Search

Rotaviruses are a major cause of diarrhea in young children, causing an estimated 215,000 deaths worldwide every year (1). These viruses are nonenveloped and have a genome consisting of 11 [...]

Despite innovations in HIV prevention and treatment, HIV outbreaks do occur in the United States. Local public health staff identified >200 persons with HIV resulting from an injection drug use [...]

Denisova Cave in the Siberian Altai (Russia) is a key site for understanding the complex relationships between hominin groups that inhabited Eurasia in the Middle and Late Pleistocene epoch. DNA sequenced from human remains found at this site has revealed the presence of a hitherto unknown hominin group, the Denisovans.sup.1,2, and high-coverage genomes from both Neanderthal and Denisovan fossils provide evidence for admixture between these two populations.sup.3. Determining the age of these fossils is important if we are to understand the nature of hominin interaction, and aspects of their cultural and subsistence adaptations. Here we present 50 radiocarbon determinations from the late Middle and Upper Palaeolithic layers of the site. We also report three direct dates for hominin fragments and obtain a mitochondrial DNA sequence for one of them. We apply a Bayesian age modelling approach that combines chronometric (radiocarbon, uranium series and optical ages), stratigraphic and genetic data to calculate probabilistically the age of the human fossils at the site. Our modelled estimate for the age of the oldest Denisovan fossil suggests that this group was present at the site as early as 195,000 years ago (at 95.4% probability). All Neanderthal fossils--as well as Denisova 11, the daughter of a Neanderthal and a Denisovan.sup.4--date to between 80,000 and 140,000 years ago. The youngest Denisovan dates to 52,000-76,000 years ago. Direct radiocarbon dating of Upper Palaeolithic tooth pendants and bone points yielded the earliest evidence for the production of these artefacts in northern Eurasia, between 43,000 and 49,000 calibrated years before present (taken as ad 1950). On the basis of current archaeological evidence, it may be assumed that these artefacts are associated with the Denisovan population. It is not currently possible to determine whether anatomically modern humans were involved in their production, as modern-human fossil and genetic evidence of such antiquity has not yet been identified in the Altai region.Bayesian modelling of chronometric, stratigraphic and genetic data from Denisova Cave provides a chronological framework for understanding Neanderthal and Denisovan presence at the site, as well as interactions between these groups., Author(s): Katerina Douka [sup.1] [sup.2] , Viviane Slon [sup.3] , Zenobia Jacobs [sup.4] [sup.5] , Christopher Bronk Ramsey [sup.2] , Michael V. Shunkov [sup.6] [sup.7] , Anatoly P. Derevianko [sup.6] [...]

Chironomid flies (non-biting midges) are among the most abundant and diverse animals in Arctic regions, but detailed analyses of species distributions and biogeographical patterns are hampered by challenging taxonomy and reliance on morphology for species-level identification. Here we take advantage of available DNA barcode data of Arctic Chironomidae in BOLD to analyse similarities in species distributions across a northern Nearctic--West Palearctic gradient. Using more than 260 000 barcodes representing 4666 BINs (Barcode Index Numbers) and 826 named species (some with interim names) from a combination of public and novel data, we show that the Greenland chironomid fauna shows affinities to both the Nearctic and the West Palearctic regions. While raw taxon counts indicate a strong Greenland--North American affinity, comparisons using Chao's dissimilarity metric support a slightly higher similarity between Greenland and West Palearctic chironomid communities. Results were relatively consistent across different definitions of species taxonomic units, including morphologically determined species, BINs, and superBINs based on a ~4.5% threshold. While most taxa found in Greenland are shared with at least one other region, reflecting circum-Arctic dispersal, our results also reveal that Greenland harbours a small endemic biodiversity. Our exploratory study showcases how DNA barcoding efforts using standardized gene regions contribute to an understanding of broad-scale patterns in biogeography by enabling joint analysis of public DNA sequence data derived from diverse prior studies.Key words: Diptera, zoogeography, biogeography, Canada, Norway, Svalbard.Les chironomides (moucherons non-piqueurs) sont parmi les animaux les plus abondants et diversifies dans les regions arctiques, mais des analyses detaillees des distributions de ces especes et de leur repartition biogeographique sont entravees par une taxonomie difficile et une dependance a la morphologie pour l'identification des especes. Ici, les auteurs tirent profit des donnees disponibles en matiere de codes a barres de l'ADN pour les chironomides arctiques au sein de la base de donnees BOLD pour analyser les similarites pour ce qui est des distributions des especes au long d'un gradient nordique Nearctique-Palearctique occidental. Au moyen de plus de 260 000 codes a barres representant 4666 BIN (<< Barcode Index Numbers >>) et 826 especes nommees (dont certaines de maniere interimaire) a partir d'une combinaison de donnees publiques et inedites, les auteurs montrent que la faune des chironomides du Groenland montre des ressemblances a la fois avec celles des regions Nearctique et Palearctique occidentale. Bien que des decomptes bruts indiquent une grande affinite Groenland--Amerique du Nord, des comparaisons a l'aide de l'indice de dissimilarite de Chao suggerent une similarite legerement plus elevee entre les communautes du Groenland et du Palearctique occidental. Les resultats etaient relativement coherents en faisant appel a diverses definitions des unites taxonomiques specifiques, incluant les especes definies sur une base morphologique, des BIN et des superBIN a un seuil de 4,5%. Bien que la plupart des taxons du Groenland soient partages avec au moins une autre region, ce qui reflete une distribution circum-arctique, les resultats revelent aussi que le Groenland recele une petite biodiversite endemique. Cette etude exploratoire demontre comment les efforts en matiere de codage a barres au moyen de regions geniques standardisees contribuent a la comprehension de la biogeographie a grande echelle en rendant possible l'analyse conjointe de donnees moleculaires publiques derivees de diverses etudes anterieures. [Traduit par la Redaction]Mots-cles: Diptera, zoogeographie, biogeographie, Canada, Norvege, Svalbard., IntroductionThe Arctic is home to about 21000 described species, many of which are specifically adapted to a cold climate (CAFF 2013). As this diversity is under pressure from several sources, [...]

Three tools have transformed biotechnology over the past decade and a half. Gene reading has made it possible to quickly sequence the genome of any living creature. Gene synthesis has [...]

The increasing availability of DNA sequence data and access to sophisticated bioinformatic algorithms mean that an unbiased bioinformatics-based assessment of the predicted impact of a genomic variant is rapidly available. [...]

Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression.sup.1,2. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recognize a pre-existing histone modification and catalyse the same modification on newly deposited histones. Recent studies suggest that in wild-type cells, histone PTM-based positive feedback is too weak to mediate epigenetic inheritance in the absence of other inputs.sup.3-7. RNA interference (RNAi)-mediated histone H3 lysine 9 methylation (H3K9me) and heterochromatin formation define a potential epigenetic inheritance mechanism in which positive feedback involving short interfering RNA (siRNA) amplification can be directly coupled to histone PTM positive feedback.sup.8-14. However, it is not known whether the coupling of these two feedback loops can maintain epigenetic silencing independently of DNA sequence and in the absence of enabling mutations that disrupt genome-wide chromatin structure or transcription.sup.15-17. Here, using the fission yeast Schizosaccharomyces pombe, we show that siRNA-induced H3K9me and silencing of a euchromatic gene can be epigenetically inherited in cis during multiple mitotic and meiotic cell divisions in wild-type cells. This inheritance involves the spreading of secondary siRNAs and H3K9me3 to the targeted gene and surrounding areas, and requires both RNAi and H3K9me, suggesting that the siRNA and H3K9me positive-feedback loops act synergistically to maintain silencing. By contrast, when maintained solely by histone PTM positive feedback, silencing is erased by H3K9 demethylation promoted by Epe1, or by interallelic interactions that occur after mating to cells containing an expressed allele even in the absence of Epe1. These findings demonstrate that the RNAi machinery can mediate transgenerational epigenetic inheritance independently of DNA sequence or enabling mutations, and reveal a role for the coupling of the siRNA and H3K9me positive-feedback loops in the protection of epigenetic alleles from erasure. In Schizosaccharomyces pombe, histone H3K9 methylation acts synergistically with short interfering RNA to perpetuate gene silencing during multiple mitotic and meiotic cell divisions., Author(s): Ruby Yu [sup.1] , Xiaoyi Wang [sup.1] , Danesh Moazed [sup.1] Author Affiliations: (1) Department of Cell Biology and Howard Hughes Medical Institute, Harvard Medical School, Boston, USA Main [...]

The virus family Filoviridae is divided into 5 genera: Cuevavirus, Marburgvirus, Ebolavirus, Striavirus, and Thamnovirus (https://talk.ictvonline.org/taxonomy). Six distinct members of Ebolavirus have been described; 4 are known to cause human [...]

Background One of the most significant public health concerns in today's world is the persistent upsurge of infections caused by multidrug resistant bacteria. As a result, clinicians are being forced to intervene with either less effective backup drugs or ones with substantial side-effects. Colistin is a last resort antimicrobial agent for the treatment of infections caused by multi-drug resistant gram-negative bacteria. Methods Escherichia coli (n = 65) isolated from street food (n = 20), hand rinse (n = 15), surface water (n = 10), and healthy human stool (n = 20) were tested for colistin resistance gene mcr-1 and response to antimicrobial agents. Antimicrobial resistance genes and virulence genes were detected by employing polymerase chain reaction. DNA fingerprinting of the strains were determined by pulsed-field gel electrophoresis. Results Screening of E. coli allowed us to confirm colistin resistance marker gene mcr-1 in 13 strains (street food, n = 4; hand rinse, n = 2; surface water, n = 4; and stool, n = 3); and two of these E. coli strains carrying mcr-1 harbored bla.sub.TEM gene encoding extended spectrum beta lactamase. Antibiotic assay results revealed all 13 E. coli strains carrying mcr-1 to be multi-drug resistant (MDR), including to colistin. The minimum inhibitory concentration (MIC) for colistin ranged from 2 to 6 [mu]g/ml. DNA sequencing confirmed homogeneity of the nucleotide sequence for mcr-1, but the E. coli strains were heterogenous, as confirmed by pulsed-field gel electrophoresis suggesting horizontal transmission of colistin resistance in Bangladesh. Conclusion Widespread dissemination of E. coli strains carrying mcr-1 encoding resistance to colistin in the present study is alarming as this is the last resort drug for the treatment of infections caused by MDR gram-negative bacteria resistant to almost all drugs used commonly. Keywords: Colistin, mcr-1, ESBL, Multi-drug resistant (MDR), Minimum inhibitory concentration (MIC), Horizontal transmission, Author(s): Fatema-Tuz Johura[sup.1], Jarin Tasnim[sup.1], Indrajeet Barman[sup.1], Sahitya Ranjan Biswas[sup.1], Fatema Tuz Jubyda[sup.1], Marzia Sultana[sup.1], Christine Marie George[sup.2], Andrew Camilli[sup.3], Kimberley D. Seed[sup.4], Niyaz Ahmed[sup.1] and Munirul Alam[sup.1] Background Antimicrobial [...]

Background Lifestyle interventions to reduce body mass index (BMI) are critical public health strategies for type 2 diabetes prevention. While weight loss interventions have shown demonstrable benefit for high-risk and prediabetic individuals, we aimed to determine whether the same benefits apply to those at lower risk. Methods and findings We performed a multi-stratum Mendelian randomization study of the effect size of BMI on diabetes odds in 287,394 unrelated individuals of self-reported white British ancestry in the UK Biobank, who were recruited from across the United Kingdom from 2006 to 2010 when they were between the ages of 40 and 69 years. Individuals were stratified on the following diabetes risk factors: BMI, diabetes family history, and genome-wide diabetes polygenic risk score. The main outcome measure was the odds ratio of diabetes per 1-kg/m.sup.2 BMI reduction, in the full cohort and in each stratum. Diabetes prevalence increased sharply with BMI, family history of diabetes, and genetic risk. Conversely, predicted risk reduction from weight loss was strikingly similar across BMI and genetic risk categories. Weight loss was predicted to substantially reduce diabetes odds even among lower-risk individuals: for instance, a 1-kg/m.sup.2 BMI reduction was associated with a 1.37-fold reduction (95% CI 1.12-1.68) in diabetes odds among non-overweight individuals (BMI < 25 kg/m.sup.2) without a family history of diabetes, similar to that in obese individuals (BMI [greater than or equal to] 30 kg/m.sup.2) with a family history (1.21-fold reduction, 95% CI 1.13-1.29). A key limitation of this analysis is that the BMI-altering DNA sequence polymorphisms it studies represent cumulative predisposition over an individual's entire lifetime, and may consequently incorrectly estimate the risk modification potential of weight loss interventions later in life. Conclusions In a population-scale cohort, lower BMI was consistently associated with reduced diabetes risk across BMI, family history, and genetic risk categories, suggesting all individuals can substantially reduce their diabetes risk through weight loss. Our results support the broad deployment of weight loss interventions to individuals at all levels of diabetes risk., Author(s): Michael Wainberg 1, Anubha Mahajan 2,3, Anshul Kundaje 1,4, Mark I. McCarthy 2,3,5, Erik Ingelsson 6,7,8,9, Nasa Sinnott-Armstrong 4,*, Manuel A. Rivas 10,* Introduction Type 2 diabetes is a [...]

The T cells of the immune system can be engineered to target a tumour, but why some people respond better than others to such therapy is unclear. One patient's striking response to treatment now offers some clues.The T cells of the immune system can be engineered to target a tumour, but why some people respond better than others to such therapy is unclear. One patient's striking response to treatment now offers some clues., Author(s): Marcela V. MausAuthor Affiliations:Tumour tamed by transfer of one T cell Therapies involving engineered immune cells use viral vectors based on retroviruses or lentiviruses to insert a DNA sequence, [...]