Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

Proyecto Esperanto

Desarrollo de una p��gina web para la biblioteca Esperanto que permita la gesti��n integral de su cat��logo de libros, usuarios, reservas y pr��stamos.

Dos nous afloraments volc��nics a l'Alt Empord�� (Girona)

Two unknown volcanic outcrops in the Alt Emporda (Girona) are described in this paper . We present their exact situation and a description of their occurrence and their mineralogical and petrological characteristics. Bothhave been classified as alkali-olivine basalts and they probably extruded during the Neogen period

Variaci��n estacional del fitoplancton en el ��rea del Callao durante El Ni��o 1987 (10-200 mn)

Se analiz�� la distribuci��n espacio temporal de la abundancia fitoplanct��nica, asoci��ndola con la temperatura, salinidad, nutrientes y clorofila "a" en el perfil Callao 12 ��S, durante el a��o 1987. Se determin�� la estructura de las asociaciones del fitoplancton mediante la composici��n espec��fica, la riqueza espec��fica (S), diversidad (H') y la dominancia ( D ) . La variaci��n anual fitoplanct��nica present�� un comportamiento similar al ciclo anual de producci��n del mar peruano, con dos picos de abundancia; el primero en primavera y el segundo en verano. Los eventos de surgencias que enriquecen de nutrientes las aguas del ��rea del Callao son los responsables de que en esta zona se hayan registrado las concentraciones m��s altas de fitoplancton. Las diatomeas, los cocolitof��ridos y los fitoflagelados fueron los componentes dominantes en los muestreos; siendo los dinoflagelados y los silicoflagelados ligeramente abundantes en el verano. La composici��n espec��fica arroj�� un total de 172 especies, comprendidos en 91 diatomeas, 52 dinoflagelados, 21 cocolitof��ridos, 6 fitoflagelados y 2 silicoflagelados . Las especies Thalassiosira m��nima, Skeletonema costatum, Nitzschia bicapitata, Nitzschia closterium, Nav��cula sp ., Guinardia delicatula, Gymnodinium splendens, Emiliania huxleyi y Eutreptiella gimnastica, fueron caracter��sticas de la temporada de la Primavera y Verano, mientras que Planktoniella sol, Rhizosolenia bergonii, Gymnodinium sp. y Nonada sp. lo fueron para la temporada del Oto��o e Invierno. La variaci��n de la diversidad espec��fica y la dominancia estuvo relacionada por la influencia del fen��meno El Ni��o, as�� tenemos que durante la ��poca de El Ni��o hasta el invierno de 1987 se observaron valores altos de diversidad y baja dominancia en la zona costera indicando una comunidad fitoplanct��nica de etapa avanzada de la sucesi��n ecol��gica . El evento "El Ni��o" 1987, provoc�� una notable ca��da de la abundancia fitoplanct��nica, desde Noviembre de 1986 hasta Marzo de 1987. Los indicios de recuperaci��n del fitoplancton se observaron a partir de setiembre de 1987, habi��ndose recuperado parcialmente en Primavera del mismo a��o. Durante el per��odo 1987, Emiliania huxleyi, Caloiosolenia murrayi y el grupo de los Fitoflagelados fueron los taxas predominantes.

ENaC inhibition stimulates Cl- secretion in the mouse cortical collecting duct through an NKCC1-dependent mechanism.

In cortical collecting ducts (CCDs) perfused in vitro, inhibiting the epithelial Na(+) channel (ENaC) reduces Cl(-) absorption. Since ENaC does not transport Cl(-), the purpose of this study was to determine how ENaC modulates Cl(-) absorption. Thus, Cl(-) absorption was measured in CCDs perfused in vitro that were taken from mice given aldosterone for 7 days. In wild-type mice, we observed no effect of luminal hydrochlorothiazide on either Cl(-) absorption or transepithelial voltage (V(T)). However, application of an ENaC inhibitor [benzamil (3 μM)] to the luminal fluid or application of a Na(+)-K(+)-ATPase inhibitor to the bath reduced Cl(-) absorption by ∼66-75% and nearly obliterated lumen-negative V(T). In contrast, ENaC inhibition had no effect in CCDs from collecting duct-specific ENaC-null mice (Hoxb7:CRE, Scnn1a(loxlox)). Whereas benzamil-sensitive Cl(-) absorption did not depend on CFTR, application of a Na(+)-K(+)-2Cl(-) cotransport inhibitor (bumetanide) to the bath or ablation of the gene encoding Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) blunted benzamil-sensitive Cl(-) absorption, although the benzamil-sensitive component of V(T) was unaffected. In conclusion, first, in CCDs from aldosterone-treated mice, most Cl(-) absorption is benzamil sensitive, whereas thiazide-sensitive Cl(-) absorption is undetectable. Second, benzamil-sensitive Cl(-) absorption occurs by inhibition of ENaC, possibly due to elimination of lumen-negative V(T). Finally, benzamil-sensitive Cl(-) flux occurs, at least in part, through transcellular transport through a pathway that depends on NKCC1.

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains.

BACKGROUND: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. RESULTS: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. CONCLUSIONS: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.

The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to &#8764;50% of the variation in both age at menarche and menopause, but to date the known genes explain <15% of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P = 1.9 �� 10(-9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility.

The emerging importance of the SPX domain-containing proteins in phosphate homeostasis

Plant growth and development are strongly influenced by the availability of nutrients in the soil solution. Among them, phosphorus (P) is one of the most essential and most limiting macro-elements for plants. In the environment, plants are often confronted with P starvation as a result of extremely low concentrations of soluble inorganic phosphate (Pi) in the soil. To cope with these conditions, plants have developed a wide spectrum of mechanisms aimed at increasing P use efficiency. At the molecular level, recent studies have shown that several proteins carrying the SPX domain are essential for maintaining Pi homeostasis in plants. The SPX domain is found in numerous eukaryotic proteins, including several proteins from the yeast PHO regulon, involved in maintaining Pi homeostasis. In plants, proteins harboring the SPX domain are classified into four families based on the presence of additional domains in their structure, namely the SPX, SPX-EXS, SPX-MFS and SPX-RING families. In this review, we highlight the recent findings regarding the key roles of the proteins containing the SPX domain in phosphate signaling, as well as providing further research directions in order to improve our knowledge on P nutrition in plants, thus enabling the generation of plants with better P use efficiency.

Aspects post-op��ratoires de l'aorte ascendante.

Messages �� retenir: Conna��tre le principe des principales chirurgies du segment I de l'aorte (Tirone David, Ross, Bentall..). Le scanner MD est l'imagerie cl�� pour visualiser la r��implantation des coronaires natives ou un pontage associ��. Le protocole scanographique le plus courant est une acquisition synchronis��e en mode prospectif. Le mode r��trospectif peut ��tre utilis�� en cas de suspicion de dysfonction d'une valve m��canique. Apr��s une TAVI, le scanner est un examen cl�� pour juger de la hauteur, de la circularit��, de l'adossement de la proth��se et de son rapport avec les coronaires. R��sum��: Les aspects post op��ratoires de l'aorte ascendante sont au mieux ��tudi��s par un scanner multid��tecteur inject�� avec synchronisation ECG. Le mode prospectif avec bas kilovoltage est privil��gi�� pour r��duire la dose dans cette population majoritairement jeune. La communication avec l'��quipe chirurgicale est importante pour l'analyse des images (le radiologue doit conna��tre le type de montage effectu��). Parmi les gestes de cardiologie interventionnelle, la TAVI est devenue courante et les ��l��ments de contr��le de la proc��dure par le scanner doivent ��tre connus.

Common variants in mendelian kidney disease genes and their association with renal function.

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency &gt;5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

A comparison of in vivo 13C MR brain glycogen quantification at 9.4 and 14.1 T.

The high molecular weight and low concentration of brain glycogen render its noninvasive quantification challenging. Therefore, the precision increase of the quantification by localized (13) C MR at 9.4 to 14.1 T was investigated. Signal-to-noise ratio increased by 66%, slightly offset by a T(1) increase of 332 �� 15 to 521 �� 34 ms. Isotopic enrichment after long-term (13) C administration was comparable (&#8776; 40%) as was the nominal linewidth of glycogen C1 (&#8776; 50 Hz). Among the factors that contributed to the 66% observed increase in signal-to-noise ratio, the T(1) relaxation time impacted the effective signal-to-noise ratio by only 10% at a repetition time = 1 s. The signal-to-noise ratio increase together with the larger spectral dispersion at 14.1 T resulted in a better defined baseline, which allowed for more accurate fitting. Quantified glycogen concentrations were 5.8 �� 0.9 mM at 9.4 T and 6.0 �� 0.4 mM at 14.1 T; the decreased standard deviation demonstrates the compounded effect of increased magnetization and improved baseline on the precision of glycogen quantification.

Pauvret�� et mise �� l'��cart : quelles politiques de lutte contre la pauvret�� ?

Ce texte vise �� mettre en ��vidence les probl��mes d'insertion que connaissent les personnes en situation de pauvret��. Les programmes qui oeuvrent �� leur int��gration s'av��rent complexes �� mettre sur pied. Leurs r��sultats sont d'ailleurs d��licats �� mesurer. Lorsqu'il est question d'insertion de personnes en marge, leur motivation �� se sortir de leur situation est souvent mise en ��vidence. Pourtant, pour qu'une int��gration puisse aboutir, il est n��cessaire qu'il y ait convergence d'int��r��ts entre, d'une part, les personnes ou les groupes �� int��grer et, de l'autre, le groupe int��grant, �� savoir la grande majorit�� de la population ou encore les employeurs potentiels. Dans une premi��re partie, ces pages d��crivent les probl��mes conceptuels qui se posent lorsque l'on d��crit le statut des pauvres dans les soci��t��s d��velopp��es. Au travers du statut de pauvret��, conf��r�� au personnes concern��es, il est surtout question d'une r��gulation sociales. Dans une seconde partie, ce texte pr��sente les r��sultats de l'observation d'une vingtaine de trajectoires de b��n��ficiaires de mesures d'insertion sociale dites "bas seuil" dans le canton de Vaud. Ces personnes se caract��risent par une situation de mise en marge des r��seaux ��conomiques et sociaux.