1,418 research outputs found

    Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing

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    Voltage-gated sodium channels are vital membrane proteins essential for electrical signalling; in humans, they are key targets for the development of pharmaceutical drugs. Here we report the crystal structure of an open-channel conformation of NavMs, the bacterial channel pore from the marine bacterium Magnetococcus sp. (strain MC-1). It differs from the recently published crystal structure of a closed form of a related bacterial sodium channel (NavAb) by having its internal cavity accessible to the cytoplasmic surface as a result of a bend/rotation about a central residue in the carboxy-terminal transmembrane segment. This produces an open activation gate of sufficient diameter to allow hydrated sodium ions to pass through. Comparison of the open and closed structures provides new insight into the features of the functional states present in the activation cycles of sodium channels and the mechanism of channel opening and closing

    The distribution of pond snail communities across a landscape: separating out the influence of spatial position from local habitat quality for ponds in south-east Northumberland, UK

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    Ponds support a rich biodiversity because the heterogeneity of individual ponds creates, at the landscape scale, a diversity of habitats for wildlife. The distribution of pond animals and plants will be influenced by both the local conditions within a pond and the spatial distribution of ponds across the landscape. Separating out the local from the spatial is difficult because the two are often linked. Pond snails are likely to be affected by both local conditions, e.g. water hardness, and spatial patterns, e.g. distance between ponds, but studies of snail communities struggle distinguishing between the two. In this study, communities of snails were recorded from 52 ponds in a biogeographically coherent landscape in north-east England. The distribution of snail communities was compared to local environments characterised by the macrophyte communities within each pond and to the spatial pattern of ponds throughout the landscape. Mantel tests were used to partial out the local versus the landscape respective influences. Snail communities became more similar in ponds that were closer together and in ponds with similar macrophyte communities as both the local and the landscape scale were important for this group of animals. Data were collected from several types of ponds, including those created on nature reserves specifically for wildlife, old field ponds (at least 150 years old) primarily created for watering livestock and subsidence ponds outside protected areas or amongst coastal dunes. No one pond type supported all the species. Larger, deeper ponds on nature reserves had the highest numbers of species within individual ponds but shallow, temporary sites on farm land supported a distinct temporary water fauna. The conservation of pond snails in this region requires a diversity of pond types rather than one idealised type and ponds scattered throughout the area at a variety of sites, not just concentrated on nature reserves

    Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

    Search for the standard model Higgs boson at LEP

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    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

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    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

    Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis

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    In addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss in other neurodegenerative diseases in which cognitive decline is apparent, such as Alzheimer's disease, we aimed to assess synaptic integrity in the ALS brain. Here, we have applied a unique combination of high-resolution imaging of post-mortem tissue with neuropathology, genetic screening and cognitive profiling of ALS cases. Analyses of more than 1 million synapses using two complimentary high-resolution techniques (electron microscopy and array tomography) revealed a loss of synapses from the prefrontal cortex of ALS patients. Importantly, synapse loss was significantly greater in cognitively impaired cases and was not due to cortical atrophy, nor associated with dementia-associated neuropathology. Interestingly, we found a trend between pTDP-43 pathology and synapse loss in the frontal cortex and discovered pTDP-43 puncta at a subset of synapses in the ALS brains. From these data, we postulate that synapse loss in the prefrontal cortex represents an underlying neurobiological substrate of cognitive decline in ALS

    Validity and reliability of a modified english version of the physical activity questionnaire for adolescents

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    BACKGROUND: Adaptation of physical activity self-report questionnaires is sometimes required to reflect the activity behaviours of diverse populations. The processes used to modify self-report questionnaires though are typically underreported. This two-phased study used a formative approach to investigate the validity and reliability of the Physical Activity Questionnaire for Adolescents (PAQ-A) in English youth. Phase one examined test content and response process validity and subsequently informed a modified version of the PAQ-A. Phase two assessed the validity and reliability of the modified PAQ-A. METHODS: In phase one, focus groups (n = 5) were conducted with adolescents (n = 20) to investigate test content and response processes of the original PAQ-A. Based on evidence gathered in phase one, a modified version of the questionnaire was administered to participants (n = 169, 14.5 ± 1.7 years) in phase two. Internal consistency and test-retest reliability were assessed using Cronbach’s alpha and intra-class correlations, respectively. Spearman correlations were used to assess associations between modified PAQ-A scores and accelerometer-derived physical activity, self-reported fitness and physical activity self-efficacy. RESULTS: Phase one revealed that the original PAQ-A was unrepresentative for English youth and that item comprehension varied. Contextual and population/cultural-specific modifications were made to the PAQ-A for use in the subsequent phase. In phase two, modified PAQ-A scores had acceptable internal consistency (α = 0.72) and test-retest reliability (ICC = 0.78). Modified PAQ-A scores were significantly associated with objectively assessed moderate-to-vigorous physical activity (r = 0.39), total physical activity (r = 0.42), self-reported fitness (r = 0.35), and physical activity self-efficacy (r = 0.32) (p ≤ 0.01). CONCLUSIONS: The modified PAQ-A had acceptable internal consistency and test-retest reliability. Modified PAQ-A scores displayed weak-to-moderate correlations with objectively measured physical activity, self-reported fitness, and self-efficacy providing evidence of satisfactory criterion and construct validity, respectively. Further testing with more diverse English samples is recommended to provide a more complete assessment of the tool. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13690-016-0115-2) contains supplementary material, which is available to authorized users

    The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.

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    A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão's historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage

    Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

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    A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of s=7  TeV \sqrt{s}=7\;\mathrm{TeV} proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40
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