172 research outputs found

    Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

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    Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Two cold inducible genes encoding lipid transfer protein LTP4 from barley show differential responses to bacterial pathogens

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    The barley genesHvLtp4.2 andHvLtp4.3 both encode the lipid transfer protein LTP4 and are less than 1 kb apart in tail-to-tail orientation. They differ in their non-coding regions from each other and from the gene corresponding to a previously reportedLtp4 cDNA (nowLtp4.1). Southern blot analysis indicated the existence of three or moreLtp4 genes per haploid genome and showed considerable polymorphism among barley cultivars. We have investigated the transient expression of genesHvLtp4.2 andHvLtp4.3 following transformation by particle bombardment, using promoter fusions to the-glucuronidase reporter sequence. In leaves, activities of the two promoters were of the same order as those of the sucrose synthase (Ss1) and cauliflower mosaic virus 35S promoters used as controls. Their expression patterns were similar, except thatLtp4.2 was more active thanLtp4.3 in endosperm, andLtp4.3 was active in roots, whileLtp4.2 was not. The promoters of both genes were induced by low temperature, both in winter and spring barley cultivars. Northern blot analysis, using theLtp4-specific probe, indicated thatXanthomonas campestris pv.translucens induced an increase over basal levels ofLtp4 mRNA, whilePseudomonas syringae pv.japonica caused a decrease. TheLtp4.3-Gus promoter fusion also responded in opposite ways to these two compatible bacterial pathogens, whereas theLtp4.2-Gus construction did not respond to infectio

    Gastrointestinal decontamination in the acutely poisoned patient

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    ObjectiveTo define the role of gastrointestinal (GI) decontamination of the poisoned patient.Data sourcesA computer-based PubMed/MEDLINE search of the literature on GI decontamination in the poisoned patient with cross referencing of sources.Study selection and data extractionClinical, animal and in vitro studies were reviewed for clinical relevance to GI decontamination of the poisoned patient.Data synthesisThe literature suggests that previously, widely used, aggressive approaches including the use of ipecac syrup, gastric lavage, and cathartics are now rarely recommended. Whole bowel irrigation is still often recommended for slow-release drugs, metals, and patients who "pack" or "stuff" foreign bodies filled with drugs of abuse, but with little quality data to support it. Activated charcoal (AC), single or multiple doses, was also a previous mainstay of GI decontamination, but the utility of AC is now recognized to be limited and more time dependent than previously practiced. These recommendations have resulted in several treatment guidelines that are mostly based on retrospective analysis, animal studies or small case series, and rarely based on randomized clinical trials.ConclusionsThe current literature supports limited use of GI decontamination of the poisoned patient

    Light regulation of metabolic pathways in fungi

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    Light represents a major carrier of information in nature. The molecular machineries translating its electromagnetic energy (photons) into the chemical language of cells transmit vital signals for adjustment of virtually every living organism to its habitat. Fungi react to illumination in various ways, and we found that they initiate considerable adaptations in their metabolic pathways upon growth in light or after perception of a light pulse. Alterations in response to light have predominantly been observed in carotenoid metabolism, polysaccharide and carbohydrate metabolism, fatty acid metabolism, nucleotide and nucleoside metabolism, and in regulation of production of secondary metabolites. Transcription of genes is initiated within minutes, abundance and activity of metabolic enzymes are adjusted, and subsequently, levels of metabolites are altered to cope with the harmful effects of light or to prepare for reproduction, which is dependent on light in many cases. This review aims to give an overview on metabolic pathways impacted by light and to illustrate the physiological significance of light for fungi. We provide a basis for assessment whether a given metabolic pathway might be subject to regulation by light and how these properties can be exploited for improvement of biotechnological processes

    Trapping in irradiated p-on-n silicon sensors at fluences anticipated at the HL-LHC outer tracker

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    The degradation of signal in silicon sensors is studied under conditions expected at the CERN High-Luminosity LHC. 200 μ\mum thick n-type silicon sensors are irradiated with protons of different energies to fluences of up to 310153 \cdot 10^{15} neq/cm2^2. Pulsed red laser light with a wavelength of 672 nm is used to generate electron-hole pairs in the sensors. The induced signals are used to determine the charge collection efficiencies separately for electrons and holes drifting through the sensor. The effective trapping rates are extracted by comparing the results to simulation. The electric field is simulated using Synopsys device simulation assuming two effective defects. The generation and drift of charge carriers are simulated in an independent simulation based on PixelAV. The effective trapping rates are determined from the measured charge collection efficiencies and the simulated and measured time-resolved current pulses are compared. The effective trapping rates determined for both electrons and holes are about 50% smaller than those obtained using standard extrapolations of studies at low fluences and suggests an improved tracker performance over initial expectations

    Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

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    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

    Search for dark matter produced in association with a single top quark or a top quark pair in proton-proton collisions at s=13 TeV

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    A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.A search for dark matter produced in association with top quarks in proton-proton collisions at a center-of-mass energy of 13 TeV is presented. The data set used corresponds to an integrated luminosity of 35.9 fb(-1) recorded with the CMS detector at the LHC. Whereas previous searches for neutral scalar or pseudoscalar mediators considered dark matter production in association with a top quark pair only, this analysis also includes production modes with a single top quark. The results are derived from the combination of multiple selection categories that are defined to target either the single top quark or the top quark pair signature. No significant deviations with respect to the standard model predictions are observed. The results are interpreted in the context of a simplified model in which a scalar or pseudoscalar mediator particle couples to a top quark and subsequently decays into dark matter particles. Scalar and pseudoscalar mediator particles with masses below 290 and 300 GeV, respectively, are excluded at 95% confidence level, assuming a dark matter particle mass of 1 GeV and mediator couplings to fermions and dark matter particles equal to unity.Peer reviewe

    Search for lepton flavour violating decays of the Higgs boson to eτand eμin proton–proton collisions at √s=8TeV

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    A direct search for lepton flavour violating decays of the Higgs boson (H) in the H →eτand H →eμchannels is described. The data sample used in the search was collected in proton–proton collisions at √s=8TeVwith the CMS detector at the LHC and corresponds to an integrated luminosity of 19.7fb−1. No evidence is found for lepton flavour violating decays in either final state. Upper limits on the branching fractions, B(H →eτ) <0.69%and B(H →eμ) <0.035%, are set at the 95% confidence level. The constraint set on B(H →eτ)is an order of magnitude more stringent than the existing indirect limits. The limits are used to constrain the corresponding flavour violating Yukawa couplings, absent in the standard model
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