Polymorphisms in the WNK1 gene are asociated with blood pressure variation and urinary potassium excretion

WNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10−3, combined with BRIGHT data-set p = 2×10−4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH

A ground-based optical transmission spectrum of WASP-6b

PublishedJournal ArticleWe present a ground-based optical transmission spectrum of the inflated sub-Jupiter-mass planet WASP-6b. The spectrum was measured in 20 spectral channels from 480 nm to 860 nm using a series of 91 spectra over a complete transit event. The observations were carried out using multi-object differential spectrophotometry with the Inamori-Magellan Areal Camera and Spectrograph on the Baade Telescope at Las Campanas Observatory. We model systematic effects on the observed light curves using principal component analysis on the comparison stars and allow for the presence of short and long memory correlation structure in our Monte Carlo Markov Chain analysis of the transit light curves for WASP-6. The measured transmission spectrum presents a general trend of decreasing apparent planetary size with wavelength and lacks evidence for broad spectral features of Na and K predicted by clear atmosphere models. The spectrum is consistent with that expected for scattering that is more efficient in the blue, as could be caused by hazes or condensates in the atmosphere of WASP-6b. WASP-6b therefore appears to be yet another massive exoplanet with evidence for a mostly featureless transmission spectrum, underscoring the importance that hazes and condensates can have in determining the transmission spectra of exoplanets. © 2013. The American Astronomical Society. All rights reserved.A.J. acknowledges support from FONDECYT project 1130857, BASAL CATA PFB-06, and the Millennium Science Initiative, Chilean Ministry of Economy (Nucleus P10-022-F). A.J., S.E., and N.E. acknowledge support from the Vicerrectoría de Investigación (VRI), Pontificia Universidad Católica de Chile (proyecto investigación interdisciplinaria 25/2011). N.E. is supported by CONICYT-PCHA/Doctorado Nacional, and M.R. is supported by FONDECYT postdoctoral fellowship 3120097. D.K.S. acknowledges support from STFC consolidated grant ST/J0016/1. J.-M.D. acknowledges funding from NASA through the Sagan Exoplanet Fellowship program administered by the NASA Exoplanet Science Institute (NExScI). A.H.M.J.T. is a Swiss National Science Foundation fellow under grant number PBGEP2-145594

De l’intérêt de l’analyse isogéométrique pour la simulation multi-physiques/multi-champs de structures en grandes déformations

International audienceNous explorons, dans cette communication, des formulations mutli-physiques et/ou multi-champs pour résoudre des problèmes d'élasticité ou de thermo-élasticité en grandes déformations avec une contrainte de quasi-incompressibilité telle que l'on peut en rencontrer avec des matériaux de type élastomères. Nous montrons que l'analyse isogéométrique est tout à fait pertinente dans ce cadre car elle présente à la fois de très bonnes propriétés de convergence (et donc de stabilité) et une grande souplesse d'utilisation dans le choix des espaces d'approximations des différents champs

The VVV Templates Project. Towards an Automated Classification of VVV Light-Curves. I. Building a database of stellar variability in the near-infrared

Context. The Vista Variables in the V\'ia L\'actea (VVV) ESO Public Survey is a variability survey of the Milky Way bulge and an adjacent section of the disk carried out from 2010 on ESO Visible and Infrared Survey Telescope for Astronomy (VISTA). VVV will eventually deliver a deep near-IR atlas with photometry and positions in five passbands (ZYJHK_S) and a catalogue of 1-10 million variable point sources - mostly unknown - which require classifications. Aims. The main goal of the VVV Templates Project, that we introduce in this work, is to develop and test the machine-learning algorithms for the automated classification of the VVV light-curves. As VVV is the first massive, multi-epoch survey of stellar variability in the near-infrared, the template light-curves that are required for training the classification algorithms are not available. In the first paper of the series we describe the construction of this comprehensive database of infrared stellar variability. Methods. First we performed a systematic search in the literature and public data archives, second, we coordinated a worldwide observational campaign, and third we exploited the VVV variability database itself on (optically) well-known stars to gather high-quality infrared light-curves of several hundreds of variable stars. Results. We have now collected a significant (and still increasing) number of infrared template light-curves. This database will be used as a training-set for the machine-learning algorithms that will automatically classify the light-curves produced by VVV. The results of such an automated classification will be covered in forthcoming papers of the series.Comment: 12 pages, 16 figures, 3 tables, accepted for publication in A&A. Most of the data are now accessible through http://www.vvvtemplates.org

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

BACKGROUND: Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. METHODS: We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. RESULTS: A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. CONCLUSION: The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean famil

The Vista Variables in the Via Lactea (VVV) ESO Public Survey: Current Status and First Results

25 pages, 18 figures. To appear in the Carnegie Observatories Astrophysics Series, Volume 525 pages, 18 figures. To appear in the Carnegie Observatories Astrophysics Series, Volume 5Vista Variables in the Via Lactea (VVV) is an ESO Public Survey that is performing a variability survey of the Galactic bulge and part of the inner disk using ESO's Visible and Infrared Survey Telescope for Astronomy (VISTA). The survey covers 520 deg^2 of sky area in the ZYJHK_S filters, for a total observing time of 1929 hours, including ~ 10^9 point sources and an estimated ~ 10^6 variable stars. Here we describe the current status of the VVV Survey, in addition to a variety of new results based on VVV data, including light curves for variable stars, newly discovered globular clusters, open clusters, and associations. A set of reddening-free indices based on the ZYJHK_S system is also introduced. Finally, we provide an overview of the VVV Templates Project, whose main goal is to derive well-defined light curve templates in the near-IR, for the automated classification of VVV light curves

Analyse Isogéométrique espace-temps pour le Calcul des Structures

International audienceLa méthode des éléments finis est aujourd'hui la méthode numérique la plus utilisée en mécanique. Généralement utilisée dans la discrétisation de l'espace, elle est souvent associée à une méthode de type différences finies pour la résolution en temps. Nous nous intéressons dans cette étude à appliquer un schéma de discrétisation en espace et en temps simultanément. Nous utilisons l'Analyse Isogéométrique (IGA) comme méthode de discrétisation (voir [1]) dans le but de profiter des qualités numériques de la méthode en résolution en temps. Dans ce papier, nous validons partiellement la stabilité de manière numérique des tests de convergence triviaux pour les équations de la chaleur et d'ondes en 1D, et vérifions qualitativement le potentiel de la méthode sur un modèle mécanique de viscoélasticité dynamique 1D

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit