100 research outputs found

    Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

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    Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections

    Mannan detecting C-type lectin receptor probes recognise immune epitopes with diverse chemical, spatial and phylogenetic heterogeneity in fungal cell walls

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    Funding Information: This work was supported by the Wellcome Trust Investigator, Collaborative, Equipment, Strategic and Biomedical Resource awards (086827, 075470, 097377, 101873, 200208, 093378 and 099197), the Applied Molecular Biosciences Unit-UCIBIO (FCT/MCTES UID/Multi/04378/2019), Wellcome Trust Biomedical Resource grant (108430/Z/15/Z), March of Dimes (Arlington, Virginia, U.S.A.) Prematurity Research Center grant (22-FY18-821) and by the MRC Centre for Medical Mycology (N006364/1). The University of Aberdeen funded a studentship to IV as part of NARG?s Wellcome Senior Investigator Award. https://wellcome.ac.uk/ - Wellcome. https://mrc.ukri.org/ - MRC. https:// www.requimte.pt/ucibio/ - the Applied Molecular Biosciences Unit-UCIBIO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2020 Vendele et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Peer reviewedPublisher PD

    Analysis of 3800-year-old Yersinia pestis genomes suggests Bronze Age origin for bubonic plague

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    该论文通过对青铜器时代的两个鼠疫杆菌分离株进行测序,深入剖析了鼠疫杆菌的历史。德国、俄罗斯、中国和瑞士等多国研究员共同参与了研究。这篇论文的第一作者是德国马克斯-普朗克研究所的考古遗传学专家Maria Spyrou。她和同事从俄罗斯墓穴中埋葬的九名古代人的牙齿样本入手,发现有两人感染鼠疫杆菌。之后,他们从这些个体中分离出距今约3800年的病原菌。在这项新研究中,研究人员利用液相捕获和Illumina鸟枪法测序技术,对青铜器时代的一名男子(RT5)的鼠疫杆菌和人类宿主序列进行测序,其中鼠疫杆菌基因组的平均覆盖度达到32倍。同时,他们还对另一名感染个体(RT6)的分离株进行测序,平均覆盖度为1.9倍。系统发育分析表明,RT5和RT6分离株是共同谱系的一部分,这个谱系的祖先是史上三次瘟疫大流行的罪魁祸首。除了众所周知的中世纪欧洲瘟疫大流行,鼠疫杆菌还曾造成公元6世纪的查士丁尼瘟疫和19世纪的中国大规模鼠疫。 马克斯-普朗克人类历史科学研究所的古病理学专家Kirsten Bos表示,这些结果表明“具有传播潜力的瘟疫存在的时间比我们想象得更久。”Bos是这篇论文的通讯作者之一。【Abstract】The origin of Yersinia pestis and the early stages of its evolution are fundamental subjects of investigation given its high virulence and mortality that resulted from past pandemics. Although the earliest evidence of Y. pestis infections in humans has been identified in Late Neolithic/Bronze Age Eurasia (LNBA 5000–3500y BP), these strains lack key genetic components required for flea adaptation, thus making their mode of transmission and disease presentation in humans unclear. Here, we reconstruct ancient Y. pestis genomes from individuals associated with the Late Bronze Age period (~3800 BP) in the Samara region of modern-day Russia. We show clear distinctions between our new strains and the LNBA lineage, and suggest that the full ability for flea-mediated transmission causing bubonic plague evolved more than 1000 years earlier than previously suggested. Finally, we propose that several Y. pestis lineages were established during the Bronze Age, some of which persist to the present day.We thank Cosimo Posth, Marcel Keller, Michal Feldman and Wolfgang Haak for useful insights to the manuscript, as well as Alexander Immel and Stephen Clayton for computational support. In addition, we are thankful to Guido Brandt, Antje Wissgott and Cäcilia Freund for laboratory support. M.A.S., A.H., K.I.B. and J.K. were supported by the ERC starting grant APGREID, and by the Max Planck Society. C.C.W. was supported by the Max Planck Society and the Nanqiang Outstanding Young Talents Program of Xiamen University. D.K. was supported by a Marie Heim-Vögtlin grant from the Swiss National Science Foundation

    Women Scientists Who Made Nuclear Astrophysics

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    Female role models reduce the impact on women of stereotype threat, i.e., of being at risk of conforming to a negative stereotype about one's social, gender, or racial group [1,2]. This can lead women scientists to underperform or to leave their scientific career because of negative stereotypes such as, not being as talented or as interested in science as men. Sadly, history rarely provides role models for women scientists; instead, it often renders these women invisible [3]. In response to this situation, we present a selection of twelve outstanding women who helped to develop nuclear astrophysics

    Polarisation of Major Histocompatibility Complex II Host Genotype with Pathogenesis of European Brown Hare Syndrome Virus.

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    A study was conducted in order to determine the occurrence of European Brown Hare Syndrome virus (EBHSV) in Denmark and possible relation between disease pathogenesis and Major Histocompatibility Complex (MHC) host genotype. Liver samples were examined from 170 brown hares (hunted, found sick or dead), collected between 2004 and 2009. Macroscopical and histopathological findings consistent with EBHS were detected in 24 (14.1%) hares; 35 (20.6%) had liver lesions not typical of the syndrome, 50 (29.4%) had lesions in other tissues and 61 (35.9%) had no lesions. Sixty five (38.2%) of 170 samples were found to be EBHSV-positive (RT-PCR, VP60 gene). In order to investigate associations between viral pathogenesis and host genotype, variation within the exon 2 DQA gene of MHC was assessed. DQA exon 2 analysis revealed the occurrence of seven different alleles in Denmark. Consistent with other populations examined so far in Europe, observed heterozygosity of DQA (H o = 0.1180) was lower than expected (H e = 0.5835). The overall variation for both nucleotide and amino acid differences (2.9% and 14.9%, respectively) were lower in Denmark than those assessed in other European countries (8.3% and 16.9%, respectively). Within the peptide binding region codons the number of nonsynonymous substitutions (dN) was much higher than synonymous substitutions (dS), which would be expected for MHC alleles under balancing selection. Allele frequencies did not significantly differ between EBHSV-positive and -negative hares. However, allele Leeu-DQA*30 was detected in significantly higher (P = 0.000006) frequency among the positive hares found dead with severe histopathological lesions than among those found sick or apparently healthy. In contrast, the latter group was characterized by a higher frequency of the allele Leeu-DQA*14 as well as the proportion of heterozygous individuals (P = 0.000006 and P = 0.027). These data reveal a polarisation between EBHSV pathogenesis and MHC class II genotype within the European brown hare in Denmark

    Community-curated and standardised metadata of published ancient metagenomic samples with AncientMetagenomeDir

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    Ancient DNA and RNA are valuable data sources for a wide range of disciplines. Within the field of ancient metagenomics, the number of published genetic datasets has risen dramatically in recent years, and tracking this data for reuse is particularly important for large-scale ecological and evolutionary studies of individual taxa and communities of both microbes and eukaryotes. AncientMetagenomeDir (archived at https://doi.org/10.5281/zenodo.3980833) is a collection of annotated metagenomic sample lists derived from published studies that provide basic, standardised metadata and accession numbers to allow rapid data retrieval from online repositories. These tables are community-curated and span multiple sub-disciplines to ensure adequate breadth and consensus in metadata definitions, as well as longevity of the database. Internal guidelines and automated checks facilitate compatibility with established sequence-read archives and term-ontologies, and ensure consistency and interoperability for future meta-analyses. This collection will also assist in standardising metadata reporting for future ancient metagenomic studies

    Synthesis of 2D Germanane (GeH):a New, Fast, and Facile Approach

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    Germanane (GeH), a germanium analogue of graphane, has recently attracted considerable interest because its remarkable combination of properties makes it an extremely suitable candidate to be used as 2D material for field effect devices, photovoltaics, and photocatalysis. Up to now, the synthesis of GeH has been conducted by substituting Ca by H in a beta-CaGe2 layered Zintl phase through topochemical deintercalation in aqueous HCl. This reaction is generally slow and takes place over 6 to 14 days. The new and facile protocol presented here allows to synthesize GeH at room temperature in a significantly shorter time (a few minutes), which renders this method highly attractive for technological applications. The GeH produced with this method is highly pure and has a band gap (E-g) close to 1.4 eV, a lower value than that reported for germanane synthesized using HCl, which is promising for incorporation of GeH in solar cells

    Phylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes

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    The second plague pandemic, caused by Yersinia pestis, devastated Europe and the nearby regions between the 14th and 18th centuries AD. Here we analyse human remains from ten European archaeological sites spanning this period and reconstruct 34 ancient Y. pestis genomes. Our data support an initial entry of the bacterium through eastern Europe, the absence of genetic diversity during the Black Death, and low within-outbreak diversity thereafter. Analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. In addition, we show the loss of a genomic region that includes virulence-related genes in strains associated with late stages of the pandemic. The deletion was also identified in genomes connected with the first plague pandemic (541–750 AD), suggesting a comparable evolutionary trajectory of Y. pestis during both events
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