Electrophoresis, Polyacrylamide Gel ; Genomics/*methods ; Humans ; Reproducibility of Results ; }, abstract = {Non-CpG methylation occurring in the context of CNG sequences is found in plants at a large number of genomic loci. However, there is still little information available about non-CpG methylation in mammals. Efficient methods that would allow detection of scarcely localized methylated sites in small quantities of DNA are required to elucidate the biological role of non-CpG methylation in both plants and animals. In this study, we tested a new whole genome approach to identify sites of CCWGG methylation (W is A or T), a particular case of CNG methylation, in genomic DNA. This technique is based on digestion of DNAs with methylation-sensitive restriction endonucleases EcoRII-C and AjnI. Short DNAs flanking methylated CCWGG sites (tags) are selectively purified and assembled in tandem arrays of up to nine tags. This allows high-throughput sequencing of tags, identification of flanking regions, and their exact positions in the genome. In this study, we tested specificity and efficiency of the approach.}, } @article {pmid17703276, year = {2007}, author = {Derenko, M and Malyarchuk, B and Denisova, G and Wozniak, M and Grzybowski, T and Dambueva, I and Zakharov, I}, title = {Y-chromosome haplogroup N dispersals from south Siberia to Europe.}, journal = {Journal of human genetics}, volume = {52}, number = {9}, pages = {763-770}, pmid = {17703276}, issn = {1434-5161}, mesh = {Chromosomes, Human, Y/*classification/*genetics ; Europe ; Genetic Variation ; *Genetics, Population ; *Haplotypes ; Humans ; Male ; Microsatellite Repeats ; Phylogeny ; Polymorphism, Single Nucleotide ; Siberia ; }, abstract = {In order to reconstruct the history of Y-chromosome haplogroup (hg) N dispersals in north Eurasia, we have analyzed the diversity of microsatellite (STR) loci within two major hg N clades, N2 and N3, in a total sample of 1,438 males from 17 ethnic groups, mainly of Siberian and Eastern European origin. Based on STR variance analysis we observed that hg N3a is more diverse in Eastern Europe than in south Siberia. However, analysis of median networks showed that there are two STR subclusters of hg N3a, N3a1 and N3a2, that are characterized by different genetic histories. Age calculation of STR variation within subcluster N3a1 indicated that its first expansion occurred in south Siberia [approximately 10,000 years (ky)] and then this subcluster spread into Eastern Europe where its age is around 8 ky ago. Meanwhile, younger subcluster N3a2 originated in south Siberia (probably in the Baikal region) approximately 4 ky ago. Median network and variance analyses of STR haplotypes suggest that south Siberian N3a2 haplotypes spread further into Volga-Ural region undergoing serial bottlenecks. In addition, median network analysis of STR data demonstrates that haplogroup N2-A is represented by two subclusters, showing recent expansion times. The data obtained allow us to suggest Siberian origin of haplogroups N3 and N2 that are currently widespread in some populations of Eastern Europe.}, } @article {pmid17694818, year = {2006}, author = {Vasil'ev, AIu and Tsyganova, LA and Ol'khova, EB and Vykliuk, MV and Serova, NS and Denisova, RB}, title = {[Radiation diagnosis for tuberculous gonitis in children].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {37-40}, pmid = {17694818}, issn = {0042-4676}, mesh = {Adolescent ; Arthrography/*methods ; Child ; Child, Preschool ; Diagnosis, Differential ; Humans ; Infant ; *Knee Joint ; Male ; Reproducibility of Results ; Severity of Illness Index ; Tuberculosis, Osteoarticular/*diagnostic imaging ; Ultrasonography ; }, abstract = {Tuberculous knee joint lesion in children is the most common form of articular pathology. The high sociomedical significance of this disease in modern society is determined by not only its prevalence, but also economic losses caused by high disability rates in children. The purpose of the study was to determine the possibilities and place of a comprehensive radiation study in the diagnosis of tuberculous gonitis in children. Sixty patients aged 10 months to 18 years were examined. Clinical studies were comprehensively assessed, by taking into account the collected history data and orhthopedic and laboratory findings. Surgery was made in 26 children. All the patients underwent mutiprojection X-ray study, knee joint ultrasound study being made in 48 patients. Knee joint X-ray study was performed on Siregraph (Siemens) apparatuses. Real-time ultrasonography was conducted on Aloka SSD-1100 and Aloka--3500+ apparatuses, by employing a 7.5-MHz linear transducer. According to P.G. Kornev (1971), three phases were identified in the course of tuberculous gonitis. These included prearthritic (the development of primary ostitis); arthritic (articular cartilage destruction, followed by the development of secondary arthritis; and postarthritic (sequels of prior tuberculous osteomyelitis) phases. Analysis indicated that the use of the routine X-ray study in combination with ultrasound scanning in the diagnosis of tuberculous gonitis in children yielded more adequate information on tissue and knee joint structural changes and made it possible to define further policy treatment and to predict the outcomes of the disease.}, } @article {pmid17677236, year = {2007}, author = {Denisov, SI and Kostur, M and Denisova, ES and Hänggi, P}, title = {Analytically solvable model of a driven system with quenched dichotomous disorder.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {75}, number = {6 Pt 1}, pages = {061123}, doi = {10.1103/PhysRevE.75.061123}, pmid = {17677236}, issn = {1539-3755}, abstract = {We perform a time-dependent study of the driven dynamics of overdamped particles that are placed in a one-dimensional, piecewise linear random potential. This setup of spatially quenched disorder then exerts a dichotomous varying random force on the particles. We derive the path integral representation of the resulting probability density function for the position of the particles and transform this quantity of interest into the form of a Fourier integral. In doing so, the evolution of the probability density can be investigated analytically for finite times. It is demonstrated that the probability density contains both a delta -singular contribution and a regular part. While the former part plays a dominant role at short times, the latter rules the behavior at large evolution times. The slow approach of the probability density to a limiting Gaussian form as time tends to infinity is elucidated in detail.}, } @article {pmid17603677, year = {2006}, author = {Cheknev, SB and Babaeva, EE and Denisova, EA and Vorob'eva, UA and Mongush, EM}, title = {Preparation of specimens of human serum gamma-globulin modified by copper and zinc and its immunochemical characteristics.}, journal = {Bulletin of experimental biology and medicine}, volume = {142}, number = {6}, pages = {710-713}, doi = {10.1007/s10517-006-0458-8}, pmid = {17603677}, issn = {0007-4888}, mesh = {Cations/chemistry ; Copper/*chemistry ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Protein Binding ; Protein Conformation ; Proteins/chemistry ; Spectrophotometry, Ultraviolet ; Ultrafiltration ; Zinc/*chemistry ; gamma-Globulins/*chemistry/*immunology ; }, abstract = {Specimens of human serum gamma-globulin modified by molar excess of copper and zinc cations were obtained by molecular ultrafiltration. Conformation characteristics of the protein were determined by UV spectrophotometry. Immunochemical study included radial immunodiffusion test and direct and sandwich enzyme-linked immunosorbent assay. After binding of copper and zinc, the gamma-globulin molecule underwent conformation changes modifying presentation of antigenic determinants on the globule surface and their availability for recognition by specific antibodies. The effects of copper were much more pronounced than those of zinc cations.}, } @article {pmid17486763, year = {2007}, author = {Derenko, MV and Maliarchuk, BA and Wozniak, M and Denisova, GA and Dambueva, IK and Dorzhu, CM and Grzybowski, T and Zakharov, IA}, title = {[Distribution of the male lineages of Genghis Khan's descendants in northern Eurasian populations].}, journal = {Genetika}, volume = {43}, number = {3}, pages = {422-426}, pmid = {17486763}, issn = {0016-6758}, mesh = {Asian People/*genetics ; Chromosomes, Human, Y/*genetics ; Ethnicity/*genetics ; Humans ; Male ; Microsatellite Repeats ; Mongolia/ethnology ; Siberia/ethnology ; }, abstract = {Data on the variation of 12 microsatellite loci of Y-chromosome haplogroup C3 were used to screen lineages included in the cluster of Genghis Khan's descendants in 18 northern Eurasian populations (Altaian Kazakhs, Altaians-Kizhi, Teleuts, Khakassians, Shorians, Tyvans, Todjins, Tofalars, Sojots, Buryats, Khamnigans, Evenks, Mongols, Kalmyks, Tajiks, Kurds, Persians, and Russians; the total sample size was 1437 people). The highest frequency of haplotypes from the cluster of the Genghis Khan's descendants was found in Mongols (34.8%). In Russia, this cluster was found in Altaian Kazakhs (8.3%), Altaians (3.4%), Buryats (2.3%), Tyvans (1.9%), and Kalmyks (1.7%).}, } @article {pmid17405285, year = {2006}, author = {Denisova, TV}, title = {[Egineering psychology and ergonomics in aviation].}, journal = {Aviakosmicheskaia i ekologicheskaia meditsina = Aerospace and environmental medicine}, volume = {40}, number = {6}, pages = {59-63}, pmid = {17405285}, issn = {0233-528X}, mesh = {Aerospace Medicine/*trends ; *Aviation ; Ergonomics/*methods ; Humans ; Russia ; }, } @article {pmid17402591, year = {2007}, author = {Bugaeva, LI and Denisova, TD and Spasov, AA}, title = {[Transplacental effects of bemithyl].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {70}, number = {1}, pages = {40-43}, pmid = {17402591}, issn = {0869-2092}, mesh = {Animals ; Antioxidants/metabolism/*pharmacology ; Behavior, Animal/drug effects ; Benzimidazoles/metabolism/*pharmacology ; Female ; Fetal Development/drug effects ; Fetus/*drug effects ; Placenta/*metabolism ; Pregnancy ; Rats ; Rats, Inbred Strains ; }, abstract = {The daily administration of bemithyl (20 mg/kg) from 6 th to 16 th day of pregnancy in female rats led to the decrease in fetal death after the implantation and increased fetal body weight. The treatment of pregnant rats also led to acceleration of the development of physical condition and sensomotor reflexes of progeny in the postnatal period.}, } @article {pmid17195631, year = {2006}, author = {Denisova, LB and Vorontsova, SV and Iaurova, NV}, title = {[Potentialities of new radiation technologies (ultrasonography, computed tomography, magnetic resonance imaging) in the diagnosis of endocrine diseases].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {1}, pages = {29-43}, pmid = {17195631}, issn = {0042-4676}, mesh = {Diagnosis, Differential ; *Endocrine System Diseases/diagnostic imaging/pathology ; Humans ; Magnetic Resonance Imaging/*methods ; Reproducibility of Results ; Tomography, X-Ray/*methods ; Ultrasonography ; }, abstract = {In the paper providing the data available in the literature and many years' experience gained by the Department of the Moscow Regional Clinical Research Institute, the authors describe the potentialities of the currently available radiation techniques in the diagnosis of surgical endocrine diseases. The incidence of various organ dysfunctions is presented. The authors also consider the introscopic symptoms of various endocrinopathies and outline the common specific features of the ultrasound, computed tomographic, and magnetic resonance imaging pattern of individual masses (including adipose tissue cysts and tumors). Emphasis is laid on the leading role of ultrasonography (USG) in the diagnosis of thyroid and parathyroid diseases and on the priorities of computed tomography (CT) and magnetic resonance imaging (MRI) in visualIzing the abnormal thymus, mediastinally ectopic glands, and pituitary tumors. The capacities of each technique in the diagnosis of endocrine space lesions of the pancreas and adrenals are defined. The increase in the frequency of endocrine abnormalities accidentally identified at USG, CT, and MRI, which is noted in the paper, fosters the development of new trends in endocrinology and points to the need for screening surveys (particularly patients who live in poor environmental areas).}, } @article {pmid17195527, year = {2006}, author = {Kulagin, AD and Lisukov, IA and Kriuchkova, IV and Sizikova, SA and Gilevich, AV and Denisova, VV and Filimonov, PN and Meniaeva, EV and Pronkina, NV and Kozhevnikov, VS and Chernykh, ER and Kozlov, VA}, title = {[Diagnosis and treatment of aquired aplastic anemia].}, journal = {Terapevticheskii arkhiv}, volume = {78}, number = {11}, pages = {48-54}, pmid = {17195527}, issn = {0040-3660}, mesh = {Anemia, Aplastic/*diagnosis/drug therapy/*therapy ; Antilymphocyte Serum/therapeutic use ; *Bone Marrow Transplantation ; Combined Modality Therapy ; Cyclosporine/therapeutic use ; Female ; Humans ; *Immunosuppression Therapy ; Immunosuppressive Agents ; Male ; Treatment Outcome ; }, abstract = {AIM: To analyse the results of diagnosis and treatment of patients with aquired aplastic anemia (AA) in one center.

MATERIAL AND METHODS: All AA patients, diagnosed and treated in one clinic in 1998-2005, were included in the trial. In severe and very severe AA (SAA/VSAA) the patients (n = 19) received combined immunosuppressive therapy (IST) with antithymocytic globulin (ATG) and cyclosporin A (CsA), in non-severe AA (NSAA) the patients (n = 9) were given monotherapy with CsA. Allogenic transplantation of bone marrow (alloTBM) was made in 4 young patients with SAA/VSAA.

RESULTS: The diagnosis of AA was established in 33 patients (19 males and 14 females): NSAA in 9, SAA in 19, VSAA in 5, idiopathic--in 26, posthepatic--in 5, associated with pregnancy--in 2 patients. Age median was 20 years (13-53). The clone of paroxysmal nocturnal hemoglobinuria (PNH) was identified in 7 of 33 patients (21%), antigen HLA-DRB1 *15 in 6 of 11 patients (55%). In median of 26-month follow-up 31 patients (94%) were alive. In IST, complete or partial remissions were obtained in 88% patients. Median of the interval to achievement of transfusion independence made up 2.5 months. All the patients after alloTBM are in complete remission, chronic extensive transplant against host reaction was observed in one case.

CONCLUSION: Introduction of updated protocols provides long-term survival of more than 80% AA patients. To optimize treatment outcomes, it is necessary to include newly diagnosed AA patients into ongoing multicenter studies.}, } @article {pmid17181064, year = {2006}, author = {Babaeva, EE and Vorobyova, UA and Denisova, EA and Medvedeva, DA and Cheknev, SB}, title = {Binding of zinc cations to human serum gamma-globulin.}, journal = {Bulletin of experimental biology and medicine}, volume = {141}, number = {5}, pages = {602-605}, doi = {10.1007/s10517-006-0232-y}, pmid = {17181064}, issn = {0007-4888}, mesh = {Cations/*metabolism ; Globins/chemistry/*metabolism ; Humans ; Phenanthrolines ; Protein Binding ; Protein Conformation ; Spectrophotometry, Ultraviolet ; Ultrafiltration ; Zinc/analysis/*metabolism ; }, abstract = {Binding of zinc cations to human serum gamma-globulin was studied by molecular ultrafiltration. The content of free metal in the filtrate was evaluated by reaction with o-phenanthroline. Conformation characteristics of the protein were determined by UV spectrophotometry. Our findings suggest that gamma-globulin molecule contains several zinc binding sites differing by corresponding constants and successively occupied with increase in the content of bound metal. The parameters of zinc binding correspond to those obtained in experiments with copper. Conformation status of protein with bound zinc differs significantly from that of protein with bound copper cations.}, } @article {pmid17114825, year = {2007}, author = {Paley, EL and Denisova, G and Sokolova, O and Posternak, N and Wang, X and Brownell, AL}, title = {Tryptamine induces tryptophanyl-tRNA synthetase-mediated neurodegeneration with neurofibrillary tangles in human cell and mouse models.}, journal = {Neuromolecular medicine}, volume = {9}, number = {1}, pages = {55-82}, pmid = {17114825}, issn = {1559-1174}, support = {EB01850/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/drug effects ; Brain/drug effects/metabolism/*pathology ; Cell Count ; Cell Line, Tumor ; Glucose/metabolism ; Hippocampus/metabolism/pathology ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Motor Activity/drug effects ; Neurodegenerative Diseases/metabolism/*pathology/psychology ; Neurofibrillary Tangles/*pathology ; Neuroglia/pathology ; Neurons/pathology ; Tryptamines/pharmacology/*physiology ; Tryptophan-tRNA Ligase/antagonists & inhibitors/*physiology ; }, abstract = {The neuropathological hallmarks of Alzheimer's disease (AD) and other taupathies include neurofibrillary tangles and plaques. Despite the fact that only 2-10% of AD cases are associated with genetic mutations, no nontransgenic or metabolic models have been generated to date. The findings of tryptophanyl-tRNA synthetase (TrpRS) in plaques of the AD brain were reported recently by the authors. Here it is shown that expression of cytoplasmic-TrpRS is inversely correlated with neurofibrillary degeneration, whereas a nonionic detergent-insoluble presumably aggregated TrpRS is simultaneously accumulated in human cells treated by tryptamine, a metabolic tryptophan analog that acts as a competitive inhibitor of TrpRS. TrpRSN- terminal peptide self-assembles in double-helical fibrils in vitro. Herein, tryptamine causes neuropathy characterized by motor and behavioral deficits, hippocampal neuronal loss, neurofibrillary tangles, amyloidosis, and glucose decrease in mice. Tryptamine induced the formation of helical fibrillary tangles in both hippocampal neurons and glia. Taken together with the authors' previous findings of tryptamine-induced nephrotoxicity and filamentous tangle formation in kidney cells, the authors' data indicates a general role of tryptamine in cell degeneration and loss. It is concluded that tryptamine as a component of a normal diet can induce neurodegeneration at the concentrations, which might be consumed along with food. Tryptophan-dependent tRNAtrp aminoacylation catalyzed by TrpRS can be inhibited by its substrate tryptophan at physiological concentrations was demonstrated. These findings indicate that the dietary supplementation with tryptophan as a tryptamine competitor may not counteract the deleterious influence of tryptamine. The pivotal role of TrpRS in protecting against neurodegeneration is suggested, providing an insight into the pathogenesis and a possible treatment of neurodegenerative diseases.}, } @article {pmid17076067, year = {2006}, author = {Denisova, K and Singh, M and Kowler, E}, title = {The role of part structure in the perceptual localization of a shape.}, journal = {Perception}, volume = {35}, number = {8}, pages = {1073-1087}, doi = {10.1068/p5518}, pmid = {17076067}, issn = {0301-0066}, mesh = {Distance Perception/physiology ; Form Perception/*physiology ; Humans ; *Optical Illusions ; Psychometrics ; Psychophysics ; }, abstract = {The process of object localization may be accomplished with respect to a particular reference location, such as the center of gravity, COG (eg Vishwanath and Kowler, 2003 Vision Research 43 1637-1653). Here, we investigated how part structure affects an object's reference location. The reference location was evaluated with a measure of the illusory displacement of an internal target element embedded within a larger object (Morgan et al, 1990 Vision Research 30 1793-1810). To examine whether the reference location is different for shapes with part structure, two shapes were tested: circle (small and large; no part structure) and bell (shape with two parts, one larger than the other). Results were examined with respect to two predictions: either the location of an object is based on its shape as a whole, disregarding part structure (ie a single, overall COG), or the parts are processed separately (different COGs). With the circles, the results showed a systematic illusory displacement of the internal target toward the COG. With the bell, the illusion was significantly weaker than with both circles--even though the main part of the bell had the same size as the small circle, and its horizontal axis had the same extent as the large circle. Moreover, the distance judgments for the bell were consistent with a (weaker) reference point being located at the COG of the larger part, rather than at the COG of the entire bell. These results show that the part structure of a shape plays a role in the representation of its location, and that for complex shapes the perceived location of an embedded element depends more on the parts within which it is embedded, rather than on the whole shape.}, } @article {pmid16881369, year = {2006}, author = {Denisova, LN}, title = {[Diet therapy of rheumatoid arthritis].}, journal = {Terapevticheskii arkhiv}, volume = {78}, number = {6}, pages = {84-88}, pmid = {16881369}, issn = {0040-3660}, mesh = {Arthritis, Rheumatoid/*diet therapy ; Humans ; }, } @article {pmid16850925, year = {2006}, author = {Karal'nik, BV and Denisova, TG and Plazun, AA and Duĭsenova, RB}, title = {[Antigen-binding lymphocytes of tuberculin specificity in M. bovis-infected rabbits in the dynamics of treatment for tuberculosis].}, journal = {Problemy tuberkuleza i boleznei legkikh}, volume = {}, number = {5}, pages = {48-53}, pmid = {16850925}, issn = {1728-2993}, mesh = {Animals ; Antigen Presentation ; Mycobacterium bovis/*immunology ; Rabbits ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/*immunology ; Tuberculin/*immunology ; Tuberculosis/*immunology/*therapy ; }, abstract = {In M. bovis-infected rabbits, antigen-binding lymphocytes (ABL) of tuberculin specificity were detected within 7-105 days after inoculation. Due to etiotropic chemotherapy, ABL disappeared 31-45 days following inoculation. At the trial's end, the seeding rate and morphological changes in the organs of M. bovis-infected correlated with the content of ABL 105 days after inoculation. The early disappearance of ABL in the rats is regarded as an index of the efficiency of treatment for tuberculosis.}, } @article {pmid16637277, year = {2006}, author = {Rechkina, EA and Denisova, GF and Masalova, OV and Lideman, LF and Denisov, DA and Lesnova, EI and Ataullakhanov, RI and Gur'ianova, SV and Kushch, AA}, title = {[Epitope mapping of antigenic determinants of hepatitis C virus proteins by phage display].}, journal = {Molekuliarnaia biologiia}, volume = {40}, number = {2}, pages = {357-368}, pmid = {16637277}, issn = {0026-8984}, mesh = {Amino Acid Sequence ; Animals ; Antibodies, Viral/*analysis/immunology ; *Epitope Mapping/methods ; Epitopes/*chemistry/genetics/immunology ; Female ; Hepacivirus/*chemistry/genetics/immunology ; Humans ; Mice ; Molecular Sequence Data ; *Peptide Library ; Protein Structure, Secondary/genetics ; Protein Structure, Tertiary/genetics ; RNA Helicases/chemistry/genetics/immunology ; Serine Endopeptidases/chemistry/genetics/immunology ; Viral Nonstructural Proteins/*chemistry/genetics/immunology ; }, abstract = {Study of individual hepatitis C (HCV) proteins could help to find a molecular structure and conformation, localization of antigenic and immunogenic determinants, to reveal of protective epitopes. It is necessary for practical medicine - development of diagnostic test-systems, vaccines and therapeutics. Linear and conformation dependent epitopes of HCV proteins was localized in this work and immunogenic properties of phage displayed peptides screened on monoclonal antibodies to HCV proteins have been investigated. Eleven epitopes of four HCV proteins have been studied. Three epitopes was found as linear, two epitopes were dependent on secondary structure of proteins and one epitope was dependent on tertiary structure of NS3 protein. Aminoacid sequences of other determinants have been determined and the distinct localization of these determinants will be continued after discovering of tertiary structure of HCV proteins. It was shown, that phage mimotope 3f4 is immunogenic and could induce specific hu- moral immune response to NS5A HCV protein. The data obtained could be useful for improving of HCV diagnostic test-systems, studying of amino acid substitutions and its influence on antigenic properties of the HCV proteins. The results could help to study an immune response in patients infected with different genotypes of HCV. Phage displayed peptides mimicking the antigenic epitopes of HCV proteins could be applied to development of HCV vaccine.}, } @article {pmid16616781, year = {2007}, author = {Paley, EL and Smelyanski, L and Malinovskii, V and Subbarayan, PR and Berdichevsky, Y and Posternak, N and Gershoni, JM and Sokolova, O and Denisova, G}, title = {Mapping and molecular characterization of novel monoclonal antibodies to conformational epitopes on NH2 and COOH termini of mammalian tryptophanyl-tRNA synthetase reveal link of the epitopes to aggregation and Alzheimer's disease.}, journal = {Molecular immunology}, volume = {44}, number = {4}, pages = {541-557}, doi = {10.1016/j.molimm.2006.02.006}, pmid = {16616781}, issn = {0161-5890}, mesh = {Alzheimer Disease/immunology ; Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/chemistry/*immunology ; Antibody Specificity ; Cattle ; Cell Line, Tumor ; Cross Reactions ; Epitope Mapping ; *Epitopes/chemistry/genetics/immunology ; Humans ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Molecular Sequence Data ; Organ Specificity ; Protein Conformation ; Rabbits ; Species Specificity ; Tryptophan-tRNA Ligase/chemistry/*immunology ; }, abstract = {Tryptophanyl-tRNA synthetase (TrpRS) is an interferon-induced phosphoprotein with autoantigenic and cytokine activities detected in addition to its canonical function in tRNA aminoacylation. The availability of monoclonal antibodies (mAbs) specific for TrpRS is important for development of tools for TrpRS monitoring. A molecular characterization of two mAbs raised in mice, using purified, enzymatically active bovine TrpRS as the inoculating antigen, is presented in this report. These IgG1 antibodies are specific for bovine, human and rabbit but not E. coli TrpRS. Immunoreactivity and specificity of mAbs were verified with purified recombinant hTrpRS expressed in E. coli and TrpRS-derived synthetic peptides. One of the mAbs, 9D7 is able to disaggregate fibrils formed by Ser32-Tyr50 TrpRS-peptide. Epitope mapping revealed that disaggregation ability correlates with binding of 9D7 to this peptide in ELISA and immunocytochemistry. This epitope covers a significant part of N-terminal extension that suggested to be proteolytically deleted in vivo from the full-length TrpRS whereas remaining COOH-fragment possesses a cytokine activity. For epitope mapping of mAb 6C10, the affinity selected phage-displayed peptides were used as a database for prediction of conformational discontinuous epitopes within hTrpRS crystal structure. Using computer algorithm, this epitope is attributed to COOH-terminal residues Asp409-Met425. In immunoblotting, the 6C10 mAb reacts preferably with (i) oligomer than monomer, and (ii) bound than free TrpRS forms. The hTrpRS expression was shown to correlate with growth rates of neuroblastoma and pancreatic cancer cells. Immunohistochemically both mAbs revealed extracellular plaque-like aggregates in hippocampus of Alzheimer's disease brain.}, } @article {pmid16579550, year = {2006}, author = {Denisova, TV and Kazeev, KSh}, title = {[The restoration of the enzyme activity of chernozem soil after gamma-irradiation].}, journal = {Radiatsionnaia biologiia, radioecologiia}, volume = {46}, number = {1}, pages = {89-93}, pmid = {16579550}, issn = {0869-8031}, mesh = {*Catalase/analysis/radiation effects ; *Gamma Rays ; Kinetics ; *Oxidoreductases/analysis/radiation effects ; Russia ; Soil/*analysis ; *beta-Fructofuranosidase/analysis/radiation effects ; }, abstract = {The Influence of gamma-radiation by dozes 1, 5, 10 and 20 kGy on enzyme activity of ordinary chemozem were studied. Dynamics of the restoration of the enzyme activity after the influence of gamma-radiation in model experiments in 3, 30, 90 and 180 days was investigated. The doze 1 kGy did no statistically significant influence on the investigated enzymes. Dehydrogenase is more radiosensitive enzyme than catalase. Values of the saccharase activity differed a significant variation so in most cases it has not been registered statistically significant changes. In 90-180 days of the incubation enzymes activity was restored up to control values. Dehydrogenase activity in 180 days in variants with dozes 10 and 20 kGy was restored up to a level of the control, over variants with dozes 1 and 5 kGy--is higher than the control over 78% and 23% accordingly. Saccharase activity in 180 days after the influence of gamma-radiation with a doze 20 kGy was on 61% lower than the control.}, } @article {pmid16566435, year = {2006}, author = {Lebron, JA and Troilol, PJ and Pacchione, S and Griffiths, TG and Harper, LB and Mixson, LA and Jackson, BE and Michna, L and Barnum, AB and Denisova, L and Johnson, CN and Maurer, KL and Morgan-Hoffman, S and Niu, Z and Roden, DF and Wang, Z and Wolf, JJ and Hamilton, TR and Laux, KM and Soper, KA and Ledwith, BJ}, title = {Adaptation of the WHO guideline for residual DNA in parenteral vaccines produced on continuous cell lines to a limit for oral vaccines.}, journal = {Developments in biologicals}, volume = {123}, number = {}, pages = {35-44; discussion 55-73}, pmid = {16566435}, issn = {1424-6074}, mesh = {Administration, Oral ; Animals ; Cell Line ; Chlorocebus aethiops ; DNA/*administration & dosage/*adverse effects/pharmacokinetics ; Deoxyribonucleases ; Endocytosis ; Endosomes/physiology ; Female ; Humans ; Male ; Practice Guidelines as Topic ; Vaccines/administration & dosage/*standards ; Vero Cells ; World Health Organization ; }, abstract = {Although there is a WHO guidance for a limit on residual DNA for parenterally administered vaccines produced on continuous cell lines, there is no corresponding guidance for oral vaccines. To help determine an oral limit, we performed a study of Vero cell DNA uptake in rats, in which the relative uptake and persistence of Vero cell DNA administered orally was compared to its uptake when delivered intramuscularly (IM). The results of this study allowed the generation of an empirically derived IM versus oral factor (10(6)) representing the relative inefficiency of DNA uptake by oral administration. This factor was then applied to the WHO recommended parenteral limit of 10 ng/dose to determine a corresponding upper limit on the level of residual Vero cell DNA for an oral vaccine of 10 mg. As a conservative approach, this empirically determined limit was reduced 100-fold to 100 microg. Thus, the results of this animal study, together with additional evidence in the literature, support a residual DNA safety limit of 100 microg per dose for an oral vaccine produced on a continuous cell line.}, } @article {pmid16297666, year = {2006}, author = {Grinshtein, N and Yang, TC and Parsons, R and Millar, J and Denisova, G and Dissanayake, D and Leitch, J and Wan, Y and Bramson, J}, title = {Recombinant adenovirus vaccines can successfully elicit CD8+ T cell immunity under conditions of extreme leukopenia.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {13}, number = {2}, pages = {270-279}, doi = {10.1016/j.ymthe.2005.09.018}, pmid = {16297666}, issn = {1525-0016}, mesh = {Adenoviridae/*genetics/*immunology ; Animals ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/*immunology/*pathology/virology ; Dendritic Cells/immunology ; Female ; Leukopenia/*immunology/pathology/*therapy ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Radiation Chimera ; Vaccines, Synthetic/administration & dosage/immunology ; Viral Vaccines/*administration & dosage/*immunology ; Whole-Body Irradiation ; }, abstract = {We have examined the efficacy of vaccination with recombinant adenovirus under conditions of extreme leukopenia in lethally irradiated mice reconstituted with autologous bone marrow. The expansion of antigen-specific CD8(+) T cells following immunization of lethally irradiated hosts paralleled the recovery of total CD8(+) T cells. Surprisingly, the numbers of antigen-specific CD8(+) T cells in lethally irradiated mice beyond 6 weeks postimmunization were comparable to the numbers found in nonirradiated controls. CD8(+) T cells elicited in the lethally irradiated hosts were functionally indistinguishable from those elicited in normal hosts. Antigen expression and presentation persisted for a longer period of time in the draining lymph nodes of irradiated mice compared to those of nonirradiated animals, suggesting that antigen presentation mechanisms were intact during the reconstitution period. Experiments employing allogeneic bone marrow demonstrated that radioresistant host antigen-presenting cells were responsible for antigen presentation during the process of immune reconstitution. These results demonstrate clear compatibility of adenovirus vaccines and cytotoxic therapy. Furthermore, these observations provide novel insights into the mechanisms of CD8(+) T cell activation following adenovirus immunization.}, } @article {pmid16283003, year = {2005}, author = {Cheknev, SB and Babaeva, EE and Vorobeva, UA and Denisova, EA}, title = {Reactions between human serum gamma-globulin and zinc cations.}, journal = {Bulletin of experimental biology and medicine}, volume = {140}, number = {2}, pages = {209-212}, doi = {10.1007/s10517-005-0447-3}, pmid = {16283003}, issn = {0007-4888}, mesh = {Cations ; Dose-Response Relationship, Drug ; Humans ; Hydrogen-Ion Concentration ; Protein Binding ; Protein Conformation ; Proteins/chemistry ; Spectrophotometry ; Time Factors ; Ultraviolet Rays ; Zinc/*chemistry ; gamma-Globulins/*chemistry ; }, abstract = {Interactions of human serum gamma-globulin with zinc cations in solution were studied by differential spectrophotometry in UV light. Supraphysiological concentrations of zinc caused an increment in optical density of protein solution reflecting the effect of gamma-globulin saturation with the metal. Zinc concentrations below physiological led to hypochromism in the protein absorption spectrum. Conformation changes in gamma-globulin during interactions with zinc are analyzed for the surface and intramolecular binding sites and are compared with the effects of copper cations.}, } @article {pmid16273932, year = {2005}, author = {Denisova, OI and Klimenko, GIa}, title = {[Logbook system application in regional multi-field hospital].}, journal = {Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsiny}, volume = {}, number = {4}, pages = {38-41}, pmid = {16273932}, issn = {0869-866X}, mesh = {Hospital Information Systems ; Hospitals, General/*organization & administration ; Humans ; *Medical Records Systems, Computerized ; Organizational Innovation ; Russia ; }, } @article {pmid16261343, year = {2006}, author = {Derenko, M and Malyarchuk, B and Denisova, GA and Wozniak, M and Dambueva, I and Dorzhu, C and Luzina, F and Miścicka-Sliwka, D and Zakharov, I}, title = {Contrasting patterns of Y-chromosome variation in South Siberian populations from Baikal and Altai-Sayan regions.}, journal = {Human genetics}, volume = {118}, number = {5}, pages = {591-604}, pmid = {16261343}, issn = {0340-6717}, mesh = {*Chromosomes, Human, Y ; Ethnicity/*genetics ; *Genetics, Population ; Haplotypes ; Humans ; Male ; Siberia ; }, abstract = {In order to investigate the genetic history of autochthonous South Siberian populations and to estimate the contribution of distinct patrilineages to their gene pools, we have analyzed 17 Y-chromosomal binary markers (YAP, RPS4Y(711), SRY-8299, M89, M201, M52, M170, 12f2, M9, M20, 92R7, SRY-1532, DYS199, M173, M17, Tat, and LLY22 g) in a total sample of 1,358 males from 14 ethnic groups of Siberia (Altaians-Kizhi, Teleuts, Shors, Tuvinians, Todjins, Tofalars, Sojots, Khakassians, Buryats, Evenks), Central/Eastern Asia (Mongolians and Koreans) and Eastern Europe (Kalmyks and Russians). Based on both, the distribution pattern of Y-chromosomal haplogroups and results on AMOVA analysis we observed the statistically significant genetic differentiation between the populations of Baikal and Altai-Sayan regions. We suggest that these regional differences can be best explained by different contribution of Central/Eastern Asian and Eastern European paternal lineages into gene pools of modern South Siberians. The population of the Baikal region demonstrates the prevalence of Central/Eastern Asian lineages, whereas in the populations of Altai and Sayan regions the highest paternal contribution resulted from Eastern European descent is revealed. Yet, our data on Y-chromosome STRs variation demonstrate the clear differences between the South Siberian and Eastern European R1a1-lineages with the evolutionary ages compatible with divergence time between these two regional groups.}, } @article {pmid16250592, year = {2005}, author = {Lideman, LF and Kasennova, EV and Denisova, GF and Stakhanova, VM and Zverev, SIa and Gibadulin, RA and Bobkov, AF}, title = {[Anti-CD4 autoimmunity in HIV-infected persons in Russia].}, journal = {Voprosy virusologii}, volume = {50}, number = {5}, pages = {15-19}, pmid = {16250592}, issn = {0507-4088}, mesh = {Amino Acid Sequence ; Autoantibodies/*blood ; CD4 Antigens/*immunology ; Consensus Sequence ; Epitopes, T-Lymphocyte ; Female ; Gene Products, nef/genetics ; HIV Infections/*blood/*virology ; HIV-1/*genetics ; Human Immunodeficiency Virus Proteins ; Humans ; Male ; Molecular Sequence Data ; Species Specificity ; Substance Abuse, Intravenous/blood ; Viral Regulatory and Accessory Proteins/genetics ; nef Gene Products, Human Immunodeficiency Virus ; }, abstract = {The frequency of anti-CD4 antibodies was determined in the sera or plasma derived from the patients infected with HIV-1 belonging to different genetic subgroups. The anti-CD4-antibodies in a dilution of > or = 1:1000 were found in 14% of the patients infected with the gagA/envA virus characteristic for injectable drug users in East Europe. The frequency of autoimmune antibodies among the HIV-infected patients with envB virus was substantially less (4.4%). Competitive ELISA using monoclonal antibodies to different CD4 domains demonstrated that irrespective of the viral genotype, the autoimmune epitope is located within the D4 or D3/D4 domains of CD4 receptor.}, } @article {pmid16201340, year = {2005}, author = {Snetkova, EV and Levin, VM and Petroniuk, IuS and Denisov, AF and Bogachenkov, AN and Denisova, LA and Khramtsova, EA}, title = {[Application of the method of acoustic microscopy for the study of eye tissues].}, journal = {Morfologiia (Saint Petersburg, Russia)}, volume = {127}, number = {2}, pages = {72-75}, pmid = {16201340}, issn = {1026-3543}, mesh = {Animals ; Coturnix/anatomy & histology/embryology ; Embryo, Nonmammalian/anatomy & histology ; Eye/*anatomy & histology ; Goats/anatomy & histology ; Larva/anatomy & histology ; Microscopy, Acoustic/*methods ; Ranidae/anatomy & histology ; }, abstract = {The paper describes the results of evaluation of potentialities of the application of scanning acoustic microscopy, which is still relatively new and as yet uncommon method of biological research, for the supravital study of animal eye structure in species with different eyeball size. Using the eyes of a goat, quail embryo (in situ) and frog tadpole (in vivo) as the examples, it was shown that non-destructive nature of the method used allows for the study of peculiarities of major morphologic structures in the state that is close to the natural one. Some acoustic images are presented showing eye structural elements along with the results of quantitative characteristic of the cornea, sclera and iris.}, } @article {pmid16078530, year = {2005}, author = {Igolkina, SN and Puzyrev, VF and Zinina, LG and Denisova, NM and Burkov, AN and Obriadina, AP and Ulanova, TI}, title = {[The enzyme immunological test systems "DS-EIA-HBeAg" and "DS-EIA-anti-HBe" for the specific diagnosis and prediction of the outcomes of acute and chronic hepatitis B].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {}, number = {6}, pages = {34-37}, pmid = {16078530}, issn = {0869-2084}, mesh = {Acute Disease ; Clinical Laboratory Techniques ; Enzyme-Linked Immunosorbent Assay/methods ; Hepatitis B/*diagnosis/physiopathology ; Hepatitis B e Antigens/*blood ; Hepatitis B, Chronic/*diagnosis/physiopathology ; Humans ; Predictive Value of Tests ; Prognosis ; }, } @article {pmid16078433, year = {2005}, author = {Lashkevich, VA and Koroleva, GA and Lukashev, AN and Denisova, EV and Katargina, LA and Khoroshilova-Maslova, IP}, title = {[Acute enterovirus uveitis in infants].}, journal = {Voprosy virusologii}, volume = {50}, number = {3}, pages = {36-45}, pmid = {16078433}, issn = {0507-4088}, mesh = {Animals ; Antibodies, Viral/blood ; Antigens, Viral/immunology ; Cataract/etiology ; Cross Reactions ; Disease Models, Animal ; *Disease Outbreaks ; *Echovirus Infections/blood/complications/diagnosis/epidemiology ; Enterovirus B, Human/genetics/immunology ; Eye/virology ; Glaucoma/etiology ; Humans ; Infant ; Iris/pathology ; Molecular Epidemiology ; Neutralization Tests ; Phylogeny ; Primates ; Pupil Disorders ; RNA, Viral/genetics ; Russia/epidemiology ; *Uveitis/blood/complications/diagnosis/epidemiology ; Vision Disorders/etiology ; }, abstract = {Enterovirus uveitis (EU) is a new infant eye disease that was first detected and identified in Russia in 1980-1981. Three subtypes of human echoviruses (EV19K, EV11A, and EV11/B) caused 5 nosocomial outbreaks of EU in different Siberian cities and towns in 1980-1989, by affecting more than 750 children mainly below one year of age. Sporadic and focal EU cases (more than 200) were also retrospectively diagnosed in other regions of Russia and in different countries of the former Soviet Union. There were following clinical manifestations: common symptoms of the infection; acute uveitis (rapid focal iridic destruction, pupillary deformities, formation of membranes in the anterior chamber of the eye); and in 15-30% of cases severe complications, cataract, glaucoma, vision impairments. Uveitis strains EV19 and EV11 caused significant uveitis in primates after inoculation into the anterior chamber of the eye, as well as sepsis-like fatal disease with liver necrosis after venous infection. The uveitis strains are phylogenetically and pathogenetically close for primates to strains EV19 and EV11 isolated from young children with sepsis-like disease. The contents of this review have been published in the Reviews in Medical Virology, 2004, vol. 14, p. 241-254.}, } @article {pmid16044839, year = {2005}, author = {Pogozheva, AV and Denisova, NN and Derbeneva, SA and Anykina, NV and Kondakova, NM}, title = {[Application of nutritional formulare in the dietotherapy in patients with cardiovascular diseases].}, journal = {Voprosy pitaniia}, volume = {74}, number = {3}, pages = {32-38}, pmid = {16044839}, issn = {0042-8833}, mesh = {Adult ; Aged ; Cardiovascular Diseases/*diet therapy ; *Enteral Nutrition ; Female ; *Food, Formulated ; Humans ; Lipid Metabolism ; Male ; Middle Aged ; Obesity/*diet therapy ; }, abstract = {It was found that the including of nutritional formulae in the dietary therapy for patients with cardiovascular diseases and obesity has been evaluated, had a positive effect on the clinical presentation of disease, lipid metabolism and the dynamic of body composition of patients.}, } @article {pmid16034353, year = {2005}, author = {Garashchenko, TI and Denisova, OA and Kotov, RV}, title = {[Initial antibiotic therapy in acute otitis media and acute sinusitis in children].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {3}, pages = {62-63}, pmid = {16034353}, issn = {0042-4668}, mesh = {Acute Disease ; Administration, Oral ; Amoxicillin/administration & dosage/*therapeutic use ; Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Otitis Media, Suppurative/*drug therapy/*epidemiology/microbiology ; Sinusitis/*drug therapy/*epidemiology/microbiology ; Suspensions ; Treatment Outcome ; }, } @article {pmid15974299, year = {2004}, author = {Malyarchuk, B and Derenko, M and Grzybowski, T and Lunkina, A and Czarny, J and Rychkov, S and Morozova, I and Denisova, G and Miścicka-Sliwka, D}, title = {Differentiation of mitochondrial DNA and Y chromosomes in Russian populations.}, journal = {Human biology}, volume = {76}, number = {6}, pages = {877-900}, doi = {10.1353/hub.2005.0021}, pmid = {15974299}, issn = {0018-7143}, mesh = {Chromosomes, Human, Y/*genetics ; DNA, Mitochondrial/*genetics ; Female ; Genetic Heterogeneity ; Genetic Variation ; *Genetics, Population ; Haplotypes ; Humans ; Male ; *Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Russia ; White People/genetics ; }, abstract = {The genetic composition of the Russian population was investigated by analyzing both mitochondrial DNA (mtDNA) and Y-chromosome loci polymorphisms that allow for the different components of a population gene pool to be studied, depending on the mode of DNA marker inheritance. mtDNA sequence variation was examined by using hypervariable segment I (HVSI) sequencing and restriction analysis of the haplogroup-specific sites in 325 individuals representing 5 Russian populations from the European part of Russia. The Y-chromosome variation was investigated in 338 individuals from 8 Russian populations (including 5 populations analyzed for mtDNA variation) using 12 binary markers. For both uniparental systems most of the observed haplogroups fell into major West Eurasian haplogroups (97.9% and 99.7% for mtDNA and Y-chromosome haplogroups, respectively). Multidimensional scaling analysis based on pairwise F(ST) values between mtDNA HVSI sequences in Russians compared to other European populations revealed a considerable heterogeneity of Russian populations; populations from the southern and western parts of Russia are separated from eastern and northern populations. Meanwhile, the multidimensional scaling analysis based on Y-chromosome haplogroup F(ST) values demonstrates that the Russian gene pool is close to central-eastern European populations, with a much higher similarity to the Baltic and Finno-Ugric male pools from northern European Russia. This discrepancy in the depth of penetration of mtDNA and Y-chromosome lineages characteristic for the most southwestern Russian populations into the east and north of eastern Europe appears to indicate that Russian colonization of the northeastern territories might have been accomplished mainly by males rather than by females.}, } @article {pmid15938103, year = {2005}, author = {Biriukova, LS and Purlo, NV and Denisova, EN and Mondoev, LG and Levina, AA and Galstian, GM}, title = {[Use of continuous high-volume hemofiltration in patients with sepsis and multiple organ dysfunction].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {2}, pages = {69-71}, pmid = {15938103}, issn = {0201-7563}, mesh = {Adult ; Biomarkers/blood ; Cytokines/blood ; Enzymes/blood ; Female ; Hemofiltration/adverse effects/*methods ; Humans ; *Kidneys, Artificial ; Male ; Middle Aged ; Multiple Organ Failure/*therapy ; Online Systems ; Sepsis/*therapy ; }, abstract = {The paper gives the authors' experience in performing continuous high-volume hemofiltration in 38 patients with sepsis and multiple organ failure. The kinetics of proinflammatory cytokines and a number of plasma enzymes as markers of substances having a relatively high molecular mass was studied. The advantages of a procedure using an artificial kidney apparatus equipped with an on-line substituting fluid preparation system are described. The possibilities of correcting the parameters of homeostasis are the principles of maintenance of a hemostatic system in this group of patients during the procedure are presented. The drawbacks of this technique are also described.}, } @article {pmid15934363, year = {2005}, author = {Spasov, AA and Bugaeva, LI and Denisova, TD and Smirnova, LA}, title = {[The effect of bemithyl on the onthogenesis of rats].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {68}, number = {2}, pages = {28-32}, pmid = {15934363}, issn = {0869-2092}, mesh = {Administration, Oral ; Animals ; Animals, Newborn ; Anticonvulsants/administration & dosage/*adverse effects ; Benzimidazoles/administration & dosage/*adverse effects ; Female ; *Lactation/drug effects ; Male ; Rats ; Sexual Maturation/*drug effects ; Time ; }, abstract = {Female rats were treated with bemithyl (20 and 100 mg/kg) via a gastric tube during a 16-day period of lactation. It was found that the drug is transferred with breast milk to the organism of newborns, which leads to nonuniformities in their development. Among the early effects of bemithyl, most pronounced is the stimulating action upon maturation (muscle strength) and the development of sensor-locomotor reflexes; in the spectrum of long-term effects, the drug influence upon pubescence processes was manifested.}, } @article {pmid15921200, year = {2005}, author = {Denisova, NN and Baturin, AK and Pogozheva, AV}, title = {[Analysis by bioelectrical impedance of body composition of patients with cardiovascular diseases and obesity].}, journal = {Voprosy pitaniia}, volume = {74}, number = {2}, pages = {20-25}, pmid = {15921200}, issn = {0042-8833}, mesh = {Adult ; Aged ; *Body Composition ; *Body Mass Index ; Cardiovascular Diseases/complications/*physiopathology ; Electric Impedance ; Female ; Humans ; Male ; Middle Aged ; Obesity/complications/diet therapy/*physiopathology ; }, abstract = {Authors of article have recently analyzed the dynamic of body composition of patients with cardiovascular diseases and obesity by bioelectrical impedance analysis. It was found a difference of body composition in different groups of patients.}, } @article {pmid15881156, year = {2005}, author = {Katargina, LA and Khvatova, AV and Kogoleva, LV and Denisova, EV}, title = {[Problems and outlooks for the preventive treatment of retinopathy in prematures].}, journal = {Vestnik oftalmologii}, volume = {121}, number = {2}, pages = {38-41}, pmid = {15881156}, issn = {0042-465X}, mesh = {Cryosurgery/*trends ; Disease Progression ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Laser Coagulation/*trends ; Refraction, Ocular/physiology ; Retina/pathology/surgery ; Retinopathy of Prematurity/pathology/physiopathology/*prevention & control ; Treatment Outcome ; }, abstract = {The immediate and remote (up to 7 years) results of preventive cryo- and/or lasercoagulation of avascular retinal zones made in 390 children with active progressing retinopathy of prematures (RP) were analyzed. The efficiency of cryocoagulation in processes localized in zones 2-3 of the eye bottom made 92%, and that of the combined technique (laser- and cryocoagulation) with lesions in zones 1-2 and with plus-diseases was up to 80%. The preventive treatment is indicated for the 3d threshold (ordinary clinical course) and before-threshold (with plus-disease and localization zone 1) stages. Such treatment is not justified when undertaken early and in developed retinal detachment. Further research of the disease pathogenesis is needed to enhance the efficiency of the RP treatment, i.e. research of growth factors of endothelial vessels, autoimmune reaction to S-antigen of the retina and of dosed oxygentherapy etc.}, } @article {pmid15881151, year = {2005}, author = {Krichevskaia, GI and Andzhelov, VO and Katargina, LA and Starikova, AV and Denisova, EV and Zvonarev, AIu and Kuliakina, MN and Tsutskiridze, NG}, title = {[Reactivation of persistent herpes virus infection as a factor of endogenous uveitis in children].}, journal = {Vestnik oftalmologii}, volume = {121}, number = {2}, pages = {22-24}, pmid = {15881151}, issn = {0042-465X}, mesh = {Adolescent ; Antibodies, Viral/blood ; Child ; Child, Preschool ; Cytomegalovirus/growth & development/immunology ; Cytomegalovirus Infections/immunology/transmission/virology ; DNA, Viral/immunology ; Follow-Up Studies ; Herpes Simplex/immunology/transmission/*virology ; Herpesvirus 1, Human/*growth & development/immunology ; Humans ; Immunoenzyme Techniques ; Infant ; Infectious Disease Transmission, Vertical ; Lymphocytes/immunology ; Recurrence ; Severity of Illness Index ; Uveitis/blood/immunology/*virology ; }, abstract = {Two hundred and fifty-five children with endogenous uveitis, aged 2 months to 15 years, were examined. 73-93% of children were chronically infected by different viruses of the human herpes group; mycoplasmal past-infection was detected in only 13% of them and Chlamydia past-infection _ in 3.7% of them. Herpes simplex virus of type 1 reactivated reliably more often versus other types of Herpesviridae. Reactivation of cytomegalovirus infection prevailed in mothers who gave birth to children with intrauterine uveitis. A prolonged active replication of herpes virus was primarily observed in children with a Suppressed cell antiviral immunity component. Uveitis in such children was notable for a severe clinical course and trend towards often relapses.}, } @article {pmid15881100, year = {2005}, author = {Denisova, TP and Shkoda, AS and Malinova, LI and Astaf'eva, NG}, title = {[Social stress as a risk factor for ischemic heart disease].}, journal = {Terapevticheskii arkhiv}, volume = {77}, number = {3}, pages = {52-55}, pmid = {15881100}, issn = {0040-3660}, mesh = {Humans ; Myocardial Infarction/*epidemiology/etiology ; Risk Factors ; Russia ; Socioeconomic Factors ; Stress, Psychological/*complications ; }, abstract = {AIM: To study dynamics of ischemic heart disease in exposure of the population of an industrial city to social-economic stress.

MATERIAL AND METHODS: Official annual records of Saratov city Health Administration for 1989-1998. In public health evaluation, cardiovascular morbidity is the index rapidly reacting to social-economic changes. Descrete data of myocardial infarction and angina prevalence for the analysed time were approximated by polynomes of high degree. As a result, the first and second derivatives--speed and acceleration--were obtained.

RESULTS: A rise in MI morbidity reflected a rise in social tension. The disturbance of the population system of an industrial center (in conditions of a social stress) is accompanied by marked deformation of the profile of cardiovascular diseases in the industrial region: the growth of MI prevalence is associated with lowering of angina pectoris morbidity.

CONCLUSION: A rise in MI incidence rate is proposed as an indicator of social-economic stability or instability. Instability of IHD morbidity in the population allows consideration of social stress as its risk factor.}, } @article {pmid15869125, year = {2005}, author = {Denisova, NA and Booth, SL}, title = {Vitamin K and sphingolipid metabolism: evidence to date.}, journal = {Nutrition reviews}, volume = {63}, number = {4}, pages = {111-121}, doi = {10.1111/j.1753-4887.2005.tb00129.x}, pmid = {15869125}, issn = {0029-6643}, mesh = {Animals ; Brain/*metabolism ; Humans ; Sphingolipids/chemistry/*metabolism ; Vitamin K/*physiology ; }, abstract = {The brain is enriched with sphingolipids, which are important membrane constituents and major lipid signaling molecules that have a role in motor and cognitive behavior. Vitamin K has been implicated in brain sphingolipid metabolism for more than 30 years. The in vitro and in vivo studies to date suggest a role of vitamin K in the regulation of multiple enzymes involved in sphingolipid metabolism within the myelin-rich regions in the brain. However, the precise mechanisms of action are not well understood. Further, the physiological consequences of the observed effects of vitamin K on sphingolipid metabolism have not been systematically studied.}, } @article {pmid15829299, year = {2005}, author = {Meyuhas, R and Noy, H and Montefiori, DC and Denisova, G and Gershoni, JM and Gross, G}, title = {HIV-1 neutralization by chimeric CD4-CG10 polypeptides fused to human IgG1.}, journal = {Molecular immunology}, volume = {42}, number = {9}, pages = {1099-1109}, doi = {10.1016/j.molimm.2004.11.002}, pmid = {15829299}, issn = {0161-5890}, mesh = {Antibodies, Monoclonal/*immunology ; CD4 Antigens/genetics/*immunology ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; Epitopes/immunology ; HIV Envelope Protein gp120/immunology ; HIV-1/*immunology ; Humans ; Immunoglobulin G/*immunology ; Immunoglobulin Variable Region/genetics/immunology ; Neutralization Tests ; Receptors, HIV/immunology ; Recombinant Fusion Proteins/immunology/isolation & purification ; Transfection ; }, abstract = {The envelope glycoprotein of HIV-1 is the principal target for entry inhibitors. The use of soluble CD4 has been found to be impractical as most clinical isolates are resistant to neutralization at feasible concentrations. CG10 is one of a small group of monoclonal antibodies specific to CD4-induced epitopes, which are structurally associated with the chemokine receptor-binding site and are capable of blocking the interaction of gp120 with its obligatory co-receptor. We have reasoned that fusing the single chain Fv of CG10 with CD4 can lead to increased HIV-1 neutralization activity and that this effect could be further enhanced by engrafting this chimeric construct onto an IgG Fc. Here we report the cloning of the genes encoding the variable regions of CG10 heavy and light chains and demonstrate that when attached to human IgG1 Fc, the single chain Fv of CG10 retains the binding properties of the original mouse antibody. Fusing CG10 single chain Fv with the gp120-binding portion of CD4 on a human IgG1 Fc backbone results in stronger binding of gp120 of different tropisms and in enhanced neutralization of laboratory-adapted strains and most, but not all, clade B and clade C isolates tested. Our findings underscore the potential use of CD4-based fusion proteins in the design of HIV immuno-therapeutics.}, } @article {pmid15822641, year = {2005}, author = {Denisova, NN and Pogozheva, AV and Baturin, AK}, title = {[The nutrition analysis of the patients with cardio-vascular diseases].}, journal = {Voprosy pitaniia}, volume = {74}, number = {1}, pages = {24-27}, pmid = {15822641}, issn = {0042-8833}, mesh = {Adult ; Age Factors ; Cardiovascular Diseases/*diet therapy ; Eating ; Energy Intake ; Feeding Behavior ; Female ; Humans ; Hypertension/diet therapy ; Male ; Middle Aged ; Myocardial Ischemia/diet therapy ; *Nutrition Assessment ; Software ; }, abstract = {Authors of article have recently analyzed the actual food intake from patients with cardiovascular diseases with the help of a new computer program, based on frequency method. It was found a disbalance of intake main food components in different groups of patients.}, } @article {pmid15751286, year = {2005}, author = {Denisova, EL and Gorshkov, AI and Liakhova, NP}, title = {[Influence of environmental factors on human health (in case of Orekhovo-Zuyevo)].}, journal = {Gigiena i sanitariia}, volume = {}, number = {1}, pages = {6-8}, pmid = {15751286}, issn = {0016-9900}, mesh = {Adolescent ; Adult ; Age Factors ; *Air Pollution ; Child ; *Health Status ; Humans ; Industry ; *Nutritional Physiological Phenomena ; Russia ; Surveys and Questionnaires ; Urban Population ; }, abstract = {The paper analyzes the actual nutrition in 301 schoolchildren (142 children and 159 adolescents), the state of ambient air and the health status of the population in 5 districts of the town of Orekhovo-Zuyevo. Non-balanced diets and ambient air pollution have been ascertained to negatively affect human health.}, } @article {pmid15727143, year = {2004}, author = {Tsinberg, MB and Deriabin, DG and Denisova, IV}, title = {[Biological characterization of Bifidobacterium and Lactobacillus preparations made with the use of hydrolysate-milk and hydrolysate-soybean media].}, journal = {Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]}, volume = {49}, number = {8-9}, pages = {29-33}, pmid = {15727143}, issn = {0235-2990}, mesh = {Animals ; *Antibiosis ; *Bacterial Adhesion ; Bifidobacterium/growth & development/*physiology ; Culture Media ; Escherichia coli/physiology ; Hydrolysis ; Lactobacillus/growth & development/*physiology ; Milk ; *Probiotics ; Soybeans ; Staphylococcus aureus/physiology ; }, abstract = {A complex of biological characteristics important for design of the therapeutic and prophylactic activities of Bifidobacterium and Lactobacillus preparations made with the use of hydrolysate-milk and hydrolysate-soybean media was comparatively estimated. The use of the hydrolysate-soybean medium resulted in an increase of the antagonistic activity of the preparations against a number of opportunistic pathogens that was not connected with changing of their acidity and the content of lysozyme, a bacteriolytic enzyme in the culture fluid. The change in the cultivation conditions due to substitution of the hydrolysate-milk medium for the hydrolysate-soybean medium stimulated the adhesive capacity of the production strains used in the study, which was especially evident with respect to the representatives of the genus Bifidobacterium.}, } @article {pmid15704443, year = {2004}, author = {Denisova, LB and Vorontsova, SV and Platonova, AG}, title = {[To the potentialities of computed tomographic diagnosis of renal lymphoma].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {39-44}, pmid = {15704443}, issn = {0042-4676}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Diagnosis, Differential ; Disease Progression ; Fatal Outcome ; Female ; Humans ; Kidney Neoplasms/*diagnostic imaging/drug therapy ; Lymphoma/*diagnostic imaging/drug therapy ; Middle Aged ; *Tomography, X-Ray Computed ; }, } @article {pmid15704441, year = {2004}, author = {Denisova, LB and Vorontsova, SV and Eme'ianova, LN}, title = {[Role of new radiation techniques (ultrasonography, computed tomography, and magnetic resonance imaging) in the diagnosis of incidentally discovered adrenal masses].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {25-33}, pmid = {15704441}, issn = {0042-4676}, mesh = {Adrenal Gland Neoplasms/*diagnosis ; Adrenal Glands/*pathology ; Diagnosis, Differential ; Diagnostic Imaging/*methods ; Humans ; Magnetic Resonance Imaging ; Reproducibility of Results ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {The authors analyze the current views of incidentally discovered adrenal masses and the potentialities of ultrasound study (US), computed tomography (CT), and magnetic resonance imaging (MRI) in their detection and presents the US, CT, and MRI symptoms of different incidentally discovered adrenal masses. Due to the availability and almost extensive application of US apparatuses, they define the importance of US screening of the adrenal region and emphasize the capacities of echographic differentiation of cystic and solid adrenal masses in patients with different diseases of the abdomen and retroperitoneal space. The authors also note the basic role of CT and MRI in the specified topical diagnosis of retroperitoneal space lesions and in the presumption of the morphological structure of some tumor and tumoroid (hyperplasia-type) adrenal changes.}, } @article {pmid15697655, year = {2005}, author = {Denisov, SI and Denisova, ES and Hänggi, P}, title = {Ratchet transport for a chain of interacting charged particles.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {71}, number = {1 Pt 2}, pages = {016104}, doi = {10.1103/PhysRevE.71.016104}, pmid = {15697655}, issn = {1539-3755}, abstract = {We study analytically and numerically the overdamped, deterministic dynamics of a chain of charged, interacting particles driven by a longitudinal alternating electric field and additionally interacting with a smooth ratchet potential. We derive the equations of motion, analyze the general properties of their solutions and find the drift criterion for chain motion. For ratchet potentials of the form of a double-sine and a phase-modulated sine it is demonstrated that both, a so-called integer and fractional transport of the chain, can occur. Explicit results for the directed chain transport for these two classes of ratchet potentials are presented.}, } @article {pmid15689127, year = {2004}, author = {Supriaga, VG and Tsybina, TN and Denisova, TN and Morozov, EN and Romanenko, NA and Starkova, TV}, title = {[The first case of diagnosis of dirofilariasis from the microfilariae detected in the human subcutaneous tumor punctate].}, journal = {Meditsinskaia parazitologiia i parazitarnye bolezni}, volume = {}, number = {4}, pages = {6-8}, pmid = {15689127}, issn = {0025-8326}, mesh = {Animals ; Diagnosis, Differential ; Dirofilaria/*isolation & purification ; Dirofilariasis/*diagnosis/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Russia/epidemiology ; Soft Tissue Neoplasms/*diagnosis/parasitology ; Subcutaneous Tissue/parasitology ; Thorax ; }, abstract = {The paper describes the first case of diagnosis of dirofilariasis from the microfilariae detected in the subcutaneous tumor punctate from a person who has the clinical manifestations of D. repens invasion and resides in the Saratov Region that is endemic in dirofilariasis. The fact of detection of microfilariae in the man undergone invasion is assessed not only as the first case in the lifetime diagnosis of the first case of diagnosis of subcutaneous dirofilariasis, but also as the first case of verification of that a female can achieve sexual maturity in the organism of an accidental host and its impregnation if there are even single specimens of both sexes, which is characteristic in human invasiveness. On this basis, the authors consider it wrong to refer this helminthiasis to as a group of diseases defined as "Larva migrans cutaneous" since this is inconsistent with the biology of a causative agent that accomplishes migration at the adult stage in the host's organism and does not orient a physician to establish a correct clinical and parasitological diagnosis.}, } @article {pmid15685857, year = {2004}, author = {Denisova, SN and Iukhtina, NV and Balabolkin, II and Korotkova, TN and Sentsova, TB and Belitskaia, MIu and Volkova, EA and Kon', IIa}, title = {[New way in dietotherapy of infants with food allergy].}, journal = {Voprosy pitaniia}, volume = {73}, number = {6}, pages = {32-35}, pmid = {15685857}, issn = {0042-8833}, mesh = {Animals ; Dermatitis, Atopic/*diet therapy/immunology ; Female ; Goats ; Humans ; Immunoglobulin E/blood/immunology ; Infant ; *Infant Food ; Male ; Milk/immunology ; Milk Hypersensitivity/*immunology ; Milk Proteins/*adverse effects ; }, abstract = {The authors followed up (in outpatient conditions) a total of fifty 1-to-9-mounth-old infants with the diagnosis of atopic dermatitis, disseminated form, of subacute course. The infants were followed up for 3-12 months, with 83% of the 113 examined patients 1-3 weeks after the beginning of treatment having shown clinical improvement of cutaneous inflammatory processes. Of the 172 infants subjected to immunological examination, in 100--the level of total IgE in blood serum was significantly elevated. These children also had elevated level of the specific IgE antibodies to cow's milk proteins. The outcomes of the carried out dietotherapy using mixture "Nanny" showed that this therapeutic product resulted in remission in the majority of the followed up infants suffering from allergy to cow's milk proteins.}, } @article {pmid15665958, year = {2004}, author = {Denisova, NA and Pletneva, TV and Baikova, VN and Berezov, TT}, title = {Kinetic characteristics of biochemical parameters during consupren therapy after allogenic transplantation of the kidney.}, journal = {Bulletin of experimental biology and medicine}, volume = {138}, number = {4}, pages = {407-411}, doi = {10.1007/s10517-005-0055-2}, pmid = {15665958}, issn = {0007-4888}, mesh = {Adolescent ; Adult ; Creatinine/blood ; Cyclosporine/administration & dosage/blood/*therapeutic use ; Female ; Humans ; Immunosuppressive Agents/administration & dosage/blood/*therapeutic use ; Kidney Transplantation/*physiology ; Kinetics ; Male ; Middle Aged ; Transplantation, Homologous ; Urea/blood ; }, abstract = {Changes in biochemical and common clinical parameters of the blood were detected in patients treated with consupren (cyclosporin) as the main immunosuppressant after allogenic transplantation of the kidney. Kinetic model for evaluation of treatment adequacy was based on therapeutic drug monitoring and monitoring of blood biochemistry in recipients of the primary kidney transplant. The k1, t1/2, C0, clearance (for hemoglobin), conditioned volume of distribution (for cyclosporin) of processes of biochemical parameters (toxicity markers) stabilization within the framework of a single-part kinetic model were determined.}, } @article {pmid15651660, year = {2004}, author = {Smetannikova, MA and Beliavskaia, VA and Smetannikova, NA and Savkin, IV and Denisova, DV and Ustinov, SN and Maksimov, VN and Shabalin, AV and Bolotnova, TV and Voevoda, MI}, title = {[Functional polymorphism of p53 and CCR5 genes in the long-lived of the Siberian region].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {11}, pages = {25-28}, pmid = {15651660}, issn = {0869-6047}, mesh = {Aged ; Aged, 80 and over ; Alleles ; *Genes, p53 ; Humans ; Longevity/*genetics ; Polymorphism, Genetic ; Receptors, CCR5/*genetics ; Siberia ; }, abstract = {The P53 protein is a key regulator of modified-cell apoptosis. The functional oligonucleotide polymorphism of the p53 gene causes the substitution of arginine (Arg) for praline (Pro) in the codon 72. A reduced apoptotic activity of p53 and, as a consequence, development of oncology pathology is associated with the above polymorphism. CCR5 is a compound transmembrane receptor-protein, which apart from chemokines, binds with some molecules and is a coreceptor for HIV-1. 32 bp deletion within the CCR5 encoding region results in the loss of the protein's receptor function. It has been demonstrated that the transmission of the "external" (in respect to cell) stimulus, via the CCR5 system, induces expression of the p53 gene and initiates apoptosis. Allele variants and p53 and CCR5 genotypes (separately and in combinations) were investigated, within the present case study, for 131 long-livers from Novosibirsk and Tyumen Regions. A trend was detected towards accumulation of the p53 Pro alleles in association with the CCR5del32 allele in the study group, which, as the authors believe, can enhance the genome resistance to variable factors that cut the life span.}, } @article {pmid15648924, year = {2004}, author = {Denisova, VV}, title = {[Detection of group-specific antigens of the ABO system in fish blood].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {47}, number = {6}, pages = {36}, pmid = {15648924}, issn = {0039-4521}, mesh = {*ABO Blood-Group System ; Animals ; *Blood Grouping and Crossmatching ; *Blood Stains ; Fishes/*blood ; Humans ; }, abstract = {The subject of the case study was blood of 8 fish species. It was examined within the ABO system. 68 tests of stains of fish blood mixed with human blood were made. It was shown as possible to differentiate between human blood and fish blood in mixed stains.}, } @article {pmid15636146, year = {2004}, author = {Kozhagel'dieva, AA and Karal'nik, BV and Denisova, TG and Tugambaev, TI}, title = {[Development of immunoreagents for the diagnostics of intestinal yersiniosis by antigen-binding lymphocytes].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {6}, pages = {73-76}, pmid = {15636146}, issn = {0372-9311}, mesh = {Animals ; Antigens, Bacterial/analysis ; Cross Reactions ; Diagnosis, Differential ; Gastroenteritis/blood/*diagnosis ; Lipopolysaccharides/administration & dosage/immunology ; Lymphocytes/*immunology ; Rabbits ; Rosette Formation/*methods ; Time Factors ; Yersinia Infections/blood/*diagnosis ; Yersinia enterocolitica/*immunology/isolation & purification ; }, abstract = {To diagnose intestinal yersiniosis, the detection of antigen-binding lymphocytes (ABL) with respect to Y. enterocolitica O3, O5 and O9 is proposed. Experiments on the immunization of rabbits with Y. enterocolitica LPS of these serovars revealed that immunoreagents, according to the data of cross antigen-dependent rosette formation and its inhibition, had species specificity (ABL of rabbits immunized with Y. enterocolitica did not interact with Salmonella, Shigella and Y. pseudotuberculosis antigens) and serovar specificity. Cross reactions in the detection of ABL by means of specific Y. enterocolitica O9 and Brucella melitensis immunoreagents in rabbits immunized with Y. enterocolitica were absent during the first days and could be detected only of day 25 after the injection of the immunogen. The method for the detection of ABL with the use of newly developed reagents could be used in clinics for the diagnostics of intestinal yersiniosis.}, } @article {pmid15602436, year = {2004}, author = {Malinova, LI and Dovgalevskiĭ, PIa and Simonenko, GV and Denisova, TP and Tuchin, VV}, title = {[Effect of high concentrations of glucose on physiological parameters of platelets in patients with ischemic heart disease.].}, journal = {Kardiologiia}, volume = {44}, number = {11}, pages = {24-27}, pmid = {15602436}, issn = {0022-9040}, mesh = {*Blood Platelets ; Coronary Artery Disease ; Diabetes Mellitus, Type 2/blood ; Erythrocytes ; *Glucose ; Humans ; Insulin/blood ; Myocardial Ischemia ; }, abstract = {Analysis of functional state of the erythrocyte system was carried out in 45 patients with stable class II and III angina including those with concomitant non insulin dependent diabetes and in 15 practically healthy subjects. The analysis was made in the process of upsetting the balance of the erythrocyte system by incubation with high concentrations of glucose in vitro. Functional state of erythrocytes was assessed by construction of fragments of a phase portrait on a plane representing relationship between dimensions of erythrocytes, glucose concentration and rate of the above mentioned process.}, } @article {pmid15496847, year = {2004}, author = {Ashurov, ZM and Synebogov, SV and Denisova, LB and Varfolomeeva, SR and Iniushkina, IV}, title = {[Non-Hodgkin's lymphoma of the Pirogov-Waldeyer pharyngeal ring].}, journal = {Vestnik otorinolaringologii}, volume = {}, number = {4}, pages = {54-55}, pmid = {15496847}, issn = {0042-4668}, mesh = {Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Head and Neck Neoplasms/diagnosis/drug therapy/pathology ; Humans ; *Lymphoma, B-Cell/diagnosis/drug therapy/pathology ; Male ; *Nasopharyngeal Neoplasms/diagnosis/drug therapy/pathology ; *Tonsillar Neoplasms/diagnosis/drug therapy/pathology ; Treatment Outcome ; }, } @article {pmid15458209, year = {2004}, author = {Lunkina, AV and Denisova, GA and Derenko, MV and Malarchuk, BA}, title = {[Mitochondrial DNA variation in two Russian populations from Novgorod oblast].}, journal = {Genetika}, volume = {40}, number = {7}, pages = {975-980}, pmid = {15458209}, issn = {0016-6758}, mesh = {DNA, Mitochondrial/*genetics ; *Genetics, Population ; Haplotypes ; Humans ; Russia ; }, abstract = {Mitochondrial DNA (mtDNA) polymorphism was examined in two Russian populations of Novgorod oblast, from the city of Velikii Novgorod (n = 81), and the settlement of Volot (n = 79). This analysis showed that the mitochondrial gene pool of Russians examined was represented by the mtDNA types belonging to 20 haplogroups and subhaplogroups distributed predominantly among the European populations. Haplogroups typical of the indigenous populations of Asia were found in the population sample from Velikii Novgorod with the average frequency of 3.7% (haplogroups A, Z, and D5), and with the frequency of 6.3% (haplogroups Z, D, and M*) in the Volot population. It was demonstrated that the frequency of the mitochondrial lineages combination, D5, Z, U5b-16144, and U8, typical of the Finnish-speaking populations of Northeastern Europe, was somewhat higher in the urban population (7.4%) compared to rural one (3.8%). The problem of genetic differentiation of Russians from Eastern Europe inferred from mtDNA data, is discussed.}, } @article {pmid15380649, year = {2004}, author = {Shamtsyan, M and Konusova, V and Maksimova, Y and Goloshchev, A and Panchenko, A and Simbirtsev, A and Petrishchev, N and Denisova, N}, title = {Immunomodulating and anti-tumor action of extracts of several mushrooms.}, journal = {Journal of biotechnology}, volume = {113}, number = {1-3}, pages = {77-83}, doi = {10.1016/j.jbiotec.2004.04.034}, pmid = {15380649}, issn = {0168-1656}, mesh = {Adjuvants, Immunologic/isolation & purification/*pharmacology ; Agaricales/*chemistry ; Animals ; Antineoplastic Agents/isolation & purification/*pharmacology ; Humans ; Melanoma/*drug therapy ; Mice ; Mice, Inbred CBA ; Neoplasm Transplantation ; Neutrophils/drug effects/metabolism ; Reactive Oxygen Species/metabolism ; Skin Neoplasms/*drug therapy ; }, abstract = {Aqueous extracts from fruit bodies and mycelia of various higher Basidiomycetes were studied in search for reliable biological effects. In vitro and in vivo experiments were conducted. The results showed that the aqueous extracts demonstrated various types of marked biological actions: an increased production of reactive oxygen forms by neutrophil cells of human peripheral blood; a significant mitogenic activity in a wide range of concentrations; stimulation on production of inflammatory cytokines interleukine 1-beta and interleukine-8 by peripheral blood cells; a decrease in both average tumor size in mice with transplanted melanoma B16 and a manifestation of tumorous intoxication; and a prolongation in the survival rate of such mice.}, } @article {pmid15340341, year = {2004}, author = {Novikova, DS and Bekbosynova, MS and Antidze, TIa and Loladze, NV and Domogatskiĭ, SP and Golitsyn, SP and Nasonov, EL and Denisova, IA and Tonevitskiĭ, SP}, title = {[Autoantibodies Against beta(1)-Adrenoreceptors in Patients With Cardiac Rhythm Disorders. Prevalence and Possible Role in Development of Arrhythmia].}, journal = {Kardiologiia}, volume = {44}, number = {7}, pages = {17-22}, pmid = {15340341}, issn = {0022-9040}, mesh = {*Autoantibodies/blood ; Cardiomyopathy, Dilated ; Humans ; Myocarditis/immunology ; Prevalence ; *Receptors, Adrenergic, beta-1 ; }, abstract = {AIM: To assess prevalence of autoantibodies against beta(1)-adrenoreceptors (beta(1)-AR) in patients with arrhythmias of various etiology.

MATERIAL: Patients with arrhythmias (n=110, including 59 patients with primary [idiopathic] electrical abnormalities, 33 - with chronic myocarditis and dilated cardiomyopathy [DCM]; 18 - with ischemic heart disease [IHD]) and healthy control subjects (n=20).

METHODS: Antibodies against beta(1)-AR were measured in blood serum by direct immunoassay. Synthetic fragment containing 26 amino acids of beta(1)-AR second loop was used as antigen.

RESULTS: Patients with primary electrical abnormalities and chronic myocarditis/DCM had similar prevalence of beta(1)-AR (49.1% and 54.5%, respectively), what was significantly higher than in controls (10%) and in patients with IHD (16.6%). These results provided evidence for the possible presence of an autoimmune process in the genesis of idiopathic arrhythmias. Among patients with idiopathic arrhythmias beta(1)-AR were found in 40% (10 of 25) of patients with ventricular tachycardia (VT), 63.6% (14 of 22) of patients with ventricular extrasystoles (VE), 41.6% (5 of 12) of patients with atrial fibrillation (AF). Among patients with chronic myocarditis and DCM beta(1)-AR were found in 72.2% (13 of 18) of patients with VT, 28.5% (2 of 7) of patients with VE, 37.5% (3 of 8) of patients with AF. Among patients with idiopathic arrhythmias female sex and frequent respiratory viral diseases were more common in beta(1)-AR-positive compared with beta(1)-AR-negative patients. VT and left ventricular ejection fraction <40% were more common in beta(1)-AR-positive than beta(1)-AR-negative patients among those with chronic myocarditis and DCM.}, } @article {pmid15340299, year = {2004}, author = {Makeeva, IM and Poiurovskaia, IIa and Ramazanova, AE and Denisova, LA}, title = {[Laboratory evaluation of the efficiency of dental root channel filling].}, journal = {Stomatologiia}, volume = {83}, number = {4}, pages = {19-21}, pmid = {15340299}, issn = {0039-1735}, mesh = {Adhesiveness ; Adhesives/chemistry/therapeutic use ; Dental Marginal Adaptation/*standards ; Gutta-Percha/chemistry/therapeutic use ; Humans ; Pressure ; Root Canal Obturation/*methods/standards ; Treatment Outcome ; }, abstract = {Adhesive strength of gutta-percha stems connection to the root channel walls was evaluated. The pressure on dental root channel walls during tooth filling by the lateral condensation method was evaluated. The study was carried out on an Instron device by the pulling out method. The study showed that for stems Nos. 15-30 the retention strength in the root channel was about 2-fold higher than for stems Nos. 35-45. The results indicate that the value of stem pressure on root channel walls during tooth filling by the lateral condensation method can be considered critical with regard to the strength of the dental root proper.}, } @article {pmid15248252, year = {2004}, author = {Lashkevich, VA and Koroleva, GA and Lukashev, AN and Denisova, EV and Katargina, LA}, title = {Enterovirus uveitis.}, journal = {Reviews in medical virology}, volume = {14}, number = {4}, pages = {241-254}, doi = {10.1002/rmv.433}, pmid = {15248252}, issn = {1052-9276}, mesh = {Adult ; Animals ; Child ; Disease Models, Animal ; *Disease Outbreaks ; Enterovirus B, Human/classification/genetics/*isolation & purification ; Enterovirus Infections/*epidemiology/virology ; Humans ; Infant ; Macaca mulatta ; Russia/epidemiology ; Uveitis/*epidemiology/virology ; }, abstract = {Enterovirus uveitis (EU) is a new infant eye disease that was first observed in 1980. Three distinct subtypes of human echoviruses, EV19/K, EV11/A and EV11/B, caused five hospital outbreaks of EU in different Siberian cities in 1980-1989, affecting approximately 750 children, predominantly below 1 year of age. Sporadic EU cases were also retrospectively diagnosed in other regions of Russia and in different countries of the Former Soviet Union. The illness was characterised by rapid iris destruction and severe complications, including cataract and glaucoma. The disease has been a subject of intensive studies and was reproduced in lower primates after intraocular inoculation of isolated enterovirus strains. Importantly, prototype EV11 and EV19 strains did not induce notable disease in experimental monkeys. Some of the EU-causing strains were shown to be similar phylogenetically and in their pathogenetic properties to the enterovirus strains associated with multisystem hemorrhagic disease of newborns. In this review we present a summary of the vast epidemiological, virological, clinical and experimental data on this new form of ophthalmic infection.}, } @article {pmid15176097, year = {2003}, author = {Tsinberg, MB and Deriabin, DG and Denisova, IV and Nikiian, AN}, title = {[Growth and morphological characteristics of industrial strains of Bifidobacterium and Lactobacillus cultivated in hydrolysate-milk and hydrolysate-soybean media].}, journal = {Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]}, volume = {48}, number = {12}, pages = {9-13}, pmid = {15176097}, issn = {0235-2990}, mesh = {Bifidobacterium/drug effects/*growth & development/ultrastructure ; Culture Media/chemistry ; Drug Industry ; Lactobacillus/drug effects/*growth & development/ultrastructure ; Microscopy, Atomic Force ; Milk Proteins/*pharmacology ; Protein Hydrolysates/*pharmacology ; Soybean Proteins/*pharmacology ; }, abstract = {Growth features of industrial strains of Bifidobacterium adolescentis MC-42, B. bifidum 1, B. longum B-379, Lactobacillus acidophilus, L. delbrueckii subsp. bulgaricus 8-79 and L. plantarum 8PA3 cultivated in hydrolysate-milk or hydrolysate-soybean media (HMM and HSM respectively) were analysed comparatively. The bacterial cells were investigated morphometrically with atom strength microscopy. It was shown that HSM vs HMM provided a higher growth rate of the strains (shortened growth phases and higher growth rates) that was more evident for the bifidobacteria as compared to the lactobacilli. At the same time, the morphological features of the bacterial cells slightly depended on the medium composition and were mainly defined by the genus.}, } @article {pmid15106842, year = {2004}, author = {Belousov, AB and Arumugam, H and Denisova, JV}, title = {Non-cholinergic excitation in neurons after a chronic glutamate receptor blockade.}, journal = {Neuroreport}, volume = {15}, number = {1}, pages = {113-117}, doi = {10.1097/00001756-200401190-00023}, pmid = {15106842}, issn = {0959-4965}, support = {RR16816/RR/NCRR NIH HHS/United States ; }, mesh = {Action Potentials/drug effects/physiology ; Animals ; Cells, Cultured ; Excitatory Amino Acid Agonists/pharmacology ; Excitatory Amino Acid Antagonists/*administration & dosage ; Neurons/*drug effects/*physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Glutamate/*physiology ; }, abstract = {Previous experiments revealed a dramatic increase in excitatory acetylcholine transmission in hypothalamic cultures during a chronic decrease in glutamate activity. Data suggested that in the absence of glutamate excitation, acetylcholine becomes the major excitatory neurotransmitter. However, non-cholinergic excitatory activity was also detected in some neurons. Here, using calcium imaging in hypothalamic cultures chronically subjected to the glutamate receptor blockade, we demonstrate the contribution of metabotropic glutamate receptors, P2-purinoreceptors, histamine receptors, adrenoreceptors, and gap junctions, but not nitric oxide to this non-cholinergic excitation. We also show that the sensitivity of neurons to receptor agonists is increased following the blockade. Data suggest that multiple components contribute to the excitatory activity in hypothalamic neurons during a long-term decrease in glutamate activity.}, } @article {pmid15021867, year = {2004}, author = {Denisova, LA}, title = {[Acoustic histology of dental tissues].}, journal = {Stomatologiia}, volume = {83}, number = {1}, pages = {4-8}, pmid = {15021867}, issn = {0039-1735}, mesh = {Animals ; Dental Enamel/*ultrastructure ; Dentin/*ultrastructure ; Dogs ; Elasticity ; Humans ; Microscopy, Acoustic ; Microscopy, Electron ; Sensitivity and Specificity ; Stress, Mechanical ; }, abstract = {New data on tooth enamel and dentin microstructure, obtained by acoustic microscopy methods, which are based on evaluation of distribution of the local elastic and mechanical properties, are presented. The results demonstrate that the acoustic microscopy methods are more sensitive to changes in mechanical properties of dental tissues in caries in comparison with optic microscopy.}, } @article {pmid15019450, year = {2004}, author = {Denisova, LA and Maev, RG and Poyurovskaya, IY and Grineva, TV and Denisov, AF and Maeva, EY and Bakulin, EY}, title = {The use of acoustic microscopy to study the mechanical properties of glass-ionomer cement.}, journal = {Dental materials : official publication of the Academy of Dental Materials}, volume = {20}, number = {4}, pages = {358-363}, doi = {10.1016/S0109-5641(03)00129-5}, pmid = {15019450}, issn = {0109-5641}, mesh = {Compressive Strength ; Elasticity ; *Glass Ionomer Cements/chemistry ; Hardness ; Microscopy, Acoustic ; Porosity ; }, abstract = {OBJECTIVES: The aim of the study was to investigate the relationship between microstructure, acoustic and mechanical properties of hardened dental cement samples, prepared with different powder/water ratios.

METHODS: Glass-ionomer dental cement samples, prepared with a standard amount of cement powder and different amounts of water have been examined after being hardened. Surface microstructure and ultrasound, longitudinal and shear velocities were obtained with a scanning acoustic microscope. Conditional effective elastic modulus and Poisson's ratio have been calculated using longitudinal and shear sound velocity values. Then on the same samples elastic modulus and microhardness have been determined by standard tests. Additional samples have been used to determine compressive strength.

RESULTS: Density; conditionally instantaneous elastic modulus; high-elasticity modulus and compression strength of the samples decrease when large amounts of water were used for their preparation. At the same time porosity and microhardness of the cement matrix increase. Acoustic parameters and parameters of elasticity, calculated on the basis of sound velocity, demonstrated changes, similar to those obtained in standard mechanical tests.

SIGNIFICANCE: The established relation between microstructure, acoustic and mechanical parameters demonstrated a high capacity of acoustic microscopy application for non-destructive characterization of dental materials. A particular advantage of the acoustic microscopy is the opportunity to evaluate microstructure and mechanical properties on the same sample.}, } @article {pmid14870584, year = {2003}, author = {Zav'ialova, LG and Denisova, DV}, title = {[Nutrition and blood lipid profile in adolescents during socioeconomic reforms in Russia: epidemiological study].}, journal = {Voprosy pitaniia}, volume = {72}, number = {6}, pages = {18-24}, pmid = {14870584}, issn = {0042-8833}, mesh = {Adolescent ; Adolescent Nutritional Physiological Phenomena/*physiology ; Cross-Sectional Studies ; Dietary Carbohydrates/administration & dosage ; Dietary Fats/administration & dosage ; Dietary Proteins/administration & dosage ; Female ; Humans ; Hyperlipidemias/blood/*epidemiology/etiology ; Lipids/*blood ; Male ; Risk Factors ; Sex Factors ; Siberia/epidemiology ; Socioeconomic Factors ; Surveys and Questionnaires ; }, abstract = {Aim of study was to assess trends in lipid profile and nutrition of adolescent population in Novosibirsk during the social and economic reforms in Russia (1989-1999). Three cross-sectional studies of school aged 14-17 in 1989 (657), in 1994 (620) and in 1999 (626) were carried out. Total sample was 1903 (914 males and 989 females). Blood lipids, such as total cholesterol (TC0, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were measured. Diet was estimated with the method of 24-hour dietary recall. During 10-year period mean serum TC decreased from 175 to 158 mg/dl in males and from 191 to 175 mg/dl in females (p < 0.001 for both genders). Females had significantly higher mean NC than did males at all surveys (p < 0.001)/Between 1989 and 1994 mean HDL-C levels decreased in boys both (p < 0.001), but in 1999 these levels were similar to 1989. During 1989-1994, TG levels significantly decreased, but between 1994 and 1999 mean TG levels increased in 1.5 times in both gender groups. Prevalence of high TC (> = 2000 mg/dl) significantly decreased from 17% to 6% in males and from 28% to 14% in females. Frequencies of low HDL-C (> = 40 mg/dl) also decreased in boys (from 28 to 8%) and girls (from 13 to 3%). Trends in diet showed similar changes and characterized by significant decreasing of total energy intakes (from 3021 to 2342 kcal in boys and from 2300 to 1644 kcal in girls) and of basic nutrient intakes (proteins? Fats? Carbohydrates). Negative trends in blood lipid profile and diet in adolescents during the unstable period of socioeconomic reforms in Russia indicate on serious changes in metabolic processes and need in large state economic programs to improve the situation.}, } @article {pmid14724672, year = {2004}, author = {Wang, Z and Troilo, PJ and Wang, X and Griffiths, TG and Pacchione, SJ and Barnum, AB and Harper, LB and Pauley, CJ and Niu, Z and Denisova, L and Follmer, TT and Rizzuto, G and Ciliberto, G and Fattori, E and Monica, NL and Manam, S and Ledwith, BJ}, title = {Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation.}, journal = {Gene therapy}, volume = {11}, number = {8}, pages = {711-721}, doi = {10.1038/sj.gt.3302213}, pmid = {14724672}, issn = {0969-7128}, mesh = {Animals ; DNA/administration & dosage/*metabolism ; Electroporation ; Erythropoietin/*genetics ; Genetic Therapy/*methods ; *Genome ; Injections, Intramuscular ; Mice ; Mice, Inbred BALB C ; Polymerase Chain Reaction/methods ; Transfection/methods ; }, abstract = {Plasmid vectors have been widely used for DNA vaccines and gene therapy. Following intramuscular injection, the plasmid that persists is extrachromosomal and integration into host DNA, if it occurs at all, is negligible. However, new technologies for improving DNA delivery could increase the frequency of integration. In the present study, we tested the effect of electroporation on plasmid uptake and potential integration following intramuscular injection in mice, using a plasmid containing the mouse erythropoietin gene. Electroporation increased plasmid tissue levels by approximately six- to 34-fold. Using a quantitative gel-purification assay for integration, electroporation was found to markedly increase the level of plasmid associated with high-molecular-weight genomic DNA. To confirm integration and identify the insertion sites, we developed a new assay - referred to as repeat-anchored integration capture (RAIC) PCR - that is capable of detecting rare integration events in a complex mixture in vivo. Using this assay, we identified four independent integration events. Sequencing of the insertion sites suggested a random integration process, but with short segments of homology between the vector breakpoint and the insertion site in three of the four cases. This is the first definitive demonstration of integration of plasmid DNA into genomic DNA following injection in vivo.}, } @article {pmid14597392, year = {2003}, author = {Denisov, DA and Denisova, GF}, title = {Hierarchical structure of donor splice site sequence multitude.}, journal = {Gene}, volume = {320}, number = {}, pages = {89-96}, doi = {10.1016/s0378-1119(03)00813-8}, pmid = {14597392}, issn = {0378-1119}, mesh = {Alternative Splicing/*genetics ; Base Sequence ; Binding Sites/genetics ; Evolution, Molecular ; Exons/genetics ; Introns/genetics ; Models, Genetic ; *Phylogeny ; Point Mutation ; }, abstract = {An analysis of donor splice site sequence (dsss) multitude was carried out. A special method was developed to study the multitude properties. The multitude of dsss was arranged as a hierarchical tree where the "root" consists of a small group of "ancestors", VAGgtVAG (gt stands in the beginning of intron, V=C,A,G). Every ancestor has its own clan of "descendants" which represent point mutants of it. The latter are split into "progenies". The first progeny looks like point mutants of the ancestors, the second as one-point mutants of sequences of the first progeny, and so forth. This picture looks like a hierarchical phylogenetic tree. The most striking property of the multitude is the successive monotonic decrease in occurrences of the sequences from one progeny to another. It is shown that such results may be modeled by a virtual mutational process.}, } @article {pmid14596802, year = {2003}, author = {Enshell-Seijffers, D and Denisov, D and Groisman, B and Smelyanski, L and Meyuhas, R and Gross, G and Denisova, G and Gershoni, JM}, title = {The mapping and reconstitution of a conformational discontinuous B-cell epitope of HIV-1.}, journal = {Journal of molecular biology}, volume = {334}, number = {1}, pages = {87-101}, doi = {10.1016/j.jmb.2003.09.002}, pmid = {14596802}, issn = {0022-2836}, mesh = {Algorithms ; Amino Acid Sequence ; Amino Acids/chemistry ; Antibodies, Monoclonal/immunology/metabolism ; B-Lymphocytes/*immunology ; *Epitopes ; HIV-1/*chemistry/*immunology ; Humans ; Models, Molecular ; Peptide Library ; *Protein Conformation ; }, abstract = {A method for the discovery of the structure of conformational discontinuous epitopes of monoclonal antibodies (mAbs) is described. The mAb is used to select specific phages from combinatorial phage-display peptide libraries that in turn are used as an epitope-defining database that is applied via a novel computer algorithm to analyze the crystalline structure of the original antigen. The algorithm is based on the following: (1) Most contacts between a mAb and an antigen are through side-chain atoms of the residues. (2) In the three-dimensional structure of a protein, amino acid residues remote in linear sequence can juxtapose to one another through folding. (3) Tandem amino acid residues of the selected phage-displayed peptides can represent pairs of juxtaposed amino acid residues of the antigen. (4) Contact residues of the epitope are accessible to the antigen surface. (5) The most frequent tandem pairs of amino acid residues in the selected phage-displayed peptides can reflect pairs of juxtaposed amino acid residues of the epitope. Application of the algorithm enabled prediction of epitopes. On the basis of these predictions, segments of an antigen were used to reconstitute an antigenic epitope mimetic that was recognized by its original mAb.}, } @article {pmid14515635, year = {2003}, author = {Panov, VO and Nadtochiĭ, AG and Ivanov, AV and Inaneishvili, MG and Denisova, LB and Safiullina, IM}, title = {[Magnetic resonance imaging and ultrasound study in the diagnosis og facial angiodysplasias in children: competition or collaboration?].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {3}, pages = {13-19}, pmid = {14515635}, issn = {0042-4676}, mesh = {Adolescent ; Adult ; Angiodysplasia/*diagnosis/diagnostic imaging ; Child ; Child, Preschool ; Face ; Female ; Humans ; Infant ; *Magnetic Resonance Angiography ; Male ; Sensitivity and Specificity ; Ultrasonography, Doppler, Color ; }, abstract = {This study deals with the capacities of noninvasive magnetic resonance imaging (MRI) with magnetic resonance angiography (MRA) without administration of magnetic resonance contrast substances in the diagnosis of facial soft tissue angiodysplasias in children. Indications for their use are defined. The methodology of the studies is proposed. Their diagnostic role and relationship with the other noninvasive technique of medical visualization--ultrasound study (USS) with Doppler color mapping (DCM) are assessed. As compared with USS, MRI may more accurately and objectively establish the organotopic characteristics of facial soft tissue angiodysplasias and detect lesions of the deep facial parts, maxillary bones, and paranasal sinuses in the diagnosis of these abnormalities. The use of MRI may define the belonging of angiodysplasias to the arterial or venous bed, reveal afferent and efferent vessels, including intracranial ones, and to detect intracranial angiodysplastic changes. USS with DSM was superior to MRI with MRA in defining functional (hemodynamic) parameters of angiodysplasias, which makes this method indispendable in planning treatment and in evaluating its efficiency. Comprehensive examination of patients with large and extensive angiodysplasias of facial soft tissues has indicated that facial angiodysplasias are external manifestations of a more generalized angiodysplastic process in most cases, which, in large and extensive facial angiodysplasias, makes it expedient to perform MRI with MRA of the brain and, if possible, the whole body. The high informative value of MRI with MRA in studying angiodysplasias makes them the method of choice in the diagnosis of this group of diseases.}, } @article {pmid12943795, year = {2003}, author = {Denisova, G and Lideman, L and Spectorman, E and Abulafia-Lapid, R and Burke, M and Yust, I and Gershoni, JM}, title = {Characterization of new monoclonal antibodies that discriminate between soluble and membrane CD4 and compete with human anti-CD4 autoimmune sera.}, journal = {Molecular immunology}, volume = {40}, number = {5}, pages = {231-239}, doi = {10.1016/s0161-5890(03)00147-0}, pmid = {12943795}, issn = {0161-5890}, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; Autoantibodies/*immunology ; CD4 Antigens/classification/genetics/*immunology ; HIV Envelope Protein gp120/immunology ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; }, abstract = {In this report we present results on immunization of hu-CD4 C57Black/6J transgenic mice with HIV-1 gp120(451) complexed with its receptor protein, CD4. In addition to development of anti-gp120 antibodies, these mice also produced two anti-CD4 monoclonal antibodies, designated T6 and T9. Both these antibodies recognize soluble CD4 but not membrane associated CD4. Their corresponding epitopes map to the D3-D4 domains of CD4. These characteristics are very similar to the HIV related anti-CD4 autoimmunity found in 10-15% of HIV-1 infected people. Therefore, 208 HIV-1 positive patients were screened for anti-CD4 humoral response of which 27 were found positive (13%). Sixteen of these patients were then tested for their ability to compete with the T6 and T9 anti-CD4 monoclonal antibodies. In such experiments saturating amounts of either T6 or T9 antibodies were able to prevent 20-80% of the human serum binding to immobilized soluble CD4 in competitive ELISA tests. The T6 and T9 antibodies therefore help to define distinct CD4 epitopes associated with clinical anti-CD4 autoimmunity.}, } @article {pmid12940914, year = {2003}, author = {Derenko, MV and Grzybowski, T and Malyarchuk, BA and Dambueva, IK and Denisova, GA and Czarny, J and Dorzhu, CM and Kakpakov, VT and Miścicka-Sliwka, D and Woźniak, M and Zakharov, IA}, title = {Diversity of mitochondrial DNA lineages in South Siberia.}, journal = {Annals of human genetics}, volume = {67}, number = {Pt 5}, pages = {391-411}, doi = {10.1046/j.1469-1809.2003.00035.x}, pmid = {12940914}, issn = {0003-4800}, mesh = {*DNA, Mitochondrial ; *Genetic Variation ; Humans ; Phylogeny ; Polymorphism, Restriction Fragment Length ; Siberia/epidemiology ; }, abstract = {To investigate the origin and evolution of aboriginal populations of South Siberia, a comprehensive mitochondrial DNA (mtDNA) analysis (HVR1 sequencing combined with RFLP typing) of 480 individuals, representing seven Altaic-speaking populations (Altaians, Khakassians, Buryats, Sojots, Tuvinians, Todjins and Tofalars), was performed. Additionally, HVR2 sequence information was obtained for 110 Altaians, providing, in particular, some novel details of the East Asian mtDNA phylogeny. The total sample revealed 81% East Asian (M*, M7, M8, M9, M10, C, D, G, Z, A, B, F, N9a, Y) and 17% West Eurasian (H, U, J, T, I, N1a, X) matrilineal genetic contribution, but with regional differences within South Siberia. The highest influx of West Eurasian mtDNAs was observed in populations from the East Sayan and Altai regions (from 12.5% to 34.5%), whereas in populations from the Baikal region this contribution was markedly lower (less than 10%). The considerable substructure within South Siberian haplogroups B, F, and G, together with the high degree of haplogroup C and D diversity revealed there, allows us to conclude that South Siberians carry the genetic imprint of early-colonization phase of Eurasia. Statistical analyses revealed that South Siberian populations contain high levels of mtDNA diversity and high heterogeneity of mtDNA sequences among populations (Fst = 5.05%) that might be due to geography but not due to language and anthropological features.}, } @article {pmid12939834, year = {2003}, author = {Denisova, OP and Pigolkin, IuI and Bogomolov, DV and Dolzhanskiĭ, OV and Bogomolova, IN and Gornostaev, DV}, title = {[Forensic and medical evaluation of vascular malformations of the brain in cranio-cerebral trauma].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {46}, number = {4}, pages = {6-10}, pmid = {12939834}, issn = {0039-4521}, mesh = {Adult ; Algorithms ; Brain/*blood supply/physiopathology ; Cerebral Hemorrhage/etiology ; Cerebrovascular Disorders/*etiology ; Craniocerebral Trauma/*complications/physiopathology ; Fatal Outcome ; *Forensic Medicine ; Humans ; Male ; }, abstract = {A classification of vascular malformations (VM) is defined in the article including a differentiation between their macroscopic and histological variations; an independently-authors-observed case of arterial-and-venous malformation (AVM) in a minor cranial-cerebral trauma (CCT) is described. Published data reflecting the forensic-and-medical value of AVM and cavernous malformations as well as of telangectasias and of arterial-and-venous fistulas in minor head traumas are analyzed. Issues of the forensic-and-medical expertise of VM and remote consequences of CCT are under consideration. VM are assessed in CCT patients with epilepsy and other pathologies. An algorithm of the forensic medical expertise of VM is suggested.}, } @article {pmid12926342, year = {2003}, author = {Portnoĭ, LM and Denisova, LB and Utkina, EV and Safiullina, IM and Denisov, VA and Sachechelashvili, GL}, title = {[Magnetic-resonance tomography in diagnosis of hepatopancreatoduodenal tumors].}, journal = {Khirurgiia}, volume = {}, number = {7}, pages = {59-65}, pmid = {12926342}, issn = {0023-1207}, mesh = {Adult ; Aged ; Cholangiopancreatography, Endoscopic Retrograde ; Female ; Gastrointestinal Neoplasms/complications/*diagnosis ; Humans ; Jaundice, Obstructive/diagnosis/etiology ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Pancreatic Neoplasms/complications/*diagnosis ; Tomography/*methods ; }, abstract = {Results of magnetic-resonance tomography (MRT) in 112 patients with diseases of hepatopancreatoduodenal zone were analyzed, 24 of them had tumors of bile ducts and pancreas. New noninvasive diagnostic method--magnetic-resonance cholangiopancreatography (MRCPG)--performed in addition to routine MRT was evaluated. The technique of MRCPG, analysis of results, manetic-resonance semiotics are presented. This method is compared with endoscopic retrograde cholangiopancreatography. It is concluded that combination of consentional MRT with MRCPG increases possibilities in diagnosis of hepatopancreatoduodenal cancers, complicated by obstructive jaundice, as a rule.}, } @article {pmid12886639, year = {2003}, author = {Denisova, TG and Karal'nik, BV and Urazov, VX and Kenzhebaeva, AT and Amireev, SA and Kuznetsova, EL and Vaneeva, NP}, title = {[Detection of lymphocytes binding erythrocytes conjugated with Salmonella antigens].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {3}, pages = {79-80}, pmid = {12886639}, issn = {0372-9311}, mesh = {Animals ; *Antigen Presentation ; Antigens, Bacterial/*immunology/metabolism ; Erythrocytes/*immunology/metabolism ; Immunization ; Immunoassay ; Lymphocytes/*immunology ; Rabbits ; Salmonella typhi/*immunology ; }, abstract = {Immune reagents for the detection of specific antigen-binding lymphocytes (ABL) with respect to different Salmonells antigens were developed. Rabbits were immunized with killed S. typhi and other salmonellae containing cross-reacting antigens, and the dynamics of the formation of ASL of each specificity was studied. Differences in the time of the appearance of ASL with receptors to thymus-independent (09, 12 or Vi) and thymus-dependent (Hd) antigens were studied. The relative content of ASL, determined with the use of immune reagents prepared from S. typhi antigens, was higher, on the whole, in rabbits immunized with S. typhi than in rabbits immunized with salmonellae containing one of cross-reacting antigens (S. enteritidis--09, 12; S. paratyphi C--Vi; S. virginia--Hd).}, } @article {pmid12819786, year = {2003}, author = {Carrasco, M and McElree, B and Denisova, K and Giordano, AM}, title = {Speed of visual processing increases with eccentricity.}, journal = {Nature neuroscience}, volume = {6}, number = {7}, pages = {699-700}, pmid = {12819786}, issn = {1097-6256}, support = {R01 MH057458-03/MH/NIMH NIH HHS/United States ; MH57458/MH/NIMH NIH HHS/United States ; }, mesh = {Differential Threshold ; Discrimination Learning ; Fovea Centralis/physiology ; Humans ; Motion Perception/*physiology ; Orientation ; Photic Stimulation ; *Psychophysics ; Random Allocation ; Reaction Time ; Sensory Thresholds ; Visual Fields/*physiology ; Visual Perception/*physiology ; }, abstract = {The visual system has a duplex design to meet conflicting environmental demands: the fovea has the resolution required to process fine spatial information, but the periphery is more sensitive to temporal properties. To investigate whether the periphery's sensitivity is partly due to the speed with which information is processed, we measured the full timecourse of visual information processing by deriving joint measures of discriminability and speed, and found that speed of information processing varies with eccentricity: processing was faster when same-size stimuli appeared at 9 degrees than 4 degrees eccentricity, and this difference was attenuated when the 9 degrees stimuli were magnified to equate cortical representation size. At the same eccentricity, larger stimuli are processed more slowly. These temporal differences are greater than expected from neurophysiological constraints.}, } @article {pmid12793519, year = {2003}, author = {Joseph, JA and Denisova, NA and Arendash, G and Gordon, M and Diamond, D and Shukitt-Hale, B and Morgan, D}, title = {Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model.}, journal = {Nutritional neuroscience}, volume = {6}, number = {3}, pages = {153-162}, doi = {10.1080/1028415031000111282}, pmid = {12793519}, issn = {1028-415X}, mesh = {Alzheimer Disease/*drug therapy/genetics/physiopathology ; Amyloid beta-Peptides/analysis ; Amyloid beta-Protein Precursor/genetics ; Animals ; *Behavior, Animal ; *Blueberry Plants ; Brain/enzymology ; *Diet ; Disease Models, Animal ; *Fruit ; GTP Phosphohydrolases/metabolism ; Genetic Predisposition to Disease ; Membrane Proteins/genetics ; Memory ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Mitogen-Activated Protein Kinases/metabolism ; Neurons/physiology ; Phytotherapy ; Plant Extracts/therapeutic use ; Presenilin-1 ; Protein Kinase C/metabolism ; Protein Kinase C-alpha ; *Signal Transduction ; Sphingomyelins/metabolism ; Type C Phospholipases/metabolism ; }, abstract = {Previously, we showed that blueberry (BB) supplementation reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BB-fed (from 4 months of age) APP + PS1 transgenic mice showed no deficits in Y-maze performance (at 12 months of age) with no alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced enhancement of memory-associated neuronal signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.}, } @article {pmid12751249, year = {2003}, author = {Bel'kova, NL and Parfenova, VV and Kostopnova, TIa and Denisova, LIa and Zaĭchikov, EF}, title = {[Microbial biodiversity in the Lake Baikal water].}, journal = {Mikrobiologiia}, volume = {72}, number = {2}, pages = {239-249}, pmid = {12751249}, issn = {0026-3656}, mesh = {Acetobacteraceae/genetics/isolation & purification ; Actinobacteria/genetics/isolation & purification ; Bacteria/cytology/genetics/*isolation & purification ; Cyanobacteria/genetics/isolation & purification ; Fresh Water/*microbiology ; Gene Silencing ; Gram-Negative Anaerobic Bacteria/genetics/isolation & purification ; Microscopy, Electron ; Phylogeny ; Proteobacteria/genetics/isolation & purification ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/genetics ; Russia ; }, abstract = {The investigation of the microbial community of Lake Baikal by the methods of general and molecular microbiology showed that culturable bacterial strains were represented by various known genera. The lake water contains a great number of bacterial morphotypes, as revealed by electron microscopy, and a great diversity of nonculturable microorganisms belonging to different phylogenetic groups, as revealed by 16S rRNA gene fragment sequencing. The inference is made that the microbial community of Lake Baikal contains not only the known species but also new, possibly endemic to the lake, bacterial species.}, } @article {pmid12722358, year = {2003}, author = {Denisova, DA and Pureskin, NP}, title = {[Loss of visual function as the result of gunshot injuries of the eye].}, journal = {Voenno-meditsinskii zhurnal}, volume = {324}, number = {2}, pages = {20-2, 78}, pmid = {12722358}, issn = {0026-9050}, mesh = {Eye Injuries/complications/etiology/surgery ; Military Medicine ; Military Personnel ; Retrospective Studies ; USSR ; Vision Disorders/*etiology ; Warfare ; Wounds, Gunshot/*complications ; }, abstract = {The article presents the clinical-and-statistical analysis of causes of visual function loss occurred after the gunshot injuries of eyes. The main cause of sight loss is the eye destruction as the result of gunshot injury (61.1%). Because of the unsuccessful treatment of posttraumatic changes in eyeball the injured eyes were removed in 38.9% of the casualties. In most cases the fragmentation and mine-explosive trauma were the cause of eye destruction. In the cases of eyeball destruction enucleation and evisceration were the main surgical interventions. In the therapy of posttraumatic changes in the injured eye (flaccid inflammatory process without tendency towards its resolution, painful syndrome as well as eyeball atrophy and subatrophy) enucleation was performed. Improvement of conservative methods in therapy of posttraumatic complications could contribute to decrease in the number of casualties with sight loss after the eye gunshot injures.}, } @article {pmid12717908, year = {2000}, author = {Portnoĭ, LM and Kazantseva, IA and Stashuk, GA and Gaganov, LE and Denisova, LB and Nefedova, VO and Legostaeva, TB and Iaurova, NV}, title = {[Current X-ray diagnosis of stomach cancer (comparison of radiologic and morphological methods of investigation)].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {6}, pages = {19-29}, pmid = {12717908}, issn = {0042-4676}, mesh = {Aged ; Female ; Gastroscopy ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Stomach/pathology ; Stomach Neoplasms/*diagnosis/diagnostic imaging/*pathology ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {By using the principles of wide comparisons of the data of radiation diagnosis (routine X-ray study, ultrasonography (USG), CT, MRI) with the morphological findings of resected gastric specimens from patients with endophytic gastric cancer (EGC) (n = 85), the authors propose some points in the problem associated with its diagnosis. They believe that by taking into account the fact that there is an obvious growth of endophytic parietally growing gastric cancer with the concurrent reduction in its intestinal forms, it is necessary to restore current radiation to its leading place, along with endoscopy, in detecting the cancer. The authors makes a highly positive assessment of USG, CT, MRI in addition to routine X-ray study and endoscopy particularly in those cases when difficulties emerge in histological verification of the existing signs of parietally growing cancer. The paper makes indications for USG, CT, MRI concrete. The authors also show how to stage gastric cancer.}, } @article {pmid12717891, year = {1999}, author = {Denisova, LB and Vorontsova, SV and Shvedov, VA}, title = {[On the diagnosis of congenital toxoplasmosis].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {1}, pages = {45-47}, pmid = {12717891}, issn = {0042-4676}, mesh = {Female ; Humans ; Middle Aged ; Toxoplasmosis, Congenital/*diagnosis ; }, } @article {pmid12622038, year = {2002}, author = {Chekunova, EV and Denisova, LB and Bazaev, VV}, title = {[Algorithms of diagnostic radiation methods in current urological pathology].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {46-49}, pmid = {12622038}, issn = {0042-4676}, mesh = {*Algorithms ; Angiography/methods ; Humans ; Radioisotope Renography/methods ; Ultrasonography ; Urography/methods ; Urologic Diseases/*diagnosis/diagnostic imaging ; }, abstract = {Based on the results of 3600 studies using all basic methods of modern radiation diagnosis, the authors show it necessary to develop diagnostic algorithms applicable to certain groups of urological diseases (urolithiasis, inflammatory processes and bulky masses in the kidney). This necessity has recently stemmed from the advent of new technologies of radiation diagnosis and from the expediency of using a certain method at the specific stage of examination. At the same time, the authors underline the importance of using standardized examination programmes (algorithms) in practice, which is also due to the fact that unreasonable use of the whole set of new radiation techniques that are of highly diagnostic value may bear great material costs.}, } @article {pmid12596516, year = {2002}, author = {Bol'shakov, VV and Sapozhkov, AV and Denisova, SV}, title = {[Effect of droperidol and tramadol combination on the hemostasis in rabbits].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {65}, number = {5}, pages = {50-52}, pmid = {12596516}, issn = {0869-2092}, mesh = {Analgesics, Opioid/administration & dosage/*adverse effects ; Animals ; Antipsychotic Agents/administration & dosage/*adverse effects ; Dose-Response Relationship, Drug ; Droperidol/administration & dosage/*adverse effects ; Drug Combinations ; Female ; Hemostasis/*drug effects ; Male ; Rabbits ; Tramadol/administration & dosage/*adverse effects ; }, abstract = {The effect of a combined administration of analgesic droperidol and neuroleptic tramadol (tramal) on the plasma coagulation and platelet aggregation was studied on awake rabbits. Both tramadol and droperidol, as well as their combination, enhance the coagulation of plasma proteins and suppress the thrombocyte deaggregation process.}, } @article {pmid12500679, year = {2002}, author = {Maliarchuk, BA and Derenko, MV and Grzybowski, T and Czarny, J and Miscicka-Slivka, D and Denisova, GA and Kostiunina, EA}, title = {[Mitochondrial DNA variation in Russian populations of Stavropol krai, Orel and Saratov oblasts].}, journal = {Genetika}, volume = {38}, number = {11}, pages = {1532-1538}, pmid = {12500679}, issn = {0016-6758}, mesh = {*DNA, Mitochondrial ; Dagestan/ethnology ; *Genetic Variation ; *Genetics, Population ; Haplotypes/genetics ; Humans ; Russia/ethnology ; }, abstract = {Mitochondrial DNA (mtDNA) polymorphism was examined in three Russian populations from the European part of Russia (Stavropol krai, Orel oblast, and Saratov oblast). This analysis showed that mitochondrial gene pool of Russians was represented by the mtDNA types belonging to haplogroups H, V, HV*, J, T, U, K, I, W, and X. A mongoloid admixture (1.5%) was revealed in the form of mtDNA types of macrohaplogroup M. Comparative analysis of the mtDNA haplogroup frequency distribution patterns in six Russian populations from the European part of Russia indicated the absence of substantial genetic differences between them. However, in Russian populations from the southern and central regions the frequency of haplogroup V (average frequency 8%) was higher than in the populations from more northern regions. Based on the data on mtDNA HVS1 sequence variation, it was shown that the diversity of haplogroup V in Russians (h = 0.72) corresponded to the highest h values observed in Europe. The reasons for genetic differentiation of the Russian population (historical, ecological, and adaptive) are discussed.}, } @article {pmid12499999, year = {2003}, author = {Reshetnikov, OV and Denisova, DV and Zavyalova, LG and Häivä, VM and Granberg, C}, title = {Helicobacter pylori seropositivity among adolescents in Novosibirsk, Russia: prevalence and associated factors.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {36}, number = {1}, pages = {72-76}, doi = {10.1097/00005176-200301000-00014}, pmid = {12499999}, issn = {0277-2116}, mesh = {Adolescent ; Age Distribution ; Enzyme-Linked Immunosorbent Assay ; Female ; Helicobacter Infections/*blood/*epidemiology/immunology ; Helicobacter pylori/*immunology ; Humans ; Life Style ; Male ; Odds Ratio ; Risk Factors ; Russia/epidemiology ; Seroepidemiologic Studies ; Sex Distribution ; Socioeconomic Factors ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: We have reported previously that infection is widespread among adults in Siberia, in whom prevalence rates range from 70% to 90%. The present study was undertaken to determine the seroprevalence of infection and its relation to social factors in a community-based population of adolescents in Novosibirsk, Western Siberia.

METHODS: All students in forms 9 to 11 of four randomly selected secondary schools participated. A total of 423 students (180 boys, 243 girls; age, 14-17 years) completed structured questionnaire concerning their lifestyle, and sera were tested for using enzyme-linked immunosorbent assay (Pyloriset -New EIA-G; Orion Diagnostica, Finland). Personal information, including parental history, educational level, occupation, and smoking habits, were collected via a questionnaire.

RESULTS: Overall, the seroprevalence of infection was 56.3%. Age, sex, smoking, alcohol consumption, number of children and pets in the household, and family history of gastric diseases were not associated with positivity. The predictors of infection were dwelling without running hot water supply and sewage (odds ratio [OR] = 2.4; 95% confidence interval [CI], 1.2-4.8), father's occupation as a manual worker (OR = 2.7; 95% CI, 1.5-5.0), mother's occupation as a manual worker (OR = 1.8; 95% CI, 1.0-3.0), father's lower educational attainment (OR = 2.1; 95% CI, 1.2-3.6), and father's smoking (OR = 1.8; 95% CI, 1.1-3.2).

CONCLUSIONS: The prevalence of seropositivity among adolescents in Russia is higher than in developed countries. The infection is associated with lower socioeconomic status.}, } @article {pmid12476838, year = {2002}, author = {Tsinberg, MB and Deriabin, DG and Denisova, IV}, title = {[Hygienic characterization of lactic acid bacteria products prepared by using hydrolysates of raw milk and soya bean materials].}, journal = {Gigiena i sanitariia}, volume = {}, number = {5}, pages = {54-56}, pmid = {12476838}, issn = {0016-9900}, mesh = {Animals ; Bacteria ; Cheese/*microbiology ; *Food Industry ; Humans ; Lactic Acid/*metabolism ; Milk/*metabolism/*microbiology ; Plant Lectins/*metabolism ; Protein Hydrolysates/*metabolism ; Soybean Proteins/*metabolism ; }, abstract = {The paper reflects the results of a comparative study of preparations of lactic acid bacteria (LAB), which are based on the hydrolysates of raw milk and soya bean materials, by using methods to determine the organoleptic and physicochemical properties, microbiological characteristics including the titer of microbial cells per ml of the preparation and the presence/absence of representatives of sanitary significant groups of microorganisms, the persistent properties of microorganisms. By summarizing the findings, it can be stated that it is possible to use a raw soya-bean hydrolysate-based nutrient medium to cultivate technical LAB strains with the compliance of the toxicological and microbiological parameters of the prepared preparations with the current sanitary standards. The LAB preparations grown on the hydrolysate-soya-bean medium have been protected with the patents of Russia. Their biological properties are highly competitive with those and, in some cases, superior to hydrolysate-milk medium-based preparations. This presents in their adhesive potential and in the formation of more pronounced antagonistic properties against opportunistic microorganisms.}, } @article {pmid12452775, year = {2002}, author = {Denisova, NA and Shukitt-Hale, B and Rabin, BM and Joseph, JA}, title = {Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation.}, journal = {Radiation research}, volume = {158}, number = {6}, pages = {725-734}, doi = {10.1667/0033-7587(2002)158[0725:bsabri]2.0.co;2}, pmid = {12452775}, issn = {0033-7587}, mesh = {Animals ; Behavior/*radiation effects ; Blotting, Western ; Body Weight/radiation effects ; Brain/*metabolism/pathology/*radiation effects ; Dopamine/metabolism ; Dose-Response Relationship, Radiation ; *Iron ; Male ; Maze Learning ; Memory/radiation effects ; Oxidative Stress ; Radiometry ; Rats ; Rats, Sprague-Dawley ; *Signal Transduction ; Synapses/metabolism ; Time Factors ; }, abstract = {Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.}, } @article {pmid12449652, year = {2002}, author = {Derenko, MV and Maliarchuk, BA and Denisova, GA and Dambueva, IK and Kakpakov, VT and Dorzhu, ChM and Luzina, FA and Lotosh, EA and Ondar, UN and Kaplina, MI and Zakharov, IA}, title = {[Molecular genetic differentiation of ethnic populations in Southern and Eastern Siberia based on mitochondrial DNA polymorphism].}, journal = {Genetika}, volume = {38}, number = {10}, pages = {1409-1416}, pmid = {12449652}, issn = {0016-6758}, mesh = {Asian People/genetics ; *DNA, Mitochondrial ; Genetic Variation ; *Genetics, Population ; Humans ; Phylogeny ; *Polymorphism, Genetic ; Siberia/ethnology ; White People/genetics ; }, abstract = {Using the data on mitochondrial DNA (mtDNA) polymorphism, genetic structures of the ethnic groups inhabiting South and East Siberia, including Altaians, Buryats, Tuvinians, Todjins, Tofalars, Yakuts, and Evenks were described. Mitochondrial gene pools of the populations examined were characterized by different ratios between Mongoloid (M*, C, D, E/G, G, A, B, and F) and Caucasoid (H, HV, I, J, K, T, U, and X) mtDNA lineages. All the populations studied carried a marked Mongoloid component, maximum frequency of which was observed in Evenks (92.4%) and Buryats (90.1%). Maximum frequencies of Caucasoid mtDNA lineages were detected in Tofalars (20.7%) and Yakuts (14.5%). Statistically significant interpopulation differences regarding the frequencies of mtDNA haplogroups were observed between all populations examined, excluding the pairs of Evenks-Yakuts, Evenks-Tuvinians, and Tuvinians-Todjins. Differentiation of the ethnic groups inhabiting South and East Siberia, as well as Central and Middle Asia, is discussed based on genetic, linguistic, and anthropological data.}, } @article {pmid12205156, year = {2002}, author = {Belousov, AB and Hunt, ND and Raju, RP and Denisova, JV}, title = {Calcium-dependent regulation of cholinergic cell phenotype in the hypothalamus in vitro.}, journal = {Journal of neurophysiology}, volume = {88}, number = {3}, pages = {1352-1362}, doi = {10.1152/jn.2002.88.3.1352}, pmid = {12205156}, issn = {0022-3077}, mesh = {Acetylcholine/*physiology ; Animals ; Bromodeoxyuridine ; Calcium/*physiology ; Cells, Cultured ; Hypothalamus/cytology/*physiology ; Neurons/*physiology ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission/physiology ; }, abstract = {Glutamate is a major fast excitatory neurotransmitter in the CNS including the hypothalamus. Our previous experiments in hypothalamic neuronal cultures showed that a long-term decrease in glutamate excitation upregulates ACh excitatory transmission. Data suggested that in the absence of glutamate activity in the hypothalamus in vitro, ACh becomes the major excitatory neurotransmitter and supports the excitation/inhibition balance. Here, using neuronal cultures, fura-2 Ca(2+) digital imaging, and immunocytochemistry, we studied the mechanisms of regulation of cholinergic properties in hypothalamic neurons. No ACh-dependent activity and a low number (0.5%) of cholinergic neurons were detected in control hypothalamic cultures. A chronic (2 wk) inactivation of N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors, L-type voltage-gated Ca(2+) channels, calmodulin, Ca(2+)/calmodulin-dependent protein kinases II/IV (CaMK II/IV), or protein kinase C (PKC) increased the number of cholinergic neurons (to 15-24%) and induced ACh activity (in 40-60% of cells). Additionally, ACh activity and an increased number of cholinergic neurons were detected in hypothalamic cultures 2 wk after a short-term (30 min) pretreatment with bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid tetrakis(acetoxy-methyl) ester (BAPTA AM; 2.5 microM), a membrane permeable Ca(2+)-chelating agent that blocks cytoplasmic Ca(2+) fluctuations. An increase in the number of cholinergic neurons following a chronic NMDA receptor blockade was likely due to the induction of cholinergic phenotypic properties in postmitotic noncholinergic neurons, as determined using 5-bromo-2'-deoxyuridine (BrdU) labeling. In contrast, a chronic inactivation of non-NMDA glutamate receptors or cGMP-dependent protein kinase had little effect on the expression of ACh properties. The data suggest that Ca(2+), at normal intracellular concentrations, tonically suppresses the development of cholinergic properties in hypothalamic neurons. However, a decrease in Ca(2+) influx into cells (through NMDA receptors or L-type Ca(2+) channels), inactivation of intracellular Ca(2+) fluctuations, or downregulation of Ca(2+)-dependent signal transduction pathways (CaMK II/IV and PKC) remove the tonic inhibition and trigger the development of cholinergic phenotype in some hypothalamic neurons. An increase in excitatory ACh transmission may represent a novel form of neuronal plasticity that regulates the activity and excitability of neurons during a decrease in glutamate excitation. This type of plasticity has apparent region-specific character and is not expressed in the cortex in vitro; neither increase in ACh activity nor change in the number of cholinergic neurons were detected in cortical cultures under all experimental conditions.}, } @article {pmid12018172, year = {2002}, author = {Maliarchuk, BA and Derenko, MV and Denisova, GA and Nassiri, MR and Rogaev, EI}, title = {[Mitochondrial DNA polymorphism in populations of the Caspian region and southeastern Europe].}, journal = {Genetika}, volume = {38}, number = {4}, pages = {534-538}, pmid = {12018172}, issn = {0016-6758}, mesh = {Asian People ; *DNA, Mitochondrial ; *Genetics, Population ; Humans ; Iran ; *Polymorphism, Genetic ; Russia/ethnology ; Turkmenistan ; Ukraine ; }, abstract = {Mitochondrial DNA (mtDNA) restriction polymorphism was examined in Turkmens, Eastern Iranians, and Ukrainians. The gene pools of all populations studied were characterized by the presence of European mtDNA lineages. Mongoloid component observed in Turkmen and Iranian populations with the frequencies of about 20% was represented by groups C, D, and E/G in Turkmens, and by M*, D, A, and B in Iranians. The relative positions of the populations studied, of populations from the Caucasus, Western Iran, and Russian populations from the Krasnodar krai and Belgorod oblast in the space of principal components revealed a geographically specific pattern of the population clustering. The data on mtDNA polymorphism indicated pronounced differentiation of Eastern and Western Iranians. The latter were characterized by a mtDNA group composition similar to that in Eastern Slavs. The historical role of the Caspian populations in the formation of the population of Southeastern Europe is discussed.}, } @article {pmid11963568, year = {2002}, author = {Derenko, MV and Maliarchuk, BA and Denisova, GA and Dorzhu, ChM and Karamchakova, ON and Luzina, FA and Lotosh, EA and Dambueva, IK and Ondar, UN and Zakharov, IA}, title = {[Polymorphism of the Y-chromosome diallelic loci in the ethnic populations of the Altai-Sayan region].}, journal = {Genetika}, volume = {38}, number = {3}, pages = {393-399}, pmid = {11963568}, issn = {0016-6758}, mesh = {Alleles ; *Genetics, Population ; Haplotypes/genetics ; Humans ; Male ; *Polymorphism, Genetic ; Siberia/ethnology ; *Y Chromosome ; }, abstract = {Using the data on five biallellic Y-chromosome loci (DYS199, 92R7, SRY1532, RBF5 and DYS287) polymorphism, genetic structures of the five Turkic-speaking ethnic groups of the Altai-Sayan highland (Tuvinians, Sojots, Shorians, Khakassians, and Southern Altaians (Altai-Kizhi), were described. The gene pools of the populations examined were characterized by the presence of pronounced paleo-Caucasoid component (92R7-T-lineages). The frequency of this component increased westward, reaching more than 70% in Shorians and Southern Altaians. Haplotype TAT-C (RBF5 locus) was observed in all populations, except Shorians, with the frequencies varying from 5.4% in Altai-Kizhi to 18.8% in Khakassians. The Alu-insertion in the DYS287 locus was revealed only in the Altaian sample with the frequency of 3.3%. It was established that the Altai-Sayan populations studied split into two statistically significantly different groups. One of the groups was represented by Tuvinians, Sojots, and Khakassians, while another one was comprised of Shorians and Altaians.}, } @article {pmid11958956, year = {2002}, author = {Hassan, WN and Cantuti-Castelevetri, I and Denisova, NA and Yee, AS and Joseph, JA and Paulson, KE}, title = {The nitrone spin trap PBN alters the cellular response to H(2)O(2): activation of the EGF receptor/ERK pathway.}, journal = {Free radical biology & medicine}, volume = {32}, number = {6}, pages = {551-561}, doi = {10.1016/s0891-5849(02)00744-x}, pmid = {11958956}, issn = {0891-5849}, support = {R01 DK 50442/DK/NIDDK NIH HHS/United States ; R01 GM 44634/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adaptor Proteins, Signal Transducing ; *Adaptor Proteins, Vesicular Transport ; Animals ; Calcium/metabolism ; Cyclic N-Oxides ; Drug Interactions ; Enzyme Activation ; ErbB Receptors/*metabolism ; Free Radical Scavengers/*pharmacology ; Hydrogen Peroxide/*pharmacology ; Mitogen-Activated Protein Kinases/*metabolism ; Nitrogen Oxides/*pharmacology ; PC12 Cells ; Phosphorylation/drug effects ; Proteins/metabolism ; Rats ; Shc Signaling Adaptor Proteins ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; }, abstract = {The nitrone spin trap PBN has been shown to protect neuronal cells from reactive oxygen species both in culture and in vivo. As an approach to understanding the molecular mechanisms by which PBN may function to protect cells, we examined whether PBN alters the cellular response to reactive oxygen species. H(2)O(2) stimulation of PC-12 cells results in weak activation of both the ERK and JNK signal transduction pathways. PBN pretreatment of PC-12 cells, followed by H(2)O(2) stimulation, results in strong and selective activation of the pro-survival ERK pathway. H(2)O(2) induction of ERK activity in PBN-pretreated cells was shown to be dependent on extracellular Ca(+2) influx. Further analysis of the ERK pathway showed that in PBN-pretreated cells, EGF receptor and the adapter protein SHC were phosphorylated in a Ca(+2)-dependent, ligand-independent manner following H(2)O(2) stimulation. Interestingly, H(2)O(2) stimulation of PBN-pretreated cells results in only 30% of the increase in intracellular Ca(+2) as compared to untreated cells following H(2)O(2) stimulation. These data suggest a model in which PBN attenuates H(2)O(2)-induced Ca(+2) entry, yet magnifies or alters Ca(+2) action, resulting in the activation of the EGF receptor/ERK pathway.}, } @article {pmid11949255, year = {2002}, author = {Karal'nik, BV and Denisova, TG and Grushina, TA and Tugambaev, TI}, title = {[Analysis of immune response of guinea pigs infected with Brucella melitensis].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {1}, pages = {52-56}, pmid = {11949255}, issn = {0372-9311}, mesh = {Animals ; Antigen Presentation ; *Brucella melitensis ; Brucellosis/*immunology ; Guinea Pigs ; *Immunity, Cellular ; T-Lymphocytes, Cytotoxic/*immunology ; }, abstract = {The dynamics of the first antigen specific stage of immune response to Brucella infection was experimentally studied with the method of binding adsorbed antigenic immunoreagents with lymphocytes. The study revealed that the content of antigen-binding lymphocytes (ABL) reached its maximum as early as on day 7 after infection, gradually decreasing afterwards (but even on day 90 ABL could be detected in the blood). The specificity of ABL was proved by the fact that they were absent in noninfected animals, while in the animals infected with Brucella their content was higher than that of ABL specific to Yersinia enterocolitica O9; Brucella-specific ABL bound Brucella lipopolysaccharide (LPS) more intensively than Yersinia LPS. The detection of Brucella-specific ABL was inhibited by Brucella LPS more actively than by Yersinia LPS. The evaluation of the affinity of ABL to homologous LPS, made by the ratio of binding immunoreagents of the same specificity, but with suboptimal and optimal specificity, proved that an increase in the avidity of ABL occurred in the dynamics of the infectious process, which corresponded to the increase of their specificity.}, } @article {pmid11899837, year = {2002}, author = {Reshetnikov, OV and Kurilovich, SA and Tereshonok, IN and Denisova, DV and Zav'ialova, LG and Krivenchuk, NA and Zimina, IIu and Granberg, C and Häivä, VM}, title = {[Dyspepsia and gastroesophageal reflux in adolescents].}, journal = {Terapevticheskii arkhiv}, volume = {74}, number = {2}, pages = {9-13}, pmid = {11899837}, issn = {0040-3660}, mesh = {Adolescent ; Dyspepsia/complications/*epidemiology/microbiology ; Female ; Gastroesophageal Reflux/complications/*epidemiology ; Helicobacter pylori ; Humans ; Male ; }, abstract = {AIM: To study the prevalence and risk factors for dyspepsia and gastroesophageal reflux (GER) among adolescents.

MATERIAL AND METHODS: Senior schoolchildren (forms 9-11) of four randomly selected secondary schools of Novosibirsk participated in the study (189 boys and 260 girls aged 14-17 years). They filled in the Bowel Disease Questionnaire, and sera were tested for antibodies against Helicobacter pylori infection.

RESULTS: Dyspepsia was reported by 21% of the schoolchildren, being more frequent in girls (25%) than boys (14%, p = 0.004). GER occurred in 22% of adolescents with the same frequency in both genders. The combination of dyspepsia with GER was found in 8%. The prevalence of H. pylori infection was 56%. No association was found between the infection and abdominal symptoms, except heartburn. Among factors associated with dyspepsia were female gender, irregular meals, family history of dyspepsia. GER was related to H. pylori infection, obesity, smoking and irregular meals, 46% of adolescents with dyspepsia and 36% of those with GER have consulted a physician, and school absenteeism was reported by 55 and 40%, respectively.

CONCLUSION: Dyspepsia and gastroesophageal reflux are widespread among the adolescent population and result in frequent use of health care resources.}, } @article {pmid11889863, year = {2002}, author = {Denisova, LA and Nasyrova, NV and Maev, RG and Grigor'ian, AS and Grigor'iants, LA and Denisov, AA and Grineva, TV and Maeva, EIu and Severin, FM}, title = {[Acoustic microscopy methods in studies of the filling materials microstructure].}, journal = {Stomatologiia}, volume = {81}, number = {1}, pages = {26-30}, pmid = {11889863}, issn = {0039-1735}, mesh = {Acoustics ; Dental Cements/*analysis ; Humans ; Microscopy, Electron, Scanning/instrumentation/*methods ; }, abstract = {The structure of filling materials (kemfil, polyacrylate cement, and Dentis, material produced by Stomadent Firm in Russia) at the interface with human dentin was studied in teeth subjected to retrograde filling with preliminary appendectomy. A prototype of table wide-field short pulse scanning acoustic microscope (50 mHz) (Acoustic Microscopy Center, Institute of Biochemical Physics of Russian Academy of Sciences) and Elsam acoustic microscope (200 mHz) (Leitz, Germany) were used. The results indicate that analysis of acoustic characteristics, including the data of acoustic microscopy, helps investigate the cement microstructure and evaluate the compactness and elasticity of samples; moreover, structural elements of the material, which are undetectable by other methods, are seen on acoustic images. These data can be used for evaluating the relationship between the microstructure and formation of mechanical properties, and, maybe, the patterns of cement interactions with dental tissues.}, } @article {pmid11879960, year = {2002}, author = {Maev, RG and Denisova, LA and Maeva, EY and Denissov, AA}, title = {New data on histology and physico-mechanical properties of human tooth tissue obtained with acoustic microscopy.}, journal = {Ultrasound in medicine & biology}, volume = {28}, number = {1}, pages = {131-136}, doi = {10.1016/s0301-5629(01)00480-x}, pmid = {11879960}, issn = {0301-5629}, mesh = {*Acoustics ; Humans ; Tooth/*anatomy & histology/*diagnostic imaging ; *Ultrasonography ; }, abstract = {Quantitative evaluation of human tooth structural elements, revealed in acoustic images, has been carried out. It has been shown that tissue elements with different acoustic impedances differed in acoustic images by intensity of grey color, and also feature with different longitudinal sound velocities (C(L)). In the layer of mantle dentin, C(L) is 7% to 8% lower than in bulk dentin, and in the layer of dentin around the pulp chamber, C(L) is 15% lower. In carious enamel and dentin, C(L) decreases up to 7% to 17%. In pathologic teeth, dentin areas with higher density can be revealed; they feature higher C(L); in transparent dentin C(L) can be 15% to 20% higher than in bulk dentin. Results of the present study show that acoustic images reflect internal biomechanical properties of tooth tissue microstructure that can be evaluated quantitatively by means of longitudinal sound velocity determination.}, } @article {pmid11767501, year = {2001}, author = {Denisova, L and Vorontsova, S and Safiullina, I and Emel'ianova, L}, title = {[X-ray diagnosis of the adrenal neoplasms].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {5}, pages = {41-48}, pmid = {11767501}, issn = {0042-4676}, mesh = {Adrenal Gland Diseases/*diagnosis/surgery ; Adrenal Gland Neoplasms/*diagnosis/diagnostic imaging/surgery ; Adult ; Cysts/*diagnosis/surgery ; Female ; Ganglioneuroma/*diagnosis/diagnostic imaging/surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Myelolipoma/*diagnosis/diagnostic imaging/surgery ; Tomography, X-Ray Computed ; Ultrasonography ; }, } @article {pmid11761619, year = {2001}, author = {Maliarchuk, BA and Denisova, GA and Derenko, MV and Rogaev, EI and Vlasenko, LV and Zhukova, SG}, title = {[Variability in mitochondrial DNA in Russian inhabitants from Krasnodar Krai, Belgorod and the lower Novgorod region].}, journal = {Genetika}, volume = {37}, number = {10}, pages = {1411-1416}, pmid = {11761619}, issn = {0016-6758}, mesh = {Asian People/genetics ; DNA, Mitochondrial/*genetics ; *Genetics, Population ; Humans ; Russia ; White People/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) polymorphism was examined in three Russian populations from the European part of Russia (Krasnodar Krai, Belgorod, and Nizhnii Novgorod oblast). This analysis revealed that mitochondrial gene pool of Russians was represented by the mtDNA types belonging to groups H, V, pre-V, HV*, J, T, U, K, I, W, and X. The major groups (average frequency over 5%) were H, V, J, T, and U. Mongoloid admixture in Russians, constituting only 1%, was revealed in the form of mtDNA types of groups C and D. Analysis of the frequency distribution of the mtDNA type groups indicated the absence of genetic differences between the Russian populations studied.}, } @article {pmid11761618, year = {2001}, author = {Derenko, MV and Denisova, GA and Maliarchuk, BA and Dambueva, IK and Luzina, FA and Lotosh, EA and Dorzhu, ChM and Karamchakova, ON and Solovenchuk, LL and Zakharov, IA}, title = {[Structure of the gene pool of ethnic groups from the Altai-Sayan region from data on mitochondrial polymorphism].}, journal = {Genetika}, volume = {37}, number = {10}, pages = {1402-1410}, pmid = {11761618}, issn = {0016-6758}, mesh = {DNA, Mitochondrial/*genetics ; *Ethnicity ; *Gene Pool ; Phylogeny ; *Polymorphism, Genetic ; Siberia ; }, abstract = {Using the data on mitochondrial DNA (mtDNA) polymorphism, genetic structures of the four Turkic-speaking ethnic groups of Altai-Sayan highlands, Southern Altaians (Altai-Kizhi), Khakassians, Shorians, and Sojots, were described. Mitochondrial gene pools of the populations examined were characterized by different ratios between Mongoloid (M*, C, D, E, G, A, B, and F) and Caucasoid (H, U, T, J, and K) mtDNA lineages. All the populations studied had a strongly pronounced Mongoloid component, the frequency of which was 88.2% in Sojots, 75.9% in Khakassians, 67.4% in Altaians, and 64.3% in Shorians. Maximum frequency of the Caucasoid component (35.7%) was observed in Shorians. Phylogenetic and statistical analyses of the mtDNA group frequency distribution patterns in the gene pools of the ethnic populations of Altai-Sayan highlands and the adjacent territories showed that the populations of the region fell into three groups. The first group included Khakassians, Tuvinians and Altaians, the second group consisted of Sojots, Buryats, and Mongols, while the third group was composed of Uigurs, Kazakhs, and Kyrgyzes. The isolated position of Shorians among the populations examined can be explained by their different anthropological composition and their presumptive relatedness to Finno-Ugric populations of Siberia.}, } @article {pmid11603326, year = {2001}, author = {Denisova, L and Vorontsova, S and Safiullina, I and Emel'ianova, L}, title = {[Role of magnetic resonance imaging in the complex radiation diagnosis of hormonally active adrenal tumors].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {4}, pages = {25-34}, pmid = {11603326}, issn = {0042-4676}, mesh = {Adenocarcinoma/*diagnosis ; Adenoma/*diagnosis ; Adrenal Gland Neoplasms/*diagnosis ; Adult ; Aged ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; }, abstract = {Based on the results of examination of 30 patients with hormonally active adrenal tumors, the authors consider the MRI sympatomatology of their different types and the potentialities of the technique in the complex radiation diagnosis of this pathology. The authors present their assessments of the relative intensity of a signal and the structure of each type of hormone-producing tumors of the glands by using different MRI pulse sequences that may be useful in establishing a presumptive morphological diagnosis. They identify MRI sequences that are of the greatest informative value for the diagnosis of each type of hormonally active adrenal tumors. There is evidence for that MRI is highly effective in detecting all types of hormonally active adrenal tumors and, in the context of their topographic and anatomic diagnosis, has an unquestionable advantage over ultrasonography and X-ray computed tomography in some cases.}, } @article {pmid11603325, year = {2001}, author = {Portnoi, L and Denisova, L and Utkina, E and Denisov, V and Safiullina, I and Emel'ianova, L}, title = {[Magnetic resonance cholangiopancreatography and a problem in diagnosis of hepatopancreatoduodenal diseases].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {4}, pages = {14-24}, pmid = {11603325}, issn = {0042-4676}, mesh = {Adult ; Aged ; Cholangiopancreatography, Endoscopic Retrograde ; Cholestasis/diagnosis ; Digestive System/anatomy & histology/diagnostic imaging ; Digestive System Diseases/*diagnosis/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; }, abstract = {Based on the findings of 54 magnetic resonance studies, the authors used 19 of them authors to study the types of normalcy. A role of the new noninvasive technique magnetic resonance cholangiopancreatography (MRCPG) in the diagnosis of hepatopancreatoduodenal diseases is assessed. The potentialities of MRCPG in the detection of most common diseases and malformations of the biliary system are demonstrated. Comparative studies of MRCPG and endoscopic retrograde cholangiopancreatography (ERCPG) were conducted in 18 cases. The paper shows a methodological approach to MRCPG and analyzes the studies by describing the MR semiotics of major diseases. Emphasis is laid on how it is important to combine routine MRI and MRCPG in certain diagnostic situations. The authors consider that MRCPG is able to replace X-ray endoscopic studies and primarily ERCPG in diagnostic terms, by reserving their therapeutical functions for itself. MRCPG has great potentialities that, require further investigations and analysis.}, } @article {pmid11588961, year = {2001}, author = {Gnusareva, NA and Duĭsenova, RB and Karal'nik, BV and Omarov, TO and Denisova, TG}, title = {[Detection of antigen-binding lymphocytes in the diagnosis of tuberculosis].}, journal = {Problemy tuberkuleza}, volume = {}, number = {5}, pages = {41-42}, pmid = {11588961}, issn = {0032-9533}, mesh = {*Cell Migration Inhibition ; Diagnosis, Differential ; Fluoroscopy ; Humans ; Indicators and Reagents ; Lymphocytes/*immunology ; Mycobacterium tuberculosis/isolation & purification ; Pneumonia/diagnosis/immunology ; Rosette Formation ; Sensitivity and Specificity ; Time Factors ; Tuberculin/*immunology ; Tuberculosis/*diagnosis/diagnostic imaging/immunology ; Tuberculosis, Pulmonary/*diagnosis/diagnostic imaging/immunology ; }, abstract = {The efficiency of diagnosis of active tuberculosis was evaluated from detection of tuberculin-receptor lymphocytes [antigen-binding lymphocytes (ABL)] by the indirect rossette-formation test with the red blood cell reagent designed. Sixty two patients with tuberculosis (of them 10 patients with extrapulmonary tuberculosis), 10 with lobular pneumonia, and 27 healthy individuals cal were examined. Positive results of fluography, smear microscopy, bacteriological study, leukocytic migration inhibition test, and test for ABL were obtained in 84, 40, 50, 39, and 100%, respectively. The controls had negative tests. Thus, ABL detection was the method of choice in tuberculosis diagnosis.}, } @article {pmid11507978, year = {2001}, author = {Reshetnikov, OV and Kurilovich, SA and Denisova, DV and Zavyalova, LG and Tereshonok, IN}, title = {Prevalence of dyspepsia and irritable bowel syndrome among adolescents of Novosibirsk, western Siberia.}, journal = {International journal of circumpolar health}, volume = {60}, number = {2}, pages = {253-257}, pmid = {11507978}, issn = {1239-9736}, mesh = {Adolescent ; Colonic Diseases, Functional/*epidemiology ; Dyspepsia/*epidemiology ; Female ; Humans ; Male ; Prevalence ; Siberia/epidemiology ; Surveys and Questionnaires ; }, abstract = {The study was undertaken to determine the prevalence of gastrointestinal symptoms in a community-based population of adolescents. All students in grades 9-11 of four randomly chosen schools in one of the typical districts of Novosibirsk were invited to participate. A total of 449 students participated (189 boys, 260 girls aged 14-17), all of them completed the Russian version of the Bowel Disease Questionnaire. Dyspepsia was reported more frequently by girls than boys (27% vs 16%). The prevalence of irritable bowel syndrome defined according to the Rome criteria was 24% in girls and 14% in boys. Among students with dyspepsia, 49% had sought medical advice, and 37% had undergone upper gastrointestinal endoscopy or X-ray series, for IBS the corresponding figures were 49% and 24%. School absenteeism was reported by 57% of dyspepsia sufferers, and by 62% of subjects with IBS. In conclusion, dyspepsia and IBS are common among adolescents of Novosibirsk with prevalence rates similar to those described in adults in Western Europe and the USA. These disorders are associated with significant disability and health care costs.}, } @article {pmid11477614, year = {2001}, author = {Marga, M and Denisova, A and Sochnev, A and Pirags, V and Farid, NR}, title = {Two HLA DRB 1 alleles confer independent genetic susceptibility to Graves disease: relevance of cross-population studies.}, journal = {American journal of medical genetics}, volume = {102}, number = {2}, pages = {188-191}, doi = {10.1002/ajmg.1431}, pmid = {11477614}, issn = {0148-7299}, mesh = {Adolescent ; Adult ; Aged ; *Alleles ; DNA/genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/*genetics ; Graves Disease/*genetics/pathology ; HLA-DR Antigens/*genetics ; HLA-DRB1 Chains ; Humans ; Male ; Middle Aged ; Odds Ratio ; }, abstract = {Recent studies of Graves disease (GD) employing genome scanning techniques excluded the major histocompatibility complex as a contributor to disease liability. These findings contradict earlier population association studies. Our own earlier studies have also emphasized that genetic variation in human populations may give novel clues to disease liability and manifestations. To this end, we studied HLA class II alleles in 47 Latvian GD patients and 111 matched healthy controls. As expected, we found that DRB1*03 and DQA1*0501 (OR = 3.6, P = 0.029 and OR 2.35, P = 0.0373, respectively) were associated with GD. Unforeseen, DRB1*04 was found to be significantly increased in the patients compared to controls (OR 3.267, corrected P = 0.0319). The two DRB1 alleles conferred two non-overlapping and independent susceptibilities to GD, in that only three patients were positive for both alleles, and the removal of each allele in turn resulted in only the other DRB1 allele showing significant association with the disease. There was no heterogeneity between the two patient groups (DRB1*03 positive and DRB1*04 positive) in clinical characteristics or disease manifestations. The phenotype DRB1*03 and/or DRB1*04 was found in 34/47 patients compared to 27/111 controls yielding an OR of 7.395 (P corrected = 0.000019). We examined the structural basis of DRB1 susceptibility to GD in light of this and previous studies, showing that DRB1*03, 04, and 08 were positively associated with the disease, whereas DRB1*07 was negatively associated. Differences in protein sequences were noted at residues 54, 57, 59, and 66; positions 54, 57, and 66 are on the same face of the alpha helix. The canonical arginine 54 is replaced by glutamine in DRB1*07. At position 66, asparagine in DRB1*03 and tyrosine in DRB1*04 are replaced by phenylalanine in DRB1*07. Residue 59, likely involved in pocket formation in the antigen binding groove, is modified by replacement of tyrosine in DRB1*03, 08, and 04 and by leucine in DRB1*07. The predicted differences in the shape and charges of the proximal reaches of the antigen binding groove between DRB1*07, and 03, 04, and 08, could determine whether or not a peptide from an auto-antigen would be bound or not. Genetic variation among human populations may yield important clues to specific disease liability.}, } @article {pmid11459075, year = {2001}, author = {Sofic, E and Denisova, N and Youdim, K and Vatrenjak-Velagic, V and De Filippo, C and Mehmedagic, A and Causevic, A and Cao, G and Joseph, JA and Prior, RL}, title = {Antioxidant and pro-oxidant capacity of catecholamines and related compounds. Effects of hydrogen peroxide on glutathione and sphingomyelinase activity in pheochromocytoma PC12 cells: potential relevance to age-related diseases.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {108}, number = {5}, pages = {541-557}, doi = {10.1007/s007020170055}, pmid = {11459075}, issn = {0300-9564}, mesh = {Animals ; Antioxidants/*pharmacology ; Biological Assay ; Catecholamines/*pharmacology ; Ceramides/biosynthesis ; Copper/pharmacology ; Dose-Response Relationship, Drug ; Free Radicals/metabolism ; Glutathione/*drug effects/metabolism ; Hydrogen Peroxide/*pharmacology ; Hydroxyl Radical/metabolism ; Neurodegenerative Diseases/*enzymology/physiopathology ; Oxidants/*pharmacology ; Oxidative Stress/drug effects/*physiology ; PC12 Cells/*drug effects/metabolism ; Peroxides/metabolism ; Rats ; Sphingomyelin Phosphodiesterase/*drug effects/metabolism ; Sphingomyelins/metabolism ; }, abstract = {The antioxidant and pro-oxidant capacity of catecholamines (CA) and related compounds were analyzed using the oxygen radical absorbance capacity (ORAC) assay. In the assay 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH), a peroxyl radical generator, ROO*; H2O2-Cu2+, mainly a hydroxyl radical generator, *OH; and Cu2+ a transition metal were used. The antioxidant effect of CA and its related compounds were in the order: neurotransmitters: dopamine (DA), norepinephrine (NE) > metabolites > amino acid precursors as measured by using AAPH. The antioxidant effect of CA and related compounds as measured by using AAPH were linearly correlated with concentration, while the antioxidant effect of CA in scavenging *OH produced by H2O2-Cu2+ increased proportionally to concentration at low concentration, but after reaching a maximum declined with increasing concentration. In the presence of Cu2+, CA acted as pro-oxidant. Glutathione (GSH) acted as a pro-oxidant when H2O2-Cu2+ or when Cu2+ alone was used as an oxidant and showed much higher pro-oxidant effect than DA, which could have relevance in the vulnerability of dopaminergic neurons to oxidative stress in the aging and aging related diseases. The antioxidant capacity of CA and many related compounds seems to be correlated with the numbers of hydroxyl groups and their position on the benzoic ring. The O-methylation and sulfate conjugation of the hydroxyl substitution inactivates both the antioxidant and pro-oxidant activities of CA. Our results show that oxidative stress induced by low (5 microM) or high (300 microM) doses H2O2 in pheochromocytoma PC12 cells significantly up-regulate the activity of Mg-dependent neutral sphingomyelinase (Sase), and significantly decreased GSH.}, } @article {pmid11338849, year = {2001}, author = {Reshetnikov, OV and Kurilovich, SA and Denisova, DV and Zav'ialova, LG and Svetlova, IO and Tereshonok, IN and Krivenchuk, NA and Eremeeva, LI}, title = {[Prevalence and risk factors of the development of irritable bowel syndrome in adolescents: a population study].}, journal = {Terapevticheskii arkhiv}, volume = {73}, number = {2}, pages = {24-29}, pmid = {11338849}, issn = {0040-3660}, mesh = {Adolescent ; Age Factors ; Colonic Diseases, Functional/diagnosis/*epidemiology/etiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Risk Factors ; Sex Factors ; Siberia/epidemiology ; }, abstract = {AIM: To determine prevalence of irritable bowel syndrome (IBS) and associated factors in a community-based population of adolescents.

MATERIAL AND METHODS: 189 schoolboys and 250 schoolgirls aged 14-17 years from four randomly chosen schools of Novosibirsk participated in the study.

RESULTS: The prevalence of IBS defined according to Rome criteria was higher in girls (24 vs 14% in boys, p = 0.01). Colonic pain frequency was similar in both genders (11% in girls vs 9% in boys, p = 0.46), however disturbed defecation occurred significantly more often in girls than in boys (16 vs 7%, p = 0.003). Half of the subjects who reported IBS had also dyspeptic symptoms. Fiber-rich diet and/or laxatives to prevent constipation were used by 2% of boys and 7% of girls (p = 0.012). However, only one third of those having less than 3 stools a week thought it abnormal. IBS is associated with the age over 15-16 years, female gender, abdominal pain in childhood, appendectomy, irregular meals and smoking (in girls). No association was found with other socio-demographic factors and serological markers of some infections and invasions (H. pylori, G. lamblia, O. felineus, hepatitis viruses B and C). Of the persons with diagnosable IBS, 49% have consulted a physician about it, 21% have undergone upper endoscopy. School absenteeism was reported by 62% of the IBS sufferers.

CONCLUSION: IBS is common among adolescents (especially girls) with the prevalence rates similar to those described in adults from West Europe and USA. These disorders are associated with significant disability and health care costs.}, } @article {pmid11305358, year = {2001}, author = {Seagal, J and Spectorman, E and Gershoni, JM and Denisova, GF}, title = {Use of human CD4 transgenic mice for studying immunogenicity of HIV-1 envelope protein gp120.}, journal = {Transgenic research}, volume = {10}, number = {2}, pages = {113-120}, pmid = {11305358}, issn = {0962-8819}, mesh = {AIDS Vaccines/immunology ; Animals ; CD4 Antigens/*genetics ; Cell Separation ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; HIV Antibodies/biosynthesis ; HIV Envelope Protein gp120/*immunology ; HIV-1/*immunology ; Humans ; Immunity, Cellular ; Lymphocytes/immunology ; Mice ; Mice, Transgenic ; Recombinant Proteins/immunology ; }, abstract = {HIV-1 envelope protein, gp120, is a major immunogenic protein of the AIDS virus. A specific feature of this protein is its interaction with the receptor protein, human CD4, an important component of the immune system. This interaction might affect the immunogenic properties of the gp 120 and modulate the immune response towards HIV. To test this hypothesis we used human CD4-transgenic mice for immunization with gp120. The dynamics of the immune response towards gp120, CD4 and other proteins was followed. The results show that the primary immune response to gp120 (two weeks) developed somewhat faster in CD4-transgenic mice versus non-transgenic mice. Both animals, however, ultimately mounted the same level of response over time. The primary immune response to gp120 when complexed with soluble CD4 before the immunization, developed similarly in both groups. The secondary immune response was earlier and markedly stronger in non-transgenic mice compared with the transgenic mice where a less efficient memory response to gp120 was observed. The ability of gp120 to directly interact with CD4+ helper lymphocytes appears to affect the humoral response towards this antigen. Moreover, these effects illustrate how viral modulation of these cells may in turn lead to potentially different states of immunological equilibrium.}, } @article {pmid11295365, year = {2001}, author = {Denisova, NA and Cantuti-Castelvetri, I and Hassan, WN and Paulson, KE and Joseph, JA}, title = {Role of membrane lipids in regulation of vulnerability to oxidative stress in PC12 cells: implication for aging.}, journal = {Free radical biology & medicine}, volume = {30}, number = {6}, pages = {671-678}, doi = {10.1016/s0891-5849(00)00513-x}, pmid = {11295365}, issn = {0891-5849}, mesh = {Acetylcysteine/pharmacology ; Aging/*metabolism ; Animals ; Calcium/metabolism ; Cell Membrane/drug effects/metabolism ; Cholesterol/metabolism/pharmacology ; Enzyme Induction/drug effects ; Fluorescent Dyes ; Glutathione/metabolism ; Hydrogen Peroxide/administration & dosage/pharmacology ; Membrane Lipids/*metabolism ; Oxidative Stress/*physiology ; PC12 Cells ; Rats ; Reactive Oxygen Species/metabolism ; Sphingomyelin Phosphodiesterase/metabolism ; Sphingomyelins/metabolism/pharmacology ; }, abstract = {Previously, we reported that PC12 cells showed increased vulnerability to oxidative stress (OS) induced by H2O2 (as assessed by decrements in calcium recovery, i.e., the ability of cells to buffer Ca(2+) after a depolarization event) when the membrane levels of cholesterol (CHL) and sphingomyelin (SPH) were modified to approximate those seen in the neuronal membranes of old animals. The present study was designed to examine whether the enrichment of the membranes with SPH-CHL and increased cellular vulnerability to OS are mediated by neutral SPH-specific phospholipase C (N-Sase) and the intracellular antioxidant GSH. The results showed a significant up-regulation of N-Sase activity by both low (5 microM) and high (300 microM) doses of H2O2. However, under high doses of H2O2 the up-regulation of N-Sase is accompanied by a significant increase in reactive oxygen species and by a decrease in intracellular GSH. The enrichment of membranes with SPH-CHL significantly potentiated the effects of high doses of H2O2, by further reducing the intracellular GSH and further up-regulating the N-Sase activity. Furthermore, repleting intracellular GSH with 20 mM N-acetylcysteine treatment was sufficient to attenuate the effect of a low dose of H2O2 on Ca(2+) recovery in SPH-CHL-treated cells. Thus, these results suggested that age-related alterations in the membrane SPH-CHL levels could be important determinants of the susceptibility of neuronal cells to OS.}, } @article {pmid11251382, year = {2000}, author = {Manam, S and Ledwith, BJ and Barnum, AB and Troilo, PJ and Pauley, CJ and Harper, LB and Griffiths, TG and Niu, Z and Denisova, L and Follmer, TT and Pacchione, SJ and Wang, Z and Beare, CM and Bagdon, WJ and Nichols, WW}, title = {Plasmid DNA vaccines: tissue distribution and effects of DNA sequence, adjuvants and delivery method on integration into host DNA.}, journal = {Intervirology}, volume = {43}, number = {4-6}, pages = {273-281}, doi = {10.1159/000053994}, pmid = {11251382}, issn = {0300-5526}, mesh = {Adjuvants, Immunologic/pharmacology ; Aluminum Compounds/pharmacology ; Animals ; Base Sequence ; DNA/analysis ; Gonads/chemistry ; Guinea Pigs ; Humans ; Mice ; Muscles/chemistry ; Oncogene Proteins, Viral/genetics ; Papillomavirus E7 Proteins ; Phosphates/pharmacology ; Plasmids/adverse effects/*genetics/*metabolism ; Skin/chemistry ; Tissue Distribution ; Vaccination ; Vaccines, DNA/*administration & dosage/*genetics ; Viral Vaccines/administration & dosage/*genetics ; Virus Diseases/prevention & control ; }, abstract = {A variety of factors could affect the frequency of integration of plasmid DNA vaccines into host cellular DNA, including DNA sequences within the plasmid, the expressed gene product (antigen), the formulation, delivery method, route of administration, and the type of cells exposed to the plasmid. In this report, we examined the tissue distribution and potential integration of plasmid DNA vaccines following intramuscular administration in mice and guinea pigs. We compared needle versus Biojector (needleless jet) delivery, examined the effect of aluminum phosphate adjuvants, compared the results of different plasmid DNA vaccines, and tested a gene (the human papilloma virus E7 gene) whose protein product is known to increase integration frequency in vitro. Six weeks following intramuscular injection, the vast majority of the plasmid was detected in the muscle and skin near the injection site; lower levels of plasmid were also detected in the draining lymph nodes. At early time points (1-7 days) after injection, a low level of systemic exposure could be detected. Occasionally, plasmid was detected in gonads, but it dissipated rapidly and was extrachromosomal - indicating a low risk of germline transmission. Aluminum phosphate adjuvant had no effect on the tissue distribution and did not result in a detectable increase in integration frequency. Biojector delivery, compared with needle injection, greatly increased the uptake of plasmid (particularly in skin at the injection site), but did not result in a detectable increase in integration frequency. Finally, injection of a plasmid DNA vaccine containing the human papilloma virus type 16 E7 gene, known to increase integration in vitro, did not result in detectable integration in mice. These results suggest that the risk of integration following intramuscular injection of plasmid DNA is low under a variety of experimental conditions.}, } @article {pmid11245685, year = {2001}, author = {Belousov, AB and O'Hara, BF and Denisova, JV}, title = {Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus in vitro in the absence of glutamate excitation.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {21}, number = {6}, pages = {2015-2027}, pmid = {11245685}, issn = {1529-2401}, support = {DA00187/DA/NIDA NIH HHS/United States ; }, mesh = {Acetylcholine/*metabolism ; Animals ; Calcium/metabolism ; Calcium Signaling/drug effects ; Cells, Cultured ; Cerebellum/cytology/drug effects/metabolism ; Cerebral Cortex/cytology/drug effects/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Postsynaptic Potentials/drug effects/physiology ; Fluorescent Dyes ; GABA Antagonists/pharmacology ; Glutamic Acid/metabolism ; Hypothalamus/cytology/drug effects/*metabolism ; Membrane Potentials/drug effects/physiology ; Neurotransmitter Agents/*metabolism ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, Glutamate/metabolism ; Synaptic Transmission/drug effects ; Up-Regulation/drug effects ; }, abstract = {Glutamate and GABA are two major fast neurotransmitters (excitatory and inhibitory, respectively) in the CNS, including the hypothalamus. They play a key role in the control of excitation/inhibition balance and determine the activity and excitability of neurons in many neuronal circuits. Using neuronal cultures, whole-cell recording, Ca(2+) imaging, and Northern blots, we studied the compensatory regulation of neuronal activity during a prolonged decrease in glutamate excitation. We report here that after a chronic (6-17 d) blockade of ionotropic glutamate receptors, neurons in hypothalamic cultures revealed excitatory electrical and Ca(2+) synaptic activity, which was not elicited in the control cultures that were not subjected to glutamate blockade. This activity was suppressed with acetylcholine (ACh) receptor antagonists and was potentiated by eserine, an inhibitor of acetylcholinesterase, suggesting its cholinergic nature. The upregulation of ACh receptors and the contribution of ACh to the control of the excitation/inhibition balance in cultures after a prolonged decrease in glutamate activity were also demonstrated. Enhanced ACh transmission was also found in chronically blocked cerebellar but not cortical cultures, suggesting the region-specific character of glutamate-ACh interactions in the brain. We believe that in the absence of glutamate excitation in the hypothalamus in vitro, ACh, a neurotransmitter normally exhibiting only weak activity in the hypothalamus, becomes the major excitatory neurotransmitter and supports the excitation/inhibition balance. The increase in excitatory ACh transmission during a decrease in glutamate excitation may represent a novel form of neuronal plasticity that regulates activity and excitability of neurons during the glutamate/GABA imbalance.}, } @article {pmid11201820, year = {2000}, author = {Denisova, TP and Malinov, IA}, title = {[Dynamics of changes in levels of insulin, glucagon, and C-peptide during glucose tolerance test in patients with coronary atherosclerosis].}, journal = {Terapevticheskii arkhiv}, volume = {72}, number = {12}, pages = {14-16}, pmid = {11201820}, issn = {0040-3660}, mesh = {C-Peptide/*blood ; Coronary Artery Disease/*blood/genetics ; Glucagon/*blood ; Glucose Tolerance Test ; Humans ; Insulin/*blood ; Myocardial Infarction/blood ; }, abstract = {AIM: To study velocity characteristics of changes in the levels of insulin, glucagon and C-peptide in the course of the intravenous glucose tolerance test (IGTT).

MATERIAL AND METHODS: Glucose, insulin, glucagon and peptide levels were measured in the course of IGTT performed in 50 patients with coronary atherosclerosis (CA) who survived transmural myocardial infarction, 32 individuals with hereditary predisposition to CA and 30 controls free of cardiovascular or endocrine pathology. The results were approximated using high-degree polynomes allowing calculation of the first and second derivatives (the velocity and rate of its change).

RESULTS: CA patients showed inhibited changes of blood glucose, immunoreactive insulin. The reduction of the latter lasted longer than that in the control group.

CONCLUSION: Under urgent mobilization of blood glucose regulation system, CA patients develop retention of immunoreactive insulin.}, } @article {pmid11164287, year = {2001}, author = {Joseph, J and Shukitt-Hale, B and Denisova, NA and Martin, A and Perry, G and Smith, MA}, title = {Copernicus revisited: amyloid beta in Alzheimer's disease.}, journal = {Neurobiology of aging}, volume = {22}, number = {1}, pages = {131-146}, doi = {10.1016/s0197-4580(00)00211-6}, pmid = {11164287}, issn = {0197-4580}, mesh = {Age Factors ; *Aging/physiology ; Alzheimer Disease/genetics/*metabolism/therapy ; Amyloid beta-Peptides/genetics/*metabolism ; Animals ; Antioxidants/therapeutic use ; Behavioral Symptoms/physiopathology ; Cytokines/*metabolism ; Humans ; Membrane Lipids/*physiology ; Mice ; Mice, Transgenic ; Oxidative Stress/*physiology ; Signal Transduction/physiology ; Synapses/*physiology ; }, abstract = {The beta-amyloid hypothesis of Alzheimer's Disease (AD) has dominated the thinking and research in this area for over a decade and a half. While there has been a great deal of effort in attempting to prove its centrality in this devastating disease, and while an enormous amount has been learned about its properties (e.g., putative toxicity, processing and signaling), Abeta has not proven to be both necessary and sufficient for the development, neurotoxicity, and cognitive deficits associated with this disease. Instead, the few treatments that are available have emerged from aging research and are primarily directed toward modification of acetylcholine levels. Clearly, it is time to rethink this position and to propose instead that future approaches should focus upon altering the age-related sensitivity of the neuronal environment to insults involving such factors as inflammation and oxidative stress. In other words "solve the problems of aging and by extension those of AD will also be reduced." This review is being submitted as a rather Lutherian attempt to "nail an alternative thesis" to the gate of the Church of the Holy Amyloid to open its doors to the idea that aging is the most pervasive element in this disease and Abeta is merely one of the planets.}, } @article {pmid19484903, year = {2001}, author = {Manning, RT and Denisova, LN}, title = {[Women of Soviet villages on the eve of World War II, 1935-40].}, journal = {Otechestvennaia istoriia}, volume = {}, number = {5}, pages = {88-106}, pmid = {19484903}, issn = {0869-5687}, mesh = {*Birth Rate/ethnology ; Communism/economics/history ; *Employment/economics/history/legislation & jurisprudence/psychology ; *Gender Identity ; *Hierarchy, Social ; History, 20th Century ; Public Policy ; *Rural Health Services/economics/history/legislation & jurisprudence ; Rural Population/history ; Social Change/history ; Social Class ; Social Identification ; USSR/ethnology ; Women/education/history/psychology ; *Women's Health/economics/ethnology/history/legislation & jurisprudence ; Women's Rights/economics/education/history/legislation & jurisprudence ; *Women, Working/education/history/legislation & jurisprudence/psychology ; }, } @article {pmid11048503, year = {2000}, author = {Portnoĭ, LM and Nefedova, VO and Chekunova, EV and Denisova, LB and Stashuk, GA}, title = {[CT in the diagnosis of gastric cancer (review of the literature)].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {4}, pages = {51-59}, pmid = {11048503}, issn = {0042-4676}, mesh = {Adenocarcinoma/diagnostic imaging ; Aged ; Contrast Media ; Diagnosis, Differential ; Esophageal Neoplasms/diagnostic imaging ; Female ; Humans ; Leiomyoma/diagnostic imaging ; Leiomyosarcoma/diagnostic imaging ; Lymphatic Metastasis/diagnostic imaging ; Lymphoma, Non-Hodgkin/diagnostic imaging ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Sensitivity and Specificity ; Stomach Neoplasms/diagnosis/*diagnostic imaging ; Time Factors ; *Tomography, X-Ray Computed/methods ; Ultrasonography ; }, } @article {pmid10996014, year = {2000}, author = {Joseph, JA and Denisova, NA and Bielinski, D and Fisher, DR and Shukitt-Hale, B}, title = {Oxidative stress protection and vulnerability in aging: putative nutritional implications for intervention.}, journal = {Mechanisms of ageing and development}, volume = {116}, number = {2-3}, pages = {141-153}, doi = {10.1016/s0047-6374(00)00128-7}, pmid = {10996014}, issn = {0047-6374}, mesh = {Aging/metabolism/*physiology ; Animals ; Cell Membrane/physiology ; Cognition/physiology ; Humans ; Neurons/cytology/physiology ; Nutritional Physiological Phenomena/*physiology ; Oxidative Stress/*physiology ; Rats ; Receptors, Muscarinic/metabolism ; }, abstract = {Research indicates that vulnerability to oxidative stress (OSV) may increase in aging, suggesting that age-related neurodegenerative diseases such as Alzheimer's disease (AD) or vascular dementia (VAD) may be superimposed upon a vulnerable neuronal environment. Determinations in cell models have suggested that the enhanced OSV may be the result of, (a) increases in membrane lipids, especially sphingomyelin and the sphingomyelin metabolite, sphingosine-1-phosphate, (b) decreases in glutathione, and (c) CNS distribution of OS-sensitive neuronal muscarinic receptor subtypes (e.g. M1, M2 and M4). These changes appear to enhance, (a) decrements in cellular calcium buffering following KCl-induced depolarization, and (b) cell death under OS conditions. Among the most effective agents that antagonized cellular OSV were the combination of polyphenolics found in fruits (e.g. blueberry extract) with high antioxidant activity. Subsequent experiments using dietary supplementation with fruit (strawberry) or vegetable (spinach) extracts have shown that such extracts are also effective in forestalling and reversing the deleterious effects of behavioral aging in F344 rats. Thus, it appears that the beneficial effects of the polyphenolics found in fruits and vegetables in neuronal aging and behavior may be similar to those seen with respect to carcinogenesis and cardiovascular disease.}, } @article {pmid10961136, year = {2000}, author = {Pigolkin, IuI and Denisova, OP and Tumanov, VP and Bogomolov, DV and Ozdamirova, IuM}, title = {[Sudden death from exacerbation of interstitial myocarditis combined with trauma and chronic alcoholism].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {43}, number = {4}, pages = {41-45}, pmid = {10961136}, issn = {0039-4521}, mesh = {Abdominal Injuries/*complications/diagnosis ; Adult ; Alcoholism/*complications/diagnosis ; *Cause of Death ; Chronic Disease ; Craniocerebral Trauma/*complications/diagnosis ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Male ; Multiple Trauma/*complications/diagnosis ; Myocarditis/*complications/diagnosis ; Recurrence ; Wounds, Nonpenetrating/*complications/diagnosis ; }, } @article {pmid10934918, year = {2000}, author = {Denisova, LB and Vorontsova, SV and Emel'ianova, LN}, title = {[Potentialities of computed tomography and ultrasound in diagnosis of hormonally active adrenal diseases: results of comparison CT and US with operative adn histological data].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {2}, pages = {23-31}, pmid = {10934918}, issn = {0042-4676}, mesh = {Adenocarcinoma/diagnosis/surgery ; Adolescent ; Adrenal Gland Diseases/*diagnosis/surgery ; Adrenal Gland Neoplasms/diagnosis/surgery ; Adrenal Hyperplasia, Congenital/diagnosis/surgery ; Adrenalectomy ; Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pheochromocytoma/diagnosis/surgery ; Retrospective Studies ; Sensitivity and Specificity ; *Tomography, X-Ray Computed ; *Ultrasonography ; }, abstract = {The data given in the paper suggest that X-ray computed tomography (CT) is highly effective in detecting all types of hormonally active adrenal abnormalities. CT used in hormonally active adrenal diseases yielded data on major quantitative and qualitative (primarily densitometric) criteria that could be used in assessing the images of the adrenal area in these patients. Ultrasound study (USS) made at the first stage of topical diagnostic searches was of informative value in detecting adrenal tumor lesions, the technique being highly sensitive in the diagnosis of adrenal pheochromocytomas and adenocarcinomas, but less informative in the detection of hormonally active adrenocortical adenomas (aldesterone-producing ones in particular) than CT. The diagnosis of various adrenocortical hyperplasies and the differentiation of hyperplastic and tumor forms of hypercorticoidism are a prerogative of CT that substantially supplements USS findings in such cases.}, } @article {pmid10864647, year = {2000}, author = {Dowling, W and Denisova, E and LaMonica, R and Mackow, ER}, title = {Selective membrane permeabilization by the rotavirus VP5* protein is abrogated by mutations in an internal hydrophobic domain.}, journal = {Journal of virology}, volume = {74}, number = {14}, pages = {6368-6376}, pmid = {10864647}, issn = {0022-538X}, support = {R01-AI31016/AI/NIAID NIH HHS/United States ; R03-AI42150/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Cell Line ; Cell Membrane Permeability ; Dextrans/chemistry ; Fluorescein-5-isothiocyanate/analogs & derivatives/chemistry ; Fluoresceins/chemistry ; Fluorescent Dyes/chemistry ; Liposomes/chemistry ; Mutagenesis, Site-Directed ; Nitrophenylgalactosides/pharmacology ; Phosphatidylcholines/chemistry ; Protein Structure, Tertiary ; RNA-Binding Proteins/metabolism ; Rotavirus/*metabolism ; Viral Nonstructural Proteins/chemistry/genetics/*metabolism ; }, abstract = {Rotavirus infectivity is dependent on the proteolytic cleavage of the VP4 spike protein into VP8* and VP5* proteins. Proteolytically activated virus, as well as expressed VP5*, permeabilizes membranes, suggesting that cleavage exposes a membrane-interactive domain of VP5* which effects rapid viral entry. The VP5* protein contains a single long hydrophobic domain (VP5*-HD, residues 385 to 404) at an internal site. In order to address the role of the VP5*-HD in permeabilizing cellular membranes, we analyzed the entry of o-nitrophenyl-beta-D-galactopyranoside (ONPG) into cells induced to express VP5* or mutated VP5* polypeptides. Following IPTG (isopropyl-beta-D-thiogalactopyranoside) induction, VP5* and VP5* truncations containing the VP5*-HD permeabilized cells to the entry and cleavage of ONPG, while VP8* and control proteins had no effect on cellular permeability. Expression of VP5* deletions containing residues 265 to 474 or 265 to 404 permeabilized cells; however, C-terminal truncations which remove the conserved GGA (residues 399 to 401) within the HD abolished membrane permeability. Site-directed mutagenesis of the VP5-HD further demonstrated a requirement for residues within the HD for VP5*-induced membrane permeability. Functional analysis of mutant VP5*s indicate that conserved glycines within the HD are required and suggest that a random coiled structure rather than the strictly hydrophobic character of the domain is required for permeability. Expressed VP5* did not alter bacterial growth kinetics or lyse bacteria following induction. Instead, VP5*-mediated size-selective membrane permeability, releasing 376-Da carboxyfluorescein but not 4-kDa fluorescein isothiocyanate-dextran from preloaded liposomes. These findings suggest that the fundamental role for VP5* in the rotavirus entry process may be to expose triple-layered particles to low [Ca](i), which uncoats the virus, rather than to effect the detergent-like lysis of early endosomal membranes.}, } @article {pmid10857800, year = {2000}, author = {Sanjeevi, CB and Miller, EN and Dabadghao, P and Rumba, I and Shtauvere, A and Denisova, A and Clayton, D and Blackwell, JM}, title = {Polymorphism at NRAMP1 and D2S1471 loci associated with juvenile rheumatoid arthritis.}, journal = {Arthritis and rheumatism}, volume = {43}, number = {6}, pages = {1397-1404}, doi = {10.1002/1529-0131(200006)43:6<1397::AID-ANR25>3.0.CO;2-6}, pmid = {10857800}, issn = {0004-3591}, mesh = {Adolescent ; Arthritis, Juvenile/ethnology/*genetics/immunology ; Carrier Proteins/*genetics ; *Cation Transport Proteins ; Child ; Child, Preschool ; *Chromosome Mapping ; *Genetic Predisposition to Disease ; HLA-DQ Antigens/analysis ; Haplotypes ; Humans ; Infant ; Latvia/ethnology ; Membrane Proteins/*genetics ; Microsatellite Repeats ; *Polymorphism, Genetic ; Russia/ethnology ; White People/*genetics ; }, abstract = {OBJECTIVE: To examine the role of NRAMP1 in susceptibility to juvenile rheumatoid arthritis (JRA).

METHODS: DNA from 119 JRA patients (72 pauciarticular, 47 polyarticular) and 111 healthy controls from Latvia was genotyped for a functional repeat polymorphism in the promoter of NRAMP1 and a linked (<150 kb) microsatellite D2S1471. The findings were compared with those from HLA-DQ alleles typed previously. Chi-square analyses were performed using the Mantel-Haenszel test and stratification according to pure Latvian or pure Russian descent. Haplotype analysis was performed using the Associate program to implement the expectation-maximization algorithm based on the gene-counting technique.

RESULTS: Allele 3 at NRAMP1 conferred increased risk (odds ratios [ORs] 2.26, 2.31, and 2.19; P = 0.0006, 0.003, and 0.019) of disease in the JRA, pauciarticular, and polyarticular patient groups, respectively. Allele 2 conferred protection (OR 0.44, 0.43, and 0.46). Alleles at D2S1471 that conferred susceptibility (6 and 12) or protection (11) did so only when on a haplotype with alleles 3 or 2, respectively, at NRAMP1. Allele 3 at NRAMP1 was additive with HLA-DQ7 for susceptibility (OR 3.71, 3.71, and 4.02), and allele 2 at NRAMP1 was additive with HLA-DQ5 for protection (OR 0.19, 0.08, and 0.12).

CONCLUSION: The NRAMP1 allele conferring susceptibility to JRA drives high levels of NRAMP1 expression, while the allele associated with protection drives low levels. These 2 alleles are inversely associated with susceptibility to infectious disease, consistent with their maintenance in populations through balancing selection.}, } @article {pmid10852036, year = {1999}, author = {Denisova, LIa and Baturina, II and Zakabunin, AI and Afinogenova, GN and Pustoshilova, NM}, title = {[The determination of lipopolysaccharide admixtures in protein preparations].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {5}, pages = {109-112}, pmid = {10852036}, issn = {0372-9311}, mesh = {Biotinylation ; Calibration ; Collodion ; *Drug Contamination ; *Escherichia coli ; Indicators and Reagents ; Lipopolysaccharides/*analysis ; Membranes, Artificial ; Periodic Acid ; Recombinant Proteins/*analysis ; Solutions ; }, abstract = {A new method for the determination of lipopolysaccharide (LPS) admixtures in protein solutions has been developed. The method includes the periodate oxidation of LPS, biotinylation with biotin hydraside, immobilization on a nitrocellulose membrane and the development of biotinylated LPS in the streptavidin--alkaline phosphatase system. Proteins are previously removed from the solution by treatment with hot phenol. Development with the use of 5-bromoinodyl phosphate and nitrotetrazolium blue makes it possible to detect about 30 pg of LPS immobilized on the nitrocellulose membrane.}, } @article {pmid10832397, year = {2000}, author = {Portnoĭ, LM and Denisova, LB and Stashuk, GA and Nefedova, VO}, title = {[Magnetic resonance imaging in the diagnosis of gastric cancer: X-ray versus MRI anatomic findings].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {1}, pages = {26-40}, pmid = {10832397}, issn = {0042-4676}, mesh = {Administration, Oral ; Adult ; Aged ; Barium Sulfate/administration & dosage ; Carcinoma/*diagnosis ; Contrast Media/administration & dosage ; Diagnosis, Differential ; Diagnostic Errors ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Radiography ; Sensitivity and Specificity ; Stomach/*diagnostic imaging/*pathology ; Stomach Neoplasms/*diagnosis ; }, abstract = {The paper assesses the present-day role of MRI in the diagnosis of gastric cancer. The authors consider the major prerequisites for the main aim of their study to be: 1) a dramatic incidence of diffuse (endophytic) gastric carcinoma, which requires significant correction of today's approaches to its diagnosis and 2) a rather biased and, in the authors' opinion, present-day mainly negative attitude towards MRI of the stomach as a diagnostic method for its tumor lesions. By applying the X-ray-MRI anatomic principle to the comparative study of MRI findings in 50 patients with predominantly gastric intramural carcinoma and in 25 patients without gastric tumors (controls), the authors present their methods for gastric MRI, the MRI semiotics of gastric cancer by concurrently touching upon a variety of problems that characterize the potentialities of MRI of the stomach in the diagnosis of its tumor lesions, including their differential diagnosis. As a result, the authors highly appreciate gastric MRI and consider this method to be included into the diagnostic algorithm of radiation techniques used in the diagnosis of gastric cancer, which should occupy its definite diagnostic place.}, } @article {pmid10802890, year = {2000}, author = {Kharitonchik, LA and Kodentsova, VM and Vrzhesinskaia, OA and Denisova, SN and Spirichev, VB}, title = {[Vitamin B 6 metabolism in phenylketonuria].}, journal = {Voprosy meditsinskoi khimii}, volume = {46}, number = {1}, pages = {81-88}, pmid = {10802890}, issn = {0042-8809}, mesh = {Child ; Female ; Humans ; Male ; Phenylketonurias/*metabolism ; Pyridoxal Phosphate/blood ; Pyridoxic Acid/urine ; Pyridoxine/*metabolism ; Riboflavin/metabolism ; }, abstract = {Based on the analysis of the dependence of 4-pyridoxic acid urinary excretion from pyridoxal-5'-phosphate blood plasma level and its statistic distribution it has been shown that vitamin B-6 metabolism in children suffering from phenylketonuria and therefore the criteria of the body saturation with this vitamin differ from those for healthy people. Increased pyridoxal-5'-phosphate blood plasma level has been demonstrated for PKU children. The concentration of 11 ng/ml should be considered as a bottom border of the adequate supply with vitamin B-6. The elevated vitamin B-2 intake approximates vitamin B-6 status indexes of sick children to those usually measured in healthy children. The necessity for the reevaluation of vitamin B-2 and B-6 optimal diet content under this disease and its biochemical validation are discussed.}, } @article {pmid10781835, year = {2000}, author = {Denisova, GF and Zerwanitzer, M and Denisov, DA and Spectorman, E and Mondor, I and Sattentau, Q and Gershoni, JM}, title = {Expansion of epitope cross-reactivity by anti-idiotype modulation of the primary humoral response.}, journal = {Molecular immunology}, volume = {37}, number = {1-2}, pages = {53-58}, doi = {10.1016/s0161-5890(00)00022-5}, pmid = {10781835}, issn = {0161-5890}, mesh = {Amino Acid Sequence ; Animals ; Antibodies, Anti-Idiotypic/*immunology ; *Antibody Formation ; Cross Reactions ; Epitopes/*immunology ; HIV Envelope Protein gp120/immunology ; HIV-1/immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; }, abstract = {The primary humoral response produces antigen-specific antibodies so to clear the initial infection, and generates a population of corresponding memory cells to prevent infection by future encounters with the same pathogen. The continuous genetic modification of a pathogen's exterior, however, is one mechanism used to evade the immune defenses of its host. Here we describe a novel means, involving anti-idiotypic antibodies, by which the host can counteract such pathogen genetic alterations by modulation of its primary humoral response. An autoimmune response against primary antibodies, Ab1's, creates anti-idiotypic antibodies (Ab2's), some of which (designated Ab2alpha) are able to bind the Ab1/antigen complex. We have discovered that binding of Ab2alpha to its corresponding Ab1 can expand Ab1's ability to bind variations of its antigen. This expanded epitope cross-reactivity is shown not only to increase the binding activity of Ab1 but also its ability to neutralize a variant infectious virus. MAb M77 is an Ab1, which is highly strain-specific for the HIV-1 envelope protein gp120(IIIB). This Ab1 can be rendered cross-reactive and neutralizing for an otherwise resistant HIV strain by its interaction with a unique anti-idiotypic Ab2alpha (GV12). Furthermore, molecular characterization of this expanded cross-reactivity was accomplished using combinatorial phage display peptide libraries.}, } @article {pmid10769463, year = {2000}, author = {Mel'nikova, EV and Shchekina, OG and Borisova, MN and Denisova, LB and Baranova, IN}, title = {[Characteristics of the strategy of intensive care of unconscious children].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {1}, pages = {36-38}, pmid = {10769463}, issn = {0201-7563}, mesh = {Adolescent ; Age Factors ; Central Nervous System Diseases/therapy ; Child ; Child, Preschool ; *Critical Care/methods ; Humans ; Infant ; Infant, Newborn ; Intensive Care, Neonatal/methods ; Meningitis, Bacterial/therapy ; Meningoencephalitis/therapy ; Unconsciousness ; }, abstract = {Three major groups can be distinguished among children hospitalized in resuscitation and intensive care wards in a state of unconsciousness: patients with bacterial meningitis and meningoencephalitis, viral meningoencephalitis, and noninfectious involvement of the NCS. Common strategy of treatment of these patients is characterized by some specific features: etiotropic antibiotic therapy in group 1 patients, antiviral drugs in group 2, and mainly symptomatic measures in group 3. Immunotherapy used in each of these groups is substitute in group 1, immunomodulating and immunostimulating in group 2 and even more so in group 3. Better results in group 1 are due to highly effective etiotropic antibiotics and drugs.}, } @article {pmid10717927, year = {2000}, author = {Denisova, GA and Oshchepkova, EV and Balakhonova, TV and Kheĭmets, GI and Arabidze, GG}, title = {[Blood flow in affected major arteries of head in hypertensive patients].}, journal = {Terapevticheskii arkhiv}, volume = {72}, number = {2}, pages = {49-52}, pmid = {10717927}, issn = {0040-3660}, mesh = {Adult ; Aged ; Arteriosclerosis/complications/diagnostic imaging/*physiopathology ; Blood Flow Velocity ; Brain/*blood supply ; Carotid Artery, Internal/diagnostic imaging/*physiopathology ; Female ; Humans ; Hypertension/complications/diagnostic imaging/*physiopathology ; Male ; Middle Aged ; Severity of Illness Index ; Ultrasonography, Doppler, Duplex ; Vertebral Artery/diagnostic imaging/*physiopathology ; }, abstract = {AIM: To assess blood flow in intracranial internal carotid and vertebral arteries in patients with essential hypertension (EH) and hemodynamically insignificant atherosclerotic lesions and deformities of major arteries of the head (MAH).

MATERIALS AND METHODS: The blood flow was assessed in 55 untreated patients (mean age 53 +/- 1 years) with mild, moderate or severe hypertension. 20 healthy patients served control. Duplex scanning was performed using ACUSON unit.

RESULTS: Total blood flow (Q) in hypertensive subjects appeared significantly subnormal. It was less in patients with hemodynamically insignificant atherosclerotic stenosis and flexures of the carotid and vertebral arteries than in patients with affection of the carotid arteries only. Q in MAH was lower in smokers than in non-smokers.}, } @article {pmid10715964, year = {1999}, author = {Denisova, TS and Govorun, VM and Bochkarev, EG}, title = {[Possible use of polymerase chain test (DNA diagnosis) in detection of mycobacterium tuberculosis].}, journal = {Problemy tuberkuleza}, volume = {}, number = {6}, pages = {54-55}, pmid = {10715964}, issn = {0032-9533}, mesh = {Adult ; DNA, Bacterial/*analysis ; Diagnosis, Differential ; Female ; Humans ; Lung Diseases, Obstructive/*diagnosis ; Male ; Middle Aged ; Mycobacterium tuberculosis/*genetics/isolation & purification ; *Polymerase Chain Reaction ; Reproducibility of Results ; Sarcoidosis, Pulmonary/diagnosis ; Sputum/microbiology ; Tuberculosis, Pulmonary/*diagnosis ; }, abstract = {The polymerase chain test (PCT) (DNA diagnosis) is comparable with other routine diagnostic methods, but has a variety of advantages over then: it is much more highly sensitive and specific, provides results more promptly than culturing. The tests have indicated that the Polytub diagnostic kit may be recommended for use at medical facilities in Russia to detect tuberculosis pathogen DNA in the sputum, urine, exudate, and spinal fluid using PCT.}, } @article {pmid10641723, year = {1999}, author = {Denisova, NA and Fisher, D and Provost, M and Joseph, JA}, title = {The role of glutathione, membrane sphingomyelin, and its metabolites in oxidative stress-induced calcium "dysregulation" in PC12 cells.}, journal = {Free radical biology & medicine}, volume = {27}, number = {11-12}, pages = {1292-1301}, doi = {10.1016/s0891-5849(99)00163-x}, pmid = {10641723}, issn = {0891-5849}, support = {AG007728/AG/NIA NIH HHS/United States ; AG04418/AG/NIA NIH HHS/United States ; }, mesh = {Aging ; Animals ; Brain/metabolism ; Calcium/*metabolism ; Cell Membrane/metabolism ; Ceramides/pharmacology ; Cycloserine/pharmacology ; Glutathione/*physiology ; *Homeostasis ; Hydrogen Peroxide/pharmacology ; *Lysophospholipids ; *Oxidative Stress ; PC12 Cells ; Rats ; Reactive Oxygen Species/metabolism ; Sphingomyelin Phosphodiesterase/pharmacology ; Sphingomyelins/metabolism/*physiology ; Sphingosine/analogs & derivatives/pharmacology ; }, abstract = {Previous research showed that increasing membrane sphingomyelin (SPH) levels in rat pheochromocytoma (PC12) cells to the same extent as that seen in some brain regions with aging dramatically increases the vulnerability to oxidative stress (OS). These increases in vulnerability were determined by assessing deficits in the ability of these cells to extrude and/or sequester Ca2+ following 30 mM KCl-induced depolarization (recovery). The purpose of the present experiments was to discern whether increasing the levels of particular SPH metabolite(s), i.e., ceramide (Cer), sphingosine (Ssine), or sphingosine-1-phosphate (SPP), or indirectly increasing the concentrations of these metabolites with sphingomylinase (Sase), would interact with the cell's sensitivity to OS induced by low (5 microM) or high (nonlethal, 300 microM) H2O2. In addition, the OS vulnerability was examined as above under decreased SPH levels by exposing the cells to L-cycloserine (Lcc), which prevents SPH synthesis. Both Sase and SPP significantly decreased Ca2+ recovery of PC12 cells after H2O2 exposure. Conversely, Lcc-treated cells showed no further OS-induced decrements in recovery below those seen in controls. SPP significantly decreased glutathione levels (GSH) in the absence of OS. Repletion of GSH with 20 mM N-acetylcysteine significantly attenuated the effect of 5 microM H2O2 on recovery in SPP-treated cells and decreased sensitivity of SPP-treated cells to low doses of OS. Overall, our results suggest a critical role for GSH and SPP in the regulation of OS vulnerability, especially as it relates to Ca2+ homeostasis.}, } @article {pmid10641280, year = {1999}, author = {Denisova, SN and Kutafina, EK and Sergeeva, TV and Savina, MI and Kon', IIa and Shilina, NM and Chizhevskaia, OL and Shilov, AV}, title = {[Effects of vitamin D metabolites on indicators of protein, phosphorus and calcium metabolism in children with chronic renal failure].}, journal = {Voprosy pitaniia}, volume = {68}, number = {5-6}, pages = {35-40}, pmid = {10641280}, issn = {0042-8833}, mesh = {Adolescent ; Calcifediol/administration & dosage/*therapeutic use ; Calcium/metabolism ; Child ; Chronic Kidney Disease-Mineral and Bone Disorder/blood/metabolism/therapy ; Fatty Acids, Nonesterified/*blood ; Humans ; Hydroxycholecalciferols/administration & dosage/*therapeutic use ; Kidney Failure, Chronic/blood/*metabolism/*therapy ; Nitrogen/metabolism ; Phosphorus/metabolism ; Time Factors ; }, abstract = {Amino acid analysis and investigation of nitrogen, calcium and phosphorus balance were done in two groups of patients with renal failure and osteodystrophy on vitamin D metabolites and analogues treatment. The results of the investigation confirm vitamin D metabolites influence on free amino acid metabolism and on nitrogen, calcium, phosphorus balance. We observed significant decreases of blood amino acids and good influence on renal osteodystrophy in patients treated with vitamin D metabolites. Vitamin D metabolites didn't influence retention, urinary and fecal excretion of endogenous nitrogen in patients with renal failure.}, } @article {pmid10582016, year = {1999}, author = {Krichevskaia, GI and Andzhelov, VO and Katargina, LA and Khvatova, AV and Denisova, EV and Zvonarev, AIu and Kuliakina, MN and Zaĭtsev, IZ}, title = {[Cytomegalovirus infection in children with endogenous uveitis].}, journal = {Vestnik oftalmologii}, volume = {115}, number = {5}, pages = {23-25}, pmid = {10582016}, issn = {0042-465X}, mesh = {Adolescent ; Antibodies, Viral/blood ; Biomarkers/blood ; Child ; Child, Preschool ; Cytomegalovirus/immunology ; Cytomegalovirus Infections/*diagnosis ; Humans ; Immunoenzyme Techniques ; Immunoglobulins/blood ; Infant ; Uveitis/congenital/*diagnosis/etiology ; }, abstract = {A total of 405 children aged 3 months to 15 years with uveitis of different origin and localization and 50 mothers of children with intrauterine uveitis were tested for cytomegaloviruses (CMV). Chronic CMV infection was detected in 79% children and 88% mothers. Active CMV infection was diagnosed in 7.1% children with various clinical forms of uveitis; it was somewhat more frequent in cases with grave posterior uveitis and panuveitis complicated by detachment of the retina and vitreous fibrosis. Anti-CMV IgG antibodies indicate an infection, but their detection is insufficient for identifying the etiology of uveitis. Active CMV infection can be a cause of uveitis or aggravate uveitis of another etiology and favor the development of postoperative complications. In many cases active CMV infection was detected in children during remission without clinical signs of uveitis activity. Individual analysis of clinical laboratory data is needed for each patient in order to evaluate the etiological and pathogenetic role of active CMV infection.}, } @article {pmid10576092, year = {1999}, author = {Denisova, LIa and Bel'kova, NL and Tulokhonov, II and Zaĭchikov, EF}, title = {[Diversity of bacteria at various depths in the southern part of lake Baikal as detected by 16S rRNA sequencing].}, journal = {Mikrobiologiia}, volume = {68}, number = {4}, pages = {547-556}, pmid = {10576092}, issn = {0026-3656}, mesh = {Bacteria/*genetics ; *Genetic Variation ; Phylogeny ; RNA, Bacterial/*genetics ; RNA, Ribosomal, 16S/*genetics ; Russia ; *Water Microbiology ; }, abstract = {Phylogenetic analysis of the bacterial community inhabiting the water of Lake Baikal was performed on the basis of 16S rRNA sequencing. The composition of the bacterial community was shown to vary significantly with depth. Cyanobacteria were dominant species at the surface of the lake. At a moderate depth (400 m), actinomycete relatives were most abundant. At a great depth and near the bottom, the community was composed mainly of proteobacteria and cyanobacteria (the latter are probably brought from the surface layers by vertical near-shore water fluxes). Most of the bacterial 16S rRNA sequences detected exhibited low similarity to those known and formed separate clusters in the phylogenetic tree, which may indicate the endemic nature of the corresponding bacteria.}, } @article {pmid10502919, year = {1999}, author = {Denisova, TP and Malinov, IA}, title = {[The functional interrelationships of blood glucose and immunoreactive insulin in the intravenous glucose tolerance test in coronary atherosclerosis patients].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {}, number = {7}, pages = {9-11}, pmid = {10502919}, issn = {0869-2084}, mesh = {Adult ; Blood Glucose/*analysis ; Coronary Artery Disease/*blood ; Genetic Predisposition to Disease/blood ; Glucose Tolerance Test/*methods/statistics & numerical data ; Humans ; Hyperinsulinism/blood ; Insulin Antibodies/*blood ; Least-Squares Analysis ; Linear Models ; Middle Aged ; Time Factors ; }, abstract = {Measurements of blood glucose and immunoreactive insulin (IRI) during glucose tolerance test (GTT) in patients with coronary atherosclerosis and with hereditary predisposition to this condition were carried out. The results were processed using programs based on the least squares method, theoretically based on the main assumptions of the probability theory. A strong (virtually linear) correlation between glucose and IRI was detected in the studied groups. Shift of the glucose level by 1 unit in patients with coronary atherosclerosis leads to an almost twofold increase in IRI level, as against subjects with hereditary liability to coronary atherosclerosis. Nonlinear relationship between glucose and IRI in the GTT is described for the control group.}, } @article {pmid10479711, year = {1999}, author = {Joseph, JA and Shukitt-Hale, B and Denisova, NA and Bielinski, D and Martin, A and McEwen, JJ and Bickford, PC}, title = {Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {19}, number = {18}, pages = {8114-8121}, pmid = {10479711}, issn = {1529-2401}, mesh = {Aging/*physiology ; Animals ; Calcium/metabolism ; Cognition/drug effects/*physiology ; Corpus Striatum/drug effects/growth & development/*physiology ; Dietary Supplements ; Dopamine/metabolism ; *Fruit ; Glutathione/metabolism ; In Vitro Techniques ; Maze Learning/drug effects/*physiology ; Motor Activity/drug effects/*physiology ; Neurons/drug effects/*physiology ; Plant Extracts/*pharmacology ; Potassium/pharmacology ; Psychomotor Performance/drug effects/*physiology ; Rats ; Rats, Inbred F344 ; Signal Transduction/drug effects ; *Spinacia oleracea ; Synaptosomes/drug effects/physiology ; }, abstract = {Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.}, } @article {pmid10392438, year = {1999}, author = {Ospel'nikova, TP and Grigorian, SS and Evseev, AA and Besaeva, TP and Denisova, EN and Kovalenko, AL and Ershov, FI}, title = {[Effectiveness of cycloferon in treating virus-associated inflammatory gynecologic diseases].}, journal = {Voprosy virusologii}, volume = {44}, number = {3}, pages = {130-133}, pmid = {10392438}, issn = {0507-4088}, mesh = {Acridines/*therapeutic use ; Acute Disease ; CD4 Lymphocyte Count ; CD4-CD8 Ratio ; CD8-Positive T-Lymphocytes ; Chronic Disease ; Female ; Genital Diseases, Female/*drug therapy/immunology ; Humans ; Inflammation/drug therapy/immunology ; Interferon Inducers/*therapeutic use ; }, abstract = {Cycloferon, a low molecular weight interferon inducer synthesized in Russia, was used for treating chronic acute gynecological inflammations. The etiology of diseases was mixed in the majority of cases. Clinical efficacy of the drug was 79%. Cycloferon, an antiviral immunomodulating drug, is recommended for combined therapy of chronic and acute gynecological inflammations.}, } @article {pmid10378305, year = {1999}, author = {Kodentsova, VM and Vrzhesinskaia, OA and Denisova, SN and Spirichev, VB}, title = {[Metabolism of vitamins B1 and B2 during phenylketonuria].}, journal = {Voprosy meditsinskoi khimii}, volume = {45}, number = {2}, pages = {150-157}, pmid = {10378305}, issn = {0042-8809}, mesh = {Child ; Erythrocytes/metabolism ; Female ; Humans ; Male ; Phenylketonurias/*blood/*urine ; Riboflavin/administration & dosage/*blood/*urine ; Thiamine/*blood/*urine ; }, abstract = {Vitamin level in blood plasma and erythrocytes and a rate of urinary excretion of vitamin metabolites were analysed in children suffering from phenylketonuria. It has been shown that vitamin B1 metabolism and therefore the criteria of the adequate sufficiency with this vitamin does not differ from those for healthy people. Increased riboflavin urinary excretion under its decreased plasma and erythrocyte levels has been demonstrated for PKU children. In consequence of this the indexes of sufficiency significantly differ from those of the healthy adequately supplied with this vitamin children and are equal to 4 ng of riboflavin per 1 ml of blood plasma and its urinary excretion more than 50 mg/h. The necessity for the redetermination of vitamin B2 diet optimal content under this disease and its biochemical validation are discussed.}, } @article {pmid10364680, year = {1999}, author = {Sistonen, P and Virtaranta-Knowles, K and Denisova, R and Kucinskas, V and Ambrasiene, D and Beckman, L}, title = {The LWb blood group as a marker of prehistoric Baltic migrations and admixture.}, journal = {Human heredity}, volume = {49}, number = {3}, pages = {154-158}, doi = {10.1159/000022864}, pmid = {10364680}, issn = {0001-5652}, mesh = {Alleles ; Baltic States ; Blood Group Antigens/*genetics ; Cell Adhesion Molecules/*genetics ; *Emigration and Immigration ; Europe ; Gene Frequency ; *Genetic Markers ; Genetics, Population ; Humans ; Time ; }, abstract = {Archaeological findings and historical records indicate frequent migrations and exchange of genetic material between populations in the Baltic Sea area. However, there have so far been very few attempts to trace migrations in this area using genetic markers. We have studied the Baltic populations with respect to exceptional variations in the frequencies of the Landsteiner-Wiener (LW) blood group. The frequency of the uncommon LWb gene was high in the Balts, around 6% among Latvians and Lithuanians, very low among the other western Europeans (0-0.1%) and apparently absent in Asiatic and African populations. From the Baltic region of peak frequency there was a regular decline of LWb incidence (a descending cline) in the neighboring populations: 4.0% in the Estonians, 2.9% in the Finns, 2. 2% in the Vologda Russians, and 2.0% in the Poles. Thus the distribution of LWb suggests considerable and extensive Baltic admixture, especially in the north and northeast direction. In Southern Sweden with an LWb frequency of 0.3%, the Baltic influence appeared slight, while in the population of the Swedish island Gotland in the middle of the Baltic Sea there was a significantly increased LWb frequency of 1.0% compared with that of Western European countries. The distinction of codominantly inherited LW antigenic forms, LWa and LWb (previously Nea), is known to be due to a single base substitution. Based on our population data, it is plausible that the expansion of this point mutation occurred only once during human history. Furthermore, our data indicate that the expansion of the LWb mutation occurred in Balts and that LWb can be considered a 'Baltic tribal marker', its presence in other populations being an indicator of the degree of Baltic genetic influence.}, } @article {pmid10321325, year = {1999}, author = {Denisov, M and Denisova, O and Cornélissen, G and Halberg, F}, title = {Toward a heart rate and axillary temperature chronome in schizophrenia: gauge of disease severity.}, journal = {Functional neurology}, volume = {14}, number = {1}, pages = {13-20}, pmid = {10321325}, issn = {0393-5264}, support = {GM-13981/GM/NIGMS NIH HHS/United States ; HL-40650/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Analysis of Variance ; Axilla ; *Body Temperature ; *Circadian Rhythm ; Female ; *Heart Rate ; Humans ; Male ; Middle Aged ; Schizophrenia/*physiopathology ; *Severity of Illness Index ; }, abstract = {The heart rate and axilliary temperature of 17 patients with schizophrenia were measured every 3 hours during waking for 4 days. In 28 profiles, large inter- and intra-individual variations notwithstanding, relations between the time structures (chronomes) of heart rate and axillary temperature are assessed and further examined from the viewpoint of their bearing on the severity of the patients's condition.}, } @article {pmid10216505, year = {1999}, author = {Blank, M and Denisova, O and Cornélissen, G and Halberg, F}, title = {Enhanced circasemiseptan (about 3.5-day) variation in the heart rate of cancer patients?.}, journal = {Anticancer research}, volume = {19}, number = {1B}, pages = {853-855}, pmid = {10216505}, issn = {0250-7005}, support = {GM-13981/GM/NIGMS NIH HHS/United States ; HL-40650/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Axilla ; Heart Rate/*physiology ; Humans ; Middle Aged ; Neoplasms/*physiopathology ; *Periodicity ; Skin Temperature/physiology ; }, abstract = {In addition to prominent circadian and circannual components, an about half-weekly (circasemiseptan) pattern was shown earlier to characterize mitotic activity in cancer patients. A circasemiseptan variation in heart rate and circadian rhythms in heart rate and axillary temperature of cancer patients are assessed herein. These variables could be tested as putative marker rhythms for the optimization of radio- and/or chemotherapy by timing which, from a practical viewpoint, may be easier to implement along the scale of the week than that of the day.}, } @article {pmid10093293, year = {1998}, author = {Denisova, DV and Beresovikova, IP and Efendieva, JB}, title = {Cardiovascular risk factors in the adolescent population of Chukotka.}, journal = {International journal of circumpolar health}, volume = {57 Suppl 1}, number = {}, pages = {299-301}, pmid = {10093293}, issn = {1239-9736}, mesh = {Adolescent ; Cardiovascular Diseases/diagnosis/*epidemiology ; Ethnicity/*statistics & numerical data ; Female ; Health Surveys ; Humans ; Incidence ; Male ; Risk Factors ; Russia/epidemiology ; Sampling Studies ; Sex Distribution ; }, abstract = {Representative samples of adolescents of both sexes, aged 15-17, who were residents of coastal and tundra Chukotka settlements (325 subjects) have been examined. The survey was conducted according to methods based on WHO recommendations. The program included a questionnaire, two measurements of arterial blood pressure, anthropometry, and assessment of blood lipid levels. The prevalence of smoking in boys was 40%; in girls, 19%. High systolic BP occurred more often in newly arrived boys (25%). Hypercholesterolemia was minimal in Chukotka Natives (5%), as was hypertriglyceridemia. The prevalence of low HDL cholesterol was highest (48%) in Native boys. Lipid disorders in Chukotka Native children obviously result from an unbalanced diet. High levels of arterial blood pressure in non-Native adolescents of Chukotka are probably caused by stress on the adaptation system under severe conditions in the North.}, } @article {pmid10093272, year = {1998}, author = {Beresovikova, IP and Efendieva, JB and Mamleeva, FR and Denisova, DV and Lebedev, GB}, title = {Nutrition of Chukotka Native children.}, journal = {International journal of circumpolar health}, volume = {57 Suppl 1}, number = {}, pages = {194-197}, pmid = {10093272}, issn = {1239-9736}, mesh = {Adolescent ; *Adolescent Nutritional Physiological Phenomena ; Arctic Regions ; Diet/*statistics & numerical data ; Energy Intake/physiology ; Ethnicity/*statistics & numerical data ; Female ; Health Planning/organization & administration ; Humans ; Male ; Nutrition Surveys ; Russia ; }, abstract = {We estimated nutrient and food intakes of adolescents aged 14 to 17 who inhabit the coastal and tundra zones of the Chukotka Autonomous Region, Russia, and developed approaches to improving their diet. We reassessed the dietary intakes of Native (n = 162) and non-Native (n = 155) adolescents of both sexes. We found that mean energy and nutrient intakes (protein, fat, carbohydrates) among schoolchildren were similar in different ethnic and sex groups. The diet of the subjects studied is high in sugar (18-19% of energy) and has an unfavorable fat composition, with saturated fatty acids (SFAs) contributing 14-15% of energy, and polyunsaturated fatty acids (PUFAs) contributing 5-6% of energy. Our results demonstrate that the children's diet approaches that of "Western society" to a greater extent than that of adults. A program on nutrition based on the national government project "Children of the North" has been developed at the Institute of Internal Medicine in collaboration with the Chukotka Sanitary and Epidemiology Supervision Services. This program includes the list of food products recommended for children. Some ecological factors and ethnic idiosyncrasies are considered.}, } @article {pmid10074166, year = {1999}, author = {Denisova, E and Dowling, W and LaMonica, R and Shaw, R and Scarlata, S and Ruggeri, F and Mackow, ER}, title = {Rotavirus capsid protein VP5* permeabilizes membranes.}, journal = {Journal of virology}, volume = {73}, number = {4}, pages = {3147-3153}, pmid = {10074166}, issn = {0022-538X}, support = {R01-AI31016/AI/NIAID NIH HHS/United States ; R03-AI42150/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biological Transport ; Capsid/*metabolism ; Capsid Proteins ; Cell Membrane Permeability ; Rotavirus/*physiology ; Virus Replication ; }, abstract = {Proteolytic cleavage of the VP4 outer capsid spike protein into VP8* and VP5* proteins is required for rotavirus infectivity and for rotavirus-induced membrane permeability. In this study we addressed the function of the VP5* cleavage fragment in permeabilizing membranes. Expressed VP5* and truncated VP5* proteins were purified by nickel affinity chromatography and assayed for their ability to permeabilize large unilamellar vesicles (LUVs) preloaded with carboxyfluorescein (CF). VP5* and VP5* truncations, but not VP4 or VP8*, permeabilized LUVs as measured by fluorescence dequenching of released CF. Similar to virus-induced CF release, VP5*-induced CF release was concentration and temperature dependent, with a pH optimum of 7.35 at 37 degrees C, but independent of the presence of divalent cations or cholesterol. VP5*-induced permeability was completely inhibited by VP5*-specific neutralizing monoclonal antibodies (2G4, M2, or M7) which recognize conformational epitopes on VP5* but was not inhibited by VP8*-specific neutralizing antibodies. In addition, N-terminal and C-terminal VP5* truncations including residues 265 to 474 are capable of permeabilizing LUVs. These findings demonstrate that VP5* permeabilizes membranes in the absence of other rotavirus proteins and that membrane-permeabilizing VP5* truncations contain the putative fusion region within predicted virion surface domains. The ability of recombinant expressed VP5* to permeabilize membranes should permit us to functionally define requirements for VP5*-membrane interactions. These findings indicate that VP5* is a specific membrane-permeabilizing capsid protein which is likely to play a role in the cellular entry of rotaviruses.}, } @article {pmid9928436, year = {1998}, author = {Joseph, JA and Denisova, N and Fisher, D and Shukitt-Hale, B and Bickford, P and Prior, R and Cao, G}, title = {Membrane and receptor modifications of oxidative stress vulnerability in aging. Nutritional considerations.}, journal = {Annals of the New York Academy of Sciences}, volume = {854}, number = {}, pages = {268-276}, doi = {10.1111/j.1749-6632.1998.tb09908.x}, pmid = {9928436}, issn = {0077-8923}, mesh = {Aging/*physiology ; Animals ; COS Cells ; Cell Membrane/*physiology ; *Cellular Senescence ; Humans ; *Nutritional Physiological Phenomena ; *Oxidative Stress ; PC12 Cells ; Rats ; Receptors, Cell Surface/*physiology ; Receptors, Muscarinic/genetics/*physiology ; Recombinant Proteins/metabolism ; Transfection ; }, abstract = {Evidence suggests that oxidative stress (OS) may contribute to the pathogenesis of age-related decrements in neuronal function and that OS vulnerability increases as a function of age. In addition to decreased endogenous protection, increases in OS vulnerability may result from changes in membrane lipids and distribution of receptor subtype. Using a PC-12 cell model system, we have shown that H2O2 or dopamine (DA) exposure induced deficits in the cell's ability to clear (extrude/sequester, E/S) Ca2+ that are similar to those seen in aging. When plasma membrane concentrations of sphingomyelin (SPM) were used, the SPM metabolite, sphingosine-1-phosphate was increased to the same levels as those seen in aging, and enhancement of OS-induced decreases in calcium E/S following KCL depolarization was observed. Differential decreases in CA2+ E/S were also seen following DA-induced OS in COS-7 cells transfected with one of five muscarinic receptor subtypes. Cells transfected with either M1, M2, or M4 receptors showed significantly greater vulnerability to OS (as expressed by greater decrements in calcium E/S and cell death) than those transfected with M3 or M5 receptors. The vitamin E analogue, Trolox, and the nitrone-trapping agent, PBN, were not effective in altering E/S decrements but were effective in preventing cell death 24 h after OS exposure. These findings suggest that putative regional (e.g., striatum and hippocampus) increases in OS vulnerability and loss of neuronal function in aging may be dependent upon membrane SPM concentration and receptor subtype. In related studies, attempts were made to determine whether increased OS protection via nutritional increases in antioxidant levels in rats [using diets supplemented with vitamin E (500IU/kg), strawberry extracts (9.4 g/kg dried aqueous extract, DAE), spinach (6.7 g/kg DAE), or blueberry extracts (10 g/kg DEA for six weeks)] would protect against exposure to 100% O2 (a model of accelerated neuronal aging). Results indicated that these diets were effective in preventing OS-induced decrements in several parameters (e.g., nerve growth factor decreases), suggesting that although there may be increases in OS vulnerability in aging, phytochemicals present in antioxidant-rich foods may be beneficial in reducing or retarding the functional central nervous system deficits seen in aging or oxidative insult.}, } @article {pmid9864825, year = {1998}, author = {Koroleva, GA and Lashkevich, VA and Denisova, EV and Tereshkina, NV and Khoroshilova-Maslova, IP and Katargina, LA and Lukashev, AN and Krichevskaia, GI and Khvatova, AV}, title = {[Enteroviral persistence in eye infections in monkeys (postuveitis syndrome)].}, journal = {Voprosy virusologii}, volume = {43}, number = {5}, pages = {204-216}, pmid = {9864825}, issn = {0507-4088}, mesh = {Animals ; Chlorocebus aethiops ; Enterovirus Infections/pathology/physiopathology/*virology ; Eye/*pathology ; Macaca ; Uveitis/pathology/physiopathology/*virology ; }, abstract = {Follow-up (5.5 years) of monkeys with a history of acute enterovirus uveitis (AEU) after intraocular infection with ophthalmotropic ECHO 11 and ECHO 19 strains showed progressive changes in the infected eye; destruction of the iris, formation of films in the anterior chamber of the eye, deformation of the pupil, and signs of cataract and glaucoma. A short (1-30 days) stage of active reproduction of infective virus (up to 10(10) TCD50/g tissue in the first days postinfection) was followed by the second very long stage of limited specific multiplication of virus in ocular tissues. The virus was not detected during the second stage, but its components (virusspecific antigen and crystalloid accumulations of virions) were found in ophthalmic and conjunctival tissues; moreover, high levels of neutralizing antibodies were detected in the blood. The results indicate AEU transformed into a stubborn persistent infection of the eye in monkeys. The findings of this follow-up and published reports about many-year follow-up of children with AEU permit us to classify a post-uveitis disease as a special nosological form of a persistent enterovirus infection and denote it as enterovirus post-uveitis syndrome. The main signs of this syndrome are a history of AEU, progressive destructive changes in the anterior segment of the eye, presence of virus components in ocular tissues in remote periods after infection, and high antibody level in the blood.}, } @article {pmid9742171, year = {1998}, author = {Joseph, JA and Shukitt-Hale, B and Denisova, NA and Prior, RL and Cao, G and Martin, A and Taglialatela, G and Bickford, PC}, title = {Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {18}, number = {19}, pages = {8047-8055}, pmid = {9742171}, issn = {0270-6474}, support = {AG04418/AG/NIA NIH HHS/United States ; AG007728/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*physiology ; Animals ; Antioxidants/pharmacology ; Body Weight ; Brain Chemistry/physiology ; Calcium Radioisotopes ; Cognition Disorders/*diet therapy ; Corpus Striatum/chemistry/metabolism ; Diet ; Dopamine/metabolism ; Eating ; Electrophysiology ; *Fruit ; GTP Phosphohydrolases/metabolism ; Male ; Norepinephrine/physiology ; Purkinje Cells/chemistry/enzymology ; Rats ; Rats, Inbred F344 ; Reactive Oxygen Species/physiology ; Signal Transduction/*drug effects ; *Spinacia oleracea ; Synaptosomes/chemistry/enzymology ; Time Factors ; Vitamin E/*pharmacology ; gamma-Aminobutyric Acid/analysis/physiology ; }, abstract = {Recent research has indicated that increased vulnerability to oxidative stress may be the major factor involved in CNS functional declines in aging and age-related neurodegenerative diseases, and that antioxidants, e.g., vitamin E, may ameliorate or prevent these declines. Present studies examined whether long-term feeding of Fischer 344 rats, beginning when the rats were 6 months of age and continuing for 8 months, with diets supplemented with a fruit or vegetable extract identified as being high in antioxidant activity, could prevent the age-related induction of receptor-mediated signal transduction deficits that might have a behavioral component. Thus, the following parameters were examined: (1) oxotremorine-enhanced striatal dopamine release (OX-K+-ERDA), (2) cerebellar beta receptor augmentation of GABA responding, (3) striatal synaptosomal 45Ca2+ clearance, (4) carbachol-stimulated GTPase activity, and (5) Morris water maze performance. The rats were given control diets or those supplemented with strawberry extracts (SE), 9.5 gm/kg dried aqueous extract (DAE), spinach (SPN 6.4 gm/kg DAE), or vitamin E (500 IU/kg). Results indicated that SPN-fed rats demonstrated the greatest retardation of age-effects on all parameters except GTPase activity, on which SE had the greatest effect, whereas SE and vitamin E showed significant but equal protection against these age-induced deficits on the other parameters. For example, OX-K+-ERDA enhancement was four times greater in the SPN group than in controls. Thus, phytochemicals present in antioxidant-rich foods such as spinach may be beneficial in retarding functional age-related CNS and cognitive behavioral deficits and, perhaps, may have some benefit in neurodegenerative disease.}, } @article {pmid9685344, year = {1998}, author = {Sawaya, BE and Khalili, K and Mercer, WE and Denisova, L and Amini, S}, title = {Cooperative actions of HIV-1 Vpr and p53 modulate viral gene transcription.}, journal = {The Journal of biological chemistry}, volume = {273}, number = {32}, pages = {20052-20057}, doi = {10.1074/jbc.273.32.20052}, pmid = {9685344}, issn = {0021-9258}, mesh = {Astrocytes/*virology ; Gene Expression Regulation, Viral/*genetics ; Gene Products, vpr/*physiology ; HIV Long Terminal Repeat/genetics ; HIV-1/*genetics ; Humans ; Mutation/genetics ; Sp1 Transcription Factor/physiology ; Suppression, Genetic/genetics ; Transcription, Genetic/genetics ; Transcriptional Activation/genetics ; Transfection/genetics ; Tumor Suppressor Protein p53/*physiology ; Viral Proteins/physiology ; vpr Gene Products, Human Immunodeficiency Virus ; }, abstract = {Transcription of the human immunodeficiency virus type-1 (HIV-1) genome is controlled by cooperative interaction of viral encoded proteins and host regulatory proteins. In this study, we have examined the capacity of the viral auxiliary protein, Vpr, to modulate transcriptional activity of the HIV-1 promoter sequence located within the long terminal repeat (LTR). We demonstrate that ectopic expression of Vpr in human astrocytic cells, U-87MG, enhances the basal activity of the viral promoter in transfected cells and that the GC-rich sequences, spanning nucleotides -80 to -43, are important for this activity. Since this region serves as the target for p53-induced suppression of LTR activity and interacts with the ubiquitous transcription factor, Sp1, we examined the cooperative activity of Vpr, p53, and Sp1 upon LTR transcription. Results from co-transfection studies indicated that overexpression of wild type p53, but not mutant p53, decreases the level of activation of the LTR by Vpr. Transcriptional activation of the LTR by Vpr required the presence of Sp1 since overexpression of Vpr in cells with no endogenous Sp1 failed to augment LTR activity. Results from protein-protein interaction studies indicated that Vpr is associated with both p53 and Sp1 in cells with ectopic expression of these proteins. Moreover, it was evident that p53 and Sp1 interact with each other in these cells. These functional and structural studies provided a working model on the cooperative interaction of Vpr with cellular proteins Sp1 and p53 and control of viral gene transcription at immediate early stage of infection prior to the participation of other viral regulatory proteins.}, } @article {pmid9680822, year = {1998}, author = {Denisova, LB and Platonova, AG and Demidov, IN and Emel'ianova, LN}, title = {[Computed tomography in refined diagnosis of abdominal aortic aneurysm: comparison of radiation therapies versus surgical outcomes and morphological studies of resected abdominal aortic fragments].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {3}, pages = {22-29}, pmid = {9680822}, issn = {0042-4676}, mesh = {Aged ; Aortic Dissection/diagnostic imaging/surgery ; Aorta, Abdominal/diagnostic imaging/pathology ; Aortic Aneurysm, Abdominal/*diagnostic imaging/surgery ; Aortic Rupture/diagnostic imaging/surgery ; Aortography ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Sensitivity and Specificity ; *Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {The results of computed tomography (CT) was compared with ultrasonographic and angiographic findings in 168 patients. All data of radiation diagnosis of abdominal aortic aneurysms (AAA) were compared with those of operations and morphological studies of the resected fragments of the aortic parts changed due to aneurysms. These comparisons provided a detailed characterization of the potentialities of CT performed on a third-generation unit in the presurgical diagnosis of this abnormality. At the same time, detailed XCT findings (semeiotics of AAA and their complications, such infiltration, dissection, and rupture) are given. The study shows benefits of the refined AAA by applying routine CT. The paper gives a diagnostic algorithm of using radiation studies (ultrasonography, CT, angiography) in the diagnosis of AAA. Third-generation CT units widely used in clinical practice are shown to provide necessary and complete information on the magnitude of AAA. This makes it possible to extend the capacities of timely detection of this abnormality and to make a successful surgical intervention.}, } @article {pmid9680665, year = {1998}, author = {Bushueva, TV and Vrzhesinskaia, OA and Kodentsova, VM and Rybakova, EP and Denisova, SN and Beketova, NA and Taranova, AG and Pereverzeva, OG and Kharitonchik, LA and Kopylova, NV}, title = {[Comparative study of special products "Tetraphen" and "Phenyl-free" in diet therapy of children with phenylketonuria].}, journal = {Voprosy pitaniia}, volume = {}, number = {2}, pages = {14-18}, pmid = {9680665}, issn = {0042-8833}, mesh = {Biomarkers/blood/urine ; Child ; *Child Nutritional Physiological Phenomena ; *Diet, Protein-Restricted ; Dietary Carbohydrates/administration & dosage/metabolism ; Dietary Fats/administration & dosage/metabolism ; Dietary Proteins/administration & dosage/metabolism ; Female ; *Food, Formulated ; Humans ; Male ; Phenylketonurias/blood/*diet therapy/urine ; Vitamins/analysis/metabolism ; }, abstract = {Basing on the comparative clinical and biochemical evaluation of the usage of the specialized product "Tetraphen" (Russia) and early utilized product "Phenyl-Free" (USA) it has been shown that "Tetraphen" does not yield to "Phenyl-Free", while some of its parameters (energy value, carbohydrate content) even in the higher degree correspond to the physiologic requirements of this aged children suffering from phenylketonuria. Intake of this product in smaller doses completely covers their requirements for the basic food ingredients. High frequency of carotenoids insufficiency in children received both "Tetraphen" and "Phenyl-Free" demonstrate necessity of the diet correction by means of beta-carotene additional supplementation.}, } @article {pmid9670843, year = {1998}, author = {Sawaya, BE and Thatikunta, P and Denisova, L and Brady, J and Khalili, K and Amini, S}, title = {Regulation of TNFalpha and TGFbeta-1 gene transcription by HIV-1 Tat in CNS cells.}, journal = {Journal of neuroimmunology}, volume = {87}, number = {1-2}, pages = {33-42}, doi = {10.1016/s0165-5728(98)00044-7}, pmid = {9670843}, issn = {0165-5728}, mesh = {Brain/*drug effects/pathology ; Gene Products, tat/genetics/*pharmacology ; HIV-1/*genetics ; Humans ; Jurkat Cells/drug effects/physiology ; Mutation ; RNA, Messenger/metabolism ; Transcription, Genetic/*drug effects ; Transcriptional Activation/genetics ; Transforming Growth Factor beta/*genetics ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/*genetics ; tat Gene Products, Human Immunodeficiency Virus ; }, abstract = {Tat is a transcription transactivator produced by the human immunodeficiency virus type 1 (HIV-1) at the early phase of infection and plays a critical role in the expression and replication of the viral genome. This 86 amino acid protein, which can be secreted from the infected cells, has the ability to enter uninfected cells and exert its activity upon the responsive genes. Earlier results indicated that in addition to the HIV-1 promoter, Tat has the capacity to induce transcription of a variety of cellular genes. In this study, we demonstrate that exposure of cells from the central nervous system (U-87MG and SK-N-MC) and the lymphoid T cells (Jurkat) to highly purified Tat increases transcriptional activity of the reporter constructs containing the promoters from the transforming growth factor beta-1 (TGFbeta-1), the tumor necrosis factor alpha (TNFalpha), and the HIV-1 LTR. In addition, Tat treatment results in increased levels of TGFbeta-1 and TNFalpha mRNAs in these cells. Activation of the TGFbeta-1 and TNFalpha promoter constructs by Tat in U-87MG and SK-N-MC cells required amino acid residues 2 to 36 which spans the acidic and the cysteine-rich domains of Tat. In both CNS and lymphoid cells, the level of endogenous TGFbeta-1 mRNA was increased by mutant Tat protein containing amino acids 1 to 48 but not with a mutant Tat protein with a deletion between residues 2 to 36. TNFalpha mRNA level was increased by mutant Tat spanning residues 1 to 48 in U-87MG cells, but not in SK-N-MC and Jurkat cells. These observations suggest that activation of cellular and viral genes by Tat in various cells may be mediated by different pathways as evidenced by the requirements of the different regions of Tat. Activation of the TGFbeta-1 and TNFalpha promoters by wild-type Tat was severely affected by the mutant peptides spanning residues 2 to 36 and 1 to 48 suggesting that both truncated Tat peptides may function as dominant negative mutants over TNFalpha and TGFbeta-1 gene transcription. The importance of these findings in Tat-induced regulation of viral and cellular genes in various cell types is discussed.}, } @article {pmid9666048, year = {1998}, author = {Joseph, JA and Denisova, N and Fisher, D and Bickford, P and Prior, R and Cao, G}, title = {Age-related neurodegeneration and oxidative stress: putative nutritional intervention.}, journal = {Neurologic clinics}, volume = {16}, number = {3}, pages = {747-755}, doi = {10.1016/s0733-8619(05)70092-x}, pmid = {9666048}, issn = {0733-8619}, mesh = {Aging/*physiology ; Humans ; Neurodegenerative Diseases/*diet therapy ; Oxidative Stress/*physiology ; }, abstract = {This review describes age-related changes that occur in neuronal function and cites evidence to show that these alterations may be the result of increased sensitivity to oxidative stress (OS). Evidence is presented to show that the abilities to mitigate the OS effects and to repair the damage from OS show decline as a function of age. Results from age- and OS-sensitive tests are given; these results indicate that one of the major sites of action of OS is the membranes, especially if compromised by high amounts of sphingomyelin, and one of the major effects of OS is to further alter the calcium disregulation in aging. It is suggested that attempts to increase antioxidant protection through diets comprised of fruits and vegetables identified as being high in total antioxidant activity might prevent or reverse the deleterious OS effects on neuronal aging.}, } @article {pmid9615923, year = {1998}, author = {Denisova, NA and Erat, SA and Kelly, JF and Roth, GS}, title = {Differential effect of aging on cholesterol modulation of carbachol-stimulated low-K(m) GTPase in striatal synaptosomes.}, journal = {Experimental gerontology}, volume = {33}, number = {3}, pages = {249-265}, doi = {10.1016/s0531-5565(97)00096-x}, pmid = {9615923}, issn = {0531-5565}, mesh = {Aging/*physiology ; Animals ; Carbachol/metabolism/*pharmacology ; Cholesterol/*pharmacology ; Corpus Striatum/drug effects/*metabolism ; GTP Phosphohydrolases/*metabolism ; Male ; Membranes/drug effects/physiology ; Phospholipids/metabolism ; Rats ; Rats, Wistar ; Receptors, Muscarinic/metabolism ; Synaptosomes/drug effects/*metabolism ; Viscosity ; }, abstract = {Previous research has suggested that age-related decline in physiological functions may be the result of substantial alterations in membrane molecular structure. The purpose of the present experiments was to elucidate the role of cholesterol domains in the age-related decline in receptor-G-protein interactions in striatal synaptosomes. We observed a significant age-related deficit in muscarinic cholinergic stimulated Low-Km GTPase activity and its age-related susceptibility to cholesterol treatment in range of 10(-10)-10(-5) M. Treatment of synaptosomes from old rats with cholesterol in range of 10(-8)-10(-6) M restored the Low-Km GTPase activity up to the level seen in young animals and reached a maximum at 10(-7) M. In synaptosomes from young rats, however, cholesterol treatment did not have any effect on striatal Low-Km GTPase activity. We observed significant alterations in the membrane lipid composition of striatal synaptosomes as a function of age. Our results suggested a significant interaction of age and cholesterol treatment on physical properties of striatal synaptosomes. Thus, the present results of experiments in vitro support our previous results of experiments in vivo and suggested an interaction of cholesterol domains with muscarinic-cholinergic receptor G-protein alpha subunit coupling/uncoupling through regulation of physical properties of striatal synaptosomes.}, } @article {pmid9606860, year = {1998}, author = {Denisova, SN and Kutafina, EK and Sergeeva, TV and Savina, MI and Kon', IIa and Shilina, NM and Chizhevskaia, OL and Shilov, AV}, title = {[Effect of vitamin D metabolites on the markers of protein, calcium and phosphorus turnover in children with chronic renal failure].}, journal = {Voprosy pitaniia}, volume = {}, number = {1}, pages = {14-17}, pmid = {9606860}, issn = {0042-8833}, mesh = {Adolescent ; Amino Acids/blood ; Biomarkers/blood ; Calcium/*blood ; Child ; Chronic Kidney Disease-Mineral and Bone Disorder/blood/complications/drug therapy ; Feces/chemistry ; Humans ; Kidney Failure, Chronic/blood/complications/*drug therapy ; Nitrogen/blood/urine ; Phosphorus/*blood ; Proteins/*metabolism ; Vitamin D/*analogs & derivatives/*therapeutic use ; }, abstract = {Amino acid analysis and investigation of nitrogen, calcium and phosphorus balance were done in two groups of the patients with renal failure and osteodystrophy on the Vitamin D metabolites and analogues treatment. The results of the investigation confirm vitamin D metabolites influence on free amino acid turnover and on nitrogen, calcium, phosphorus balance. We observed significant decreases of blood amino acids and good influence on renal osteodystrophy in patients treated with the vitamin D metabolites. Vitamin D metabolites didn't influence on the retention, urinary and fecal excretion of endogenous nitrogen in patients with renal failure.}, } @article {pmid9573233, year = {1998}, author = {Sullivan, N and Sun, Y and Sattentau, Q and Thali, M and Wu, D and Denisova, G and Gershoni, J and Robinson, J and Moore, J and Sodroski, J}, title = {CD4-Induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: consequences for virus entry and neutralization.}, journal = {Journal of virology}, volume = {72}, number = {6}, pages = {4694-4703}, pmid = {9573233}, issn = {0022-538X}, support = {R37 AI024755/AI/NIAID NIH HHS/United States ; R01 AI031783/AI/NIAID NIH HHS/United States ; R01 AI039420/AI/NIAID NIH HHS/United States ; AI 39420/AI/NIAID NIH HHS/United States ; R37 AI036082/AI/NIAID NIH HHS/United States ; AI 24755/AI/NIAID NIH HHS/United States ; R01 AI036082/AI/NIAID NIH HHS/United States ; AI 36082/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/chemistry ; CD4 Antigens/*chemistry/physiology ; COS Cells ; Cross-Linking Reagents ; HIV Envelope Protein gp120/*chemistry/physiology ; HIV-1/*physiology ; Humans ; Jurkat Cells ; *Protein Conformation ; Temperature ; *Virus Replication ; }, abstract = {Human immunodeficiency virus type 1 (HIV-1) entry into target cells involves sequential binding of the gp120 exterior envelope glycoprotein to CD4 and to specific chemokine receptors. Soluble CD4 (sCD4) is thought to mimic membrane-anchored CD4, and its binding alters the conformation of the HIV-1 envelope glycoproteins. Two cross-competing monoclonal antibodies, 17b and CG10, that recognize CD4-inducible gp120 epitopes and that block gp120-chemokine receptor binding were used to investigate the nature and functional significance of gp120 conformational changes initiated by CD4 binding. Envelope glycoproteins derived from both T-cell line-adapted and primary HIV-1 isolates exhibited increased binding of the 17b antibody in the presence of sCD4. CD4-induced exposure of the 17b epitope on the oligomeric envelope glycoprotein complex occurred over a wide range of temperatures and involved movement of the gp120 V1/V2 variable loops. Amino acid changes that reduced the efficiency of 17b epitope exposure following CD4 binding invariably compromised the ability of the HIV-1 envelope glycoproteins to form syncytia or to support virus entry. Comparison of the CD4 dependence and neutralization efficiencies of the 17b and CG10 antibodies suggested that the epitopes for these antibodies are minimally accessible following attachment of gp120 to cell surface CD4. These results underscore the functional importance of these CD4-induced changes in gp120 conformation and illustrate viral strategies for sequestering chemokine receptor-binding regions from the humoral immune response.}, } @article {pmid9590633, year = {1998}, author = {Miller, SL and Denisova, L}, title = {Cycloserine-induced decrease of cerebroside in myelin.}, journal = {Lipids}, volume = {33}, number = {4}, pages = {441-443}, pmid = {9590633}, issn = {0024-4201}, support = {NS26844/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Antibiotics, Antitubercular/administration & dosage/*pharmacology ; Body Weight/drug effects ; Brain/*anatomy & histology/drug effects/metabolism ; Brain Chemistry/drug effects ; Cycloserine/administration & dosage/*pharmacology ; Female ; Galactosylceramides/*metabolism ; Myelin Sheath/*chemistry/*drug effects/metabolism ; Organ Size/drug effects ; Phospholipids/metabolism ; Proteins/drug effects/metabolism ; Rats ; Rats, Wistar ; }, abstract = {L-Cycloserine has been shown specifically to lower brain cerebroside levels in vivo, but the extent to which the decrease in whole brain cerebroside content reflects lower myelin cerebroside levels is not known since a substantial portion of cerebroside is found in nonmyelin membranes. The present report demonstrates that chronically administered cycloserine lowers the proportion of cerebroside in rat brain myelin. Cycloserine-induced decrease of myelin cerebroside should provide a useful tool in investigating the role of cerebroside in maintaining myelin stability.}, } @article {pmid9586813, year = {1998}, author = {Joseph, JA and Erat, S and Denisova, N and Villalobos-Molina, R}, title = {Receptor- and age-selective effects of dopamine oxidation on receptor-G protein interactions in the striatum.}, journal = {Free radical biology & medicine}, volume = {24}, number = {5}, pages = {827-834}, doi = {10.1016/s0891-5849(97)00379-1}, pmid = {9586813}, issn = {0891-5849}, mesh = {Aging/*metabolism ; Animals ; Antioxidants/pharmacology ; Chromans/pharmacology ; Corpus Striatum/*metabolism ; Dopamine/*metabolism ; Dopamine Agonists/pharmacology ; Free Radicals ; GTP-Binding Proteins/*metabolism ; In Vitro Techniques ; Muscarinic Agonists/pharmacology ; Nerve Tissue Proteins/*metabolism ; Oxidation-Reduction ; Rats ; Rats, Inbred F344 ; Receptors, Dopamine/*metabolism ; Serotonin Receptor Agonists/pharmacology ; Vitamin E/analogs & derivatives ; }, abstract = {The striatum contains a high concentration of oxidizable dopamine (DA), and the aged organism shows a decreased ability to respond to oxidative stress (OS), making this area extremely vulnerable to free radical insult. To determine the receptor specificity of this putative increase in OS sensitivity, striatal slices from 6- and 24-month-old animals were incubated (30 min, 37 degrees C) in a modified Krebs medium containing 0 to 500 microM DA with or without a preincubation (15 min) in a nitrone trapping agent, 1 or 5 mM alpha-phenyl-n-tert-butyl nitrone (PBN), and changes in low Km GTPase activity (an index of receptor-G protein coupling/uncoupling) assessed in muscarinic, 5-HT1A D1, and D2 receptors stimulated with carbachol, 8 OH-DPAT-HBr, SKF 38393, or quinelorane, respectively. DA exposure induced selective decreases in the stimulated activity in all of these receptor systems, and an overall increase in conjugated dienes (56%) of the young. In the case of carbachol and 8 OH-DPAT-HBr, the DA-induced deficits in GTPase stimulation were seen primarily in the young (61 and 32%, respectively), while DA-induced deficits in quinelorane (D2) stimulation were seen in both age groups. In the case of SKF 38393-stimulation (D1) the DA-induced deficits were higher in the striatal tissue from the old. The DA-induced decreases in carbachol stimulated GTPase activity in the tissue from the young could be prevented by pretreatment with PBN or the DA uptake inhibitor, nomifensin. No effect of nomifensin was seen in the old, because their DA uptake mechanisms were already compromised. These results suggest that although age-related declines in DA uptake may provide some protection against the OS effects in muscarinic or 5-HT1A receptors, other factors may increase the vulnerability of DA neurons to OS, even with reductions in DA uptake.}, } @article {pmid9532679, year = {1998}, author = {Adlova, GP and Denisova, SV and Ilidzhev, AK and Smirnova, GA and Ratnikova, TN and Arep'eva, AA and Mel'nikova, VA}, title = {[The development of bacterial growth stimulants from plants].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {1}, pages = {13-17}, pmid = {9532679}, issn = {0372-9311}, mesh = {Bacteria/*drug effects/growth & development ; Dose-Response Relationship, Drug ; Escherichia coli/drug effects/growth & development ; Growth Substances/*pharmacology ; Plant Extracts/*pharmacology ; Seasons ; Solutions ; Stimulation, Chemical ; Streptococcus pyogenes/drug effects/growth & development ; }, abstract = {Dried bacterial growth stimulators in the form of water extracts of wild marjoram were developed; they produced a stimulating effect on Escherichia coli and Streptococcus pyogenes Dick 1 and had no influence on the growth of Corynebacterium xerosis 1911. The study aimed at finding out the active principle of the stimulator prepared from marjoram extract revealed that under experimental conditions marjoram extract could be divided into 3 fractions of these: fraction 1 contained terpenic hydrocarbons, fraction 2 contained vitamins and vitamin-like substances, fraction 3 contained phenols, flavonoids, phenolcarbonic and fatty acids. Fraction 3 at a concentration of 0.0001% produced the best effect. The stimulating effect of extracts obtained from lime and aspen leaves, haw berries was demonstrated.}, } @article {pmid9508745, year = {1997}, author = {Krichevskaia, GI and Katargina, LA and Andzhelov, VO and Khvatova, AV and Koroleva, GA and Denisova, EV and Lashkevich, VA}, title = {[Persistence of ophthalmotropic enteroviruses in ocular tissues after enterovirus uveitis].}, journal = {Vestnik oftalmologii}, volume = {113}, number = {5}, pages = {26-29}, pmid = {9508745}, issn = {0042-465X}, mesh = {Animals ; Antibodies, Viral/analysis ; Antigens, Viral/analysis ; Child ; Disease Models, Animal ; Enterovirus/immunology/isolation & purification/*pathogenicity ; Enterovirus Infections/immunology/pathology/*virology ; Eye/pathology/*virology ; Eye Infections, Viral/immunology/pathology/*virology ; Fluorescent Antibody Technique, Direct ; Follow-Up Studies ; Haplorhini ; Humans ; Uveitis/immunology/pathology/*virology ; }, abstract = {Thirteen monkeys were infected with ophthalmotropic strains of ECHO11 and ECHO19 in the anterior chamber of one eye. Echovirus antigens were detected by direct immunofluorescence in the membranes of the infected and paired eyes in various periods after inoculation (from 3 days to 5 years 8 months). Virus antigen was detected both in the infected and intact eyes. During the acute period of uveitis the antigen was detected mainly in the anterior segment of the infected eye, whereas in remote period it was found mainly in the posterior segment. Long persistence of the virus antigen in various ocular membranes may explain many of the late complications observed in children with enterovirus uveitis.}, } @article {pmid9483996, year = {1997}, author = {Katargina, LA and Khvatova, AV and Denisova, EV and Koroleva, GA and Krichevskaia, GI and Andzhelov, VO}, title = {[Clinical and experimental parallels in children with enterovirus uveitis].}, journal = {Vestnik oftalmologii}, volume = {113}, number = {6}, pages = {25-27}, pmid = {9483996}, issn = {0042-465X}, mesh = {Acute Disease ; Animals ; Anterior Chamber/virology ; Child ; Disease Models, Animal ; Echovirus Infections/*pathology/virology ; Enterovirus B, Human/*physiology ; Eye Infections, Viral/*pathology/virology ; Follow-Up Studies ; Haplorhini ; Humans ; Uveitis/*pathology/virology ; }, abstract = {Clinical features of acute and remote periods of experimental enterovirus uveitis were studied. The disease was induced in 22 monkeys by inoculation of ECHO 11 and ECHO 19 strains in the anterior chamber. The animals were followed up for 3 months to 5 years 8 months. The main clinical manifestations of the acute and remote periods of experimental disease were similar to its clinical presentation in children. The developed experimental model can be used to study the pathogenesis of complications of enterovirus uveitis.}, } @article {pmid9383706, year = {1997}, author = {Thatikunta, P and Sawaya, BE and Denisova, L and Cole, C and Yusibova, G and Johnson, EM and Khalili, K and Amini, S}, title = {Identification of a cellular protein that binds to Tat-responsive element of TGF beta-1 promoter in glial cells.}, journal = {Journal of cellular biochemistry}, volume = {67}, number = {4}, pages = {466-477}, pmid = {9383706}, issn = {0730-2312}, mesh = {Astrocytes ; Base Sequence ; Binding Sites ; Cell Line ; DNA Footprinting ; DNA Primers ; Gene Products, tat/biosynthesis/*metabolism ; HIV-1/genetics/metabolism ; Humans ; Molecular Sequence Data ; Neuroglia/*metabolism ; Polymerase Chain Reaction ; *Promoter Regions, Genetic ; Recombinant Proteins/biosynthesis/metabolism ; Transfection ; Transforming Growth Factor beta/*biosynthesis/*genetics ; tat Gene Products, Human Immunodeficiency Virus ; }, abstract = {Tat is a transcriptional transactivator produced by the human immunodeficiency virus type 1 (HIV-1) and plays a pivotal role in enhancing expression of the viral genome in the infected cells. Although initial studies have suggested that interaction of Tat with the transactivation responsive element (TAR); located within the LTR, is essential for Tat function, subsequent studies indicated that Tat has the ability to augment transcription of viral and cellular genes by a TAR-independent mechanism. In early studies we demonstrated that HIV-1 Tat stimulates transcription of the transforming growth factor, TGF beta-1, gene in glial cells. In this study, we have identified a cellular protein that interacts with the Tat-responsive region located between nucleotides -323 to -453 of the regulatory sequence of the TGF beta-1 promoter. Results from footprinting analysis revealed association of cellular proteins with the 130 nucleotide sequence located in the Tat-responsive region. Analysis of the associated protein by UV-crosslinking suggested the involvement of a protein between 40-45 kDa in size which preferentially interacts with the GC/GA rich sequence of the TGF beta-1 Tat-responsive sequence in a single-stranded configuration. The ability of the previously identified 40 kDa protein, named Pur alpha to bind to the GC/GA sequence in the single-stranded configuration, similar to those from TGF beta-1 promoter prompted us to investigate its binding capacity to the TGF beta-1 sequence and its transcriptional activity on the TGF beta-1 promoter. Results from band shift studies indicated the association of the bacterially produced Pur alpha to the TGF beta-1 DNA sequences positioned within the Tat-responsive region. Overexpression of Pur alpha in glial cells constitutively producing Tat augmented transcription of the TGF beta-1 gene. These results are consistent with previous reports on the cooperative action of Pur alpha and Tat in modulating other eukaryotic promoters. The importance of these findings with regard to deregulation of other cellular genes by HIV-1 Tat is discussed.}, } @article {pmid9282951, year = {1997}, author = {Denisova, NA and Strain, JG and Joseph, JA}, title = {Oxidant injury in PC12 cells--a possible model of calcium "dysregulation" in aging: II. Interactions with membrane lipids.}, journal = {Journal of neurochemistry}, volume = {69}, number = {3}, pages = {1259-1266}, doi = {10.1046/j.1471-4159.1997.69031259.x}, pmid = {9282951}, issn = {0022-3042}, mesh = {Aging/*physiology ; Analysis of Variance ; Animals ; Calcium/*metabolism ; Cholesterol/metabolism/pharmacology ; Homeostasis ; Hydrogen Peroxide/*toxicity ; Kinetics ; Membrane Lipids/*metabolism ; Models, Neurological ; *Oxidative Stress ; PC12 Cells ; Phospholipids/*metabolism ; Potassium/pharmacology ; Rats ; Sphingomyelins/metabolism/pharmacology ; }, abstract = {In a model recently developed to study the parameters altering vulnerability to oxidative stress, it was shown via image analysis that H2O2-exposed PC12 cells exhibited increased levels of intracellular Ca2+ (baseline), decreases in K+-stimulated Ca2+ levels (peak), and decreased poststimulation Ca2+ clearance (recovery). The present experiments were performed to determine if the response patterns in these parameters to oxidative stress would be altered after modification of membrane lipid composition induced by incubating the PC12 cells with 660 microM cholesterol (CHL) in the presence or absence of 500 microM sphingomyelin (SPH) before low (5 microM) or high (300 microM) H2O2 exposure. Neither CHL nor SPH had synergistic effects with high concentrations of H2O2 on baseline. However, CHL in the presence or absence of SPH reversed the effect of low concentrations of H2O2 on baseline. SPH decreased significantly the cell's ability to clear excess Ca2+ in the presence or absence of H2O2 and increased significantly the level of conjugated dienes (CDs). It is surprising that in the cells pretreated with CHL, the CD levels were not significantly different from controls. However, in the presence of SPH, the effects of CHL on CDs were altered. These results suggest that the ratios of membrane lipids could be of critical importance in determining the vulnerability to oxidative stress and Ca2+ translocation in membranes. This may be of critical importance in aging where there is increased membrane SPH and significant loss of calcium homeostasis.}, } @article {pmid9295190, year = {1997}, author = {Tian, M and Hagg, T and Denisova, N and Knusel, B and Engvall, E and Jucker, M}, title = {Laminin-alpha2 chain-like antigens in CNS dendritic spines.}, journal = {Brain research}, volume = {764}, number = {1-2}, pages = {28-38}, doi = {10.1016/s0006-8993(97)00420-4}, pmid = {9295190}, issn = {0006-8993}, mesh = {Animals ; Blotting, Western ; Cells, Cultured ; Central Nervous System/*metabolism/ultrastructure ; Dendrites/*metabolism/ultrastructure ; Immunohistochemistry ; Laminin/immunology/*metabolism ; Male ; Microscopy, Immunoelectron ; Rabbits ; Rats ; Rats, Inbred F344 ; Rats, Sprague-Dawley ; Synaptosomes/drug effects/metabolism ; }, abstract = {The laminin-alpha2 chain is a component of brain capillary basement membranes and appears also to be present in neurons of rat, rabbit, pig and non-human primate brain as evidenced by immunohistochemistry. In the present study, we have further characterized this very distinct neuronal laminin-alpha2 chain-like immunoreactivity in the hippocampus of various species. Immunoelectron microscopy with poly- and monoclonal antibodies to the laminin-alpha2 chain G-domain localized laminin-alpha2 chain immunoreactivity in adult rat and rabbit hippocampus to dendritic processes, primarily to dendritic spines. In the developing rat hippocampus, spine-associated laminin-alpha2 chain-like immunoreactivity first appeared at a time corresponding to that of active synaptogenesis. After an entorhinal cortex lesion in adult rats, the time course of denervation-induced loss and reactive reappearance of spines in the molecular layer of the dentate gyrus was correlated closely to the loss and reappearance of laminin-alpha2 chain immunoreactivity. Immunoblot analysis of normal adult rat, rabbit and pig brain revealed a protein similar in size to the reported 80-kDa laminin-alpha2 chain fragment of human placenta as well as 140/160-kDa proteins. These results suggest the presence of proteins with antigenic homology to the laminin-alpha2 chain and/or laminin-alpha2 isoforms in dendrites and dendritic spines in selected areas of the brain, predominately in the hippocampus and other limbic structures. Given the adhesion and neurite promoting functions of laminins, it is possible that neuronal laminin-alpha2 chain-like proteins play a role in synaptic function and plasticity in the CNS.}, } @article {pmid9223495, year = {1997}, author = {Lee, S and Peden, K and Dimitrov, DS and Broder, CC and Manischewitz, J and Denisova, G and Gershoni, JM and Golding, H}, title = {Enhancement of human immunodeficiency virus type 1 envelope-mediated fusion by a CD4-gp120 complex-specific monoclonal antibody.}, journal = {Journal of virology}, volume = {71}, number = {8}, pages = {6037-6043}, pmid = {9223495}, issn = {0022-538X}, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; CD4 Antigens/*physiology ; Chemokine CCL4 ; HIV Envelope Protein gp120/*physiology ; HIV-1/*physiology ; HeLa Cells ; Humans ; Immunoglobulin Fab Fragments/immunology ; Macrophage Inflammatory Proteins/physiology ; Mice ; Mice, Inbred BALB C ; Tetradecanoylphorbol Acetate/pharmacology ; }, abstract = {The entry of human immunodeficiency virus type 1 (HIV-1) into cells is initiated by binding of the viral glycoprotein gp120-gp41 to its cellular receptor CD4. The gp120-CD4 complex formed at the cell surface undergoes conformational changes that may allow its association with an additional membrane component(s) and the eventual formation of the fusion complex. These conformational rearrangements are accompanied by immunological changes manifested by altered reactivity with monoclonal antibodies specific for the individual components and presentation of new epitopes unique to the postbinding complex. In order to analyze the structure and function of the gp120-CD4 complex, monoclonal antibodies were generated from splenocytes of BALB/c mice immunized with soluble CD4-gp120 (IIIB) molecules (J. M. Gershoni, G. Denisova, D. Raviv, N. I. Smorodinsky, and D. Buyaner, FASEB J. 7:1185-1187 1993). One of those monoclonal antibodies, CG10, was found to be strictly complex specific. Here we demonstrate that this monoclonal antibody can significantly enhance the fusion of CD4+ cells with effector cells expressing multiple HIV-1 envelopes. Both T-cell-line-tropic and macrophage-tropic envelope-mediated cell fusion were enhanced, albeit at different optimal doses. Furthermore, infection of HeLa CD4+ (MAGI) cells by HIV-1 LAI, ELI1, and ELI2 strains was increased two- to fourfold in the presence of CG10 monoclonal antibodies, suggesting an effect on viral entry. These findings indicate the existence of a novel, conserved CD4-gp120 intermediate structure that plays an important role in HIV-1 cell fusion.}, } @article {pmid9304260, year = {1997}, author = {Pigolkin, IuI and Denisova, OP and Komarov, SV}, title = {[The forensic medical diagnosis of kidney trauma].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {40}, number = {3}, pages = {6-8}, pmid = {9304260}, issn = {0039-4521}, mesh = {Accidental Falls ; Adolescent ; Autopsy ; Humans ; Kidney/*injuries/pathology/surgery ; Male ; Nephrectomy ; Reoperation ; Rupture/etiology/pathology/surgery ; Time Factors ; Wounds, Stab/complications/*pathology/surgery ; }, abstract = {Penetrating cut wounds of the chest and abdomen involving the perirenal fat can be complicated by chronic inflammations of the kidney. Latent progress of the pathological process in the kidney and perirenal fat caused paranephritis which was diagnosed only 51 days after the injury and removal of the kidney. This case once again confirms that pathologically changed organs (kidneys) are liable to be injured even during a slight indirect traumatic exposure, for example, just falling on the plane surface.}, } @article {pmid9108796, year = {1997}, author = {Schick, PK and Walker, J and Profeta, B and Denisova, L and Bennett, V}, title = {Synthesis and secretion of von Willebrand factor and fibronectin in megakaryocytes at different phases of maturation.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {17}, number = {4}, pages = {797-801}, doi = {10.1161/01.atv.17.4.797}, pmid = {9108796}, issn = {1079-5642}, support = {HL-25455/HL/NHLBI NIH HHS/United States ; HL-51481/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cytoplasmic Granules/metabolism ; Fibronectins/*biosynthesis/*metabolism ; Guinea Pigs ; Megakaryocytes/cytology/*metabolism ; Molecular Weight ; Precipitin Tests ; von Willebrand Factor/*biosynthesis/*metabolism ; }, abstract = {Our goals have been to define the biochemical characteristics of megakaryocytes during maturation that are critical for platelet assembly and release into the circulation and to introduce biochemical markers for megakaryocytes. To achieve these goals, we have studied fibronectin (FN) and von Willebrand factor (vWF), which are large adhesive proteins that are synthesized by megakaryocytes, stored in alpha granules, and thought to have a fundamental role in hemostasis. The study demonstrated that vWF is primarily synthesized in mature megakaryocytes, which synthesized 7.5 times more vWF than immature megakaryocytes. Brefeldin A, which blocks the exit of proteins from the rough endoplasmic reticulum (RER), inhibited the formation of vWF multimers but did not affect the synthesis of monomers and dimers in mature megakaryocytes. These data are consistent with the formation of vWF dimers in the RER and the assembly of vWF multimers in the trans- and post-golgi. The synthesis of both the 260-kD and 275-kD pro-vWF was detected. However, the synthesis of 275-kD pro-vWF and 220-kD mature vWF was only evident after 2 hours, suggesting that the transit time of nascent vWF through the RER is about 2 hours. Constitutive secretion of vWF was demonstrated in megakaryocytes. About 14.5% and 4.6% of synthesized vWF was secreted by mature and immature megakaryocytes, respectively. In contrast, the synthesis of FN monomers and dimers was established in immature megakaryocytes, and their synthesis in mature megakaryocytes was very similar. Constitutive secretion of FN was not seen in megakaryocytes. Brefeldin A did not inhibit the synthesis of FN dimers; thus, formation of FN dimers occurs in the RER. The demonstration that vWF and FN are synthesized at different phases of megakaryocyte maturation and that only vWF is constitutively secreted by megakaryocytes provides new information relevant to alpha granule formation and possibly bone marrow matrix assembly.}, } @article {pmid9078681, year = {1997}, author = {Gershoni, JM and Stern, B and Denisova, G}, title = {Combinatorial libraries, epitope structure and the prediction of protein conformations.}, journal = {Immunology today}, volume = {18}, number = {3}, pages = {108-110}, doi = {10.1016/s0167-5699(97)01024-4}, pmid = {9078681}, issn = {0167-5699}, mesh = {Amino Acid Sequence ; Epitope Mapping ; Epitopes/*chemistry/*genetics ; Gene Library ; HIV Envelope Protein gp120/chemistry/genetics/immunology ; HIV-1/chemistry/genetics/immunology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; }, } @article {pmid9039957, year = {1997}, author = {Stern, B and Denisova, G and Buyaner, D and Raviv, D and Gershoni, JM}, title = {Helical epitopes determined by low-stringency antibody screening of a combinatorial peptide library.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {11}, number = {2}, pages = {147-153}, doi = {10.1096/fasebj.11.2.9039957}, pmid = {9039957}, issn = {0892-6638}, mesh = {Amino Acid Sequence/immunology ; Animals ; Antibodies, Monoclonal/*chemistry ; Antibody Affinity ; Coliphages/genetics ; Epitopes/*chemistry/immunology ; Genetic Vectors ; HIV Envelope Protein gp120/immunology ; HIV-1/immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Peptides/*chemistry/genetics/*immunology ; *Protein Structure, Secondary ; Sequence Homology, Amino Acid ; }, abstract = {Combinatorial phage display peptide libraries are routinely used to map epitopes of specific monoclonal antibodies. In this study we illustrate that these libraries can be used in the analysis of protein structure. By screening libraries at low stringency, a collection of phages can be obtained. These are characterized by the fact that they are recognized by a given monoclonal antibody yet with various affinities. Comparing the random peptides of these phages indicates the common essential residues necessary for antibody recognition. Aligning the inserts based on the detected homology has revealed structural motifs that correspond to secondary protein structures. The envelope protein of HIV-1 has been studied using this approach. A combinatorial phage display library containing a 20 mer random peptide in protein III of the filamentous phage fd-tet has been used to analyze two different monoclonal antibodies directed against gp120. Our results provide experimental evidence that indicate that the C1 domain of gp120 contains an alpha helix.}, } @article {pmid9013955, year = {1997}, author = {Denisova, G and Raviv, D and Mondor, I and Sattentau, QJ and Gershoni, JM}, title = {Conformational transitions in CD4 due to complexation with HIV envelope glycoprotein gp120.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {158}, number = {3}, pages = {1157-1164}, pmid = {9013955}, issn = {0022-1767}, mesh = {Animals ; Antibodies, Monoclonal/immunology ; Binding, Competitive ; CD4 Antigens/chemistry/*ultrastructure ; CD4-Positive T-Lymphocytes/immunology ; Epitope Mapping ; HIV Envelope Protein gp120/chemistry/*ultrastructure ; Humans ; Macromolecular Substances ; Mice ; Mice, Inbred BALB C ; Protein Binding ; Protein Conformation ; Sequence Deletion ; Solubility ; }, abstract = {The binding of the surface envelope glycoprotein gp120 to its receptor, CD4, has been well characterized and is the primary basis for the cell tropism of HIV. In this study, the interaction between recombinant soluble CD4 and native membrane-associated CD4 with gp120 is probed by the use of mAbs. Complexation of gp120 with both forms of CD4 induces conformational epitopes that can be defined with specific mAbs. CG1, CG7, and CG8 are three novel mAbs that have a distinct preference for CD4 complexed over noncomplexed with gp120. The epitopes of these unique mAbs were mapped by cross-inhibition with previously characterized mAbs to a region encompassing the CDR2 and CDR3 loops in domain 1 of CD4. Systematic analysis of CG mAbs binding to CD4 and CD4/gp120 complex delineates a region in the D1 domain of CD4 that undergoes conformational rearrangements upon gp120 binding to its receptor.}, } @article {pmid9376720, year = {1997}, author = {Savel'eva, GM and Antonova, LV and Evseev, AA and Shtyrov, SV and Prozorovskaia, KN and Denisova, EN}, title = {[New approaches to the diagnosis and treatment of inflammatory diseases of the adnexa uteri].}, journal = {Vestnik Rossiiskoi akademii meditsinskikh nauk}, volume = {}, number = {2}, pages = {12-16}, pmid = {9376720}, issn = {0869-6047}, mesh = {Abdomen, Acute/diagnosis ; Adjuvants, Immunologic/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Diagnosis, Differential ; Drainage ; Female ; Humans ; Laparoscopy ; *Pelvic Inflammatory Disease/diagnosis/drug therapy/surgery ; }, abstract = {The paper summarizes follow-ups of 2500 patients with inflammatory diseases of the uterine appendages, provides evidence for the benefits of laparoscopic diagnosis and treatment of all types of this condition, which makes it possible to verify the diagnosis and perform less traumatic organ-sparing operations. To use combined antiinflammatory antibiotic therapy in view of the etiology of inflammation, as well as immunomodulators is the requisite condition for treating acute types of a disease. The new approaches to the diagnosis and treatment of inflammatory diseases of the uterine appendages substantially improved therapeutical outcomes and maintained female reproductive function.}, } @article {pmid9364950, year = {1997}, author = {Denisova, O and Shapiro, EP and Weiss, JL and Azhari, H}, title = {Localization of ischemia in canine hearts using tagged rotated long axis MR images, endocardial surface stretch and wall thickening.}, journal = {Magnetic resonance imaging}, volume = {15}, number = {9}, pages = {1037-1043}, doi = {10.1016/s0730-725x(97)00161-6}, pmid = {9364950}, issn = {0730-725X}, support = {HL-17655-16/HL/NHLBI NIH HHS/United States ; R01-HL-43722/HL/NHLBI NIH HHS/United States ; R01-HL-46223/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Dogs ; Evaluation Studies as Topic ; Heart Ventricles/*pathology/physiopathology ; Image Processing, Computer-Assisted ; *Magnetic Resonance Imaging ; Models, Cardiovascular ; Models, Structural ; Myocardial Contraction ; Myocardial Ischemia/*diagnosis/pathology/physiopathology ; Sensitivity and Specificity ; Stress, Mechanical ; Systole/physiology ; }, abstract = {Tagged magnetic resonance imaging allows the noninvasive measurement of regional systolic myocardial deformations and helps localize ischemic regions in the left ventricle (LV). The objective of this study was to evaluate the potential accuracy of localizing ischemic regions in the LV using endocardial and epicardial data obtained from tagged rotated long axis images. Nine canine hearts with acute ischemia induced by coronary artery ligation were imaged along four long axis planes rotated around the LV long axis, at end diastole and end systole. Each plane was tagged by four parallel lines perpendicular to the LV long axis. Tracing the endocardial and epicardial intersection points of the tag lines, 24 myocardial cuboids were reconstructed for each LV at end diastole and end systole. Endocardial surface stretch and transmural systolic thickening were calculated for each cuboid. The functional data were compared to perfusion data obtained from postmortem monastral blue staining of the heart. The ability of each functional index to discriminate between ischemic and non-ischemic regions was assessed using the "t"-statistic. The potential accuracy in localizing ischemia was evaluated by studying the corresponding sensitivity-specificity curves. The results demonstrate that adequate discrimination and localization can be obtained with both functional indices. However, endocardial surface stretch is advantageous as it uses only endocardial data and can save 50% of the post-processing time.}, } @article {pmid9343480, year = {1997}, author = {Gorbachevskaia, NL and Denisova, LV}, title = {[Brain bioelectrical activity in patients with the fragile X-chromosome syndrome and in their mothers].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {97}, number = {8}, pages = {33-37}, pmid = {9343480}, issn = {1997-7298}, mesh = {Adolescent ; Adult ; Aging/physiology ; Brain/*physiopathology ; Child ; Child, Preschool ; Electroencephalography/statistics & numerical data ; Female ; Fragile X Syndrome/diagnosis/genetics/*physiopathology ; Heterozygote ; Humans ; Male ; }, abstract = {30 patients (4-22 years old) and their 12 mothers were examined by means of method of electroencephalography (EEG). Healthy individuals of corresponding age were included in the control group. EEG changes of the same type were observed in all the patients with syndrome of fragile X-chromosome: reduction of occipital alpha-rhythm, prevalence of theta-rhythm in central-parietal and central frontal regions as well as epileptoid activity in parietal and central-parietal cortical regions. These peculiarities could be considered as the markers in syndrome's diagnostics. EEG of mothers (heterozygous carriers of mutant gene) were characterised by considerable variations: increase of rolandic rhythm's presentation in central cortical zones, accumulation of hypersynchronous EEG, increase of rhythmical theta-activity, etc. EEG of mother with shift-like schizophrenia resembled one of proband in one case.}, } @article {pmid9214577, year = {1997}, author = {Shukitt-Hale, B and Denisova, NA and Strain, JG and Joseph, JA}, title = {Psychomotor effects of dopamine infusion under decreased glutathione conditions.}, journal = {Free radical biology & medicine}, volume = {23}, number = {3}, pages = {412-418}, doi = {10.1016/s0891-5849(97)00094-4}, pmid = {9214577}, issn = {0891-5849}, mesh = {Aging/physiology ; Animals ; Behavior, Animal/drug effects ; Body Weight/drug effects ; Brain/drug effects/*metabolism ; Buthionine Sulfoximine/administration & dosage/*pharmacology ; Dopamine/administration & dosage/*pharmacology ; Glutathione/deficiency/*metabolism ; Male ; *Oxidative Stress ; Psychomotor Performance/*drug effects ; Rats ; Rats, Inbred F344 ; }, abstract = {Administration of buthionine sulfoximine (BSO) selectively inhibits glutathione (GSH) biosynthesis, thereby inducing a GSH deficiency. Because GSH plays a critical role in intracellular antioxidant defense, decreased GSH levels in the brain may result in less oxidative stress (OS) protection. Thus, the pro-oxidant effects of dopamine (DA), which rapidly oxidizes to form reactive oxygen species, may increase. In this study, the behavioral consequences of reduced OS protection were examined by administering BSO (3.2 mg in 30 microl Ringer's solution, intracerebroventricularly) every other day for 12 d to male Fischer 344 rats. In addition, DA (15 microl of 500 microM) was administered every day; when given on the same day as BSO, it was either 1 h after BSO (BSO + DA group) or 1 h before BSO (DA + BSO group). Tests of psychomotor behavior--rod walking, wire suspension, and plank walking--were performed five times during the experiment. BSO + DA administration, but not DA + BSO, impaired performance by decreasing latency to fall in the rod and plank walk tests compared to a vehicle only (Ringer's) group. Therefore, depletion of GSH with BSO, followed by DA treatment, produced deficits in psychomotor behavior. These deficits are similar to those seen in aged rats, suggesting that the oxidation of DA coupled with a reduced capacity to respond to OS may be responsible for the induction of age-related motor behavioral deficits.}, } @article {pmid9198983, year = {1997}, author = {Shormanov, VK and Denisova, NG}, title = {[The characteristics of extracting 4-methyl-2,6-dinitrophenol and 2-(1-methylpropyl)-4,6-dinitrophenol from aqueous solutions].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {40}, number = {1}, pages = {36-38}, pmid = {9198983}, issn = {0039-4521}, mesh = {Calibration ; Dinitrobenzenes/*isolation & purification ; Hydrogen-Ion Concentration ; Pesticides/*isolation & purification ; Phenyl Ethers/*isolation & purification ; Solutions ; Solvents ; }, } @article {pmid9181796, year = {1997}, author = {Zheleznaia, LA and Denisova, EA and Kostiuchenko, LN and Gerasimov, VS}, title = {[Roentgenographic study of the duodenal juice components in the dog].}, journal = {Biofizika}, volume = {42}, number = {1}, pages = {234-238}, pmid = {9181796}, issn = {0006-3029}, mesh = {Animals ; Dogs ; Duodenum/*physiology ; Electrophoresis, Polyacrylamide Gel ; Intestinal Secretions/*chemistry ; X-Ray Diffraction ; }, abstract = {It is shown that X-ray pattern rich in reflections that we have received earlier from concentrated canine duodenal juice is the sum of the patterns arising from both mucin macromolecules and from unknown component of the juice. The functional role of the duodenal juice regularity observed is discussed.}, } @article {pmid9027967, year = {1997}, author = {Rumba, I and Denisova, A and Sochnev, A and Nilsson, B and Sanjeevi, CB}, title = {HLA class II genes in Latvian patients with juvenile rheumatoid arthritis.}, journal = {Tissue antigens}, volume = {49}, number = {1}, pages = {56-60}, doi = {10.1111/j.1399-0039.1997.tb02711.x}, pmid = {9027967}, issn = {0001-2815}, mesh = {Alleles ; Arthritis, Juvenile/genetics/*immunology ; HLA-DQ Antigens/*genetics ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; HLA-DR Antigens/*genetics ; HLA-DRB1 Chains ; Humans ; Latvia ; Rheumatoid Factor/blood ; }, abstract = {PCR-based HLA genotyping was used to analyze the association of HLA-DR and -DQ genes in 127 juvenile rheumatoid arthritis patients and 111 population-based controls from Latvia. The results show DQA1*03 to be positively associated in overall patients and DRB1*01-DQA1*0101-DQB1*0501 to be negatively associated with JRA in overall patients and in polyarthritis patients compared to controls. These data indicate the immunogenetic heterogeneity in the JRA patients, in the disease subgroups and in different ethnic groups. Rheumatoid factor (RF) was assayed in patients (n = 119) and controls (n = 98). RF was present in patients (7/119, 6%) compared to controls (5/98, 5%). None of the DQA1, DQB1 alleles, DQ and DR-DQ haplotypes was associated in seropositive patients compared to seropositive controls. DR1-DQ5 (DQA1*0101-B*0501) was decreased in seronegative patients (11/111, 10%) compared to seronegative controls (24/105, 23%), but the difference was not significant after correction of the p value.}, } @article {pmid8981037, year = {1997}, author = {Joseph, JA and Villalobos-Molinas, R and Denisova, NA and Erat, S and Strain, J}, title = {Cholesterol: a two-edged sword in brain aging.}, journal = {Free radical biology & medicine}, volume = {22}, number = {3}, pages = {455-462}, doi = {10.1016/s0891-5849(96)00376-0}, pmid = {8981037}, issn = {0891-5849}, mesh = {Aging/*physiology ; Animals ; Brain/drug effects/*physiology ; Carbachol/pharmacology ; Cholesterol/metabolism/pharmacology/*physiology ; Corpus Striatum/drug effects/physiology ; Dopamine/metabolism ; Drug Synergism ; GTP Phosphohydrolases/metabolism ; Glutathione/metabolism ; Hydrogen Peroxide/pharmacology ; Nitric Oxide/pharmacology ; Oxidation-Reduction ; Potassium/pharmacology ; Proteins/metabolism ; Rats ; Rats, Inbred F344 ; }, abstract = {Previous research from several laboratories has indicated that cholesterol (CHO) accumulates in neuronal membranes and alters their structural and signal transduction (ST) properties during aging. The possible reasons for these increases in membrane CHO have not been specified. However, present findings suggest that such accumulation may actually serve to protect neuronal tissue from oxidative damage. Striatal slices (6, 24 month rats) were preincubated in 1 mM CHO (30 min) followed by incubation with H2O2 (10 microM, 30 min). The slices were then either superfused with 30 mM KCl in the presence or absence of 500 microM oxotremorine (Ox), and K(+)-evoked dopamine release (K(+)-ERDA) examined or assessed for carbachol-stimulated low K(m) GTPase activity. The results indicated that CHO incubation prior to H2O2 in either age group was effective in preventing H2O2 reductions in both non-Ox-enhanced K(+)-ERDA and Ox conditions, as well as sodium nitroprusside (SNP 150 microM)-induced decreases in K(+)-ERDA. In addition, H2O2-induced deficits in carbachol-stimulated low K(m) GTPase activity were reduced in the striatal tissue from the old animals pretreated with CHO. However, if the slices were incubated in H2O2 prior to CHO exposure, CHO enhanced the H2O2 effects in the tissue from the old animals. Thus, depending upon the order of exposure, CHO functioned to enhance or retard the effects of oxidative stress, in an age-dependent manner.}, } @article {pmid9026961, year = {1996}, author = {Gurtovaia, SV and Bliznetsova, VI and Revnitskaia, LA and Vdovina, NR and Shelkovskaia, VN and Grechko, EO and Sabanova, LS and Maiatskaia, MV and Isakova, IV and Denisova, VV and Korneenkova, VA and Trapeznikova, TA}, title = {[The detection of ABO system antigens in bone, nail and tooth fragments].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {39}, number = {4}, pages = {23-25}, pmid = {9026961}, issn = {0039-4521}, mesh = {ABO Blood-Group System/*analysis ; Bone and Bones/*immunology/pathology ; Forensic Dentistry/methods ; Forensic Medicine/methods ; Humans ; Nails/*immunology/pathology ; Postmortem Changes ; Russia ; Time Factors ; Tooth/*immunology/pathology ; }, abstract = {Fragments of the bones, nails, and teeth were examined in 12 forensic biological departments of bureaus for forensic medical expert evaluation of the Russian Federation. A total of 790 experiments were carried out with 145 bones, 5 teeth, and nails from 12 cadavers. In the overwhelming majority of cases the experiments were carried out with control investigations of blood, hair, salivary, and sweat samples. Modifications of the absorption-elution method were used to detect the AB0 antigens, these modifications involving all stages of the test (fixation, fat extraction, medium for elution, reagents, time factors in absorption and elution, etc.). Analysis of the data permitted the authors to make some conclusions and offer recommendations for practical biological experts.}, } @article {pmid9082737, year = {1996}, author = {Karal'nik, BV and Denisova, TG}, title = {[The evaluation of different agglutination and adhesion tests with erythrocytic reagents in determining antibodies to the O and H antigens of Salmonella typhimurium in comparison with immunoenzyme analysis (IEA)].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {5}, pages = {76-80}, pmid = {9082737}, issn = {0372-9311}, mesh = {Agglutination Tests/methods ; Antibodies, Bacterial/*blood ; Antigens, Bacterial/*immunology ; Erythrocytes/*immunology ; Evaluation Studies as Topic ; Humans ; Immunoenzyme Techniques ; Immunoglobulin Isotypes/blood ; Immunologic Tests/*methods ; Infant ; O Antigens/*immunology ; Salmonella Infections/diagnosis ; Salmonella typhimurium/*immunology ; Sensitivity and Specificity ; }, abstract = {The comparison of the effectiveness of EIA with that of a number of agglutination and adhesion tests with erythrocyte diagnostica in the determination of antibodies to different S.typhimurium antigens demonstrated higher sensitivity of EIA. The relative specificity of the determination of O- and H-antibodies in EIA and in agglutination and adhesion tests depended on the isotype of antibodies to be determined and the specificity of sensitins used in the production of immunoreagents.}, } @article {pmid8798975, year = {1996}, author = {Denisova, G and Stern, B and Raviv, D and Zwickel, J and Smorodinsky, NI and Gershoni, JM}, title = {Humoral immune response to immunocomplexed HIV envelope glycoprotein 120.}, journal = {AIDS research and human retroviruses}, volume = {12}, number = {10}, pages = {901-909}, doi = {10.1089/aid.1996.12.901}, pmid = {8798975}, issn = {0889-2229}, mesh = {Amino Acid Sequence ; Animals ; Antibody Formation ; Antigen Presentation ; Epitope Mapping ; HIV Envelope Protein gp120/*immunology ; Immunization ; Immunodominant Epitopes/immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Peptide Fragments/*immunology ; Recombinant Proteins/immunology ; }, abstract = {To further our understanding of the nature of HIV-1 immunogenicity, we injected mice with the virus envelope protein gp120 in different configurations: free, complexed with its receptor CD4, and as an immunocomplex with a monoclonal antibody directed against the V3 loop of the protein. Analyses of the polyclonal sera, as well as of monoclonal antibodies produced in each case, allowed us to conclude that the quality of the humoral immune response depended on the complexation state of the antigen. For the free gp120 and gp120-CD4 complex the responses were directed mainly toward conformational epitopes. However, gp120 immunocomplexed with anti-V3 loop Mab produced, in addition, numerous MAbs directed toward linear epitopes. Epitopes were mapped using immunoblots of gp120 cleaved with S. aureus V8 protease and a combinatorial epitope phage-display library. It was found that some of the linear epitopes had been previously identified as T cell epitopes. These results suggest that the immunocomplexed gp120 may be particularly well taken up by antigen-presenting cells, leading to the processing of the gp120 and the efficient presentation of T cell epitopes. Thus immunocomplexation should afford a means for enhancing the immunogenicity of gp120 and improving its presentation.}, } @article {pmid8687012, year = {1996}, author = {Joseph, JA and Villalobos-Molina, R and Denisova, N and Erat, S and Jimenez, N and Strain, J}, title = {Increased sensitivity to oxidative stress and the loss of muscarinic receptor responsiveness in senescence.}, journal = {Annals of the New York Academy of Sciences}, volume = {786}, number = {}, pages = {112-119}, doi = {10.1111/j.1749-6632.1996.tb39056.x}, pmid = {8687012}, issn = {0077-8923}, mesh = {Aging/*metabolism ; Animals ; Cholesterol/pharmacology ; Nitric Oxide/pharmacology ; *Oxidative Stress ; Receptors, Muscarinic/*metabolism ; Sensitivity and Specificity ; }, abstract = {Although there are numerous findings which suggest that the pathogenesis of age-related neurodegenerative disorders (e.g., AD and PD) may involve oxidative stress (OS), relationships between functional age-related neuronal deficits, especially those with behavioral correlates, and OS have been difficult to establish. We have attempted to establish such relationships by determining the role of OS in the loss of muscarinic receptor (mAChR) sensitivity in aging. These decrements are expressed as age-related reductions in oxotremorine enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from superfused striatal slices. Using this model we have found that: a) The reductions can be restored with in vivo administration of the free-radical trapping agent, N-tert-butyl-alpha-phenylnitrone (PBN); b) Striatal slices from old animals showed increased sensitivity (e.g., reduced DA release or oxo-enhancement of K(+)-ERDA) to the in vitro application of sodium nitroprusside, a potent NO generator or to H2O2 which treatment of striatal slices from young animals with these agents or exposure of young animals to low doses of whole-body 56Fe irradiation decreased mAChR sensitivity and signal transduction (ST). Protection from the NO- or H2O2-induced deficits could be prevented with Trolox, PBN or cholesterol pretreatment. Evidence derived from PC-12 cells suggests that OS may directly affect ST by decreasing Ca2+ flux and increasing the length of the recovery period (i.e., return to baseline Ca2+ levels) after KCI (30 mM) depolarization.}, } @article {pmid8963207, year = {1996}, author = {Bel'kova, NL and Denisova, LIa and Manakova, EN and Zaĭchikov, EF and Grachev, MA}, title = {[Species diversity of deep water microorganisms in Lake Baikal, detected by 16S rRNA sequences].}, journal = {Doklady Akademii nauk}, volume = {348}, number = {5}, pages = {692-695}, pmid = {8963207}, issn = {0869-5652}, mesh = {Bacteria/*classification/genetics ; Ecosystem ; Fresh Water ; RNA, Ribosomal, 16S/*genetics ; Siberia ; *Water Microbiology ; }, } @article {pmid8871939, year = {1996}, author = {Joseph, JA and Denisova, N and Villalobos-Molina, R and Erat, S and Strain, J}, title = {Oxidative stress and age-related neuronal deficits.}, journal = {Molecular and chemical neuropathology}, volume = {28}, number = {1-3}, pages = {35-40}, doi = {10.1007/BF02815202}, pmid = {8871939}, issn = {1044-7393}, mesh = {Aging/*physiology ; Animals ; Antioxidants/pharmacology ; Chromans/*pharmacology ; Corpus Striatum/drug effects/growth & development/*physiology ; Cyclic N-Oxides ; Dopamine/metabolism ; Hydrogen Peroxide/*pharmacology ; In Vitro Techniques ; Lipid Peroxidation/drug effects ; Neurons/drug effects/pathology/*physiology ; Nitrogen Oxides/pharmacology ; *Oxidative Stress ; Oxotremorine/pharmacology ; Potassium/pharmacology ; Rats ; Rats, Inbred F344 ; Spin Labels ; Vitamin E/pharmacology ; }, abstract = {Research from our laboratory has indicated that the loss of sensitivity that occurs in several receptor systems as a function of age may be an index of an increasing inability to respond to oxidative stress (OS). This loss occurs partially as a result of altered signal transduction (ST). Assessments have involved determining the nature of age-related reductions in oxotremorine enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from superfused striatal slices. Using this model, we have found that 1. Reductions can be restored with in vivo administration of the free-radical trapping agent, N-tert-butyl-alpha-phenylnitrone (PBN); 2. Decrements in DA release induced by NO or H2O2 from striatal slices from both young and old animals could be restored with alpha-tocopherol or PBN; 3. ST decrements, such as those seen in aging, could be induced with radiation exposure; and 4. Pre-incubation of the striatal slices with cholesterol decreased subsequent deleterious effects of NO or OH. on DA release. Thus, cholesterol, which increases in neuronal membranes as a function of age, may function as a potent antioxidant and protectant against neuronal damage. These results suggest that therapeutic efforts to restore cognitive deficits in aging and age-related disease might begin with antioxidant reversal of ST decrements.}, } @article {pmid11012224, year = {1996}, author = {Schick, PK and Wojensk, CM and Bennett, V and Denisova, L}, title = {Fibronectin isoforms in megakaryocytes.}, journal = {Stem cells (Dayton, Ohio)}, volume = {14 Suppl 1}, number = {}, pages = {212-219}, doi = {10.1002/stem.5530140728}, pmid = {11012224}, issn = {1066-5099}, support = {AR40184/AR/NIAMS NIH HHS/United States ; HL25455/HL/NHLBI NIH HHS/United States ; HL51481/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Blood Platelets/metabolism ; Blotting, Western ; Bone Marrow Cells/metabolism ; Cell Division ; Cell Movement ; Electrophoresis, Polyacrylamide Gel ; Fibronectins/biosynthesis/*chemistry ; Guinea Pigs ; Humans ; Megakaryocytes/*chemistry/metabolism ; Microscopy, Confocal ; Protein Isoforms ; Thrombin/pharmacology ; }, abstract = {Our studies have shown that megakaryocytes (MK) can synthesize fibronectin (FN) and alternatively spliced fibronectin, FN EIIIB. FN EIIIB is primarily present in embryonic, proliferating and migrating cells, and thought to be important for cell maturation. MK, but not nonmegakaryocytic bone marrow cells, contain FN EIIIB and thus, MK and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. Thrombin can induce the secretion of general FN, but does not cause the secretion of FN EIIIB into the medium. Analysis of immunostained cells by confocal microscopy revealed that both general FN and FN EIIIB accumulated on the MK surface following thrombin treatment. Thus, FN EIIIB can be released only to be bound to the MK surface. The expression of FN EIIIB on the MK surface may have a unique role in MK migration and maturation.}, } @article {pmid9123919, year = {1996}, author = {Denisova, SN and Kutafina, EK and Kon', IIa and Sergeeva, TV and Savina, MI}, title = {[Effects of vitamin D on protein turnover in children with renal osteopathy].}, journal = {Voprosy pitaniia}, volume = {}, number = {6}, pages = {31-34}, pmid = {9123919}, issn = {0042-8833}, mesh = {Adolescent ; Amino Acids/blood/metabolism ; Child ; Chronic Kidney Disease-Mineral and Bone Disorder/blood/diet therapy/*drug therapy ; Erythrocytes/chemistry ; Humans ; Nitrogen/metabolism ; Proteins/*metabolism ; Vitamin D/*pharmacology/therapeutic use ; }, abstract = {Amino acid analysis and investigation of nitrogen balance were done in 2 groups of the patients with renal failure and osteodystrophy on the diet and vitamin D treatment. The results of the investigations confirm vitamin D influence on free amino acid turnover. We observed significant elevations of plasma amino acids in patients treated with the diet and vitamin D in comparison with the patients without vitamin D supplementation. Vitamin D didn't influence on the retention, urinary and fecal excretion of endogenous nitrogen in patients with renal failure}, } @article {pmid9060052, year = {1996}, author = {Liitsola, K and Laukkanen, T and Denisova, A and Grishkevichius, A and Smolskaja, T and Ustina, V and Vlasov, N and Leinikki, P and Salminen, MO}, title = {Genetic characterization of HIV-1 strains in the Baltic countries and Russia.}, journal = {Scandinavian journal of infectious diseases}, volume = {28}, number = {6}, pages = {537-541}, doi = {10.3109/00365549609037956}, pmid = {9060052}, issn = {0036-5548}, mesh = {Baltic States/epidemiology ; Female ; HIV Infections/epidemiology/*virology ; HIV-1/*classification/*genetics ; Homosexuality, Male ; Humans ; Male ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Russia/epidemiology ; }, abstract = {Proviral nucleotide sequences from the p7 region of the gag gene were compared among 40 Baltic and Russian HIV-1 strains. 33 of the infected persons carried a virus belonging to subtype B. Thus subtype B, which is most prevalent in Western Europe, was the most common subtype in all 3 Baltic countries (Estonia, Latvia and Lithuania) and Russia, and was associated with homosexual transmission. It also seemed that viruses of the same origin have been circulating in these countries; most of the subtype B viruses studied (n = 22) belonged to a closely related virus pool with average inter-nucleotide sequence distances of 2.7%. In 7 cases, viruses of non-B subtypes were found (1 subtype D from Estonia, 1 subtype C from Latvia, 1 subtype A from Lithuania and 1 subtype G from Russia). Three closely related viruses (1 from Lithuania and 2 from Russia) remained unclassified.}, } @article {pmid9005794, year = {1996}, author = {Savel'eva, GM and Evseev, AA and Denisova, EN}, title = {[Comparative evaluation of the effectiveness of ofloxacin in comprehensive treatment of acute inflammatory diseases of the uterus and uterine appendages].}, journal = {Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic]}, volume = {41}, number = {9}, pages = {81-83}, pmid = {9005794}, issn = {0235-2990}, mesh = {Acute Disease ; Administration, Oral ; Adolescent ; Adult ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Anti-Infective Agents/adverse effects/*therapeutic use ; Combined Modality Therapy ; Drug Administration Schedule ; Endometritis/*drug therapy/surgery ; Evaluation Studies as Topic ; Female ; Humans ; Infusions, Intravenous ; Middle Aged ; Ofloxacin/adverse effects/*therapeutic use ; Pelvic Inflammatory Disease/*drug therapy/surgery ; Treatment Outcome ; }, abstract = {Ofloxacin was used in the complex therapy of acute inflammatory diseases of the uterus and uterine appendages. The patients were divided into 2 groups. Group 1 included 15 patients treated with ofloxacin in a dose of 200 mg administered intravenously twice a day for 4 to 6 days. After that period the drug was used orally in the same dosage for 4 to 6 days. Group II was control and included 20 patients treated with some other broad spectrum antibiotics such as amplox, gentamicin and 3rd generation cephalosporins. Because of the disease severity in 33 patients they were subjected to surgical operations. The clinical recovery was stated in all the 35 patients. However, by a complex of the indices the efficacy of ofloxacin was higher than that of the other antibiotics. An improvement of the general state (no headache or weakness and normalization of the body temperature) was observed in the patients of group I 2-3 days earlier as compared to the patients of group II. Purulent discharge from the genitalia ceased 3-4 days earlier in the patients of group I by comparison with the control patients. Good tolerance of ofloxacin was observed and no severe adverse reactions were recorded.}, } @article {pmid8897366, year = {1996}, author = {Azhari, H and Denisova, OE and Montag, A and Shapiro, EP}, title = {Circular sampling: perspective of a time-saving scanning procedure.}, journal = {Magnetic resonance imaging}, volume = {14}, number = {6}, pages = {625-631}, doi = {10.1016/0730-725x(96)00089-6}, pmid = {8897366}, issn = {0730-725X}, support = {2RO1-HL 4622304/HL/NHLBI NIH HHS/United States ; }, mesh = {Computer Simulation ; Heart/anatomy & histology ; Humans ; Magnetic Resonance Imaging/*methods ; }, abstract = {A time-saving pulse sequence that requires relatively low gradients and slow rise time is suggested herein. With this pulse sequence the entire k domain is sampled along a set of concentric circles using only 50% of the number of pulses required by the standard line sampling technique (2DFT). This can result in saving about half the total scanning time in gated cardiac imaging. The sampling configuration in the k domain is identical to MR projection reconstruction, with the advantage that a considerably smaller number of excitations is required. Furthermore, computer simulations indicate that the proposed method is also advantageous over the "half-Fourier" method, as it provides better SNR for equal acquisition time (0.83 vs. 0.707 of the 2DFT SNR respectively.}, } @article {pmid8820683, year = {1996}, author = {Denisova, II and Gennad'eva, TIa and Zhdanova, TV and Khristova, M and Khazenson, LB}, title = {[The action of lactoperoxidase, lactoferrin and lactoglobulin on Shigella sonnei in an in-vivo experiment].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {1}, pages = {66-69}, pmid = {8820683}, issn = {0372-9311}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Drug Evaluation, Preclinical ; Drug Synergism ; Dysentery, Bacillary/*drug therapy/microbiology ; Lactoferrin/*therapeutic use ; Lactoglobulins/*therapeutic use ; Lactoperoxidase/*therapeutic use ; Lung/microbiology ; Mice ; *Shigella sonnei/isolation & purification ; Time Factors ; }, abstract = {The synergism of the protective action of lactoperoxidase, lactoferrin and lactoglobulin obtained from cow milk, as well as lactoferrin obtained from human milk, was shown in experiments on white mice, infected intranasally with S. sonnei and used as an experimental model. The combined administration of these preparations in doses, each one having no protective action, contributed to the elimination of the bacteria from the lungs and prevented the death of the animals. This phenomenon was found to be nonspecific and suitable for use in the development of preparations for passive immunization against a wide spectrum of microorganisms.}, } @article {pmid8728030, year = {1996}, author = {Joseph, JA and Villalobos-Molina, R and Denisova, N and Erat, S and Cutler, R and Strain, J}, title = {Age differences in sensitivity to H2O2- or NO-induced reductions in K(+)-evoked dopamine release from superfused striatal slices: reversals by PBN or Trolox.}, journal = {Free radical biology & medicine}, volume = {20}, number = {6}, pages = {821-830}, doi = {10.1016/0891-5849(95)02225-2}, pmid = {8728030}, issn = {0891-5849}, mesh = {Aging/*metabolism ; Animals ; Antioxidants/pharmacology ; Chromans/pharmacology ; Cyclic N-Oxides ; Dopamine/*metabolism ; Free Radicals/metabolism/pharmacology ; Glutathione/metabolism ; Hydrogen Peroxide/*pharmacology ; In Vitro Techniques ; Lipid Peroxidation/drug effects ; Nitric Oxide/*pharmacology ; Nitrogen Oxides/pharmacology ; Nitroprusside/pharmacology ; Potassium/pharmacology ; Rats ; Rats, Inbred F344 ; Visual Cortex/*drug effects/metabolism ; }, abstract = {Previous research has indicated that many age-related functional alterations may be the result of a decreased ability of the organism to respond to oxidative stress (OS). However, this hypothesis is based on indirect indices of function (e.g., increased vulnerability of hepatocytes from senescent animals to H2O2-induced DNA damage, increases in lipofuscin accumulation). More direct tests of this hypothesis, especially as it relates to brain aging, have not been extensively undertaken. Present experiments were carried out to make such tests by examining age differences in the sensitivity to OS on reductions in striatal dopamine (DA) release. Thus, K(+)-evoked DA (K(+)-ERDA) release from superfused striatal slices from young (6-8 month) and old (24-25 month) animals was examined following either: (a) application of the NO-generator sodium nitroprusside or (b) preincubation with H2O2. In order to assess the specific effects of OS on muscarinic (mAChR) sensitivity, oxotremorine-enhancement of K(+) -ERDA was examined following incubation with H2O2. Results showed that the striatal tissue from the old animals showed greater sensitivity to both H2O2 and NO than young animals, and stimulated DA decreased at lower concentrations of these agents (e.g., NO--100 microM young, 30 microM old). In addition, H2O2 was also effective in reducing oxo-enhanced K(+)-ERDA and was more effective as a function of age. If the striatal tissue was incubated in either Trolox (alpha-tocopherol) or alpha-phenyl-n-tert-butyl nitrone (PBN) prior to OS, the negative effects of NO. and H2O2 were reversed in both age groups. Results are discussed in terms of age-related membrane and endogenous antioxidant alterations that could induce increases in sensitivity to OS and the specificity of antioxidants in reducing this sensitivity in key functional systems.}, } @article {pmid8718587, year = {1996}, author = {Gershoni, JM and Denisova, GF and Raviv, D and Stern, B and Zwickel, J}, title = {Complexed HIV envelope as a target for an AIDS vaccine.}, journal = {Advances in experimental medicine and biology}, volume = {397}, number = {}, pages = {91-96}, doi = {10.1007/978-1-4899-1382-1_13}, pmid = {8718587}, issn = {0065-2598}, mesh = {*AIDS Vaccines ; Acquired Immunodeficiency Syndrome/immunology ; Amino Acid Sequence ; Animals ; Antibodies, Monoclonal ; Drug Design ; Epitopes/analysis ; Gene Products, env/*immunology ; HIV/*immunology ; HIV Envelope Protein gp120/*immunology ; Humans ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; }, } @article {pmid8714471, year = {1996}, author = {Zheleznaia, LA and Denisova, EA and Deshcherevskaia, NP and Gerasimov, VS}, title = {[Effect of thiol reagents on the structure of mucus glycoproteins (mucins)].}, journal = {Biofizika}, volume = {41}, number = {1}, pages = {198-204}, pmid = {8714471}, issn = {0006-3029}, mesh = {Animals ; Chromatography, Gel ; Indicators and Reagents ; Mucins/*chemistry/isolation & purification ; Protein Conformation ; Rats ; Sulfhydryl Compounds/*chemistry ; X-Ray Diffraction ; }, abstract = {The structure of both native mucins and subunits obtained by thiol reduction was studied by small-angle X-ray diffraction. X-ray pattern from the subunits significantly differs from that of the native mucins in the number, spacings and width of the reflections observed. Decrease in the number of the reflections and increase of their width pointed out that isolated subunits are less regular structure than the whole mucin molecule. This may be due to the two reasons: 1) conformation of the subunits in native molecule differs from that of in isolate state; 2) native mucin molecule is not a simple polymer, formed by the subunits.}, } @article {pmid8644474, year = {1996}, author = {Portnoĭ, LM and Sherman, LA and Denisova, LB and Kuz'mina, LG}, title = {[Classical roentgenology and computerized tomography in the diagnosis of pituitary adenomas].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {1}, pages = {5-9}, pmid = {8644474}, issn = {0042-4676}, mesh = {Adenoma/*diagnostic imaging ; Adolescent ; Adult ; Aged ; Evaluation Studies as Topic ; Female ; Humans ; Male ; Middle Aged ; Pituitary Neoplasms/*diagnostic imaging ; *Tomography, X-Ray Computed/methods ; }, abstract = {The potentialities of diagnosis of pituitary adenomas using radiation techniques are analyzed on the basis of a material comprising 456 cases with this abnormality. The potentialities of CT and classical X-ray diagnoses are compared and recommendations are given for specific cases when, despite CT, routine craniograms must be made. The involvement and contribution of CT in the diagnosis of pituitary adenomas are considered. The results from the application of a fixed and mobile CT mounts are presented. At the same time the possibilities of achieving a greater efficiency by employing its mobile mount by the author's protocol are emphasized.}, } @article {pmid8604234, year = {1995}, author = {Doronin, KK and Iurov, GK and Grinenko, NF and Zakharchuk, AN and Denisova, TS and Baburina, TM and Krugliak, VA and Naroditskiĭ, BS}, title = {[Expression of a gene encoding the porcine rotavirus VP7 capsid using a nondefective recombinant adenoviral genome].}, journal = {Molekuliarnaia genetika, mikrobiologiia i virusologiia}, volume = {}, number = {4}, pages = {35-39}, pmid = {8604234}, issn = {0208-0613}, mesh = {Adenoviridae/*genetics ; *Antigens, Viral ; Base Sequence ; Capsid/*genetics ; *Capsid Proteins ; DNA Primers ; Electrophoresis, Polyacrylamide Gel ; *Gene Expression Regulation, Viral ; HeLa Cells ; Humans ; Molecular Sequence Data ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Radioimmunoprecipitation Assay ; Recombination, Genetic ; Rotavirus/*genetics ; }, abstract = {A nondefective recombinant human adenovirus 5 (Ad5) carrying the gene encoding for the porcine rotavirus outer capsid protein VP7 in the E3 region of the Ad5 genome has been obtained. mRNA for VP7 in recombinant Ad5KV14/VP7 infected cells was demonstrated by means of RT-PCR. Radioimmunoprecipitation of cell extracts infected with Ad5KV14/VP7 on early (12 h p.i.) and late (24 h p.i.) stages of adenovirus infection with rabbit polyclonal antiserum raised to purified rotavirus virions revealed a recombinant protein possessing the same electrophoretic mobility, 37 kDa, as the native rotavirus K VP7. One-dimensional peptide mapping also demonstrated the identity of the recombinant and native VP7.}, } @article {pmid7654249, year = {1995}, author = {Kelly, JF and Mason, RP and Denisova, NA and Joseph, JA and Erat, S and Roth, GS}, title = {Age-related impairment in striatal muscarinic cholinergic signal transduction is associated with reduced membrane bilayer width measured by small angle X-ray diffraction.}, journal = {Biochemical and biophysical research communications}, volume = {213}, number = {3}, pages = {869-874}, doi = {10.1006/bbrc.1995.2209}, pmid = {7654249}, issn = {0006-291X}, mesh = {Aging/*metabolism ; Animals ; Carbachol/pharmacology ; Cell Membrane/metabolism ; Corpus Striatum/drug effects/enzymology/*metabolism ; GTP Phosphohydrolases/metabolism ; Male ; Neurons/*metabolism ; Rats ; Rats, Inbred F344 ; Receptors, Muscarinic/*metabolism ; *Signal Transduction ; X-Ray Diffraction ; }, abstract = {In order to determine whether age-related changes in neuronal membrane structure contribute to previously reported changes in muscarinic cholinergic signal transduction, striata from 3, 13 and 23 month old F344 male rats were examined for both carbachol-stimulated low Km GTPase activity and membrane one-dimensional electron density profile using small angle X-ray diffraction. Increasing age was associated with both a reduction in stimulated GTPase activity and a decrease in membrane bilayer width. These findings suggest the possibility that fundamental membrane structural changes may contribute to alterations in signal transduction seen with aging.}, } @article {pmid7476936, year = {1995}, author = {Kowatch, MA and Kelly, JF and Denisova, NA and Roth, GS}, title = {Partial restoration of impaired alpha 1-adrenergic responsiveness in parotid cells of aged rats by S-adenosylmethionine treatment.}, journal = {Molecular and cellular biochemistry}, volume = {148}, number = {1}, pages = {73-77}, pmid = {7476936}, issn = {0300-8177}, mesh = {*Adrenergic alpha-1 Receptor Agonists ; Adrenergic alpha-Agonists/*pharmacology ; Aging/*metabolism ; Animals ; Fluorescence Polarization ; Inositol 1,4,5-Trisphosphate/*biosynthesis ; Male ; Membrane Fluidity/drug effects ; Membrane Lipids/metabolism ; Methylation/drug effects ; Parotid Gland/cytology/*drug effects/metabolism ; Phosphatidylcholines/biosynthesis ; Phosphatidylethanolamines/metabolism ; Rats ; Rats, Wistar ; S-Adenosylhomocysteine/pharmacology ; S-Adenosylmethionine/antagonists & inhibitors/*pharmacology ; Signal Transduction/*drug effects ; Viscosity ; }, abstract = {The age related decrease in alpha 1-adrenergic stimulated inositol 1, 4, 5 trisphosphate (IP3) production in parotid cells of aged rats can be partially restored by treatment with S-adenosylmethionine (SAM). This effect is completely blocked by S-adenosyl homocysteine (SAH) and occurs in association with an increase in the conversion of phosphatidylethanolamine to phosphatidylcholine and a decrease in membrane viscosity. In contrast, SAM treatment actually inhibits stimulated IP3 production in cells of young rats. The membrane viscosity of these cells is lower than that of those from aged rats. Although conversion of phosphatidylethanolamine to phosphatidylcholine is enhanced, no further decrease in membrane viscosity is elicited in young cell preparations. These findings suggest that age changes in the membrane environment may result in impaired alpha 1-adrenergic signal transduction and that such alterations may be at least partially reversible by SAM treatment.}, } @article {pmid7580758, year = {1995}, author = {Denisova, SV and Sapozhkov, AV}, title = {[The effect of cardiovascular agents on the hemostatic system in myocardial ischemia].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {58}, number = {4}, pages = {63-68}, pmid = {7580758}, issn = {0869-2092}, mesh = {Animals ; Blood Viscosity/drug effects ; Cardiovascular Agents/*therapeutic use ; Hemostasis/*drug effects ; Humans ; Myocardial Infarction/blood/drug therapy/etiology ; Myocardial Ischemia/blood/*drug therapy/etiology ; }, } @article {pmid7483954, year = {1995}, author = {Portnoĭ, LM and Kalinin, AP and Shumskiĭ, VI and Sherman, LA and Denisova, LB}, title = {[Experience with using mobile x-ray computed tomography in the diagnosis of hypophyseal adenomas].}, journal = {Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko}, volume = {}, number = {3}, pages = {28-30}, pmid = {7483954}, issn = {0042-8817}, mesh = {Adenoma/*diagnostic imaging ; Adolescent ; Adult ; Aged ; Evaluation Studies as Topic ; Female ; Humans ; Male ; Middle Aged ; *Mobile Health Units ; Pituitary Gland/diagnostic imaging ; Pituitary Neoplasms/*diagnostic imaging ; Tomography, X-Ray Computed/*instrumentation ; }, } @article {pmid7760056, year = {1995}, author = {Kelly, JF and Joseph, JA and Denisova, NA and Erat, S and Mason, RP and Roth, GS}, title = {Dissociation of striatal GTPase and dopamine release responses to muscarinic cholinergic agonists in F344 rats: influence of age and dietary manipulation.}, journal = {Journal of neurochemistry}, volume = {64}, number = {6}, pages = {2755-2764}, doi = {10.1046/j.1471-4159.1995.64062755.x}, pmid = {7760056}, issn = {0022-3042}, mesh = {Aging/*physiology ; Animals ; Carbachol/pharmacology ; Cholesterol/metabolism ; Cholinergic Agents/*pharmacology ; Corpus Striatum/*enzymology ; *Diet ; Dopamine/*metabolism ; GTP Phosphohydrolases/*metabolism ; Male ; Oxotremorine/pharmacology ; Phospholipids/metabolism ; Potassium Chloride/pharmacology ; Rats ; Rats, Inbred F344 ; Synaptosomes/metabolism ; }, abstract = {There is evidence that dietary lipids and age both influence neuronal membrane composition and receptor G protein-linked signal transduction, but very little information is available on the interaction between these two factors. To investigate this, we obtained striata from 2, 12, and 22-month-old male F344 rats who were fed either a high-cholesterol, high-saturated fat or low-fat diet for 1 month. The striata were assayed for muscarinic agonist-stimulated low-Km GTPase activity using 10(-3) M carbachol and 10(-5) M oxotremorine and for KCl-evoked dopamine release enhancement by 10(-5) M oxotremorine. Membrane cholesterol and phospholipid content and phospholipid class composition were also determined. Mature animals showed significant but divergent changes in GTPase activity and dopamine release for high-cholesterol and low-fat diets: GTPase activity decreased, whereas dopamine release increased in these groups. Alterations in GTPase activity but not in dopamine release were inversely correlated with the cholesterol/phospholipid molar ratio. Old control animals showed reductions in both GTPase activity and oxotremorine-enhanced dopamine release compared with young animals. Whereas none of the experimental diets affected GTPase activity in old animals, the low-fat diet produced a marked decrease in dopamine release. In contrast to mature and old groups, young rats showed no significant change in either GTPase or dopamine release, suggesting a relative "resistance" to such dietary lipid modulation. The observed dissociation in GTPase and dopamine release responses to diet may reflect differing effects of these diets on discrete membrane lipid domains that preferentially influence different signal transduction components. The substantial age-related differences in striatal membrane response to dietary lipid modulation may represent the effects of underlying age differences in membrane lipid metabolism, structure, and/or dynamics. Our findings support the work of other groups that have shown that brain membranes are susceptible to modification by exogenous lipids. They also suggest the need for a more systematic examination of the influence of age on the response to other types of dietary lipid changes.}, } @article {pmid7653140, year = {1995}, author = {Iurov, SV and Pchelintsev, SIu and Denisov, LA and Afanas'eva, SS and Uraeva, VI and Denisova, NB and Cherenkova, GV and Vorob'ev, AA}, title = {[The effect of recombinant tumor necrosis factor on antibody formation in mice immunized with a preparation of the outer membranes from Francisella tularensis].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {2}, pages = {64-67}, pmid = {7653140}, issn = {0372-9311}, mesh = {Animals ; Antibodies, Bacterial/biosynthesis/blood/*drug effects ; Antibody-Producing Cells/drug effects/immunology ; Bacterial Outer Membrane Proteins/*immunology ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Immunologic ; Female ; Francisella tularensis/*immunology ; Humans ; Immunization/*methods ; Male ; Mice ; Mice, Inbred CBA ; Recombinant Proteins/pharmacology ; Stimulation, Chemical ; Time Factors ; Tumor Necrosis Factor-alpha/*pharmacology ; }, abstract = {The influence of exogenic human recombinant tumor necrosis factor (TNF-alpha) on antibody production in mice immunized with the preparation of F.tularensis outer membranes (OM) was studied. TNF-alpha was injected into mice in doses of 0.001-10 I.U. before and simultaneously with the injection of the preparation of F.tularensis OM. The levels of tularemia antibodies, determined by ELISA techniques, and the number of antibody-producing cells (APC) were studied. The study revealed that recombinant TNF-alpha in the range of doses used in this investigation stimulated the formation of humoral immunity. The injection of TNF-alpha in a dose of 0.001 I.U. was found to produce the most pronounced effect on the level of tularemia antibodies and the number of antibody-producing cells. The use TNF-alpha as immunomodulator made it possible to decrease the dose of the preparation of F.tularensis OM introduced as immunogenic agent without essential changes in the number of splenic APC and in the level of tularemia antibodies.}, } @article {pmid7784976, year = {1995}, author = {Dotsenko, EA and Novikov, DK and Kolosova, TS and Samsonov, NM and Ryzhova, TV and Denisova, TM}, title = {[Postcoital allergy: the possibilities for a specific diagnosis].}, journal = {Terapevticheskii arkhiv}, volume = {67}, number = {4}, pages = {47-49}, pmid = {7784976}, issn = {0040-3660}, mesh = {Acute Disease ; Adult ; Coitus/*physiology ; Diagnosis, Differential ; Female ; Humans ; Hypersensitivity, Immediate/*diagnosis/etiology/immunology ; Immunologic Tests/methods ; Male ; Spermatozoa/immunology ; Time Factors ; }, } @article {pmid7529735, year = {1995}, author = {Denisova, G and Zwickel, J and Gershoni, JM}, title = {Binding of HIV-1 gp120 to an anti-V3 loop antibody reveals novel antigen-induced epitopes.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {9}, number = {1}, pages = {127-132}, doi = {10.1096/fasebj.9.1.7529735}, pmid = {7529735}, issn = {0892-6638}, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; Binding Sites, Antibody ; Epitopes/*immunology ; HIV Antibodies/*immunology ; HIV Antigens/*immunology ; HIV Envelope Protein gp120/*immunology ; Immunoglobulin Fab Fragments/immunology ; Immunoglobulin G/chemistry/immunology ; Mice ; Mice, Inbred BALB C ; Peptide Fragments/*immunology ; }, abstract = {Antigen association to its corresponding binding site in the immunoglobulin molecule can elicit conformational rearrangements, generating novel epitopes termed metatopes. Such metatopes were characterized for the immunocomplex between the AIDS virus envelope protein, gp120, and M77, a mAb directed against the V3 loop. Five novel mAbs were described (GV1, GV3, GV7, GV8, and GV12). These mAbs were found to bind epitopes harbored in the M77 Fab fragment. Binding to the epitopes was shown to require the complexation of Fab with its antigen. The degree of this antigen requirement was found to be variable for the different mAbs and also for the state of IgG fragmentation. Binding of GV12 to its antigen increased the affinity of M77 for gp120. Moreover, in the presence of GV12, M77 acquired extended cross-reactivity for a second gp120 variant, namely BaL. These results could indicate a novel approach towards improving the performance of anti-HIV antibodies.}, } @article {pmid7793058, year = {1994}, author = {Nazarenko, ES and Denisova, LB and Bazaev, VV and Fedosov, SN}, title = {[Diagnosis of cancer of solitary kidney].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {6}, pages = {55-57}, pmid = {7793058}, issn = {0042-4676}, mesh = {Carcinoma, Renal Cell/*diagnosis/surgery ; Female ; Humans ; Kidney/*abnormalities ; Kidney Neoplasms/*diagnosis/surgery ; Middle Aged ; }, } @article {pmid7793048, year = {1994}, author = {Portnoĭ, LM and Nefedova, VO and Denisova, LB and Shumskiĭ, VI and Iureskul, IV}, title = {[Computed tomography in the diagnosis of gastric cancer].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {6}, pages = {10-14}, pmid = {7793048}, issn = {0042-4676}, mesh = {Aged ; Contrast Media ; Diagnosis, Differential ; False Negative Reactions ; False Positive Reactions ; Female ; Humans ; Male ; Middle Aged ; Pneumoperitoneum, Artificial ; Predictive Value of Tests ; Sensitivity and Specificity ; Stomach Neoplasms/*diagnostic imaging ; Tomography, X-Ray Computed/*methods ; }, abstract = {The potentialities of x-ray computer-aided tomography (CAT) in the studies of intraparietal blastomatous infiltration are analyzed as shown by examinations of 134 patients with gastric cancer. The diagnostic efficacies of various modifications of CAT (filling of the stomach with liquid, pneumoscanning of the stomach with or without tubes) are assessed. Good diagnostic potentialities of tubal scanning of the stomach in the assessment of intraparietal tumor infiltration are demonstrated. CAT semeiotics of gastric cancer is presented, characterizing the tumors with predominantly intraparietal dissemination of blastomatous infiltration. The existent projection limitations of axial CAT of individual portions of the stomach and high price of the examination imply that the indications to the use of this method in gastrooncology should be clearly defined. At the same time, scrupulous adherance to methodologic requirements aimed at imaging of intraparietal changes in gastric cancer may help to solve a number of differential diagnostic difficulties, primarily those connected with predominantly submucously growing carcinomas.}, } @article {pmid7533465, year = {1994}, author = {Raskin, BM and Borisova, VN and Kostromina, TI and Denisova, SV and Smirnova, GA and Mel'nikova, VA}, title = {[The development of Russian nutrient media for isolating the recombinant surface antigen of the hepatitis B virus].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {6}, pages = {23-24}, pmid = {7533465}, issn = {0372-9311}, mesh = {Chromatography, Gel ; *Culture Media ; Dextrans ; Gels ; Hepatitis B Surface Antigens/*isolation & purification ; Recombinant Proteins/isolation & purification ; }, } @article {pmid7879486, year = {1994}, author = {Santsevich, NI and Kadomtseva, VM and Aminov, RI and Denisova, SV and Smirnova, GA and Mel'nikova, VA}, title = {[The development of nutrient media for the cultivation of recombinant Escherichia coli strains].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {5}, pages = {6-10}, pmid = {7879486}, issn = {0372-9311}, mesh = {Bacterial Proteins/biosynthesis ; Cellulase/analysis/metabolism ; Culture Media/analysis/*metabolism ; Escherichia coli/*growth & development ; Protein Hydrolysates/analysis/metabolism ; Recombinant Proteins/biosynthesis ; *Recombination, Genetic ; }, abstract = {The study of the qualitative and quantitative composition of peptides and free amino acids in commercial casein hydrolysates, produced in Russia, has provided grounds for the choice of the nutrient base in the medium for the cultivation of E. coli recombinant strains. In the newly developed medium specific endoglucanase activity is 1.5- to 1.7-fold greater than in Luria-Bertani broth ("Difco" Laboratories, USA).}, } @article {pmid7819319, year = {1994}, author = {Zheleznaia, LA and Kostiuchenko, LN and Denisova, EA and Gerasimov, VS}, title = {[X-ray diffraction study of adaptive changes in the structure of dense phase juice from the duodenum].}, journal = {Biofizika}, volume = {39}, number = {5}, pages = {911-914}, pmid = {7819319}, issn = {0006-3029}, mesh = {Adaptation, Physiological ; Animals ; Chemical Precipitation ; Digestion ; Dogs ; Duodenum/chemistry/metabolism/*physiology ; Fasting ; Glycoproteins/chemistry ; Intestinal Secretions/physiology ; X-Ray Diffraction ; }, abstract = {Low-angle X-ray diffraction patterns of canine duodenal juice precipitates taken at two stages of digestion, after 20 h fasting and after food stimulation have been obtained. Both diffraction patterns are due to glycoproteins. However, the glycoproteins contained in the precipitate after food stimulation occur in the native form while in fasting animals they are partially degraded.}, } @article {pmid8133280, year = {1994}, author = {Arduini, A and Denisova, N and Virmani, A and Avrova, N and Federici, G and Arrigoni-Martelli, E}, title = {Evidence for the involvement of carnitine-dependent long-chain acyltransferases in neuronal triglyceride and phospholipid fatty acid turnover.}, journal = {Journal of neurochemistry}, volume = {62}, number = {4}, pages = {1530-1538}, doi = {10.1046/j.1471-4159.1994.62041530.x}, pmid = {8133280}, issn = {0022-3042}, mesh = {Animals ; Carnitine O-Palmitoyltransferase/antagonists & inhibitors/*metabolism ; Cell Membrane/drug effects/metabolism ; Cells, Cultured ; Cerebral Cortex/cytology ; Embryo, Mammalian ; Epoxy Compounds/pharmacology ; Fatty Acids/*metabolism/pharmacology ; Membrane Lipids/metabolism ; Neurons/*enzymology ; Phosphatidylcholines/metabolism ; Phosphatidylethanolamines/metabolism ; Phospholipids/*metabolism ; Rats ; Rats, Sprague-Dawley ; Triglycerides/*metabolism ; }, abstract = {This study focuses on the potential involvement of carnitine palmitoyltransferase (CPT) on the phospholipid and triglyceride fatty acid turnover in neurons. This category of enzymes, which has been identified in several rat brain tissues, is well known for its role in modulating cellular fatty acid oxidation. Neuronal cell cultures from rat brain cortex incorporated radioactive palmitate or oleate into phospholipids and triglycerides. The largest fraction of radioactive fatty acids was recovered in phosphatidylcholine followed by triglycerides and, to a lesser extent, phosphatidylethanolamine. CPT activity measured in neuronal lysates obtained from neurons treated with 40 microM 2-tetradecylglycidic acid (TDGA) was almost completely abolished. Furthermore, between 2 and 10 microM TDGA CPT activity dropped more rapidly than between 10 and 40 microM. When the cells were pretreated with TDGA, the incorporation process of either radioactive fatty acid into triglycerides was dose-dependently suppressed. Radioactive fatty acid incorporation into phosphatidylcholine was significantly decreased in cells treated with TDGA. In contrast, phosphatidylethanolamine reacylation was essentially not affected by the CPT inhibitor. Similar results on the fatty acid incorporation into triglycerides and phospholipids were observed with neurons treated with palmitoyl-DL-aminocarnitine (PAC), a reversible CPT inhibitor, which does not consume free CoA. These effects do not seem to be the result of an inhibitory activity toward one of the steps involved in the acylation-deacylation process of triglycerides or phospholipids, as cellular lysates from TDGA-treated cells or lysates containing PAC incorporated radioactive fatty acids at rates comparable to controls. Our results suggest that CPT may be an important partner in the pathway of phospholipid and triglyceride fatty acid turnover in neurons.}, } @article {pmid8302185, year = {1993}, author = {Studenikina, FG and Mironov, MM and Denisova, VP and Pokrovskaia, GM}, title = {[The antimicrobial properties of metals and coatings for medical articles].}, journal = {Meditsinskaia tekhnika}, volume = {}, number = {5}, pages = {6-8}, pmid = {8302185}, issn = {0025-8075}, mesh = {Alloys/pharmacology ; Bacteria/*drug effects ; *Equipment Contamination ; Equipment Design ; *Equipment and Supplies ; Metals/*pharmacology ; Microbial Sensitivity Tests/methods ; }, abstract = {The in vitro experimental studies have shown that samples coated with vacuum technology-made materials, such as titanium mixtures with chromium, hafnium, zirconium, and copper have antimicrobial properties against staphylococci, Escherichia coli, Proteus, Pseudomonas aeruginosa. The impact of the coatings on bacterial cells is selective and ambiguous.}, } @article {pmid8302178, year = {1993}, author = {Studenikina, FG and Kosova, VN and Denisova, VP}, title = {[The physicochemical properties and biological characteristics of metals for medical instruments].}, journal = {Meditsinskaia tekhnika}, volume = {}, number = {5}, pages = {31-34}, pmid = {8302178}, issn = {0025-8075}, mesh = {Bacteria/drug effects ; Chemical Phenomena ; Chemistry, Physical ; Dose-Response Relationship, Drug ; *Equipment and Supplies ; Humans ; Metals/adverse effects/*chemistry/pharmacology ; Microbial Sensitivity Tests ; Prostheses and Implants ; }, abstract = {The metals having antimicrobial properties are of great interest in reducing pyoseptic complications in patients operated on when implants and medical instruments which contact with the body long are manufactured. The paper gives brief information on the physicochemical, antimicrobial, and toxic properties of a number of metals, on the mechanism of their toxic action.}, } @article {pmid7690724, year = {1993}, author = {Gershoni, JM and Denisova, G and Raviv, D and Smorodinsky, NI and Buyaner, D}, title = {HIV binding to its receptor creates specific epitopes for the CD4/gp120 complex.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {7}, number = {12}, pages = {1185-1187}, doi = {10.1096/fasebj.7.12.7690724}, pmid = {7690724}, issn = {0892-6638}, mesh = {AIDS Vaccines/*immunology ; Animals ; Antibodies, Monoclonal/immunology ; CD4 Antigens/*immunology ; *Epitopes ; HIV Envelope Protein gp120/*immunology ; Mice ; Protein Conformation ; }, abstract = {Effective vaccines against the human immunodeficiency virus (HIV) must cope with the genetic variation of the viral envelope (gp120) to combat or prevent acquired immunodeficiency syndrome (AIDS). Here we describe novel epitopes that are accentuated when gp120 complexes with its receptor (CD4). The presentation of these epitopes results through conformational rearrangements in the CD4/gp120 complex. Monoclonal antibodies directed to these epitopes inhibit syncytium formation, thus indicating the potential use of these epitopes as subunit vaccines.}, } @article {pmid8379109, year = {1993}, author = {Kodentsova, VM and Vrzhesinskaia, OA and Denisova, SN and Sokol'nikov, AA and Beketova, NA and Isaeva, VA and Netrebenko, OK and Spirichev, VB}, title = {[Standards of hourly excretion of B group vitamins with urine for children aged 9 to 13 years].}, journal = {Voprosy meditsinskoi khimii}, volume = {39}, number = {4}, pages = {27-31}, pmid = {8379109}, issn = {0042-8809}, mesh = {Adolescent ; Child ; Erythrocytes/enzymology ; Humans ; Reference Values ; Time Factors ; Transaldolase/antagonists & inhibitors ; Transketolase/blood ; Vitamin B Complex/*urine ; }, abstract = {Values of hour excretion of vitamins B1, B2, B6 and PP with urine in children of 9-13 years, studied under conditions of normal consumption of these vitamins, were estimated considering the correlation between the vitamins B concentration in blood and excretion of their metabolites with urine as well as using these parameters dependence on content of the vitamins in daily ration; for this purpose 35 adult persons and 31 children of both sexes were examined. Normal rate of riboflavin excretion with urine constituted 10-11 micrograms/h in children of this age, while of thiamine-11-12 micrograms/h. Under conditions of normal thiamine consumption, activity of erythrocyte transketolase, measured after preinactivation of transaldolase, exceeded 35 mumol/h/I ml of erythrocytes. Rates of excretion with urine of 4-pyridoxic acid and I-methyl nicotinamide were similar both in children and in adult persons and were equal to more than 40 micrograms/h and 400-600 micrograms/h, respectively.}, } @article {pmid8271738, year = {1993}, author = {Reshetnikov, EA and Denisova, AL}, title = {[Clinical course of asymptomatic cholecystolithiasis].}, journal = {Khirurgiia}, volume = {}, number = {7}, pages = {3-7}, pmid = {8271738}, issn = {0023-1207}, mesh = {Adult ; Aged ; Cholecystitis/complications/*diagnosis/physiopathology ; Cholelithiasis/complications/*diagnosis/physiopathology ; Female ; Follow-Up Studies ; Gastrointestinal Diseases/etiology ; Humans ; Male ; Middle Aged ; }, abstract = {Gallbladder concrements were found in 6.7% of 30,000 persons over 40 years of age during dispensary screening. In 720 (2.4%) of them the clinical and laboratory findings corresponded to those in chronic calculous cholecystitis, whereas in 1,290 persons gallbladder concrements were asymptomatic. Detailed study of 84 records of patients with asymptomatic cholecystolithiasis made in possible to recognize in most of them also chronic inflammatory diseases and dyskinesia of the gastrointestinal tract which could be conducive to the formation of concrements. During a 4-year follow-up period, signs of chronic calculous cholecystitis appeared in only 6% of these patients. The authors conclude that most patients with asymptomatic cholecystolithiasis must be subjected to regular medical examination and only with the development of a clinical picture of chronic calculous cholecystitis only some of them should be treated by surgery.}, } @article {pmid7690100, year = {1993}, author = {Maulik, N and Das, DK and Gogineni, M and Cordis, GA and Avrova, N and Denisova, N}, title = {Reduction of myocardial ischemic reperfusion injury by sialylated glycosphingolipids, gangliosides.}, journal = {Journal of cardiovascular pharmacology}, volume = {22}, number = {1}, pages = {74-81}, doi = {10.1097/00005344-199307000-00013}, pmid = {7690100}, issn = {0160-2446}, support = {HL 22559/HL/NHLBI NIH HHS/United States ; HL 33889/HL/NHLBI NIH HHS/United States ; HL 34360/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Coronary Circulation/drug effects ; Creatine Kinase/drug effects ; Free Radical Scavengers ; Gangliosides/*pharmacology ; Glycosphingolipids/chemistry/*pharmacology ; Hydroxides ; Hydroxyl Radical ; In Vitro Techniques ; Male ; Malondialdehyde/metabolism ; Myocardial Reperfusion Injury/*prevention & control ; N-Acetylneuraminic Acid ; Rats ; Rats, Sprague-Dawley ; *Sialic Acids ; Ventricular Function, Left/drug effects ; }, abstract = {Gangliosides, sialic acid-containing glycosphigolipids, are localized mostly to the outer leaflet of the lipid bilayer in the plasma membrane, particularly in brain. Gangliosides reduce edema formation, restore glucose metabolism, and increase cerebral blood flow after focal ischemia in the rat brain. We wished to determine whether gangliosides could also reduce myocardial ischemic and reperfusion injury. Isolated rat heart perfused by Langendorff technique was pretreated with gangliosides (1 microM) purified from the rat brain. After 15-min perfusion with gangliosides, hearts were made ischemic for 30 min by termination of coronary flow, followed by 60-min reperfusion. Ganglioside-treated heart exhibited better myocardial preservation, as evidenced by reduction in creatine kinase release and lipid peroxidation product formation enhanced coronary flow and contractile functions [left ventricular developed pressure (LVDP) and maximum first derivative of LVDP, LVdp/dtmax]. In addition, gangliosides reduced the hydroxyl radical formed during reperfusion of ischemic myocardium, as shown by high-performance liquid chromatography (HPLC)-electrochemical detection technique. In vitro studies demonstrated that these gangliosides were direct scavengers of superoxide anions (IC50 0.8 microM), and hydroxyl radicals (IC50 10 microM), as well hypohalite radicals (IC50 0.7 microM). Furthermore, ganglioside pretreatment was accompanied by reduced intracellular calcium overloading during ischemia and reperfusion as compared with untreated controls. The results of this study thus suggest that gangliosides can reduce ischemic reperfusion injury in isolated heart, probably by inhibiting intracellular calcium overloading and/or by directly scavenging the free radicals generated during reperfusion of ischemic myocardium.}, } @article {pmid8394508, year = {1993}, author = {Kaverina, EN and Akopian, TA and Denisova, TS and Karpov, VA and Ponomareva, TI and Naroditskiĭ, BS and Tikhonenko, TI}, title = {[Analysis of RAT2 cells, transformed by the CELO (FAV1) virus, using the polymerase chain reaction].}, journal = {Molekuliarnaia genetika, mikrobiologiia i virusologiia}, volume = {}, number = {3}, pages = {31-36}, pmid = {8394508}, issn = {0208-0613}, mesh = {Animals ; *Aviadenovirus ; Cell Line, Transformed ; *Cell Transformation, Viral ; DNA/genetics ; Genome, Viral ; Polymerase Chain Reaction ; Rats ; }, abstract = {DNAs extracted from the RAT2 cells transformed by the CELO virus (strain Phelps) have been analyzed by polymerase chain reaction. Sequences belonging to the left end of the viral genome (according to Ishibashi & Yasue, 1984) were not found in the tested DNAs. On the other hand, the polymerase chain reaction data have revealed the presence of fragments specific of the opposite end. We conclude that this region may have included the genes responsible for cell transformation, at least as far as Phelps viral strain is concerned.}, } @article {pmid8333193, year = {1993}, author = {Volozhin, AI and Vinogradova, SI and Denisova, IA and Zhuravleva, TP}, title = {[Lysozyme level in animal tissues in the simulation and treatment of periodontitis].}, journal = {Voprosy meditsinskoi khimii}, volume = {39}, number = {3}, pages = {53-57}, pmid = {8333193}, issn = {0042-8809}, mesh = {Animals ; Gingiva/*enzymology ; Gingivitis/enzymology ; Muramidase/blood/*metabolism ; Periodontitis/*enzymology ; Rabbits ; Rats ; }, abstract = {Inflammation developed after sewing of silk ligature into the rat and rabbit gingiva (parodonitis) was accompanied by increase in lysozyme content in gingiva tissue and in blood serum. Exogenous egg lysozyme, administered into normal animal gingiva tissue by means of ultrasound treatment (880 kHz, impulse regimen, 0.2 w/cm2), penetrated through the epithelial mucosal membrane layer, but did not accumulate in the membrane. However, lysozyme administered into the inflammation-injured gingiva tissue by ultrasound was accumulated in the tissue and arrested the inflammation and restored the impaired parodontium within shorter periods.}, } @article {pmid7975415, year = {1993}, author = {Bushueva, TV and Ladodo, KS and Spirichev, VB and Denisova, SN and Rybakova, EP}, title = {[Calcium homeostasis and calcium-regulating hormones in young children with phenylketonuria].}, journal = {Voprosy pitaniia}, volume = {}, number = {3}, pages = {16-21}, pmid = {7975415}, issn = {0042-8833}, mesh = {Calcitonin/blood ; Calcium/*blood ; Dehydrocholesterols/blood ; *Energy Intake ; Female ; *Food, Formulated ; Homeostasis ; Humans ; Infant ; Male ; Osteocalcin/blood ; Parathyroid Hormone/*blood ; Phenylketonurias/*blood/*diet therapy ; Phosphorus/blood ; }, abstract = {Calcium and calcium-regulating hormones were investigated in 19 infants with phenylketonuria. Parathyroid hormone, osteocalcin, dehydrocholecalciferol were found elevated while calcitonin reduced in the serum of the infants prior to the diet. Total calcium and phosphorus remained stable in the course of the study. Element diet resulted in reduced serum parathormone levels though surpassing those of healthy subjects. This fact is attributed to primary metabolic disorders responsible for the onset of hyperparathyroidism. The conclusion is made that element diet is unable to change calcium homeostasis and that of calcium-regulating hormones in infants with phenylketonuria.}, } @article {pmid8046907, year = {1993}, author = {Sheptulin, AA and Burkov, SG and Denisova, NA}, title = {[Clinical course of ulcer disease in women].}, journal = {Klinicheskaia meditsina}, volume = {71}, number = {1}, pages = {44-46}, pmid = {8046907}, issn = {0023-2149}, mesh = {*Duodenal Ulcer/diagnosis/epidemiology/etiology/physiopathology/therapy ; Female ; Gastric Acid/metabolism ; Humans ; Incidence ; Male ; Ovarian Diseases/complications ; Pregnancy ; Pregnancy Complications/physiopathology ; Sex Factors ; *Stomach Ulcer/diagnosis/epidemiology/etiology/physiopathology/therapy ; Treatment Outcome ; }, } @article {pmid10013770, year = {1991}, author = {Chamorro, A and Manko, VS and Denisova, TE}, title = {New exact solution for the exterior gravitational field of a charged spinning mass.}, journal = {Physical review. D, Particles and fields}, volume = {44}, number = {10}, pages = {3147-3151}, doi = {10.1103/physrevd.44.3147}, pmid = {10013770}, issn = {0556-2821}, } @article {pmid7186148, year = {1982}, author = {Serova, LV and Denisova, LA}, title = {The effect of weightlessness on the reproductive function of mammals.}, journal = {The Physiologist}, volume = {25}, number = {6}, pages = {S9-12}, pmid = {7186148}, issn = {0031-9376}, mesh = {Animals ; Female ; Male ; *Mammals ; Rats ; *Reproduction ; Space Flight ; *Weightlessness ; }, } @article {pmid7181462, year = {1982}, author = {Emanuél', NM and Konovalova, NP and D'iachkovskaia, RF and Denisova, LK}, title = {[Nitroxyl derivatives of rubomycin].}, journal = {Antibiotiki}, volume = {27}, number = {11}, pages = {811-815}, pmid = {7181462}, issn = {0003-5637}, mesh = {Animals ; Cyclic N-Oxides/*toxicity ; Daunorubicin/*analogs & derivatives/therapeutic use/toxicity ; Drug Evaluation, Preclinical ; Electrocardiography ; Kinetics ; Lethal Dose 50 ; Leukemia, Experimental/drug therapy ; Mice ; Neoplasm Transplantation ; Spin Labels ; Time Factors ; }, abstract = {The toxic and antitumor effects of new analogs of rubomycin were studied. It was shown that the spin-labeled derivatives had the lowest toxicity and highest antitumor activity. The diamagnetic analog was similar to rubomycin in its antitumor effect. It was demonstrated that ruboxyl-l had a lower cardiotoxicity than rubomycin and did not inhibit hemopoiesis at the maximum tolerated doses.}, } @article {pmid7185744, year = {1982}, author = {Ilyukhina, VA and Sychev, AG and Shcherbakova, NI and Baryshev, GI and Denisova, VV}, title = {The omega-potential: a quantitative parameter of the state of brain structures and of the individual. II. Possibilities and limitations of the use of the omega-potential for rapid assessment of the state of the individual.}, journal = {Human physiology}, volume = {8}, number = {5}, pages = {328-339}, pmid = {7185744}, issn = {0362-1197}, mesh = {Alcoholism/physiopathology ; Brain/physiopathology ; *Electroencephalography ; Female ; Humans ; Neurotic Disorders/physiopathology ; Schizophrenia/physiopathology ; Sports Medicine ; Time Factors ; }, } @article {pmid7147908, year = {1982}, author = {Denisova, TS and Gibadulin, RA}, title = {[Detailed study of the structure of simian adenovirus genome DNA and identification of its sequence in transformed cells].}, journal = {Voprosy virusologii}, volume = {27}, number = {5}, pages = {77-83}, pmid = {7147908}, issn = {0507-4088}, mesh = {Adenoviridae/*genetics ; Adenoviruses, Simian/*genetics ; Base Sequence ; Cell Transformation, Viral ; *DNA, Viral ; *Genes, Viral ; }, abstract = {The paper describes physical maps of SA-7P DNA drawn with the help of XhoI, HpaI and BglII enzymes. DNA nucleotide sequence in the left side of the viral genome was found to have the length of 150 nucleotides. It contains codon for initiation of protein synthesis and coincides in this area with the known primary structure of Ela operon for human adenoviruses Ad5, Ad7, and Ad12. Study on the cells of two lines transformed by fragments of SA-7P DNA showed DNA of these cells to contain elements of the viral genome in different numbers of copies.}, } @article {pmid7201545, year = {1982}, author = {Uspenskiĭ, LV and Denisova, OP and Ablitsov, IuA}, title = {[Primary lung chorioepithelioma in a male].}, journal = {Khirurgiia}, volume = {}, number = {5}, pages = {106-108}, pmid = {7201545}, issn = {0023-1207}, mesh = {Choriocarcinoma/*pathology/surgery ; Humans ; Lung Neoplasms/*pathology/surgery ; Male ; Middle Aged ; }, } @article {pmid7347805, year = {1981}, author = {Denisova, AS}, title = {Effect of electrical stimulation of the somatosensory cortex and caudate nucleus on extinctive inhibition of a food conditioned reflex to sound.}, journal = {Neuroscience and behavioral physiology}, volume = {11}, number = {6}, pages = {576-581}, pmid = {7347805}, issn = {0097-0549}, mesh = {Acoustic Stimulation ; Animals ; Caudate Nucleus/*physiology ; Conditioning, Classical/*physiology ; Dogs ; Eating ; Electric Stimulation ; Extinction, Psychological/*physiology ; Motor Cortex/physiology ; *Neural Inhibition ; Neural Pathways/physiology ; Somatosensory Cortex/*physiology ; Thalamic Nuclei/physiology ; }, } @article {pmid7311339, year = {1981}, author = {Kiselev, IuI and Denisova, OP}, title = {[Rare case of a biliary tract anomaly].}, journal = {Khirurgiia}, volume = {}, number = {10}, pages = {109-110}, pmid = {7311339}, issn = {0023-1207}, mesh = {Biliary Tract/*abnormalities/pathology ; Gallbladder/abnormalities/pathology ; Humans ; Male ; Middle Aged ; }, } @article {pmid7303158, year = {1981}, author = {Parkhomenko, II and Denisova, TS and Sitnikov, BS and Bogatyrenko, TN and Eliseeva, LV}, title = {[Oncogen localization in simian adenovirus DNA. I. In vitro rat cell transformation using the SV20 virus and its DNA].}, journal = {Tsitologiia}, volume = {23}, number = {8}, pages = {932-936}, pmid = {7303158}, issn = {0041-3771}, mesh = {Adenoviridae/*pathogenicity ; Adenoviruses, Simian/genetics/*pathogenicity ; Animals ; Animals, Newborn ; *Carcinogens ; *Cell Transformation, Viral ; DNA, Viral/*pharmacology ; Defective Viruses/genetics/pathogenicity ; Embryo, Mammalian ; Genes, Viral ; In Vitro Techniques ; Kidney ; Rats ; Rats, Inbred Strains ; Virus Cultivation ; }, abstract = {Cell transformation by the complete and the incomplete virus SV20 was investigated. To compare the oncogenic properties of human adenoviruses, two types of cell systems--the primary rat embryonic cell culture and the primary rat kidney cell culture--were used. The dependence of DNA concentration on transformation frequency was investigated. With the incomplete virus SV20, the transformation efficiency was more than that with the complete virus (16 and 1-3 percent, resp.). In addition, it has been shown that the primary rat kidney cell culture is more sensitive to transformation than the primary rat embryonic cells culture. The new-born Sirian hamsters being inoculated with virus SV20 DNA, the growth of a tumor being registered in the point of injection 120 days afterwards.}, } @article {pmid7293099, year = {1981}, author = {Moĭseenok, AG and Komar, VI and Denisova, NK and Khil'manovich, AP}, title = {[Urinary excretion of microbiologically detectable forms of pantothenic acid in viral hepatitis].}, journal = {Voprosy pitaniia}, volume = {}, number = {4}, pages = {18-22}, pmid = {7293099}, issn = {0042-8833}, mesh = {Adolescent ; Adult ; Biological Assay ; Convalescence ; Female ; Free Radicals ; Hepatitis A/*urine ; Hepatitis B/*urine ; Humans ; Male ; Middle Aged ; Pantothenic Acid/*urine ; Saccharomycetales/metabolism ; }, abstract = {The content of free and total pantothenic acid (PA) in the daily urine was studied microbiologically in 55 patients with virus hepatitis. At the height of the disease the excretion of the test vitamin forms with the urine noticeably decreased whatever the disease severity. During reconvalescence PA excretion rose because of the increase diuresis. However, the concentration of the vitamin in the urine did not reach normal. No disorders in PA metabolism were found in patients with hyperbilirubinemia of non-infectious genesis. Unlike normal subjects, oral administration of calcium pantothenate (50 ng) to patients with hepatitis results in a decrease of the excretion of the free form of PA. It is suggested that disorders in PA metabolism in patients with virus hepatitis are manifestations of functional vitamin deficiency which is a consequence of its reduced utilization.}, } @article {pmid7316826, year = {1981}, author = {Denisova, OP and Guznov, GI and Zalit, NIu}, title = {[Primary fibrosarcoma of the lung].}, journal = {Arkhiv patologii}, volume = {43}, number = {10}, pages = {45-48}, pmid = {7316826}, issn = {0004-1955}, mesh = {Female ; Fibrosarcoma/*pathology ; Humans ; Lung/pathology ; Lung Neoplasms/*pathology ; Middle Aged ; }, abstract = {A case of primary pulmonary fibrosarcoma in a women of 50 is described as a rare disease which is difficult to diagnose intravitally due to the absence of pathognomonic clinical and roentgenological data. The danger of prolonged time-course observation of the patient with a rounded shadow in the lung is emphasized. The importance of electron microscopic study to specify the morphological diagnosis is demonstrated.}, } @article {pmid7194473, year = {1980}, author = {Krymova, LIa and Kulikova, AI and Volkova, AA and Denisova, OM}, title = {[Changes in luteinizing hormone excretion in boys with chronic hepatitis].}, journal = {Pediatriia}, volume = {}, number = {12}, pages = {23-24}, pmid = {7194473}, issn = {0031-403X}, mesh = {Child ; Child, Preschool ; Chronic Disease ; Circadian Rhythm ; Hepatitis/*urine ; Humans ; Luteinizing Hormone/*urine ; Male ; }, } @article {pmid7431777, year = {1980}, author = {Uspenskiĭ, LV and Kurguzov, OP and Savchenko, AP and Lapchinskiĭ, VA and Denisova, OP}, title = {[Cancer of the adrenal cortex].}, journal = {Khirurgiia}, volume = {}, number = {10}, pages = {108-109}, pmid = {7431777}, issn = {0023-1207}, mesh = {Adrenal Cortex Neoplasms/*pathology ; Adrenal Rest Tumor/*pathology ; Female ; Humans ; Middle Aged ; }, } @article {pmid7416401, year = {1980}, author = {Sheveleva, GA and Kiriushchenkov, AP and Denisova, LA}, title = {[Effect of prostaglandin E2 on fetal development (experimental data)].}, journal = {Akusherstvo i ginekologiia}, volume = {}, number = {8}, pages = {53-55}, pmid = {7416401}, issn = {0300-9092}, mesh = {Animals ; Embryo, Mammalian/drug effects ; Female ; Fetus/*drug effects ; Pregnancy ; Prostaglandins E/*toxicity ; Rats ; }, } @article {pmid7383799, year = {1980}, author = {Fedorova, EV and Denisova, LN and Kasatkina, NV and Fedorov, AM and Berestova, EV}, title = {[Congenital progeria].}, journal = {Pediatriia}, volume = {}, number = {4}, pages = {66-68}, pmid = {7383799}, issn = {0031-403X}, mesh = {Female ; Humans ; Infant ; Progeria/*congenital/pathology ; }, } @article {pmid11635445, year = {1980}, author = {Denisova, E and Moskvina, M}, title = {[Not Available].}, journal = {Narodonaselenie}, volume = {}, number = {32}, pages = {43-57}, pmid = {11635445}, mesh = {*Demography ; History, Modern 1601- ; Statistics as Topic/*history ; USSR ; }, } @article {pmid7384905, year = {1980}, author = {Denisova, AP and Libenzon, LL}, title = {[Complex decompression and antibacterial therapy of inflammatory diseases of the internal genitalia].}, journal = {Sovetskaia meditsina}, volume = {}, number = {5}, pages = {74-76}, pmid = {7384905}, issn = {0038-5077}, mesh = {Adult ; Decompression/*methods ; Endometritis/*therapy ; Female ; Humans ; Immunity, Innate ; Lower Body Negative Pressure/*methods ; Muramidase/*therapeutic use ; Pelvic Inflammatory Disease/*therapy ; Pregnancy ; Recurrence ; }, } @article {pmid7213828, year = {1980}, author = {Kudriavtseva, GV and Denisova, II}, title = {[Determination of half-life time for the key enzymes of the pentose phosphate pathway--glucose-6-phosphate dehydrogenase and transketolase].}, journal = {Biokhimiia (Moscow, Russia)}, volume = {45}, number = {1}, pages = {118-123}, pmid = {7213828}, issn = {0320-9725}, mesh = {Animals ; Glucosephosphate Dehydrogenase/*metabolism ; Half-Life ; Kinetics ; Male ; Myocardium/enzymology ; Pentosephosphates/*metabolism ; Rats ; Thyroxine/*pharmacology ; Transketolase/*metabolism ; }, abstract = {Using hormonal induction by thyroxin, the half-life time and the rate constants for the synthesis and degradation of glucose-6-phosphate dehydrogenase and transketolase were determined. It was shown that the mechanisms of activation of these enzymes by thyroxin are different. Under hyperthyrosis an increase in the activity of glucose-6-phosphate dehydrogenase is induced by a decrease (2-fold) of the degradation rate constant; the rate constant of synthesis is not changed thereby, while the half-life time for the enzyme increases 2-fold. The activation of transketolase in this case can be accounted for by an almost 1,5-fold increase in the rate of the enzyme synthesis, whereas the degradation rate constant and the half-life time of the enzyme remain practically unchanged.}, } @article {pmid14270383, year = {1965}, author = {ZHURKIN, VP and DENISOVA, EA and KIRSANOVA, GI and LVOVSKAIA, EN}, title = {[CHARACTERISTICS OF VASCULAR DYSTONIA IN SUBJECTS EXPOSED TO CHRONIC IRRADIATION].}, journal = {Terapevticheskii arkhiv}, volume = {37}, number = {}, pages = {46-50}, pmid = {14270383}, issn = {0040-3660}, mesh = {*Dystonia ; *Electric Impedance ; Humans ; *Hypertension ; *Hypotension ; *Intraocular Pressure ; *Manometry ; *Ophthalmoscopy ; *Oscillometry ; *Plethysmography ; *Plethysmography, Impedance ; *Pulse ; *Radiation Injuries ; }, } @article {pmid14348322, year = {1965}, author = {DENISOVA, MG}, title = {[LABORATORY DIAGNOSIS OF DISSEMINATED LUPUS ERYTHRMATOSUS].}, journal = {Laboratornoe delo}, volume = {42}, number = {}, pages = {9-10}, pmid = {14348322}, issn = {0023-6748}, mesh = {*Clinical Laboratory Techniques ; Humans ; *Leukocytes ; *Lupus Erythematosus, Discoid ; *Lupus Erythematosus, Systemic ; *Neutrophils ; }, } @article {pmid14295802, year = {1964}, author = {BAKHRAKH, EE and EGOROVA, VD and DENISOVA, EP}, title = {[DISTRIBUTION OF PROTEINS AND POLYSACCHARIDES IN THE CELLS OF PASTEURELLA PESTIS CULTIVATED AT 28 DEGREES AND 37 DEGREES].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {41}, number = {}, pages = {135-139}, pmid = {14295802}, issn = {0372-9311}, mesh = {*Bacterial Proteins ; *Polysaccharides ; *Polysaccharides, Bacterial ; *Research ; *Yersinia pestis ; }, } @article {pmid14259408, year = {1964}, author = {GOLODETS, RG and DENISOVA, EA and PONIZOVSKAIA, AI}, title = {[EXPERIENCE WITH THE USE OF FUBROMEGAN IN CLINICAL PRACTICE IN THE TREATMENT OF OCCUPATIONAL DISEASES].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {8}, number = {}, pages = {49-51}, pmid = {14259408}, issn = {0016-9919}, mesh = {*Drug Therapy ; *Furans ; *Ganglionic Blockers ; Humans ; *Occupational Diseases ; *Quaternary Ammonium Compounds ; }, } @article {pmid14259407, year = {1964}, author = {KLIMOV, VS and DENISOVA, EA and GORBARENKO, NI}, title = {[TREATMENT OF LEUKOPENIA WITH BATYL ALCOHOL IN PATIENTS WITH CHRONIC RADIATION SICKNESS].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {8}, number = {}, pages = {47-49}, pmid = {14259407}, issn = {0016-9919}, mesh = {*Alcohols ; *Drug Therapy ; *Glyceryl Ethers ; Humans ; *Leukocyte Disorders ; *Leukopenia ; *Radiation Injuries ; }, } @article {pmid14252335, year = {1964}, author = {ILINA, LI and GORBARENKO, NI and DENISOVA, EA}, title = {[THE RELATION BETWEEN THE ELECTRICAL ACTIVITY OF THE CEREBRAL CORTEX AND PROTEIN METABOLISM IN THE CHRONIC ACTION OF IONIZING RADIATIONS].}, journal = {Meditsinskaia radiologiia}, volume = {9}, number = {}, pages = {8-13}, pmid = {14252335}, issn = {0025-8334}, mesh = {*Cerebral Cortex ; *Electroencephalography ; Liver/*physiology ; *Nervous System Physiological Phenomena ; Proteins/*metabolism ; *Radiation Effects ; *Radiation, Ionizing ; }, } @article {pmid14232039, year = {1964}, author = {DENISOVA, AA and SIVASH, KM}, title = {[ON THE MECHANICAL CHARACTERISTICS OF NORMAL BONES AND METAL FIXATIONS FOR OSTEOSYNTHESIS. (EXPERIMENTAL STUDY)].}, journal = {Ortopediia travmatologiia i protezirovanie}, volume = {25}, number = {}, pages = {63-64}, pmid = {14232039}, issn = {0030-5987}, mesh = {Animals ; *Bone and Bones ; Dogs ; *Fracture Fixation, Internal ; *Fractures, Bone ; *Metals ; *Research ; }, } @article {pmid14260470, year = {1964}, author = {DENISOVA, ZV}, title = {[RELATIONS BETWEEN SIGNALING SYSTEMS IN YOUNG PRE-SCHOOL CHILDREN DURING THE PROCESS OF DEVELOPMENT OF CONDITIONED REFLEXES TO OBJECT STIMULI].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {14}, number = {}, pages = {427-435}, pmid = {14260470}, issn = {0044-4677}, mesh = {*Biomedical Research ; *Cerebral Cortex ; Child ; *Conditioning, Classical ; *Nervous System Physiological Phenomena ; *Reflex ; }, } @article {pmid14223626, year = {1964}, author = {MENSHIKOV, GP and KUCHERIAVENKO, LP and DENISOVA, SI}, title = {[AMINO ACID COMPOSITION OF ACTINOMYCINS, (ANTIBIOTIC NO. 2703)].}, journal = {Antibiotiki}, volume = {9}, number = {}, pages = {309-311}, pmid = {14223626}, issn = {0003-5637}, mesh = {*Amino Acids ; *Anti-Bacterial Agents ; *Antibiotics, Antitubercular ; *Chemistry Techniques, Analytical ; *Chemistry, Pharmaceutical ; *Dactinomycin ; *Dermatologic Agents ; *Pharmacy ; *Research ; }, } @article {pmid14278544, year = {1964}, author = {MIKHAILOV, A and KRYLOV, AA and TOLSTOPIATOVA, NS and DENISOVA, LA and ANIKINA, LV and KHRIPUNKOV, DE and TITKOV, SI}, title = {[ON HEMATOLOGIC INDICES IN HEALTHY YOUNG MALES].}, journal = {Voenno-meditsinskii zhurnal}, volume = {11}, number = {}, pages = {68-70}, pmid = {14278544}, issn = {0026-9050}, mesh = {*Blood Cell Count ; *Blood Sedimentation ; *Hematocrit ; *Hemoglobinometry ; Humans ; Male ; }, } @article {pmid14161490, year = {1964}, author = {LIPOVETSKII, GS and GOLDINA, BG and KULKOVA, Ia and PEREPELKIN, VP and DENISOVA, AA and MANEVICH, EI and SMIRNOVA, MG}, title = {[SUTURELESS JOINING OF TISSUES (EXPERIMENTAL STUDY ON CYACRINE GLUE)].}, journal = {Eksperimental'naia khirurgiia i anesteziologiia}, volume = {29}, number = {}, pages = {3-6}, pmid = {14161490}, issn = {0013-3329}, mesh = {*Acrylic Resins ; *Adhesives ; *Bone and Bones ; *Cyanates ; *Cyanoacrylates ; *Fracture Fixation ; Humans ; *Muscles ; *Research ; *Suture Techniques ; *Tissue Adhesives ; *Vascular Surgical Procedures ; }, } @article {pmid14148658, year = {1964}, author = {DENISOVA, AS}, title = {[MODIFICATION OF HIGHER NERVOUS ACTIVITY IN THE DOG FOLLOWING THE ADMINISTRATION OF NORADRENALIN].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {14}, number = {}, pages = {40-46}, pmid = {14148658}, issn = {0044-4677}, mesh = {*Blood Pressure ; *Conditioning, Classical ; Dogs ; *Higher Nervous Activity ; *Nervous System Physiological Phenomena ; *Norepinephrine ; *Pharmacology ; *Reflex ; *Research ; *Salivation ; }, } @article {pmid14138427, year = {1964}, author = {DENISOVA, Ia}, title = {[ON SEPARATION BY ELECTROPHORESIS OF ALPHA AND BETA GLOBULIN FRACTIONS IN THE BLOOD SERUM OF DIFFERENT RODENTS].}, journal = {Laboratornoe delo}, volume = {10}, number = {}, pages = {12-13}, pmid = {14138427}, issn = {0023-6748}, mesh = {*Alpha-Globulins ; *Beta-Globulins ; *Blood Protein Electrophoresis ; *Research ; *Rodentia ; *Serum ; *Serum Globulins ; *Veterinary Medicine ; }, } @article {pmid14136193, year = {1964}, author = {GAMBURG, AL and DENISOVA, AM}, title = {[THE EFFECT OF CERTAIN PHARMACOLOGICAL PREPARATIONS ON THE CEREBRAL BIOELECTRICAL ACTIVITY IN SCHIZOPHRENIA].}, journal = {Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952)}, volume = {64}, number = {}, pages = {116-124}, pmid = {14136193}, issn = {0044-4588}, mesh = {*Acetylcholine ; *Adrenocorticotropic Hormone ; *Atropine ; *Cortisone ; *Desoxycorticosterone ; *Electroencephalography ; *Electrophysiological Phenomena ; *Epinephrine ; Humans ; *Pharmacology ; *Schizophrenia ; *Thyroid Hormones ; }, } @article {pmid14141391, year = {1963}, author = {DENISOVA, MV}, title = {[FOR THE FURTHER GROWTH OF PUBLIC HEALTH].}, journal = {Zdravookhranenie Belorussii}, volume = {9}, number = {}, pages = {44-46}, pmid = {14141391}, mesh = {*Biological Phenomena ; *Biometry ; *Hospitals ; Humans ; *Physiological Phenomena ; *Public Health ; *State Medicine ; *Statistics as Topic ; USSR ; }, } @article {pmid14075579, year = {1963}, author = {ASOEVA, EZ and DAUKSHA, AD and DENISOVA, EK}, title = {[GALANTHAMINE FROM AMARYLLIS HYBRIDA].}, journal = {Meditsinskaia promyshlennost' SSSR}, volume = {17}, number = {}, pages = {35-36}, pmid = {14075579}, mesh = {*Chemical Phenomena ; *Chemistry ; *Galantamine ; Humans ; *Liliaceae ; *Plants, Medicinal ; }, } @article {pmid14027004, year = {1963}, author = {DENISOVA, LG and TABOLIN, VA and FROM, AA}, title = {[On the use of low molecular polyvinylpyrrolidone in the combined treatment of hemolytic disease in newborn infants].}, journal = {Problemy gematologii i perelivaniia krovi}, volume = {8}, number = {}, pages = {48-52}, pmid = {14027004}, issn = {0552-2080}, mesh = {Combined Modality Therapy ; *Erythroblastosis, Fetal ; *Fetus ; *Hematologic Diseases ; *Povidone ; }, } @article {pmid14027005, year = {1962}, author = {DENISOVA, MV and VEISENBERG, VN}, title = {[Therapeutic-prophylactic work at the Orshanka flax factory].}, journal = {Zdravookhranenie Belorussii}, volume = {8}, number = {}, pages = {56-58}, pmid = {14027005}, mesh = {*Flax ; Humans ; *Occupational Medicine ; *Textiles ; *Work ; }, } @article {pmid14027003, year = {1962}, author = {DENISOVA, EA}, title = {[The rate of spreading of pulse waves as a method for the functional evaluation of the cardiovascular system in human subjects exposed to chronic radiation effects].}, journal = {Medical radiology}, volume = {10}, number = {}, pages = {28-32}, pmid = {14027003}, mesh = {*Cardiovascular System ; *Heart Function Tests ; *Heart Rate ; Humans ; *Pulse ; *Radiation Injuries ; }, } @article {pmid13885445, year = {1962}, author = {DENISOVA, NA}, title = {[Ambulant therapy of inflammatory processes of the female genitalia by infections of novocain with antibodies].}, journal = {Kazanskii meditsinskii zhurnal}, volume = {4}, number = {}, pages = {49}, pmid = {13885445}, issn = {0368-4814}, mesh = {Anti-Bacterial Agents/*therapy ; *Antibodies ; *Exercise Therapy ; Female ; *Genitalia, Female ; Gynecology/*therapy ; Humans ; Procaine/*therapy ; }, } @article {pmid14472500, year = {1962}, author = {MEN'SHIKOV, GP and DENISOVA, SI}, title = {[Isolation of actinomycetes from the Actinomyces fluorescens group].}, journal = {Antibiotiki}, volume = {7}, number = {}, pages = {31-32}, pmid = {14472500}, issn = {0003-5637}, mesh = {*Actinobacteria ; *Actinomyces ; *Streptomyces ; }, } @article {pmid13939139, year = {1962}, author = {NOVIKOVA, ECh and FARBER, DA and SHULEIKINA, KV and DENISOVA, LG}, title = {[On the early topical diagnosis of intracranial injuries in newborn infants].}, journal = {Vestnik Akademii meditsinskikh nauk SSSR}, volume = {17(10)}, number = {}, pages = {44-48}, pmid = {13939139}, issn = {0002-3027}, mesh = {*Birth Injuries ; *Brain Diseases ; *Craniocerebral Trauma ; *Early Diagnosis ; Humans ; }, } @article {pmid13885444, year = {1962}, author = {DENISOVA, AS}, title = {[Dynamics of volumetric changes of conditioned reflexes following increased physical intensity of conditioned stimuli].}, journal = {Trudy - Institut fiziologii imeni I. P. Pavlova}, volume = {10}, number = {}, pages = {13-22}, pmid = {13885444}, issn = {0568-5745}, mesh = {*Conditioning, Classical ; *Conditioning, Psychological ; *Nervous System Physiological Phenomena ; *Reflex ; }, } @article {pmid13885446, year = {1961}, author = {DENISOVA, ZV}, title = {[Effect of extra stimuli on speech reactions in children].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {11}, number = {}, pages = {991-998}, pmid = {13885446}, issn = {0044-4677}, mesh = {Child ; Humans ; Speech/*physiology ; }, } @article {pmid13721874, year = {1961}, author = {DENISOVA, ZV}, title = {[Disorder of the "law of strength" in differentiation of weak components of single complex (object) stimuli].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {11}, number = {}, pages = {438-443}, pmid = {13721874}, issn = {0044-4677}, mesh = {*Color Perception Tests ; Humans ; }, } @article {pmid13721872, year = {1961}, author = {DENISOVA, MG}, title = {[Modification of glycoproteins in the blood serum in experimental atherosclerosis and in clinical coronary insufficiency].}, journal = {Klinicheskaia meditsina}, volume = {39}, number = {}, pages = {56-59}, pmid = {13721872}, issn = {0023-2149}, mesh = {Arteriosclerosis/*etiology ; *Atherosclerosis ; Coronary Disease/*blood ; Glycoproteins/*blood ; *Heart ; Humans ; *Serum ; }, } @article {pmid13721875, year = {1961}, author = {DENISOVA, ZV}, title = {[On functional changes in the cerebral cortex of children during the action of weak extraneous stimuli].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {11}, number = {}, pages = {249-253}, pmid = {13721875}, issn = {0044-4677}, mesh = {Cerebral Cortex/*physiology ; Child ; Humans ; *Nervous System Physiological Phenomena ; }, } @article {pmid13698320, year = {1960}, author = {FATEEVA, MN and PONIZOVSKAIA, AI and SOKOLOV, VV and GORBARENKO, NI and DENISOVA, EA and OSTAPKOVICH, VE}, title = {[Initial reactions of the human organism to the action of ionizing radiations].}, journal = {Meditsinskaia radiologiia}, volume = {5}, number = {}, pages = {3-7}, pmid = {13698320}, issn = {0025-8334}, mesh = {*Radiation Effects ; *Radiation, Ionizing ; }, } @article {pmid13809702, year = {1960}, author = {CHERTKOVA, FA and GRODKO, NS and USHAKOVA, AA and DENISOVA, IIa and KATS, FM and DUDARENKO, GV}, title = {[A standard antibotulism serum type E].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {31}, number = {}, pages = {84-87}, pmid = {13809702}, issn = {0372-9311}, mesh = {Botulism/*immunology ; Humans ; }, } @article {pmid13815924, year = {1960}, author = {DENISOVA, MG}, title = {[Glycoproteins in the blood serum in rheumatic lesions of the heart].}, journal = {Terapevticheskii arkhiv}, volume = {32}, number = {}, pages = {16-18}, pmid = {13815924}, issn = {0040-3660}, mesh = {Glycoproteins/*blood ; *Heart ; Humans ; Rheumatic Fever/*blood ; *Serum ; }, } @article {pmid13721873, year = {1960}, author = {DENISOVA, SI and MEN'SHIKOVA, GP and KARAULOVA, EIa}, title = {[Isolation of a dark violet amorphous pigment from the mycelium of Actinomyces fulvoviolaceus strain 9700].}, journal = {Trudy Instituta biologii}, volume = {8}, number = {}, pages = {338}, pmid = {13721873}, issn = {0301-2387}, mesh = {*Actinomyces ; *Biological Products ; *Mycelium ; *Sprains and Strains ; *Viola ; }, } @article {pmid13661009, year = {1959}, author = {DENISOVA, LG}, title = {[Symptomatology of intracranial parturient trauma of newborns].}, journal = {Akusherstvo i ginekologiia}, volume = {35}, number = {3}, pages = {75-78}, pmid = {13661009}, issn = {0300-9092}, mesh = {*Birth Injuries ; *Craniocerebral Trauma ; Humans ; Infant, Newborn ; }, } @article {pmid13516195, year = {1957}, author = {DENISOVA, EA}, title = {[Functional state of liver in persons exposed to radioactive substances].}, journal = {Meditsinskaia radiologiia}, volume = {2}, number = {6}, pages = {44-49}, pmid = {13516195}, issn = {0025-8334}, mesh = {Humans ; Liver/*radiation effects ; *Radiation ; *Radiation Effects ; }, } @article {pmid13482814, year = {1957}, author = {DENISOVA, ZV}, title = {[Problem of physiological effect of gamma rays on the cerebral cortex].}, journal = {Meditsinskaia radiologiia}, volume = {2}, number = {4}, pages = {3-11}, pmid = {13482814}, issn = {0025-8334}, mesh = {Cerebral Cortex/*radiation effects ; Conditioning, Classical/*radiation effects ; *Gamma Rays ; Humans ; *Radiation ; *Reflex ; }, } @article {pmid13479534, year = {1957}, author = {DENISOVA, AA}, title = {[Paper partition chromatography in quantitative determination of amino acids].}, journal = {Biokhimiia (Moscow, Russia)}, volume = {22}, number = {4}, pages = {755-760}, pmid = {13479534}, issn = {0320-9725}, mesh = {Amino Acids/*analysis ; *Antifibrinolytic Agents ; *Chromatography ; *Chromatography, Liquid ; *Paper ; }, } @article {pmid13556953, year = {1957}, author = {DENISOVA, AS}, title = {[Effect of optimal doses of bromine on liminal extension of differentiation].}, journal = {Trudy - Institut fiziologii imeni I. P. Pavlova}, volume = {6}, number = {}, pages = {230-241}, pmid = {13556953}, issn = {0568-5745}, mesh = {Bromides/*pharmacology ; *Bromine ; *Cell Differentiation ; Conditioning, Classical/*drug effects ; Humans ; *Nervous System Physiological Phenomena ; *Reflex ; }, } @article {pmid13332907, year = {1956}, author = {DENISOVA, MG}, title = {[Paper electrophoresis of serum proteins in liver diseases].}, journal = {Klinicheskaia meditsina}, volume = {34}, number = {4}, pages = {40-43}, pmid = {13332907}, issn = {0023-2149}, mesh = {*Blood Proteins ; *Electrophoresis, Paper ; Humans ; *Liver Diseases ; }, } @article {pmid14386733, year = {1955}, author = {FATEEVA, MN and KLIMOV, VS and GORBARENKO, NI and DENISOVA, EA and ERINA, EV and OSTAPKOVICH, VE}, title = {[Early diagnosis of chronic radiation sickness].}, journal = {Vestnik rentgenologii i radiologii}, volume = {2}, number = {}, pages = {16-23}, pmid = {14386733}, issn = {0042-4676}, mesh = {*Chronic Disease ; *Early Diagnosis ; Humans ; Radiation Injuries/*diagnosis ; }, } @article {pmid14383043, year = {1955}, author = {BARASHKOV, SG and MOSKALIK, EK and DENISOVA, LI}, title = {[Soluble streptocid albumin].}, journal = {Meditsinskaia promyshlennost' SSSR}, volume = {1}, number = {}, pages = {7-10}, pmid = {14383043}, mesh = {*Albumins ; Sulfanilamide ; *Sulfanilamides ; }, } @article {pmid14383028, year = {1955}, author = {DENISOVA, ZM}, title = {[New strain of Aedes (Ochlerotatus)].}, journal = {Meditsinskaia parazitologiia i parazitarnye bolezni}, volume = {24}, number = {1}, pages = {58-61}, pmid = {14383028}, issn = {0025-8326}, mesh = {*Aedes ; Animals ; *Culicidae ; *Ochlerotatus ; }, } @article {pmid14359725, year = {1954}, author = {DENISOVA, AA}, title = {[Surgical treatment of craniostenosis].}, journal = {Voprosy neirokhirurgii}, volume = {18}, number = {6}, pages = {49-54}, pmid = {14359725}, mesh = {*Craniofacial Abnormalities ; *Craniosynostoses ; Humans ; *Musculoskeletal Abnormalities ; Skull/*abnormalities ; }, } @article {pmid13097818, year = {1953}, author = {SATAEVA, RM and BEILIN, PE and LAGEDZA, IA and DENISOVA, NP}, title = {Data on the problem of prophylactic and therapeutic regime in its efficacy.}, journal = {Klinicheskaia meditsina}, volume = {31}, number = {9}, pages = {71-74}, pmid = {13097818}, issn = {0023-2149}, mesh = {*Hospitals ; Sleep/*therapeutic use ; }, } @article {pmid13216980, year = {1953}, author = {DENISOVA, AS}, title = {[Effect of small doses of luminal on the higher nervous function in dogs].}, journal = {Trudy - Institut fiziologii imeni I. P. Pavlova}, volume = {2}, number = {}, pages = {31-51}, pmid = {13216980}, issn = {0568-5745}, mesh = {Animals ; Barbiturates/*pharmacology ; *Conditioning, Classical ; Dogs ; *Nervous System Physiological Phenomena ; *Reflex ; }, } @article {pmid15413225, year = {1949}, author = {DENISOVA, ZV}, title = {[Manifestations of association in the formation of conditioned reflexes to complex stimulants].}, journal = {Trudy fiziologicheskikh laboratorii akademika I.P. Pavlova}, volume = {16}, number = {}, pages = {162-175}, pmid = {15413225}, mesh = {*Central Nervous System Agents ; *Central Nervous System Stimulants ; *Conditioning, Classical ; *Generalization, Stimulus ; *Kinesthesis ; }, } @article {pmid1305870, year = {1992}, author = {Denisova, SV and Sapozhkov, AV}, title = {[The effect of bonnecor on blood coagulability and thrombocyte aggregation in transient myocardial ischemia].}, journal = {Eksperimental'naia i klinicheskaia farmakologiia}, volume = {55}, number = {6}, pages = {29-31}, pmid = {1305870}, issn = {0869-2092}, mesh = {Animals ; Anti-Arrhythmia Agents/pharmacology/*therapeutic use ; Blood Coagulation/*drug effects ; Dibenzazepines/pharmacology/*therapeutic use ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Female ; Male ; Myocardial Ischemia/blood/*drug therapy ; Platelet Aggregation/*drug effects ; Rabbits ; Time Factors ; }, abstract = {The experiments on conscious rabbits have indicated that bonnecor given in doses of 0.05 mg/kg and 0.5 mg/kg accelerates clot formation and platelet aggregation, without changing the density of a thrombus. In experimental transient myocardial ischemia, the agent decreases the hypercoagulative change associated with the damaging effect of occlusion and reperfusion.}, } @article {pmid1345663, year = {1992}, author = {Portnoĭ, LM and Dibirov, MP and Denisova, LB}, title = {[Diagnostic perspectives of mobile radiographic computerized tomography].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {4}, pages = {44-48}, pmid = {1345663}, issn = {0042-4676}, mesh = {Forecasting ; Hospitals, Special ; Mobile Health Units/*organization & administration/trends ; Neoplasms/*diagnostic imaging ; *Program Development ; Russia ; Tomography, X-Ray Computed/economics/*instrumentation/methods ; }, abstract = {The authors assess mobile methods of x-ray computer-aided tomography (CAT) and suggest an organization and methodological scheme of its application. Their program of the first and up to now the only one in this country mobile CAT device is based on the new principles of mobile CAT application. It is realized in special hospitals of large regions, where the patients with the optimal indications for CAT are assembled. Over 15,000 examinations were carried out with the use of the suggested CAT program over 4 years, that resulted in detection of 1295 brain tumors, 804 cases with neoplastic involvement of the abdominal cavity and the retroperitoneal space. The authors claim that wide application of mobile CAT devices according to the program they suggest will help decide the problem of unavailability of such examinations, for it will rule out the principal cause of this unavailability--economic problems arising because of high price of this equipment. One mobile device may replace 3 permanent CAT devices, if used according to the program suggested by the authors.}, } @article {pmid1441212, year = {1992}, author = {Iureskul, IV and Denisova, LB}, title = {[The differential diagnosis of an abdominal aortic aneurysm and a retroperitoneal para-aortal hematoma].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {3}, pages = {55-57}, pmid = {1441212}, issn = {0042-4676}, mesh = {Adult ; Aneurysm, False/*diagnosis/diagnostic imaging ; Aortic Aneurysm, Abdominal/*diagnosis/diagnostic imaging ; Diagnosis, Differential ; Humans ; Male ; Radiography ; *Retroperitoneal Space ; Ultrasonography ; }, } @article {pmid1441207, year = {1992}, author = {Nefedova, VO and Arablinskiĭ, AV and Davydova, IV and Iureskul, IV and Denisova, LB and Petrova, GA and Dibirov, MP and Role, MP}, title = {[The role of x-ray computed tomography in the topical diagnosis of insulinomas of the pancreatic gland].}, journal = {Vestnik rentgenologii i radiologii}, volume = {}, number = {3}, pages = {39-41}, pmid = {1441207}, issn = {0042-4676}, mesh = {Female ; Humans ; Insulinoma/*diagnostic imaging ; Male ; Pancreatic Neoplasms/*diagnostic imaging ; *Tomography, X-Ray Computed ; }, abstract = {Pancreatic insulinomas were intraoperatively revealed in 15 patients. X-ray computed tomography (CAT) revealed the tumor in only 6 (40 %) patients. The mean size of detectable insulinomas was 2.4 cm, that of undetectable ones 1.2 cm. X-ray CAT diagnosis is facilitated in case of a superficial localization of the tumor on the body or tail of the gland .}, } @article {pmid1534407, year = {1992}, author = {Lebedev, LR and Andreeva, IS and Serov, GD and Denisova, LIa and Pustoshilova, NM}, title = {[BME 361 I--a new site-specific deoxyribonuclease type II from Bacillus megaterium 361].}, journal = {Prikladnaia biokhimiia i mikrobiologiia}, volume = {28}, number = {2}, pages = {173-177}, pmid = {1534407}, issn = {0555-1099}, mesh = {Autoradiography ; Bacillus megaterium/*enzymology ; Bacteriophage lambda/metabolism ; Chromatography, Liquid ; DNA, Bacterial/metabolism ; DNA, Viral/metabolism ; Deoxyribonucleases/*metabolism ; Electrophoresis, Polyacrylamide Gel ; Hydrolysis ; Plasmids ; Substrate Specificity ; }, abstract = {Bme 361 I, a new site-specific type II deoxyribonuclease, was purified from Bacillus megaterium 361 by chromatography on phosphocellulose P 11 and hydroxylapatite. The enzyme recognizes and cleaves the nucleotide sequence 5'-GG decreases CC-3' in double-strand DNA. Thus it is a true isoschizomer of deoxyribonucleases Hae III and BspR I.}, } @article {pmid1413708, year = {1992}, author = {Trushinskaia, GN and Grudinin, MP and Denisova, GF and Gibadulin, RA}, title = {[The antigenic and immunogenic properties of a recombinant protein of the HIV-1 gag-pol gene secreted by Saccharomyces cerevisiae yeast cells].}, journal = {Voprosy virusologii}, volume = {37}, number = {1}, pages = {19-22}, pmid = {1413708}, issn = {0507-4088}, mesh = {Animals ; Antigens, Viral/blood/*immunology ; Bacterial Proteins/blood/immunology ; Escherichia coli/physiology ; Fungal Proteins/blood/immunology/*metabolism ; Gene Products, gag/blood/*immunology ; Gene Products, pol/blood/*immunology ; HIV Antibodies/blood ; HIV-1/genetics/*immunology ; Humans ; Immunization/methods ; Immunoblotting ; Immunoenzyme Techniques ; Rabbits ; Recombinant Proteins/blood/immunology ; Saccharomyces cerevisiae/*physiology ; }, abstract = {Analysis of the immunological properties of recombinant proteins of HIV-1 gene gag-pol secreted by yeast cells S. cerevisiae was carried out. The proteins under study interacted with antibodies from HIV-1-seropositive human subjects and with antibodies of rabbit immune serum to the native virus as effectively and specifically as natural HIV-1 proteins. The yeast gag-pol-protein complex was markedly immunogenic and induced in animals synthesis of antibodies of a certain specificity spectrum. A comparative immunochemical analysis of the properties of the recombinant proteins carried out by EIA and immune blot showed a certain degree of similarity between the yeast proteins and those of analogous construction produced in E. coli system.}, } @article {pmid1413335, year = {1992}, author = {Trapeznikova, MF and Zakhmatov, IuM and Denisova, LB and Mezentsev, VA and Dutov, VV and Arablinskiĭ, AV and Aiukaev, RIa}, title = {[The functional assessment of the renal parenchyma and perirenal fatty tissue during electropiezolithotripsy by x-ray computed tomography].}, journal = {Urologiia i nefrologiia}, volume = {}, number = {1-3}, pages = {25-28}, pmid = {1413335}, issn = {0042-1154}, mesh = {Adipose Tissue/*diagnostic imaging/physiopathology ; Adolescent ; Adult ; Evaluation Studies as Topic ; Female ; Humans ; Kidney/*diagnostic imaging/physiopathology ; Kidney Calculi/diagnostic imaging/physiopathology/therapy ; Lithotripsy/adverse effects/*instrumentation ; Male ; Middle Aged ; Time Factors ; *Tomography, X-Ray Computed ; }, abstract = {Computed tomography was performed before and after telelithotripsy to evaluate changes in renal parenchyma induced by the procedure in 34 patients with nephroliths. Piezolith-2300 lithotriptor ("Wolf", FRG) was employed. The images showed no serious parenchymal injuries or paranephric hematomas, on the one hand, but density changes in the parenchyma, on the other hand. These were of 3 types: focal reduction in 3, diffuse reduction in 4 and diffuse increase of the density in 2 patients. As shown by comparison with literature data, telelithotripsy on "Piezolith-2300" causes minimal changes in renal parenchyma and perirenal fat. In view of this, the procedure is recommended for wide clinical and outpatient practice.}, } @article {pmid1950288, year = {1991}, author = {Iurov, SV and Pchelintsev, SIu and Afanas'ev, SS and Vorob'ev, AA and Urakov, NN and Cherenkova, GV and Denisova, NB and Fedortsov, KK}, title = {[The characteristics of the antibody response of animals immunized with components of the surface structures of Francisella tularensis].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {8}, pages = {54-58}, pmid = {1950288}, issn = {0372-9311}, mesh = {Animals ; Antibodies, Bacterial/*biosynthesis/blood ; Antigens, Bacterial/*immunology ; Antigens, Surface/immunology ; Bacterial Vaccines/*immunology ; Dose-Response Relationship, Immunologic ; Female ; Francisella tularensis/*immunology ; Immunization/*methods ; Immunoglobulin A/blood ; Immunoglobulin G/blood ; Immunoglobulin Isotypes/blood ; Immunoglobulin M/blood ; Male ; Papio ; Time Factors ; }, abstract = {Antibody formation in animals immunized with one of the components of F. tularensis surface structures was studied. The time course of antibody formation in 20 hamadryas baboons was studied in the passive hemagglutination (PHA) test, microagglutination (MA) test, and indirect enzyme immunoassay, used for the determination of IgG, IgA and IgM antibodies. The character of antibody response in the animals immunized with components of F. tularensis surface structures (S-complex) and with live tularemia vaccine was compared. The study revealed that immunization with the S-complex induced the formation of antibodies detected by all three methods. Antibody formation to the S-complex was found to be dose-dependent. With the increase of the injected dose of the S-complex, antibody titers determined in the PHA test decreased and those determined in the MA test increased, which was seemingly due to the induction of antibodies differing in their isotypes. After immunization with the S-complex the levels of IgG antibodies were lower and the levels of IgM antibodies by day 28 after immunization higher than after the injection of live tularemia vaccine.}, } @article {pmid1792744, year = {1991}, author = {Naumova, VN and Denisova, SN and Savina, MI and Ladodo, KS and Kutafina, EK}, title = {[The amino acid spectrum of plasma and erythrocytes in children with kidney diseases at the stage of chronic kidney insufficiency].}, journal = {Voprosy pitaniia}, volume = {}, number = {4}, pages = {30-34}, pmid = {1792744}, issn = {0042-8833}, mesh = {Adolescent ; Amino Acids/*blood ; Child ; Dietary Proteins/*administration & dosage ; Erythrocytes/*chemistry ; Humans ; Kidney Failure, Chronic/blood/*diet therapy ; }, abstract = {The effect of diets with varying protein restrictions on the amino-acid spectrum of plasma and erythrocytes was studied in 46 children with total chronic renal insufficiency (CRI), stages I and II, resultant from tubulo-interstitial diseases of the kidneys and glomerulonephritis. Qualitative and quantitative changes in the spectrum of blood amino acids are recorded at the initial stage of CRI and depend on the degree of protein restriction in the diet. The diet with a sharp protein restriction (Giordano-Giovanetti type) produces hypoazotemic effect and possesses anabolic properties. Disorders in amino-acid metabolism serve indications for using essential amino acids and their ketoanalogues in children with uremia.}, } @article {pmid1872100, year = {1991}, author = {Iurov, SV and Pchelintsev, SIu and Afanas'ev, SS and Vorob'ev, AA and Urakov, NN and Cherenkova, GV and Fedortsov, KK and Krasnoproshina, LI and Vlasov, GS and Denisova, NB}, title = {[The use of microdot immunoenzyme analysis with visual detection for the determination of tularemia antibodies].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {3}, pages = {61-64}, pmid = {1872100}, issn = {0372-9311}, mesh = {Animals ; Antibodies, Bacterial/*blood ; Bacterial Vaccines/immunology ; Collodion ; Evaluation Studies as Topic ; Female ; Francisella tularensis/*immunology ; Immunization/methods ; Immunoblotting/instrumentation/*methods ; *Immunoenzyme Techniques/instrumentation ; Male ; Membranes, Artificial ; Papio ; Time Factors ; }, abstract = {The possibility of using the micropoint enzyme immunoassay (EIA) on a nitrocellulose membrane with the visual evaluation of results for the detection of tularemia IgG antibodies in hamadryas baboons at the postvaccinal period has been studied. The sensitivity of this assay has been compared with that of the passive hemagglutination (PHA) test, the microagglutination (MA) test and EIA with the spectrophotometric evaluation of results in plates. As shown in this study, EIA in the above-mentioned modification can be successfully used for the detection of tularemia antibodies in the blood serum. The sensitivity of micropoint EIA has proved to be not inferior to that of EIA in plates, while exceeding the sensitivity of the PHA test 10- to 20-fold and the sensitivity of the MA test 10- to 1,000-fold. This method is simple, reliable, highly sensitive, economic and requires no special equipment, which makes it highly promising for the diagnosis of tularemia and the evaluation of humoral immunity at the postvaccinal period.}, } @article {pmid1851536, year = {1991}, author = {Terent'ev, MA and Ovadis, MI and Denisova, TS and Chernin, LS}, title = {[A comparative study of the functions of recBCD-nuclease from Escherichia coli and "recombinase", encoded by plasmid R1drd-19].}, journal = {Molekuliarnaia genetika, mikrobiologiia i virusologiia}, volume = {}, number = {2}, pages = {19-23}, pmid = {1851536}, issn = {0208-0613}, mesh = {Bacteriophage lambda/metabolism ; DNA Nucleotidyltransferases/*genetics ; DNA Topoisomerases, Type I/*genetics ; DNA-Binding Proteins/metabolism ; Escherichia coli/*enzymology/genetics ; *Escherichia coli Proteins ; Exodeoxyribonuclease V ; Exodeoxyribonucleases/*genetics ; Genes, Bacterial ; *Integrases ; Plasmids ; Recombinases ; Recombination, Genetic ; Viral Proteins/metabolism ; }, abstract = {The RecBCD nuclease of Escherichia coli and "recombinase" determined by R1drd-19 plasmid (the latter is able to replace at least partially the indicated cellular enzyme) were shown to differ from each other in some essential features. The product encoded by the plasmid as distinct from RecBCD nuclease practically is not sensitive to inhibition by GamS protein of the lambda phage. Earlier, it was found that the presence of R1drd-19 plasmid in the recBC cells restores the level of the total ATP-dependent exonuclease activity because of appearance in such cells of a new exonuclease activity also ATP-dependent. The exonuclease activity determined by R1drd-19 plasmid was found to differ from the corresponding activity of the RecBCD enzyme. The plasmid enzyme was able to prevent reproduction of T4g2- mutant on recBC cells. The ability of the plasmid "recombinase" to some stimulation of intrachromosomal recombination in recA mutant witness to incomplete RecA-dependence of its function. No significant homology was registered between Escherichia coli DNA fragment containing the recB, recC, recD genes and the EcoRI-C-fragment of R1drd-19 carrying the sequences responsible for recombination and repair functions of the plasmid.}, } @article {pmid2041688, year = {1991}, author = {Kostenko, EV and Denisova, MF and Iakovlev, AA}, title = {[Prostaglandin levels in the blood and gastric mucosa of children with functional disorders of the stomach and chronic gastroduodenitis].}, journal = {Pediatriia}, volume = {}, number = {1}, pages = {21-24}, pmid = {2041688}, issn = {0031-403X}, mesh = {Adolescent ; Child ; Child, Preschool ; Chronic Disease ; Dinoprost/blood/*metabolism ; Dinoprostone/blood/*metabolism ; Duodenitis/*physiopathology ; Gastric Acid/*metabolism ; Gastric Mucosa/*metabolism ; Gastritis/*physiopathology ; Gastroenteritis/*physiopathology ; Humans ; }, abstract = {In patients with functional disorders of the stomach and chronic gastroduodenitis, the content of cellular bioregulaters (prostaglandins) in the blood and gastric mucosa was abnormal. The revealed alterations may give rise to a reduction of mucosal resistance because of cytoprotection weakening and derangement of the control over gastric secretion. The data obtained make great contributions to our concepts of the pathogenesis of gastroduodenal pathology and children and provide evidence for new approaches to its prevention and treatment.}, } @article {pmid1869078, year = {1991}, author = {Stolbun, BM and Kolesnikova, AV and Dubinina, IM and Murzinova, NI and Aliaeva, MN and Rapoport, IK and Serzhantov, AB and Denisova, IV}, title = {[Assessment of the functional status of the engineering-technical staff at a machine-building plant].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {5}, pages = {18-21}, pmid = {1869078}, issn = {0016-9919}, mesh = {Adult ; *Engineering ; Female ; *Health Status ; Humans ; Male ; Middle Aged ; *Occupations ; Physical Examination ; }, abstract = {For early detection of functional disorders and risk-factors among the engineering staff at a machine-building plant, a set of highly informative, physiologically grounded and accessible techniques were used. To improve the patterns of out-patient screening of the staff, the contributors used physiologic and psychologic testing techniques, ECG monitoring registration in dynamics in the real occupational conditions, and riskometry, which facilitated the substantiation procedures for individual medical recommendations.}, } @article {pmid1858336, year = {1991}, author = {Zubareva, EV and Seferova, RI and Denisova, NA}, title = {[Change in the lipid composition of the inner mitochondrial membranes in rat organs during adaptation to heat].}, journal = {Voprosy meditsinskoi khimii}, volume = {37}, number = {1}, pages = {28-31}, pmid = {1858336}, issn = {0042-8809}, mesh = {*Adaptation, Physiological ; Animals ; Cholesterol/metabolism ; Fatty Acids/metabolism ; *Hot Temperature ; Membrane Lipids/*metabolism ; Mitochondria/*metabolism ; Phospholipids/metabolism ; Rats ; }, abstract = {Under conditions of adaptation to heating lipid composition in mitochondrial membranes of rat inner tissues was altered as follows: an increase in relative concentration of plasmalogenous forms of phospholipids (kidney, heart) and in content of saturated fatty acids (liver tissue), a decrease in the index of fatty acids unsaturation and in the ratio of fatty acids omega-3/omega-6. The alterations observed enabled the membranes to keep sufficient amount of liquidity essential for functional activity of mitochondria in heating.}, } @article {pmid1788232, year = {1991}, author = {Derbikova, TI and Reĭkhrud, VM and Kononenko, VG and Martynov, IuD and Egunova, SM and Denisova, SG}, title = {[Pathology of the mediastinum in phthisiological practice].}, journal = {Problemy tuberkuleza}, volume = {}, number = {10}, pages = {50-53}, pmid = {1788232}, issn = {0032-9533}, mesh = {Diagnosis, Differential ; Diagnostic Errors ; Female ; Fibrosarcoma/diagnosis ; Humans ; Male ; Mediastinal Cyst/diagnosis ; Mediastinal Diseases/*diagnosis ; Mediastinal Neoplasms/diagnosis ; Middle Aged ; Teratoma/diagnosis ; Thymoma/diagnosis ; Tuberculosis, Pulmonary/*diagnosis ; }, } @article {pmid1773885, year = {1991}, author = {Denisova, NA and Gorbunov, NV and Avrova, NF}, title = {Fatty acid composition of phospholipids of myelin and synaptosomal proteolipid complexes from vertebrate brain.}, journal = {The International journal of biochemistry}, volume = {23}, number = {9}, pages = {811-818}, doi = {10.1016/0020-711x(91)90064-t}, pmid = {1773885}, issn = {0020-711X}, mesh = {Animals ; *Brain Chemistry ; Fatty Acids/*analysis ; Myelin Sheath/*chemistry ; Phospholipids/*chemistry ; Proteolipids/*chemistry ; Synaptosomes/*chemistry ; Vertebrates ; }, abstract = {1. Fatty acid composition of five main phospholipids of vertebrate brain myelin and synaptosomal proteolipids and membranes was studied. 2. Higher content of monoenoic and lower content of saturated and polyenoic fatty acids was found to be characteristic of phospholipids from myelin and myelin proteolipids as compared to phospholipids from synaptosomal proteolipids and membranes of vertebrates (from fishes to mammalians). Fatty acid composition of phospholipids of proteolipid complexes and of the membranes, from which they were isolated, were found to be similar in various species studied. 3. Microviscosity was found to be higher in myelin as compared to synaptosomal membranes of frog Rana temporaria and in rabbit Lepus cuniculus. It appears to be due to the difference in proteolipid content and in lipid composition of myelin and synaptosomal membranes.}, } @article {pmid1724040, year = {1991}, author = {Karal'nik, BV and Denisova, TG and Abdrakhmanova, LSh and Sarbasova, ShI and Kadyrov, SO}, title = {[The serologic diagnosis of group B salmonelloses].}, journal = {Laboratornoe delo}, volume = {}, number = {7}, pages = {52-54}, pmid = {1724040}, issn = {0023-6748}, mesh = {*Citrobacter ; Diagnosis, Differential ; Enterobacteriaceae Infections/*diagnosis ; Humans ; Salmonella Infections/*diagnosis ; *Salmonella typhimurium ; Serologic Tests ; }, abstract = {Antibacterial sera activities towards Citrobacter O22 and Salmonella typhimurium were tested with O22, O1, O4, O5, O12 erythrocytic diagnostic agents. Cross activities of O22, O1, O4, O5, O12, and Hi antigens were tested with the same and Hi erythrocytic diagnostic agents in the antibody neutralization test. The findings have confirmed the identity or very close relationship between the tested O antigens. Screening for antigens of the excretions from patients with S. typhimurium and Citrobacter O22 infections has shown that indication of Hi antigen may be considered as the differentiating criterion between these infections.}, } @article {pmid2127502, year = {1990}, author = {Rumiantsev, SN and Avrova, NF and Pospelov, VF and Denisova, NA}, title = {[The effect of gangliosides on the adhesive interaction of Neisseria meningitidis with human cells].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {10}, pages = {29-32}, pmid = {2127502}, issn = {0372-9311}, mesh = {Animals ; Bacterial Adhesion/*drug effects ; Cells, Cultured/drug effects/microbiology ; Dose-Response Relationship, Drug ; Epithelial Cells ; Epithelium/drug effects/microbiology ; Erythrocytes/drug effects/microbiology ; Gangliosides/isolation & purification/*pharmacology ; Humans ; Leukocytes/drug effects/microbiology ; Mouth Mucosa/cytology/drug effects/microbiology ; N-Acetylneuraminic Acid ; Neisseria meningitidis/*drug effects/pathogenicity ; Sialic Acids/pharmacology ; Swine ; }, abstract = {The influence of a number of gangliosides and sialic acid on the adhesive interaction of meningococci and human cells have been studied. Sialic acid has been found to produce no influence on adhesion, and the preliminary treatment of meningococci with gangliosides or their preparations suppresses the capacity of meningococci for attachment to epithelial cells and erythrocytes. At the same time the degree of the inhibition of adhesion depends on the kind and concentration of gangliosides. On the contrary, after the treatment of target cells with gangliosides (1.25 micrograms/ml) the adhesion indices of meningococci with respect to these cells increase 5- to 8-fold. These data are indicative of the participation of gangliosides in the adhesive interaction of meningococci and human cells.}, } @article {pmid2288984, year = {1990}, author = {Shaginian, KA and Alekhina, IA and Denisova, NP}, title = {[Serine proteinase from the higher basidiomycetes of Coprinus genus].}, journal = {Biokhimiia (Moscow, Russia)}, volume = {55}, number = {8}, pages = {1387-1395}, pmid = {2288984}, issn = {0320-9725}, mesh = {Amino Acid Sequence ; Amino Acids/chemistry ; Coprinus/*enzymology ; Hydrogen-Ion Concentration ; Hydrolysis ; Molecular Sequence Data ; Serine Endopeptidases/chemistry/*isolation & purification ; Substrate Specificity ; Temperature ; }, abstract = {A thiol-dependent serine proteinase has been isolated for the first time from a higher basidiomycete Coprinus 7N culture filtrate by affinity chromatography on bacitracin-Sepharose combined with ion-exchange chromatography on DEAE-Sepharose. This procedure resulted in a homogeneous enzyme with 32-fold purification and 55% yield. The enzyme has a molecular mass of 33,000 Da and pI of 8.5; its amino acid composition appears as follows: Lys7, His7, Arg10, Asx29, Thr24, Ser30, Glx19, Pro13, Gly39, Ala40, Cys2-3, Val23, Met1-2, Ile14, Leu13, Tyr6, Phe7. The enzyme shows the optimal activity towards Z-Ala-Ala-Leu-pNA at 8.5 and is stable at pH 6-9. The temperature optimum of the enzyme activity lies at 37 degrees C. The proteinase is completely inactivated by the specific inhibitors of serine proteinases, diisopropylfluorophosphate and phenylmethylsulfonylfluoride, as well as by the SH-group reagent, p-chloromercuribenzoate. The Coprinus 7N proteinase hydrolyzes, azocasein, azoalbumin, hemoglobin, fibrin and synthetic chromogenic peptide substrates, e. g., Z-Ala-Ala-Leu-pNA, Z-Gly-gly-Leu-pNA. Some properties of the Coprinus 7N proteinase are very similar to those of thiol-dependent serine proteinases from bacilli, actinomycetes, fungi and plants which form a subfamily of thiol-dependent serine proteinases within the family of subtilisins.}, } @article {pmid2233784, year = {1990}, author = {Denisova, TS and Raspopova, VIu and Avdienko, ID and Tikhonenko, TI and Chernin, LS}, title = {[New shuttle-type vectors for cloning in Escherichia coli and Agrobacterium tumefaciens].}, journal = {Molekuliarnaia genetika, mikrobiologiia i virusologiia}, volume = {}, number = {8}, pages = {12-15}, pmid = {2233784}, issn = {0208-0613}, mesh = {Cloning, Molecular/*methods ; Escherichia coli/*genetics ; *Genetic Vectors ; Plasmids ; Rhizobium/*genetics ; }, abstract = {The vectors capable of replication in Escherichia coli and Agrobacterium tumefaciens have been constructed on the basis of the plasmid pUB5502. The constructed vectors pVA12, pVA12-2, pVA12-4 contain the mini-replicon and trimethoprim resistance gene (Tp) of a broad host-range plasmid R388 (IncW). The pVA12 vector (8.8 kb) has been constructed by insertion of a kanamycin resistance gene (Km) from the plasmid pUC-4K into a Psti site. It possesses 7 unique restriction sites for XhoI, SmaI, PvuI, PvuII, HindIII, EcoRI, BamHI and the markers for kanamycin and trimethoprim resistance (Km and Tp). The pVA12-2 and pVA12-4 vectors were obtained as a result of changing of the PvuII-EcoI fragment of pVA12 carrying the Tp gene for the PvuII-EcoRI fragment of pBR322 carrying the Tc gene. These plasmids have the same size of 9.7 kb and 8 unique sites for restriction endonucleases XhoI, SmaI, PvuI, PvuII, EcoRI, EcoRV, SalI, BalI and Km and Tc genes. No difference has been registered between the two plasmids by restriction analysis, but pVA12-4 has the dramatically increased copy number in Escherichia coli cells. All three vectors are transferable to Agrobacterium tumefaciens with the same frequencies by transformation or conjugation and do not affect the oncogenicity of pTi.}, } @article {pmid2177002, year = {1990}, author = {Gal'perin, IuM and Kostiuchenko, LN and Zheleznaia, LA and Denisova, EA}, title = {[The role of glycoproteins in the formation of the floccular gel structures of normal digestion].}, journal = {Fiziologicheskii zhurnal SSSR imeni I. M. Sechenova}, volume = {76}, number = {8}, pages = {1068-1071}, pmid = {2177002}, issn = {0015-329X}, mesh = {Animals ; Digestion/*physiology ; Dogs ; Enzyme Activation/physiology ; Enzymes, Immobilized/metabolism ; Flocculation ; Gels ; Glycoproteins/*physiology ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Intestine, Small/enzymology ; Rats ; Trypsin/metabolism ; alpha-Amylases/metabolism ; }, } @article {pmid2353816, year = {1990}, author = {Kagan, VE and Bakalova, RA and Zhelev, ZZ and Rangelova, DS and Serbinova, EA and Tyurin, VA and Denisova, NK and Packer, L}, title = {Intermembrane transfer and antioxidant action of alpha-tocopherol in liposomes.}, journal = {Archives of biochemistry and biophysics}, volume = {280}, number = {1}, pages = {147-152}, doi = {10.1016/0003-9861(90)90529-8}, pmid = {2353816}, issn = {0003-9861}, support = {CA47597/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Antioxidants ; Cerebral Cortex/analysis ; Dimyristoylphosphatidylcholine ; Kinetics ; *Lipid Peroxidation ; *Liposomes ; Male ; Membranes, Artificial ; Models, Biological ; Phosphatidylcholines ; Phospholipids/isolation & purification ; Rats ; Rats, Inbred Strains ; *Vitamin E ; }, abstract = {Intermembrane transfer and exchange of tocopherol are not well understood. To study this we tested the ability of alpha-tocopherol containing unilamellar donor liposomes to inhibit the accumulation of lipid peroxidation products in acceptor liposomes. With molar ratios of alpha-tocopherol:phospholipids from 1:100 to 1:1000 in donor liposomes prepared by sonication of lipid dispersions, alpha-tocopherol was incorporated into both monolayers and was homogenously distributed in monomeric form without forming clusters in the liposomes. Concentrations of alpha-tocopherol which completely prevented the peroxidation of lipids were chosen for donor liposomes. Hence inhibition of lipid peroxidation in mixtures of donor and acceptor liposomes was determined by the antioxidant effect of alpha-tocopherol in acceptor liposomes which resulted from intermembrane transfer and exchange of alpha-tocopherol. Evidence was obtained that this was not due to fusion of donor with acceptor liposomes. The efficiency of the "intermembrane" antioxidant action of tocopherol was more pronounced when donor liposomes contained unsaturated phospholipids, indicating that the presence of unsaturated fatty acids in the outer monolayer phospholipids facilitates intermembrane tocopherol exchange.}, } @article {pmid2396773, year = {1990}, author = {Ender, LA and Vatazin, AV and Abakumova, LIa and Denisova, IV and Tsyplokova, GIu}, title = {[The informativeness of clinical laboratory indices of the effectiveness of exchange plasmapheresis in patients with peritonitis].}, journal = {Anesteziologiia i reanimatologiia}, volume = {}, number = {3}, pages = {56-59}, pmid = {2396773}, issn = {0201-7563}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Peritonitis/epidemiology/*therapy ; *Plasmapheresis ; *Predictive Value of Tests ; }, abstract = {The results of the application of exchange plasmapheresis in 51 patients with suppurative peritonitis have been processed statistically using "MEDSTAT-85" software. 2-3 exchange plasmapheresis procedures at an up to 2-day interval, with exfusion of 1000-1200 ml plasma and adequate replacement of plasma loss by freshly frozen donor plasma and specific hyperimmune plasma were shown to be an optimum regimen. Blood toxicity, concentration of medium molecular toxins and leukocytic index of intoxication were the most informative criteria of the efficacy of exchange plasmapheresis.}, } @article {pmid2347423, year = {1990}, author = {Denisova, NA}, title = {Phospholipid composition of myelin and synaptosomal proteolipid from vertebrate brain.}, journal = {The International journal of biochemistry}, volume = {22}, number = {5}, pages = {439-442}, doi = {10.1016/0020-711x(90)90255-2}, pmid = {2347423}, issn = {0020-711X}, mesh = {Animals ; *Brain Chemistry ; Cell Membrane/analysis ; Chickens ; Myelin Sheath/*analysis ; Phospholipids/*analysis ; Proteolipids/*analysis ; Rabbits ; Rana temporaria ; Rats ; Salmon ; Skates, Fish ; Species Specificity ; Synaptosomes/*analysis ; Turtles ; }, abstract = {1. The phospholipid composition of the main proteolipid complexes of the nervous system was studied in myelin and synaptosomal membranes from brains of representatives of various vertebrate classes. 2. The relative content of acid phospholipids was much higher in proteolipid complexes from myelin and synaptosomal membranes of all vertebrates studied as compared to their content in the initial lipid extract (28-80% and 11-20% of total phospholipid content, respectively). 3. The relative content of acid phospholipids in proteolipid complexes of myelin membranes was much lower in brain of fishes and amphibia as compared to higher vertebrates. 4. The main acid phospholipids of proteolipid complexes was phosphatidylserine, phosphatidic acid being characteristic for myelin proteolipids and diphosphatidyl glycerol for synaptosomal proteolipids of all vertebrates studied.}, } @article {pmid2336611, year = {1990}, author = {Filimonbov, RM and Denisova, NA}, title = {[The outlook for the ambulatory treatment of adolescents with duodenal peptic ulcer].}, journal = {Terapevticheskii arkhiv}, volume = {62}, number = {2}, pages = {136-138}, pmid = {2336611}, issn = {0040-3660}, mesh = {Adolescent ; Ambulatory Care/methods/*trends ; Combined Modality Therapy/methods ; Duodenal Ulcer/diagnosis/*therapy ; Duodenoscopy ; Evaluation Studies as Topic ; Female ; Humans ; Male ; Wound Healing ; }, abstract = {An analysis was made of the potentialities and efficacy of the treatment of adolescents suffering from duodenal ulcer under outpatient conditions. 65 patients aged 14 to 18 years with duodenal ulcer in the stage of clinical exacerbation and with the presence of ulcer in the acute phase were placed under observation. Outpatient treatment appeared effective in 83.3% of patients. The time of ulcer healing under out- and inpatient conditions was 21.5 +/- 2.5 and 23.5 +/- 3.1 days, respectively. Therefore, selection of adolescent patients with duodenal ulcer for outpatient treatment requires a strictly differentiated approach depending on the disease stage and the character of macroscopic changes in the gastric and duodenal mucosae. At the same time it is necessary to take into consideration the rate and accuracy of removing the painful and dyspeptic syndromes, the lack of complications, consent and interest on the part of adolescents and their parents.}, } @article {pmid2334795, year = {1990}, author = {Rangelova, DS and Zhelev, Zh and Bakalova, RA and Tiurin, VA and Denisova, NA and Serbinova, EA and Paker, L and Kagan, VE}, title = {[Intermembrane transport and antioxidant action of alpha-tocopherol in liposomes].}, journal = {Biulleten' eksperimental'noi biologii i meditsiny}, volume = {109}, number = {1}, pages = {37-39}, pmid = {2334795}, issn = {0365-9615}, mesh = {Animals ; *Antioxidants ; Biological Transport ; Cerebral Cortex/metabolism ; Fluorescence ; Indicators and Reagents ; Intracellular Membranes/metabolism ; Lipid Peroxidation/drug effects ; Liposomes/*metabolism ; Male ; Rats ; Rats, Inbred Strains ; Vitamin E/*metabolism/pharmacology ; }, abstract = {Studies were made of the ability of alpha-tocopherol, incorporated into unilamellar liposomes from saturated or unsaturated phospholipids (donor liposomes) to inhibit the accumulation of lipid peroxidation (LPO) products in unilamellar liposomes from rat cerebral cortex lipids (acceptor liposomes) in the presence of LPO inducer (Fe + ascorbate). With the molar alpha-tocopherol: phospholipids rations from 1:1000 to 1:100 in donor liposomes, obtained through sonication of lipid dispersions, alpha-tocopherol was incorporated into both monolayers of liposomes and was distributed in monomeric form without forming clusters. Based on the dependencies of LPO inhibition on the alpha-tocopherol concentrations, we chose the ones that completely prevented the accumulation of LPO products in donor liposomes. Under these conditions LPO inhibition in mixtures of donor and acceptors liposomes was fully determined by the antioxidant effect of alpha-tocopherol in acceptor liposomes due to its intermembrane transfer. The efficiency of the "intermembrane" antioxidant action of alpha-tocopherol increased in the course of preincubation of donor and acceptor liposomes (up to 60 min) and this increase was more pronounced when the donor liposomes contained unsaturated phospholipids. Evidence was obtained that the intermembrane transfer of alpha-tocopherol did not result from the fusion of donor and acceptor liposomes during preincubation.}, } @article {pmid2298141, year = {1990}, author = {Naumets, LV and Denisova, OP and Kulik, VP}, title = {[Morphological changes in fetal small intestine and pancreas implanted in Fisher and August rats].}, journal = {Eksperimental'naia onkologiia}, volume = {12}, number = {1}, pages = {37-41}, pmid = {2298141}, issn = {0204-3564}, mesh = {Adenocarcinoma/*etiology ; Animals ; Embryo, Mammalian ; Intestinal Neoplasms/*etiology/pathology ; Intestine, Small/pathology/*transplantation ; *Pancreas Transplantation ; Pancreatic Neoplasms/*etiology/pathology ; Rats ; Rats, Inbred Strains ; Sarcoma, Experimental/*etiology ; Time Factors ; }, abstract = {Fragments of fetal small intestine of Fischer rats aged 16-20 days were implanted to rats aged 3 months of the same Fischer strain (syngeneic implantation). The morphological changes in the implants were investigated. It has been shown that serious modifications of the implant including the neoplasm formation are possible during the evolution process. After syngeneic implantation of fetal pancreas to Fischer and August rats under identical conditions no malignization of the implants was observed.}, } @article {pmid2291330, year = {1990}, author = {Portnoĭ, LM and Shumskiĭ, VI and Zhakova, II and Abakumova, LIa and Denisova, II and Abalin, AI}, title = {[Methodological aspects of formation of groups at risk for cancer of the stomach and large intestine].}, journal = {Vestnik Akademii meditsinskikh nauk SSSR}, volume = {}, number = {12}, pages = {54-56}, pmid = {2291330}, issn = {0002-3027}, mesh = {Aged ; *Algorithms ; Colonic Neoplasms/diagnostic imaging/*prevention & control ; Fluoroscopy ; Humans ; Male ; *Mass Screening ; Risk Factors ; Stomach Neoplasms/diagnostic imaging/*prevention & control ; }, abstract = {An algorithm for selection of groups at high risk of cancer of the stomach and colon has been developed with the aim of improving the diagnosis of these diseases in mass screening of the population. A multidimensional statistical analysis realized in MEDSTAT-85 programme package was used to identify the most informative risk factors and to formulate the regularity having these factors expressed in percent by weight. The proposed programme of targeted screening allows for rapid and effective selection of risk groups and, in combination with the conventional gastric and colon fluorography techniques, facilitates timely detection of gastric and colonic cancer.}, } @article {pmid2288124, year = {1990}, author = {Rogachikova, TA and Abakumova, LIa and Denisova, II}, title = {[Determination of groups at risk for laryngeal tumors].}, journal = {Voprosy onkologii}, volume = {36}, number = {12}, pages = {1466-1469}, pmid = {2288124}, issn = {0507-3758}, mesh = {Age Factors ; Alcohol Drinking/adverse effects ; Female ; Humans ; Laryngeal Neoplasms/etiology/*prevention & control ; Male ; Middle Aged ; Precancerous Conditions/etiology/*prevention & control ; Risk Factors ; Sex Factors ; Smoking/adverse effects ; }, abstract = {A procedure for development of an adequate screening program for detecting precancer and cancer of the larynx was elaborated on the basis of outpatient charts and regular check-up data. Patients with laryngeal neoplasia were included into the "cancer" group (47), those with hyperplastic laryngitis--"precancer" (189) and disease-free subjects--into the "normal" group (260). Cancer suspects as identified by the procedure should be referred to the otolaryngologist for closer examination.}, } @article {pmid2251069, year = {1990}, author = {Denisova, MF}, title = {[Current principles of chemotherapy of nonspecific ulcerative colitis in children].}, journal = {Pediatriia}, volume = {}, number = {7}, pages = {97-101}, pmid = {2251069}, issn = {0031-403X}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Child ; Colitis, Ulcerative/*drug therapy ; Drug Evaluation ; Humans ; Sulfanilamides/*therapeutic use ; }, } @article {pmid2174768, year = {1990}, author = {Zaĭtsevskaia, TE and Chernov, MV and Komarova, EA and Grigorian, IA and Denisova, RA and Heinar, I and Nechiba, I and Svoboda, J and Gudkov, AV}, title = {[The tissue specificity of the expression of the avian sarcoma-leukosis complex viruses].}, journal = {Doklady Akademii nauk SSSR}, volume = {313}, number = {4}, pages = {983-986}, pmid = {2174768}, issn = {0002-3264}, mesh = {Alpharetrovirus/*genetics ; Animals ; Avian Leukosis/genetics ; Avian Myeloblastosis Virus/genetics ; Avian Sarcoma Viruses/genetics ; Chick Embryo ; Gene Expression Regulation, Viral/*genetics ; Organ Specificity/*genetics ; RNA, Viral/genetics ; Sarcoma, Avian/genetics ; }, } @article {pmid2665754, year = {1989}, author = {Denisova, LIa and Zagrebel'nyy, SN and Pustoshilova, NM and Ven'iaminova, AG and Gorn, VV}, title = {[Synthesis of oligoribonucleotides with the use of RNA polymerases of E. coli and immobilized synthetic DNA-templates].}, journal = {Bioorganicheskaia khimiia}, volume = {15}, number = {4}, pages = {562-565}, pmid = {2665754}, issn = {0132-3423}, mesh = {Autoradiography ; Base Sequence ; *DNA-Directed RNA Polymerases ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/*enzymology ; Molecular Sequence Data ; Oligoribonucleotides/*chemical synthesis ; Templates, Genetic ; }, abstract = {A new approach to synthesis of oligoribonucleotides is suggested, based on transcription by E. coli RNA polymerase of synthetic immobilized DNA-templates with AUG as primer. The approach has been experimentally verified by synthesis of two oligonucleotides, viz., a RNA fragment of the fr phage (16 nucleotides long) and a RNA fragment of the tickborne encephalitis virus (18 nucleotides long). Fraction of the synthesized RNA fragments in the whole nucleotide material is about 20%. The templates can be used repeatedly. Sequences of the oligoribonucleotides were confirmed. Advantages of this approach and its usefulness for SP6 DNA-dependent RNA polymerase are discussed.}, } @article {pmid2770724, year = {1989}, author = {Skopinov, SA and Iakovleva, SV and Denisova, EA and Vazina, AA and Zheleznaia, LA}, title = {[Influence of low-intensity laser radiation on the formation of liquid crystalline structures in a solution of glycoproteins].}, journal = {Molekuliarnaia biologiia}, volume = {23}, number = {2}, pages = {416-421}, pmid = {2770724}, issn = {0026-8984}, mesh = {Crystallization ; Glycoproteins/*radiation effects ; *Lasers ; Microscopy, Polarization ; Molecular Weight ; Solutions ; Spectrophotometry ; }, abstract = {Liquid-crystalline structure formation in glycoprotein solutions irradiated by helium-neon laser in the presence of hydrogen peroxide was observed by both polarizing microscopy and spectrophotometry. High molecular weight (2.10(6) Da) and heavily glycosylated (about 80%) glycoprotein was isolated from the mucus layer of pig small intestine. Remarkable changes of both optic parameters of the solutions and the morphology of liquid-crystalline structures were detected in irradiated samples compared to the non-irradiated ones.}, } @article {pmid2727100, year = {1989}, author = {Serova, LV and Denisova, LA and Baikova, OV}, title = {The effect of microgravity on the reproductive function of male-rats.}, journal = {The Physiologist}, volume = {32}, number = {1 Suppl}, pages = {S29-30}, pmid = {2727100}, issn = {0031-9376}, mesh = {Animals ; *Gravitation ; Male ; Rats ; Rats, Inbred Strains ; *Space Flight ; Spermatozoa/*physiology ; Testis/*cytology ; }, } @article {pmid2780155, year = {1989}, author = {Denisova, SN and Savina, MI and Kutafina, EK and Kushelev, AR}, title = {[Amino acid spectrum of the blood in children with total chronic renal failure].}, journal = {Pediatriia}, volume = {}, number = {7}, pages = {112}, pmid = {2780155}, issn = {0031-403X}, mesh = {Amino Acids/*blood ; Child ; Erythrocytes/*metabolism ; Humans ; Kidney Failure, Chronic/*blood ; }, } @article {pmid2739640, year = {1989}, author = {Andreeva, IS and Denisova, LIa and Zagrebel'nyĭ, SN and Kileva, EV and Pustoshilova, NM}, title = {[Effect of poly(dA).poly(dT) sequence inserted into EcoR1 site of pBr322 plasmid on the expression of tet and bla genes].}, journal = {Molekuliarnaia biologiia}, volume = {23}, number = {1}, pages = {101-106}, pmid = {2739640}, issn = {0026-8984}, mesh = {Ampicillin Resistance/genetics ; Base Sequence ; DNA/genetics ; *Deoxyribonuclease EcoRI ; Electrophoresis, Agar Gel ; *Gene Expression Regulation ; Plasmids ; *Poly dA-dT ; *Polydeoxyribonucleotides ; Promoter Regions, Genetic ; Tetracycline Resistance/genetics ; Transformation, Genetic ; }, abstract = {The 99 base pair poly(dA).poly(dT) stretch was inserted into EcoRI site of pBR plasmid. The effect of this insertion on tet-gene expression from P2 promoter, and bla-gene expression from P1 and P3 promoters was studied. The insertion results in a slight enhancement of the resistance of the cells to tetracycline and a decreased sensitivity to ampicillin. It is suggested that these findings reflect the effect of insertion on the transcription of the corresponding genes.}, } @article {pmid2629181, year = {1989}, author = {Shapoval, AN and Kamalov, II and Denisova, EIu and Sokolova, ED and Luzin, PM and Shamarina, AG and Gusmanova, AG and Pinaeva, NI}, title = {[Study of the distant consequences of immunizing people with a live vaccine against tick-borne encephalitis].}, journal = {Trudy Instituta imeni Pastera}, volume = {65}, number = {}, pages = {133-135}, pmid = {2629181}, issn = {0202-1447}, mesh = {Encephalitis, Tick-Borne/*prevention & control ; Humans ; Immunization/*adverse effects ; Time Factors ; Viral Vaccines/*administration & dosage ; }, } @article {pmid2516926, year = {1989}, author = {Kamalov, II and Sokolova, ED and Denisova, EIu}, title = {[Prospects for developing a live vaccine against tick-borne encephalitis].}, journal = {Trudy Instituta imeni Pastera}, volume = {65}, number = {}, pages = {98-120}, pmid = {2516926}, issn = {0202-1447}, mesh = {Animals ; Cells, Cultured ; Encephalitis Viruses, Tick-Borne/immunology/pathogenicity ; Encephalitis, Tick-Borne/*immunology/prevention & control ; Haplorhini ; Humans ; Mice ; *Viral Vaccines ; }, } @article {pmid3243469, year = {1988}, author = {Denisova, SV and Lobova, EA and Raskin, BM}, title = {[Possibility of the development of low-waste production of sera and the rational use of recycled materials].}, journal = {Gigiena i sanitariia}, volume = {}, number = {12}, pages = {24-26}, pmid = {3243469}, issn = {0016-9900}, mesh = {Animals ; *Biotechnology ; *Blood Proteins ; *Culture Media ; *Erythrocytes ; Horses ; *Industrial Waste ; Methods ; *Protein Hydrolysates ; *Serology ; }, } @article {pmid2855090, year = {1988}, author = {Mashkovskaia, GV and Denisova, TS and Lovanok, EV and Fomicheva, VV and Kartel', NA}, title = {[Deletional and insertional analysis of the antitumorigenicity of the plasmid R388 in Agrobacterium tumefaciens].}, journal = {Molekuliarnaia genetika, mikrobiologiia i virusologiia}, volume = {}, number = {12}, pages = {11-16}, pmid = {2855090}, issn = {0208-0613}, mesh = {Carcinogenicity Tests ; *Chromosome Deletion ; *DNA Transposable Elements ; Mutation ; Operon ; *Plasmids ; Restriction Mapping ; Rhizobium/*genetics ; }, abstract = {The study of the plasmid R388 deletional derivatives has shown the antitumorigenicity determinant of the plasmid to be contained by the tra-operon. Transposon Tn5 has been used for selection of a number of insertional mutants having lost the antitumorigenic properties. The difference in the locations of Tn5 inserts was found, all of the latter being localized within the tra-operon. The data obtained suggest the locus of the plasmid R388 responsible for its antitumorigenic properties to be located in the region of tra-genes distally to the rep-region.}, } @article {pmid3226118, year = {1988}, author = {Denisova, LA and Tikhonova, GP and Apanasenko, ZI and Pustynnikova, AM and Ivanov, IuV}, title = {[The reproductive function of male rats following space flight on the Cosmos-1667 biosatellite].}, journal = {Kosmicheskaia biologiia i aviakosmicheskaia meditsina}, volume = {22}, number = {6}, pages = {58-63}, pmid = {3226118}, issn = {0321-5040}, mesh = {Animals ; Male ; Rats ; Rats, Inbred Strains ; *Reproduction ; *Space Flight ; }, abstract = {After the 7-day space flight of Cosmos-1667 the reproductive system of white rats was investigated. No differences between the flight rats and synchronous and vivarium controls were detected with respect to such parameters as the testis and epididymis weight, testicular content of spermatogonia, spermatocytes, spermatids, spermatozoa, Leydig's cells and Sertoli's cells, and the number of normal and atypical spermatozoa in the epididymis. Nuclei of Sertoli's cells were similar in size in the flight and control rats. Electron microscopy of the first order spermatocytes showed no increase in the frequency of chromosome aberrations. Postflight, the flown males were mated with control females; their sex activity and their offspring were normal; the pups did not differ from the norm with respect to the litter size, proportion of males and females in the litter, growth rate in the postnatal period, physical development or function of the nervous system. These observations allow the conclusion that short-term space flight produces no effect on the reproductive system of white rats.}, } @article {pmid3236656, year = {1988}, author = {Denisova, OS and Sidorenko, BA and Pakulin, IA and Surovov, IuA and Ugriumova, MO}, title = {[Effect of nifedipine (corinfar) on pulmonary ventilation at the peak of the action of propranolol in patients with ischemic heart disease associated with chronic obstructive bronchitis].}, journal = {Kardiologiia}, volume = {28}, number = {9}, pages = {90-92}, pmid = {3236656}, issn = {0022-9040}, mesh = {Adult ; Aged ; Bronchi/drug effects ; Bronchitis/complications/*drug therapy/physiopathology ; Chronic Disease ; Coronary Disease/complications/*drug therapy/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nifedipine/*therapeutic use ; Propranolol/antagonists & inhibitors/*therapeutic use ; Respiration/*drug effects ; }, } @article {pmid2464156, year = {1988}, author = {Pustynnikova, AM and Denisova, LA and Wachtel, E and Hecht, K and Oehme, P}, title = {[The action of substance P on the course of pregnancy and fetal function in white rats].}, journal = {Patologicheskaia fiziologiia i eksperimental'naia terapiia}, volume = {}, number = {5}, pages = {72-75}, pmid = {2464156}, issn = {0031-2991}, mesh = {Animals ; Body Weight/drug effects ; Female ; Fetus/*drug effects ; Organ Size/drug effects ; Pregnancy ; Pregnancy, Animal/*drug effects ; Rats ; Rats, Inbred Strains ; Reproduction/drug effects ; Substance P/*pharmacology ; Time Factors ; }, } @article {pmid3289627, year = {1988}, author = {Denisova, OV and Chasovnikova, LV and Aleshkin, VA}, title = {[The difference between rheumatoid factors and normal immunoglobulins disclosed by a monomolecular layer technic].}, journal = {Biulleten' eksperimental'noi biologii i meditsiny}, volume = {105}, number = {5}, pages = {570-573}, pmid = {3289627}, issn = {0365-9615}, mesh = {Arthritis, Rheumatoid/immunology ; Humans ; Immunoglobulin G/*analysis ; Immunoglobulin M/*analysis ; Immunologic Techniques ; Rheumatoid Factor/*analysis ; }, abstract = {20 rheumatoid factors of two classes, namely IgG and IgM, were isolated from the serum of 11 patients with rheumatoid arthritis. The method of monolayer analysis revealed that these proteins differ from normal ones either by the instability of their native structure, or by their anomalous hydrophilic properties. Dialysis resulted in partial or complete restoration of normal properties in the majority of samples studied. It has been concluded that at least some of the rheumatoid factors are complex structures that contain, beside IgG and IgM molecules, also certain smaller molecules.}, } @article {pmid3176425, year = {1988}, author = {Gibadulin, RA and Lazarenko, AA and Iuferov, VP and Lideman, LF and Denisova, GF}, title = {[Design of a recombinant strain of the vaccinia virus containing an expressible gene for influenza A virus hemagglutinin].}, journal = {Voprosy virusologii}, volume = {33}, number = {3}, pages = {275-278}, pmid = {3176425}, issn = {0507-4088}, mesh = {Animals ; Antibodies, Viral/analysis ; *DNA, Recombinant ; DNA, Viral/*genetics ; *Gene Expression Regulation ; *Genes, Viral ; Hemagglutinins, Viral/*genetics/immunology ; Immunization ; Influenza A virus/*genetics/immunology ; Plasmids ; Rabbits ; Transfection ; Vaccinia virus/*genetics/immunology ; Virus Cultivation ; }, abstract = {A recombinant vaccinia virus (VV) strain containing a cloned gene of influenza A/Udorn/307/72 (H3N2) hemagglutinin (HA) gene has been produced. HA expression in CV-1 cells infected with the recombinant virus was determined by enzyme immunoassay. The influenza virus HA titer was 1:64-1:128. When rabbits were inoculated intravenously with the recombinant VaV, antibody titres were 1:5120. The recombinant VaV preparation may be used for generation of monospecific antibody to influenza virus.}, } @article {pmid3400160, year = {1988}, author = {Filimonov, RM and Lukich, VL and Negrebova, ZE and Denisova, NA}, title = {[The microwave electromagnetic field (2450 c.) in the complex treatment of erosive gastroduodenitis in adolescents].}, journal = {Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury}, volume = {}, number = {2}, pages = {14-17}, pmid = {3400160}, issn = {0042-8787}, mesh = {Adolescent ; Duodenitis/*radiotherapy ; Female ; Gastroenteritis/*radiotherapy ; Humans ; Male ; Microwaves/*therapeutic use ; Radiotherapy Dosage ; }, } @article {pmid3164117, year = {1988}, author = {Dmitrieva, LA and Denisova, IA and Barabash, AG and Khalikova, NV and Frolova, TA}, title = {[Clinico-morphological validation of the use of a lysozyme-containing paste for preserving dental pulp viability in pulpitis].}, journal = {Stomatologiia}, volume = {67}, number = {2}, pages = {19-21}, pmid = {3164117}, issn = {0039-1735}, mesh = {Acute Disease ; Adolescent ; Adult ; Animals ; Dental Pulp/*drug effects/ultrastructure ; Dogs ; Drug Evaluation ; Drug Evaluation, Preclinical ; Female ; Humans ; Male ; Muramidase/*administration & dosage ; Ointments ; Pulpitis/*drug therapy/pathology ; Time Factors ; }, } @article {pmid2967903, year = {1988}, author = {Denisova, LA and Lavrova, EA and Natochin, IuV and Serova, LV}, title = {[Water and electrolyte content of the organs and tissues of male rats following a flight on the Kosmos 1667 biosatellite].}, journal = {Kosmicheskaia biologiia i aviakosmicheskaia meditsina}, volume = {22}, number = {2}, pages = {33-37}, pmid = {2967903}, issn = {0321-5040}, mesh = {Adaptation, Physiological ; Animals ; Body Water/analysis ; Electrolytes/analysis ; Male ; Rats ; Rats, Inbred Strains ; Sex Characteristics ; *Space Flight ; Specific Pathogen-Free Organisms ; Time Factors ; USSR ; *Water-Electrolyte Balance ; Weightlessness ; }, abstract = {After the 7-day space flight onboard the biosatellite Cosmos-1667 the water, Na, K, Ca and Mg content of the liver, kidney, heart, skin and bone of male rats was measured. No significant changes in the weight or water content of the above organs were seen. The exception was a decrease of water contained in the heart and an increase of water contained in the caudal appendage of the epididymis. After flight the mineral composition of the liver was identical to that after control studies. The K content of the heart of the flight rats was lower and that of Na, Ca and Mg was identical to the parameter in the controls. The K content of the skin and bone increased and the Na content of the skin also grew. In the kidney the Ca content did not change whereas the content of K, Na and Mg decreased significantly. In the testis Na decreased and K increased after flight. Thus, changes in fluid-electrolyte homeostasis at the organ and tissue level can develop within 7 days of space flight. They occur not only in the musculoskeletal system but may also evolve in the nonweight-bearing organs.}, } @article {pmid3187646, year = {1988}, author = {Portnoĭ, LM and Mosunova, TD and Pachin, MV and Denisova, II and Vasil'ev, IuD}, title = {[Model of an automated system for selection and differential fluorographic examination].}, journal = {Sovetskoe zdravookhranenie}, volume = {}, number = {7}, pages = {11-15}, pmid = {3187646}, issn = {0038-5239}, mesh = {*Computer Systems ; Diagnosis, Differential ; Fluoroscopy/methods ; Humans ; Lung Neoplasms/prevention & control ; Mass Chest X-Ray/methods/*organization & administration ; Microcomputers ; Risk Factors ; USSR ; }, } @article {pmid3077723, year = {1988}, author = {Klimovich, VB and Pashkova, SF and Samoĭlovich, MP and Sirota, NS and Griazeva, IV and Denisova, GN and Zheludov, VI and Zakrevskaia, AV}, title = {[Monoclonal antibodies against horseradish peroxidase: properties and use in immunoenzyme analysis].}, journal = {Trudy Instituta imeni Pastera}, volume = {64}, number = {}, pages = {90-94}, pmid = {3077723}, issn = {0202-1447}, mesh = {Animals ; *Antibodies, Monoclonal ; Cattle ; Horseradish Peroxidase/*immunology ; Humans ; *Immunoenzyme Techniques ; Isoelectric Focusing ; Mice ; Peroxidases/*immunology ; }, } @article {pmid2461476, year = {1988}, author = {Denisova, OV and Miagkova, MA and Balabanova, RM and Solov'ev, SK and Ivanov, AE}, title = {[Preparation of highly-purified rheumatoid factor from human blood serum for physicochemical and immunologic studies].}, journal = {Laboratornoe delo}, volume = {}, number = {9}, pages = {48-51}, pmid = {2461476}, issn = {0023-6748}, mesh = {Arthritis, Rheumatoid/blood ; Humans ; Methods ; Rheumatoid Factor/*isolation & purification ; }, } @article {pmid3324588, year = {1987}, author = {Denisova, II and Vasser, NR and Bel'kova, EI and Velichko, LN and Gennad'eva, TIa}, title = {[Action of the lactoperoxidase system on Salmonellae and Shigellae].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {11}, pages = {99-103}, pmid = {3324588}, issn = {0372-9311}, mesh = {Culture Media/metabolism ; Dose-Response Relationship, Drug ; Hydrogen Peroxide/metabolism ; Lactobacillus/enzymology/immunology ; Lactoperoxidase/*immunology ; Peroxidases/*immunology ; Salmonella/growth & development/*immunology ; Salmonella typhimurium/growth & development/immunology ; Shigella sonnei/growth & development/*immunology ; Time Factors ; }, abstract = {In vitro experiments have demonstrated that the lactoperoxidase system produces a bactericidal effect on salmonellae and shigellae. The physiological concentrations of the components of this system, making it possible to obtain a pronounced bactericidal effect, have been established. Lactobacilli have been shown to potentiate the effect of the lactoperoxidase system. The possibility of realizing the bactericidal properties of the lactoperoxidase system with respect to salmonellae and shigellae in the preparations of immune lactosera, intended for passive enteral immunization against intestinal infections, has been suggested.}, } @article {pmid3309618, year = {1987}, author = {Denisova, LIa and Zagrebel'nyĭ, SN and Zakabunin, AI and Kileva, EV and Kovzhov, VA}, title = {[Effectiveness of the promoter Ptac' in vitro and in mini-cells].}, journal = {Molekuliarnaia biologiia}, volume = {21}, number = {4}, pages = {1060-1069}, pmid = {3309618}, issn = {0026-8984}, mesh = {Escherichia coli/genetics ; *Genetic Engineering ; Lac Operon ; *Nucleic Acid Hybridization ; Plasmids ; *Promoter Regions, Genetic ; Tryptophan/genetics ; }, abstract = {The efficiency of hybrid promotor Ptac', comprising a synthetic trp-promoter and lacUV5 "-10" sequence, was studied. By means of electrophoresis and hybridization of RNA-products obtained in vitro and in minicells, with promotor-containing plasmids; the hybrid promotor was found to be 6 times and 3-4 times as efficient as trp and lacUV5 promoters, respectively.}, } @article {pmid3475827, year = {1987}, author = {Denisova, IA and Dzhafarova, AD and Ul'ianova, TV and Serova, RI}, title = {[Use of lysozyme electrophoresis for treating chronic forms of periodontitis].}, journal = {Stomatologiia}, volume = {66}, number = {3}, pages = {28-30}, pmid = {3475827}, issn = {0039-1735}, mesh = {Adult ; Chronic Disease ; Drug Evaluation ; Drug Evaluation, Preclinical ; Humans ; In Vitro Techniques ; Iontophoresis/*methods ; Middle Aged ; Muramidase/*administration & dosage ; Periapical Granuloma/drug therapy ; Periodontitis/*drug therapy ; Solutions ; }, } @article {pmid3472384, year = {1987}, author = {Komnova, ZD and Dmitrieva, LA and Burda, GK and Denisova, IA}, title = {[Effect of a lysozyme-vitamin paste and potassium nitrate on the dental pulp during the experimental creation of a deep cavity in hard tissues].}, journal = {Stomatologiia}, volume = {66}, number = {2}, pages = {24-26}, pmid = {3472384}, issn = {0039-1735}, mesh = {Animals ; Calcium Hydroxide/therapeutic use ; Carboxymethylcellulose Sodium/therapeutic use ; Chlorocebus aethiops ; Dental Caries/*therapy ; Dental Pulp/*drug effects ; Dental Pulp Capping/methods ; Dogs ; Drug Combinations/therapeutic use ; Drug Evaluation, Preclinical ; Muramidase/*therapeutic use ; Nitrates/*therapeutic use ; Ointments ; *Potassium Compounds ; Time Factors ; Vitamin A/*therapeutic use ; Zinc Oxide/therapeutic use ; }, } @article {pmid3033485, year = {1987}, author = {Chernov, MV and Tikhonenko, AT and Zaĭtsevskaia, TE and Denisova, RA and Obukh, IB}, title = {[The genome of chickens free of endogenous avian leukosis-sarcoma proviruses contains sequences distantly related to Rous sarcoma virus].}, journal = {Molekuliarnaia genetika, mikrobiologiia i virusologiia}, volume = {}, number = {3}, pages = {6-11}, pmid = {3033485}, issn = {0208-0613}, mesh = {Alpharetrovirus/*genetics ; Animals ; Avian Sarcoma Viruses/*genetics ; *Base Sequence ; Chickens/*genetics/microbiology ; Chromosome Mapping ; Cloning, Molecular ; *Genes, Viral ; *Sequence Homology, Nucleic Acid ; }, abstract = {Line of Brown leghorn chickens free of RAV-O-type endogenous proviruses was obtained by selection under blot hybridization control. A set of dispersed sequences distantly related to avian leukosis virus genome was found in DNA of these chickens by means of hybridization in non-stringent conditions. Different restriction fragments were detected by gag, pol and env hybridization probes.}, } @article {pmid3560846, year = {1987}, author = {Shakhmatova, EI and Lavrova, EA and Natochin, IuV and Serova, LV and Denisova, LA}, title = {[Concentration of water and electrolytes in pregnant rats and their offspring after a flight aboard the biosatellite "Cosmos-1514"].}, journal = {Kosmicheskaia biologiia i aviakosmicheskaia meditsina}, volume = {21}, number = {1}, pages = {42-47}, pmid = {3560846}, issn = {0321-5040}, mesh = {Animals ; Body Composition ; Body Weight ; Electrolytes/analysis ; Female ; Fetus/*metabolism ; Placenta/analysis ; Pregnancy ; Pregnancy, Animal/*metabolism ; Rats ; Rats, Inbred Strains ; *Space Flight ; Water/analysis ; *Water-Electrolyte Balance ; }, abstract = {The female rats were flown on Cosmos-1514 for 5 days during gestation days 13 through 18. The rats showed a significant reduction of the Ca concentration in the liver and kidneys, its smaller decrease in the skin, and no changes in bones. The fetus weight decreased, its water content increased, and the content of Na, K, Ca and Mg remained unchanged. The 15- and 30-day pups of the flown rats did not exhibit any differences in the water and electrolyte content in bones, skin, liver or kidneys as compared to the controls. These data indicate that water and electrolyte homeostasis of growing fetuses was highly stable and the deviations that emerged under the influence of space flight factors on the mother-fetus system rapidly returned to the norm.}, } @article {pmid2435961, year = {1987}, author = {Aref'ev, IM and Denisova, GP and Dobrovol'skiĭ, NA and Kirpatovskiĭ, ID and Peshkov, AV}, title = {[Determination of the concentration of spermatozoids in ejaculates using a laser flow-type counter-analyzer of microparticles].}, journal = {Laboratornoe delo}, volume = {}, number = {1}, pages = {22-25}, pmid = {2435961}, issn = {0023-6748}, mesh = {*Ejaculation ; Flow Cytometry/methods ; Humans ; Lasers ; Male ; Sperm Count/*instrumentation/methods ; }, } @article {pmid3541464, year = {1986}, author = {Pivovarova, NI and Denisova, SV and Salov, VF}, title = {[Ultrastructural study of intestinal bacteria grown on Endo- and Levine-type nutrient media based on nonfood raw materials].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {10}, pages = {27-29}, pmid = {3541464}, issn = {0372-9311}, mesh = {Culture Media/*metabolism ; Escherichia coli/growth & development/*ultrastructure ; Intestines/*microbiology ; Microscopy, Electron ; Protein Hydrolysates/metabolism ; Salmonella typhi/growth & development/*ultrastructure ; Shigella flexneri/growth & development/*ultrastructure ; }, abstract = {The comparative electron-microscopic study of several test strains (Salmonella typhi H-901, Shigella flexneri la 8516, and Escherichia coli 055) grown in experimental Endo and Levine media prepared on the basis of raw materials unsuitable for human consumption and in commonly used similar media prepared on the basis of sprat hydrolysate has shown the test strains grown in media containing aminopeptide and fodder yeast hydrolysate to retain their typical ultrastructure, which confirms the possibility of using these protein bases for the preparation of Endo and Levine media.}, } @article {pmid3765979, year = {1986}, author = {Denisova, II}, title = {[Production of a monospecific antiserum to lactoperoxidase using immunoprecipitants].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {8}, pages = {88-90}, pmid = {3765979}, issn = {0372-9311}, mesh = {Animals ; Antigen-Antibody Complex/immunology ; Immune Sera/*isolation & purification ; Immunity, Innate ; Immunization ; Immunoelectrophoresis/methods ; Lactoperoxidase/*immunology ; Peroxidases/*immunology ; Precipitin Tests/methods ; Rabbits ; }, abstract = {To prepare monospecific antiserum to lactoperoxidase, one of the factors of the nonspecific protection of the body from infections, the complexes of lactoperoxidase with antibodies to it were used as antigens; precipitates were obtained by linear immunoelectrophoresis with the use of partially purified lactoperoxidase and antisera to it. This method does not require obtaining the highly purified enzyme and the subsequent adsorption of antisera.}, } @article {pmid3765214, year = {1986}, author = {Es'kov, AP and Luzhetskiĭ, AS and Gurilev, OM and Riazanova, IuN and Denisova, GP}, title = {[Assessment of human sperm motility by using a laser device].}, journal = {Urologiia i nefrologiia}, volume = {}, number = {4}, pages = {57-59}, pmid = {3765214}, issn = {0042-1154}, mesh = {Equipment Design ; Humans ; *Lasers ; Male ; Methods ; *Sperm Motility ; Time Factors ; }, } @article {pmid3762055, year = {1986}, author = {Denisova, LA}, title = {[Effect of weightlessness on the skeletal development of the rat fetus].}, journal = {Kosmicheskaia biologiia i aviakosmicheskaia meditsina}, volume = {20}, number = {4}, pages = {60-63}, pmid = {3762055}, issn = {0321-5040}, mesh = {Animals ; Animals, Newborn ; Bone and Bones/*embryology ; Female ; Osteogenesis ; Pregnancy ; Rats ; Space Flight ; Time Factors ; USSR ; Weightlessness/*adverse effects ; }, abstract = {The size of the ossified areas of skeletal bones of fetuses of white rats flown onboard Cosmos-1514 during their pregnancy days 13 to 18 was compared with that of synchronous and vivarium controls. The effect of zero-g on the pregnant animals in the course of an active formation of fetal bones involved a distinct (13-17%) arrest of the development of nearly every area of the fetal skeleton. The signs of the arrest development were more manifest in less mature skeletal structures. Since the Ca2 content was identical in the flight and control rats, it can be concluded that the inhibited ossification of the flight fetuses was produced by the impairment of mechanisms controlling Ca2+ incorporation into the growing skeleton. The ossified areas in the skeleton of the flight newborns were significantly larger than those of the synchronous and vivarium controls. This means that during the readaptation period (pregnancy days 18 to 23) the inhibited ossification of the fetal skeleton was completely compensated and that the flight newborns (i. e. the rats whose prenatal development occurred in part in zero-g) were ahead of the controls with respect to the ossification rate.}, } @article {pmid3490079, year = {1986}, author = {Denisova, NA and Zabelinskiĭ, SA}, title = {[Proteolipids of brain myelin and synaptosomes in the frog and hen].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {22}, number = {4}, pages = {394-399}, pmid = {3490079}, issn = {0044-4529}, mesh = {Animals ; Brain/*metabolism ; Chickens/*metabolism ; Fatty Acids/analysis ; Female ; Lipids/analysis ; Myelin Sheath/*metabolism ; Phospholipids/analysis ; Proteolipids/analysis/*isolation & purification ; Rana temporaria/*metabolism ; Synaptosomes/*metabolism ; }, abstract = {Proteolipid complex of Folch-Lees has been obtained and purified from the myelin and synaptosomes of the brain of the frog Rana temporaria and hen Gallus domesticus. Relative content of this proteolipid and glycolipids in the myelin is almost twice higher, whereas that of phospholipids--1 1/2 times lower than in the synaptosomal membranes of the same animal. Protein content of this complex is higher for myelin than for synaptosomal membranes; opposite relation was found with respect to phospholipid content. Within this complex, lipids are presented mainly by phospholipids, especially by acid ones which amount to 30-60%. Proteolipid complexes fro the myelin and synaptosomes differ from each other by their lipid component. Myelin proteolipid complex contains mainly phosphatidylserine and phosphatid acid, whereas synaptosomal one--phosphatidylserine and diphosphatediglycerol. No significant differences were found in fatty acid composition of phospholipids from proteolipid complex from myelin and synaptosomes as compared to this composition in the initial membranes.}, } @article {pmid3487071, year = {1986}, author = {Denisova, MF}, title = {[Clinico-immunologic comparisons in nonspecific ulcerative colitis in children].}, journal = {Pediatriia}, volume = {}, number = {4}, pages = {40-43}, pmid = {3487071}, issn = {0031-403X}, mesh = {Adolescent ; B-Lymphocytes/immunology ; Child ; Child, Preschool ; Colitis, Ulcerative/*diagnosis/immunology ; Female ; Humans ; Hypersensitivity, Delayed/immunology ; Immunoglobulins/analysis ; Leukocyte Count ; Male ; Rosette Formation ; T-Lymphocytes/immunology ; }, } @article {pmid3714323, year = {1986}, author = {Iakovlev, VM and Dolgikh, VT and Iakovleva, TA and Denisova, IA}, title = {[Quercetin as an agent to prevent the cardiotoxic action of antituberculosis preparations].}, journal = {Patologicheskaia fiziologiia i eksperimental'naia terapiia}, volume = {}, number = {2}, pages = {68-71}, pmid = {3714323}, issn = {0031-2991}, mesh = {Animals ; Antitubercular Agents/*antagonists & inhibitors/toxicity ; Blood Pressure/drug effects ; Calcium/metabolism ; Flavonoids/*pharmacology ; Heart/*drug effects ; Lipid Peroxides/metabolism ; Male ; Myocardial Contraction/drug effects ; Myocardium/metabolism ; Quercetin/*pharmacology ; Rats ; Time Factors ; }, } @article {pmid3014752, year = {1986}, author = {Chernov, MV and Gudkov, AV and Obukh, IB and Denisova, RA and Gorbacheva, NS}, title = {[Characteristics of new loci of endogenous proviruses in chickens].}, journal = {Voprosy virusologii}, volume = {31}, number = {2}, pages = {216-220}, pmid = {3014752}, issn = {0507-4088}, mesh = {Animals ; Avian Leukosis Virus/genetics/isolation & purification ; Avian Sarcoma Viruses/genetics/isolation & purification ; Base Sequence ; Chick Embryo ; Chickens/genetics/*microbiology ; Chromosome Deletion ; DNA/genetics ; DNA, Viral/genetics ; Defective Viruses/genetics/isolation & purification ; Female ; Genes ; Genes, Viral ; Genetic Variation ; Nucleic Acid Hybridization ; }, abstract = {The composition and structure of endogenous proviruses in the genome of Italian partridge chicken was studied by the blot-hybridization method using 32P-DNA of RAV-2 virus as a probe. Among 34 fowls examined, 5-contained no endogenous proviruses related to fowl leukemia viruses. DNA of the other fowls contained various combinations of 4 previously undescribed endogenous proviruses varying in structure and localization. None of them was identical in its structure with DNA of endogenous fowl virus RAV-0, all the four discovered loci have deletions. The origin, modes of genetic variability, and function of endogenous proviruses are discussed.}, } @article {pmid3953004, year = {1986}, author = {Denisova, II and Krasheniuk, AI and Azhitskiĭ, GIu and Sharaeva, TK and Umovskaia, EA}, title = {[Isolation and purification of lactoperoxidase from cow's milk].}, journal = {Voprosy meditsinskoi khimii}, volume = {32}, number = {1}, pages = {116-119}, pmid = {3953004}, issn = {0042-8809}, mesh = {Animals ; Cattle ; Electrophoresis, Polyacrylamide Gel ; Female ; Isoelectric Focusing ; Lactoperoxidase/*isolation & purification ; Milk/*enzymology ; Peroxidases/*isolation & purification ; }, abstract = {A procedure is described for isolation and purification of lactoperoxidase from cow milk. The procedure involved the following steps: isolation of casein from milk, sorption of lactoperoxidase on CM-Sephadex, concentration of the eluate using ultrafiltration, salting out with ammonium sulfate; isoelectric focusing was carried out in the borate-polyol system. Highly purified, active preparation of lactoperoxidase was obtained within a relatively short period by means of the procedure, where the available reagents were used.}, } @article {pmid3823078, year = {1986}, author = {Iakovlev, VM and Dolgikh, VT and Iakovleva, TA and Denisova, IA}, title = {[Use of quercetin to prevent and treat cardiovascular disorders in pulmonary tuberculosis].}, journal = {Problemy tuberkuleza}, volume = {}, number = {12}, pages = {35-38}, pmid = {3823078}, issn = {0032-9533}, mesh = {Animals ; Antitubercular Agents/*antagonists & inhibitors ; Cardiomyopathies/*prevention & control ; Flavonoids/*therapeutic use ; Humans ; Male ; Quercetin/*therapeutic use ; Rats ; Tuberculosis, Pulmonary/*complications ; }, } @article {pmid3307274, year = {1986}, author = {Klimovich, VB and Samoilovich, MP and Denisova, GN and Sirota, NS and Schuls, TS and Zeludov, VI and Bertók, L}, title = {Comparison of adjuvanticity and autoantibody inducing capacity of endotoxin and radio-detoxified endotoxin in mice.}, journal = {Acta microbiologica Hungarica}, volume = {33}, number = {4}, pages = {311-315}, pmid = {3307274}, issn = {0231-4622}, mesh = {*Adjuvants, Immunologic ; Animals ; Autoantibodies/*biosynthesis ; Endotoxins/*immunology ; Erythrocytes/immunology ; *Escherichia coli ; Lipopolysaccharides/*immunology ; Male ; Mice ; }, abstract = {Endotoxin (LPS) and radio-detoxified endotoxin (RD-LPS: 150 kGy 60Co-gamma irradiated) preparations were compared in mice (C57Bl X CBA: F1/Rapo) for capacity to enhance the immune response against sheep red blood cells and to induce the production of antibody against autologous (bromelain-treated) erythrocytes. As RD-LPS retains its capacity to stimulate immune response against heterologous antigen, it may be used as an immuno-adjuvant. The LPS preparation gave rise to a significant increase of autoreactive cells. However, RD-LPS activated the autoantibody forming cells only to a very small degree.}, } @article {pmid3834483, year = {1985}, author = {Serova, LV and Denisova, LA and Pustynnikova, AM}, title = {Comparative analysis of hypo - and hypergravity effects on prenatal development of mammals.}, journal = {The Physiologist}, volume = {28}, number = {6 Suppl}, pages = {S5-8}, pmid = {3834483}, issn = {0031-9376}, mesh = {Animals ; *Embryonic and Fetal Development ; Female ; *Gravitation ; Male ; Mice ; Pregnancy ; Rats ; Space Flight ; }, } @article {pmid2934103, year = {1985}, author = {Sergeev, AV and Revazova, ES and Denisova, SI and Kalatskaia, OV and Rytenko, AN}, title = {[Immunomodulating and antitumor activity of polysaccharides of plant origin].}, journal = {Biulleten' eksperimental'noi biologii i meditsiny}, volume = {100}, number = {12}, pages = {741-743}, pmid = {2934103}, issn = {0365-9615}, mesh = {Adjuvants, Immunologic/*pharmacology/therapeutic use ; Animals ; Antineoplastic Agents, Phytogenic/*pharmacology/therapeutic use ; Cytotoxicity Tests, Immunologic ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; L Cells/drug effects ; Lymphocyte Culture Test, Mixed ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Neoplasm Transplantation ; Phytotherapy ; Plants, Medicinal ; Polysaccharides/*pharmacology/therapeutic use ; Sarcoma 180/drug therapy ; T-Lymphocytes, Cytotoxic/drug effects ; Time Factors ; }, abstract = {The effect of the polysaccharides tagetan, palustran, and zymosan injections to BALB/c mice on the formation of cytotoxic T-lymphocytes in allogenic mixed culture has been studied. Lymphocytes from a 5-day-old mixed culture were characterized by the greatest cytotoxic activity, with spleenocytes serving as reacting cells in mice injected 12-50 mg/kg of tagetan, 20 mg/kg of zymosan and 10-100 mg/kg of palustran, 7, 3 and 5 days, respectively, before the beginning of allogeneic stimulation in vitro. To determine correlation between immunostimulating and antitumor activity 25 mg/kg of tagetan every 14 days, 20 mg/kg of zymosan every 6 days, and 10 mg/kg of palustran every 6 days, were injected to BALB/c and BALB/c nu/nu mice prior to and following subcutaneous implantation of Crocker sarcoma cells. By the end of the first month of immunotherapy the tumour size in mice on tagetan or zymosan was 2-2,5 times smaller than in control animals. Tumour growth inhibition with palustran was about 30%. Polysaccharide administration to BALB/c nu/nu mice was not accompanied by tumour growth inhibition. The data obtained suggest that inhibition of Crocker sarcoma growth in mice injected the above polysaccharides is mediated by stimulation of antitumour T-cell activity.}, } @article {pmid3841480, year = {1985}, author = {Khomutov, RM and Denisova, GF and Khomutov, AR and Belostotskaia, KM and Shlosman, RB}, title = {[Aminooxypropylamine--an effective inhibitor of ornithine decarboxylase in vitro and in vivo].}, journal = {Bioorganicheskaia khimiia}, volume = {11}, number = {11}, pages = {1574-1576}, pmid = {3841480}, issn = {0132-3423}, mesh = {Animals ; Butylamines/chemical synthesis/*pharmacology ; In Vitro Techniques ; Liver/enzymology ; Mice ; *Ornithine Decarboxylase Inhibitors ; Propylamines/chemical synthesis/*pharmacology ; Putrescine/pharmacology ; }, abstract = {Hydroxylamine-containing analogues of putrescine and cadaverine have been found effective in inhibiting the mouse liver ornithine decarboxylase, the best among synthesized were 1-aminooxy-3-aminopropane (I50 2.10(-8) M) and 1-aminooxy-4-aminobutane (I50 2.10(-7) M). The inhibitory effect of these substances on the mouse liver ornithine-transaminase and S-adenosylmethionine decarboxylase from E. coli was displayed at concentrations higher by several orders of magnitude, that demonstrated the specificity of the compounds of this type. 1-Aminooxy-3-aminopropane in experiments in vivo suppressed the ornithine decarboxylase activity in mouse liver at 16 mg/kg by 75%, the toxic effect being insignificant.}, } @article {pmid4052481, year = {1985}, author = {Lavrent'ev, VV and Denisova, OV and Aleshkin, VA and Chasovnikova, LV}, title = {[Orientation and kinetics of surface denaturation of normal human and myeloma IgA in monolayers at the interface of air-NaCl aqueous solutions].}, journal = {Biofizika}, volume = {30}, number = {5}, pages = {797-801}, pmid = {4052481}, issn = {0006-3029}, mesh = {Air ; Chemical Phenomena ; Chemistry, Physical ; Humans ; Immunoglobulin A/*analysis ; Kinetics ; Myeloma Proteins/*analysis ; Protein Denaturation ; Sodium Chloride ; Solutions ; }, abstract = {Normal serum immunoglobulin A (IgA) and abnormal IgA isolated from serum of patients with multiple A-myeloma have been studied by monolayer technique at air--NaCl solution interfaces. Normal IgA analogous to human normal IgG and secretory IgA was shown to have horizontal orientation at air--water interface. Only some abnormal IgA were similar to myeloma IgG and differed from the normal ones by their orientation at phase border. Majority of myeloma IgA under study could not be distinguished from the normal ones by orientation and denaturation kinetics at interface. B-lymphocytes of the first group of patients were assumed to carry IgA-receptors at their surface, but B-lymphocytes of the second group of patients carried Ig receptors of some other class of immunoglobulins.}, } @article {pmid3990234, year = {1985}, author = {Serova, LV and Denisova, LA and Apanasenko, ZI and Briantseva, LA and Chel'naia, NA}, title = {[General characteristics of an experiment to study the ontogeny of rats on board the Kosmos-1514 biosatellite].}, journal = {Kosmicheskaia biologiia i aviakosmicheskaia meditsina}, volume = {19}, number = {2}, pages = {49-53}, pmid = {3990234}, issn = {0321-5040}, mesh = {Animals ; Animals, Newborn ; Body Weight ; Female ; Fetal Growth Retardation/embryology ; Organ Size ; Pregnancy ; Rats/*embryology ; Rats, Inbred Strains ; Research Design ; *Space Flight ; Time Factors ; USSR ; Weightlessness ; }, abstract = {Ten female Wistar rats were exposed to zero-g during 5 days, i. e., from gestation day 13 to day 18. After recovery the flight animals showed a significant delay in weight gain, thymus involution, decreased liver weight, hemoglobin concentration. Nevertheless, their reproductive function did not differ from that of the controls: the rate of preimplantation and total fetal mortality as well as the number of live fetuses were very similar in the experimental and control animals. The flight group showed a slight decline of fetal weight and water content. The size of the litters produced by the flight and control rats was identical but the mortality rate of those former during the first 7 days after birth was significantly higher. This experiment has demonstrated that the mammalian fetus exposed to zero-g during the last term of pregnancy, i. e., at the stage of active organogenesis, can grow and develop in the normal way. A large body of biological material has been obtained for biochemical and histological examinations that will help evaluate the condition of dams, fetuses, and newborns.}, } @article {pmid3889588, year = {1985}, author = {Denisova, LIa and Zagrebel'nyĭ, SN and Zakabunin, AI and Kileva, EV and Pustoshilova, NM}, title = {[Circular transcription map of the plasmid pBR322].}, journal = {Molekuliarnaia biologiia}, volume = {19}, number = {2}, pages = {537-544}, pmid = {3889588}, issn = {0026-8984}, mesh = {Autoradiography ; Base Sequence ; *Chromosome Mapping ; DNA, Bacterial/genetics ; DNA, Circular/genetics ; DNA-Directed RNA Polymerases/genetics ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/enzymology/*genetics ; *Plasmids ; *Transcription, Genetic ; }, abstract = {The plasmid pBR322 transcription in the isolated E. coli DNA-dependent RNA-polymerase system was studied. Transcription regions as well as transcripts orientation were defined using both the technique of "criss-cross" hybridization and the annealing of RNA-products with L- and H-strands of plasmid. Summing up obtained data together with available data on promoter localization a circular transcription map of plasmid pBR322 was constructed. Effects of heparin, ion strength and E. coli S-30 system on in vitro transcripts were also studied. The 110-long RNA transcript synthesized in Ori region of pBR322 was found to be the most sensitive to all these factors. RNA-transcripts obtained in in vitro system are able to direct protein synthesis in cell-free S-30 system.}, } @article {pmid4059993, year = {1985}, author = {Egorkina, DA and Gurevich, LE and Denisova, II}, title = {[Genetic indices in diseases of the lungs].}, journal = {Sovetskaia meditsina}, volume = {}, number = {8}, pages = {8-12}, pmid = {4059993}, issn = {0038-5077}, mesh = {Cysts/*genetics ; Female ; Humans ; Lung Diseases/*genetics ; Lung Neoplasms/*genetics ; Male ; Pneumonia/*genetics ; }, } @article {pmid4006687, year = {1985}, author = {Vazina, AA and Denisova, EA and Zheleznaia, LA and Lazarev, PI}, title = {[Roentgenographic study of glycoproteins isolated from the duodenal juice of dogs].}, journal = {Doklady Akademii nauk SSSR}, volume = {281}, number = {4}, pages = {975-978}, pmid = {4006687}, issn = {0002-3264}, mesh = {Animals ; Chromatography, Gel ; Dogs ; *Duodenum ; Electrophoresis, Polyacrylamide Gel ; Glycoproteins/*analysis/isolation & purification ; Intestinal Secretions/*analysis ; Mucus/analysis ; X-Ray Diffraction ; }, } @article {pmid4000614, year = {1985}, author = {Denisova, VI}, title = {[A rare case of the presence of a drop of fat in the anterior chamber].}, journal = {Oftalmologicheskii zhurnal}, volume = {}, number = {1}, pages = {61-62}, pmid = {4000614}, issn = {0030-0675}, mesh = {*Anterior Chamber ; *Corneal Injuries ; Eye Foreign Bodies/*diagnosis ; *Fats ; Female ; Humans ; }, } @article {pmid3996982, year = {1985}, author = {Volc, J and Denisova, NP and Nerud, F and Musílek, V}, title = {Glucose-2-oxidase activity in mycelial cultures of basidiomycetes.}, journal = {Folia microbiologica}, volume = {30}, number = {2}, pages = {141-147}, pmid = {3996982}, issn = {0015-5632}, mesh = {Basidiomycota/*enzymology ; Carbohydrate Dehydrogenases/*metabolism ; Culture Media ; Kinetics ; Species Specificity ; }, abstract = {The activity of intracellular glucose-2-oxidase was tested in 40 species of 26 basidiomycete genera. The enzyme catalyzing the oxidation of D-glucose to the dicarbonyl sugar D-arabino-2-hexosulose was demonstrated in mycelial extracts of 9 species of Aphyllophorales and 6 species of Agaricales cultivated in liquid media. In the majority of species exhibiting this activity hexosulose was detected in the cultivation medium. The highest enzyme activity was detected in Oudemansiella mucida, Coriolopsis occidentalis, Fomes fomentarius, Trametes versicolor and a not-yet-classified species of the genus Trametes.}, } @article {pmid3984577, year = {1985}, author = {Denisova, LA and Dolgopolova, GV and Iliushko, NA and Lavrova, EA and Natochin, IuV}, title = {[Changes in the electrolyte composition of the heart, liver and kidneys of the rat in pre- and postnatal ontogeny].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {21}, number = {1}, pages = {13-18}, pmid = {3984577}, issn = {0044-4529}, mesh = {Animals ; Animals, Newborn ; Electrolytes/*metabolism ; Gestational Age ; Heart/*embryology/growth & development ; Kidney/embryology/growth & development/*metabolism ; Liver/embryology/growth & development/*metabolism ; Myocardium/*metabolism ; Rats ; Rats, Inbred Strains ; }, abstract = {From the 19th day of embryonic period, within 4 days, i. e. up to the beginning of postnatal life, the weight of the heart in rats increases by 3.3 times, that of the liver--by 2.2 times, and kidneys--by 5.7 times, whereas the content of water (calculated per dry weight of the organs) decreases. Changes in the content of sodium, potassium, calcium and magnesium in these organs are the lowest provided calculations are made per wet weight; during organogenesis, gradual decrease in the content of electrolytes (calculated per dry weight of the tissue) takes place. The value of Na/K ratio decreases during organogenesis. The content of iron and copper in these organs is higher in adult animals, than in younger ones.}, } @article {pmid3843162, year = {1985}, author = {Samotolkin, KN and Cherkasov, VL and Suzdaleva, VV and Denisova, NA}, title = {[Initial results of using the new detoxifying preparation neohemodes in the treatment of viral hepatitis patients].}, journal = {Trudy Instituta imeni Pastera}, volume = {63}, number = {}, pages = {95-100}, pmid = {3843162}, issn = {0202-1447}, mesh = {Adolescent ; Adult ; Aged ; Female ; Hepatitis, Viral, Human/*drug therapy ; Humans ; Male ; Middle Aged ; Povidone/*therapeutic use ; }, } @article {pmid2986356, year = {1985}, author = {Zaval'naia, OB and Shevliagin, VIa and Khrustalev, SA and Denisova, RA}, title = {[Isolation of high titers of the Schmidt-Ruppin strain of Rous sarcoma virus in a cell culture].}, journal = {Voprosy virusologii}, volume = {30}, number = {1}, pages = {104-106}, pmid = {2986356}, issn = {0507-4088}, mesh = {Animals ; Avian Sarcoma Viruses/growth & development/*isolation & purification ; Chick Embryo ; Chickens ; Sarcoma, Avian/microbiology ; Virus Cultivation/methods ; Virus Replication ; }, } @article {pmid2581060, year = {1985}, author = {Iurgilevich, VP and Denisova, NK}, title = {[Quality control of biochemical studies in Grodno Oblast].}, journal = {Laboratornoe delo}, volume = {}, number = {3}, pages = {182-183}, pmid = {2581060}, issn = {0023-6748}, mesh = {Laboratories/*standards ; Quality Control ; Republic of Belarus ; }, } @article {pmid6092520, year = {1984}, author = {Dekker, BM and Konings, DA and Denisova, TS and Gibadulin, RA and Van Ormondt, H}, title = {The nucleotide sequence of the leftmost XhoI fragment (6%) of simian adenovirus SA7P.}, journal = {The Journal of general virology}, volume = {65 (Pt 10)}, number = {}, pages = {1699-1708}, doi = {10.1099/0022-1317-65-10-1699}, pmid = {6092520}, issn = {0022-1317}, mesh = {Adenoviridae/*genetics ; Adenoviruses, Human/genetics ; Adenoviruses, Simian/*genetics ; Base Sequence ; Cloning, Molecular ; DNA Restriction Enzymes/*metabolism ; DNA, Viral/*analysis ; *Deoxyribonucleases, Type II Site-Specific ; RNA, Viral/analysis ; Repetitive Sequences, Nucleic Acid ; }, abstract = {The DNA of simian adenovirus SA7P was cloned in pBR322. The nucleotide sequences of the leftmost 2238 bp and the rightmost 188 bp of the viral genome were determined. SA7P DNA has an inverted terminal repeat of 183 bp. The sequence at the left terminus exhibits extensive homology with that of the E1 regions of human adenovirus 5, 7 and 12 DNAs. Based on this homology, the RNA coordinates and coding regions could be deduced. The sequenced SA7P DNA contains the entire E1A and part of the E1B region.}, } @article {pmid6593915, year = {1984}, author = {Groshikov, MI and Volozhin, AI and Denisova, IA and Zhuravleva, TP and Pasternak, NA}, title = {[Experimental basis for the clinical use of lysozyme for treating chronic periodontitis].}, journal = {Stomatologiia}, volume = {63}, number = {5}, pages = {4-5}, pmid = {6593915}, issn = {0039-1735}, mesh = {Animals ; Chronic Disease ; Dental Pulp Cavity ; Drug Evaluation ; Drug Evaluation, Preclinical ; Drug Therapy, Combination ; Exudates and Transudates/analysis ; Humans ; Muramidase/analysis/*therapeutic use ; Ointments ; Periodontitis/*drug therapy/enzymology ; Rabbits ; }, } @article {pmid6565496, year = {1984}, author = {Krizhevskaia, IuV and Gomazkov, OA and Ionov, BV and Denisova, MN}, title = {[Importance of the thrombocyte count and form for contact activation of the blood kallikrein-kinin system in vitro].}, journal = {Biulleten' eksperimental'noi biologii i meditsiny}, volume = {98}, number = {8}, pages = {131-134}, pmid = {6565496}, issn = {0365-9615}, mesh = {Animals ; Blood Platelets/*physiology/ultrastructure ; Cell Fractionation ; Enzyme Activation ; Factor XII/physiology ; Kallikreins/*blood ; Kinetics ; Kinins/*blood ; Male ; Microscopy, Electron ; Platelet Count ; Rats ; Rats, Inbred Strains ; }, abstract = {The importance of the platelet count and intactness for contact Hageman's factor-dependent activation of blood plasma kallikrein has been demonstrated. The degree of kallikrein activation was in agreement with the count of platelets contained by the sample. Kallikrein activation was also found to be potentiated by the membrane fraction of washed platelets and of those destroyed by freezing and thawing. The cellular contents did not produce any significant effect on the activation in question.}, } @article {pmid6748461, year = {1984}, author = {Agapova, EN and Denisova, TP and Eliseeva, LN}, title = {[Effect of isoptin on the microcirculation of hypertension patients].}, journal = {Kardiologiia}, volume = {24}, number = {5}, pages = {101-102}, pmid = {6748461}, issn = {0022-9040}, mesh = {Adult ; Calcium Channel Blockers/*therapeutic use ; Conjunctiva/*blood supply ; Humans ; Hypertension/*drug therapy/physiopathology ; Microcirculation/drug effects ; Middle Aged ; Verapamil/*therapeutic use ; }, } @article {pmid6540839, year = {1984}, author = {Denisova, GF and Belostotskaia, KM}, title = {[Two variants of ornithine decarboxylase activity in the mouse liver. The nature of enzyme induction].}, journal = {Molekuliarnaia biologiia}, volume = {18}, number = {3}, pages = {659-666}, pmid = {6540839}, issn = {0026-8984}, mesh = {Animals ; Cell Nucleus/enzymology ; Chromatography, DEAE-Cellulose ; Circadian Rhythm ; Cytoplasm/enzymology ; DNA/biosynthesis ; Diethylnitrosamine/pharmacology ; Electrophoresis, Polyacrylamide Gel ; Enzyme Induction ; Hydrogen-Ion Concentration ; Liver/*enzymology ; Mice ; Ornithine Decarboxylase/*biosynthesis/isolation & purification ; Thioacetamide/pharmacology ; }, abstract = {Ornithine decarboxylase activity in mouse liver is predominantly located in the cell nuclei. After injection of some inducing agents (thioacetamide, diethylnitrosamine, hydrocortisone) the enzyme leaves the nucleus for cytosol. A circadian rhythm of ornithine decarboxylase activity has been observed in nucleus and cytosol, the decrease of enzyme activity in the nucleus being accompanied by its increase in cytosol. The enzyme obtained from intact mice with a minimal level of ornithine decarboxylase activity in the cytosol differs in ion-exchange properties, pH-optimum and Km for ornithine from the thioacetamide stimulated (nucleus enzyme).}, } @article {pmid6088967, year = {1984}, author = {Denisova, LIa and Zagrebel'nyĭ, SN and Pustoshilova, NM and Putintseva, NI and Puchkova, LI}, title = {[Termination of DNA transcription by a poly(dA).poly(dT) fragment inserted into pBR325 plasmid].}, journal = {Molekuliarnaia biologiia}, volume = {18}, number = {3}, pages = {599-606}, pmid = {6088967}, issn = {0026-8984}, mesh = {Base Composition ; Chromosome Mapping ; DNA Restriction Enzymes ; *DNA Transposable Elements ; DNA, Bacterial/genetics ; *DNA, Recombinant ; Electrophoresis, Agar Gel ; Escherichia coli/genetics ; Nucleic Acid Hybridization ; *Plasmids ; Poly dA-dT/*genetics ; Polydeoxyribonucleotides/*genetics ; *Transcription, Genetic ; }, abstract = {A recombinant DNA was constructed by inserting polynucleotide (dA).(dT) of 80-100 base pairs long into EcoRI site of the pBR325 plasmid DNA. Transcription of this DNA was studied in E. coli RNA polymerase system in vitro. Some transcripts obtained with the recombinant plasmid were shown to have poly(U) clusters at the 3'-ends. Obtained data indicate that poly(dA).poly(dT) sequence acts as a terminator of RNA synthesis. Orientation of this sequence in recombinant DNA was also established.}, } @article {pmid6741016, year = {1984}, author = {Denisova, SN and Trofimenko, LS and Sirota, AV}, title = {[Exocrine function of the pancreas in children].}, journal = {Voprosy pitaniia}, volume = {}, number = {2}, pages = {26-28}, pmid = {6741016}, issn = {0042-8833}, mesh = {Adolescent ; Child ; Dietary Carbohydrates/administration & dosage/metabolism ; Dietary Fats/administration & dosage/metabolism ; Enzyme Activation ; Female ; Humans ; Male ; Obesity/*metabolism ; Pancreas/*enzymology ; Trypsin/blood ; Trypsin Inhibitors/blood ; }, abstract = {Thirty-three children were followed up. There were 14 girls and 7 boys with constitutional-exogenous obesity and 12 normal children. To study proteolytic function of the pancreas, the activity of trypsin was determined by the Erlanger method modified by V.A. Shaternikov and that of its inhibitor in the blood serum by the Haverback et al. method modified by V.A. Shaternikov . Activation of trypsin and its inhibitor, depending on the degree of obesity was discovered. Activation of trypsin inhibitor points to the preservation of the compensatory possibilities of the pancreas in children with constitutional-exogenous obesity. Therefore, it is desirable that a complex of different measures should include wise dietetics promoting the normalization of disturbed processes in pathology under consideration.}, } @article {pmid6542287, year = {1984}, author = {Marincheva, GS and Denisova, LV and Gorbachevskaia, NL}, title = {[Clinical features of sex-linked recessive mental retardation with fragile X-chromosome].}, journal = {Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952)}, volume = {84}, number = {10}, pages = {1560-1565}, pmid = {6542287}, issn = {0044-4588}, mesh = {Adolescent ; Child ; Child, Preschool ; Electroencephalography ; Emotions ; Face ; Fantasy ; Female ; Genes, Recessive ; Humans ; Intellectual Disability/*genetics ; Intelligence ; Speech ; X Chromosome ; }, abstract = {The clinical description of 28 boys with recessive sex-linked mental retardation with an X-chromosome fracture is presented. The peculiarities of the relevant somatic and electrophysiological disturbances have been identified which in some cases make it possible to diagnose and in the remaining patients at least to suspect this disease before application of the cytogenetic methods of investigation. The authors also describe the characteristic psychopathological symptomatology manifested in peculiar schizophreniform disorders.}, } @article {pmid6510211, year = {1984}, author = {Vazina, AA and Denisova, EA and Zheleznaia, AA and Lazarev, PI}, title = {[X-ray diffraction study of the floccular structures in the endogenous dense phase of chyme].}, journal = {Doklady Akademii nauk SSSR}, volume = {278}, number = {5}, pages = {1240-1242}, pmid = {6510211}, issn = {0002-3264}, mesh = {Animals ; Colloids ; Dialysis ; Dogs ; *Duodenum ; Hydrogen-Ion Concentration ; Intestinal Secretions/*analysis ; Temperature ; Time Factors ; X-Ray Diffraction ; }, } @article {pmid6390708, year = {1984}, author = {Korol', GG and Denisova, TP and Naumenko, AM}, title = {[From the history of the N. V. Sklifosovskiĭ Institute].}, journal = {Sovetskoe zdravookhranenie}, volume = {}, number = {10}, pages = {53-55}, pmid = {6390708}, issn = {0038-5239}, mesh = {Academies and Institutes/*history ; Emergency Medicine/*history ; History, 19th Century ; History, 20th Century ; Moscow ; }, } @article {pmid6686668, year = {1983}, author = {Serova, LV and Denisova, LA}, title = {[Effect of stress experienced before pregnancy on the reproductive ability of the rat and the condition of the progeny].}, journal = {Patologicheskaia fiziologiia i eksperimental'naia terapiia}, volume = {}, number = {6}, pages = {38-42}, pmid = {6686668}, issn = {0031-2991}, mesh = {Animals ; Animals, Newborn/*growth & development ; *Estrus ; Female ; Humans ; Pregnancy ; *Pregnancy, Animal ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Inbred Strains ; Stress, Psychological/*complications ; }, } @article {pmid6663996, year = {1983}, author = {Denisova, OP and Uspenskiĭ, LV}, title = {[Giant cystic-cavernous lymphhemangioma of the anterior and posterior mediastinum].}, journal = {Khirurgiia}, volume = {}, number = {11}, pages = {130-133}, pmid = {6663996}, issn = {0023-1207}, mesh = {Hemangioma/*diagnosis/surgery ; Humans ; Lymphangioma/*diagnosis/surgery ; Male ; Mediastinal Neoplasms/*diagnosis/surgery ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis/surgery ; }, } @article {pmid6632653, year = {1983}, author = {Kulakova, AM and Denisova, OP}, title = {[Malignancy of foliaceous breast fibroadenomas].}, journal = {Khirurgiia}, volume = {}, number = {9}, pages = {18-20}, pmid = {6632653}, issn = {0023-1207}, mesh = {Adenofibroma/*pathology/surgery ; Adult ; Breast Neoplasms/*pathology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; }, } @article {pmid6314671, year = {1983}, author = {Gibadulin, RA and Denisova, TS and Zavgorodniĭ, SG and Florent'ev, VL and Zhdanov, VM}, title = {[Isolation and characteristics of a mutant herpes simplex virus type 1 resistant to phosphonoacetic acid].}, journal = {Voprosy virusologii}, volume = {28}, number = {4}, pages = {59-63}, pmid = {6314671}, issn = {0507-4088}, mesh = {DNA, Viral/genetics ; Drug Resistance, Microbial ; Genetic Markers ; *Mutation ; Organophosphorus Compounds/*antagonists & inhibitors ; Phosphonoacetic Acid/*antagonists & inhibitors ; Recombination, Genetic ; Simplexvirus/drug effects/genetics/*isolation & purification ; Virus Cultivation ; }, abstract = {By successive passages and triple cloning of herpes simplex virus type 1 (HSV-1) in Vero cell culture in the presence of increasing concentrations of phosphonoacetic acid (PAA) a mutant of HSV-1 resistant to PAA (PAAr) was derived and characterized. The resistance to the inhibitor was transmitted from PAAr-mutant to a sensitive strain (L2) by recombination performed by the marker rescue method using DNA fragmented by Hpa-1 restrictase. The resulting recombinant (R-551) was resistant to the inhibitor and had an altered primary structure of DNA.}, } @article {pmid6880163, year = {1983}, author = {Malyshkin, NP and Denisova, AI and Sigaev, AA and Gorshkov, EV}, title = {[Characteristics of the course of pneumonia in myocardial infarct patients].}, journal = {Vrachebnoe delo}, volume = {}, number = {5}, pages = {34-37}, pmid = {6880163}, issn = {0049-6804}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/administration & dosage ; Diagnosis, Differential ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction/*complications ; Pneumonia/*diagnosis/drug therapy/etiology ; }, } @article {pmid6843496, year = {1983}, author = {Kovalenko, LG and Viktorov-Nabokov, OV and Ruban, EM and Skrynik, EM and Denisova, ZA}, title = {[Repellent properties of Mannich bases and cresol and phenol derivatives for Aedes aegypti L. mosquitoes and the flea Xenopsylla cheopis Roths].}, journal = {Meditsinskaia parazitologiia i parazitarnye bolezni}, volume = {52}, number = {1}, pages = {46-48}, pmid = {6843496}, issn = {0025-8326}, mesh = {*Aedes ; *Amines ; Animals ; *Cresols ; *Insect Repellents ; *Mannich Bases ; *Phenols ; *Siphonaptera ; Structure-Activity Relationship ; }, } @article {pmid6683054, year = {1983}, author = {Denisova, LV and Bedel'baeva, KA}, title = {[Sex-linked recessive mental retardation without specific clinical manifestations].}, journal = {Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952)}, volume = {83}, number = {3}, pages = {92-97}, pmid = {6683054}, issn = {0044-4588}, mesh = {Child ; Female ; Genes, Recessive ; Humans ; Intellectual Disability/*genetics ; Male ; Pedigree ; Sex Chromosomes/*ultrastructure ; X Chromosome/*ultrastructure ; }, } @article {pmid6316565, year = {1983}, author = {Denisova, OP and Kulakova, AM}, title = {[Sarcoma developing from phyllode tumors of the breast].}, journal = {Sovetskaia meditsina}, volume = {}, number = {9}, pages = {121-124}, pmid = {6316565}, issn = {0038-5077}, mesh = {Breast Neoplasms/*pathology ; Female ; Fibrosarcoma/*pathology ; Humans ; Liposarcoma/*pathology ; Middle Aged ; Phyllodes Tumor/*pathology ; }, } @article {pmid6303280, year = {1983}, author = {Kogan, EA and Sklianskaia, OA and Denisova, OP and Berestova, AV and Uspenskiĭ, LV}, title = {[Association of small peripheral lung cancer and early stomach cancer].}, journal = {Arkhiv patologii}, volume = {45}, number = {2}, pages = {60-66}, pmid = {6303280}, issn = {0004-1955}, mesh = {Adenocarcinoma/*pathology/ultrastructure ; Carcinoma, Small Cell/*pathology/ultrastructure ; Humans ; Lung Neoplasms/*pathology/ultrastructure ; Male ; Microscopy, Electron ; Middle Aged ; Neoplasms, Multiple Primary/*pathology/ultrastructure ; Stomach Neoplasms/*pathology/ultrastructure ; }, abstract = {A combination of peripheral lung oat-cell carcinoma and early gastric highly differentiated adenocarcinoma in a man of 52 with long-term chronic peptic ulcer existing for 20 years is described. Electron microscopic and histochemical examinations of pulmonary carcinoma revealed neurosecretory granules and keratohyalin in the tumor cells. The gastric tumor on the ultrastructural level had cells differentiating in the direction of the glandular and intestinal epithelium. The presence of two independent malignant tumors in the patient was proven by the use of several morphological methods (cytologic, histologic, histochemical and electron microscopic).}, } @article {pmid6890601, year = {1982}, author = {Serova, LV and Denisova, LA and Apanasenko, ZI and Kuznetsova, MA and Meĭzerov, ES}, title = {[Reproductive function of the male rat after a flight on the Kosmos-1129 biosatellite].}, journal = {Kosmicheskaia biologiia i aviakosmicheskaia meditsina}, volume = {16}, number = {5}, pages = {62-65}, pmid = {6890601}, issn = {0321-5040}, mesh = {Animals ; Female ; Fetus/physiology ; Growth ; Humans ; Male ; Organ Size ; Pregnancy ; Rats ; Rats, Inbred Strains ; *Reproduction ; *Space Flight ; Spermatozoa/physiology ; Stress, Psychological/blood ; USSR ; Weightlessness/adverse effects ; }, abstract = {Male rats that were flown for 18.5 days on Cosmos-1129 were mated postflight with intact females. The mating 5 days postflight when the ejaculate consisted of spermatozoids that were exposed to zero-g effects in the mature stage yielded the litter which lagged behind the controls with respect to the growth and development during the first postnatal month. The mating 2.5-3 months postflight when the ejaculate consisted of spermatozoids that were exposed to zero-g effects at the stem cell stage yielded the litter which did not differ from the control.}, } @article {pmid7135929, year = {1982}, author = {Denisova, TS and Makhov, AM and Gibadulin, RA}, title = {[Identification of a new antigenic variant of simian adenovirus SA7 P].}, journal = {Voprosy virusologii}, volume = {27}, number = {4}, pages = {483-488}, pmid = {7135929}, issn = {0507-4088}, mesh = {Adenoviridae/*immunology ; Adenoviruses, Simian/classification/genetics/*immunology ; Antigens, Viral/classification/*immunology ; Chemical Phenomena ; Chemistry, Physical ; Cross Reactions ; DNA, Viral/genetics ; *Genetic Variation ; Neutralization Tests ; Nucleic Acid Heteroduplexes/genetics ; Serotyping ; Virus Cultivation ; }, abstract = {Serological, biological, and physico-chemical properties of a new antigenic variant of simian adenovirus SA7P were studied. Neutralization tests with hyperimmune specific antisera demonstrated the new antigenic variant SA7P to have very significant antigenic similarity with the prototype SA7 strain. Same as the latter, SA7P does not agglutinate rat red blood cells, is highly oncogenic for newborn Syrian hamsters and capable of transforming rat kidney cell cultures. At the same time, the method of heteroduplex analysis showed SA7P DNA to be homologous to DNA of the reference SA7 strain by 85% and to contain 3 non-homologous regions in the right part of the virus genome. Comparison of the physical maps of the 2 virus DNAs by 4 restrictases established considerable differences in the number of recognition sites and their location.}, } @article {pmid7133870, year = {1982}, author = {Fedorova, EV and Golubeva, LG and Denisova, LN and Blinovskaia, OP and Kholodniak, TN}, title = {[Rachitis and rachitis-like changes in children receiving anticonvulsant therapy].}, journal = {Pediatriia}, volume = {}, number = {7}, pages = {36-38}, pmid = {7133870}, issn = {0031-403X}, mesh = {Anticonvulsants/*adverse effects ; Child, Preschool ; Humans ; Infant ; Rickets/*chemically induced ; }, } @article {pmid7120822, year = {1982}, author = {Uspenskiĭ, LV and Kurguzov, OP and Lapchinskii, VA and Denisova, OP}, title = {[Malignant degeneration of a retroperitoneal teratoma].}, journal = {Khirurgiia}, volume = {}, number = {7}, pages = {114-115}, pmid = {7120822}, issn = {0023-1207}, mesh = {Adult ; Humans ; Male ; Retroperitoneal Neoplasms/*pathology ; Teratoma/*pathology ; }, } @article {pmid7052148, year = {1982}, author = {Morozova, EN and Falina, NN and Denisova, NP and Barkova, LV and Psurtseva, NV}, title = {[Analysis of the component constitution and substrate specificity of a fibrinolytic preparation from the fungus Flammulina velutipes].}, journal = {Biokhimiia (Moscow, Russia)}, volume = {47}, number = {7}, pages = {1181-1185}, pmid = {7052148}, issn = {0320-9725}, mesh = {Agaricales/*enzymology ; *Fibrinolysis ; Hydrogen-Ion Concentration ; Kinetics ; Peptide Hydrolases/*metabolism ; Substrate Specificity ; }, abstract = {The degree of heterogeneity of the proteolytic complex from the fungus Flammulina velutipes was studied by gel chromatography and analytical isoelectrofocusing. The fibrinolytic, thrombolytic, caseinolytic, endo- and aminopeptidase activities of the enzyme complex were compared to those of Aspergillus terricola and Streptomyces griseus proteinases. The proteolytic complex under study consists of at least two proteinases with pI 6.1 and 7.1, which possess fibrinolytic, thrombolytic and endopeptidase activities and of two aminopeptidases with pI 5.5 and 6.05. All these activities are inhibited by metal-chelating reagents. A low caseinolytic activity of the complex suggests that it can successfully be employed as a therapeutic agent.}, } @article {pmid6281178, year = {1982}, author = {Kisselev, V and Denisova, G and Kisselev, O and Nosikov, V and Ishenko, A and Polyanovsky, O}, title = {Immunochemical identification of products of the mitochondrial cytochromoxidase gene expressed in E. coli cells.}, journal = {Immunology letters}, volume = {4}, number = {3}, pages = {145-147}, doi = {10.1016/0165-2478(82)90026-8}, pmid = {6281178}, issn = {0165-2478}, mesh = {Animals ; Cloning, Molecular ; DNA Restriction Enzymes/pharmacology ; DNA, Mitochondrial/*genetics ; DNA, Recombinant ; Deoxyribonuclease BamHI ; Electron Transport Complex IV/*genetics/immunology ; Escherichia coli/genetics ; Genes ; Rats ; }, abstract = {Bacterial clones containing hybrid plasmids with mitochondrial DNA insertions were obtained. Among them, a clone synthesizing immunoreactive protein with molecular weight 45,000 was discovered by means of antibodies against mitochondrial cytochromoxidase. The synthesis of the protein depended on orientation of the mitochondrial DNA insertion in the hybrid plasmid. The size of the protein was in excess of the coding capacity of the insertion, which speaks of chimeric nature of the protein. Absorption of the protein by the immunoglobulin fraction containing antibodies against cytochromoxidase resulted in a loss of antibody binding to cytochromoxidase subunit III.}, } @article {pmid6280036, year = {1982}, author = {Gibadulin, RA and Dejkema, R and Denisova, TS and van Ormondt, H}, title = {[Simian adenovirus genome. II. Identification of specific fragments of viral DNA possessing transforming activity].}, journal = {Molekuliarnaia biologiia}, volume = {16}, number = {2}, pages = {315-321}, pmid = {6280036}, issn = {0026-8984}, mesh = {Adenoviridae/*genetics ; Adenoviruses, Simian/*genetics ; Animals ; *Cell Transformation, Viral ; Cells, Cultured ; DNA Restriction Enzymes ; DNA, Viral/*genetics/isolation & purification ; *Genes, Viral ; Kidney ; Rats ; }, abstract = {The antigenic variant of simian adenovirus 7 (SA7) DNA was cleaved by restriction endonucleases EcoRI, XbaI, BamHI, SalI. The resulted digests of viral DNA were tested for transforming activity using the "calcium" technique. It was shown that BamHI. XbaI and SalI digests transformed primary baby rat kidney cells as well as native viral DNA. The transforming activity of separated BamHI and SalI fragments was tested also. The viral DNA fragments with transforming activity (BamHI-B and SalI-B) were localised on the left of the physical map of the viral genome. It was also shown that fragment-transformed cell lines were able to form colonies in 0.33% agarose medium.}, } @article {pmid6461147, year = {1982}, author = {Fel'ker, AIa and Shchetinina, RI and Denisova, TV and Kuntuganov, DK}, title = {[Role of serological studies in the detection of syphilis among patients in internal disease hospitals].}, journal = {Vestnik dermatologii i venerologii}, volume = {}, number = {2}, pages = {69-70}, pmid = {6461147}, issn = {0042-4609}, mesh = {Adult ; Female ; Hospitals, Special ; Humans ; Internal Medicine ; Kazakhstan ; Male ; Middle Aged ; Syphilis/epidemiology ; *Syphilis Serodiagnosis ; }, } @article {pmid7144076, year = {1982}, author = {Ado, AD and Lobkova, OS and Egunova, SM and Laĭvin, AN and Denisova, SD}, title = {[Broncho-alveolar lavage in bronchial asthma].}, journal = {Klinicheskaia meditsina}, volume = {60}, number = {8}, pages = {30-33}, pmid = {7144076}, issn = {0023-2149}, mesh = {Adolescent ; Adult ; Asthma/*diagnosis/pathology ; Bronchi/*pathology ; Bronchitis/diagnosis ; Bronchoscopy ; Cytodiagnosis/methods ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Alveoli/*pathology ; Therapeutic Irrigation ; }, } @article {pmid6759083, year = {1982}, author = {Denisova, LIa and Zagrebel'nyĭ, SN and Kutiavin, IV and Pustoshilova, NM}, title = {[Continuous copying of the short matrices of DNA-dependent RNA-polymerase].}, journal = {Doklady Akademii nauk SSSR}, volume = {267}, number = {2}, pages = {475-478}, pmid = {6759083}, issn = {0002-3264}, mesh = {Amino Acid Sequence ; Chromatography, DEAE-Cellulose ; DNA-Directed RNA Polymerases/*biosynthesis/genetics ; Electrophoresis, Polyacrylamide Gel ; Enzyme Induction ; Escherichia coli/enzymology ; Kinetics ; *Transcription, Genetic ; }, } @article {pmid6270854, year = {1981}, author = {Parkhomenko, II and Denisova, TS and Sitnikov, BS}, title = {[Oncogen localization in the DNA composition of simian adenoviruses. II. The identification in SV20 virus DNA of a specific fragment possessing transforming activity].}, journal = {Tsitologiia}, volume = {23}, number = {9}, pages = {1026-1030}, pmid = {6270854}, issn = {0041-3771}, mesh = {Adenoviridae/*analysis ; Adenoviruses, Simian/*analysis/genetics ; Animals ; *Carcinogens ; *Cell Transformation, Viral/drug effects ; DNA Restriction Enzymes/pharmacology ; DNA, Viral/*analysis/genetics ; Genes, Viral/drug effects ; Rats ; Rats, Inbred Strains ; Virus Cultivation ; }, abstract = {Simian adenovirus 20 DNA was specifically cleavered by restriction endonucleases EcoRI, BamHI, XbaI and HindIII. The transformation activity of the DNA digest was investigated. BamHI, XbaI, and HindII DNA digests were able to transform the primary rat kidney cell culture (Wistar) as well as the native SV20 DNA. The transforming activity was revealed in a specific fragment of the viral DNA, obtained after the treatment of the DNA with BamHI (fragment B), with molecular weight 5.4 x 10(6) dalton. This fragment is located in the left end of the viral genome. The lack of cell transformation by the EcoRI-hydrolysate of viral DNA may serve a proof of the extremely left position of the oncogene in the viral genome, since of EcoRI-fragment chips off a fragment with molecular weight 3 x 10(5) dalton fr om the left side of DNA molecule.}, } @article {pmid6117672, year = {1981}, author = {Postolov, PM and Kuzin, NM and Denisova, OP}, title = {[Multiple endocrine adenomatosis].}, journal = {Khirurgiia}, volume = {}, number = {9}, pages = {66-69}, pmid = {6117672}, issn = {0023-1207}, mesh = {Adenoma/diagnosis ; Adrenal Cortex Neoplasms/diagnosis ; Adult ; Carcinoma/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Multiple Endocrine Neoplasia/*diagnosis ; Pancreatic Neoplasms/diagnosis ; Parathyroid Neoplasms/diagnosis ; Pituitary Neoplasms/diagnosis ; Zollinger-Ellison Syndrome/diagnosis ; }, } @article {pmid6268964, year = {1981}, author = {Denisova, LIa and Zagrebel'nyi, SN and Kileva, EV and Pustoshilova, NM and Filippov, VA}, title = {[Col E1 DNA transcription in Escherichia coli RNA-polymerase system in vitro].}, journal = {Molekuliarnaia biologiia}, volume = {15}, number = {4}, pages = {768-778}, pmid = {6268964}, issn = {0026-8984}, mesh = {DNA Restriction Enzymes ; DNA, Bacterial/*genetics ; DNA-Directed RNA Polymerases/*metabolism ; *Deoxyribonucleases, Type II Site-Specific ; Escherichia coli/*enzymology ; Kinetics ; Plasmids ; Templates, Genetic ; *Transcription, Genetic ; }, abstract = {The ColEI plasmid DNA transcription in E. coli RNA-polymerase system in vitro was studied. Three RNA types: of 110-140 residues long, 1700 residues long and of the length similar to that of DNA-template were synthesized in the reaction, containing 10 mM MgCl2, 50 mM KCl and 15% glycerol. The transcription was shown to be asymmetric, the DNA H-chain being transcribed. The ColEI DNA region transcribed in vitro was located by the blotting techniques. This region comprised most of the ColEI genome except the colicin EI gene. The addition of mitomycin C to the reaction mixture caused only a little stimulation of colicin EI gene transcription. Four fragments of HaeIII digest of ColEI DNA were shown to have affinity to RNA-polymerase in the absence of NTPs and two fragments to have it in the presence of 3 NTPs (in the RNA initiation conditions). These two fragments seem to contain two strong promoters. One of them is in the HaeIIIA fragment, where the colicin EI gene origin is situated, and another one is the HaeIIIB fragment (in the immunity region).}, } @article {pmid7015760, year = {1981}, author = {Denisova, SV and Lobova, EA and Raskin, BM and Likhoded, VG and Tabachnik, AL}, title = {[Nutrient medium ensuring incorporation of radioactive thymidine into bacterial DNA].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {1}, pages = {22-24}, pmid = {7015760}, issn = {0372-9311}, mesh = {Animals ; Culture Media ; DNA, Bacterial/*biosynthesis ; Erythrocytes ; Escherichia coli/*metabolism ; Horses/blood ; Salmonella typhimurium/metabolism ; Species Specificity ; Thymidine/*metabolism ; }, } @article {pmid6912118, year = {1981}, author = {Denisova, LN and Fedorova, EV}, title = {[Infantile cerebral palsy].}, journal = {Fel'dsher i akusherka}, volume = {}, number = {7}, pages = {17-20}, pmid = {6912118}, issn = {0014-9772}, mesh = {Cerebral Palsy/classification/*diagnosis/drug therapy ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; }, } @article {pmid7003355, year = {1980}, author = {Denisova, LIa and Zagrebel'nyĭ, SN and Pustoshilova, NM}, title = {[Reiterative poly(A) synthesis on oligonucleotide templates in an Escherichia coli RNA-polymerase system].}, journal = {Molekuliarnaia biologiia}, volume = {14}, number = {6}, pages = {1372-1377}, pmid = {7003355}, issn = {0026-8984}, mesh = {Base Sequence ; DNA-Directed RNA Polymerases/*metabolism ; Escherichia coli/enzymology/*metabolism ; Oligonucleotides/metabolism ; Poly A/*biosynthesis ; RNA Polymerase I/*metabolism ; Templates, Genetic ; *Transcription, Genetic ; }, abstract = {The poly(A) synthesis in the E. coli RNA-polymerase system on the oligothymidilates, oligouridilates and oligonucleotides d(5'-OH-CCATCTTTT-3'-OH) and d(5'-HO-TCTTTT-3'-OH) as templates was studied. The reaction was shown to proceed more intensively on the oligothymidilates compared to oligouridilates. The insertion of phosphate residues into 3' end of oligouridilates deteriorates properties of their templates though the length of the synthesized poly(A) is not changed in this case. The synthesis of poly(A) on the nonanucleotide d(CCATCTTTT) proceeds intensively, but there is no AMP incorporation on the hexanucleotide of similar structure. The author's data combined with certain literature results suppose that the template activity of the oligonucleotides containing homopolymer sequences is determined in the RNA-polymerase system in reiterative regime by two factors: by the total amount of oligonucleotide links and by the homopolymer block size. The total amount of links seems to be important for the oligonucleotide enzyme bind stability and must comprise not less than 6 charges of the phosphate groups. The homopolymer block size must be no less than of 4 links.}, } @article {pmid6159737, year = {1980}, author = {Zaval'nyĭ, MA and Grachev, VP and Denisova, TN and Popova, VL and Mironova, LL}, title = {[Cultivation of primary animal cells on microcarriers of various types].}, journal = {Voprosy virusologii}, volume = {}, number = {5}, pages = {583-589}, pmid = {6159737}, issn = {0507-4088}, mesh = {Animals ; Cell Line ; *Cells, Cultured ; Chick Embryo ; *DEAE-Dextran/*analogs & derivatives ; Dextrans ; Ethanolamines ; Haplorhini ; In Vitro Techniques ; Kidney/embryology ; Methods ; Swine ; }, abstract = {Primary cells of chick embryos (CEC), new-born piglet kidneys (NPK), and green monkey kidney (GMK) obtained by the conventional method of tissue trypsinization were shown to grow satisfactorily on microcarriers of various types. CEC formed a confluent monolayer on Supperbead particles within 38--48 hours when seeded in a dose of 3 x 10(5) cells/ml and on DEAE-Sephadex A-50 within 60--72 hours when seeded in a dose of 4 x 10(5) cells/ml. In both instances, with microcarriers used in a concentration of 1 mg/ml the number of CEC by the end of the cultivation period reached 0.9 million cells/ml. Primary NPK and GMK cells formed monolayers not on all microcarrier particles, nevertheless the number of cells in both cultures increased 2--2 1/2-fold in 7 days. The optimal seed concentration of cells depended both on the quality of the primary cell suspension and on the microcarrier type. The monolayer of CEC cells formed on DEAE-Sephadex A-50 particles persisted for 7--14 days.}, } @article {pmid6250025, year = {1980}, author = {Denisova, TS and Gibadulin, RA and Sitnikov, BS and Senkevich, TG and Medvedkina, OA}, title = {[Simian adenovirus 20 genome. I. DNA mapping using restriction enconucleases BamHI, EcoRi, XbaI, HindIII].}, journal = {Molekuliarnaia biologiia}, volume = {14}, number = {3}, pages = {708-720}, pmid = {6250025}, issn = {0026-8984}, mesh = {Adenoviridae/*analysis ; Adenoviruses, Human ; Adenoviruses, Simian/*analysis ; Base Sequence ; *DNA Restriction Enzymes ; *DNA, Viral ; Deoxyribonuclease BamHI ; Deoxyribonuclease HindIII ; *Deoxyribonucleases, Type II Site-Specific ; *Genes, Viral ; Molecular Weight ; Species Specificity ; Substrate Specificity ; Terminology as Topic ; }, abstract = {The effect of specific restriction endonuclease on the simian adenovirus SV20 DNA was studied. It was shown that endonucleases SalI, XbaI, EcoRI, BamHI, HindIII cleaved the viral DNA into 3, 4, 5, 5, 8 specific fragments respectively. The sequence of fragments (physical map) was determined and found to be B-C-A for enzyme SalI, C-D-B-A--for enzyme Xbal, E-A-C-D-B--for enzyme EcoRI, B-E-C-A-D--for enzyme BamHI and B-E-A-C-(GH)-D-F--for enzyme HindIII. The G-C content of specific fragments was studied. The "right"-"left" orientation of the physical map of the simian adenovirus 20 DNA based on the G-C content was made in respect with the nomenclature of human adenoviruses.}, } @article {pmid6770539, year = {1980}, author = {Kurshin, MA and Kholkina, GF and Denisova, NA and Kotova, OA}, title = {[Lactose tolerance in premature infants and infants with acute and chronic diseases of the small intestine].}, journal = {Voprosy okhrany materinstva i detstva}, volume = {25}, number = {1}, pages = {50-52}, pmid = {6770539}, issn = {0042-8825}, mesh = {Adolescent ; Child ; Diarrhea, Infantile/enzymology ; Duodenitis/enzymology ; Enzyme Activation ; Escherichia coli Infections/enzymology ; Humans ; Infant ; Infant, Newborn ; *Infant, Premature ; Intestinal Diseases/*enzymology ; *Intestine, Small/enzymology ; *Lactose Tolerance Test ; beta-Galactosidase/metabolism ; }, } @article {pmid6450800, year = {1980}, author = {Kravchenko, NA and Berezkina, GN and Belogurova, VA and Zhdanova, KG and Didenko, ES and Karas', SR and Nurieva, LS and Varshava, BL and Kareyeva, VA and Arkhipova, TV and Karpová, SL and Petrov, VI and Mikhailova, MV and Denisova, BD}, title = {Some aspects of phage typing of diphtheria microbes in epidemiological practice.}, journal = {Journal of hygiene, epidemiology, microbiology, and immunology}, volume = {24}, number = {4}, pages = {482-488}, pmid = {6450800}, issn = {0022-1732}, mesh = {*Bacteriophage Typing ; Corynebacterium diphtheriae/*classification ; Diphtheria/epidemiology ; Humans ; Russia ; }, } @article {pmid6260443, year = {1980}, author = {Denisova, GF and Kiselev, VI and Nosikov, VV and Polianovskiĭ, OL and Filina, GS}, title = {[Rat cytochrome oxidase polypeptide chain synthesis in Escherichia coli cells].}, journal = {Doklady Akademii nauk SSSR}, volume = {255}, number = {4}, pages = {1002-1005}, pmid = {6260443}, issn = {0002-3264}, mesh = {Animals ; Clone Cells/enzymology ; Electron Transport Complex IV/*biosynthesis/genetics ; Enzyme Induction ; Escherichia coli/*enzymology/genetics ; Gene Expression Regulation ; Genetic Code ; *Peptide Biosynthesis ; Peptides/genetics ; Rats ; }, } @article {pmid506161, year = {1979}, author = {Baranov, AA and Stroinskaia, GA and Denisova, LI and Polamarchuk, SI}, title = {[Risk factors in the prevention and early detection of digestive organ diseases in children].}, journal = {Voprosy okhrany materinstva i detstva}, volume = {24}, number = {11}, pages = {13-15}, pmid = {506161}, issn = {0042-8825}, mesh = {Adolescent ; Child ; Child, Preschool ; Digestive System Diseases/diagnosis/*prevention & control ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Risk ; Time Factors ; }, } @article {pmid494792, year = {1979}, author = {Denisova, AS}, title = {[Effect of electric stimulation of the somatosensory cortex and caudate nucleus on extinctive inhibition of a conditioned alimentary reflex to sound].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {29}, number = {5}, pages = {899-905}, pmid = {494792}, issn = {0044-4677}, mesh = {Animals ; Brain Mapping ; Caudate Nucleus/*physiology ; Conditioning, Classical/physiology ; Dogs ; Electric Stimulation ; Extinction, Psychological/*physiology ; Food ; Reinforcement Schedule ; Salivation ; Somatosensory Cortex/*physiology ; Sound ; }, abstract = {In experiments performed on 9 dogs with alimentary method, extinctive inhibition was deepened and its elaboration was aceelerated by electrical stimulation of somatosensory and motor cortical areas and ventral segment of the caudate nucleus head. The extinction of the conditioned reflex was slowed down by stimulation of the anterolateral gyrus and the central segment of the caudate nucleus head. General motor excitation of animals during stimulation of the dorsal zone of caudate nucleus head impaired the elaboration of extinctive inhibition.}, } @article {pmid228178, year = {1979}, author = {Denisova, TS and Sitnikov, BS and Gibadulin, RA}, title = {[DNA fragmentation of chicken adenovirus CELO by specific endonucleases R. HpaI, R. EcoRI, R. HindIII].}, journal = {Molekuliarnaia biologiia}, volume = {13}, number = {5}, pages = {1021-1034}, pmid = {228178}, issn = {0026-8984}, mesh = {Adenoviridae/*analysis ; Aviadenovirus/*analysis ; Base Sequence ; *DNA Restriction Enzymes/metabolism ; *DNA, Viral ; Escherichia coli/enzymology ; Haemophilus/enzymology ; Oligodeoxyribonucleotides/analysis ; Substrate Specificity ; }, abstract = {The effect of specific endonucleases on DNA chiken adenovirus CELO was studed. It was shown that endonucleases R. HpaI, R. EcoRI and R. HindIII cleaved viral DNA into 5,7 and 9 specific fragments, respectively. The sequence of fragments (physical map) was determined and found to be: D-A-E-C-B for enzyme R. HpaI; B-(EG)-C-A-D-F for enzyme R. EcoRI; H-F-A-C-G-B-D-E-I for enzyme R. HindIII.}, } @article {pmid505132, year = {1979}, author = {Vermel', AE and Bal', LV and Denisova, EA and Kirdanova, GI and Kochanova, EM}, title = {[Neurocirculatory asthenia in present-day clinical cases of occupational diseases].}, journal = {Sovetskaia meditsina}, volume = {}, number = {7}, pages = {65-69}, pmid = {505132}, issn = {0038-5077}, mesh = {Adult ; Hemodynamics/radiation effects ; Humans ; Maximum Allowable Concentration ; Middle Aged ; Neurocirculatory Asthenia/*etiology ; Occupational Diseases/*etiology ; Radiation Dosage ; }, } @article {pmid381899, year = {1979}, author = {Belova, NV and Denisova, LIa and Zagrebel'nyĭ, SN and Pustoshilova, NM and Saĭkovich, EG}, title = {[Transcription of synthetic oligonucleotides].}, journal = {Molekuliarnaia biologiia}, volume = {13}, number = {4}, pages = {845-853}, pmid = {381899}, issn = {0026-8984}, mesh = {DNA-Directed RNA Polymerases/*metabolism ; Escherichia coli/*enzymology ; Kinetics ; *Oligodeoxyribonucleotides ; *Oligonucleotides ; Templates, Genetic ; *Transcription, Genetic ; }, abstract = {The decadeoxynucleotides d(pTTC)3 and d(CCATCTTTT) transcription by E. coli RNA-polymerase was studied. The nucleotide composition of d(pTTC)3 transcript was shown to be consistent with that of the template, but RNA-product was several times longer than the template. With nonanucleotide d(CCATCTTTT) the poly(A) synthesis was observed. This fact may be attributed to the reiteration on the TTTT-cluster. When using the oligonucleotide primers d(pGGA) and r(pAAAA) complementary to the templates d(pTTC)3 and d(CCATCTTTT), accordingly, the nucleosidetriphosphates concentration being reduced and the RNA-polymerase "holo" being replaced by "core", the considerable decrease in the unhomogeneity of the transcript length and in the length itself was found. With d(pTTC)3 as a template the length of RNA-product was found to be of 24-25 nucleotides and with d(CCATCTTTT) it was of 18-19 nucleotides. The sequence of RNA transcribed from both templates in the presence of primers was in accordance with the structure of templates.}, } @article {pmid571357, year = {1979}, author = {Novikova, LS and Denisova, LE and Shvager, IG and Zakarian, LM}, title = {[Antimicrobial activity of the total alkaloids and preparations of celandine].}, journal = {Farmatsiia}, volume = {28}, number = {2}, pages = {54}, pmid = {571357}, issn = {0367-3014}, mesh = {Alkaloids/*pharmacology ; Bacteria/*drug effects ; Dose-Response Relationship, Drug ; Microbial Sensitivity Tests ; *Plants, Medicinal ; }, } @article {pmid669368, year = {1978}, author = {Larionov, AG and Denisova, LG and Cherkasova, TE}, title = {[Hygienic evaluation of foundry brands of Arylox].}, journal = {Gigiena i sanitariia}, volume = {}, number = {8}, pages = {99-100}, pmid = {669368}, issn = {0016-9900}, mesh = {Animals ; Environmental Exposure ; *Metallurgy ; Mice ; Phenyl Ethers/toxicity ; Polymers/*toxicity ; Rats ; Temperature ; Time Factors ; Volatilization ; }, } @article {pmid693115, year = {1978}, author = {Denisova, MF and Revuts'ka, AIe}, title = {[Characteristics of the absorptive function of the intestine in children with chronic cholecystocholangitis].}, journal = {Pediatriia akusherstvo i ginekologiia}, volume = {}, number = {4}, pages = {9-11}, pmid = {693115}, issn = {0031-4048}, mesh = {Adolescent ; Child ; Child, Preschool ; Cholangitis/*physiopathology ; Cholecystitis/*physiopathology ; Chronic Disease ; Female ; Humans ; *Intestinal Absorption ; Male ; }, } @article {pmid355863, year = {1978}, author = {Denisova, LIa and Zagrebel'nyĭ, SN and Kileva, EV and Pustoshilova, NM and Torbina, AI}, title = {[Conversion of nucleoside triphosphates in an RNA polymerase system].}, journal = {Molekuliarnaia biologiia}, volume = {12}, number = {4}, pages = {766-771}, pmid = {355863}, issn = {0026-8984}, mesh = {Adenosine Triphosphate ; Catalysis ; Cytidine Triphosphate ; *DNA-Directed RNA Polymerases ; Escherichia coli/*enzymology/metabolism ; Guanosine Triphosphate ; Kinetics ; *Nucleotides ; RNA, Bacterial/biosynthesis ; Uridine Triphosphate ; }, abstract = {The behavior of nucleoside triphosphates (NTP) in the RNA-polymerase system from E. coli was studied. The conversion of NTP to the corresponding nucleoside diphosphate (NDP) was observed. This phenomenon was accounted for a contaminating enzyme activity in the RNA-polymerase preparations. The possibility to remove such a contamination was demonstrated, the best technique being the DNA-cellulose affinity chromatography. The purified enzyme does not catalyze the intermediate formation of NDP's from NTP's during RNA synthesis with poly(U) and poly(dG)-poly(dC) as templates.}, } @article {pmid97885, year = {1978}, author = {Raskin, BM and Mel'nikova, VA and Denisova, SV and Perel'man, EV and Lobova, EA}, title = {[Prospects for the use of blood substitutes made in the USSR with the expired date of validity].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {6}, pages = {85-89}, pmid = {97885}, issn = {0372-9311}, mesh = {Amino Acids ; Bacteria/*growth & development ; Caseins ; Corynebacterium diphtheriae/growth & development ; *Culture Media ; Drug Utilization ; Peptides ; *Plasma Substitutes ; Shigella flexneri/growth & development ; Species Specificity ; Streptococcus/growth & development ; USSR ; }, abstract = {As revealed, blood substitutes--aminopeptide, caseine hydrolysate, and hydrolysine with the expired date of validity could be used as the basis of nutrient media for the cultivation of bacteria. Bacterial growth proved to be the optimum in addition to the blood substitutes of a 0.25--0.5% of yeast extract.}, } @article {pmid349360, year = {1978}, author = {Badashkeeva, AG and Denisova, LIa and Zagrebel'nyĭ, SN and Knorre, DG and Pustoshilova, NM}, title = {[Template properties of the decadeoxynucleotide d(pCCACGAAACC) in the RNA polymerase system of Escherichia coli].}, journal = {Molekuliarnaia biologiia}, volume = {12}, number = {2}, pages = {327-333}, pmid = {349360}, issn = {0026-8984}, mesh = {Chemical Phenomena ; Chemistry ; Chromatography, DEAE-Cellulose ; DNA-Directed RNA Polymerases/*metabolism ; Escherichia coli/metabolism ; Hydrolysis ; Kinetics ; Magnetic Resonance Spectroscopy ; Nucleotides/*metabolism ; RNA, Bacterial/biosynthesis ; Ribonucleases ; *Transcription, Genetic ; }, abstract = {The decadeoxynucleotide d(pCCACGAAACC) transcription by E. coli RNA-polymerase was studied. The transcript was shown to be several times longer than the template. The oligonucleotide GpGpGpGpUp complementary to the "contact" of two neighbouring template molecules was found in the pancreatic RNase digest of the RNA-product. This fact is consistent with our hypothesis reported recently. Pentanucleotide d(pGGTTT) may funtion as a primer in the decadeoxynucleotide transcription being incorporated into RNA.}, } @article {pmid733163, year = {1978}, author = {Denisova, VI}, title = {[Case of bilateral cataract caused by lightning].}, journal = {Oftalmologicheskii zhurnal}, volume = {33}, number = {7}, pages = {555-556}, pmid = {733163}, issn = {0030-0675}, mesh = {Adolescent ; Cataract/*etiology ; *Electric Injuries ; Humans ; Lens, Crystalline/*injuries ; *Lightning ; Male ; }, } @article {pmid636643, year = {1978}, author = {Denisova, ZV and Brendsted, AN and Tarakanov, PV}, title = {[Interhemispheric asymmetry of theta-activity in children during emotional loading].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {28}, number = {1}, pages = {169-172}, pmid = {636643}, issn = {0044-4677}, mesh = {Brain/*physiology ; Brain Mapping ; Child ; Dominance, Cerebral/*physiology ; Emotions/*physiology ; Female ; Humans ; Male ; Stress, Psychological/physiology ; Theta Rhythm ; }, } @article {pmid143643, year = {1977}, author = {Gerasimova, NG and Denisova, NG and Denisov, PS and Kniazeva, TV and Lavrovskiĭ, AA}, title = {[Species composition and population dynamics of fleas on the small suslik in stable foci of plague on the Ergenin ridge].}, journal = {Parazitologiia}, volume = {11}, number = {5}, pages = {446-452}, pmid = {143643}, issn = {0031-1847}, mesh = {Animals ; Ecology ; Plague/*epidemiology ; *Rodentia ; Russia ; *Sciuridae ; *Siphonaptera ; }, abstract = {The paper presents results of investigations of fleas from Citellus pygmaeus obtained during epizootological surveys in 1972-1974 (the Ergenin ridge, Kalmyk ASSR). The most high number of the main species of fleas of C. pygmaeus was observed in the first year of epizootic on the background of great abundance of the host (over 30 specimens per 1 hectare). In the following years the decrease in the number of C. pygmaeus was accompanied by the fall in the fleas number. The distribution of different species of fleas in a microbiotope is uneven in various periods. In all periods in nests fleas of N. setosa were dominant while fleas of C. tesquorum were most abundant on the host. In burrows there was noted a change of dominant species: in the period of intensive epizootic of 1972 they were Ct. pollex and C. tesquorum, in 1973 during a slump of epizootic--C. tesquorum and N. setosa and in 1974 when epizootic was not discovered at all--N. setosa.}, } @article {pmid72455, year = {1977}, author = {Zueva, IuN and Iakovleva, LS and Denisova, RA and Mazurenko, NP}, title = {[Properties of pigeon sera containing complement-fixing antibodies to the gs-antigen of the avian leukosis-sarcoma complex].}, journal = {Voprosy virusologii}, volume = {}, number = {4}, pages = {470-473}, pmid = {72455}, issn = {0507-4088}, mesh = {Alpharetrovirus/*immunology ; Animals ; Antibodies, Viral/analysis ; *Antigen-Antibody Reactions ; Antigens, Viral/analysis ; Avian Sarcoma Viruses/immunology ; Chick Embryo ; Chickens ; Columbidae/*immunology ; Complement Fixation Tests ; *Complement System Proteins ; Cricetinae ; *Epitopes ; Sarcoma, Avian/immunology ; }, abstract = {Pigeons bearing tumors caused by the Schmidt-Ruppin strain of Rous sarcoma virus were used for withdrawing sera containing complement-fixing (CF) antibody to the gs-antigen of avian leukosis-sarcoma complex. In the course of this study it was found that some of these sera, while having a high titer of CF antibody to the gs-antigen of the tumor tissue, did not detect this antigen in chicken embryonal tissue and feather follicles. It is suggested that these sera distinguish different components of gs-antigen in the tumor tissue on the one hand and in the embryonal tissue and feather follicles on the other. There was a correlation in the detection or lack of gs-antigen in preparations of feather follicles and embryonal tissue with all the sera examined. Feather follicles may serve as a convenient source of gs-antigen in practical work.}, } @article {pmid27023, year = {1977}, author = {Denisova, GF}, title = {[Multiple enzyme forms].}, journal = {Uspekhi sovremennoi biologii}, volume = {84}, number = {4}, pages = {22-37}, pmid = {27023}, issn = {0042-1324}, mesh = {Animals ; Cattle ; Chemical Phenomena ; Chemistry ; Chemistry, Physical ; Deoxyribonucleases ; Escherichia coli/enzymology ; Fructose-Bisphosphatase ; Glucose Oxidase ; Glucuronidase ; Glutamate-Ammonia Ligase ; Glycogen Synthase ; Humans ; *Isoenzymes/genetics ; Methods ; Molecular Conformation ; Monoamine Oxidase ; Phosphorylases ; Pyruvate Dehydrogenase Complex ; Ribonucleases ; Substrate Specificity ; Xanthine Oxidase ; }, } @article {pmid21492, year = {1977}, author = {Denisova, FG}, title = {[Multiple forms of enzymes].}, journal = {Uspekhi sovremennoi biologii}, volume = {84}, number = {1}, pages = {22-37}, pmid = {21492}, issn = {0042-1324}, mesh = {Animals ; Aspartate Aminotransferases ; Cattle ; Chemical Phenomena ; Chemistry ; Deoxyribonucleases ; Fructose-Bisphosphatase ; Glucuronidase ; Glutamate-Ammonia Ligase ; Glycogen Synthase ; *Isoenzymes/genetics ; Molecular Conformation ; Monoamine Oxidase ; Pancreas/enzymology ; Phosphofructokinase-1 ; Phosphorylase Kinase ; Phosphorylases ; Pyruvate Dehydrogenase Complex ; Ribonucleases ; Substrate Specificity ; Sucrase ; Xanthine Oxidase ; }, } @article {pmid894893, year = {1977}, author = {Khalfen, ESh and Denisova, SG}, title = {[Activity of enzymes controlling adenosine metabolism in ischemic heart disease].}, journal = {Kardiologiia}, volume = {17}, number = {6}, pages = {106-111}, pmid = {894893}, issn = {0022-9040}, mesh = {Adenosine/*metabolism ; Adenosine Deaminase/*metabolism ; Adult ; Coronary Disease/*metabolism ; Exercise Test ; Female ; Humans ; Male ; Middle Aged ; Myocardium/metabolism ; Nucleoside Deaminases/*metabolism ; Nucleotidases/*metabolism ; Physical Exertion ; }, abstract = {It is shown that patients with acute myocardial infarction and with chronic coronary insufficiency present an elevated 5'-nucleotidase and adenosine-desaminase activity. In clinically healthy persons examined after a physical exercise test the activity of 5'-nucleotidase and adenosine-desaminase declines. In most patients with chronic coronary insufficiency an increased activity of enzymes responsible for the metabolism of adenosine, above all of 5'-nucleotidase, is registered after a graded physical exertion test.}, } @article {pmid883284, year = {1977}, author = {Petrun', NM and Terekhov, NT and Mel'man, NIa and Denisova, AT}, title = {[Level of metalloenzymes transferring and ceruloplasmin as an index of erythropoistic disorders in patients with glomerulonephritis].}, journal = {Vrachebnoe delo}, volume = {}, number = {6}, pages = {69-73}, pmid = {883284}, issn = {0049-6804}, mesh = {Anemia/*diagnosis ; Ceruloplasmin/*analysis ; Chronic Disease ; *Erythropoiesis ; Glomerulonephritis/*blood ; Humans ; Transferrin/*analysis ; }, } @article {pmid875666, year = {1977}, author = {Gus'kova, AK and Soldatova, VA and Denisova, EA and Gribova, IA and Gorbarenko, NI}, title = {[Late sequelae of occupational irradiation of varying intensity (the mechanisms of pathogenesis)].}, journal = {Meditsinskaia radiologiia}, volume = {22}, number = {5}, pages = {49-54}, pmid = {875666}, issn = {0025-8334}, mesh = {Adult ; Humans ; Maximum Allowable Concentration ; Neoplasms/etiology ; Occupational Diseases/*etiology ; Radiation Dosage ; Radiation Effects ; Radiation Injuries/*etiology ; Time Factors ; }, } @article {pmid331201, year = {1977}, author = {Tarakhovskiĭ, ML and Luk'ianova, EM and Emaĭkina, VP and Denisova, MF and Oleshko, LD}, title = {[Development of experimental hepatocholecystitis in rabbits].}, journal = {Patologicheskaia fiziologiia i eksperimental'naia terapiia}, volume = {}, number = {3}, pages = {72-74}, pmid = {331201}, issn = {0031-2991}, mesh = {Animals ; Cholecystitis/*etiology ; Escherichia coli Infections/*etiology ; Hepatitis/*etiology ; Rabbits ; }, } @article {pmid888385, year = {1977}, author = {Krasnopol'skiĭ, VI and Polushkina, SP and Denisova, AP and Korzhova, VV}, title = {[Rehabilitation of patients operated on for saccular inflammatory formations of the adnexa uteri].}, journal = {Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury}, volume = {}, number = {2}, pages = {64-68}, pmid = {888385}, issn = {0042-8787}, mesh = {Adult ; Female ; Humans ; Middle Aged ; Pelvic Inflammatory Disease/*rehabilitation/surgery ; Postoperative Care ; }, } @article {pmid857517, year = {1977}, author = {Zakarian, LM and Denisova, LE and Sokolov, AA and Rybakov, MM}, title = {[Heterogeneity of natural populations of staphylococci].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {2}, pages = {36-39}, pmid = {857517}, issn = {0372-9311}, mesh = {Adult ; Bacteriophage Typing ; Carrier State/microbiology ; Child ; Drug Resistance, Microbial ; Humans ; Intestinal Diseases/microbiology ; Polymorphism, Genetic ; Staphylococcal Infections/microbiology ; Staphylococcus aureus/*isolation & purification/pathogenicity ; }, abstract = {It was revealed by the replique method that the Staphylococcus aureus populations were (in the primary cultures of material obtained from sick and healthy individuals) heterogeneous by phage type, pathogenicity signs and by the resistance to the antibacterial preparations. The extent of heterogeneity could be assessed by the number of variants and by the percentage of the most numerous variant. It differed in different groups of the patients examined. The extent of heterogeneity decreased in cloning the subcultures; this was in favour of the fact that heterogeneity of the primary cultures was caused chiefly by the entrance into the human organism of staphylococci of different biotypes. The replique method permitted to reveal the changes in the clonic structure of the staphylococcus population in the course of the disease, the effect of antibacterial therapy, the appearance of exogenous staphylococci, and their further fate.}, } @article {pmid838344, year = {1977}, author = {Sadchikova, MN and Nikonova, KV and Denisova, EA and Snegova, GV and L'vovskaia, EN}, title = {[Arterial pressure after exposure to low-intensity microwaves and high temperature].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {2}, pages = {17-21}, pmid = {838344}, issn = {0016-9919}, mesh = {Adult ; *Electronics ; Female ; Hot Temperature/*adverse effects ; Humans ; Male ; Microwaves/*adverse effects ; Middle Aged ; Occupational Diseases/*etiology ; Radio ; }, } @article {pmid266637, year = {1977}, author = {Gus'kova, AK and Denisova, EA and Chernega, GV and Soldatova, VA and Gorbarenko, NI}, title = {[Chief results and tasks of the organization of medical supervision of workers with radiation sources].}, journal = {Meditsinskaia radiologiia}, volume = {22}, number = {1}, pages = {5-15}, pmid = {266637}, issn = {0025-8334}, mesh = {Blood Cell Count ; Bone Neoplasms/prevention & control ; Chronic Disease ; Gamma Rays ; Humans ; Leukemia/prevention & control ; Lung Neoplasms/prevention & control ; Neoplasms, Radiation-Induced/prevention & control ; Occupational Diseases/diagnosis/*prevention & control ; *Occupational Health Services ; Organization and Administration ; Osteosarcoma/prevention & control ; Plutonium ; Radiation Dosage ; Radiation Injuries/diagnosis/*prevention & control ; Radiation Protection ; Radiology ; Skin Neoplasms/prevention & control ; X-Rays ; }, } @article {pmid68135, year = {1977}, author = {Palkina, NA and Raskin, BM and Denisova, SV and Kushnarev, VM and Levadnaia, TB}, title = {[Nutrient medium for obtaining alpha hemolysin from Escherichia coli].}, journal = {Laboratornoe delo}, volume = {}, number = {2}, pages = {106-108}, pmid = {68135}, issn = {0023-6748}, mesh = {*Culture Media ; Erythrocytes ; *Escherichia coli/growth & development ; Hemolysin Proteins/biosynthesis/*isolation & purification ; }, } @article {pmid67272, year = {1977}, author = {Denisova, NN and Liapunova, AD and Chaĭkina, TN and Brilliantova, SA}, title = {[Characteristics of the growth of tuberculosis mycobacteria on solid asparagine-free medium Finn-2].}, journal = {Laboratornoe delo}, volume = {}, number = {3}, pages = {171-172}, pmid = {67272}, issn = {0023-6748}, mesh = {*Culture Media ; Mycobacterium tuberculosis/*growth & development ; }, } @article {pmid1021655, year = {1976}, author = {Smirnova, MI and Kirsanova, GI and Denisova, EA and Kochanova, EM}, title = {[Study of cerebral blood flow in neurocirculatory dystonia using 133xe].}, journal = {Meditsinskaia radiologiia}, volume = {21}, number = {11}, pages = {41-45}, pmid = {1021655}, issn = {0025-8334}, mesh = {Adult ; Brain/*blood supply ; Female ; Humans ; Intracranial Arteriosclerosis/physiopathology ; Male ; Middle Aged ; Neurocirculatory Asthenia/*physiopathology ; Radionuclide Imaging ; Regional Blood Flow ; *Xenon Radioisotopes ; }, } @article {pmid1014889, year = {1976}, author = {Suvorov, NF and Denisova, AS}, title = {[Inhibiting and facilitating influences from the caudate nucleus on alimentary conditioned reflexes].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {26}, number = {6}, pages = {1174-1179}, pmid = {1014889}, issn = {0044-4677}, mesh = {Animals ; Brain Mapping ; Caudate Nucleus/*physiology ; Conditioning, Classical/*physiology ; Corpus Striatum/physiology ; Dogs ; Electric Stimulation ; Food ; Light ; Orientation/physiology ; Salivation ; Sound ; }, abstract = {Alimentary conditioned reflexes were studied in dogs during electrical stimulation of different zones of the caudate nucleus head with a 80 to 100 microampere current, of 5 c/s frequency and 0.5 msec pulse duration. The inhibitory influences came from the ventrolateral, and the activating ones, from the dorsal and central zones of the caudate nucleus head. Changes of conditioned reflexes resulting from its stimulation depended on the strength of the conditioned signals: the conditioned reflex to a weak stimulus (light) was more readily subject to changes as compared with the one to a strong signal (a metronome). The magnitude of unconditioned reflexes did not change in these experiments.}, } @article {pmid1014476, year = {1976}, author = {Denisova, GF and Polianovskiĭ, OL}, title = {[Native and artificial sub-forms of cytoplasmic aspartate transaminase from swine heart].}, journal = {Voprosy meditsinskoi khimii}, volume = {22}, number = {5}, pages = {652-655}, pmid = {1014476}, issn = {0042-8809}, mesh = {Animals ; Aspartate Aminotransferases/*isolation & purification ; Catalysis ; Electrophoresis, Polyacrylamide Gel ; Isoenzymes/*isolation & purification ; Myocardium/*enzymology ; Protein Denaturation ; Time Factors ; }, abstract = {Multiple forms of aspartate transaminase from cytosol of pig heart (alpha, beta and psi) were incubated in 0.05 M acetate buffer, pH 5.0 at 4 degrees within 5 and 8 months. Gradual accumulation of denaturated forms was observed on incubation of alpha- and beta-forms; these forms possessed higher mobility in polyacrylamide gel disc electrophoresis and decreased enzymatic activity as compared with the native forms. Multiple forms, produced during ageing of alpha-form, were separated by chromatography on CM-cellulose. Chromatographic resolution of the forms, their activity and spectral properties suggest that they are not identical with the native isoenzymes found in the cell.}, } @article {pmid1021668, year = {1976}, author = {Gus'kova, AK and Soldatova, VA and Denisova, EA and Gorbarenko, NI and Gribova, IA}, title = {[Remote sequelae of occupational radiation exposure].}, journal = {Meditsinskaia radiologiia}, volume = {21}, number = {4}, pages = {34-40}, pmid = {1021668}, issn = {0025-8334}, mesh = {Adult ; Aged ; Environmental Exposure ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neurocirculatory Asthenia/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Radiation Dosage ; Radiation Injuries/*epidemiology ; }, } @article {pmid1276280, year = {1976}, author = {Denisova, GF and Polianovskiĭ, OL}, title = {[A proteolytic enzyme bound to the aspartate transaminase of swine heart cytosol].}, journal = {Biokhimiia (Moscow, Russia)}, volume = {41}, number = {3}, pages = {469-475}, pmid = {1276280}, issn = {0320-9725}, mesh = {Animals ; *Aspartate Aminotransferases/isolation & purification ; Catalysis ; Chemical Phenomena ; Chemistry ; Cytosol/enzymology ; Myocardium/*enzymology/ultrastructure ; *Peptide Hydrolases/isolation & purification ; Swine ; }, abstract = {Purified preparations of aspartate transaminase from pig heart cytosol contain a tightly bound proteolytic enzyme (approximately 2, 5%). The enzyme was separated from aspartate transaminase by gel-filtration on Sephadex G-100 in the presence of sodium dodecyl sulfate and by affinity chromatography on the column with Sepharose, containing covalently bound denaturated aspartate transaminase. Protease has a pH optimum of 9.0 and molecular weight of about 23.000-25.000. The proteolysis rates of different subforms of aspartate transaminase depend on their denaturation lability. A more stable choloenzyme is split at a slower rate than the apoenzyme. An enriched preparation of protease was also shown to split glutamate decarboxylase from E. coli and had no effect on cysteinlyase from hen egg, as well as on lactate dehydrogenase and albumin.}, } @article {pmid1014180, year = {1976}, author = {Kondrat'eva, TS and Denisova, TV and Bunin AAi, and Iakovlev, AA}, title = {[Examination of hypotensive and miotic effects of different pilocarpine solutions (experimental investigations)].}, journal = {Vestnik oftalmologii}, volume = {}, number = {2}, pages = {29-31}, pmid = {1014180}, issn = {0042-465X}, mesh = {Animals ; Glaucoma/drug therapy ; Intraocular Pressure/*drug effects ; *Miotics ; Pilocarpine/administration & dosage/*pharmacology/therapeutic use ; Pupil/drug effects ; Rabbits ; Solutions ; }, } @article {pmid1004986, year = {1976}, author = {Denisova, MF}, title = {[Pentoxyl in complex therapy of chronic angiocholecystitis in children].}, journal = {Pediatriia}, volume = {}, number = {3}, pages = {62-63}, pmid = {1004986}, issn = {0031-403X}, mesh = {Child ; Child, Preschool ; Cholecystitis/*drug therapy ; Female ; Humans ; Infant ; Male ; Uracil/*analogs & derivatives/therapeutic use ; }, } @article {pmid816627, year = {1976}, author = {Domaradskiĭ, IV and Levadnaia, TB and Sitnikov, BS and Rassadin, AS and Denisova, TS}, title = {[Transformation of Bacillus subtilis by isolated plasmid R DNA].}, journal = {Doklady Akademii nauk SSSR}, volume = {226}, number = {6}, pages = {1443-1445}, pmid = {816627}, issn = {0002-3264}, mesh = {*Bacillus subtilis ; *DNA ; *Drug Resistance, Microbial ; *Extrachromosomal Inheritance ; *Transformation, Genetic ; }, } @article {pmid1088228, year = {1976}, author = {Denisova, NP and Mikhaĭlova, GN}, title = {[Production of purified antisera and pure antibodies to immunoglobulins G, M, A and isolation of these immunoglobulins from different substrates using immunosorbents].}, journal = {Trudy Leningradskogo nauchno-issledovatel'skogo instituta epidemiologii i mikrobiologii imeni Pastera}, volume = {44}, number = {}, pages = {17-26}, pmid = {1088228}, issn = {0131-4955}, mesh = {*Antibodies, Anti-Idiotypic/isolation & purification ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Immunosorbents ; }, } @article {pmid983277, year = {1976}, author = {Stepanova, LK and Sergeeva, NS and Belaia, IuA and Denisova, TP and Mel'nik, EG}, title = {[Relationship between surface K-antigens of salmonellae and their virulence].}, journal = {Vestnik Akademii meditsinskikh nauk SSSR}, volume = {}, number = {1}, pages = {43-48}, pmid = {983277}, issn = {0002-3027}, mesh = {Animals ; *Antigens, Bacterial ; Cell Membrane/*immunology ; Guinea Pigs ; Mice ; Salmonella/immunology/*pathogenicity ; Virulence ; }, } @article {pmid828781, year = {1976}, author = {Denisova, NP}, title = {[Immunosorbents and their use for isolating and purifying biologically active substances].}, journal = {Trudy Leningradskogo nauchno-issledovatel'skogo instituta epidemiologii i mikrobiologii imeni Pastera}, volume = {44}, number = {}, pages = {5-16}, pmid = {828781}, issn = {0131-4955}, mesh = {Acrylamides ; Animals ; Antibodies/analysis ; *Antigen-Antibody Complex ; Antigens/analysis ; Cellulose/analogs & derivatives ; Glutaral ; Histocytochemistry ; Humans ; Immunochemistry ; *Immunosorbents ; Polymers ; Rabbits ; Sepharose ; }, } @article {pmid66777, year = {1976}, author = {Denisova, NP}, title = {[Role of several functional groups in the biological activity of allergenic preparations].}, journal = {Trudy Leningradskogo nauchno-issledovatel'skogo instituta epidemiologii i mikrobiologii imeni Pastera}, volume = {44}, number = {}, pages = {127-130}, pmid = {66777}, issn = {0131-4955}, mesh = {*Allergens ; Animals ; Epitopes ; Guinea Pigs ; Hypersensitivity/immunology ; Shigella flexneri/*immunology ; Skin Tests ; }, } @article {pmid128880, year = {1975}, author = {Gurtsevich, VE and Denisova, RA and Tyvis, LI and Stepanova, EN}, title = {[Disinfection of feeds in a SPF-type poultry farm].}, journal = {Veterinariia}, volume = {}, number = {10}, pages = {28-30}, pmid = {128880}, issn = {0042-4846}, mesh = {*Animal Feed ; Animals ; *Disinfection ; Food Contamination ; *Germ-Free Life ; *Poultry ; *Specific Pathogen-Free Organisms ; *Sterilization ; USSR ; }, } @article {pmid1196051, year = {1975}, author = {Gorbarenko, NI and Denisova, EA and Pavlova, IV}, title = {[Functional state of the sympathetic-adrenal system in occupational irradiation].}, journal = {Meditsinskaia radiologiia}, volume = {20}, number = {9}, pages = {46-52}, pmid = {1196051}, issn = {0025-8334}, mesh = {Adrenal Glands/*physiopathology ; Adult ; Catecholamines/urine ; Dose-Response Relationship, Radiation ; Epinephrine ; Female ; Humans ; Insulin ; Male ; Middle Aged ; Occupational Diseases/*physiopathology ; Radiation Injuries/*physiopathology ; Sympathetic Nervous System/*physiopathology ; USSR ; }, } @article {pmid1196050, year = {1975}, author = {Gus'kova, AK and Denisova, EA and Sel'tser, VK and L'vovskaia, EN and Kirsanova, GI}, title = {[Results of clinical physiological observations of persons who have undergone occupational irradiation].}, journal = {Meditsinskaia radiologiia}, volume = {20}, number = {9}, pages = {36-46}, pmid = {1196050}, issn = {0025-8334}, mesh = {Electroencephalography ; Gamma Rays/adverse effects ; Humans ; Neutrons ; Occupational Diseases/*physiopathology ; Radiation Effects ; Radiation Injuries/*physiopathology ; USSR ; X-Rays/adverse effects ; }, } @article {pmid1195539, year = {1975}, author = {Denisova, EA and Smirnova, MI}, title = {[State of hemodynamics, according to radiocardiographic data, in persons working in contact with ionizing radiation sources].}, journal = {Kardiologiia}, volume = {15}, number = {8}, pages = {106-110}, pmid = {1195539}, issn = {0022-9040}, mesh = {Angiocardiography ; Heart/physiopathology/*radiation effects ; Hemodynamics/*radiation effects ; Humans ; Occupational Diseases/etiology/*physiopathology ; Radiation Injuries/*physiopathology ; }, abstract = {The presented results illustrate the study of the cardiovascular system by means of radiocardiography conducted in normal individuals working in contact with sources of ionizing radiation. The study includes 51 persons in the test group and 42 in the control group that was similar to the test one in terms of age, sex and type of work performed, with the only exception that these in the control group had no contact with ionizing radiation. Persons working under the effect of ionizing radiation displayed a moderate increase in the stroke and minute index and the circulating blood volume, with the blood flow rate somewhat decelerated. The changes were deeper in those with over 5 years of service, and in those with functional changes in the nervous system, like neurocirculatory dystonia. The moderate level of these reactions and their reversibility permit to interpret them as an adaptative reaction to the effect of low doses of ionizing radiation.}, } @article {pmid1098929, year = {1975}, author = {Denisova, LY and Pustoshilova, NM and Zagrebelny, N}, title = {The incorporation of GMP-residues from GTP into the polynucleotide fraction during poly-U directed poly-A synthesis catalyzed by E. coli RNA polymerase.}, journal = {FEBS letters}, volume = {56}, number = {1}, pages = {92-95}, doi = {10.1016/0014-5793(75)80118-9}, pmid = {1098929}, issn = {0014-5793}, mesh = {Chromatography, DEAE-Cellulose ; DNA-Directed RNA Polymerases/*metabolism ; Escherichia coli/*enzymology ; Guanine Nucleotides/*metabolism ; Guanosine Triphosphate/*metabolism ; Molecular Weight ; Poly A/*biosynthesis ; Poly U/*metabolism ; Transcription, Genetic ; }, } @article {pmid1206988, year = {1975}, author = {Aznaur'ian, MS and Denisova, IF}, title = {[Diagnostic importance of food test in detection of latent coronary insufficiency].}, journal = {Klinicheskaia meditsina}, volume = {53}, number = {7}, pages = {34-35}, pmid = {1206988}, issn = {0023-2149}, mesh = {Adult ; Coronary Disease/*diagnosis/physiopathology ; Electrocardiography ; *Food ; Heart/physiopathology ; Humans ; Methods ; Middle Aged ; }, } @article {pmid131400, year = {1975}, author = {Mikriukova, LI and Bel'skaia, LA and Bivol, VM and Denisova, AP and Ishchuk, PM}, title = {[Myopia of high degree as a cause of disability].}, journal = {Vestnik oftalmologii}, volume = {}, number = {4}, pages = {31-33}, pmid = {131400}, issn = {0042-465X}, mesh = {*Disability Evaluation ; *Disabled Persons ; Female ; Humans ; Male ; Moldova ; Myopia/*complications ; *Occupational Diseases ; Occupational Medicine ; }, } @article {pmid1571, year = {1975}, author = {Khalfen, ESh and Denisova, SG}, title = {[Effect of certain drugs, used in treatment of chronic coronary insufficiency, on adenosine metabolism].}, journal = {Kardiologiia}, volume = {15}, number = {7}, pages = {51-56}, pmid = {1571}, issn = {0022-9040}, mesh = {Adenosine/*metabolism ; Adenosine Deaminase/metabolism ; Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Coronary Disease/*drug therapy/enzymology/metabolism ; Female ; Humans ; Male ; Middle Aged ; Myocardium/enzymology ; Nucleotidases/metabolism ; Vasodilator Agents/*therapeutic use ; }, abstract = {It has been demonstrated that the study of the activity of 5'-nucleotidase and adenosine-desaminase permits to interpret the metabolism of adenosine. Curanthil, Sustac and Intensain influence the adenosine metabolism favouring an elevation of its content. The therapeutic effect of Obsidan is not conditioned by the "adenosine" metabolism.}, } @article {pmid1205215, year = {1975}, author = {Saĭtanov, AO and Denisova, EA and Losev, AA}, title = {[Methodological possibilities of evaluating the functional state of the cardiovascular and autonomic nervous systems in the clinic].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {}, number = {6}, pages = {47-49}, pmid = {1205215}, issn = {0016-9919}, mesh = {Adult ; Autonomic Nervous System/*physiology ; *Cardiovascular Physiological Phenomena ; Female ; Heart Function Tests/methods ; Humans ; Male ; Neurologic Examination/methods ; Psychological Tests/methods ; USSR ; }, } @article {pmid1228534, year = {1975}, author = {Denisova, VI}, title = {[Rare case of favorable outcome in extensive penetrating injury of the eyeball with intraocular foreign body].}, journal = {Oftalmologicheskii zhurnal}, volume = {30}, number = {6}, pages = {474}, pmid = {1228534}, issn = {0030-0675}, mesh = {*Eye Foreign Bodies/surgery ; Wounds, Penetrating/surgery ; }, } @article {pmid1153036, year = {1975}, author = {Pukhalskaya, EC and Chernyakhovskaya IYu, and Petrova, MF and Denisova, SI and Alieva, TA}, title = {Macromolecular antitumor agents from Chamaenerium angustifolium.}, journal = {Neoplasma}, volume = {22}, number = {1}, pages = {29-37}, pmid = {1153036}, issn = {0028-2685}, mesh = {ABO Blood-Group System ; Animals ; Antineoplastic Agents/*analysis/therapeutic use ; Carcinoma, Ehrlich Tumor/*drug therapy ; Erythrocytes/drug effects/immunology ; Hemagglutination Tests ; In Vitro Techniques ; Lectins/analysis/therapeutic use ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Phenols/*analysis/therapeutic use ; Plant Extracts ; Plant Lectins ; }, abstract = {The antineoplastic substances isolated from Chamaenerium angustifolium, Chanerol, a macromolecular polyphenol, and its complex with polysaccharide, Chanerozan, have been studied in vitro in tests of haemagglutination, tumor cell agglutination, leucoagglutination and some others. The results obtained show Chanerol as a new phytohaemagglutinin (lectin) which has no group specificity for human erythrocytes (ABO system). As distinct from other lectins (proteins) Chanerol belongs to another chemical class (macromolecular polyphenols) and has no effect on lymphocytes in leukoagglutination and blast transformation tests. Both preparations have been shown capable of agglutinating tumor cells in vitro and revealed antitumor activity in the intravenous and intraperitoneal administration to mice with transplanted tumors. The toxicity of Chanerozan and its titre of human and mouse erythrocyte agglutination are considerably lower than those of Chanerol. Thus, judging by haemagglutination test Chanerozan behaves as a typical complex of agglutinin with concurrent sugar.}, } @article {pmid1114020, year = {1975}, author = {Danilov, VN}, title = {[The probable identity of mosquitoes aedes (ochlerotatus) beklemishevi denisova and a. (o.) barri rueger (diptera, culicidae)].}, journal = {Parazitologiia}, volume = {09}, number = {1}, pages = {61-63}, pmid = {1114020}, issn = {0031-1847}, mesh = {Aedes/*classification ; Animals ; Canada ; Classification ; Europe ; Terminology as Topic ; USSR ; United States ; }, } @article {pmid1110538, year = {1975}, author = {Akopian, VG and Pshenichnikov, VN and Kleĭmenova, II and Doletskiĭ, AS and Denisova, SI}, title = {[Periarterial neurectomy of the common hepatic artery in chronic hepatitis and liver cirrhosis in children].}, journal = {Khirurgiia}, volume = {}, number = {1}, pages = {81-87}, pmid = {1110538}, issn = {0023-1207}, mesh = {Adolescent ; Child ; Child, Preschool ; Chronic Disease ; Collateral Circulation ; Hepatic Artery/*innervation ; Hepatitis/*surgery ; Humans ; Infant ; Liver Cirrhosis/*surgery ; Splenectomy ; }, } @article {pmid57272, year = {1975}, author = {Denisova, TP and Stepanova, LK and Sergeeva, NS and Ivanov, KK}, title = {[Isolation of surface K-antigen from Salmonella cholerae suis by the method of preparative electrophoresis in polyacrylamide gel and the study of its properties].}, journal = {Laboratornoe delo}, volume = {}, number = {12}, pages = {738-742}, pmid = {57272}, issn = {0023-6748}, mesh = {Antigens, Bacterial/analysis/*isolation & purification ; Electrophoresis, Disc ; *Electrophoresis, Polyacrylamide Gel/instrumentation ; Salmonella/*immunology ; }, } @article {pmid4469847, year = {1974}, author = {Denisova, RA and Khrustalev, SA}, title = {[Karyotype of normal guinea fowl].}, journal = {TSitologiia i genetika}, volume = {8}, number = {6}, pages = {535-536}, pmid = {4469847}, issn = {0564-3783}, mesh = {Animals ; *Birds ; *Chromosomes ; Female ; Male ; }, } @article {pmid4217513, year = {1974}, author = {Volgin, IB and Denisova, LI and Serpkova, NN}, title = {[Immunochemical characteristics of the antigenic makeup of native tetanus toxin].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {11}, pages = {72-77}, pmid = {4217513}, issn = {0372-9311}, mesh = {Antigens, Bacterial/*analysis ; Bacterial Proteins/analysis ; Binding Sites, Antibody ; Culture Media ; Electrophoresis, Polyacrylamide Gel ; Hemolysis ; Immunochemistry ; Immunodiffusion ; Immunoelectrophoresis ; Tetanus Toxin/analysis/*immunology ; }, } @article {pmid4620012, year = {1974}, author = {Denisova, LIa and Zagrebel'nyĭ, SN and Pustoshilova, NM}, title = {[Template activity of pyrimidine deoxyribooligonucleotides in the E. coli polymerase system].}, journal = {Molecular biology}, volume = {8}, number = {5}, pages = {643-650}, pmid = {4620012}, issn = {0026-8933}, mesh = {Alkaline Phosphatase/metabolism ; DNA Nucleotidyltransferases/*metabolism ; Escherichia coli/*enzymology ; Molecular Weight ; Oligodeoxyribonucleotides/*pharmacology ; Oligonucleotides/*pharmacology ; Pyrimidine Nucleotides/pharmacology ; Templates, Genetic ; }, } @article {pmid4454868, year = {1974}, author = {Dalmatov, VV and Dun'kov, VG and Gotval'd, RN and Denisova, BD and Arshinova, TM}, title = {[Experience with the wide practical application of the indirect hemagglutination reaction for determining antitoxic immunity to diphtheria].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {}, number = {7}, pages = {75-77}, pmid = {4454868}, issn = {0372-9311}, mesh = {Adolescent ; Child ; Child, Preschool ; Diphtheria/*immunology ; Hemagglutination Tests ; Humans ; Skin Tests ; }, } @article {pmid4450783, year = {1974}, author = {Denisova, AS}, title = {[The role of different regions of the head of the caudate nucleus in accomplishing differentiation and extinctive inhibition].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {24}, number = {4}, pages = {735-742}, pmid = {4450783}, issn = {0044-4677}, mesh = {Animals ; Brain Mapping ; Caudate Nucleus/*physiology ; Conditioning, Classical/*physiology ; Dogs ; Electric Stimulation ; Extinction, Psychological/*physiology ; Inhibition, Psychological/*physiology ; Salivation ; }, } @article {pmid4419612, year = {1974}, author = {Sagalovich, BM and Denisova, GA}, title = {[Level of hearing discomfort normally and in various forms of hearing disorder].}, journal = {Zhurnal ushnykh, nosovykh i gorlovykh boleznei = The journal of otology, rhinology, and laryngologie [sic]}, volume = {0}, number = {4}, pages = {59-65}, pmid = {4419612}, issn = {0044-4650}, mesh = {Acoustic Stimulation ; Adolescent ; Adult ; Age Factors ; Aged ; Audiometry ; Ear Diseases/physiopathology ; Hearing Disorders/*physiopathology ; *Hearing Tests ; Humans ; Middle Aged ; }, } @article {pmid4820927, year = {1974}, author = {Grechushkina, NN and Denisova, SV and Kolesnikova, NS}, title = {[Isolation and some properties of the polysaccharide synthesized by Mycobacterium lacticolum on a medium with n-dodecane].}, journal = {Nauchnye doklady vysshei shkoly. Biologicheskie nauki}, volume = {1}, number = {}, pages = {95-99}, pmid = {4820927}, issn = {0470-4606}, mesh = {Alkanes/*metabolism ; Culture Media ; Hydrogen-Ion Concentration ; Hydrolysis ; Monosaccharides/analysis ; Mycobacterium/*metabolism ; Polysaccharides, Bacterial/analysis/biosynthesis/*isolation & purification ; }, } @article {pmid4442340, year = {1974}, author = {Denisova, GF and Polianovskiĭ, OL}, title = {[Proteolytic enzyme specifically cleaving cytoplasmic aspartate transaminase from swine heart].}, journal = {Doklady Akademii nauk SSSR}, volume = {219}, number = {5}, pages = {1263-1266}, pmid = {4442340}, issn = {0002-3264}, mesh = {Animals ; *Aspartate Aminotransferases ; Chromatography, Gel ; Cytoplasm/enzymology ; Electrophoresis, Polyacrylamide Gel ; Hydrogen-Ion Concentration ; Myocardium/*enzymology ; *Peptide Hydrolases ; Sodium Dodecyl Sulfate ; *Swine ; }, } @article {pmid4373915, year = {1974}, author = {Myshkin, KI and Il'iutenko, VIu and Uts, RA and Denisova, LA}, title = {[Trepan-biopsy of breast tumors].}, journal = {Voprosy onkologii}, volume = {20}, number = {3}, pages = {82-87}, pmid = {4373915}, issn = {0507-3758}, mesh = {Adenocarcinoma, Scirrhous/diagnosis ; Adenofibroma/diagnosis ; Adult ; Biopsy, Needle/*instrumentation ; Breast Neoplasms/*diagnosis ; Diagnostic Techniques, Surgical ; Female ; Humans ; Mastitis/diagnosis ; Middle Aged ; Papilloma/diagnosis ; Pregnancy ; Trephining/*instrumentation ; }, } @article {pmid4280864, year = {1974}, author = {Tyshetskiĭ, VI and Kulaeva, VA and Kukushkina, TN and Kleĭmenov, IuP and Denisova, LI}, title = {[Characteristics of spread and outcome of acute and chronic pneumonia among the adult population of the city of Sestroretsk].}, journal = {Zdravookhranenie Rossiiskoi Federatsii}, volume = {}, number = {1}, pages = {19-21}, pmid = {4280864}, issn = {0044-197X}, mesh = {Acute Disease ; Adolescent ; Adult ; Age Factors ; Chronic Disease ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; *Pneumonia/diagnosis/rehabilitation/therapy ; Russia ; Seasons ; }, } @article {pmid4777942, year = {1973}, author = {Denisova, EV and Maletskii, SI and Lutkov, AN}, title = {Self-fertility in sugar beet under different ecological conditions.}, journal = {Soviet genetics}, volume = {7}, number = {7}, pages = {852-855}, pmid = {4777942}, issn = {0038-5409}, mesh = {Adaptation, Physiological ; Altitude ; Aneuploidy ; Diploidy ; Environment ; *Fertility ; Genotype ; Plants/*metabolism ; Pollen ; }, } @article {pmid4781608, year = {1973}, author = {Denisova, OP}, title = {[Anatomy and anastomotic connections of the extraorgan and intraorgan arteries of the tongue].}, journal = {Arkhiv anatomii, gistologii i embriologii}, volume = {65}, number = {11}, pages = {92-95}, pmid = {4781608}, issn = {0004-1947}, mesh = {Adolescent ; Adult ; Aged ; Arteries/*anatomy & histology ; Cadaver ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Radiography ; Tongue/anatomy & histology/*blood supply/diagnostic imaging ; }, } @article {pmid4798485, year = {1973}, author = {Denisova, MF}, title = {[Effect of pentoxyl on the processes of antibody formation in albino mouse spleen during immunosuppression].}, journal = {Biulleten' eksperimental'noi biologii i meditsiny}, volume = {75}, number = {10}, pages = {71-73}, pmid = {4798485}, issn = {0365-9615}, mesh = {Animals ; Antibody-Producing Cells/*drug effects ; Erythrocytes/immunology ; Female ; Immunization ; *Immunosuppression Therapy ; Immunosuppressive Agents/pharmacology ; Male ; Mice ; Sheep/immunology ; Spleen/*immunology ; Sulfhydryl Compounds/pharmacology ; Thiazoles/pharmacology ; Uracil/*pharmacology ; }, } @article {pmid4751987, year = {1973}, author = {Denisova, GF and Polyanovsky, OL}, title = {Carbohydrate components of aspartate transaminase: multiple forms of the enzyme from pig heart cytosol.}, journal = {FEBS letters}, volume = {35}, number = {1}, pages = {129-132}, doi = {10.1016/0014-5793(73)80593-9}, pmid = {4751987}, issn = {0014-5793}, mesh = {Animals ; Aspartate Aminotransferases/*analysis/isolation & purification ; Carbohydrates/analysis ; Chromatography, Ion Exchange ; Chromatography, Paper ; Cytosol/enzymology ; Electrophoresis, Polyacrylamide Gel ; Galactose/analysis ; Glucose/analysis ; Hexosamines/analysis ; Hydrolysis ; Isoenzymes/*analysis ; Mannose/analysis ; Myocardium/cytology/*enzymology ; Neuraminic Acids/analysis ; Rhamnose/analysis ; Spectrophotometry ; Xylose/analysis ; }, } @article {pmid4204861, year = {1973}, author = {Krylova, TV and Denisova, AV}, title = {[Effect of Sevin on the Mongolian treecreeper].}, journal = {Nauchnye doklady vysshei shkoly. Biologicheskie nauki}, volume = {118}, number = {10}, pages = {25-30}, pmid = {4204861}, issn = {0470-4606}, mesh = {Animals ; Birds/*physiology ; Carbaryl/*poisoning ; Ecology ; Male ; Siberia ; Spermatogenesis/*drug effects ; }, } @article {pmid4201592, year = {1973}, author = {Krylova, TV and Denisova, AV}, title = {[Effect of seven on the Mongolian tree creeper].}, journal = {Nauchnye doklady vysshei shkoly. Biologicheskie nauki}, volume = {10}, number = {118}, pages = {25-30}, pmid = {4201592}, issn = {0470-4606}, mesh = {Animals ; Bird Diseases/*chemically induced ; Birds ; Carbaryl/*poisoning ; Infertility, Male/*chemically induced ; Male ; Spermatogenesis/*drug effects ; Spermatozoa/drug effects ; }, } @article {pmid4539597, year = {1972}, author = {Strugatskiĭ, VM and Tikhomirova, NM and Denisova, EA and Portnova, DTs}, title = {[Treatment of certain forms of menstruation disorders using galvanization and drug electrophoresis].}, journal = {Meditsinskaia sestra}, volume = {31}, number = {10}, pages = {51-54}, pmid = {4539597}, issn = {0025-8342}, mesh = {Electric Stimulation Therapy ; Electrophoresis ; Female ; Menstruation Disturbances/therapy ; }, } @article {pmid4660396, year = {1972}, author = {Kratovskaia, OV and Zalaldinova, NB and Afaunova, VI and Denisova, TP and Lebedeva, SN}, title = {[Shifts in coagulating and fibrinolytic activity of the blood following the administration of nerobol in patients with coronary atherosclerosis].}, journal = {Terapevticheskii arkhiv}, volume = {44}, number = {9}, pages = {29-31}, pmid = {4660396}, issn = {0040-3660}, mesh = {Aged ; Arteriosclerosis/blood/drug therapy ; Blood Coagulation/*drug effects ; Coronary Disease/blood/*drug therapy ; Female ; Fibrinogen ; Fibrinolysis/drug effects ; Heparin/therapeutic use ; Humans ; Male ; Methandrostenolone/pharmacology/*therapeutic use ; Middle Aged ; Prothrombin ; }, } @article {pmid5051500, year = {1972}, author = {Denisova, AP}, title = {[Some hematological and biochemical shifts in stimulating labor pains through therapeutic fasting].}, journal = {Sovetskaia meditsina}, volume = {35}, number = {7}, pages = {115-118}, pmid = {5051500}, issn = {0038-5077}, mesh = {Adult ; *Fasting ; Female ; Humans ; Obstetric Labor Complications/blood/*therapy ; Pregnancy ; Pregnancy, Prolonged ; }, } @article {pmid5049173, year = {1972}, author = {Kozlovskiĭ, VN and Denisova, EA}, title = {[Lipid and protein metabolism in chronic occupational radiation exposure].}, journal = {Meditsinskaia radiologiia}, volume = {17}, number = {6}, pages = {63-67}, pmid = {5049173}, issn = {0025-8334}, mesh = {Adult ; Aged ; Environmental Exposure ; Female ; Humans ; *Lipid Metabolism ; Male ; Middle Aged ; Occupational Diseases/etiology/*metabolism ; Proteins/*metabolism ; Radiation Injuries/etiology/*metabolism ; }, } @article {pmid4639373, year = {1972}, author = {Gus'kova, AK and Denisova, EA and L'vovskaia, EN}, title = {[Basis for the scope of somato-neurologic studies in carrying out medical examinations in persons working with sources of ionizing radiation under modern conditions].}, journal = {Gigiena truda i professional'nye zabolevaniia}, volume = {16}, number = {6}, pages = {17-21}, pmid = {4639373}, issn = {0016-9919}, mesh = {Humans ; *Occupational Medicine ; Physical Examination ; *Radiation Effects ; Radiation Protection ; }, } @article {pmid5048157, year = {1972}, author = {Denisova, AS}, title = {[Role of caudate nuclei in the mechanism of extinction of conditioned alimentary reactions].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {22}, number = {2}, pages = {260-265}, pmid = {5048157}, issn = {0044-4677}, mesh = {Animals ; Bromides/pharmacology ; Caudate Nucleus/*physiology ; Chlorpromazine/pharmacology ; *Conditioning, Classical ; Dogs ; *Extinction, Psychological/drug effects ; Sodium/pharmacology ; }, } @article {pmid5034464, year = {1972}, author = {Denisova, VI}, title = {[Dislocation of the eyeball in the maxillary sinus].}, journal = {Oftalmologicheskii zhurnal}, volume = {27}, number = {3}, pages = {224-225}, pmid = {5034464}, issn = {0030-0675}, mesh = {Adult ; *Eye Injuries ; Female ; Humans ; *Maxillary Sinus ; }, } @article {pmid5014184, year = {1972}, author = {Denisova, IM and Kosilov, SA}, title = {[Bioelectrical processes in the cerebral cortex and in antagonistic muscles during formation of precision movements in dogs].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {22}, number = {1}, pages = {16-25}, pmid = {5014184}, issn = {0044-4677}, mesh = {Animals ; Cerebral Cortex/*physiology ; Dogs ; Electroencephalography ; Electromyography ; *Motor Activity ; Motor Neurons/physiology ; Muscles/*physiology ; Neuromuscular Junction/physiology ; Visual Cortex/physiology ; Visual Perception ; }, } @article {pmid4675628, year = {1972}, author = {Denisova, AV and Mirkin, BM}, title = {[Alternative indices of association used in the analysis of biological phenomena].}, journal = {Nauchnye doklady vysshei shkoly. Biologicheskie nauki}, volume = {3}, number = {99}, pages = {121-128}, pmid = {4675628}, issn = {0470-4606}, mesh = {Cannabis ; *Classification ; Ecology ; Methods ; Models, Biological ; *Plants ; Plants, Medicinal ; Species Specificity ; *Statistics as Topic ; USSR ; }, } @article {pmid4335352, year = {1972}, author = {Denisova, AS}, title = {[Differentiating and extinguishing inhibition in dogs following destruction of the caudate nuclei].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {22}, number = {1}, pages = {54-59}, pmid = {4335352}, issn = {0044-4677}, mesh = {Animals ; Auditory Perception ; Caudate Nucleus/*physiology ; Conditioning, Classical ; *Discrimination, Psychological ; Dogs ; *Extinction, Psychological ; Food ; Light ; Neural Inhibition ; Sound ; *Synaptic Transmission ; }, } @article {pmid4335751, year = {1971}, author = {Suvorov, NF and Danilova, LK and Denisova, AS and Zeval'd, LO}, title = {[Dynamics of disorders of internal inhibition following damage to the caudate nuclei and amygdala].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {21}, number = {6}, pages = {1131-1139}, pmid = {4335751}, issn = {0044-4677}, mesh = {Amygdala/*physiology ; Animals ; Caudate Nucleus/*physiology ; *Conditioning, Classical ; Dogs ; Neural Inhibition ; *Synaptic Transmission ; }, } @article {pmid4256866, year = {1971}, author = {Biriukova, LA and Denisova, LM}, title = {[Some problems of organizing hospital service to children of rural areas].}, journal = {Voprosy okhrany materinstva i detstva}, volume = {16}, number = {10}, pages = {89}, pmid = {4256866}, issn = {0042-8825}, mesh = {Child ; Child, Preschool ; *Hospitals ; Humans ; *Pediatrics ; *Rural Health ; Russia ; }, } @article {pmid5124642, year = {1971}, author = {Guglin, ER and Denisova, OP}, title = {[A case of primary amyloidosis with portal hypertension and erythrocytosis].}, journal = {Problemy gematologii i perelivaniia krovi}, volume = {16}, number = {7}, pages = {52-53}, pmid = {5124642}, issn = {0552-2080}, mesh = {Amyloidosis/*complications ; Humans ; Hypertension, Portal/*etiology ; Male ; Middle Aged ; Polycythemia/*etiology ; }, } @article {pmid5116760, year = {1971}, author = {Denisova, EA and Gorbarenko, NI}, title = {[Variants of the neurocirculatory dystonia syndrome during chronic radiation exposure].}, journal = {Meditsinskaia radiologiia}, volume = {16}, number = {6}, pages = {43-48}, pmid = {5116760}, issn = {0025-8334}, mesh = {Adult ; Cardiovascular Diseases/*etiology ; Cardiovascular System/radiation effects ; Endocrine Glands/radiation effects ; Environmental Exposure ; Female ; Humans ; Male ; Middle Aged ; Nervous System/radiation effects ; Nervous System Diseases/*etiology ; Occupational Diseases/*etiology ; *Radiation Injuries ; }, } @article {pmid4108776, year = {1971}, author = {Lupinosov, IuV and Denisova, SI and Syrkin, AB and Gogoleva, IA}, title = {[Toxicity and cumulative properties of actinomycins C1, C2 and C3, contained in preparations in various combinations].}, journal = {Antibiotiki}, volume = {16}, number = {5}, pages = {443-446}, pmid = {4108776}, issn = {0003-5637}, mesh = {Animals ; Body Weight/drug effects ; Cats ; Dactinomycin/administration & dosage/analysis/therapeutic use/*toxicity ; Depression, Chemical ; Diarrhea/chemically induced ; Feeding and Eating Disorders/chemically induced ; Hemoglobins/analysis ; Humans ; Injections, Intraperitoneal ; Injections, Intravenous ; Isoleucine/analysis ; Male ; Mice ; Neoplasms, Experimental/*therapy ; Stomatitis/chemically induced ; Valine/analysis ; Vomiting/chemically induced ; }, } @article {pmid5562619, year = {1971}, author = {Brensted, AN and Denisova, ZV}, title = {[Changes in the galvanic skin response of children during play].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {21}, number = {1}, pages = {164-168}, pmid = {5562619}, issn = {0044-4677}, mesh = {Child ; Child, Preschool ; *Galvanic Skin Response ; Humans ; *Play and Playthings ; }, } @article {pmid5160956, year = {1971}, author = {Shershevskaia, SF and Fuks, BB and Potapova, LN and Levina, FG and Denisova, TP}, title = {[Experience in the use of RNA in the complex treatment of tapetoretinal dystrophy].}, journal = {Vestnik oftalmologii}, volume = {3}, number = {}, pages = {59-63}, pmid = {5160956}, issn = {0042-465X}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; RNA/*therapeutic use ; Retinal Degeneration/*drug therapy ; }, } @article {pmid5005573, year = {1971}, author = {Smirnov, AA and Lobachev, VS and Denisova, AV}, title = {[Effect of sevin on the reproductive capacity of the great gerbil following treatment of vegetation on its colonies].}, journal = {Nauchnye doklady vysshei shkoly. Biologicheskie nauki}, volume = {3}, number = {87}, pages = {29-33}, pmid = {5005573}, issn = {0470-4606}, mesh = {Abnormalities, Drug-Induced ; Animals ; Carbamates/*toxicity ; Carbaryl/toxicity ; Female ; Fetal Death ; Gerbillinae/*physiology ; Insecticides/*toxicity ; Pregnancy ; Pregnancy, Animal/drug effects ; Reproduction/*drug effects ; }, } @article {pmid5513415, year = {1970}, author = {Grechushkina, NN and Denisova, SV}, title = {[Some physiological properties of Mycobacterium lacticolum 121 during growth on a medium with n-dodecane].}, journal = {Mikrobiologiia}, volume = {39}, number = {6}, pages = {965-969}, pmid = {5513415}, issn = {0026-3656}, mesh = {Alkanes/metabolism ; Culture Media ; Mycobacterium/*growth & development ; Nitrogen/metabolism ; }, } @article {pmid5536919, year = {1970}, author = {Pukhal'skaia, ECh and Petrova, MF and Kibal'chich, PN and Alieva, TA and Denisova, SI}, title = {[Isolation of a polymer from Chamaenerium angustifolium and study of its antineoplastic action].}, journal = {Antibiotiki}, volume = {15}, number = {9}, pages = {782-785}, pmid = {5536919}, issn = {0003-5637}, mesh = {Adenocarcinoma/drug therapy ; Animals ; Antineoplastic Agents/*therapeutic use ; Body Weight/drug effects ; Carcinoma 256, Walker/drug therapy ; Carcinoma, Ehrlich Tumor/drug therapy ; Carcinoma, Squamous Cell/drug therapy ; Lung Neoplasms/drug therapy ; Lymphoma, Non-Hodgkin/drug therapy ; Melanoma/drug therapy ; Mice ; Neoplasms, Experimental/*drug therapy ; Organ Size ; Phenols/administration & dosage/isolation & purification/*therapeutic use/toxicity ; Plants, Medicinal ; Polymers/administration & dosage/isolation & purification/*therapeutic use/toxicity ; Polysaccharides/isolation & purification/*therapeutic use ; Rats ; Sarcoma 37/drug therapy ; Sarcoma, Experimental/drug therapy ; Spleen/anatomy & histology ; }, } @article {pmid5504944, year = {1970}, author = {Denisova, AS}, title = {[The role of the head of the caudate nucleus in the conditioned reflex behavior of dogs].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {20}, number = {5}, pages = {947-954}, pmid = {5504944}, issn = {0044-4677}, mesh = {Animals ; Caudate Nucleus/*physiology ; *Conditioning, Classical ; Dogs ; Food ; Light ; Salivation ; Sound ; Time Factors ; }, } @article {pmid5477610, year = {1970}, author = {Denisova, NP and Shapiro, NI}, title = {[Data towards the physico-chemical characteristic of preparations of native and purified dysenterin].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {47}, number = {4}, pages = {72-77}, pmid = {5477610}, issn = {0372-9311}, mesh = {Allergens/*analysis ; Chemical Phenomena ; Chemistry Techniques, Analytical ; Chemistry, Physical ; Chromatography ; Chromatography, Gel ; Chromatography, Paper ; Dysentery/diagnosis ; Electrophoresis ; Molecular Weight ; Skin Tests ; Spectrum Analysis ; }, } @article {pmid4924160, year = {1970}, author = {Shapiro, NI and Denisova, NP}, title = {[The presence of common peptide fragments in the protein-allergens of enterobacteria].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {47}, number = {3}, pages = {77-80}, pmid = {4924160}, issn = {0372-9311}, mesh = {Antigens/*analysis ; Antigens, Heterophile ; Bacterial Proteins/*analysis ; Enterobacteriaceae/*immunology ; Escherichia coli/immunology ; Peptides/*analysis ; Salmonella paratyphi A/immunology ; Salmonella typhi/immunology ; Shigella/immunology ; Species Specificity ; }, } @article {pmid5424251, year = {1970}, author = {Denisova, GA}, title = {[The significance of cholinergic mediation in the central regulation of respiration].}, journal = {Biulleten' eksperimental'noi biologii i meditsiny}, volume = {69}, number = {2}, pages = {9-12}, pmid = {5424251}, issn = {0365-9615}, mesh = {Acetylcholine/physiology ; Animals ; Cats ; Medulla Oblongata/*physiology ; Parasympathetic Nervous System/*physiology ; Psyllium/pharmacology ; *Respiration/drug effects ; Respiratory Center/physiology ; Reticular Formation/*physiology ; }, } @article {pmid5198451, year = {1970}, author = {Denisova, ZI}, title = {[Epidemic control measures in foot-and-mouth disease].}, journal = {Fel'dsher i akusherka}, volume = {35}, number = {2}, pages = {51-52}, pmid = {5198451}, issn = {0014-9772}, mesh = {Animals ; Foot-and-Mouth Disease/prevention & control ; }, } @article {pmid5494602, year = {1970}, author = {Denisova, ZV and Logunova, GI}, title = {[EEG-component of play behavior in children].}, journal = {Doklady Akademii nauk SSSR}, volume = {195}, number = {1}, pages = {246-248}, pmid = {5494602}, issn = {0002-3264}, mesh = {Cerebral Cortex/*physiology ; Child ; *Child Behavior ; Child, Preschool ; *Electroencephalography ; Humans ; *Play and Playthings ; Psychophysiology ; }, } @article {pmid5464992, year = {1970}, author = {Denisova, IM and Kosilov, SA}, title = {[Formation and perfection of purposeful precise movements in animals].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {20}, number = {1}, pages = {78-84}, pmid = {5464992}, issn = {0044-4677}, mesh = {Animals ; *Discrimination, Psychological ; Dogs ; Habits ; Humans ; Kinesthesis ; *Motor Skills ; *Weight Perception ; }, } @article {pmid4929266, year = {1970}, author = {Iurin, VL and Denisova, TP}, title = {[Antigen-binding capacity of spleen polysomes in immunized animals].}, journal = {Doklady Akademii nauk SSSR}, volume = {195}, number = {5}, pages = {1211-1214}, pmid = {4929266}, issn = {0002-3264}, mesh = {Animals ; *Antigens ; Erythrocytes ; Escherichia coli/enzymology ; Galactosidases ; Male ; *Protein Binding ; Rats ; Ribonucleases/pharmacology ; Ribosomes/enzymology/*immunology ; Sheep ; Spleen/*immunology ; }, } @article {pmid5376961, year = {1969}, author = {Denisova, ZV}, title = {[Dynamics of the bioelectrical activity of children's brains during drawing].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {19}, number = {6}, pages = {1067-1073}, pmid = {5376961}, issn = {0044-4677}, mesh = {*Art ; *Association ; Brain/*physiology ; Child ; Child, Preschool ; Electroencephalography ; *Higher Nervous Activity ; Humans ; Mathematics ; }, } @article {pmid5810947, year = {1969}, author = {Denisova, MI and Rabotnikov, IuM}, title = {[On the anti-inflammatory effect of pyridoxine].}, journal = {Farmakologiia i toksikologiia}, volume = {32}, number = {3}, pages = {306-308}, pmid = {5810947}, issn = {0014-8318}, mesh = {Animals ; Anti-Inflammatory Agents/*therapeutic use ; Capillary Permeability/*drug effects ; Dextrans ; Female ; Formaldehyde ; Inflammation/chemically induced/*drug therapy/prevention & control ; Male ; Pyridoxine/*therapeutic use ; Rats ; Serotonin ; }, } @article {pmid4308063, year = {1969}, author = {Denisova, TP}, title = {[Extraction of a highly purified agglutinogen of B. pertussis].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {46}, number = {5}, pages = {97-101}, pmid = {4308063}, issn = {0372-9311}, mesh = {Antigens/*isolation & purification ; Bordetella pertussis/*analysis ; Drug Hypersensitivity ; Immunodiffusion ; Immunoelectrophoresis ; Methods ; Skin Tests ; Whooping Cough/immunology ; }, } @article {pmid4310311, year = {1969}, author = {Zakharova, MS and Denisova, TP}, title = {[Identification of an antigen isolated from B. pertussis with agglutinogen factor 2].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {46}, number = {6}, pages = {92-93}, pmid = {4310311}, issn = {0372-9311}, mesh = {Agglutination Tests ; Antigens/*analysis ; Bordetella pertussis/*immunology ; Immunodiffusion ; Methods ; }, } @article {pmid4889717, year = {1968}, author = {Zakharova, MS and Malivanova, OM and Denisova, TP}, title = {[The use of fluorescent antibodies in the differential diagnosis of pertussis and parapertussis. I. Use of antibacterial type- and species-- specific fluorescent globulins].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {45}, number = {9}, pages = {154-155}, pmid = {4889717}, issn = {0372-9311}, mesh = {Diagnosis, Differential ; *Fluorescent Antibody Technique ; Humans ; Methods ; Species Specificity ; Whooping Cough/*diagnosis ; }, } @article {pmid4970817, year = {1968}, author = {Denisova, LG}, title = {[The course of pregnancy and labor in women with Rh negative blood].}, journal = {Fel'dsher i akusherka}, volume = {32}, number = {5}, pages = {53-56}, pmid = {4970817}, issn = {0014-9772}, mesh = {Female ; Nursing ; Obstetric Labor Complications ; Pregnancy ; Pregnancy Complications, Hematologic ; Rh-Hr Blood-Group System ; }, } @article {pmid4193614, year = {1968}, author = {Matveeva, GE and D'iachenko, PN and Mineeva, RM and Denisova, LN}, title = {[Epidemiologic basis for planned gamma globulin prophylaxis of Botkin's disease according to records of institutions for pre-school children of the town of Frunze].}, journal = {Sovetskoe zdravookhranenie Kirgizii}, volume = {3}, number = {}, pages = {40-44}, pmid = {4193614}, mesh = {Child, Preschool ; Hepatitis A/*prevention & control ; Humans ; Immunization Schedule ; Kyrgyzstan ; Schools, Nursery ; gamma-Globulins/*administration & dosage ; }, } @article {pmid5300989, year = {1968}, author = {Denisova, LL}, title = {[Phagocytic activity of leukocytes in children with primary forms of tuberculosis].}, journal = {Problemy tuberkuleza}, volume = {46}, number = {1}, pages = {72-75}, pmid = {5300989}, issn = {0032-9533}, mesh = {Adolescent ; Child ; Female ; Humans ; Male ; *Phagocytosis ; Tuberculosis, Pulmonary/*blood ; }, } @article {pmid5183965, year = {1968}, author = {Denisova, NM}, title = {[Modern anesthesia and the role of an anesthesiologist].}, journal = {Fel'dsher i akusherka}, volume = {32}, number = {1}, pages = {38-40}, pmid = {5183965}, issn = {0014-9772}, mesh = {Anesthesia ; Anesthesiology ; Nursing ; }, } @article {pmid5622927, year = {1967}, author = {Denisova, ZV}, title = {[A physiological analysis of the graphic activity of children].}, journal = {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}, volume = {17}, number = {6}, pages = {986-991}, pmid = {5622927}, issn = {0044-4677}, mesh = {Art ; *Association ; Cerebral Cortex/*physiology ; Child ; Child, Preschool ; *Conditioning, Classical ; *Cues ; Electroencephalography ; Electromyography ; Electrophysiology ; Humans ; }, } @article {pmid5615410, year = {1967}, author = {Gus'kova, AK and Denisova, EA and Moiseĭtsev, PI and Korliakova, EA and Sizikova, NV}, title = {[Working conditions and status of health of workers in the operation of nuclear research reactors].}, journal = {Gigiena i sanitariia}, volume = {32}, number = {9}, pages = {39-43}, pmid = {5615410}, issn = {0016-9900}, mesh = {Humans ; Maximum Allowable Concentration ; *Nuclear Reactors ; *Occupational Medicine ; *Radiation Protection ; *Research ; USSR ; }, } @article {pmid5609590, year = {1967}, author = {Ratner, AIu and Denisova, MG}, title = {[Cerebral atherosclerosis and the cervical migraine symptom complex].}, journal = {Klinicheskaia meditsina}, volume = {45}, number = {9}, pages = {79-82}, pmid = {5609590}, issn = {0023-2149}, mesh = {Adult ; Humans ; Intracranial Arteriosclerosis/*complications ; Middle Aged ; Migraine Disorders/*etiology ; *Neck ; }, } @article {pmid5600211, year = {1967}, author = {Pozdniakova, VT and Denisova, EV}, title = {[Reactions for the identification of ephedrine hydrochloride and their use in examination of drug mixtures].}, journal = {Farmatsevtychnyi zhurnal}, volume = {22}, number = {1}, pages = {46-50}, pmid = {5600211}, issn = {0367-3057}, mesh = {Chemistry Techniques, Analytical ; Chlorides/analysis ; Drug Compounding ; Ephedrine/*analysis ; Methods ; Pharmaceutical Preparations/*analysis ; }, } @article {pmid5591636, year = {1967}, author = {Nikolaeva, VV and Denisova, AS}, title = {[The effect of chronic irritation of upper cervical sympathetic ganglia upon the function of the cerebral cortex].}, journal = {Doklady Akademii nauk SSSR}, volume = {172}, number = {1}, pages = {239-241}, pmid = {5591636}, issn = {0002-3264}, mesh = {Animals ; Cerebral Cortex/*physiology ; *Conditioning, Classical ; Diaphragmatic Eventration ; Dogs ; Electric Stimulation ; Electrophysiology ; Ganglia, Autonomic/*physiology ; Light ; Male ; Sound ; }, } @article {pmid4887976, year = {1967}, author = {Erenkov, VA and Denisova, AG}, title = {[Development of child health services in the Lugansk region under the Radiansk regime].}, journal = {Pediatriia akusherstvo i ginekologiia}, volume = {5}, number = {}, pages = {30}, pmid = {4887976}, issn = {0031-4048}, mesh = {Child Health Services/*history ; History, 20th Century ; Humans ; Ukraine ; }, } @article {pmid5225269, year = {1966}, author = {Gus'kova, AK and Ponizovskaya, AI and Denisova, EA and Volkovitskaya, VV and L'vovskaya, EN and Kotova, ES and Gribova, IA}, title = {Working conditions and health of workers at United Institute of Nuclear Research.}, journal = {Federation proceedings. Translation supplement; selected translations from medical-related science}, volume = {25}, number = {6}, pages = {1063-1065}, pmid = {5225269}, issn = {0430-2494}, mesh = {Adult ; Aging ; Blood Cell Count ; Blood Pressure ; Electrocardiography ; Female ; Humans ; Lens, Crystalline ; Male ; Middle Aged ; *Nuclear Energy ; *Occupational Medicine ; Ophthalmodynamometry ; *Radiation Protection ; Sex ; Sweat ; USSR ; }, } @article {pmid4194255, year = {1966}, author = {Mikhaĭlov, VV and Denisova, DA}, title = {[Role of axoplasm synthesis disorders in the nerve cell in lesions of the peripheral neuromuscular apparatus induced by botulinum toxin].}, journal = {Biulleten' eksperimental'noi biologii i meditsiny}, volume = {31}, number = {11}, pages = {44-47}, pmid = {4194255}, issn = {0365-9615}, mesh = {Animals ; Anura ; Axonal Transport/drug effects ; Axons/*drug effects ; Botulinum Toxins/pharmacology ; Botulism/etiology ; *Clostridium botulinum ; Myelin Sheath ; Nerve Fibers, Myelinated/drug effects ; Neurons/*drug effects ; Peripheral Nervous System Diseases/*etiology ; *Toxins, Biological ; }, } @article {pmid6011867, year = {1966}, author = {Denisova, SI and Kuimova, TF and Men'shikov, GP and Krasil'nikov, NA}, title = {[Anti-phage and antineoplastic substance, isolated from Actinomyces globisporus, specifically interacting with DNA].}, journal = {Doklady Akademii nauk SSSR}, volume = {170}, number = {4}, pages = {970-973}, pmid = {6011867}, issn = {0002-3264}, mesh = {Amino Acids/analysis ; Animals ; *Antibiotics, Antineoplastic ; *Antiviral Agents ; Carbohydrates/analysis ; Cattle ; Chromatography, Paper ; DNA/*pharmacology ; DNA, Bacterial ; Deoxyribonucleases ; RNA/pharmacology ; *Streptomyces ; Thymus Gland ; }, } @article {pmid6001615, year = {1966}, author = {Gus'kova, AK and Denisova, EA and Moiseĭtsev, PI and Korliakova, EA}, title = {[Working conditions and the health status of persons working with reactors].}, journal = {Meditsinskaia radiologiia}, volume = {11}, number = {8}, pages = {37-42}, pmid = {6001615}, issn = {0025-8334}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Morbidity ; *Nuclear Reactors ; *Occupational Medicine ; *Radiation Protection ; }, } @article {pmid5999195, year = {1966}, author = {Denisov, VP and Denisova, IA}, title = {[Seasonal changes in blood protein composition of some hibernating mammals].}, journal = {Zhurnal obshchei biologii}, volume = {27}, number = {3}, pages = {324-330}, pmid = {5999195}, issn = {0044-4596}, mesh = {Animals ; Blood Protein Electrophoresis ; Blood Proteins/*analysis ; Female ; *Hibernation ; Male ; Periodicity ; Sciuridae ; Seasons ; }, } @article {pmid5300528, year = {1966}, author = {Beshanova, IuV and Denisova, VA and Evtushenko, RA and Pugacheva, AN and Rodionova, NM}, title = {[Experience with use of diadinamic currents for treatment of patients with lumbosacral radiculitis].}, journal = {Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury}, volume = {31}, number = {3}, pages = {203-205}, pmid = {5300528}, issn = {0042-8787}, mesh = {Electric Stimulation Therapy ; Humans ; *Lumbosacral Region ; Polyradiculopathy/*therapy ; }, } @article {pmid5984047, year = {1966}, author = {Denisova, EA}, title = {[Experience in the use of the rheographic method for evaluating the status of the peripheral circulation].}, journal = {Sovetskaia meditsina}, volume = {29}, number = {4}, pages = {7-12}, pmid = {5984047}, issn = {0038-5077}, mesh = {Adult ; Arteriosclerosis/*physiopathology ; Female ; Humans ; Hypertension/*physiopathology ; Hypotension/*physiopathology ; Male ; Methods ; Middle Aged ; *Plethysmography, Impedance ; }, } @article {pmid4233708, year = {1966}, author = {Ratner, AIu and Krasnova, VM and Denisova, MG and Bilialov, MSh and Efimova, OA and Chizhova, EI and Abyzéova, TA and Vertlib, IaM and Sharshun, NN}, title = {[On the clinico-physiologic characteristics of diencephalic disorders in cervical osteochondrosis].}, journal = {Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952)}, volume = {66}, number = {10}, pages = {1467-1472}, pmid = {4233708}, issn = {0044-4588}, mesh = {17-Ketosteroids/urine ; Adult ; Basal Metabolism ; Blood Proteins ; Brain Diseases/*etiology/urine ; *Cervical Vertebrae ; Dehydroepiandrosterone/urine ; *Diencephalon ; Female ; Glaucoma/etiology ; Humans ; Hypertension/etiology ; Hypothalamus/physiopathology ; Intraocular Pressure ; Male ; Memory ; Middle Aged ; Migraine Disorders/complications ; Muscles/physiopathology ; Osteochondritis/*complications/urine ; Pituitary-Adrenal System/physiology ; }, } @article {pmid5871434, year = {1965}, author = {Korobkova, EI and Pavlova, LP and Denisova, EP}, title = {[Intradermal allergic reaction as an index of immunity against plague. IV. Allergens of Pasteurella pestis for intradermal reactions in persons vaccinated by various methods].}, journal = {Zhurnal mikrobiologii, epidemiologii i immunobiologii}, volume = {42}, number = {10}, pages = {30-35}, pmid = {5871434}, issn = {0372-9311}, mesh = {Humans ; Plague/*prevention & control ; Plague Vaccine/*administration & dosage ; *Skin Tests ; }, } @article {pmid5868302, year = {1965}, author = {Prishchep, AG and Korzhenevskaia, IaI and Denisova, AA and Lipovetskiĭ, GS and Kul'kova, IA}, title = {[Sterilization of medical instruments made of plastic materials using a mixture of ethylene oxide and methyl bromate].}, journal = {Meditsinskaia promyshlennost' SSSR}, volume = {19}, number = {9}, pages = {20-24}, pmid = {5868302}, mesh = {Ethylene Oxide ; *Sterilization ; *Surgical Instruments ; }, }