From mutation to mechanism: deciphering the molecular function of genetic variants linked to human ageing

Many of the leading causes of death in humans, such as cardiovascular disease, type 2 diabetes and Alzheimer’s disease are influenced by biological mechanisms that become dysregulated with increasing age. Hence, by targeting these ageing-related mechanisms, we may be able to improve health in old age. Ageing is partly heritable and genetic studies have been moderately successful in identifying genetic variants associated with ageing-related phenotypes (lifespan, healthspan and longevity). To decipher the mechanisms by which the identified variants influence ageing, studies that focus on their functional validation are vital. In this perspective, we describe the steps that could be taken in the process of functional validation: (1) in silico characterisation using bioinformatic tools; (2) in vitro characterisation using cell lines or organoids; and (3) in vivo characterisation studies using model organisms. For the in vivo characterisation, it is important to focus on translational phenotypes that are indicative of both healthspan and lifespan, such as the frailty index, to inform subsequent intervention studies. The depth of functional validation of a genetic variant depends on its location in the genome and conservation in model organisms. Moreover, some variants may prove to be hard to characterise due to context-dependent effects related to the experimental environment or genetic background. Future efforts to functionally characterise the (newly) identified genetic variants should shed light on the mechanisms underlying ageing and will help in the design of targeted interventions to improve health in old age

Extractibilityof Residual Rock and Superphosphate on Limed and Unlimed Bungor Soil.

The possibility of using soil extractants to monitor the transformation of phosphorus (P) fertilizer on a Bungor series soil was investigated. Three soil extractants - Bray 2, Ammonium acetate lactate (AAL) and Olsen - were evaluated. The soil was treated with three levels of P each from rock phosphate and superphosphate at 0, 150 and 300kg Plha, no lime and limed at 4 tons/ha and a P fertilizer application interval of one year. Bray 2 and AAL were able to detect recent P from aged P applications with a higher amount of P being extracted from the recent. These extracts were able to differentiate between the 150 and 300kg Plha treatments but were not able to distinguish the forms of P. Olsen extractant on the other hand was able to detect the two P forms and showed P release from rock phosphate with time

Ensembles of Breathing Nucleosomes: A Computational Study

Theoretical PhysicsBiological and Soft Matter Physic

Ensembles of breathing nucleosomes: a computational study

Theoretical Physic

Increased stress in Asiatic black bears relates to food limitation, crop raiding, and foraging beyond nature reserve boundaries in China

AbstractAsiatic black bears (Ursus thibetanus) are declining throughout much of their range. In China they are partially protected by a nature reserve system and rely heavily on hard mast as a food source prior to winter denning. Bears may compensate for mast shortages by raiding agricultural crops and killing livestock, mainly outside reserves where they are exposed to increased threats of poaching. We hypothesized that stress would vary with availability of high-quality refugia and fluctuations in mast abundance. We collected fecal samples from free-ranging bears in and around nature reserves in southwestern China, recorded habitat characteristics at each fecal sample location, and quantified abundance of hard mast. We used feces for genetic and endocrine analysis and identified 106 individuals. Feces collected outside reserves, or in agricultural fields within reserves, contained elevated concentrations of glucocorticoid metabolites compared to samples collected in intact, mast-producing forests within reserves. Relationships with habitat variables indicated that the hypothalamic–pituitary–adrenal (HPA) axis of the Asiatic black bear is responsive to human activity, abundance of hard mast, extent of forest cover, and quality of diet. Our findings demonstrate biological reactions of a large mammal to variable forest quality, human threats, and foraging relative to boundaries of protected areas

Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Using Bayesian state-space models with Age-At-Harvest data to estimate black bear abundance and demographic parameters.

Ope

Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals