The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

On the reappearance of some plant species after a long time

Es wird über das Wiederauftreten von Hyoscyamus niger, Datura stramonium, Orobanche minor, Ranunculus arvensis und Stachys annua berichtet.Report on the reappearance of Hyoscyamus niger, Datura stramonium, Orobanche minor, Ranunculus arvensis and Stachys annua

Patterning of lithium lanthanum titanium oxide films by soft lithography as electrolyte for all-solid-state Li-ion batteries

The combination of sol–gel processing and soft-lithographic patterning presents a promising route towards three-dimensional (3D) micro Li-ion electrodes, and may offer a viable approach for the fabrication of all-solid-state 3D Li-ion batteries. The methods are relatively simple and therefore cheap and moreover easy to scale up. In this paper, micro-patterned films of the Li-ion conducting perovskite-type phase with nominal composition Li0.29La0.57TiO3 (LLT) were prepared on silicon, using sol-gel synthesis in combination with micro-molding. After thermal annealing at 700 °C, the phase formation, morphology, chemical composition and LLT film thickness were investigated by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive Analysis of X-rays (EDAX) and Atomic Force Microscopy (AFM). The ionic conductivity of the LLT powder prepared during this study, determined by impedance spectroscopy, was 2.68·10−6 S/cm at 25 °C

Investigating the energy saving potential of thermochromic coatings on building envelopes

Thermochromic (TC) materials can switch solar absorptance (α) based on temperature stimuli. When coatings with TC properties are applied on building envelope surfaces, the amount of solar heat gains can be controlled to reduce the heating and cooling demand of buildings. To date, limited research has been conducted in investigating optimal TC coating properties for application on opaque building envelopes in various scenarios. In this research, a method to model TC coatings using building performance simulation (BPS) tools has been developed and coupled with python to optimize solar absorption states (α) and switching temperatures and reduce the annual heating and cooling demand. The simulation-based approach has been employed to perform early-stage exploration studies on multiple building types and climates to support material R&D in developing optimized coatings for target applications and assess the potential energy savings. The results indicate that the optimum TC properties are unique to climate and building types. TC coatings with high switching temperatures result in larger energy savings for scenarios with high heating demands, while TC coatings with low switching temperatures produce larger energy savings in scenarios with high cooling demands. Similarly, increasing the high solar absorption (αhigh) to 1 increases the heating savings, while reducing the low solar absorption (αlow) to 0 results in higher cooling savings. Furthermore, it was found that solar irradiance causes temperature spikes triggering the TC coatings to unnecessarily switch from high to low absorptance state in winters leading to heating penalties. Replacing optimal static with TC coatings on terraced houses in the Spanish climate with a 2:3 heating to cooling demand ratio results in 2 to 13% energy savings

Homocysteine level is associated with aortic stiffness in elderly: cross-sectional results from the B-PROOF study

OBJECTIVE: Homocysteine has been shown to be a more accurate predictor of cardiovascular mortality in very old persons than models based on classical risk factors. Arterial stiffening is a structural abnormality involved in the pathway of cardiovascular disease. We expect this underlying pathophysiology to be a possible explanation for the association between homocysteine and cardiovascular risk, particularly in older populations. METHODS: Baseline cross-sectional data of the B-PROOF study were used to determine associations between homocysteine and outcomes of vascular function and structure. The cardiovascular subgroup of the B-PROOF study was included [n = 560, 58% men, age 72.6 ± 5.5 years, median homocysteine level 14.2 μmol/l (IQR 13.0-16.6)]. We assessed carotid distensibility coefficient, carotid compliance coefficient, aortic pulse wave velocity (aPWV), augmentation index (AIx) and aortic pulse pressure (aortic PP). Associations were tested using linear regression analysis and ANCOVA and were adjusted for possible confounders including age, sex, renal function, mean arterial pressure and heart rate. RESULTS: Ln-homocysteine was strongly associated with aPWV [β 0.005 95% confidence interval (0.001-0.009)]. Furthermore, this association was shown to be age-dependent (P = 0.02) and it was most strong in the upper tertile of age (77-98 years). No significant associations with ln-homocysteine were observed for AIx, carotid distensibility coefficient and compliance coefficient and aortic PP. Sex stratification shows the association between ln-homocysteine and aPWV is only significant in men. CONCLUSION: In older persons, homocysteine is associated with aortic stiffness, predominantly in the oldest old. This suggests that the strong association between homocysteine and cardiovascular mortality in the elderly may be mediated by aortic stiffness

Physical fitness, activity and hand-grip strength are not associated with arterial stiffness in older individuals

Objectives: Whereas evidence exists about the benefits of intensive exercise on cardiovascular outcomes in older adults, data are lacking regarding long-term effects of physical fitness and physical activity on cardiovascular health. Therefore, we aimed to investigate the longitudinal association of physical fitness, physical activity and muscle strength with arterial stiffness measures. Design: a longitudinal follow-up study (2 years) of data from the B-PROOF study. Setting: a subgroup of the B-PROOF study (n=497). Participants: Four hundred ninety-seven participants with a mean age of 72.1 years (SD 5.4) of which 57% was male. Measurements: All performed at baseline and after two-year follow-up. Arterial stiffness was estimated by pulse wave velocity (PWV) measured with applanation tonometry. Furthermore, augmentation index (AIx) and aortic pulse pressure (PP) were assessed. Physical activity was estimated using a validated questionnaire regarding daily activities. Physical fitness was measured with a physical performance score, resulting from a walking, chair-stand and balance test. Muscle strength was assessed with hand-grip strength using a handheld dynamometer. Results: The median performance score was 9.0 [IQR 8.0–11.0], the mean physical activity was 744.4 (SD 539.4) kcal/day and the mean hand-grip strength was 33.1 (SD 10.2) kg. AIx differed between the baseline and follow-up measurement (26.2% (SD 10.1) vs. 28.1% (SD 9.9); p < 0.01), whereas PWV and aortic PP did not. In multivariable linear regression analysis, physical performance, physical activity and hand-grip strength at baseline were not associated with the amount of arterial stiffness after two years of follow-up. Conclusion: Physical fitness, activity and muscle strength were not associated with arterial stiffness. More research is warranted to elucidate the long-term effects of daily and intensive physical activity on arterial stiffness in an elderly population

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Objective. Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches. Design. Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr−/−. Leiden and ApoE*3Leiden.CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls. Results. Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden.CETP mice. C57BL/6J and LDLr−/−. Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender. Conclusions. Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L.CETP) were identified as important contributing factors