797 research outputs found

    Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

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    © 2012 Millet 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.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

    High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

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    Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (Ξsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/Ξ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

    Exploring Species Limits in Two Closely Related Chinese Oaks

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    Background. The species status of two closely related Chinese oaks, Quercus liaotungensis and Q. mongolica, has been called into question. The objective of this study was to investigate the species status and to estimate the degree of introgression between the two taxa using different approaches. [br/] Methodology/Principal Findings. Using SSR (simple sequence repeat) and AFLP (amplified fragment length polymorphism) markers, we found that interspecific genetic differentiation is significant and higher than the differentiation among populations within taxa. Bayesian clusters, principal coordinate analysis and population genetic distance trees all classified the oaks into two main groups consistent with the morphological differentiation of the two taxa rather than with geographic locations using both types of markers. Nevertheless, a few individuals in Northeast China and many individuals in North China have hybrid ancestry according to Bayesian assignment. One SSR locus and five AFLPs are significant outliers against neutral expectations in the interspecific FST simulation analysis, suggesting a role for divergent selection in differentiating species.[br/] Main Conclusions/Significance. All results based on SSRs and AFLPs reached the same conclusion: Q. liaotungensis and Q. mongolica maintain distinct gene pools in most areas of sympatry. They should therefore be considered as discrete taxonomic units. Yet, the degree of introgression varies between the two species in different contact zones, which might be caused by different population history or by local environmental factors

    In-situ evidence for dextral active motion at the Arabia-India plate boundary

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    International audienceThe Arabia-India plate boundary--also called theOwen fracture zone--is perhaps the least-known boundary among large tectonic plates1-6. Although it was identified early on as an example of a transform fault converting the divergent motion along the Carlsberg Ridge to convergent motion in the Himalayas7, its structure and rate of motion remains poorly constrained. Here we present the first direct evidence for active dextral strike-slip motion along this fault, based on seafloor multibeam mapping of the Arabia-India-Somalia triple junction in the northwest Indian Ocean. There is evidence for 12km of apparent strike-slip motion along the mapped segment of the Owen fracture zone, which is terminated to the south by a 50-km-wide pull-apart basin bounded by active faults. By evaluating these new constraints within the context of geodetic models of global plate motions, we determine a robust angular velocity for the Arabian plate relative to the Indian plate that predicts 2-4mmyr−1 dextral motion along the Owen fracture zone. This transformfault was probably initiated around 8 million years ago in response to a regional reorganization of plate velocities and directions8-11, which induced a change in configuration of the triple junction. Infrequent earthquakes of magnitude 7 and greater may occur along the Arabia-India plate boundary, unless deformation is in the formof aseismic creep

    Investigation of Chlamydophila spp. in dairy cows with reproductive disorders

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    <p>Abstract</p> <p>Background</p> <p>Reports worldwide indicate high prevalence of <it>Chlamydophila </it>spp. infection in cattle. To assess the prevalence in Sweden, 525 cows in 70 dairy herds with reproductive disorders was investigated.</p> <p>Methods</p> <p>To detect antibodies two commercially available kits were used. Moreover, 107 specimens, including vaginal swabs, organ tissues and milk were analysed by Polymerase Chain Reaction (PCR).</p> <p>Results</p> <p>Two (0.4%) cows were seropositive in the Pourquier <it>Cp. abortus </it>ELISA. The seroprevalence with the Chekit ELISA was 28% with no difference between cases and controls. Five specimens were positive in real-time PCR and further analysed by nested PCR. <it>Cp. pecorum </it>was confirmed by partial <it>omp1 </it>DNA sequencing of the nested PCR product of vaginal swabs from control cows.</p> <p>Conclusion</p> <p>The results suggest that <it>Cp. abortus </it>infection is absent or rare in Swedish cows whereas <it>Cp. pecorum </it>is probably more spread. They also suggest that <it>Chlamydophila </it>spp. are not related to reproduction disorders in Swedish cattle.</p

    Efficient screening for ‘genetic pollution’ in an anthropogenic crested newt hybrid zone

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    Genetic admixture between endangered native and non-native invasive species poses a complex conservation problem. Decision makers often need to quickly screen large numbers of individuals and distinguish natives from morphologically similar invading species and their genetically admixed offspring. We describe a protocol using the fast and economical Kompetitive Allele Specific PCR (KASP) technology for genotyping on a large scale. We apply this protocol to a case study of hybridization between a native and an invasive crested newt species. Using previously published data, we designed a panel of ten nuclear and one mitochondrial diagnostic SNP markers. We observed only minor differences between KASP and next-generation sequencing data previously produced with the Ion Torrent platform. We briefly discuss practical considerations for tackling the insidious conservation problem of genetic admixture between native and invasive species. The KASP genotyping protocol facilitates policy decision making for the crested newt case and is generally applicable to invasive hybridization with endangered taxa

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    A highly polymorphic insertion in the Y-chromosome amelogenin gene can be used for evolutionary biology, population genetics and sexing in Cetacea and Artiodactyla

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    <p>Abstract</p> <p>Background</p> <p>The early radiation of the <it>Cetartiodactyla </it>is complex, and unambiguous molecular characters are needed to clarify the positions of hippotamuses, camels and pigs relative to the remaining taxa (<it>Cetacea </it>and <it>Ruminantia</it>). There is also a need for informative genealogic markers for Y-chromosome population genetics as well as a sexing method applicable to all species from this group. We therefore studied the sequence variation of a partial sequence of the evolutionary conserved amelogenin gene to assess its potential use in each of these fields.</p> <p>Results and discussion</p> <p>We report a large interstitial insertion in the Y amelogenin locus in most of the <it>Cetartiodactyla </it>lineages (cetaceans and ruminants). This sex-linked size polymorphism is the result of a 460–465 bp inserted element in intron 4 of the amelogenin gene of Ruminants and Cetaceans. Therefore, this polymorphism can easily be used in a sexing assay for these species.</p> <p>When taking into account this shared character in addition to nucleotide sequence, gene genealogy follows sex-chromosome divergence in <it>Cetartiodactyla </it>whereas it is more congruent with zoological history when ignoring these characters. This could be related to a loss of homology between chromosomal copies given the old age of the insertion.</p> <p>The 1 kbp <it>Amel-Y </it>amplified fragment is also characterized by high nucleotide diversity (64 polymorphic sites spanning over 1 kbp in seven haplotypes) which is greater than for other Y-chromosome sequence markers studied so far but less than the mitochondrial control region.</p> <p>Conclusion</p> <p>The gender-dependent polymorphism we have identified is relevant not only for phylogenic inference within the <it>Cetartiodactyla </it>but also for Y-chromosome based population genetics and gender determination in cetaceans and ruminants. One single protocol can therefore be used for studies in population and evolutionary genetics, reproductive biotechnologies, and forensic science.</p

    Global and local sea level during the Last Interglacial: A probabilistic assessment

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    The Last Interglacial (LIG) stage, with polar temperatures likely 3-5 C warmer than today, serves as a partial analogue for low-end future warming scenarios. Based upon a small set of local sea level indicators, the Intergovernmental Panel on Climate Change (IPCC) inferred that LIG global sea level (GSL) was about 4-6 m higher than today. However, because local sea levels differ from GSL, accurately reconstructing past GSL requires an integrated analysis of globally distributed data sets. Here we compile an extensive database of sea level indicators and apply a novel statistical approach that couples Gaussian process regression of sea level to Markov Chain Monte Carlo modeling of geochronological errors. Our analysis strongly supports the hypothesis that LIG GSL was higher than today, probably peaking at 6-9 m. Our results highlight the sea level hazard associated with even relatively low levels of sustained global warming.Comment: Preprint version of what has since been published in Natur
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