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16 Nov 2018 at 01:33
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Bibliography on: Current Literature — Recent Full Contents


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Current Literature — Recent Full Contents

Current Literature: Full, recent table-of-contents listings for a few selected journals.

Created with PubMed® Query: 2018[PDAT] AND ( 0003-0147[issn] or 0006-3568[issn] or 0006-8977[issn] or 0012-1606[issn] or 0014-3820[issn] or 0022-0930[issn] or 0022-2844[issn] or 0025-9241[issn] or 0028-0836[issn] or 0031-8248[issn] or 0033-5770[issn] or 0039-3681[issn] or 0047-2484[issn] or 0066-4154[issn] or 0066-4162[issn] or 0066-4197[issn] or 0066-4227[issn] or 0068-6735[issn] or 0071-3260[issn] or 0085-0748[issn] or 0090-4996[issn] or 0095-134x[issn] or 0165-0157[issn] or 0168-6445[issn] or 0168-6496[issn] or 0168-9525[issn] or 0169-3867[issn] or 0169-5347[issn] or 0169-6149[issn] or 0269-7653[issn] or 0343-8651[issn] or 0346-8313[issn] or 0378-2697[issn] or 0393-9375[issn] or 0394-9370[issn] or 0737-4038[issn] or 0743-4634[issn] or 0923-2508[issn] or 0947-5745[issn] or 0949-944x[issn] or 0960-8788[issn] or 0962-8436[issn] or 0966-842x[issn] or 0967-3849[issn] or 0972-7736[issn] or 0972-8422[issn] or 1010-061x[issn] or 1055-7903[issn] or 1060-1538[issn] or 1061-4036[issn] or 1064-7554[issn] or 1081-0706[issn] or 1090-5138[issn] or 1091-6490[issn] or 1095-9203[issn] or 1121-7138[issn] or 1176-9343[issn] or 1369-5274[issn] or 1369-8486[issn] or 1399-560x[issn] or 1433-8319[issn] or 1439-6092[issn] or 1462-2912[issn] or 1464-7931[issn] or 1466-5026[issn] or 1471-0056[issn] or 1471-2091[issn] or 1471-2105[issn] or 1471-2121[issn] or 1471-213x[issn] or 1471-2148[issn] or 1471-2156[issn] or 1471-2164[issn] or 1471-2180[issn] or 1471-2199[issn] or 1471-2229[issn] or 1471-4922[issn] or 1472-6785[issn] or 1474-7049[issn] or 1520-541x[issn] or 1522-0613[issn] or 1527-8204[issn] or 1543-5008[issn] or 1543-592x[issn] or 1552-4884[issn] or 1552-5007[issn] or 1661-5425[issn] or 1674-4918[issn] or 1740-1526[issn] or 1741-7007[issn] or 1752-0509[issn] or 1752-4571[issn] or 1753-6561[issn] or 1756-0500[issn] or 1758-2229[issn] or 1759-6653[issn] or 1933-5377[issn] or 1935-7877[issn] or 1936-6426[issn] or 1941-1405[issn] or 1943-0264[issn] or 1944-3277[issn] or 2036-2641[issn] or 2041-210x[issn] or 2045-7758[issn] or 2049-2618[issn] or 2050-6201[issn] or 2058-5276[issn] or 2090-8032[issn] or 2163-9434[issn] or 2165-3402[issn] or 2210-6502[issn] or 2296-701x[issn] or 2326-8298[issn] or 2329-9002[issn] or 2333-9683[issn] or 2397-334x[issn] or freeble ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2018-11-15

Banla LI, Salzman NH, CJ Kristich (2018)

Colonization of the mammalian intestinal tract by enterococci.

Current opinion in microbiology, 47:26-31 pii:S1369-5274(18)30096-1 [Epub ahead of print].

Enterococci are colonizers of the mammalian gastrointestinal tract (GIT) and normally live in healthy association with their human host. However, enterococci are also major causes of healthcare-acquired infections, prompting the US Centers for Disease Control and Prevention to declare vancomycin-resistant enterococci (VRE) a serious threat to public health. Because of both intrinsic and acquired antibiotic resistance, enterococci proliferate in the GIT during antibiotic therapy, leading to dissemination and disease. The recognition that colonization of the GIT is a pre-requisite for enterococcal infections has prompted research to study mechanisms used by enterococci to colonize this niche. This review discusses major findings of recent research to understand GIT colonization by enterococci using diverse experimental models, each of which exhibits unique strengths. This work has revealed enterococcal transcriptional reprogramming in the GIT, contributions of specific enterococcal genes encoded by the core genome to GIT colonization, the impact of genome plasticity, and roles for intra-species and inter-species interactions in modulation of GIT colonization.

RevDate: 2018-11-15

Niimi Y, Imai A, Nishimura H, et al (2018)

Essential role of mouse Dead end1 in the maintenance of spermatogonia.

Developmental biology pii:S0012-1606(18)30502-5 [Epub ahead of print].

Dead end is a vertebrate-specific RNA-binding protein implicated in germ cell development. We have previously shown that mouse Dead end1 (DND1) is expressed in male embryonic germ cells and directly interacts with NANOS2 to cooperatively promote sexual differentiation of fetal germ cells. In addition, we have also reported that NANOS2 is expressed in self-renewing spermatogonial stem cells and is required for the maintenance of the stem cell state. However, it remains to be determined whether DND1 works with NANOS2 in the spermatogonia. Here, we show that DND1 is expressed in a subpopulation of differentiating spermatogonia and undifferentiated spermatogonia, including NANOS2-positive spermatogonia. Conditional disruption of DND1 depleted both differentiating and undifferentiated spermatogonia; however, the numbers of Asingle and Apaired spermatogonia were preferentially decreased as compared with those of Aaligned spermatogonia. Finally, we found that postnatal DND1 associates with NANOS2 in vivo, independently of RNA, and interacts with some of NANOS2-target mRNAs. These data not only suggest that DND1 is a partner of NANOS2 in undifferentiated spermatogonia as well as in male embryonic germ cells, but also show that DND1 plays an essential role in the survival of differentiating spermatogonia.

RevDate: 2018-11-15

Son JS, Hwang YJ, Lee SY, et al (2018)

Bacillus salidurans sp. nov., isolated from salt-accumulated pepper rhizospheric soil.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

A Gram-stain-positive, facultatively anaerobic, motile and rod-shaped bacterium, designated KNUC7312T, was isolated from salt-accumulated rhizospheric soil in a pepper greenhouse in Miryang city, Republic of Korea. Cell growth of strain KNUC7312T occurred at 10-45 °C (optimum, 30 °C) and pH 7-12 (optimum, pH 7). In addition, this strain was able to tolerate 0-12 % NaCl (w/v) concentration (optimum, 0-1 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain KNUC7312T clustered together with other species of the genus Bacillus and was most closely related to Bacillus humi DSM 16318T (98.0 %). The predominant respiratory quinone was menaquinone-7 (MK-7). The major cellular fatty acids were anteiso C15 : 0, iso-C15 : 0 and iso-C14 : 0. The polar lipid profile contained the major components diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and two unidentified aminolipids. The cell-wall peptidoglycan contained meso-diaminopimelic acid as the major diagnostic diamino acid. Strain KNUC7312T showed a low DNA-DNA relatedness value (47.36 %) with B. humi DSM 16318T, which supported that this strain represents a novel Bacillusspecies. On the basis of phenotypic, chemotaxonomic and phylogenetic evidence, strain KNUC7312T represents a novel species within the genera Bacillus. The name Bacillus salildurans sp. nov. is proposed. The type strain is KNUC7312T (KCTC 33852T=CGMCC 1.13629T).

RevDate: 2018-11-15

Phurbu D, Pema Y, Ma C, et al (2018)

Nitrincola tibetensis sp. nov., isolated from Lake XuguoCo on the Tibetan Plateau.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

A novel Gram-stain-negative, motile and rod-shaped bacterium, designated xg18T, was isolated from Lake XuguoCo on the Tibetan Plateau. The strain was able to grow optimally at 0-2 % NaCl and tolerate up to 6 % NaCl. Growth occurred at pH 7.0-11.0 (optimum, pH 9.0-10.0) and 15-40 °C (optimum, 37 °C). Vitamins were not required for growth. The major polar lipids of strain xg18T were phosphatidyl ethanolamine and phosphatidylglycerol. The predominant respiratory quinone was Q-8. The major fatty acids were summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The G+C content of genomic DNA was 46.1 mol%. Analysis of 16S rRNA sequences showed that strain xg18T belongs to the genus Nitrincola, with Nitrincola alkalisediminis MEB087T (KC822363, 98.6 %) as its closest neighbour. The DNA-DNA relatedness value of strain xg18T with its closest phylogenetic neighbour, N. alkalisediminis JCM 19317T, was 43.1±3.2 %. Strain xg18T was clearly distinguishable from the type strain of the genus Nitrincola through phylogenetic analysis, fatty acid composition data and a range of physiological and biochemical characteristics comparisons. Based on its phenotypic and chemotaxonomic characteristics, strain xg18T could be classified as a representative of a novel species of the genus for which the name Nitrincola tibetensis sp. nov. is proposed. The type strain is xg18T (=CICC 24457T=KCTC 62401T).

RevDate: 2018-11-15

Thanh VN, DD Hien (2018)

Moniliella floricola sp. nov., a species of black yeast isolated from flowers.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

Moniliella yeasts were isolated from flower samples collected in Vietnam using an enrichment medium containing 50 % (w/w) glucose. The yeasts were identified as M. byzovii, M. dehoogii, M. megachiliensis, M. mellis, M. nigrescens and M. spathulata. A group of 20 strains representing a hitherto undescribed species of Moniliella was detected. ITS sequences indicated the presence of four genetic variants differing from each other by 4-14 nt. The strains, however, were identical in the TEF1 sequences and shared 1-2 nt differences in the D1/D2 regions. In the ITS-D1/D2 phylogenetic tree, the strains grouped together and formed a well-supported clade with insect-associated Moniliella species, including M. pollinis, M. megachiliensis and M. oedocephalis. The new group was most closely related to M. pollinis but differed from the latter by 95 nt (58 substitutions, 37 indels) in the ITS, 36 nt (31 substitutions, five indels) in the D1/D2, and 30 nt (30 substitutions) in the TEF1 sequences. Moniliella floricola sp. nov. is proposed to accommodate this group of isolates. The type strain and MycoBank number of M. floricola sp. nov. are TBY 30.1T (=CBS 12758T=NRRL Y-63660T) and MB 825274, respectively.

RevDate: 2018-11-15

Perez-Lopez E, Vincent C, Moreau D, et al (2018)

A novel 'Candidatus Phytoplasma asteris' subgroup 16SrI-(E/AI)AI associated with blueberry stunt disease in eastern Canada.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

Phytoplasmas ('Candidatus Phytoplasma' species) are phytopathogenic bacteria vectored by insects and are associated with crop diseases that cause severe yield losses by affecting reproductive tissue development. Infection of northern highbush blueberry plants (Vaccinium corymbosum; Ericaceae) with phytoplasma leads to yield losses by altering plant development resulting in stunting and subsequent plant death. Samples collected from symptomatic blueberry plants in two important blueberry-producing areas in Canada, in the provinces of Québec and Nova Scotia, were analysed for the presence of DNA sequences associated with phytoplasma. Analysis of the 16S rRNA gene sequences demonstrated that the plants were infected with a strain of 'Candidatus Phytoplasma asteris', which was previously identified as blueberry stunt phytoplasma (BBS; 16SrI-E). Examination of further bacterial sequences revealed that two distinct 16S rRNA-encoding gene sequences were present in each sample in combination with a single chaperonin-60 (cpn60) sequence and a single rpoperon sequence, suggesting that this strain displays 16S rRNA-encoding gene sequence heterogeneity. Two distinct rrnoperons, rrnE and the newly described rrnAI, were identified in samples analysed from all geographic locations. We propose, based on the sequences obtained, delineating the new subgroup 16SrI-(E/AI)AI, following the nomenclature proposed for heterogeneous subgroups. To our knowledge, this is the first report of a heterogeneous phytoplasma strain affecting blueberry plants and associated with blueberry stunt disease.

RevDate: 2018-11-15

Oren A, GM Garrity (2018)

Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 10 of the IJSEM.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

RevDate: 2018-11-15

Shi YL, Sun Y, Jiang ZM, et al (2018)

Simplicispira lacusdiani sp. nov., a novel betaproteobacterium isolated from a freshwater reservoir.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

A Gram-stain-negative, motile, rod-shaped bacterium, designated CPCC 100842T, was isolated from a freshwater reservoir in south-west China. The 16S rRNA gene sequence comparison of strain CPCC 100842T with the available sequences in the GenBank database showed that the isolate was closely related to members of the family Comamonadaceae, with the highest similarities to Simplicispira metamorpha DSM 1837T (98.05 %), Simplicispira limi KCTC 12608T (97.86 %), Simplicispira psychrophila LMG 5408T (97.04 %) and Simplicispira piscis JCM 19291T (97.0 %). In the phylogenetic tree based on 16S rRNA gene sequences, strain CPCC 100842T formed a distinct phylogenetic subclade within the genus Simplicispira. The major cellular fatty acids were as C16 : 0 and summed feature 3 (C16 : 1 ω7c/C16 : 1ω6c). Q-8 was detected as the only respiratory quinone. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, aminophospholipid and glycolipid were found in the polar lipid extraction. The genomic DNA G+C content was 67.4 mol%. The average nucleotide identity value was 80.4 % by comparing the draft genome sequences of strain CPCC 100842T and S. metamorpha DSM 1837T. The DNA-DNA hybridization result between strain CPCC 100842T and S. metamorpha DSM 1837T showed 37±3 % genomic relatedness. On the basis of the genotypic analysis and phenotypic characteristics, we propose that strain CPCC 100842T represents a novel species of the genus Simplicispira in the family Comamonadaceae with the name Simplicispira lacusdiani sp. nov. Strain CPCC 100842T (=KCTC 52093T=DSM 102231T) is the type strain of the species.

RevDate: 2018-11-15

Berry D (2018)

Up-close-and-personal with the human microbiome.

Environmental microbiology reports [Epub ahead of print].

RevDate: 2018-11-15

Koskella B (2018)

New approaches to characterizing bacteria-phage interactions in microbial communities and microbiomes.

Environmental microbiology reports [Epub ahead of print].

RevDate: 2018-11-15

Wahl LM, Betti MI, Dick DW, et al (2018)

Evolutionary stability of the lysis-lysogeny decision: why be virulent?.

Evolution; international journal of organic evolution [Epub ahead of print].

Lytic viruses infect and kill host cells, producing a large number of viral copies. Temperate viruses, in contrast, are able to integrate viral genetic material into the host cell DNA, leaving a viable host cell. The evolutionary advantage of this strategy, lysogeny, has been demonstrated in complex environments that include spatial structure, oscillating population dynamics, or periodic environmental collapse. Here, we examine the evolutionary stability of the lysis-lysogeny decision, that is, we predict the longterm outcome of the evolution of lysogeny rates. We demonstrate that viruses with high rates of lysogeny are stable against invasion by more virulent viral strains even in simple environments, as long as the pool of susceptible hosts is not unlimited. This mirrors well-known results in both r-K selection theory and virulence evolution: although virulent viruses have a faster potential growth rate, temperate strains are able to maintain positive growth on a lower density of the limiting resource, susceptible hosts. We then outline scenarios in which the rate of lysogeny is predicted to evolve either toward full lysogeny or full lysis. Finally, we demonstrate conditions under which intermediate rates of lysogeny, as observed in temperate viruses in nature, can be sustained longterm. In general, intermediate lysogeny rates persist when the coupling between susceptible host density and virus density is relaxed. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-15

Wright JT (2018)

Milan M. Ćirković: The Great Silence: The Science and Philosophy of Fermi's Paradox : Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, United Kingdom, 2018, (ISBN 9780199646302) USD 32.95, 432 pages.

Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life pii:10.1007/s11084-018-9568-3 [Epub ahead of print].

RevDate: 2018-11-15

Fujimoto K, Hasebe T, Kajita M, et al (2018)

Expression of hyaluronan synthases upregulated by thyroid hormone is involved in intestinal stem cell development during Xenopus laevis metamorphosis.

Development genes and evolution pii:10.1007/s00427-018-0623-x [Epub ahead of print].

During amphibian intestinal remodeling, thyroid hormone (TH) induces adult stem cells, which newly generate the absorptive epithelium analogous to the mammalian one. We have previously shown that hyaluronan (HA) is newly synthesized and plays an essential role in the development of the stem cells via its major receptor CD44 in the Xenopus laevis intestine. We here focused on HA synthase (HAS) and examined how the expression of HAS family genes is regulated during natural and TH-induced metamorphosis. Our quantitative RT-PCR analysis indicated that the mRNA expression of HAS2 and HAS3, but not that of HAS1 and HAS-rs, a unique Xenopus HAS-related sequence, is upregulated concomitantly with the development of adult epithelial primordia consisting of the stem/progenitor cells during the metamorphic climax. In addition, our in situ hybridization analysis indicated that the HAS3 mRNA is specifically expressed in the adult epithelial primordia, whereas HAS2 mRNA is expressed in both the adult epithelial primordia and nearby connective tissue cells during this period. Furthermore, by treating X. laevis tadpoles with 4-methylumbelliferone, a HA synthesis inhibitor, we have experimentally shown that inhibition of HA synthesis leads to suppression of TH-upregulated expression of leucine-rich repeat-containing G protein-coupled 5 (LGR5), an intestinal stem cell marker, CD44, HAS2, HAS3, and gelatinase A in vivo. These findings suggest that HA newly synthesized by HAS2 and/or HAS3 is required for intestinal stem cell development through a positive feedback loop and is involved in the formation of the stem cell niche during metamorphosis.

RevDate: 2018-11-15

Klein LD, Huang J, Quinn EA, et al (2018)

Variation among populations in the immune protein composition of mother's milk reflects subsistence pattern.

Evolution, medicine, and public health, 2018(1):230-245 pii:eoy031.

Lay Summary: Adaptive immune proteins in mothers' milk are more variable than innate immune proteins across populations and subsistence strategies. These results suggest that the immune defenses in milk are shaped by a mother's environment throughout her life.

Background and objectives: Mother's milk contains immune proteins that play critical roles in protecting the infant from infection and priming the infant's developing immune system during early life. The composition of these molecules in milk, particularly the acquired immune proteins, is thought to reflect a mother's immunological exposures throughout her life. In this study, we examine the composition of innate and acquired immune proteins in milk across seven populations with diverse disease and cultural ecologies.

Methodology: Milk samples (n = 164) were collected in Argentina, Bolivia, Nepal, Namibia, Philippines, Poland and the USA. Populations were classified as having one of four subsistence patterns: urban-industrialism, rural-shop, horticulturalist-forager or agro-pastoralism. Milk innate (lactalbumin, lactoferrin and lysozyme) and acquired (Secretory IgA, IgG and IgM) protein concentrations were determined using triple-quadrupole mass spectrometry.

Results: Both innate and acquired immune protein composition in milk varied among populations, though the acquired immune protein composition of milk differed more among populations. Populations living in closer geographic proximity or having similar subsistence strategies (e.g. agro-pastoralists from Nepal and Namibia) had more similar milk immune protein compositions. Agro-pastoralists had different milk innate immune protein composition from horticulturalist-foragers and urban-industrialists. Acquired immune protein composition differed among all subsistence strategies except horticulturist-foragers and rural-shop.

Conclusions and implications: Our results reveal fundamental variation in milk composition that has not been previously explored in human milk research. Further study is needed to understand what specific aspects of the local environment influence milk composition and the effects this variation may have on infant health outcomes.

RevDate: 2018-11-15

Matthews BJ, Dudchenko O, Kingan SB, et al (2018)

Improved reference genome of Aedes aegypti informs arbovirus vector control.

Nature pii:10.1038/s41586-018-0692-z [Epub ahead of print].

Female Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector.

RevDate: 2018-11-15

Liang Q, Monetti C, Shutova MV, et al (2018)

Linking a cell-division gene and a suicide gene to define and improve cell therapy safety.

Nature pii:10.1038/s41586-018-0733-7 [Epub ahead of print].

Human pluripotent cell lines hold enormous promise for the development of cell-based therapies. Safety, however, is a crucial prerequisite condition for clinical applications. Numerous groups have attempted to eliminate potentially harmful cells through the use of suicide genes1, but none has quantitatively defined the safety level of transplant therapies. Here, using genome-engineering strategies, we demonstrate the protection of a suicide system from inactivation in dividing cells. We created a transcriptional link between the suicide gene herpes simplex virus thymidine kinase (HSV-TK) and a cell-division gene (CDK1); this combination is designated the safe-cell system. Furthermore, we used a mathematical model to quantify the safety level of the cell therapy as a function of the number of cells that is needed for the therapy and the type of genome editing that is performed. Even with the highly conservative estimates described here, we anticipate that our solution will rapidly accelerate the entry of cell-based medicine into the clinic.

RevDate: 2018-11-15

Fadrique B, Báez S, Duque Á, et al (2018)

Widespread but heterogeneous responses of Andean forests to climate change.

Nature pii:10.1038/s41586-018-0715-9 [Epub ahead of print].

Global warming is forcing many species to shift their distributions upward, causing consequent changes in the compositions of species that occur at specific locations. This prediction remains largely untested for tropical trees. Here we show, using a database of nearly 200 Andean forest plot inventories spread across more than 33.5° latitude (from 26.8° S to 7.1° N) and 3,000-m elevation (from 360 to 3,360 m above sea level), that tropical and subtropical tree communities are experiencing directional shifts in composition towards having greater relative abundances of species from lower, warmer elevations. Although this phenomenon of 'thermophilization' is widespread throughout the Andes, the rates of compositional change are not uniform across elevations. The observed heterogeneity in thermophilization rates is probably because of different warming rates and/or the presence of specialized tree communities at ecotones (that is, at the transitions between distinct habitats, such as at the timberline or at the base of the cloud forest). Understanding the factors that determine the directions and rates of compositional changes will enable us to better predict, and potentially mitigate, the effects of climate change on tropical forests.

RevDate: 2018-11-15

Sawangjit A, Oyanedel CN, Niethard N, et al (2018)

The hippocampus is crucial for forming non-hippocampal long-term memory during sleep.

Nature pii:10.1038/s41586-018-0716-8 [Epub ahead of print].

There is a long-standing division in memory research between hippocampus-dependent memory and non-hippocampus-dependent memory, as only the latter can be acquired and retrieved in the absence of normal hippocampal function1,2. Consolidation of hippocampus-dependent memory, in particular, is strongly supported by sleep3-5. Here we show that the formation of long-term representations in a rat model of non-hippocampus-dependent memory depends not only on sleep but also on activation of a hippocampus-dependent mechanism during sleep. Rats encoded non-hippocampus-dependent (novel-object recognition6-8) and hippocampus-dependent (object-place recognition) memories before a two-hour period of sleep or wakefulness. Memory was tested either immediately thereafter or remotely (after one or three weeks). Whereas object-place recognition memory was stronger for rats that had slept after encoding (rather than being awake) at both immediate and remote testing, novel-object recognition memory profited from sleep only three weeks after encoding, at which point it was preserved in rats that had slept after encoding but not in those that had been awake. Notably, inactivation of the hippocampus during post-encoding sleep by intrahippocampal injection of muscimol abolished the sleep-induced enhancement of remote novel-object recognition memory. By contrast, muscimol injection before remote retrieval or memory encoding had no effect on test performance, confirming that the encoding and retrieval of novel-object recognition memory are hippocampus-independent. Remote novel-object recognition memory was associated with spindle activity during post-encoding slow-wave sleep, consistent with the view that neuronal memory replay during slow-wave sleep contributes to long-term memory formation. Our results indicate that the hippocampus has an important role in long-term consolidation during sleep even for memories that have previously been considered hippocampus-independent.

RevDate: 2018-11-15

Lax G, Eglit Y, Eme L, et al (2018)

Hemimastigophora is a novel supra-kingdom-level lineage of eukaryotes.

Nature pii:10.1038/s41586-018-0708-8 [Epub ahead of print].

Almost all eukaryote life forms have now been placed within one of five to eight supra-kingdom-level groups using molecular phylogenetics1-4. The 'phylum' Hemimastigophora is probably the most distinctive morphologically defined lineage that still awaits such a phylogenetic assignment. First observed in the nineteenth century, hemimastigotes are free-living predatory protists with two rows of flagella and a unique cell architecture5-7; to our knowledge, no molecular sequence data or cultures are currently available for this group. Here we report phylogenomic analyses based on high-coverage, cultivation-independent transcriptomics that place Hemimastigophora outside of all established eukaryote supergroups. They instead comprise an independent supra-kingdom-level lineage that most likely forms a sister clade to the 'Diaphoretickes' half of eukaryote diversity (that is, the 'stramenopiles, alveolates and Rhizaria' supergroup (Sar), Archaeplastida and Cryptista, as well as other major groups). The previous ranking of Hemimastigophora as a phylum understates the evolutionary distinctiveness of this group, which has considerable importance for investigations into the deep-level evolutionary history of eukaryotic life-ranging from understanding the origins of fundamental cell systems to placing the root of the tree. We have also established the first culture of a hemimastigote (Hemimastix kukwesjijk sp. nov.), which will facilitate future genomic and cell-biological investigations into eukaryote evolution and the last eukaryotic common ancestor.

RevDate: 2018-11-15

Lei Z, Liu X, Wu Y, et al (2018)

Enhanced strength and ductility in a high-entropy alloy via ordered oxygen complexes.

Nature pii:10.1038/s41586-018-0685-y [Epub ahead of print].

Oxygen, one of the most abundant elements on Earth, often forms an undesired interstitial impurity or ceramic phase (such as an oxide particle) in metallic materials. Even when it adds strength, oxygen doping renders metals brittle1-3. Here we show that oxygen can take the form of ordered oxygen complexes, a state in between oxide particles and frequently occurring random interstitials. Unlike traditional interstitial strengthening4,5, such ordered interstitial complexes lead to unprecedented enhancement in both strength and ductility in compositionally complex solid solutions, the so-called high-entropy alloys (HEAs)6-10. The tensile strength is enhanced (by 48.5 ± 1.8 per cent) and ductility is substantially improved (by 95.2 ± 8.1 per cent) when doping a model TiZrHfNb HEA with 2.0 atomic per cent oxygen, thus breaking the long-standing strength-ductility trade-off11. The oxygen complexes are ordered nanoscale regions within the HEA characterized by (O, Zr, Ti)-rich atomic complexes whose formation is promoted by the existence of chemical short-range ordering among some of the substitutional matrix elements in the HEAs. Carbon has been reported to improve strength and ductility simultaneously in face-centred cubic HEAs12, by lowering the stacking fault energy and increasing the lattice friction stress. By contrast, the ordered interstitial complexes described here change the dislocation shear mode from planar slip to wavy slip, and promote double cross-slip and thus dislocation multiplication through the formation of Frank-Read sources (a mechanism explaining the generation of multiple dislocations) during deformation. This ordered interstitial complex-mediated strain-hardening mechanism should be particularly useful in Ti-, Zr- and Hf-containing alloys, in which interstitial elements are highly undesirable owing to their embrittlement effects, and in alloys where tuning the stacking fault energy and exploiting athermal transformations13 do not lead to property enhancement. These results provide insight into the role of interstitial solid solutions and associated ordering strengthening mechanisms in metallic materials.

RevDate: 2018-11-15

Houbaert A, Zhang C, Tiwari M, et al (2018)

POLAR-guided signalling complex assembly and localization drive asymmetric cell division.

Nature pii:10.1038/s41586-018-0714-x [Epub ahead of print].

Stomatal cell lineage is an archetypal example of asymmetric cell division (ACD), which is necessary for plant survival1-4. In Arabidopsis thaliana, the GLYCOGEN SYNTHASE KINASE3 (GSK3)/SHAGGY-like kinase BRASSINOSTEROID INSENSITIVE 2 (BIN2) phosphorylates both the mitogen-activated protein kinase (MAPK) signalling module5,6 and its downstream target, the transcription factor SPEECHLESS (SPCH)7, to promote and restrict ACDs, respectively, in the same stomatal lineage cell. However, the mechanisms that balance these mutually exclusive activities remain unclear. Here we identify the plant-specific protein POLAR as a stomatal lineage scaffold for a subset of GSK3-like kinases that confines them to the cytosol and subsequently transiently polarizes them within the cell, together with BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL), before ACD. As a result, MAPK signalling is attenuated, enabling SPCH to drive ACD in the nucleus. Moreover, POLAR turnover requires phosphorylation on specific residues, mediated by GSK3. Our study reveals a mechanism by which the scaffolding protein POLAR ensures GSK3 substrate specificity, and could serve as a paradigm for understanding regulation of GSK3 in plants.

RevDate: 2018-11-15

Shen SY, Singhania R, Fehringer G, et al (2018)

Sensitive tumour detection and classification using plasma cell-free DNA methylomes.

Nature pii:10.1038/s41586-018-0703-0 [Epub ahead of print].

The use of liquid biopsies for cancer detection and management is rapidly gaining prominence1. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these methods may be low among patients with early-stage cancer given the limited number of recurrent mutations2-5. By contrast, large-scale epigenetic alterations-which are tissue- and cancer-type specific-are not similarly constrained6 and therefore potentially have greater ability to detect and classify cancers in patients with early-stage disease. Here we develop a sensitive, immunoprecipitation-based protocol to analyse the methylome of small quantities of circulating cell-free DNA, and demonstrate the ability to detect large-scale DNA methylation changes that are enriched for tumour-specific patterns. We also demonstrate robust performance in cancer detection and classification across an extensive collection of plasma samples from several tumour types. This work sets the stage to establish biomarkers for the minimally invasive detection, interception and classification of early-stage cancers based on plasma cell-free DNA methylation patterns.

RevDate: 2018-11-15

Poillet-Perez L, Xie X, Zhan L, et al (2018)

Autophagy maintains tumour growth through circulating arginine.

Nature pii:10.1038/s41586-018-0697-7 [Epub ahead of print].

Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and to enable survival during starvation1-5. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect that manifests as starvation intolerance and gradual loss of white adipose tissue, liver glycogen and muscle mass1. Cancer cells also benefit from autophagy. Deletion of essential autophagy genes impairs the metabolism, proliferation, survival and malignancy of spontaneous tumours in models of autochthonous cancer6,7. Acute, systemic deletion of Atg7 or acute, systemic expression of a dominant-negative ATG4b in mice induces greater regression of KRAS-driven cancers than does tumour-specific autophagy deletion, which suggests that host autophagy promotes tumour growth1,8. Here we show that host-specific deletion of Atg7 impairs the growth of multiple allografted tumours, although not all tumour lines were sensitive to host autophagy status. Loss of autophagy in the host was associated with a reduction in circulating arginine, and the sensitive tumour cell lines were arginine auxotrophs owing to the lack of expression of the enzyme argininosuccinate synthase 1. Serum proteomic analysis identified the arginine-degrading enzyme arginase I (ARG1) in the circulation of Atg7-deficient hosts, and in vivo arginine metabolic tracing demonstrated that serum arginine was degraded to ornithine. ARG1 is predominantly expressed in the liver and can be released from hepatocytes into the circulation. Liver-specific deletion of Atg7 produced circulating ARG1, and reduced both serum arginine and tumour growth. Deletion of Atg5 in the host similarly released circulating arginine and suppressed tumorigenesis, which demonstrates that this phenotype is specific to autophagy function rather than to deletion of Atg7. Dietary supplementation of Atg7-deficient hosts with arginine partially restored levels of circulating arginine and tumour growth. Thus, defective autophagy in the host leads to the release of ARG1 from the liver and the degradation of circulating arginine, which is essential for tumour growth; this identifies a metabolic vulnerability of cancer.

RevDate: 2018-11-15

Beier J, Anthes N, Wahl J, et al (2018)

Similar cranial trauma prevalence among Neanderthals and Upper Palaeolithic modern humans.

Nature pii:10.1038/s41586-018-0696-8 [Epub ahead of print].

Neanderthals are commonly depicted as leading dangerous lives and permanently struggling for survival. This view largely relies on the high incidences of trauma that have been reported1,2 and have variously been attributed to violent social behaviour3,4, highly mobile hunter-gatherer lifestyles2 or attacks by carnivores5. The described Neanderthal pattern of predominantly cranial injuries is further thought to reflect violent encounters with large prey mammals, resulting from the use of close-range hunting weapons1. These interpretations directly shape our understanding of Neanderthal lifestyles, health and hunting abilities, yet mainly rest on descriptive, case-based evidence. Quantitative, population-level studies of traumatic injuries are rare. Here we reassess the hypothesis of higher cranial trauma prevalence among Neanderthals using a population-level approach-accounting for preservation bias and other contextual data-and an exhaustive fossil database. We show that Neanderthals and early Upper Palaeolithic anatomically modern humans exhibit similar overall incidences of cranial trauma, which are higher for males in both taxa, consistent with patterns shown by later populations of modern humans. Beyond these similarities, we observed species-specific, age-related variation in trauma prevalence, suggesting that there were differences in the timing of injuries during life or that there was a differential mortality risk of trauma survivors in the two groups. Finally, our results highlight the importance of preservation bias in studies of trauma prevalence.

RevDate: 2018-11-15

Trenkmann M (2018)

Cancer chromatin accessed.

Nature reviews. Genetics pii:10.1038/s41576-018-0075-1 [Epub ahead of print].

RevDate: 2018-11-15

Gayden T, Sepulveda FE, Khuong-Quang DA, et al (2018)

Author Correction: Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome.

In the version of this article originally published, the main-text sentence "In three patients of European ancestry, we identified the germline variant encoding p.Ile97Met in TIM-3, which was homozygous in two (P12 and P13) and heterozygous in one (P15) in the germline but with no TIM-3 plasma membrane expression in the tumor" misstated the identifiers of the two homozygous individuals, which should have been P13 and P14. The error has been corrected in the HTML, PDF and print versions of the paper.

RevDate: 2018-11-15

Evangelou E, Warren HR, Mosen-Ansorena D, et al (2018)

Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

RevDate: 2018-11-15

Anonymous (2018)

Keystone pipeline blocked, statistics prize and horse cull.

Nature, 563(7731):298-299.

RevDate: 2018-11-15

Abbott A (2018)

In the Palestinian territories, science struggles against all odds.

Nature, 563(7731):308-311.

RevDate: 2018-11-15

Eisenstein M (2018)

Lymphoma: 4 big questions.

Nature, 563(7731):S55.

RevDate: 2018-11-15

Ainsworth C (2018)

Building a better lymphoma vaccine.

Nature, 563(7731):S52-S54.

RevDate: 2018-11-15

DeWeerdt S (2018)

How dogs are teaching researchers new tricks for treating cancer.

Nature, 563(7731):S50-S51.

RevDate: 2018-11-15

Nogrady B (2018)

Genetically modified T cells target lymphoma.

Nature, 563(7731):S42-S43.

RevDate: 2018-11-15

Drew L (2018)

Towards the better diagnosis of lymphoma.

Nature, 563(7731):S38-S40.

RevDate: 2018-11-15

Dolgin E (2018)

Precision therapies take aim at non-Hodgkin's lymphoma.

Nature, 563(7731):S46-S47.

RevDate: 2018-11-15

Eisenstein M (2018)

The cost of surviving cancer.

Nature, 563(7731):S44-S45.

RevDate: 2018-11-15

Arney K (2018)

Solving lymphoma's stem-cell problem.

Nature, 563(7731):S48-S49.

RevDate: 2018-11-15

Brody H (2018)


Nature, 563(7731):S37.

RevDate: 2018-11-15

Shillington DJ (2018)

Water takes a deep dive into an oceanic tectonic plate.

Nature, 563(7731):335-336.

RevDate: 2018-11-15

Rajagopalan S, EO Long (2018)

Cell atlas reveals the landscape of early pregnancy.

Nature, 563(7731):337-338.

RevDate: 2018-11-15

Díaz RF (2018)

A key piece in the exoplanet puzzle.

Nature, 563(7731):329-330.

RevDate: 2018-11-15

Marin da Fonte LF (2018)

3D print so more scholars can access unique specimens.

Nature, 563(7731):325.

RevDate: 2018-11-15

Bernstein E, Meissner A, M Ramalho-Santos (2018)

Paying PIs from grants blocks talent and diversity.

Nature, 563(7731):325.

RevDate: 2018-11-15

Hagerty S, Barger N, Taylor S, et al (2018)

Written lab agreements improve mentoring.

Nature, 563(7731):325.

RevDate: 2018-11-15

Baghi HB (2018)

Networks and mentors help female scientists in Africa and Middle East.

Nature, 563(7731):325.

RevDate: 2018-11-15

Lymbery P (2018)

Governments should unite to curb meat consumption.

Nature, 563(7731):325.

RevDate: 2018-11-15

Lingen M (2018)

Say it with mastodons.

Nature, 563(7731):436.

RevDate: 2018-11-15

Sohn E (2018)

How to turn your interests into a career.

Nature, 563(7731):431-433.

RevDate: 2018-11-15

Ribas I, Tuomi M, Reiners A, et al (2018)

A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Nature, 563(7731):365-368.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

RevDate: 2018-11-15

Zhang W, Villarini G, Vecchi GA, et al (2018)

Urbanization exacerbated the rainfall and flooding caused by hurricane Harvey in Houston.

Nature, 563(7731):384-388.

Category 4 landfalling hurricane Harvey poured more than a metre of rainfall across the heavily populated Houston area, leading to unprecedented flooding and damage. Although studies have focused on the contribution of anthropogenic climate change to this extreme rainfall event1-3, limited attention has been paid to the potential effects of urbanization on the hydrometeorology associated with hurricane Harvey. Here we find that urbanization exacerbated not only the flood response but also the storm total rainfall. Using the Weather Research and Forecast model-a numerical model for simulating weather and climate at regional scales-and statistical models, we quantify the contribution of urbanization to rainfall and flooding. Overall, we find that the probability of such extreme flood events across the studied basins increased on average by about 21 times in the period 25-30 August 2017 because of urbanization. The effect of urbanization on storm-induced extreme precipitation and flooding should be more explicitly included in global climate models, and this study highlights its importance when assessing the future risk of such extreme events in highly urbanized coastal areas.

RevDate: 2018-11-15

Patricola CM, MF Wehner (2018)

Anthropogenic influences on major tropical cyclone events.

Nature, 563(7731):339-346.

There is no consensus on whether climate change has yet affected the statistics of tropical cyclones, owing to their large natural variability and the limited period of consistent observations. In addition, projections of future tropical cyclone activity are uncertain, because they often rely on coarse-resolution climate models that parameterize convection and hence have difficulty in directly representing tropical cyclones. Here we used convection-permitting regional climate model simulations to investigate whether and how recent destructive tropical cyclones would change if these events had occurred in pre-industrial and in future climates. We found that, relative to pre-industrial conditions, climate change so far has enhanced the average and extreme rainfall of hurricanes Katrina, Irma and Maria, but did not change tropical cyclone wind-speed intensity. In addition, future anthropogenic warming would robustly increase the wind speed and rainfall of 11 of 13 intense tropical cyclones (of 15 events sampled globally). Additional regional climate model simulations suggest that convective parameterization introduces minimal uncertainty into the sign of projected changes in tropical cyclone intensity and rainfall, which allows us to have confidence in projections from global models with parameterized convection and resolution fine enough to include tropical cyclones.

RevDate: 2018-11-15

Cai C, Wiens DA, Shen W, et al (2018)

Water input into the Mariana subduction zone estimated from ocean-bottom seismic data.

Nature, 563(7731):389-392.

The water cycle at subduction zones remains poorly understood, although subduction is the only mechanism for water transport deep into Earth. Previous estimates of water flux1-3 exhibit large variations in the amount of water that is subducted deeper than 100 kilometres. The main source of uncertainty in these calculations is the initial water content of the subducting uppermost mantle. Previous active-source seismic studies suggest that the subducting slab may be pervasively hydrated in the plate-bending region near the oceanic trench4-7. However, these studies do not constrain the depth extent of hydration and most investigate young incoming plates, leaving subduction-zone water budgets for old subducting plates uncertain. Here we present seismic images of the crust and uppermost mantle around the central Mariana trench derived from Rayleigh-wave analysis of broadband ocean-bottom seismic data. These images show that the low mantle velocities that result from mantle hydration extend roughly 24 kilometres beneath the Moho discontinuity. Combined with estimates of subducting crustal water, these results indicate that at least 4.3 times more water subducts than previously calculated for this region3. If other old, cold subducting slabs contain correspondingly thick layers of hydrous mantle, as suggested by the similarity of incoming plate faulting across old, cold subducting slabs, then estimates of the global water flux into the mantle at depths greater than 100 kilometres must be increased by a factor of about three compared to previous estimates3. Because a long-term net influx of water to the deep interior of Earth is inconsistent with the geological record8, estimates of water expelled at volcanic arcs and backarc basins probably also need to be revised upwards9.

RevDate: 2018-11-15

Vento-Tormo R, Efremova M, Botting RA, et al (2018)

Single-cell reconstruction of the early maternal-fetal interface in humans.

Nature, 563(7731):347-353.

During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and communicate with maternal cells. Trophoblast-decidual interactions underlie common diseases of pregnancy, including pre-eclampsia and stillbirth. Here we profile the transcriptomes of about 70,000 single cells from first-trimester placentas with matched maternal blood and decidual cells. The cellular composition of human decidua reveals subsets of perivascular and stromal cells that are located in distinct decidual layers. There are three major subsets of decidual natural killer cells that have distinctive immunomodulatory and chemokine profiles. We develop a repository of ligand-receptor complexes and a statistical tool to predict the cell-type specificity of cell-cell communication via these molecular interactions. Our data identify many regulatory interactions that prevent harmful innate or adaptive immune responses in this environment. Our single-cell atlas of the maternal-fetal interface reveals the cellular organization of the decidua and placenta, and the interactions that are critical for placentation and reproductive success.

RevDate: 2018-11-15

Samant RS, Livingston CM, Sontag EM, et al (2018)

Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control.

Nature, 563(7731):407-411.

Protein misfolding is linked to a wide array of human disorders, including Alzheimer's disease, Parkinson's disease and type II diabetes1,2. Protective cellular protein quality control (PQC) mechanisms have evolved to selectively recognize misfolded proteins and limit their toxic effects3-9, thus contributing to the maintenance of the proteome (proteostasis). Here we examine how molecular chaperones and the ubiquitin-proteasome system cooperate to recognize and promote the clearance of soluble misfolded proteins. Using a panel of PQC substrates with distinct characteristics and localizations, we define distinct chaperone and ubiquitination circuitries that execute quality control in the cytoplasm and nucleus. In the cytoplasm, proteasomal degradation of misfolded proteins requires tagging with mixed lysine 48 (K48)- and lysine 11 (K11)-linked ubiquitin chains. A distinct combination of E3 ubiquitin ligases and specific chaperones is required to achieve each type of linkage-specific ubiquitination. In the nucleus, however, proteasomal degradation of misfolded proteins requires only K48-linked ubiquitin chains, and is thus independent of K11-specific ligases and chaperones. The distinct ubiquitin codes for nuclear and cytoplasmic PQC appear to be linked to the function of the ubiquilin protein Dsk2, which is specifically required to clear nuclear misfolded proteins. Our work defines the principles of cytoplasmic and nuclear PQC as distinct, involving combinatorial recognition by defined sets of cooperating chaperones and E3 ligases. A better understanding of how these organelle-specific PQC requirements implement proteome integrity has implications for our understanding of diseases linked to impaired protein clearance and proteostasis dysfunction.

RevDate: 2018-11-15

Thume K, Gebser B, Chen L, et al (2018)

The metabolite dimethylsulfoxonium propionate extends the marine organosulfur cycle.

Nature, 563(7731):412-415.

Algae produce massive amounts of dimethylsulfoniopropionate (DMSP), which fuel the organosulfur cycle1,2. On a global scale, several petagrams of this sulfur species are produced annually, thereby driving fundamental processes and the marine food web1. An important DMSP transformation product is dimethylsulfide, which can be either emitted to the atmosphere3,4 or oxidized to dimethylsulfoxide (DMSO) and other products5. Here we report the discovery of a structurally unusual metabolite, dimethylsulfoxonium propionate (DMSOP), that is synthesized by several DMSP-producing microalgae and marine bacteria. As with DMSP, DMSOP is a low-molecular-weight zwitterionic metabolite that carries both a positively and a negatively charged functional group. Isotope labelling studies demonstrate that DMSOP is produced from DMSP, and is readily metabolized to DMSO by marine bacteria. DMSOP was found in near nanomolar amounts in field samples and in algal culture media, and thus represents-to our knowledge-a previously undescribed biogenic source for DMSO in the marine environment. The estimated annual oceanic production of oxidized sulfur from this pathway is in the teragram range, similar to the calculated dimethylsulfide flux to the atmosphere3. This sulfoxonium metabolite is therefore a key metabolite of a previously undescribed pathway in the marine sulfur cycle. These findings highlight the importance of DMSOP in the marine organosulfur cycle.

RevDate: 2018-11-15

Srinivas V, Lebrette H, Lundin D, et al (2018)

Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens.

Nature, 563(7731):416-420.

Ribonucleotide reductase (RNR) catalyses the only known de novo pathway for the production of all four deoxyribonucleotides that are required for DNA synthesis1,2. It is essential for all organisms that use DNA as their genetic material and is a current drug target3,4. Since the discovery that iron is required for function in the aerobic, class I RNR found in all eukaryotes and many bacteria, a dinuclear metal site has been viewed as necessary to generate and stabilize the catalytic radical that is essential for RNR activity5-7. Here we describe a group of RNR proteins in Mollicutes-including Mycoplasma pathogens-that possess a metal-independent stable radical residing on a modified tyrosyl residue. Structural, biochemical and spectroscopic characterization reveal a stable 3,4-dihydroxyphenylalanine (DOPA) radical species that directly supports ribonucleotide reduction in vitro and in vivo. This observation overturns the presumed requirement for a dinuclear metal site in aerobic ribonucleotide reductase. The metal-independent radical requires new mechanisms for radical generation and stabilization, processes that are targeted by RNR inhibitors. It is possible that this RNR variant provides an advantage under metal starvation induced by the immune system. Organisms that encode this type of RNR-some of which are developing resistance to antibiotics-are involved in diseases of the respiratory, urinary and genital tracts. Further characterization of this RNR family and its mechanism of cofactor generation will provide insight into new enzymatic chemistry and be of value in devising strategies to combat the pathogens that utilize it. We propose that this RNR subclass is denoted class Ie.

RevDate: 2018-11-15

Goban A, Hutson RB, Marti GE, et al (2018)

Emergence of multi-body interactions in a fermionic lattice clock.

Nature, 563(7731):369-373.

Alkaline-earth atoms have metastable 'clock' states with minute-long optical lifetimes, high-spin nuclei and SU(N)-symmetric interactions, making them powerful platforms for atomic clocks1, quantum information processing2 and quantum simulation3. Few-particle systems of such atoms provide opportunities to observe the emergence of complex many-body phenomena with increasing system size4. Multi-body interactions among particles are emergent phenomena, which cannot be broken down into sums over underlying pairwise interactions. They could potentially be used to create exotic states of quantum matter5,6, but have yet to be explored in ultracold fermions. Here we create arrays of isolated few-body systems in an optical clock based on a three-dimensional lattice of fermionic 87Sr atoms. We use high-resolution clock spectroscopy to directly observe the onset of elastic and inelastic multi-body interactions among atoms. We measure the frequency shifts of the clock transition for varying numbers of atoms per lattice site, from n = 1 to n = 5, and observe nonlinear interaction shifts characteristic of elastic multi-body effects. These measurements, combined with theory, elucidate an emergence of SU(N)-symmetric multi-body interactions, which are unique to fermionic alkaline-earth atoms. To study inelastic multi-body effects, we use these frequency shifts to isolate n-occupied sites in the lattice and measure the corresponding lifetimes of the clock states. This allows us to access the short-range few-body physics without experiencing the systematic effects that are encountered in a bulk gas. The lifetimes that we measure in the isolated few-body systems agree very well with numerical predictions based on a simple model for the interatomic potential, suggesting a universality in ultracold collisions. By connecting these few-body systems through tunnelling, the favourable energy and timescales of the interactions will allow our system to be used for studies of high-spin quantum magnetism7,8 and the Kondo effect3,9.

RevDate: 2018-11-15

Hepting M, Chaix L, Huang EW, et al (2018)

Three-dimensional collective charge excitations in electron-doped copper oxide superconductors.

Nature, 563(7731):374-378.

High-temperature copper oxide superconductors consist of stacked CuO2 planes, with electronic band structures and magnetic excitations that are primarily two-dimensional1,2, but with superconducting coherence that is three-dimensional. This dichotomy highlights the importance of out-of-plane charge dynamics, which has been found to be incoherent in the normal state3,4 within the limited range of momenta accessible by optics. Here we use resonant inelastic X-ray scattering to explore the charge dynamics across all three dimensions of the Brillouin zone. Polarization analysis of recently discovered collective excitations (modes) in electron-doped copper oxides5-7 reveals their charge origin, that is, without mixing with magnetic components5-7. The excitations disperse along both the in-plane and out-of-plane directions, revealing its three-dimensional nature. The periodicity of the out-of-plane dispersion corresponds to the distance between neighbouring CuO2 planes rather than to the crystallographic c-axis lattice constant, suggesting that the interplane Coulomb interaction is responsible for the coherent out-of-plane charge dynamics. The observed properties are hallmarks of the long-sought 'acoustic plasmon', which is a branch of distinct charge collective modes predicted for layered systems8-12 and argued to play a substantial part in mediating high-temperature superconductivity10-12.

RevDate: 2018-11-15

Snyder BER, Bols ML, Rhoda HM, et al (2018)

Mechanism of selective benzene hydroxylation catalyzed by iron-containing zeolites.

Proceedings of the National Academy of Sciences of the United States of America pii:1813849115 [Epub ahead of print].

A direct, catalytic conversion of benzene to phenol would have wide-reaching economic impacts. Fe zeolites exhibit a remarkable combination of high activity and selectivity in this conversion, leading to their past implementation at the pilot plant level. There were, however, issues related to catalyst deactivation for this process. Mechanistic insight could resolve these issues, and also provide a blueprint for achieving high performance in selective oxidation catalysis. Recently, we demonstrated that the active site of selective hydrocarbon oxidation in Fe zeolites, named α-O, is an unusually reactive Fe(IV)=O species. Here, we apply advanced spectroscopic techniques to determine that the reaction of this Fe(IV)=O intermediate with benzene in fact regenerates the reduced Fe(II) active site, enabling catalytic turnover. At the same time, a small fraction of Fe(III)-phenolate poisoned active sites form, defining a mechanism for catalyst deactivation. Density-functional theory calculations provide further insight into the experimentally defined mechanism. The extreme reactivity of α-O significantly tunes down (eliminates) the rate-limiting barrier for aromatic hydroxylation, leading to a diffusion-limited reaction coordinate. This favors hydroxylation of the rapidly diffusing benzene substrate over the slowly diffusing (but more reactive) oxygenated product, thereby enhancing selectivity. This defines a mechanism to simultaneously attain high activity (conversion) and selectivity, enabling the efficient oxidative upgrading of inert hydrocarbon substrates.

RevDate: 2018-11-15

Hou J, Shi X, Chen C, et al (2018)

Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa.

Proceedings of the National Academy of Sciences of the United States of America pii:1807796115 [Epub ahead of print].

Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids, triploids, and tetraploids of Arabidopsis thaliana was studied. The trisomies displayed a greater spread of expression modulation than the ploidy series. In general, expression of genes on the varied chromosome ranged from compensation to dosage effect, whereas genes from the remainder of the genome ranged from no effect to reduced expression approaching the inverse level of chromosomal imbalance (2/3). Genome-wide DNA methylation was examined in each genotype and found to shift most prominently with trisomy 4 but otherwise exhibited little change, indicating that genetic imbalance is generally mechanistically unrelated to DNA methylation. Independent analysis of gene functional classes demonstrated that ribosomal, proteasomal, and gene body methylated genes were less modulated compared with all classes of genes, whereas transcription factors, signal transduction components, and organelle-targeted protein genes were more tightly inversely affected. Comparing transcription factors and their targets in the trisomies and in expression networks revealed considerable discordance, illustrating that altered regulatory stoichiometry is a major contributor to genetic imbalance. Reanalysis of published data on gene expression in disomic yeast and trisomic mouse cells detected similar stoichiometric effects across broad phylogenetic taxa, and indicated that these effects reflect normal gene regulatory processes.

RevDate: 2018-11-15

Ando H, Hirose M, K Mikoshiba (2018)

Aberrant IP3 receptor activities revealed by comprehensive analysis of pathological mutations causing spinocerebellar ataxia 29.

Proceedings of the National Academy of Sciences of the United States of America pii:1811129115 [Epub ahead of print].

Spinocerebellar ataxia type 29 (SCA29) is autosomal dominant congenital ataxia characterized by early-onset motor delay, hypotonia, and gait ataxia. Recently, heterozygous missense mutations in an intracellular Ca2+ channel, inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1), were identified as a cause of SCA29. However, the functional impacts of these mutations remain largely unknown. Here, we determined the molecular mechanisms by which pathological mutations affect IP3R1 activity and Ca2+ dynamics. Ca2+ imaging using IP3R-null HeLa cells generated by genome editing revealed that all SCA29 mutations identified within or near the IP3-binding domain of IP3R1 completely abolished channel activity. Among these mutations, R241K, T267M, T267R, R269G, R269W, S277I, K279E, A280D, and E497K impaired IP3 binding to IP3R1, whereas the T579I and N587D mutations disrupted channel activity without affecting IP3 binding, suggesting that T579I and N587D compromise channel gating mechanisms. Carbonic anhydrase-related protein VIII (CA8) is an IP3R1-regulating protein abundantly expressed in cerebellar Purkinje cells and is a causative gene of congenital ataxia. The SCA29 mutation V1538M within the CA8-binding site of IP3R1 completely eliminated its interaction with CA8 and CA8-mediated IP3R1 inhibition. Furthermore, pathological mutations in CA8 decreased CA8-mediated suppression of IP3R1 by reducing protein stability and the interaction with IP3R1. These results demonstrated the mechanisms by which pathological mutations cause IP3R1 dysfunction, i.e., the disruption of IP3 binding, IP3-mediated gating, and regulation via the IP3R-modulatory protein. The resulting aberrant Ca2+ homeostasis may contribute to the pathogenesis of cerebellar ataxia.

RevDate: 2018-11-15

Barth A, Hendrix J, Fried D, et al (2018)

Dynamic interactions of type I cohesin modules fine-tune the structure of the cellulosome of Clostridium thermocellum.

Proceedings of the National Academy of Sciences of the United States of America pii:1809283115 [Epub ahead of print].

Efficient degradation of plant cell walls by selected anaerobic bacteria is performed by large extracellular multienzyme complexes termed cellulosomes. The spatial arrangement within the cellulosome is organized by a protein called scaffoldin, which recruits the cellulolytic subunits through interactions between cohesin modules on the scaffoldin and dockerin modules on the enzymes. Although many structural studies of the individual components of cellulosomal scaffoldins have been performed, the role of interactions between individual cohesin modules and the flexible linker regions between them are still not entirely understood. Here, we report single-molecule measurements using FRET to study the conformational dynamics of a bimodular cohesin segment of the scaffoldin protein CipA of Clostridium thermocellum We observe compacted structures in solution that persist on the timescale of milliseconds. The compacted conformation is found to be in dynamic equilibrium with an extended state that shows distance fluctuations on the microsecond timescale. Shortening of the intercohesin linker does not destabilize the interactions but reduces the rate of contact formation. Upon addition of dockerin-containing enzymes, an extension of the flexible state is observed, but the cohesin-cohesin interactions persist. Using all-atom molecular-dynamics simulations of the system, we further identify possible intercohesin binding modes. Beyond the view of scaffoldin as "beads on a string," we propose that cohesin-cohesin interactions are an important factor for the precise spatial arrangement of the enzymatic subunits in the cellulosome that leads to the high catalytic synergy in these assemblies and should be considered when designing cellulosomes for industrial applications.

RevDate: 2018-11-15

Kim JS, Liu L, Fitzsimmons LF, et al (2018)

DksA-DnaJ redox interactions provide a signal for the activation of bacterial RNA polymerase.

Proceedings of the National Academy of Sciences of the United States of America pii:1813572115 [Epub ahead of print].

RNA polymerase is the only known protein partner of the transcriptional regulator DksA. Herein, we demonstrate that the chaperone DnaJ establishes direct, redox-based interactions with oxidized DksA. Cysteine residues in the zinc finger of DksA become oxidized in Salmonella exposed to low concentrations of hydrogen peroxide (H2O2). The resulting disulfide bonds unfold the globular domain of DksA, signaling high-affinity interaction of the C-terminal α-helix to DnaJ. Oxidoreductase and chaperone activities of DnaJ reduce the disulfide bonds of its client and promote productive interactions between DksA and RNA polymerase. Simultaneously, guanosine tetraphosphate (ppGpp), which is synthesized by RelA in response to low concentrations of H2O2, binds at site 2 formed at the interface of DksA and RNA polymerase and synergizes with the DksA/DnaJ redox couple, thus activating the transcription of genes involved in amino acid biosynthesis and transport. However, the high concentrations of ppGpp produced by Salmonella experiencing oxidative stress oppose DksA/DnaJ-dependent transcription. Cumulatively, the interplay of DksA, DnaJ, and ppGpp on RNA polymerase protects Salmonella from the antimicrobial activity of the NADPH phagocyte oxidase. Our research has identified redox-based signaling that activates the transcriptional activity of the RNA polymerase regulator DksA.

RevDate: 2018-11-15

Yang K, Park D, Tretyakova NY, et al (2018)

Histone tails decrease N7-methyl-2'-deoxyguanosine depurination and yield DNA-protein cross-links in nucleosome core particles and cells.

Proceedings of the National Academy of Sciences of the United States of America pii:1813338115 [Epub ahead of print].

Monofunctional alkylating agents preferentially react at the N7 position of 2'-deoxyguanosine in duplex DNA. Methylated DNA, such as that produced by methyl methanesulfonate (MMS) and temozolomide, exists for days in organisms. The predominant consequence of N7-methyl-2'-deoxyguanosine (MdG) is widely believed to be abasic site (AP) formation via hydrolysis, a process that is slow in free DNA. Examination of MdG reactivity within nucleosome core particles (NCPs) provided two general observations. MdG depurination rate constants are reduced in NCPs compared with when the identical DNA sequence is free in solution. The magnitude of the decrease correlates with proximity to the positively charged histone tails, and experiments in NCPs containing histone variants reveal that positively charged amino acids are responsible for the decreased rate of abasic site formation from MdG. In addition, the lysine-rich histone tails form DNA-protein cross-links (DPCs) with MdG. Cross-link formation is reversible and is ascribed to nucleophilic attack at the C8 position of MdG. DPC and retarded abasic site formation are observed in NCPs randomly damaged by MMS, indicating that these are general processes. Histone-MdG cross-links were also detected by mass spectrometry in chromatin isolated from V79 Chinese hamster lung cells treated with MMS. The formation of DPCs following damage by a monofunctional alkylating agent has not been reported previously. These observations reveal the possibility that such DPCs may contribute to the cytotoxicity of monofunctional alkylating agents, such as MMS, N-methyl-N-nitrosourea, and temozolomide.

RevDate: 2018-11-15

Smith KL, Ruhl HA, Huffard CL, et al (2018)

Episodic organic carbon fluxes from surface ocean to abyssal depths during long-term monitoring in NE Pacific.

Proceedings of the National Academy of Sciences of the United States of America pii:1814559115 [Epub ahead of print].

Growing evidence suggests substantial quantities of particulate organic carbon (POC) produced in surface waters reach abyssal depths within days during episodic flux events. A 29-year record of in situ observations was used to examine episodic peaks in POC fluxes and sediment community oxygen consumption (SCOC) at Station M (NE Pacific, 4,000-m depth). From 1989 to 2017, 19% of POC flux at 3,400 m arrived during high-magnitude episodic events (≥mean + 2 σ), and 43% from 2011 to 2017. From 2011 to 2017, when high-resolution SCOC data were available, time lags between changes in satellite-estimated export flux (EF), POC flux, and SCOC on the sea floor varied between six flux events from 0 to 70 days, suggesting variable remineralization rates and/or particle sinking speeds. Half of POC flux pulse events correlated with prior increases in EF and/or subsequent SCOC increases. Peaks in EF overlying Station M frequently translated to changes in POC flux at abyssal depths. A power-law model (Martin curve) was used to estimate abyssal fluxes from EF and midwater temperature variation. While the background POC flux at 3,400-m depth was described well by the model, the episodic events were significantly underestimated by ∼80% and total flux by almost 50%. Quantifying episodic pulses of organic carbon into the deep sea is critical in modeling the depth and intensity of POC sequestration and understanding the global carbon cycle.

RevDate: 2018-11-15

Krause MD, Huang RT, Wu D, et al (2018)

Genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics.

Proceedings of the National Academy of Sciences of the United States of America pii:1810568115 [Epub ahead of print].

Biomechanical cues dynamically control major cellular processes, but whether genetic variants actively participate in mechanosensing mechanisms remains unexplored. Vascular homeostasis is tightly regulated by hemodynamics. Exposure to disturbed blood flow at arterial sites of branching and bifurcation causes constitutive activation of vascular endothelium contributing to atherosclerosis, the major cause of coronary artery disease (CAD) and ischemic stroke (IS). Conversely, unidirectional flow promotes quiescent endothelium. Genome-wide association studies (GWAS) have identified chromosome 1p32.2 as strongly associated with CAD/IS; however, the causal mechanism related to this locus remains unknown. Using statistical analyses, assay of transposase accessible chromatin with whole-genome sequencing (ATAC-seq), H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs), our results demonstrate that rs17114036, a common noncoding polymorphism at 1p32.2, is located in an endothelial enhancer dynamically regulated by hemodynamics. CRISPR-Cas9-based genome editing shows that rs17114036-containing region promotes endothelial quiescence under unidirectional shear stress by regulating phospholipid phosphatase 3 (PLPP3). Chromatin accessibility quantitative trait locus (caQTL) mapping using HAECs from 56 donors, allelic imbalance assay from 7 donors, and luciferase assays demonstrate that CAD/IS-protective allele at rs17114036 in PLPP3 intron 5 confers increased endothelial enhancer activity. ChIP-PCR and luciferase assays show that CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. These results demonstrate that a human SNP contributes to critical endothelial mechanotransduction mechanisms and suggest that human haplotypes and related cis-regulatory elements provide a previously unappreciated layer of regulatory control in cellular mechanosensing mechanisms.

RevDate: 2018-11-15

Cartella A, Nova TF, Fechner M, et al (2018)

Parametric amplification of optical phonons.

Proceedings of the National Academy of Sciences of the United States of America pii:1809725115 [Epub ahead of print].

We use coherent midinfrared optical pulses to resonantly excite large-amplitude oscillations of the Si-C stretching mode in silicon carbide. When probing the sample with a second pulse, we observe parametric optical gain at all wavelengths throughout the reststrahlen band. This effect reflects the amplification of light by phonon-mediated four-wave mixing and, by extension, of optical-phonon fluctuations. Density functional theory calculations clarify aspects of the microscopic mechanism for this phenomenon. The high-frequency dielectric permittivity and the phonon oscillator strength depend quadratically on the lattice coordinate; they oscillate at twice the frequency of the optical field and provide a parametric drive for the lattice mode. Parametric gain in phononic four-wave mixing is a generic mechanism that can be extended to all polar modes of solids, as a means to control the kinetics of phase transitions, to amplify many-body interactions or to control phonon-polariton waves.

RevDate: 2018-11-15

Bigi R, Landis JT, An H, et al (2018)

Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus.

Proceedings of the National Academy of Sciences of the United States of America pii:1810128115 [Epub ahead of print].

Primary effusion lymphoma (PEL) is a B cell lymphoma that is always associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and in many cases also with Epstein-Barr virus (EBV); however, the requirement for EBV coinfection is not clear. Here, we demonstrate that adding exogenous EBV to KSHV+ single-positive PEL leads to increased KSHV genome maintenance and KSHV latency-associated nuclear antigen (LANA) expression. To show that EBV was necessary for naturally coinfected PEL, we nucleofected KSHV+/EBV+ PEL cell lines with an EBV-specific CRISPR/Cas9 plasmid to delete EBV and observed a dramatic decrease in cell viability, KSHV genome copy number, and LANA expression. This phenotype was reversed by expressing Epstein-Barr nuclear antigen 1 (EBNA-1) in trans, even though EBNA-1 and LANA do not colocalize in infected cells. This work reveals that EBV EBNA-1 plays an essential role in the pathogenesis of PEL by increasing KSHV viral load and LANA expression.

RevDate: 2018-11-15

Tseng WC, Pryde DC, Yoger KE, et al (2018)

TRPA1 ankyrin repeat six interacts with a small molecule inhibitor chemotype.

Proceedings of the National Academy of Sciences of the United States of America pii:1808142115 [Epub ahead of print].

TRPA1, a member of the transient receptor potential channel (TRP) family, is genetically linked to pain in humans, and small molecule inhibitors are efficacious in preclinical animal models of inflammatory pain. These findings have driven significant interest in development of selective TRPA1 inhibitors as potential analgesics. The majority of TRPA1 inhibitors characterized to date have been reported to interact with the S5 transmembrane helices forming part of the pore region of the channel. However, the development of many of these inhibitors as clinical drug candidates has been prevented by high lipophilicity, low solubility, and poor pharmacokinetic profiles. Identification of alternate compound interacting sites on TRPA1 provides the opportunity to develop structurally distinct modulators with novel structure-activity relationships and more desirable physiochemical properties. In this paper, we have identified a previously undescribed potent and selective small molecule thiadiazole structural class of TRPA1 inhibitor. Using species ortholog chimeric and mutagenesis strategies, we narrowed down the site of interaction to ankyrinR #6 within the distal N-terminal region of TRPA1. To identify the individual amino acid residues involved, we generated a computational model of the ankyrinR domain. This model was used predictively to identify three critical amino acids in human TRPA1, G238, N249, and K270, which were confirmed by mutagenesis to account for compound activity. These findings establish a small molecule interaction region on TRPA1, expanding potential avenues for developing TRPA1 inhibitor analgesics and for probing the mechanism of channel gating.

RevDate: 2018-11-15

Castaño C, Kalko S, Novials A, et al (2018)

Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice.

Proceedings of the National Academy of Sciences of the United States of America pii:1808855115 [Epub ahead of print].

Obesity is frequently associated with metabolic disease. Here, we show that obesity changes the miRNA profile of plasma exosomes in mice, including increases in miR-122, miR-192, miR-27a-3p, and miR-27b-3p Importantly, treatment of lean mice with exosomes isolated from obese mice induces glucose intolerance and insulin resistance. Moreover, administration of control exosomes transfected with obesity-associated miRNA mimics strongly induces glucose intolerance in lean mice and results in central obesity and hepatic steatosis. Expression of the candidate target gene Ppara is decreased in white adipose tissue but not in the liver of mimic-treated (MIMIC) mice, and this is accompanied by increased circulating free fatty acids and hypertriglyceridemia. Treatment with a specific siRNA targeting Ppara transfected into exosomes recapitulates the phenotype induced by obesity-associated miRNAs. Importantly, simultaneously reducing free fatty acid plasma levels in MIMIC mice with either the lipolysis inhibitor acipimox or the PPARα agonist fenofibrate partially protects against these metabolic alterations. Overall, our data highlight the central role of obesity-associated exosomal miRNAs in the etiopathogeny of glucose intolerance and dyslipidemia.

RevDate: 2018-11-15

Oishi H, Takemura H, Aoki SC, et al (2018)

Microstructural properties of the vertical occipital fasciculus explain the variability in human stereoacuity.

Proceedings of the National Academy of Sciences of the United States of America pii:1804741115 [Epub ahead of print].

Stereopsis is a fundamental visual function that has been studied extensively. However, it is not clear why depth discrimination (stereoacuity) varies more significantly among people than other modalities. Previous studies have reported the involvement of both dorsal and ventral visual areas in stereopsis, implying that not only neural computations in cortical areas but also the anatomical properties of white matter tracts connecting those areas can impact stereopsis. Here, we studied how human stereoacuity relates to white matter properties by combining psychophysics, diffusion MRI (dMRI), and quantitative MRI (qMRI). We performed a psychophysical experiment to measure stereoacuity and, in the same participants, we analyzed the microstructural properties of visual white matter tracts on the basis of two independent measurements, dMRI (fractional anisotropy, FA) and qMRI (macromolecular tissue volume; MTV). Microstructural properties along the right vertical occipital fasciculus (VOF), a major tract connecting dorsal and ventral visual areas, were highly correlated with measures of stereoacuity. This result was consistent for both FA and MTV, suggesting that the behavioral-structural relationship reflects differences in neural tissue density, rather than differences in the morphological configuration of fibers. fMRI confirmed that binocular disparity stimuli activated the dorsal and ventral visual regions near VOF endpoints. No other occipital tracts explained the variance in stereoacuity. In addition, the VOF properties were not associated with differences in performance on a different psychophysical task (contrast detection). These series of experiments suggest that stereoscopic depth discrimination performance is, at least in part, constrained by dorso-ventral communication through the VOF.

RevDate: 2018-11-15

Hilbe C, Schmid L, Tkadlec J, et al (2018)

Indirect reciprocity with private, noisy, and incomplete information.

Proceedings of the National Academy of Sciences of the United States of America pii:1810565115 [Epub ahead of print].

Indirect reciprocity is a mechanism for cooperation based on shared moral systems and individual reputations. It assumes that members of a community routinely observe and assess each other and that they use this information to decide who is good or bad, and who deserves cooperation. When information is transmitted publicly, such that all community members agree on each other's reputation, previous research has highlighted eight crucial moral systems. These "leading-eight" strategies can maintain cooperation and resist invasion by defectors. However, in real populations individuals often hold their own private views of others. Once two individuals disagree about their opinion of some third party, they may also see its subsequent actions in a different light. Their opinions may further diverge over time. Herein, we explore indirect reciprocity when information transmission is private and noisy. We find that in the presence of perception errors, most leading-eight strategies cease to be stable. Even if a leading-eight strategy evolves, cooperation rates may drop considerably when errors are common. Our research highlights the role of reliable information and synchronized reputations to maintain stable moral systems.

RevDate: 2018-11-15

Sossin WS (2018)

"Fragile" equilibrium between translation and transcription.

Proceedings of the National Academy of Sciences of the United States of America pii:1817562115 [Epub ahead of print].

RevDate: 2018-11-15

Li B, Dou SX, Yuan JW, et al (2018)

Intracellular transport is accelerated in early apoptotic cells.

Proceedings of the National Academy of Sciences of the United States of America pii:1810017115 [Epub ahead of print].

Intracellular transport of cellular proteins and organelles is critical for establishing and maintaining intracellular organization and cell physiology. Apoptosis is a process of programmed cell death with dramatic changes in cell morphology and organization, during which signaling molecules are transported between different organelles within the cells. However, how the intracellular transport changes in cells undergoing apoptosis remains unknown. Here, we study the dynamics of intracellular transport by using the single-particle tracking method and find that both directed and diffusive motions of endocytic vesicles are accelerated in early apoptotic cells. With careful elimination of other factors involved in the intracellular transport, the reason for the acceleration is attributed to the elevation of adenosine triphosphate (ATP) concentration. More importantly, we show that the accelerated intracellular transport is critical for apoptosis, and apoptosis is delayed when the dynamics of intracellular transport is regulated back to the normal level. Our results demonstrate the important role of transport dynamics in apoptosis and shed light on the apoptosis mechanism from a physical perspective.

RevDate: 2018-11-15

Plikus MV, B Andersen (2018)

Skin as a window to body-clock time.

Proceedings of the National Academy of Sciences of the United States of America pii:1817419115 [Epub ahead of print].

RevDate: 2018-11-15

Karp AT, Behrensmeyer AK, KH Freeman (2018)

Grassland fire ecology has roots in the late Miocene.

Proceedings of the National Academy of Sciences of the United States of America pii:1809758115 [Epub ahead of print].

That fire facilitated the late Miocene C4 grassland expansion is widely suspected but poorly documented. Fire potentially tied global climate to this profound biosphere transition by serving as a regional-to-local driver of vegetation change. In modern environments, seasonal extremes in moisture amplify the occurrence of fire, disturbing forest ecosystems to create niche space for flammable grasses, which in turn provide fuel for frequent fires. On the Indian subcontinent, C4 expansion was accompanied by increased seasonal extremes in rainfall (evidenced by δ18Ocarbonate), which set the stage for fuel accumulation and fire-linked clearance during wet-to-dry seasonal transitions. Here, we test the role of fire directly by examining the abundance and distribution patterns of fire-derived polycyclic aromatic hydrocarbons (PAHs) and terrestrial vegetation signatures in n-alkane carbon isotopes from paleosol samples of the Siwalik Group (Pakistan). Two million years before the C4 grassland transition, fire-derived PAH concentrations increased as conifer vegetation declined, as indicated by a decrease in retene. This early increase in molecular fire signatures suggests a transition to more fire-prone vegetation such as a C3 grassland and/or dry deciduous woodland. Between 8.0 and 6.0 million years ago, fire, precipitation seasonality, and C4-grass dominance increased simultaneously (within resolution) as marked by sharp increases in fire-derived PAHs, δ18Ocarbonate, and 13C enrichment in n-alkanes diagnostic of C4 grasses. The strong association of evidence for fire occurrence, vegetation change, and landscape opening indicates that a dynamic fire-grassland feedback system was both a necessary precondition and a driver for grassland ecology during the first emergence of C4 grasslands.

RevDate: 2018-11-15

Willis IM, Moir RD, N Hernandez (2018)

Metabolic programming a lean phenotype by deregulation of RNA polymerase III.

Proceedings of the National Academy of Sciences of the United States of America pii:1815590115 [Epub ahead of print].

As a master negative regulator of RNA polymerase (Pol) III, Maf1 modulates transcription in response to nutrients and stress to balance the production of highly abundant tRNAs, 5S rRNA, and other small noncoding RNAs with cell growth and maintenance. This regulation of Pol III transcription is important for energetic economy as mice lacking Maf1 are lean and resist weight gain on normal and high fat diets. The lean phenotype of Maf1 knockout (KO) mice is attributed in part to metabolic inefficiencies which increase the demand for cellular energy and elevate catabolic processes, including autophagy/lipophagy and lipolysis. A futile RNA cycle involving increased synthesis and turnover of Pol III transcripts has been proposed as an important driver of these changes. Here, using targeted metabolomics, we find changes in the liver of fed and fasted Maf1 KO mice consistent with the function of mammalian Maf1 as a chronic Pol III repressor. Differences in long-chain acylcarnitine levels suggest that energy demand is higher in the fed state of Maf1 KO mice versus the fasted state. Quantitative metabolite profiling supports increased activity in the TCA cycle, the pentose phosphate pathway, and the urea cycle and reveals changes in nucleotide levels and the creatine system. Metabolite profiling also confirms key predictions of the futile RNA cycle hypothesis by identifying changes in many metabolites involved in nucleotide synthesis and turnover. Thus, constitutively high levels of Pol III transcription in Maf1 KO mice reprogram central metabolic pathways and waste metabolic energy through a futile RNA cycle.

RevDate: 2018-11-15

Chin AS, Worley KE, Ray P, et al (2018)

Epithelial Cell Chirality Revealed by Three-Dimensional Spontaneous Rotation.

Proceedings of the National Academy of Sciences of the United States of America pii:1805932115 [Epub ahead of print].

Our understanding of the left-right (LR) asymmetry of embryonic development, in particular the contribution of intrinsic handedness of the cell or cell chirality, is limited due to the confounding systematic and environmental factors during morphogenesis and a ack of physiologically relevant in vitro 3D platforms. Here we report an efficient two-layered biomaterial platform for determining the chirality of individual cells, cell aggregates, and self-organized hollow epithelial spheroids. This bioengineered niche provides a uniform defined axis allowing for cells to rotate spontaneously with a directional bias toward either clockwise or counterclockwise directions. Mechanistic studies reveal an actin-dependent, cell-intrinsic property of 3D chirality that can be mediated by actin cross-linking via α-actinin-1. Our findings suggest that the gradient of extracellular matrix is an important biophysicochemical cue influencing cell polarity and chirality. Engineered biomaterial systems can serve as an effective platform for studying developmental asymmetry and screening for environmental factors causing birth defects.

RevDate: 2018-11-15

Pineda JJ, Miller MA, Song Y, et al (2018)

Site occupancy calibration of taxane pharmacology in live cells and tissues.

Proceedings of the National Academy of Sciences of the United States of America pii:1800047115 [Epub ahead of print].

Drug receptor site occupancy is a central pharmacology parameter that quantitatively relates the biochemistry of drug binding to the biology of drug action. Taxanes and epothilones bind to overlapping sites in microtubules (MTs) and stabilize them. They are used to treat cancer and are under investigation for neurodegeneration. In cells, they cause concentration-dependent inhibition of MT dynamics and perturbation of mitosis, but the degree of site occupancy required to trigger different effects has not been measured. We report a live cell assay for taxane-site occupancy, and relationships between site occupancy and biological effects across four drugs and two cell lines. By normalizing to site occupancy, we were able to quantitatively compare drug activities and cell sensitivities independent of differences in drug affinity and uptake/efflux kinetics. Across all drugs and cells tested, we found that inhibition of MT dynamics, postmitotic micronucleation, and mitotic arrest required successively higher site occupancy. We also found interesting differences between cells and drugs, for example, insensitivity of the spindle assembly checkpoint to site occupancy. By extending our assay to a mouse xenograft tumor model, we estimated the initial site occupancy required for paclitaxel to completely prevent tumor growth as 80%. The most important cellular action of taxanes for cancer treatment may be formation of micronuclei, which occurs over a broad range of site occupancies.

RevDate: 2018-11-15

Conix S (2018)

Radical pluralism, classificatory norms and the legitimacy of species classifications.

Studies in history and philosophy of biological and biomedical sciences pii:S1369-8486(17)30168-1 [Epub ahead of print].

Moderate pluralism is a popular position in contemporary philosophy of biology. Despite its popularity, various authors have argued that it tends to slide off into a radical form of pluralism that is both normatively and descriptively unacceptable. This paper looks at the case of biological species classification, and evaluates a popular way of avoiding radical pluralism by relying on the shared aims and norms of a discipline. The main contention is that while these aims and norms may play an important role in the legitimacy of species classifications, they fail to fend off radical pluralism. It follows from this that the legitimacy of species classifications is also determined by local decisions about the aims of research and how to operationalize and balance these. This is important, I argue, because it means that any acceptable view on the legitimacy of classification should be able to account for these local decisions.

RevDate: 2018-11-15

Darré T, Saka B, Walla A, et al (2018)

Sexuality, sexually transmitted infections and contraception among health sciences students in university of Lomé, Togo.

BMC research notes, 11(1):808 pii:10.1186/s13104-018-3923-3.

OBJECTIVES: Evaluate the practice of sexuality, contraception and the risk of sexually transmitted infections among students in the Faculty of Health Sciences, University of Lomé, Togo.

RESULTS: Three hundred and sixteen (316) students were interviewed, with a response rate of 43.3%. The average age of students completing the form was 21.4 ± 2.7 years and their sex ratio was 2.2. Of this number of students who completed the form, 51.8% have already had sex. The mean age of first intercourse was 17.9 ± 3.2 years; 70.3% were heterosexual. Regarding the number of sexual partners, 48.5% of students had more than one partner, of whom 15.9% had at least 5 sexual partners. 21.5% of these students had only one sexual intercourse per month. Regarding contraception among students with the card, 67.5% of students used a method of contraception. Among those using contraceptives, it was a 55.3% condom, followed by the Ogino method at 14.1%. Some of our respondents used more than one method of contraception and 28.5% of respondents indicated that their partners used a method of contraception. For STIs, 10.8% of students completing the form were already infected. Gonorrhea was reported in 30.4% of cases, candidiasis in 26.1% of cases.

RevDate: 2018-11-15

Aguilar-Luis MA, Palacios-Cuervo F, Espinal-Reyes F, et al (2018)

Highly clarithromycin-resistant Helicobacter pylori infection in asymptomatic children from a rural community of Cajamarca-Peru.

BMC research notes, 11(1):809 pii:10.1186/s13104-018-3919-z.

OBJECTIVE: The objective of this study was to determine the prevalence of clarithromycin-resistant Helicobacter pylori in asymptomatic children in a rural community of Cajamarca (northern Peru).

RESULTS: Helicobacter pylori was detected in 17.2% (49/285) of the samples. Unboiled water consumption the most frequent associated factor in patients with positive PCR for H. pylori infection (93.9%). Clarithromycin resistant mutations were found in 79.6% (39/49) of the positive samples for H. pylori. The most frequent mutation was A2142G (46.9%), followed by the double-mutation A2142G-A2143G (28.6%).

RevDate: 2018-11-15

Arteaga-Tlecuitl R, Sanchez-Sandoval AL, Ramirez-Cordero BE, et al (2018)

Increase of CaV3 channel activity induced by HVA β1b-subunit is not mediated by a physical interaction.

BMC research notes, 11(1):810 pii:10.1186/s13104-018-3917-1.

OBJECTIVE: Low voltage-activated (LVA) calcium channels are crucial for regulating oscillatory behavior in several types of neurons and other excitable cells. LVA channels dysfunction has been implicated in epilepsy, neuropathic pain, cancer, among other diseases. Unlike for High Voltage-Activated (HVA) channels, voltage-dependence and kinetics of currents carried by recombinant LVA, i.e., CaV3 channels, are quite similar to those observed in native currents. Therefore, whether these channels are regulated by HVA auxiliary subunits, remain controversial. Here, we used the α1-subunits of CaV3.1, CaV3.2, and CaV3.3 channels, together with HVA auxiliary β-subunits to perform electrophysiological, confocal microscopy and immunoprecipitation experiments, in order to further explore this possibility.

RESULTS: Functional expression of CaV3 channels is up-regulated by all four β-subunits, although most consistent effects were observed with the β1b-subunit. The biophysical properties of CaV3 channels were not modified by any β-subunit. Furthermore, although β1b-subunits increased colocalization of GFP-tagged CaV3 channels and the plasma membrane of HEK-293 cells, western blots analysis revealed the absence of physical interaction between CaV3.3 and β1b-subunits as no co-immunoprecipitation was observed. These results provide solid evidence that the up-regulation of LVA channels in the presence of HVA-β1b subunit is not mediated by a high affinity interaction between both proteins.

RevDate: 2018-11-15

García-Angulo A, Merlo MA, Portela-Bens S, et al (2018)

Evidence for a Robertsonian fusion in Solea senegalensis (Kaup, 1858) revealed by zoo-FISH and comparative genome analysis.

BMC genomics, 19(1):818 pii:10.1186/s12864-018-5216-6.

BACKGROUND: Solea senegalensis (Kaup, 1858) is a commercially important flatfish species, belonging to the Pleuronectiformes order. The taxonomy of this group has long been controversial, and the karyotype of the order presents a high degree of variability in diploid number, derived from chromosomal rearrangements such as Robertsonian fusions. Previously it has been proposed that the large metacentric chromosome of S. senegalensis arises from this kind of chromosome rearrangement and that this is a proto-sex chromosome.

RESULTS: In this work, the Robertsonian origin of the large metacentric chromosome of S. senegalensis has been tested by the Zoo-FISH technique applied to two species of the Soleidae family (Dicologlossa cuneata and Dagetichthys lusitanica), and by comparative genome analysis with Cynoglossus semilaevis. From the karyotypic analysis we were able to determine a chromosome complement comprising 2n = 50 (FN = 54) in D. cuneata and 2n = 42 (FN = 50) in D. lusitanica. The large metacentric painting probe gave consistent signals in four acrocentric chromosomes of the two Soleidae species; and the genome analysis proved a common origin with four chromosome pairs of C. semilaevis. As a result of the genomic analysis, up to 61 genes were annotated within the thirteen Bacterial Artificial Chromosome clones analysed.

CONCLUSIONS: These results confirm that the large metacentric chromosome of S. senegalensis originated from a Robertsonian fusion and provide new data about the chromosome evolution of S. senegalensis in particular, and of Pleuronectiformes in general.

RevDate: 2018-11-15

Baccarella A, Williams CR, Parrish JZ, et al (2018)

Empirical assessment of the impact of sample number and read depth on RNA-Seq analysis workflow performance.

BMC bioinformatics, 19(1):423 pii:10.1186/s12859-018-2445-2.

BACKGROUND: RNA-Sequencing analysis methods are rapidly evolving, and the tool choice for each step of one common workflow, differential expression analysis, which includes read alignment, expression modeling, and differentially expressed gene identification, has a dramatic impact on performance characteristics. Although a number of workflows are emerging as high performers that are robust to diverse input types, the relative performance characteristics of these workflows when either read depth or sample number is limited-a common occurrence in real-world practice-remain unexplored.

RESULTS: Here, we evaluate the impact of varying read depth and sample number on the performance of differential gene expression identification workflows, as measured by precision, or the fraction of genes correctly identified as differentially expressed, and by recall, or the fraction of differentially expressed genes identified. We focus our analysis on 30 high-performing workflows, systematically varying the read depth and number of biological replicates of patient monocyte samples provided as input. We find that, in general for most workflows, read depth has little effect on workflow performance when held above two million reads per sample, with reduced workflow performance below this threshold. The greatest impact of decreased sample number is seen below seven samples per group, when more heterogeneity in workflow performance is observed. The choice of differential expression identification tool, in particular, has a large impact on the response to limited inputs.

CONCLUSIONS: Among the tested workflows, the recall/precision balance remains relatively stable at a range of read depths and sample numbers, although some workflows are more sensitive to input restriction. At ranges typically recommended for biological studies, performance is more greatly impacted by the number of biological replicates than by read depth. Caution should be used when selecting analysis workflows and interpreting results from low sample number experiments, as all workflows exhibit poorer performance at lower sample numbers near typically reported values, with variable impact on recall versus precision. These analyses highlight the performance characteristics of common differential gene expression workflows at varying read depths and sample numbers, and provide empirical guidance in experimental and analytical design.

RevDate: 2018-11-15

Ta KN, Khong NG, Ha TL, et al (2018)

A genome-wide association study using a Vietnamese landrace panel of rice (Oryza sativa) reveals new QTLs controlling panicle morphological traits.

BMC plant biology, 18(1):282 pii:10.1186/s12870-018-1504-1.

CONTEXT: Yield improvement is an important issue for rice breeding. Panicle architecture is one of the key components of rice yield and exhibits a large diversity. To identify the morphological and genetic determinants of panicle architecture, we performed a detailed phenotypic analysis and a genome-wide association study (GWAS) using an original panel of Vietnamese landraces.

RESULTS: Using a newly developed image analysis tool, morphological traits of the panicles were scored over two years: rachis length; primary, secondary and tertiary branch number; average length of primary and secondary branches; average length of internode on rachis and primary branch. We observed a high contribution of spikelet number and secondary branch number per panicle to the overall phenotypic diversity in the dataset. Twenty-nine stable QTLs associated with seven traits were detected through GWAS over the two years. Some of these QTLs were associated with genes already implicated in panicle development. Importantly, the present study revealed the existence of new QTLs associated with the spikelet number, secondary branch number and primary branch number traits.

CONCLUSIONS: Our phenotypic analysis of panicle architecture variation suggests that with the panel of samples used, morphological diversity depends largely on the balance between indeterminate vs. determinate axillary meristem fate on primary branches, supporting the notion of differences in axillary meristem fate between rachis and primary branches. Our genome-wide association study led to the identification of numerous genomic sites covering all the traits studied and will be of interest for breeding programs aimed at improving yield. The new QTLs detected in this study provide a basis for the identification of new genes controlling panicle development and yield in rice.

RevDate: 2018-11-15

Huang X, Cheng X, Sun P, et al (2018)

Characteristics of NDM-1-producing Klebsiella pneumoniae ST234 and ST1412 isolates spread in a neonatal unit.

BMC microbiology, 18(1):186 pii:10.1186/s12866-018-1334-1.

BACKGROUND: The emergence of carbapenem-resistant Klebsiella pneumoniae (CR-KP) has become a significant problem worldwide and also being a major threat to children and newborns. Here we report an outbreak of NDM-1-producing K. pneumoniae in a neonatal unit.

RESULTS: Six CR-KP strains, isolated from neonates with symptoms of infection, were identified using a VITEK-2 compact system, and the clinical data were retrieved from the electronic case records. In vitro susceptibility testing with broth dilution method showed that all six K. pneumoniae isolates were resistant to carbapenems and susceptible to colistin, aminoglycosides, fluoroquinolones and tigecycline. Based on the polymerase chain reaction results, each isolate was found to be blaNDM-1 gene positive. Clonal relationships were analysed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) and showed that two different PFGE patterns were formed, which belonged to sequence types ST234 and ST1412. Plasmids carrying blaNDM-1 were successfully transferred from four of the six isolates to an Escherichia coli recipient through conjugative assays. S1-PFGE and Southern blot hybridization showed that four NDM-1-producing K. pneumoniae were clonal and carried blaNDM-1 on the same plasmid. The outbreak was effectively controlled by reducing the potential infection sources. All the patients were successfully treated and recovered after receiving an increased dose of carbapenems. Although the source of this outbreak was not clear, comprehensive measures were carried out and the outbreak was effectively controlled.

CONCLUSIONS: ST234 and ST1412 of NDM-1-producing Klebsiella pneumoniae are the resistant clone spread in the neonatal unit, comprehensive infection control measures and optimized carbapenem therapy played an important role in controlling this NDM-1-producing K. pneumoniae outbreak.

RevDate: 2018-11-15

Kolberg L, Kuzmin I, Adler P, et al (2018)

funcExplorer: a tool for fast data-driven functional characterisation of high-throughput expression data.

BMC genomics, 19(1):817 pii:10.1186/s12864-018-5176-x.

BACKGROUND: A widely applied approach to extract knowledge from high-throughput genomic data is clustering of gene expression profiles followed by functional enrichment analysis. This type of analysis, when done manually, is highly subjective and has limited reproducibility. Moreover, this pipeline can be very time-consuming and resource-demanding as enrichment analysis is done for tens to hundreds of clusters at a time. Thus, the task often needs programming skills to form a pipeline of different software tools or R packages to enable an automated approach. Furthermore, visualising the results can be challenging.

RESULTS: We developed a web tool, funcExplorer, which automatically combines hierarchical clustering and enrichment analysis to detect functionally related gene clusters. The functional characterisation is achieved using structured knowledge from data sources such as Gene Ontology, KEGG and Reactome pathways, Human Protein Atlas, and Human Phenotype Ontology. funcExplorer includes various measures for finding biologically meaningful clusters, provides a modern graphical user interface, and has wide-ranging data export and sharing options as well as software transparency by open-source code. The results are presented in a visually compact and interactive format, enabling users to explore the biological essence of the data. We compared our results with previously published gene clusters to demonstrate that funcExplorer can perform the data characterisation equally well, but without requiring labour-intensive manual interference.

CONCLUSIONS: The open-source web tool funcExplorer enables scientists with high-throughput genomic data to obtain a preliminary interactive overview of the expression patterns, gene names, and shared functionalities in their dataset in a visually pleasing format. funcExplorer is publicly available at https://biit.cs.ut.ee/funcexplorer.

RevDate: 2018-11-15

Choo-Wosoba H, Albert PS, B Zhu (2018)

hsegHMM: hidden Markov model-based allele-specific copy number alteration analysis accounting for hypersegmentation.

BMC bioinformatics, 19(1):424 pii:10.1186/s12859-018-2412-y.

BACKGROUND: Somatic copy number alternation (SCNA) is a common feature of the cancer genome and is associated with cancer etiology and prognosis. The allele-specific SCNA analysis of a tumor sample aims to identify the allele-specific copy numbers of both alleles, adjusting for the ploidy and the tumor purity. Next generation sequencing platforms produce abundant read counts at the base-pair resolution across the exome or whole genome which is susceptible to hypersegmentation, a phenomenon where numerous regions with very short length are falsely identified as SCNA.

RESULTS: We propose hsegHMM, a hidden Markov model approach that accounts for hypersegmentation for allele-specific SCNA analysis. hsegHMM provides statistical inference of copy number profiles by using an efficient E-M algorithm procedure. Through simulation and application studies, we found that hsegHMM handles hypersegmentation effectively with a t-distribution as a part of the emission probability distribution structure and a carefully defined state space. We also compared hsegHMM with FACETS which is a current method for allele-specific SCNA analysis. For the application, we use a renal cell carcinoma sample from The Cancer Genome Atlas (TCGA) study.

CONCLUSIONS: We demonstrate the robustness of hsegHMM to hypersegmentation. Furthermore, hsegHMM provides the quantification of uncertainty in identifying allele-specific SCNAs over the entire chromosomes. hsegHMM performs better than FACETS when read depth (coverage) is uneven across the genome.

RevDate: 2018-11-15

Baig MA, Ahmad J, Bagheri R, et al (2018)

Proteomic and ecophysiological responses of soybean (Glycine max L.) root nodules to Pb and hg stress.

BMC plant biology, 18(1):283 pii:10.1186/s12870-018-1499-7.

BACKGROUND: Lead (Pb) and mercury (Hg) are persistent hazardous metals in industrially polluted soils which can be toxic in low quantities. Metal toxicity can cause changes at cellular and molecular level which should be studied for better understanding of tolerance mechanism in plants. Soybean (Glycine max L.) is an important oilseed crop of the world including India. Indian soils growing soybean are often contaminated by Pb and Hg. The aim of this study was to explore how soybean root nodule responds to Pb and Hg through proteomic and ecophysiological alterations in order to enhance tolerance to metal stress.

RESULTS: Soybean plants were exposed to Pb (30 ppm PbCl2) and Hg (0.5 ppm HgCl2) to study histological, histochemical, biochemical and molecular response of N2-fixing symbiotic nodules. Both Pb and Hg treatment increased the level of oxidative stress in leaves and nodules. Chlorosis in leaves and morphological/anatomical changes in nodules were observed. Activities of ascorbate peroxidase, glutathione reductase and catalase were also modulated. Significant changes were observed in abundance of 76 proteins by Pb and Hg. Pb and Hg influenced abundance of 33 proteins (17 up and 16 down) and 43 proteins (33 up and 10 down), respectively. MS/MS ion search identified 55 proteins which were functionally associated with numerous cellular functions. Six crucial proteins namely catalase (CAT), allene oxide synthase (AOS), glutathione S-transferase (GST), calcineurin B like (CBL), calmodulin like (CML) and rapid alkalinisation factor (RAF) were selected for transcript abundance estimation. The qRT-PCR based real time expression exhibited a positive correlation with proteomics expression except for GST and RAF.

CONCLUSION: Soybean root nodule responds to metal stress by increased abundance of defence, development and repair related proteins. An efficient proteomic modulation might lead to metal-induced stress tolerance in N2-fixing nodules. Although concentrations of Pb and Hg used in the study cannot be considered equimolar, yet Hg seems to induce more changes in nodule proteomic profile, and higher damage to both bacteroides and root anatomy.

RevDate: 2018-11-15

Mutai WC, Muigai AWT, Waiyaki P, et al (2018)

Multi-drug resistant Salmonella enterica serovar Typhi isolates with reduced susceptibility to ciprofloxacin in Kenya.

BMC microbiology, 18(1):187 pii:10.1186/s12866-018-1332-3.

BACKGROUND: Typhoid fever remains a public health concern in developing countries especially among the poor who live in informal settlements devoid of proper sanitation and clean water supply. In addition antimicrobial resistance poses a major challenge in management of the disease. This study assessed the antimicrobial susceptibility patterns of Salmonella enterica serotype Typhi (S. Typhi) isolated from typhoid fever cases (2004-2007).

METHODS: A cross sectional study was conducted on 144 archived S. Typhi isolates (2004-2007) tested against 11 antimicrobial agents by quality controlled disk diffusion technique. Isolates resistant to ampicillin, chloramphenicol, and cotrimoxazole were considered Multidrug resistant (MDR). Thirty MDR isolates were selected randomly and further tested using minimum inhibitory concentration (MIC) E-test.

RESULTS: Sixteen percent (23/144) of the isolates were susceptible to all the antibiotics tested while 68% were resistant to three or more of the 11 antibiotics tested. The isolates showed a high susceptibility to ceftriaxone (94%) and gentamicin (97%). A high percentage of resistance was observed for the conventional first-line antibiotics; ampicillin (72%), chloramphenicol (72%), and cotrimoxazole (70%). Sixty-nine percent of the isolates (100/144) showed reduced susceptibility to ciprofloxacin. All the 30 (100%) isolates selected for MIC test were susceptible to amoxicillin-clavulanic acid. All except one of the 30 isolates were susceptible to ceftriaxone while majority 21 (70%) recorded an intermediate susceptibility to ciprofloxacin with MIC of 0.12-0.5 μg/mL.

CONCLUSION: A large proportion of S. Typhi isolates were MDR and also showed reduced susceptibility to ciprofloxacin. Fluoroquinolone resistance is emerging and this may pose a challenge in treatment of typhoid in future. There is need for routine surveillance to monitor this phenotype in clinical settings.

RevDate: 2018-11-15

March E, Van Doorn G, R Grieve (2018)

Netflix and Chill? What Sex Differences Can Tell Us About Mate Preferences in (Hypothetical) Booty-Call Relationships.

Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior, 16(4):1474704918812138.

The booty-call relationship is defined by both sexual characteristics and emotional involvement. In the current study, men's and women's preferences for a booty-call mate were explored. Men and women were predicted to exhibit different mate preferences depending on whether they considered a booty-call relationship a short- or long-term relationship. Participants (N = 559, 74% women) completed an anonymous online questionnaire, designing their ideal booty-call mate using the mate dollars paradigm. Both sexes considered the physical attractiveness and kindness of a booty-call mate a necessity, expressing both short- and long-term mate preferences. The current study highlights the need to explore mate preferences outside the dichotomy of short- and long-term relationships, providing evidence of a compromise relationship.

RevDate: 2018-11-14

Mourad AMI, Sallam A, Belamkar V, et al (2018)

Genetic architecture of common bunt resistance in winter wheat using genome-wide association study.

BMC plant biology, 18(1):280 pii:10.1186/s12870-018-1435-x.

BACKGROUND: Common bunt (caused by Tilletia caries and T. foetida) has been considered as a major disease in wheat (Triticum aestivum) following rust (Puccinia spp.) in the Near East and is economically important in the Great Plains, USA. Despite the fact that it can be easily controlled using seed treatment with fungicides, fungicides often cannot or may not be used in organic and low-input fields. Planting common bunt resistant genotypes is an alternative.

RESULTS: To identify resistance genes for Nebraska common bunt race, the global set of differential lines were inoculated. Nine differential lines carrying nine different genes had 0% infected heads and seemed to be resistant to Nebraska race. To understand the genetic basis of the resistance in Nebraska winter wheat, a set of 330 genotypes were inoculated and evaluated under field conditions in two locations. Out of the 330 genotypes, 62 genotypes had different degrees of resistance. Moreover, plant height, chlorophyll content and days to heading were scored in both locations. Using genome-wide association study, 123 SNPs located on fourteen chromosomes were identified to be associated with the resistance. Different degrees of linkage disequilibrium was found among the significant SNPs and they explained 1.00 to 9.00% of the phenotypic variance, indicating the presence of many minor QTLs controlling the resistance.

CONCLUSION: Based on the chromosomal location of some of the known genes, some SNPs may be associated with Bt1, Bt6, Bt11 and Bt12 resistance loci. The remaining significant SNPs may be novel alleles that were not reported previously. Common bunt resistance seems to be an independent trait as no correlation was found between a number of infected heads and chlorophyll content, days to heading or plant height.

RevDate: 2018-11-14

Teufel AI, Johnson MM, Laurent JM, et al (2018)

The many nuanced evolutionary consequences of duplicated genes.

Molecular biology and evolution pii:5182502 [Epub ahead of print].

Gene duplication is seen as a major source of structural and functional divergence in genome evolution. Under the conventional models of sub- or neofunctionalizaton, functional changes arise in one of the duplicates after duplication. However, we suggest here that the presence of a duplicated gene can result in functional changes to its interacting partners. We explore this hypothesis by in-silico evolution of a heterodimer when one member of the interacting pair is duplicated. We examine how a range of selection pressures and protein structures leads to differential patterns of evolutionary divergence. We find that a surprising number of distinct evolutionary trajectories can be observed even in a simple three member system. Further, we observe that selection to correct dosage imbalance can affect the evolution of the initial function in several unexpected ways. For example, if a duplicate is under selective pressure to avoid binding its original binding partner, this can lead to changes in the binding interface of a non-duplicated interacting partner to exclude the duplicate. Hence, independent of the fate of the duplicate, its presence can impact how the original function operates. Additionally, we introduce a conceptual framework to describe how interacting partners cope with dosage imbalance after duplication. Contextualizing our results within this framework reveals that the evolutionary path taken by a duplicate's interacting partners is highly stochastic in nature. Consequently, the fate of duplicate genes may not only be controlled by their own ability to accumulate mutations but also by how interacting partners cope with them.

RevDate: 2018-11-14

Hallmark B, Karafet TM, Hsieh P, et al (2018)

Genomic Evidence of Local Adaptation to Climate and Diet in Indigenous Siberians.

Molecular biology and evolution pii:5182504 [Epub ahead of print].

The indigenous inhabitants of Siberia live in some of the harshest environments on earth, experiencing extended periods of severe cold temperatures, dramatic variation in photoperiod, and limited and highly variable food resources. While the successful long-term settlement of this area by humans required multiple behavioral and cultural innovations, the nature of the underlying genetic changes has generally remained elusive. In this study, we used a three-part approach to identify putative targets of positive natural selection in Siberians. We first performed selection scans on whole exome and genome-wide SNP array data from multiple Siberian populations. We then annotated candidates in the tails of the empirical distributions, focusing on candidates with evidence linking them to biological processes and phenotypes previously identified as relevant to adaptation in circumpolar groups. The top candidates were then genotyped in additional populations to determine their spatial allele frequency distributions and associations with climate variables. Our analysis reveals missense mutations in three genes involved in lipid metabolism (PLA2G2A, PLIN1, ANGPTL8) that exhibit genomic and spatial patterns consistent with selection for cold climate and/or diet. These variants are unified by their connection to brown adipose tissue, and may help to explain previously observed physiological differences in Siberians such as low serum lipid levels and increased basal metabolic rate. These results support the hypothesis that indigenous Siberians have genetically adapted to their local environment by selection on multiple genes.

RevDate: 2018-11-14

Zeng K, BC Jackson (2018)

Methods for estimating demography and detecting between-locus differences in the effective population size and mutation rate.

Molecular biology and evolution pii:5182503 [Epub ahead of print].

It is known that the effective population size (Ne) and the mutation rate (u) vary across the genome. Here we show that ignoring this heterogeneity may lead to biased estimates of past demography. To solve the problem, we develop new methods for jointly inferring past changes in population size and detecting variation in Ne and u between loci. These methods rely on either polymorphism data alone or both polymorphism and divergence data. In addition to inferring demography, we can use the methods to study a variety of questions: (1) comparing sex chromosomes to autosomes (for finding evidence for male-driven evolution, an unequal sex ratio, or sex-biased demographic changes); (2) analysing multi-locus data from within autosomes or sex chromosomes (for studying determinants of variability in Ne and u). Simulations suggest that the methods can provide accurate parameter estimates and have substantial statistical power for detecting difference in Ne and u. As an example, we use the methods to analyse a polymorphism dataset from Drosophila simulans. We find clear evidence for rapid population expansion. The results also indicate that the autosomes have a higher mutation rate than the X chromosome, and that the sex ratio is probably female-biased. The new methods have been implemented in a user-friendly package.

RevDate: 2018-11-14

MacFadyen AC, Drigo I, Harrison EM, et al (2018)

Staphylococcus caeli sp. nov., isolated from air sampling in an industrial rabbit holding.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

Strain 82T, a Gram-stain-positive, coagulase-negative staphylococcus was isolated from an air sample obtained from an industrial rabbit holding in Italy. It is phylogenetically closely related to the coagulase-negative species Staphylococcus saprophyticus, Staphylococcus xylosus and Staphylococcus edaphicus. However, it could be distinguished from these species by sequence differences between the 16S rRNA, hsp60, rpoB, dnaJ and gap genes. At the whole genome level, the isolate had an average nucleotide identity of <95 % and an inferred DNA-DNA hybridization of <70 % when compared to these species. Based on the genotypic results, it is proposed that this isolate is a novel species, with the name Staphylococcus caeli sp. nov. The type strain is 82BT (=NCTC 14063T=CCUG 71912T).

RevDate: 2018-11-14

Xi ZW, Huang LN, Li Y, et al (2018)

Vanrija jinghongensis sp. nov., an asexual basidiomycetous yeast from rotting wood.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

Three strains of a novel basidiomycetous yeast were isolated from the Xishuangbanna Tropical Rainforest, Yunnan Province, PR China. Sequence analysis of the D1/D2 domains of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) regions indicated that the novel species represents a member of the genus Vanrija. It differed from the most closely related known species, Vanrija albida CBS 2839T, by 1.5 % sequence divergence (seven substitutions and two gaps out of 597 bp) in the D1/D2 domains and by 7.4 % sequence divergence (17 substitutions and 20 gaps over 495 bp) in the ITS regions, respectively. The three strains of the novel species reproduced asexually, and no mating could be found. In contrast to V. albida, the novel yeast species was able to assimilate d-glucosamine, inulin, erythritol and galactitol and unable to assimilate raffinose. The name Vanrija jinghongensis sp. nov. is proposed to accommodate these strains, with NYNU 17910T (=CICC 33269=CBS 15229) as the type strain.

RevDate: 2018-11-14

Li L, Wang J, Zhou YJ, et al (2018)

Streptomyces reniochalinae sp. nov. and Streptomyces diacarni sp. nov., from marine sponges.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

Two marine actinomycete strains, LHW50302T and LHW51701T, were isolated from marine sponges collected in Sansha, Hainan Province, China. The morphological, chemotaxonomic and phylogenetic characteristics were consistent with their classification in the genus Streptomyces. The strains formed hooked and looped chains of arthrospores with smooth surfaces. The cell-wall hydrolysates of the strains contained ll-diaminopimelic acid as the diagnostic diamino acid. MK-9(H8) was the predominant menaquinone. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. Major fatty acids of the strains were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The 16S rRNA gene sequences indicated that the strains clustered together with Streptomyces albus CGMCC 4.1640T and Streptomyces qinglanensis CGMCC 4.6825T. Multilocus sequence analysis (MLSA) confirmed their relationship. Genome relatedness in forms of average nucleotide identity, digital DNA-DNA hybridization value and MLSA evolutionary distance between each of the strains and its closest relatives showed that they belonged to distinct species. On the basis of these results, strains LHW50302T and LHW51701T belong to two novel species in the genus Streptomyces, for which the names Streptomyces reniochalinae sp. nov. (type strain LHW50302T=CCTCC AA 2018013T=DSM 106194T) and Streptomyces diacarni sp. nov. (type strain LHW51701T=CCTCC AA 2018017T=DSM 106126T) are proposed, respectively.

RevDate: 2018-11-14

Betancur-R R, Arcila D, Vari RP, et al (2018)

Phylogenomic incongruence, hypothesis testing, and taxonomic sampling: The monophyly of characiform fishes.

Evolution; international journal of organic evolution [Epub ahead of print].


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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E-mail: RJR8222@gmail.com

Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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