175 research outputs found

    Repressive and non-repressive chromatin at native telomeres in Saccharomyces cerevisiae

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    <p>Abstract</p> <p>Background</p> <p>In <it>Saccharomyces cerevisiae </it>genes that are located close to a telomere can become transcriptionally repressed by an epigenetic process known as telomere position effect. There is large variation in the level of the telomere position effect among telomeres, with many native ends exhibiting little repression.</p> <p>Results</p> <p>Chromatin analysis, using microccocal nuclease and indirect end labelling, reveals distinct patterns for ends with different silencing states. Differences were observed in the promoter accessibility of a subtelomeric reporter gene and a characteristic array of phased nucleosomes was observed on the centromere proximal side of core X at a repressive end. The silent information regulator proteins 2 - 4, the yKu heterodimer and the subtelomeric core X element are all required for the maintenance of the chromatin structure of repressive ends. However, gene deletions of particular histone modification proteins can eliminate the silencing without the disruption of this chromatin structure.</p> <p>Conclusion</p> <p>Our data identifies chromatin features that correlate with the silencing state and indicate that an array of phased nucleosomes is not sufficient for full repression.</p

    Complete Genome Sequences of Two Temperate Bacillus subtilis Phages Isolated at Tumamoc Hill Desert Laboratory

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    Bacteriophages are important in structuring bacterial communities, including desert soils dominated by Bacillus species. Here, we describe two genetically similar temperate phages isolated on a Bacillus subtilis strain from soil in Tucson, Arizona. Their double-stranded DNA (dsDNA) genomes contain 98 and 102 genes, with a set of 4 genes being found in only one phage

    Review of Large Carnivore Conservation: Integrating Science and Policy in the North American West

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    The management and conservation of large carnivores is of worldwide concern and is as much about human values, interactions, and governance as carnivore biology. Susan Clark and Murray Rutherford continue their work on coexisting with large carnivores ( Clark et al. 2005 ) with a new edited volume Large Carnivore Conservation: Integrating Science and Policy in the North American West . Large Carnivore Conservation that expands on the same themes as their previous work with case studies from Arizona to the Yukon. While focusing on the North American West, Clark and Rutherford hope to provide a holistic approach to carnivore management in general

    SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses

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    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus that causes the respiratory disease known as coronavirus disease 2019 (COVID-19). Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the signal recognition particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses

    SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses

    Get PDF
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus that causes the respiratory disease known as coronavirus disease 2019 (COVID-19). Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the signal recognition particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses

    Resource Concentration Modulates the Fate of Dissimilated Nitrogen in a Dual-Pathway Actinobacterium

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    Respiratory ammonification and denitrification are two evolutionarily unrelated dissimilatory nitrogen (N) processes central to the global N cycle, the activity of which is thought to be controlled by carbon (C) to nitrate (NO_3^−) ratio. Here we find that Intrasporangium calvum C5, a novel dual-pathway denitrifier/respiratory ammonifier, disproportionately utilizes ammonification rather than denitrification when grown under low C concentrations, even at low C:NO_3^− ratios. This finding is in conflict with the paradigm that high C:NO_3^− ratios promote ammonification and low C:NO_3^− ratios promote denitrification. We find that the protein atomic composition for denitrification modules (NirK) are significantly cost minimized for C and N compared to ammonification modules (NrfA), indicating that limitation for C and N is a major evolutionary selective pressure imprinted in the architecture of these proteins. The evolutionary precedent for these findings suggests ecological importance for microbial activity as evidenced by higher growth rates when I. calvum grows predominantly using its ammonification pathway and by assimilating its end-product (ammonium) for growth under ammonium-free conditions. Genomic analysis of I. calvumfurther reveals a versatile ecophysiology to cope with nutrient stress and redox conditions. Metabolite and transcriptional profiles during growth indicate that enzyme modules, NrfAH and NirK, are not constitutively expressed but rather induced by nitrite production via NarG. Mechanistically, our results suggest that pathway selection is driven by intracellular redox potential (redox poise), which may be lowered when resource concentrations are low, thereby decreasing catalytic activity of upstream electron transport steps (i.e., the bc1 complex) needed for denitrification enzymes. Our work advances our understanding of the biogeochemical flexibility of N-cycling organisms, pathway evolution, and ecological food-webs

    Wakefield Generation in Hydrogen and Lithium Plasmas at FACET-II: Diagnostics and First Beam-Plasma Interaction Results

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    Plasma Wakefield Acceleration (PWFA) provides ultrahigh acceleration gradients of 10s of GeV/m, providing a novel path towards efficient, compact, TeV-scale linear colliders and high brightness free electron lasers. Critical to the success of these applications is demonstrating simultaneously high gradient acceleration, high energy transfer efficiency, and preservation of emittance, charge, and energy spread. Experiments at the FACET-II National User Facility at SLAC National Accelerator Laboratory aim to achieve all of these milestones in a single stage plasma wakefield accelerator, providing a 10 GeV energy gain in a <1 m plasma with high energy transfer efficiency. Such a demonstration depends critically on diagnostics able to measure emittance with mm-mrad accuracy, energy spectra to determine both %-level energy spread and broadband energy gain and loss, incoming longitudinal phase space, and matching dynamics. This paper discusses the experimental setup at FACET-II, including the incoming beam parameters from the FACET-II linac, plasma sources, and diagnostics developed to meet this challenge. Initial progress on the generation of beam ionized wakes in meter-scale hydrogen gas is discussed, as well as commissioning of the plasma sources and diagnostics

    Resource Concentration Modulates the Fate of Dissimilated Nitrogen in a Dual-Pathway Actinobacterium

    Get PDF
    Respiratory ammonification and denitrification are two evolutionarily unrelated dissimilatory nitrogen (N) processes central to the global N cycle, the activity of which is thought to be controlled by carbon (C) to nitrate (NO3−) ratio. Here we find that Intrasporangium calvum C5, a novel dual-pathway denitrifier/respiratory ammonifier, disproportionately utilizes ammonification rather than denitrification when grown under low C concentrations, even at low C:NO3− ratios. This finding is in conflict with the paradigm that high C:NO3− ratios promote ammonification and low C:NO3− ratios promote denitrification. We find that the protein atomic composition for denitrification modules (NirK) are significantly cost minimized for C and N compared to ammonification modules (NrfA), indicating that limitation for C and N is a major evolutionary selective pressure imprinted in the architecture of these proteins. The evolutionary precedent for these findings suggests ecological importance for microbial activity as evidenced by higher growth rates when I. calvum grows predominantly using its ammonification pathway and by assimilating its end-product (ammonium) for growth under ammonium-free conditions. Genomic analysis of I. calvum further reveals a versatile ecophysiology to cope with nutrient stress and redox conditions. Metabolite and transcriptional profiles during growth indicate that enzyme modules, NrfAH and NirK, are not constitutively expressed but rather induced by nitrite production via NarG. Mechanistically, our results suggest that pathway selection is driven by intracellular redox potential (redox poise), which may be lowered when resource concentrations are low, thereby decreasing catalytic activity of upstream electron transport steps (i.e., the bc1 complex) needed for denitrification enzymes. Our work advances our understanding of the biogeochemical flexibility of N-cycling organisms, pathway evolution, and ecological food-webs
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