1,950 research outputs found

    Photo-antagonism of the GABAA receptor

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    Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

    Sedentary Time and Physical Activity Surveillance Through Accelerometer Pooling in Four European Countries.

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    OBJECTIVE: The objective of this study was to pool, harmonise and re-analyse national accelerometer data from adults in four European countries in order to describe population levels of sedentary time and physical inactivity. METHODS: Five cross-sectional studies were included from England, Portugal, Norway and Sweden. ActiGraph accelerometer count data were centrally processed using the same algorithms. Multivariable logistic regression analyses were conducted to study the associations of sedentary time and physical inactivity with sex, age, weight status and educational level, in both the pooled sample and the separate study samples. RESULTS: Data from 9509 participants were used. On average, participants were sedentary for 530 min/day, and accumulated 36 min/day of moderate to vigorous intensity physical activity. Twenty-three percent accumulated more than 10 h of sedentary time/day, and 72% did not meet the physical activity recommendations. Nine percent of all participants were classified as high sedentary and low active. Participants from Norway showed the highest levels of sedentary time, while participants from England were the least physically active. Age and weight status were positively associated with sedentary time and not meeting the physical activity recommendations. Men and higher-educated people were more likely to be highly sedentary, while women and lower-educated people were more likely to be inactive. CONCLUSIONS: We found high levels of sedentary time and physical inactivity in four European countries. Older people and obese people were most likely to display these behaviours and thus deserve special attention in interventions and policy planning. In order to monitor these behaviours, accelerometer-based cross-European surveillance is recommended.The original studies were funded by the Norwegian Directorate of Health and the Norwegian School of Sport Sciences; the Portuguese Institute of Sport; a grant from the Stockholm County Council; and grants from the Swedish Council for Working Life and Social Research, and The Swedish Research Council for Environment, Agricultural Sciences, and Spatial Planning. AL, JL, JB and HvdP were supported by the Netherlands Organisation for Health Research and Development (Grant no. 200.600.001). KS was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health (award no. R01HL116381). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. KW was supported by the British Heart Foundation (Grant FS/12/58/29709). KW and SB were supported by the UK Medical Research Council (Grant MC_UU_12015/3)

    The population of close double white dwarfs in the Galaxy

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    We present a new model for the Galactic population of close double white dwarfs. The model accounts for the suggestion of the avoidance of a substantial spiral-in during mass transfer between a giant and a main-sequence star of comparable mass and for detailed cooling models. It agrees well with the observations of the local sample of white dwarfs if the initial binary fraction is close to 50% and an ad hoc assumption is made that white dwarfs with mass less than about 0.3 solar mass cool faster than the models suggest. About 1000 white dwarfs brighter than V=15 have to be surveyed for detection of a pair which has total mass greater than the Chandrasekhar mass and will merge within 10 Gyr.Comment: 15 pages, 7 figures, to appear in Proc. ``The influence of binaries on stellar population studies'', Brussels, August 2000 (Kluwer, D. Vanbeveren ed.

    The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

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    Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

    Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study.

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    Objectives Decreased thyroid volume has been related to increased prevalence of thyroid cancer.Subjects and methods One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63).Results Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%).Conclusions Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects

    Lactation curves of Montbéliarde-sired and Viking Red-sired crossbred cows and their Holstein herdmates in commercial dairies

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    Lactation curves were estimated for Montbéliarde (MO) × Holstein (HO) and Viking Red (VR) × HO 2-breed crossbred cows and for MO × VR/HO and VR × MO/HO 3-breed crossbred cows and their HO herdmates from test-day observations in 7 high-performance herds that participated in a designed study. Cows calved from 2010 to 2017. Test-day observations from milk recording were used to fit the lactation curves of cows in their first 3 lactations. Lactations of cows were required to have at least 250 DIM and to have at least 6 test days ≤265 DIM. Lactation curves from random regression (RR) were compared for 305-d production (kg), peak production (kg), peak day of production, and production from 4 to 103 DIM (kg), from 104 to 205 DIM (kg), and from 206 to 305 DIM (kg) for milk, fat, and protein. Also, the persistency of production was compared. First-lactation versus second- and third-lactation cows were analyzed separately for both the 2-breed and 3-breed crossbred cows and their respective HO herdmates. Legendre polynomial RR had the best goodness of fit for the lactation curves compared with Ali-Schaeffer and Wilmink RR from the test-day observations of milk, fat, and protein production. For fluid milk production of first-lactation cows, the MO × HO 2-breed crossbreds were not different from their HO herdmates for any of the lactation-curve characteristics, except persistency. However, the VR × HO 2-breed crossbreds had less fluid milk production compared with their HO herdmates. For first lactation, the MO × HO 2-breed crossbreds had more persistency of milk, fat, and protein production compared with their HO herdmates. The first-lactation MO × VR/HO 3-breed crossbreds had more persistency of fluid milk production compared with their HO herdmates. For second and third lactations, both the MO × HO and the VR × HO 2-breed crossbreds had higher fat production compared with their HO herdmates. Furthermore, the MO × HO 2-breed crossbreds had more protein production (kg) in all 3 periods of lactation compared with their HO herdmates. Crossbred cows may have advantages over HO cows for persistency of production in high-performance herds.fals

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    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
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