@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.},
}

Child
Humans
*Stress, Psychological/genetics
Russia
Socioeconomic Factors
*Protein Serine-Threonine Kinases/genetics

@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.},
}

Humans
Familial Exudative Vitreoretinopathies/genetics
Endothelin-1/genetics
*Eye Diseases, Hereditary/diagnosis/genetics
Mutation
*Retinal Diseases
Pedigree

@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.},
}

Rats
Animals
*Antiviral Agents/pharmacology
*Antibodies/pharmacology
Toxicity Tests, Acute

@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.},
}

Animals
Phylogeny
*Trematoda
Fishes
Life Cycle Stages
DNA, Ribosomal/genetics

@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.},
}

Spectroscopy, Mossbauer
*Iron/chemistry
Ferric Compounds/chemistry
*Iron Compounds
Pharmaceutical Preparations

@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.},
}

Animals
Humans
Rabbits
*Lipopolysaccharides
*O Antigens/chemistry
Klebsiella pneumoniae
Serogroup
Oligosaccharides
Galactans
Antibodies

@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.},
}

Animals
Laos
*Forests
*Biological Evolution
Caves
China

@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.},
}

Animals
Humans
HEK293 Cells
*Hominidae/genetics
Homeostasis/genetics
Zinc
Human Genetics
Selection, Genetic
Haplotypes
Genome, Human

@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.},
}

Humans
Adaptor Proteins, Signal Transducing
Altitude
*Asian People/genetics
Haplotypes
Tibet

@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.},
}

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

@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.},
}

Humans
Female
*DNA, Ancient
*Anthropology
Body Remains
Sequence Analysis, DNA
Universities

@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.},
}

Animals
Humans
Fossils
Gene Flow
*Neanderthals/genetics
*Climate Change

@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.},
}

Animals
Humans
Mice
*Antimicrobial Peptides
*Anti-Infective Agents
Peptides/pharmacology
Anti-Bacterial Agents/pharmacology
Machine Learning
Peptide Hydrolases
Microbial Sensitivity Tests

@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.},
}

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

@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.},
}

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

@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.},
}

Animals
Humans
Gorilla gorilla/genetics
Pan paniscus/genetics
Bayes Theorem
*Hominidae/genetics
Pan troglodytes
*Neanderthals/genetics

@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.},
}

Humans
*Bupivacaine/toxicity
*Lidocaine
Anesthetics, Local/toxicity

@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.},
}

Humans
Herpesvirus 4, Human/genetics
*Epstein-Barr Virus Infections/genetics/metabolism
Mutation
Prognosis
*Lymphoma/genetics
Tumor Microenvironment

@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.},
}

Humans
Proto-Oncogene Proteins c-akt/metabolism
Protein Phosphatase 2/metabolism
*Cytostatic Agents/therapeutic use
*Brain Neoplasms/drug therapy
Apoptosis
Brain
Cell Line, Tumor

@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.},
}

Humans
Male
Asian People/genetics
*Diploidy
*East Asian People/ethnology/genetics
*Genome, Human/genetics
Genomics
*Telomere/genetics

@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.},
}

*Bone Marrow
Antigens, CD34
*Erythroid Cells
Bone Marrow Cells
Cell Adhesion Molecules

@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.},
}

Humans
*DNA, Mitochondrial/genetics
Genetic Variation/genetics
*Genomics
*North Asian People/ethnology/genetics
Phylogeography
Indigenous Peoples/genetics

@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.},
}

Animals
*Bryozoa
Cecum
Epidermal Cells
Extracellular Matrix
*Gastropoda

@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.},
}

Humans
Infant, Newborn
Mongolia
Africa
*Archaeology
Europe

@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.},
}

Male
Animals
Humans
*Neanderthals/genetics
Semen
*Hominidae/genetics
Alleles
Gene Expression Regulation
Genome, Human

@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.},
}

Animals
Humans
*Hominidae/genetics
*Neanderthals/genetics
Alternative Splicing
Genome, Human
Population Density

@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.},
}

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

@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.},
}

Animals
Humans
DNA
Genome, Human
*Hominidae/genetics
*Neanderthals/genetics

@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.},
}

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

@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.},
}

Animals
Humans
Infant, Newborn
*Neanderthals/genetics
Rare Diseases/genetics
*Hominidae/genetics
Genome, Human
DNA

@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.},
}

Animals
Humans
*Adenomatous Polyposis Coli/genetics/pathology
*Colorectal Neoplasms/genetics
Genetic Predisposition to Disease
Germ Cells
Germ-Line Mutation
Mutation
*Neanderthals/genetics
Oxidative Stress

@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.},
}

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

@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.},
}

Animals
Female
Humans
Breast Neoplasms/genetics
*Genetics, Population
Genome, Human
*Glucuronosyltransferase/genetics
Hominidae/genetics
Neanderthals/genetics
Phenotype

@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.},
}

Adult
Female
Humans
Male
Middle Aged
Cross-Sectional Studies
Ethnicity
*Exophthalmos
Hispanic or Latino
Prospective Studies
Aged

@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.},
}

*Forensic Medicine
*Lower Extremity

@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.},
}

Humans
Animals
*Neanderthals/genetics
Genome
Genome, Human
Membrane Proteins/genetics

@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.},
}

Rats
Animals
Brain/metabolism
*Stroke/complications
*Brain Ischemia/metabolism
Infarction, Middle Cerebral Artery/complications
Transcriptome
Disease Models, Animal

@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.},
}

Animals
Humans
Genome-Wide Association Study
*Hominidae/genetics
Polymorphism, Genetic
Genome
Genomics
*Neanderthals/genetics
Selection, Genetic

@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.},
}

Humans
Animals
*Neanderthals/genetics
Reproducibility of Results
Genetics, Population
Adaptation, Physiological
Selection, Genetic
Genome, Human

@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.},
}

Rats
Animals
Rats, Wistar
*Interleukin-6
Peptides/genetics/pharmacology/therapeutic use
*Brain Ischemia/drug therapy/genetics/metabolism
Cerebral Infarction

@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.},
}

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

@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.},
}

Animals
Humans
DNA, Ancient
Body Remains
*Hominidae/genetics
DNA/genetics
Genome, Microbial
*Neanderthals/genetics
Sequence Analysis, DNA/methods

@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.},
}

*MicroRNAs/metabolism
Ascitic Fluid/metabolism
*Extracellular Vesicles/metabolism
*Exosomes/metabolism

@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.},
}

Humans
*Immune System
*Hominidae/genetics
*Neanderthals/genetics
Papua New Guinea
*Evolution, Molecular

@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.},
}

Adolescent
Humans
Young Adult
Europe
Exome Sequencing
Prognosis
*Sarcoma/genetics/therapy
*Soft Tissue Neoplasms
Proof of Concept Study

@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.},
}

Humans
*Myeloid-Derived Suppressor Cells
B7-H1 Antigen/genetics
*Multiple Myeloma/therapy
HLA-DR Antigens

@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.},
}

*Zinc Oxide/pharmacology/chemistry
Polystyrenes
Anti-Bacterial Agents/pharmacology/chemistry
Escherichia coli
Polymers
Solvents
Toluene

@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.},
}

Adult
Humans
*Transcriptome/genetics
Cell Count
*Erythrocytes/metabolism
Fetal Blood
RNA/genetics/metabolism

@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.},
}

Animals
Humans
*Hominidae
Phylogeny
Biological Evolution
Fossils
*Neanderthals

@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.},
}

Infant, Newborn
Infant
Humans
Child, Preschool
*Autistic Disorder/complications
*Autism Spectrum Disorder/psychology
Cross-Sectional Studies
Intelligence
Cognition
Early Diagnosis

@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.},
}

Humans
Animals
*Neanderthals/genetics
Multifactorial Inheritance
Genome-Wide Association Study
Genome, Human
Asian People

@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.},
}

Rats
Animals
Male
Microcirculation
Rats, Wistar
*Ozone/toxicity
Noise
Technology

@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.},
}

Humans
History, Ancient
Animals
*Human Migration
Genomics
Genome, Human
*Neanderthals
Brazil

@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.},
}

Humans
*Ischemic Attack, Transient/epidemiology/etiology
Incidence
*Hypertension/complications/epidemiology/drug therapy
Blood Pressure
*Myocardial Infarction/complications
*Stroke/etiology/complications
Antihypertensive Agents/pharmacology

@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.},
}

Humans
*Antihypertensive Agents/therapeutic use
*Hypertension/diagnosis/drug therapy
Blood Pressure
Kidney
Combined Modality Therapy
Sympathectomy
Treatment Outcome

@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.},
}

Animals
Female
*Hominidae/genetics
Humans
Male
Nucleotides
*Pseudoautosomal Regions
Receptor, PAR-1/genetics
Y Chromosome/genetics

@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.},
}

Humans
Animals
*Genome, Human
*Neanderthals/genetics
Genetics, Population

@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.},
}

Adolescent
Child
*Diet
*Energy Intake
Feeding Behavior
Humans
Meals
Nutritional Status
Sugars

@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.},
}

Animals
DNA, Ancient
Fossils
*Hominidae/anatomy & histology/genetics
Humans
Hybridization, Genetic
Mammals/genetics
*Neanderthals/genetics

@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.},
}

Animals
Archaeology
Cognition/physiology
Evolution, Molecular
Genome, Human
*Hominidae/genetics
Humans
Mammals
*Neanderthals/genetics
Phenotype

@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.},
}

*Antineoplastic Agents
*Glioblastoma/drug therapy
Humans
Protein Kinase Inhibitors/pharmacology/therapeutic use
Protein Phosphatase 2
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
Staurosporine/pharmacology

@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.},
}

Alleles
CpG Islands
*DNA Methylation
*Epigenesis, Genetic
Haplotypes
Humans

@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.},
}

Adult
*Arginase
*Bone Marrow
Erythroid Cells
Humans
Liver
RNA, Messenger
Secretome
Transcriptome

@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.},
}

Animals
Biological Evolution
Black People
Fossils
Gene Flow
*Hominidae/genetics
Humans
*Neanderthals/genetics

@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.},
}

Alleles
Amino Acids
Animals
Cognition
*Grandparents
*Hominidae/genetics
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.},
}

Animals
Brain/metabolism
*Brain Ischemia/metabolism
Disease Models, Animal
Infarction, Middle Cerebral Artery/complications/genetics
Rats
Sequence Analysis, RNA
*Stroke/etiology

@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.},
}

Animals
DNA, Ancient
DNA, Mitochondrial/genetics
Genome, Human
*Hominidae/genetics
Humans
*Neanderthals/genetics