Effects of X-Linkage and Sex-Biased Gene Expression on the Rate of Adaptive Protein Evolution in Drosophila

Patterns of polymorphism and divergence in Drosophila protein-coding genes suggest that a considerable fraction of amino acid differences between species can be attributed to positive selection and that genes with sex-biased expression, that is, those expressed predominantly in one sex, have especially high rates of adaptive evolution. Previous studies, however, have been restricted to autosomal sex-biased genes and, thus, do not provide a complete picture of the evolutionary forces acting on sex-biased genes across the genome. To determine the effects of X-linkage on sex-biased gene evolution, we surveyed DNA sequence polymorphism and divergence in 45 X-linked genes, including 17 with male-biased expression, 13 with female-biased expression, and 15 with equal expression in the 2 sexes. Using both single- and multilocus tests for selection, we found evidence for adaptive evolution in both groups of sex-biased genes. The signal of adaptive evolution was particularly strong for X-linked male-biased genes. A comparison with data from 91 autosomal genes revealed a ‘‘fast-X’’ effect, in which the rate of adaptive evolution was greater for X-linked than for autosomal genes. This effect was strongest for male-biased genes but could be seen in the other groups as well. A genome-wide analysis of coding sequence divergence that accounted for sex-biased expression also uncovered a fast-X effect for male-biased and unbiased genes, suggesting that recessive beneficial mutations play an important role in adaptation.Organismic and Evolutionary Biolog

X-33 Metallic TPS Tests in NASA-LaRC High Temperature Tunnel

Conclusions The first series of metallic TPS tests in the NASA-LaRC Mach 7 High Temperature Tunnel has been completed. Additional testing is 'in progress and shall provide data for off-design configurations for the metallic TPS. The available data are being analyzed and being used to correlate analytical models to be used for X-33 flight design analysis. The final paper shan present additional data from these tests and comparisons between the data and analytical predictions

Statistical Inference of Selection and Divergence from a Time-Dependent Poisson Random Field Model

We apply a recently developed time-dependent Poisson random field model to aligned DNA sequences from two related biological species to estimate selection coefficients and divergence time. We use Markov chain Monte Carlo methods to estimate species divergence time and selection coefficients for each locus. The model assumes that the selective effects of non-synonymous mutations are normally distributed across genetic loci but constant within loci, and synonymous mutations are selectively neutral. In contrast with previous models, we do not assume that the individual species are at population equilibrium after divergence. Using a data set of 91 genes in two Drosophila species, D. melanogaster and D. simulans, we estimate the species divergence time (or 1.68 million years, assuming the haploid effective population size years) and a mean selection coefficient per generation . Although the average selection coefficient is positive, the magnitude of the selection is quite small. Results from numerical simulations are also presented as an accuracy check for the time-dependent model

MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload.

Heart failure remains a major public-health problem with an increase in the number of patients worsening from this disease. Despite current medical therapy, the condition still has a poor prognosis. Heart failure is complex but mitochondrial dysfunction seems to be an important target to improve cardiac function directly. Our goal was to analyze the effects of MitoQ (100 µM in drinking water) on the development and progression of heart failure induced by pressure overload after 14 weeks. The main findings are that pressure overload-induced heart failure in rats decreased cardiac function in vivo that was not altered by MitoQ. However, we observed a reduction in right ventricular hypertrophy and lung congestion in heart failure animals treated with MitoQ. Heart failure also decreased total mitochondrial protein content, mitochondrial membrane potential in the intermyofibrillar mitochondria. MitoQ restored membrane potential in IFM but did not restore mitochondrial protein content. These alterations are associated with the impairment of basal and stimulated mitochondrial respiration in IFM and SSM induced by heart failure. Moreover, MitoQ restored mitochondrial respiration in heart failure induced by pressure overload. We also detected higher levels of hydrogen peroxide production in heart failure and MitoQ restored the increase in ROS production. MitoQ was also able to improve mitochondrial calcium retention capacity, mainly in the SSM whereas in the IFM we observed a small alteration. In summary, MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload, by decreasing hydrogen peroxide formation, improving mitochondrial respiration and improving mPTP opening

Measurements of single top quark production cross sections and |Vtb| in ppbar collisions at sqrt{s}=1.96 TeV

We present measurements of production cross sections of single top quarks in \ppbar collisions at $\sqrt{s}=1.96\;\rm TeV$ in a data sample corresponding to an integrated luminosity of $5.4\;\rm fb^{-1}$ collected by the D0 detector at the Fermilab Tevatron Collider. We select events with an isolated electron or muon, an imbalance in transverse energy, and two, three, or four jets, with one or two of them containing a bottom hadron. We obtain an inclusive cross section of \sigma({\ppbar}{\rargap}tb+X, tqb+X) = 3.43\pm^{0.73}_{0.74}\;\rm pb and use it to extract the CKM matrix element $0.79 < |V_{tb}| \leq 1$ at the 95% C.L. We also measure \sigma({\ppbar}{\rargap}tb+X) = 0.68\pm^{0.38}_{0.35}\;\rm pb and \sigma({\ppbar}{\rargap}tqb+X) = 2.86\pm^{0.69}_{0.63}\;\rm pb when assuming, respectively, $tqb$ and $tb$ production rates as predicted by the standard model.Comment: 11 pages, 8 figures, submitted to Phys. Rev.

Obscured phylogeny and possible recombinational dormancy in Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>is one of the best studied organisms in all of biology, but its phylogenetic structure has been difficult to resolve with current data and analytical techniques. We analyzed single nucleotide polymorphisms in chromosomes of representative strains to reconstruct the topology of its emergence.</p> <p>Results</p> <p>The phylogeny of <it>E. coli </it>varies according to the segment of chromosome analyzed. Recombination between extant <it>E. coli </it>groups is largely limited to only three intergroup pairings.</p> <p>Conclusions</p> <p>Segment-dependent phylogenies most likely are legacies of a complex recombination history. However, <it>E. coli </it>are now in an epoch in which they no longer broadly share DNA. Using the definition of species as organisms that freely exchange genetic material, this recombinational dormancy could reflect either the end of <it>E. coli </it>as a species, or herald the coalescence of <it>E. coli </it>groups into new species.</p

Foregone health care in adolescents from school and community settings in Indonesia: a cross-sectional study

Background Adolescence is a development period marked by the onset of a new set of health needs. The present study sought to quantify the prevalence of foregone care (not seeking medical care when needed) and identify which adolescents are at greater risk of having unmet healthcare needs. Methods A multi-stage random sampling strategy was used to recruit school participants (grade 10–12) in two provinces in Indonesia. Respondent driven sampling was used to recruit out-of-school adolescents in the community. All participants completed a self-reported questionnaire which measured healthcare seeking behaviours, psychosocial wellbeing, use of healthcare services, and perceived barriers to accessing healthcare. Multivariable regression analysis was performed to examine factors associated with foregone care. Findings A total of 2161 adolescents participated in the present study and nearly one in four adolescents reported foregone care in the past year. Experiences of poly-victimisation and seeking care for mental health needs increased the risk of foregone care. In-school adolescents who reported psychological distress [adjusted risk ratio (aRR) = 1.88, 95%CI = 1.48–2.38] or had high body mass index (aRR = 1.25, 95%CI = 1.00–1.57) were at greater risk of foregone care. The leading reason for foregone care was lack of knowledge of available services. In-school adolescents predominantly reported non-access barriers to care (e.g., perception of the health concern or anxiety about accessing care) whereas most out-of-school adolescents reported access barriers (e.g., did not know where to get care or could not pay). Interpretation Foregone care is common among Indonesian adolescents, especially in adolescents with mental and physical health risks. Differences between in-school and out-of-school adolescents suggest that interventions to promote appropriate healthcare use will need tailoring. Further research is needed to determine causal relationships around barriers in access to healthcare

Signatures of Environmental Genetic Adaptation Pinpoint Pathogens as the Main Selective Pressure through Human Evolution

Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some susceptibility alleles for autoimmune diseases may be maintained in human population due to past selective processes

Model-independent measurement of t\boldsymbol{t}-channel single top quark production in ppˉ\boldsymbol{p\bar{p}} collisions at s=1.96\boldsymbol{\sqrt{s}=1.96} TeV

We present a model-independent measurement of $t$-channel electroweak production of single top quarks in \ppbar collisions at $\sqrt{s}=1.96\;\rm TeV$. Using $5.4\;\rm fb^{-1}$ of integrated luminosity collected by the D0 detector at the Fermilab Tevatron Collider, and selecting events containing an isolated electron or muon, missing transverse energy and one or two jets originating from the fragmentation of $b$ quarks, we measure a cross section \sigma({\ppbar}{\rargap}tqb+X) = 2.90 \pm 0.59\;\rm (stat+syst)\; pb for a top quark mass of $172.5\;\rm GeV$. The probability of the background to fluctuate and produce a signal as large as the one observed is $1.6\times10^{-8}$, corresponding to a significance of 5.5 standard deviations.Comment: 8 pages, 4 figures, submitted to Phys. Lett.