56 research outputs found
A meta-analysis of genome-wide association studies identifies multiple longevity genes
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) Δ4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE Δ2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity
Vegetation history across the Permian-Triassic boundary in Pakistan (Amb section, Salt Range)
Hypotheses about the PermianâTriassic floral turnover range from a catastrophic extinction of terrestrial plant communities to a gradual change in floral composition punctuated by intervals indicating dramatic changes in the plant communities. The shallow marine PermianâTriassic succession in the Amb Valley, Salt Range, Pakistan, yields palynological suites together with well-preserved cuticle fragments in a stratigraphically well-constrained succession across the PermianâTriassic boundary. Palynology and cuticle analysis indicate a mixed GlossopterisâDicroidium flora in the Late Permian. For the first time Dicroidium cuticles are documented from age-constrained Upper Permian deposits on the Indian subcontinent. Close to the PermianâTriassic boundary, several sporomorph taxa disappear. However, more than half of these taxa reappear in the overlying Smithian to Spathian succession. The major floral change occurs towards the Dienerian. From the PermianâTriassic boundary up to the middle Dienerian a gradual increase of lycopod spore abundance and a decrease in pteridosperms and conifers are evident. Synchronously, the generic richness of sporomorphs decreases. The middle Dienerian assemblages resemble the previously described spore spikes observed at the end-Permian (Norway) and in the middle Smithian (Pakistan) and might reflect a similar ecological crisis
Cytokines promote the survival of mouse cranial sensory neurones at different developmental stages
To investigate when the neurotrophic cytokines ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), oncostatin-M (OSM), interleukin-6 (IL-6) and cardiotrophin-1 (CT-1) act on developing sensory neurones and whether they co-operate with neurotrophins in regulating neuronal survival, we studied the in vitro trophic effects of these factors on two well-characterized populations of cranial sensory neurones at closely staged intervals throughout embryonic development. The cutaneous sensory neurones of the trigeminal ganglion, which show an early, transient survival response to BDNF and NT3 before becoming NGF-dependent, were supported by CNTF, LIF, OSM and CT-1 during the late fetal period, several days after the neurones become NGF-dependent. At this stage of development, these cytokines promoted the survival of a subset of NGF-responsive neurones. The enteroceptive neurones of the nodose ganglion, which retain dependence on BDNF throughout fetal development, were supported throughout their development by CNTF, LIF, OSM and CT-1, and displayed an additional survival response to IL-6 in the late fetal period, These findings indicate that populations of sensory neurones display different developmental patterns of cytokine responsiveness and show that embryonic trigeminal neurones pass through several phases of differing neurotrophic factor survival requirements
Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: an integrated analysis.
The impact of a gluten-free diet on adults with coeliac disease: results of a national survey
Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis
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