367 research outputs found

    Drosophila studies support a role for a presynaptic synaptotagmin mutation in a human congenital myasthenic syndrome.

    Get PDF
    During chemical transmission, the function of synaptic proteins must be coordinated to efficiently release neurotransmitter. Synaptotagmin 2, the Ca2+ sensor for fast, synchronized neurotransmitter release at the human neuromuscular junction, has recently been implicated in a dominantly inherited congenital myasthenic syndrome associated with a non-progressive motor neuropathy. In one family, a proline residue within the C2B Ca2+-binding pocket of synaptotagmin is replaced by a leucine. The functional significance of this residue has not been investigated previously. Here we show that in silico modeling predicts disruption of the C2B Ca2+-binding pocket, and we examine the in vivo effects of the homologous mutation in Drosophila. When expressed in the absence of native synaptotagmin, this mutation is lethal, demonstrating for the first time that this residue plays a critical role in synaptotagmin function. To achieve expression similar to human patients, the mutation is expressed in flies carrying one copy of the wild type synaptotagmin gene. We now show that Drosophila carrying this mutation developed neurological and behavioral manifestations similar to those of human patients and provide insight into the mechanisms underlying these deficits. Our Drosophila studies support a role for this synaptotagmin point mutation in disease etiology

    Search for the lepton-family-number nonconserving decay \mu -> e + \gamma

    Full text link
    The MEGA experiment, which searched for the muon- and electron-number violating decay \mu -> e + \gamma, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio of \mu -> e + \gamma) < 1.2 x 10^{-11} was obtained

    ESBL displace: a protocol for an observational study to identify displacing Escherichia coli strain candidates from ESBL-colonized travel returners using phenotypic, genomic sequencing and metagenome analysis

    Get PDF
    Introduction: Invading extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-PE), non-ESBL E. coli, and other bacteria form a complex environment in the gut. The duration and dynamics of ESBL-PE colonization varies among individuals. Understanding the factors associated with colonization may lead to decolonization strategies. In this study, we aim to identify (i) single E. coli strains and (ii) microbiome networks that correlate with retention or decline of colonization, and (iii) pan-sensitive E. coli strains that potentially could be used to displace ESBL-PE during colonization. Methods and analysis: We recruit healthy travellers to Southeast Asia for a one-year prospective observational follow-up study. We collect and biobank stool, serum, and peripheral blood mononuclear cells (PBMCs) at predefined timepoints. Additional information is collected with questionnaires. We determine the colonization status with ESBL-PE and non-ESBL E. coli and quantify cell densities in stools and ratios over time. We characterize multiple single bacterial isolates per patient and timepoint using whole genome sequencing (WGS) and 16S/ITS amplicon-based and shotgun metagenomics. We determine phylogenetic relationships between isolates, antimicrobial resistance (AMR; phenotypic and genotypic), and virulence genes. We describe the bacterial and fungal stool microbiome alpha and beta diversity on 16S/ITS metagenomic data. We describe patterns in microbiome dynamics to identify features associated with protection or risk of ESBL-PE colonization. Ethics and dissemination: The study is registered (clinicaltrials.gov; NCT04764500 on 09/02/2019) and approved by the Ethics Committee (EKNZ project ID 2019-00044). We will present anonymized results at conferences and in scientific journals. Bacterial sequencing data will be shared via publicly accessible databases according to FAIR principles

    Effects of Ultraviolet Radiation and Contaminant-related Stressors on Arctic Freshwater Ecosystems

    Get PDF
    Climate change is likely to act as a multiple stressor, leading to cumulative and/or synergistic impacts on aquatic systems. Projected increases in temperature and corresponding alterations in precipitation regimes will enhance contaminant influxes to aquatic systems, and independently increase the susceptibility of aquatic organisms to contaminant exposure and effects. The consequences for the biota will in most cases be additive (cumulative) and multiplicative (synergistic). The overall result will be higher contaminant loads and biomagnifi-cation in aquatic ecosystems. Changes in stratospheric ozone and corresponding ultraviolet radiation regimes are also expected to produce cumulative and/or synergistic effects on aquatic ecosystem structure and function. Reduced ice cover is likely to have a much greater effect on underwater UV radiation exposure than the projected levels of stratospheric ozone depletion. A major increase in UV radiation levels will cause enhanced damage to organisms (biomolecular, cellular, and physiological damage, and alterations in species composition). Alloca-tions of energy and resources by aquatic biota to UV radiation protection will increase, probably decreasing trophic-level productivity. Elemental fluxes will increase via photochemical pathways

    Morphological variation in a secondary contact between divergent lineages of brown trout (Salmo trutta) from the Iberian Peninsula

    Get PDF
    The aim of this study was to analyze the morphological variation of brown trout (Salmo trutta) in the Duero basin, an Atlantic river basin in the Iberian Peninsula, where a spatial segregation of two divergent lineages was previously reported, based on isozyme, microsatellite and mtDNA data. In these studies, two divergent pure regions (Pisuerga and Lower-course) and several hybrid populations between them were identified. Morphological variation was evaluated in 11 populations representative of the genetic differentiation previously observed in the Duero basin, using multivariate analysis on 12 morphometric and 4 meristic traits. A large differentiation between populations was observed (interpopulation component of variance: 41.8%), similar to that previously detected with allozymes and microsatellites. Morphometric differentiation was also reflected by the high classification success of pure and hybrid individuals to their respective populations, using multivariate discriminant functions (94.1% and 79.0%, respectively). All multivariate and clustering analyses performed demonstrated a strong differentiation between the pure regions. The hybrid populations, though showing large differentiation among them, evidenced an intermediate position between the pure samples. Head and body shape traits were the most discriminant among the morphometric characters, while pectoral rays and gillrakers were the most discriminant among the meristic traits. These results confirmed the high divergence of the brown trout from the Duero basin and suggest some traits on which selection could be acting to explain the spatial segregation observed
    corecore