Toward an internally consistent astronomical distance scale

Accurate astronomical distance determination is crucial for all fields in astrophysics, from Galactic to cosmological scales. Despite, or perhaps because of, significant efforts to determine accurate distances, using a wide range of methods, tracers, and techniques, an internally consistent astronomical distance framework has not yet been established. We review current efforts to homogenize the Local Group's distance framework, with particular emphasis on the potential of RR Lyrae stars as distance indicators, and attempt to extend this in an internally consistent manner to cosmological distances. Calibration based on Type Ia supernovae and distance determinations based on gravitational lensing represent particularly promising approaches. We provide a positive outlook to improvements to the status quo expected from future surveys, missions, and facilities. Astronomical distance determination has clearly reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press (chapter 8 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

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

The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin expression and release by endothelial cells: implications in rheumatoid arthritis

none11Objective. Complement activation products contribute to a large number of inflammatory diseases, including RA. We have investigated whether osteoprotegerin (OPG) may concur with the soluble terminal complement complex (SC5b-9) to the inflammatory cascade characterizing RA. Methods. Levels of SC5b-9 and OPG in the plasma and SF of patients with active RA were determined by ELISA. The presence of SC5b-9 and OPG in RA synovial lesions was analysed by immunohistochemistry. Cultured endothelial cells were used for in vitro leucocyte/endothelial cell adhesion assays. In addition, endothelial cells were exposed to SC5b-9 in order to evaluate the effects on the production of OPG protein, as well as the activation of the OPG promoter. Results. Patients affected by active RA are characterized by elevated levels of both SC5b-9 and OPG in plasma and/or SF. Of note, we have observed a co-localization of SC5b-9 and OPG in endothelial cells of post-capillary venules of RA synovial lesions. Data on endothelial cell cultures showed that exposure to SC5b-9 induced the up-regulation of OPG expression/release, stimulating the transcriptional activity of the OPG promoter, and synergized with TNF- in up-regulating OPG production. Conclusions. Our findings demonstrate that SC5b-9 induces OPG production by endothelial cells and we propose that the SC5b-9-mediated up-regulation of OPG may be an important mechanism whereby complement contributes in promoting and/or enhancing the inflammation in RA.noneCorallini F; Bossi F; Gonelli A; Tripodo C; Castellino G; Mollnes TF; Tedesco F; Rizzi L; Trotta F; Zauli G; Secchiero PCorallini, Federica; Bossi, F; Gonelli, Arianna; Tripodo, C; Castellino, Gabriella; Mollnes, Tf; Tedesco, F; Rizzi, L; Trotta, Francesco; Zauli, Giorgio; Secchiero, Paol

Search for hyperdeformed structures populated in the 37^{37}Cl+120^{120}Sn reaction by using EUROBALL III

The ridge structure with $\Delta$E$_\gamma$=$\pm$ 30 keV, observed in the past in coincidence with protons emitted in the reaction 187 MeV $^{37}$Cl + $^{120}$Sn and attributed to an hyperdeformed nuclear shape in $^{152}$Dy, has been studied in a new experiment performed with the EUROBALL III array. The ridge is now observed in coincidence with transitions in the yrast superdeformed band of $^{152}$Dy but no discrete rotational bands have been identified