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

<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

Guidelines for Community‐Based Partners for Reviewing Research Grant Applications: Lessons from the Michigan Institute for Clinical and Health Research (MICHR) Community Engagement Research Core (CERC)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102046/1/cts12126.pd

Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process

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

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

The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

Constructing public health policies in post crisis countries: lessons to learn from the associations between free-sugars consumption and diabetes, obesity and dental caries before, during and after sanctions in Iraq.

BACKGROUND: This article aims to provide evidence for an informed public health policy on free-sugar consumption in post-crisis countries. METHODS: Iraq was selected as a case study. A systematic search for published data on the prevalence/incidence of type-2 diabetes, overweight/obesity, dental caries and free-sugar consumption levels in Iraq was conducted using MEDLINE, the Iraqi Academic Scientific journals and relevant international organisations' websites. Comparable data before (1980-1990), during (1991-2002) and after (2003-2015) the United Nations sanctions (UNS) were included. RESULTS: Ten studies were included. Quality scores ranged between 3 and 7/8. Free-sugar consumption decreased dramatically during the UNS (from 50 to 16.3 kg/person/year) and started increasing afterwards (24.1 kg/person/year). Changes in type-2 diabetes, overweight/obesity and caries levels mirrored those of free-sugar consumption. Caries declined markedly during UNS and started increasing afterwards. Comparable data on diabetes and overweight/obesity were only available for the periods during and after the UNS. Both of these conditions started increasing with increased free-sugar consumption after lifting the UNS. CONCLUSIONS: There is a need to develop a public health policy in post-crisis countries to maintain the reduction in free-sugar consumption, and hence promote both general and dental health, by integrating the common risk factor approach into the social determinant framework

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

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

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

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

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