34 research outputs found

    Patterns of nucleotide diversity at the regions encompassing the Drosophila insulin-like peptide (dilp) genes: demography vs positive selection in Drosophila melanogaster.

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    In Drosophila, the insulin-signaling pathway controls some life history traits, such as fertility and lifespan, and it is considered to be the main metabolic pathway involved in establishing adult body size. Several observations concerning variation in body size in the Drosophila genus are suggestive of its adaptive character. Genes encoding proteins in this pathway are, therefore, good candidates to have experienced adaptive changes and to reveal the footprint of positive selection. The Drosophila insulin-like peptides (DILPs) are the ligands that trigger the insulin-signaling cascade. In Drosophila melanogaster, there are several peptides that are structurally similar to the single mammalian insulin peptide. The footprint of recent adaptive changes on nucleotide variation can be unveiled through the analysis of polymorphism and divergence. With this aim, we have surveyed nucleotide sequence variation at the dilp1-7 genes in a natural population of D. melanogaster. The comparison of polymorphism in D. melanogaster and divergence from D. simulans at different functional classes of the dilp genes provided no evidence of adaptive protein evolution after the split of the D. melanogaster and D. simulans lineages. However, our survey of polymorphism at the dilp gene regions of D. melanogaster has provided some evidence for the action of positive selection at or near these genes. The regions encompassing the dilp1-4 genes and the dilp6 gene stand out as likely affected by recent adaptive events

    Wellbeing and arthritis incidence:The survey of health, ageing and retirement in Europe

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    BACKGROUND: A number of studies provide evidence for an association between psychosocial factors and risk of incident arthritis. Current evidence is largely limited to the examination of negative factors such as perceived stress, but positive factors such as subjective wellbeing may also play a role. PURPOSE: The purpose of the current study was to investigate whether people with higher subjective wellbeing have a lower risk of developing arthritis. METHODS: We used Cox proportional hazards regression to examine the prospective relationship between wellbeing (measured using the CASP-12) and incidence of arthritis over a 9-year period. The sample consisted of 13,594 participants aged ≥50 years from the Survey of Health, Ageing and Retirement in Europe. RESULTS: There was a significant association between greater wellbeing and reduced incident arthritis that was stronger at younger ages. In sex-adjusted analyses, for a standard deviation increase in CASP-12 score, the hazard ratios (95 % confidence intervals) for incident arthritis in people aged <65 and ≥65 years were 0.73 (0.69–0.77) and 0.80 (0.77–0.85), respectively. After further adjustment for other established risk factors, these associations were attenuated but remained significant in both age groups: the fully adjusted hazard ratios were 0.82 (0.77–0.87) and 0.88 (0.82–0.95), respectively. CONCLUSIONS: These results provide evidence for an association between greater wellbeing and reduced risk of incident arthritis and, more generally, support the theory that psychosocial factors are implicated in the aetiology of this disease. Future research needs to delineate the mechanisms underlying the association between wellbeing and arthritis risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12160-015-9764-6) contains supplementary material, which is available to authorized users

    Early-Life Nutritional Factors and Mucosal Immunity in the Development of Autoimmune Diabetes

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    Type 1 diabetes (T1D) is an immune-mediated disease with a strong genetic basis but might be influenced by non-genetic factors such as microbiome development that “programs” the immune system during early life as well. Factors influencing pathogenesis, including a leaky intestinal mucosal barrier, an aberrant gut microbiota composition, and altered immune responsiveness, offer potential targets for prevention and/or treatment of T1D through nutritional or pharmacologic means. In this review, nutritional approaches during early life in order to protect against T1D development have been discussed. The critical role of tolerogenic dendritic cells in central and peripheral tolerance has been emphasized. In addition, since the gut microbiota affects the development of T1D through short-chain fatty acid (SCFA)-dependent mechanisms, we hypothesize that nutritional intervention boosting SCFA production may be used as a novel prevention strategy. Current retrospective evidence has suggested that exclusive and prolonged breastfeeding might play a protective role against the development of T1D. The beneficial properties of human milk are possibly attributed to its bioactive components such as unique immune-modulatory components human milk oligosaccharides and metabolites derived thereof, including SCFAs. These components might play a key role in healthy immune development and creating a fit and resilient immune system in early and later life

    Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis

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    BackgroundAtopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th) 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and CCL22 chemokines.ObjectiveTo explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE).Subjects and methodsSerum samples (n = 41) obtained from a randomized, double-blind, and clinical dietary intervention study were used to study biomarkers in infants with AD. Baseline- and post-intervention samples (4 months) were used, six chemokines and nine ratios thereof were analyzed using Luminex and correlated to AD severity. In the initial study, the infants were randomized to receive extensively hydrolyzed whey-based formula without (control) or with short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (9:1) and Bifidobacterium breve M-16V (active).Results31 Infants up to 11 months of age, with an objective-SCORAD score (oSCORAD) ≥ 20 and elevated total-IgE and/or specific-IgE levels were included. In time, the median oSCORAD decreased in both groups by −8 (control, p &lt; 0.05; active, p &lt; 0.01). Irrespective of dietary intervention, several changes in Th2 chemokines (CCL17 and CCL22), inflammatory chemokine (CCL20), and the Th1 chemokine, CXC chemokine ligand (CXCL) 9, were detected over time. Overall CCL17 correlated to oSCORAD (r = 0.446, p &lt; 0.01). After 4 months of dietary intervention, CXCL9 was higher (p &lt; 0.01) in the active group compared with control [active, 2.33 (1.99–2.89); controls, 1.95 (1.77–2.43) log 10 median (range)]. In addition, a reduction in Th2/Th1 chemokine ratios for CCL17/CXCL9, CCL22/CXCL9, CCL20/CXCL10, and CCL20/CXCL11 was detected associated with the active intervention.ConclusionWhile this study is small and exploratory in nature, these data contribute to immune biomarker profiling and understanding of AD in infants
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