1,077 research outputs found

    Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

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    The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

    BB flavour tagging using charm decays at the LHCb experiment

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    An algorithm is described for tagging the flavour content at production of neutral BB mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a BB meson with the charge of a reconstructed secondary charm hadron from the decay of the other bb hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes B+J/ψK+B^+ \to J/\psi \, K^+ and B0J/ψK0B^0 \to J/\psi \, K^{*0} using 3.0fb13.0\mathrm{\,fb}^{-1} of data collected by the LHCb experiment at pppp centre-of-mass energies of 7TeV7\mathrm{\,TeV} and 8TeV8\mathrm{\,TeV}. Its tagging power on these samples of BJ/ψXB \to J/\psi \, X decays is (0.30±0.01±0.01)%(0.30 \pm 0.01 \pm 0.01) \%.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm

    Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

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    Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

    African Americans, Gentrification, and Neoliberal Urbanization: the Case of Fort Greene, Brooklyn

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    This article examines the gentrification of Fort Greene, which is located in the western part of black Brooklyn, one of the largest contiguous black urban areas in the USA. Between the late 1960s and 2003, gentrification in Fort Greene followed the patterns discovered by scholars of black neighborhoods; the gentrifying agents were almost exclusively black and gentrification as a process was largely bottom-up because entities interested in the production of space were mostly not involved. Since 2003, this has changed. Whites have been moving to Fort Greene in large numbers and will soon represent the numerical majority. Public and private interventions in and around Fort Greene have created a new top-down version of gentrification, which is facilitating this white influx. Existing black residential and commercial tenants are replaced and displaced in the name of urban economic development

    Echium oil is not protective against weight loss in head and neck cancer patients undergoing curative radio(chemo)therapy: a randomised-controlled trial

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    Background: Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. Methods: In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. Results: Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs −5%) and n-6 GLA (42% vs −20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs −1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. Conclusions: Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. Trial registration: ClinicalTrials.gov Identifier NCT01596933

    Emerging New Crop Pests: Ecological Modelling and Analysis of the South American Potato Psyllid Russelliana solanicola (Hemiptera: Psylloidea) and Its Wild Relatives

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    © 2017 Syfert 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

    Search for rare quark-annihilation decays, B --> Ds(*) Phi

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    We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

    A multicentre observational study of presentation and early assessment of acute stroke

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    Objective To investigate delays in the presentation to hospital and evaluation of patients with suspected stroke.Design Multicentre prospective observational study.Setting 22 hospitals in the United Kingdom and Dublin.Participants 739 patients with suspected stroke presenting to hospital.Main outcome measures Time from onset of stroke symptoms to arrival at hospital, and time from arrival to evaluation by a senior doctor.Results The median age of patients was 75 years, and 400 were women. The median delay between onset of symptoms and arrival at hospital was 6 hours (interquartile range 1 hour 48 minutes to 19 hours 12 minutes). 37% of patients arrived within 3 hours, 50% within 6 hours. The median delay for patients using the emergency service was 2 hours 3 minutes (47 minutes to 7 hours 12 minutes) compared with 7 hours 12 minutes (2 hours 5 minutes to 20 hours 37 minutes) for referrals from general practitioners (P < 0.0001). Use of emergency services reduced delays to hospital (odds ratio 0.45, 95% confidence interval 0.23 to 0.61). The median titre to evaluation by a senior doctor was 1 hour 9 minutes (interquartile range 33 minutes to 1 flour 50 minutes) but was undertaken in only 477 (65%) patients within 3 hours of arrival. This was not influenced by age, sex, time of presentation, mode of referral, hospital type, or the presence of a stroke unit. Computed tomography was requested within 3 hours of arrival in 166 (22%) patients but undertaken in only 60 (8%).Conclusion Delays in patients arriving at hospital with suspected stroke can be reduced by the increased use of emergency services. Over a third of patients arrive at hospital within three hours of stroke; their management can be improved by expediting medical evaluation and performing computed tomography early

    Multiscale Modeling of Red Blood Cell Mechanics and Blood Flow in Malaria

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    Red blood cells (RBCs) infected by a Plasmodium parasite in malaria may lose their membrane deformability with a relative membrane stiffening more than ten-fold in comparison with healthy RBCs leading to potential capillary occlusions. Moreover, infected RBCs are able to adhere to other healthy and parasitized cells and to the vascular endothelium resulting in a substantial disruption of normal blood circulation. In the present work, we simulate infected RBCs in malaria using a multiscale RBC model based on the dissipative particle dynamics method, coupling scales at the sub-cellular level with scales at the vessel size. Our objective is to conduct a full validation of the RBC model with a diverse set of experimental data, including temperature dependence, and to identify the limitations of this purely mechanistic model. The simulated elastic deformations of parasitized RBCs match those obtained in optical-tweezers experiments for different stages of intra-erythrocytic parasite development. The rheological properties of RBCs in malaria are compared with those obtained by optical magnetic twisting cytometry and by monitoring membrane fluctuations at room, physiological, and febrile temperatures. We also study the dynamics of infected RBCs in Poiseuille flow in comparison with healthy cells and present validated bulk viscosity predictions of malaria-infected blood for a wide range of parasitemia levels (percentage of infected RBCs with respect to the total number of cells in a unit volume).United States. National Institutes of Health (Grant R01HL094270)National Science Foundation (U.S.). (Grant CBET-0852948)Singapore-MIT Alliance for Research and Technology Cente

    Measurement of triple gauge-boson couplings at 172 GeV

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    The triple gauge-boson couplings, Awp, Aw and Abp, have been measured using 34 semileptonically and 54 hadronically decaying WW candidate events. The events were selected in the data recorded during 1996 with the ALEPH detector at 172 GeV, corresponding to an integrated luminosity of 10.65 pb^-1. The triple gauge-boson couplings have been measured using optimal observables constructed from kinematic information of WW events. The results are in agreement with the Standard Model expectation
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