415 research outputs found

    Inorganic Nitrate Promotes Glucose Uptake and Oxidative Catabolism in White Adipose Tissue through the XOR Catalyzed Nitric Oxide Pathway

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    An ageing global population combined with sedentary lifestyles and unhealthy diets has contributed to an increasing incidence of obesity and type 2 diabetes. These metabolic disorders are associated with perturbations to nitric oxide (NO) signaling and impaired glucose metabolism. Dietary inorganic nitrate, found in high concentration in green leafy vegetables, can be converted to NO in vivo and demonstrates anti-diabetic and anti-obesity properties in rodents. Alongside tissues including skeletal muscle and liver, white adipose tissue is also an important physiological site of glucose disposal. However, the distinct molecular mechanisms governing the effect of nitrate on adipose tissue glucose metabolism, and the contribution of this tissue to the glucose tolerant phenotype, remain to be determined. Using a metabolomic and stable-isotope labeling approach, combined with transcriptional analysis, we found that nitrate increases glucose uptake and oxidative catabolism in primary adipocytes and white adipose tissue of nitrate-treated rats. Mechanistically, we determine that nitrate induces these phenotypic changes in primary adipocytes through the xanthine oxidoreductase catalysed reduction of nitrate to nitric oxide and independently of Peroxisome Proliferator-Activated Receptor α. The nitrate-mediated enhancement of glucose uptake and catabolism in white adipose tissue may be a key contributor to the anti-diabetic effects of this anion

    A Golf Programme for People with Severe and Enduring Mental Health Problems

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    This article reports a pioneering golf programme for people with severe and enduring mental health problems. Following a discussion of the problems and possibilities of golf as a form of physical activity for this group, we outline the structure, organisation, and ethos of the golf programme. Through an analysis of qualitative case study data collected during the programme, we discuss the response to the programme from service users and mental health professionals. We conclude by highlighting aspects of the programme which were critical to its success and offering suggestions for further initiatives in this area

    Carpet-dust chemicals as measures of exposure: Implications of variability

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    <p>Abstract</p> <p>Background</p> <p>There is increasing interest in using chemicals measured in carpet dust as indicators of chemical exposures. However, investigators have rarely sampled dust repeatedly from the same households and therefore little is known about the variability of chemical levels that exist within and between households in dust samples.</p> <p>Results</p> <p>We analyzed 9 polycyclic aromatic hydrocarbons, 6 polychlorinated biphenyls, and nicotine in 68 carpet-dust samples from 21 households in agricultural communities of Fresno County, California collected from 2003-2005. Chemical concentrations (ng per g dust) ranged from < 2-3,609 for 9 polycyclic aromatic hydrocarbons, from < 1-150 for 6 polychlorinated biphenyls, and from < 20-7,776 for nicotine. We used random-effects models to estimate variance components for concentrations of each of these carpet-dust chemicals and calculated the variance ratio, λ, defined as the ratio of the within-household variance component to the between-household variance component. Subsequently, we used the variance ratios calculated from our data, to illustrate the potential effect of measurement error on the attenuation of odds ratios in hypothetical case-control studies. We found that the median value of the estimated variance ratios was 0.33 (range: 0.13-0.72). Correspondingly, in case-control studies of associations between these carpet-dust chemicals and disease, given the collection of only one measurement per household and a hypothetical odds ratio of 1.5, we expect that the observed odds ratios would range from 1.27 to 1.43. Moreover, for each of the chemicals analyzed, the collection of three repeated dust samples would limit the expected magnitude of odds ratio attenuation to less than 20%.</p> <p>Conclusions</p> <p>Our findings suggest that attenuation bias should be relatively modest when using these semi-volatile carpet-dust chemicals as exposure surrogates in epidemiologic studies.</p

    People with higher interoceptive sensitivity are more altruistic, but improving interoception does not increase altruism

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    People consistently show preferences and behaviors that benefit others at a cost to themselves, a phenomenon termed altruism. We investigated if perception of one’s body signals – interoception - may be underlying such behaviors. We tested if participants’ sensitivity to their own heartbeat predicted their decision on a choice between self-interest and altruism, and if improving this sensitivity through training would make participants more altruistic. Across these two experiments, interoceptive sensitivity predicted altruism measured through monetary generosity. Improving interoceptive sensitivity did, however, not lead to more altruistic behaviour. We conclude that there is a unique link between interoception and altruistic behaviour, likely established over an individual’s history of altruistic acts, and the body responses they elicit. The findings suggest that humans might literally ‘listen to their heart’ to guide their altruistic behavior

    Micro-CT imaging reveals<i> Mekk3 </i>heterozygosity prevents cerebral cavernous malformations in <i>Ccm2</i>-deficient mice

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    Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5ÎŒm (leading to a minimum feature size of approximately 25ÎŒm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases

    Hsa-miR-196a2 Rs11614913 Polymorphism Contributes to Cancer Susceptibility: Evidence from 15 Case-Control Studies

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    BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR=1.18, 95% CI=1.03-1.34, P<0.001 for heterogeneity test). In the stratified analyses, we observed that the CC genotype might modulate breast cancer risk (OR=1.11, 95%CI=1.01-1.23, Pheterogeneity=0.210) and lung cancer risk (OR=1.25, 95%CI=1.06-1.46, Pheterogeneity=0.958), comparing with the TC/TT genotype. Moreover, a significantly increased risk was found among Asian populations in a dominant model (TC/CC versus TT, OR=1.24, 95% CI=1.07-1.43, Pheterogeneity=0.006). CONCLUSIONS: These findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers

    Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

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    The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≄20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≀pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≀{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

    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

    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  Όb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) 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 ÎŁETPb. 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 ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ÎŁETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁥2Δϕ modulation for all ÎŁETPb ranges and particle pT
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