1,144 research outputs found

    Alveolar macrophages and Toll-like receptor 4 mediate ventilated lung ischemia reperfusion injury in mice.

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    BackgroundIschemia-reperfusion (I-R) injury is a sterile inflammatory process that is commonly associated with diverse clinical situations such as hemorrhage followed by resuscitation, transient embolic events, and organ transplantation. I-R injury can induce lung dysfunction whether the I-R occurs in the lung or in a remote organ. Recently, evidence has emerged that receptors and pathways of the innate immune system are involved in recognizing sterile inflammation and overlap considerably with those involved in the recognition of and response to pathogens.MethodsThe authors used a mouse surgical model of transient unilateral left pulmonary artery occlusion without bronchial involvement to create ventilated lung I-R injury. In addition, they mimicked nutritional I-R injury in vitro by transiently depriving cells of all nutrients.ResultsCompared with sham-operated mice, mice subjected to ventilated lung I-R injury had up-regulated lung expression of inflammatory mediator messenger RNA for interleukin-1β, interleukin-6, and chemokine (C-X-C motif) ligand-1 and -2, paralleled by histologic evidence of lung neutrophil recruitment and increased plasma concentrations of interleukin-1β, interleukin-6, and high-mobility group protein B1 proteins. This inflammatory response to I-R required toll-like receptor-4 (TLR4). In addition, the authors demonstrated in vitro cooperativity and cross-talk between human macrophages and endothelial cells, resulting in augmented inflammatory responses to I-R. Remarkably, the authors found that selective depletion of alveolar macrophages rendered mice resistant to ventilated lung I-R injury.ConclusionsThe data reveal that alveolar macrophages and the pattern recognition receptor toll-like receptor-4 are involved in the generation of the early inflammatory response to lung I-R injury

    Polygenic risk scores for cigarettes smoked per day do not generalize to a Native American population

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    Recent studies have demonstrated the utility of polygenic risk scores (PRSs) for exploring the genetic etiology of psychiatric phenotypes and the genetic correlations between them. To date, these studies have been conducted almost exclusively using participants of European ancestry, and thus, there is a need for similar studies conducted in other ancestral populations. However, given that the predictive ability of PRSs are sensitive to differences in linkage disequilibrium (LD) patterns and minor allele frequencies across discovery and target samples, the applicability of PRSs developed in European ancestry samples to other ancestral populations has yet to be determined. Therefore, the current study derived PRSs for cigarettes per day (CPD) from predominantly European-ancestry samples and examined their ability to predict nicotine dependence (ND) in a Native American (NA) population sample

    Equilibrium and transport properties of CO2+N2O and CO2+NO mixtures : a molecular simulation and equation of state modelling study.

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    International audienceIn the present study, the thermodynamic behaviour and transport properties of CO2+N2O and CO2+NO mixtures have been investigated using molecular simulation and equation of state modelling. Molecular simulations were based on Monte Carlo and Molecular Dynamics calculations using force fields calibrated from pure component properties and no adjustment of mixture properties was performed. Original force fields were proposed for N2O, NO and N2O2 molecules. Special attention must be paid when studying nitric oxide containing systems because this compound can exist as a mixture of monomers (NO) and dimers (N2O2) under certain pressure and temperature conditions. Liquid-vapour coexistence properties of the reacting NO-N2O2 system were thus first investigated using combined reaction ensemble and Gibbs ensemble Monte Carlo methods. Using the new force fields proposed, phase compositions, phase densities and phase viscosities were determined for CO2+NOx mixtures. Due to the strong similarities between carbon dioxide and nitrous oxide (Tc(CO2) = 304.21 K; Tc(N2O) = 309.57 K; Pc(CO2) = 7.38 MPa; Pc(N2O) = 7.24 MPa), the obtained thermodynamic and transport properties for a CO2+N2O mixture with 10 mol% of N2O are similar to pure CO2 properties in the whole range of studied temperatures (273 - 293 K), in agreement with available experimental data. Calculations of CO2+NO equilibrium and transport properties were also performed at three different temperatures in the range of 253 - 273 K. At these temperatures, only the monomer form of the nitric oxide (NO) has to be accounted for. The performed calculations are pure predictions since no experimental data are available in the open literature for this system. For a mixture containing 10 mol% of NO, the simulation results show a decrease of the liquid densities and viscosities of 9% and 24% with respect to corresponding pure CO2 values, respectively. The new pseudo-experimental data generated in this work were finally used to calibrate binary interaction parameters required in standard cubic equations of states. Both Peng-Robinson and Soave-Redlich-Kwong equations of state have been considered and after the regression, they display a decent match with experimental and pseudo-experimental data of the vapour-liquid equilibrium for the two studied mixtures

    Communication: Tolman length and rigidity constants of water and their role in nucleation

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    A proper understanding of nucleation is crucial in several natural and industrial processes. However, accurate quantitative predictions of this phenomenon have not been possible. The most popular tool for calculating nucleation rates, classical nucleation theory (CNT), deviates by orders of magnitude from experiments for most substances. We investigate whether part of this discrepancy can be accounted for by the curvature-dependence of the surface tension. To that end, we evaluate the eading order corrections for water, the Tolman length and the rigidity constants, using square gradient theory coupled with the accurate cubic plus association equation of state. The Helfrich expansion is then used to incorporate them into the CNT-framework. For water condensation, the modified framework successfully corrects the erroneous temperature dependence of the nucleation rates given by the classical theory and reproduces experimental nucleation rates

    Protective variant associated with alcohol dependence in a Mexican American cohort

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    Abstract Background Mexican Americans, particularly those born in the United States, are at greater risk for alcohol associated morbidity and mortality. The present study sought to investigate whether specific genetic variants may be associated with alcohol use disorder phenotypes in a select population of Mexican American young adults. Methods The study evaluated a cohort of 427 (age 18 – 30 years) Mexican American men (n = 171) and women (n = 256). Information on alcohol dependence was obtained through interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). For all subjects, DNA was extracted from blood samples, followed by genotyping using an Affymetrix Axiom Exome1A chip. Results A protective variant (rs991316) located downstream from the ADH7 (alcohol dehydrogenase 7) gene showed suggestive significance in association with alcohol dependence symptom counts derived from DSM-III-R and DSM-IV criteria, as well as to clustered alcohol dependence symptoms. Additional linkage analysis suggested that nearby variants in linkage disequilibrium with rs991316 were not responsible for the observed association with the alcohol dependence phenotypes in this study. Conclusions ADH7 has been shown to have a protective role against alcohol dependence in previous studies involving other ethnicities, but has not been reported for Mexican Americans. These results suggest that variants near ADH7 may play a role in protection from alcohol dependence in this Mexican American cohort

    Low-lying resonance states in the Be-9 continuum

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    Excited states in Be-9 from 2 to 9 MeV are studied via beta delayed particle emission from Li-9. The broad overlapping particle unbound states are investigated using an extension of an experimental method developed for dealing with three-body decays of broad isolated levels. The results confirm the existence of a broad state at 5 MeV, with a width of 2 MeV. Angular correlations are used for firm spin determinations for this and other levels
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