721 research outputs found

    Complex Signatures of Natural Selection at the Duffy Blood Group Locus

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    The Duffy blood group locus (FY) has long been considered a likely target of natural selection, because of the extreme pattern of geographic differentiation of its three major alleles (FY*B, FY*A, and FY*O). In the present study, we resequenced the FY region in samples of Hausa from Cameroon (fixed for FY*O), Han Chinese (fixed for FY*A), Italians, and Pakistanis. Our goals were to characterize the signature of directional selection on FY*O in sub-Saharan Africa and to understand the extent to which natural selection has also played a role in the extreme geographic differentiation of the other derived allele at this locus, FY*A. The data from the FY region are compared with the patterns of variation observed at 10 unlinked, putatively neutral loci from the same populations, as well as with theoretical expectations from the neutral-equilibrium model. The FY region in the Hausa shows evidence of directional selection in two independent properties of the data (i.e., level of sequence variation and frequency spectrum), observations that are consistent with the FY*O mutation being the target. The Italian and Chinese FY data show patterns of variation that are very unusual, particularly with regard to frequency spectrum and linkage disequilibrium, but do not fit the predictions of any simple model of selection. These patterns may represent a more complex and previously unrecognized signature of positive selection

    Functional constraints on the constitutive androstane receptor inferred from human sequence variation and cross-species comparisons

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    <p>Abstract</p> <p>Members of the NR1I subfamily of nuclear receptors play a role in the transcriptional activation of genes involved in drug metabolism and transport. NR1I3, the constitutive androstane receptor (CAR), mediates the induction of several genes involved in drug response, including members of the <it>CYP3A</it>, <it>CYP2B </it>and <it>UGT1A </it>subfamilies. Large inter-individual variation in drug clearance has been reported for many drug metabolising enzyme genes. Sequence variation at the <it>CAR </it>locus could potentially contribute to variation in downstream targets, as well as to the substantial variation in expression level reported. We used a comparative genomics-based approach to select resequencing segments in 70 subjects from three populations. We identified 21 polymorphic sites, one of which results in an amino acid substitution. Our study reveals a common haplotype shared by all three populations which is remarkably similar to the ancestral sequence, confirming that CAR is under strong functional constraints. The level and pattern of sequence variation is approximately similar across populations, suggesting that interethnic differences in drug metabolism are not likely to be due to genetic variation at the <it>CAR </it>locus. We also identify several common non-coding variants that occur at highly conserved sites across four major branches of the mammalian phylogeny, suggesting that they may affect <it>CAR </it>expression and, ultimately, the activity of its downstream targets.</p

    Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis.

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    OBJECTIVE: To assess the association between leucocyte telomere length and risk of cardiovascular disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Studies published up to March 2014 identified through searches of Medline, Web of Science, and Embase. ELIGIBILITY CRITERIA: Prospective and retrospective studies that reported on associations between leucocyte telomere length and coronary heart disease (defined as non-fatal myocardial infarction, coronary heart disease death, or coronary revascularisation) or cerebrovascular disease (defined as non-fatal stroke or death from cerebrovascular disease) and were broadly representative of general populations--that is, they did not select cohort or control participants on the basis of pre-existing cardiovascular disease or diabetes. RESULTS: Twenty four studies involving 43,725 participants and 8400 patients with cardiovascular disease (5566 with coronary heart disease and 2834 with cerebrovascular disease) were found to be eligible. In a comparison of the shortest versus longest third of leucocyte telomere length, the pooled relative risk for coronary heart disease was 1.54 (95% confidence interval 1.30 to 1.83) in all studies, 1.40 (1.15 to 1.70) in prospective studies, and 1.80 (1.32 to 2.44) in retrospective studies. Heterogeneity between studies was moderate (I(2) = 64%, 41% to 77%, Phet<0.001) and was not significantly explained by mean age of participants (P = 0.23), the proportion of male participants (P = 0.45), or distinction between retrospective versus prospective studies (P = 0.32). Findings for coronary heart disease were similar in meta-analyses restricted to studies that adjusted for conventional vascular risk factors (relative risk 1.42, 95% confidence interval 1.17 to 1.73); studies with ≥ 200 cases (1.44, 1.20 to 1.74); studies with a high quality score (1.53, 1.22 to 1.92); and in analyses that corrected for publication bias (1.34, 1.12 to 1.60). The pooled relative risk for cerebrovascular disease was 1.42 (1.11 to 1.81), with no significant heterogeneity between studies (I(2) = 41%, 0% to 72%, Phet = 0.08). Shorter telomeres were not significantly associated with cerebrovascular disease risk in prospective studies (1.14, 0.85 to 1.54) or in studies with a high quality score (1.21, 0.83 to 1.76). CONCLUSION: Available observational data show an inverse association between leucocyte telomere length and risk of coronary heart disease independent of conventional vascular risk factors. The association with cerebrovascular disease is less certain

    Systematic review of resilience-enhancing, universal, primary school-based mental health promotion programs

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    En: BMC Psychology, 6:30. doi: 10.1186/s40359-018-0242-3Background: Wellbeing and resilience are essential in preventing and reducing the severity of mental health problems. Equipping children with coping skills and protective behavior can help them react positively to change and obstacles in life, allowing greater mental, social and academic success. This systematic review studies the implementation and evaluation of universal, resilience-focused mental health promotion programs based in primary schools. Methods: A systematic review of literature used five primary databases: PsycINFO; Web of Science; PubMed; Medline; Embase and The Cochrane Library; and keywords related to (a) health education, health promotion, mental health, mental health promotion, social and emotional wellbeing; (b) school health service, student, schools, whole-school; (c) adolescent, child, school child, pre-adolescent; (d) emotional intelligence, coping behavior, emotional adjustment, resilienc*, problem solving, to identify relevant articles. Articles included featured programs that were universally implemented in a primary school setting and focused on teaching of skills, including coping skills, help-seeking behaviors, stress management, and mindfulness, and were aimed at the overall goal of increasing resilience among students. Results: Of 3087 peer-reviewed articles initially identified, 475 articles were further evaluated with 11 reports on evaluations of 7 school-based mental health promotion programs meeting the inclusion criteria. Evaluation tools used in program evaluation are also reviewed, with successful trends in evaluations discussed. Encouraging results were seen when the program was delivered by teachers within the schools. Length of programing did not seem important to outcomes. Across all 7 programs, few long-term sustained effects were recorded following program completion. Conclusions: This review provides evidence that mental health promotion programs that focus on resilience and coping skills have positive impacts on the students’ ability to manage daily stressors

    School-based intervention study examining approaches for well-being and mental health literacy of pupils in Year 9 in England: study protocol for a multischool, parallel group cluster randomised controlled trial (AWARE) (vol 12, artne029044corr1, 20022)

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    The authors would like to notify that the co-authors Sara Evans-Lacko, Bettina Moltrecht, Kirsty Nisbet, Emma Thornton, Aurelie Lange, Paul Stallard, Abigail Thompson were missed including in the authorship list of the paper. The supplementary file has been also updated

    Marginal Reefs Under Stress: Physiological Limits Render Galápagos Corals Susceptible to Ocean Acidification and Thermal Stress

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    Ocean acidification (OA) and thermal stress may undermine corals' ability to calcify and support diverse reef communities, particularly in marginal environments. Coral calcification depends on aragonite supersaturation (Ω » 1) of the calcifying fluid (cf) from which the skeleton precipitates. Corals actively upregulate pHcf relative to seawater to buffer against changes in temperature and dissolved inorganic carbon, which together control Ωcf. Here we assess the buffering capacity of modern and fossil corals from the Galápagos Islands that have been exposed to sub-optimal conditions, extreme thermal stress, and OA. We demonstrate a significant decline in pHcf and Ωcf since the pre-industrial era, trends which are exacerbated during extreme warm years. These results suggest that there are likely physiological limits to corals' pH buffering capacity, and that these constraints render marginal reefs particularly susceptible to OA

    Intragroup competition predicts individual foraging specialisation in a group-living mammal

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    Individual foraging specialisation has important ecological implications, but its causes in group-living species are unclear. One of the major consequences of group living is increased intragroup competition for resources. Foraging theory predicts that with increased competition, individuals should add new prey items to their diet, widening their foraging niche (‘optimal foraging hypothesis’). However, classic competition theory suggests the opposite: that increased competition leads to niche partitioning and greater individual foraging specialisation (‘niche partitioning hypothesis’). We tested these opposing predictions in wild, group-living banded mongooses (Mungos mungo), using stable isotope analysis of banded mongoose whiskers to quantify individual and group foraging niche. Individual foraging niche size declined with increasing group size, despite all groups having a similar overall niche size. Our findings support the prediction that competition promotes niche partitioning within social groups and suggest that individual foraging specialisation may play an important role in the formation of stable social groupings.Peer reviewe

    Associations within school-based same-sex friendship networks of children's physical activity and sedentary behaviours:A cross-sectional social network analysis

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    Abstract Background Physical activity in children is associated with better physical and mental health but many children do not meet physical activity guidelines. Friendship groups are potentially an important influence on children’s physical activity and sedentary time. This paper examines the association between children of physical activity and sedentary time in school-based same-sex friendship networks, for both moderate-to-vigorous intensity physical activity (MVPA) and sedentary time. Moreover, considering the methodological challenges of conducting and interpreting these analyses, we provide examples of how to analyse these data and interpret results to encourage further work in the area. Methods Accelerometer data for 1223 children, aged 8-9 years, were collected in 2015-2016 and analysed in 2017. Mean accelerometer minutes of MVPA and sedentary time were calculated. Children named up to four school friends and same-sex school-based friendship networks were constructed. Network models, which include correlation between friends, were fitted by sex. Results Both MVPA and sedentary time were found to be associated via the friendship networks, for both boys and girls. The network autocorrelation was 0.21 (95% CI: 0.15 to 0.26) for boys’ MVPA, and 0.14 (95% CI: 0.07 to 0.21) for sedentary time. Network autocorrelation between girls was weaker, with 0.13 (95% CI: 0.06 to 0.19) for MVPA and 0.11 (95% CI: 0.05 to 0.17) for sedentary time. Conclusions Physical activity and sedentary time of boys and girls are associated with the physical activity and sedentary time respectively of others within same-sex friendship networks, and these associations are comparable to other known factors. In this study, the correlation between friends was stronger for boys than girls, and stronger for MVPA than for sedentary time. These findings suggest that friendship networks play a part in understanding children’s physical activity and sedentary time and could play a valuable role in developing effective interventions
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