117 research outputs found

    Temperature Dependence Of Brillouin Light Scattering Spectra Of Acoustic Phonons In Silicon

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    Electrons, optical phonons, and acoustic phonons are often driven out of local equilibrium in electronic devices or during laser-material interaction processes. The need for a better understanding of such non-equilibrium transport processes has motivated the development of Raman spectroscopy as a local temperature sensor of optical phonons and intermediate frequency acoustic phonons, whereas Brillouin light scattering (BLS) has recently been explored as a temperature sensor of low-frequency acoustic phonons. Here, we report the measured BLS spectra of silicon at different temperatures. The origins of the observed temperature dependence of the BLS peak position, linewidth, and intensity are examined in order to evaluate their potential use as temperature sensors for acoustic phonons. (C) 2015 AIP Publishing LLC.National Science Foundation (NSF) Thermal Transport Processes Program CBET-1336968PhysicsCenter for Complex Quantum SystemsMaterials Science and EngineeringTexas Materials InstituteMechanical Engineerin

    Phosphatidylinositol 3,5-bisphosphate: A Molecular Switch of Vacuolar Fusion and Fission

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    Abstract Vacuoles purified from Saccharomyces cerevisiae are a well-studied model for membrane fusion and fission as the machinery is highly conserved throughout eukaryotes. Vacuole membranes undergo cycles of fusion and fission which have distinct mechanisms but are in part controlled by overlapping regulators. Both processes are dependent on proteins, ion concentrations, and lipid composition, highlighting the complex regulation of vacuole homeostasis. Previous studies have shown the lipid PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) is a crucial activator of vacuolar fission. PI(3,5)P2 is generated by the PI3P 5-kinase Fab1 . Fab1 is activated in response to osmotic stress leading to a sharp rise in PI(3,5)P2 levels. Increases in PI(3,5)P2 activates the calcium channel Yvc1, causing calcium to efflux from the vacuole. This, along with PI(3,5)P2 activation of Vph1 (a subunit of a vacuolar V-ATPase) results in fragmentation of the vacuole. Here we show that PI(3,5)P2 is a novel inhibitor of vacuolar fusion. Additionally we found PI(3,5)P2 does not prevent fusion by inhibiting priming and trans-SNARE pairing (the early steps of fusion). In order to look at the later steps of fusion, we conducted lipid mixing experiments to measure it’s effects on hemi-fusion, the precursor step to vacuolar fusion. Our results show that PI(3,5)P2 inhibits hemi-fusion, but the exact mechanism is still unclear. We also hypothesized that PI(3,5)P2 acts to inhibit fusion through either the Yvc1 calcium efflux or the Vph1 V-ATPase pathway. Vph1 interactions promote either vacuolar fusion or fission depending on binding partners. We predicted PI(3,5)P2 to disrupt Vph1 fusion complexes while promoting fission complexes. But, experiments using TAP-tagged Vph1 were inconclusive. Also, experiments with Yvc1 knockout yeast retained sensitivity to PI(3,5)P2 - interestingly, the calcium influx pump Pmc1 was found to be enhanced by PI(3,5)P2, which may explain decreased calcium influx.Ope

    Interrogating marine virus-host interactions and elemental transfer with BONCAT and nanoSIMS-based methods

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    While the collective impact of marine viruses has become more apparent over the last decade, a deeper understanding of virus-host dynamics and the role of viruses in nutrient cycling would benefit from direct observations at the single-virus level. We describe two new complementary approaches - stable isotope probing coupled with nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence-based biorthogonal non-canonical amino acid tagging (BONCAT) - for studying the activity and biogeochemical influence of marine viruses. These tools were developed and tested using several ecologically relevant model systems (Emiliania huxleyi/EhV207, Synechococcus sp. WH8101/Syn1, and Escherichia coli/T7). By resolving carbon and nitrogen enrichment in viral particles, we demonstrate the power of nanoSIMS tracer experiments in obtaining quantitative estimates for the total number of viruses produced directly from a particular production pathway (by isotopically labeling host substrates). Additionally, we show through laboratory experiments and a pilot field study that BONCAT can be used to directly quantify viral production (via epifluorescence microscopy) with minor sample manipulation and no dependency on conversion factors. This technique can also be used to detect newly synthesized viral proteins. Together these tools will help fill critical gaps in our understanding of the biogeochemical impact of viruses in the ocean

    CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence

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    The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A–HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a “lock and key” interaction is typical of innate receptor–ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors

    Mapping species distributions: A comparison of skilled naturalist and lay citizen science recording

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    To assess the ability of traditional biological recording schemes and lay citizen science approaches to gather data on species distributions and changes therein, we examined bumblebee records from the UK’s national repository (National Biodiversity Network) and from BeeWatch. The two recording approaches revealed similar relative abundances of bumblebee species but different geographical distributions. For the widespread common carder (Bombus pascuorum), traditional recording scheme data were patchy, both spatially and temporally, reflecting active record centre rather than species distribution. Lay citizen science records displayed more extensive geographic coverage, reflecting human population density, thus offering better opportunities to account for recording effort. For the rapidly spreading tree bumblebee (Bombus hypnorum), both recording approaches revealed similar distributions due to a dedicated mapping project which overcame the patchy nature of naturalist records. We recommend, where possible, complementing skilled naturalist recording with lay citizen science programmes to obtain a nation-wide capability, and stress the need for timely uploading of data to the national repository

    Biomarker-Based HIV Incidence in a Community Sample of Men Who Have Sex with Men in Paris, France

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    BACKGROUND: Population-based estimates of HIV incidence in France have revealed that men who have sex with men (MSM) are the most affected population and contribute to nearly half of new infections each year. We sought to estimate HIV incidence among sexually active MSM in Paris gay community social venues. METHODOLOGY/ PRINCIPAL FINDINGS: A cross-sectional survey was conducted in 2009 in a sample of commercial venues such as bars, saunas and backrooms. We collected a behavioural questionnaire and blood sample. Specimens were tested for HIV infection and positive specimens then tested for recent infection by the enzyme immunoassay for recent HIV-1 infection (EIA-RI). We assessed the presence of antiretroviral therapy among infected individuals to rule out treated patients in the algorithm that determined recent infection. Biomarker-based cross-sectional incidence estimates were calculated. We enrolled 886 MSM participants among which 157 (18%) tested HIV positive. In positive individuals who knew they were infected, 75% of EIA-RI positive results were due to ART. Of 157 HIV positive specimens, 15 were deemed to be recently infected. The overall HIV incidence was estimated at 3.8% person-years (py) [95%CI: 1.5-6.2]. Although differences were not significant, incidence was estimated to be 3.5% py [0.1-6.1] in men having had a negative HIV test in previous year and 4.8% py [0.1-10.6] in men having had their last HIV test more than one year before the survey, or never tested. Incidence was estimated at 4.1% py [0-8.3] in men under 35 years and 2.5% py [0-5.4] in older men. CONCLUSIONS/ SIGNIFICANCE: This is the first community-based survey to estimate HIV incidence among MSM in France. It includes ART detection and reveals a high level of HIV transmission in sexually active individuals, despite a high uptake of HIV testing. These data call for effective prevention programs targeting MSM engaged in high-risk behaviours

    Interrogating marine virus-host interactions and elemental transfer with BONCAT and nanoSIMS-based methods

    Get PDF
    While the collective impact of marine viruses has become more apparent over the last decade, a deeper understanding of virus-host dynamics and the role of viruses in nutrient cycling would benefit from direct observations at the single-virus level. We describe two new complementary approaches - stable isotope probing coupled with nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence-based biorthogonal non-canonical amino acid tagging (BONCAT) - for studying the activity and biogeochemical influence of marine viruses. These tools were developed and tested using several ecologically relevant model systems (Emiliania huxleyi/EhV207, Synechococcus sp. WH8101/Syn1, and Escherichia coli/T7). By resolving carbon and nitrogen enrichment in viral particles, we demonstrate the power of nanoSIMS tracer experiments in obtaining quantitative estimates for the total number of viruses produced directly from a particular production pathway (by isotopically labeling host substrates). Additionally, we show through laboratory experiments and a pilot field study that BONCAT can be used to directly quantify viral production (via epifluorescence microscopy) with minor sample manipulation and no dependency on conversion factors. This technique can also be used to detect newly synthesized viral proteins. Together these tools will help fill critical gaps in our understanding of the biogeochemical impact of viruses in the ocean

    Vers une nouvelle érudition : numérisation et recherche en histoire du livre

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    En décembre 1999, à l\u27Enssib, s’est déroulé le colloque "Vers une nouvelle érudition : numérisation et recherche en histoire du livre", organisé dans le cadre des 12e Entretiens du Centre Jacques Cartier sous la responsabilité de Dominique Varry (enssib), Annie Charon (école nationale des chartes) et Guylaine Baudry (Université de Montréal)

    Gut Microbiome Dysbiosis in Antibiotic-Treated COVID-19 Patients is Associated with Microbial Translocation and Bacteremia

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    Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19

    Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.

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    The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO\u27s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes
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