Old ferricrete landscape dismantling in Central Africa rain forest zone: formation of the present downslope iron accumulations.

Present downslope iron accumulations were investigated in the rainforest zone in southern Cameroon. Six clay and Fe-hydroxide dominated patterns have been identified and occur on the lower part of hill slopes. They can be subdivided in three different sequences, related to gentle, moderate or steep slopes. They are discontinuous with respect to the dismantling zone of the old ferricrete cap formed at Cretaceous period. They show a gradual development from a soft Fe-crust (carapace) to a vesicular facies that will, with time, cover the whole landscape again.

Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6×10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

Impact de l'organisation institutionnelle sur le déficit protéino-énergétique des patients dialysés hospitalisés

Introduction et but de l'étude. - Le Nutrition Day 2010 réalisédans le service de dialyse aiguë de notre CHU a montré un taux dedénutrition de 64 % chez le patient dialysé hospitalisé avec un déficitnutritionnel moyen le jour de dialyse de 1 000 kcal et 45 g deprotéines. Les horaires de repas dans l'unité d'hospitalisation et dedialyse au centre de dialyse se chevauchent. Le but de cette étude estd'évaluer l'impact de l'organisation institutionnelle sur l'apportprotéino-énergétique du patient hémodialysé hospitalisé.Matériel et Méthodes. - Étude exploratoire et transversale. Laconsommation alimentaire et les obstacles potentiels à l'alimentationd'origine logistique ont été relevés durant deux jours consécutifs,un jour de dialyse (JD) et un jour sans dialyse (JSD). Les motifsde non consommation ou de consommation partielle des repas etcollations ont été relevés auprès des patients immédiatement aprèsles repas principaux, au moyen d'entretiens semi-dirigés. Lesingesta ont été comparés aux besoins protéino-énergétiques pour lespatients hémodialysés (ESPEN, 2006). Une évaluation nutritionnellea été réalisée chez tous les patients.Résultats. - Vingt-six patients (85 % d'hommes) ont été inclus,âgés de 65,7 ± 10,6 ans (moy ± ET). Le BMI moyen est de 24,9± 5,9 kg/m2, le score de Charlson de 7,2 ± 2,7 et 54 % ont un NRS-2002 ≥ 3. Plus de deux tiers des patients (68 %) ont perdu du poidset 64 % sont dénutris. Au total, 147 repas et 56 collations ont été étudiés,dont 74 repas et 32 collations pour le JD. Le JD, 56 % des collationsne sont pas consommées contre 21 % le JSD. La couverturemoyenne des besoins énergétiques et protéiques le JD est respectivementde 48 % et 57 %, sans différence avec le JSD. Les motifs denon consommation les plus fréquemment cités sont, par ordredécroissant : satiété précoce, inappétence, dégoût des mets proposés,peurs et représentations alimentaires et mises à jeun pour procéduresmédicales. Ils sont identiques les JD et les JSD. Lesobstacles à l'alimentation inhérents au patient sont 2,6 fois plus fréquentsque ceux liés à l'organisation hospitalière. Une douleur(légère à modérée), une dyspnée et une xérostomie affectent respectivement100 %, 54 % et 48 % des patients, qui ne considèrent pasces symptômes comme une cause de non consommation alimentaire.Conclusion. - Les apports protéino-énergétiques sont insuffisantset près de deux tiers des sujets sont dénutris. L'organisationhospitalière n'est pas identifiée par les patients comme un obstacleexpliquant le déficit énergétique et protéique quotidien. Les obstaclesà l'alimentation orale sont principalement inhérents à l'état desanté des patients. L'instauration d'une alimentation spécifique auxpatients dialysés hospitalisés (« humide », fractionnée, enrichie enprotéines et en énergie) de même que la prescription plus systématiqued'un support nutritionnel devraient contribuer à la couverturede leurs besoins nutritionnels.

Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.

Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.

Brachial or wrist blood pressure in obese patients: which is the best?

OBJECTIVE: Blood pressure (BP) measured in obese patients with a large arm circumference using a cuff of standard width may be overestimated. METHODS: We compared in this study the BP readings obtained with oscillometric devices at the left arm (OMRON HEM 705-CP) and the left wrist (OMRON R6) (Omron Medizintechnik, Mannheim, Germany) in lean (n=15) and obese (n=11) patients. RESULTS: No difference was found in diastolic BP between the two groups, nor between the arm and the wrist. Systolic BP measured at the arm was, however, significantly lower in obese (99+/-9 mmHg, mean+/-SD) than in lean (107+/-14 mmHg; P<0.001) patients, whereas systolic BP determined at the wrist averaged 106 mmHg in both groups. CONCLUSION: The use of validated wrist BP measuring devices appears therefore particularly appealing in obese individuals with a large arm circumference

Role of peroxynitrite in the redox regulation of cell signal transduction pathways.

Peroxynitrite is a potent oxidant and nitrating species formed from the reaction between the free radicals nitric oxide and superoxide. An excessive formation of peroxynitrite represents an important mechanism contributing to cell death and dysfunction in multiple cardiovascular pathologies, such as myocardial infarction, heart failure and atherosclerosis. Whereas initial works focused on direct oxidative biomolecular damage as the main route of peroxynitrite toxicity, more recent evidence, mainly obtained in vitro, indicates that peroxynitrite also behaves as a potent modulator of various cell signal transduction pathways. Due to its ability to nitrate tyrosine residues, peroxynitrite affects cellular processes dependent on tyrosine phosphorylation. Peroxynitrite also exerts complex effects on the activity of various kinases and phosphatases, resulting in the up- or downregulation of signalling cascades, in a concentration- and cell-dependent manner. Such roles of peroxynitrite in the redox regulation of key signalling pathways for cardiovascular homeostasis, including protein kinase B and C, the MAP kinases, Nuclear Factor Kappa B, as well as signalling dependent on insulin and the sympatho-adrenergic system are presented in detail in this review.

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

Job switching in ants: role of a kinase

Reproductive division of labour is a defining characteristic of eusociality in insect societies. The task of reproduction is performed by the fertile males and queens of the colony, while the non-fertile female worker caste performs all other tasks related to colony upkeep, foraging and nest defence. Division of labour, or polyethism, within the worker caste is organized such that specific tasks are performed by discrete groups of individuals. Ordinarily, workers of one group will not participate in the tasks of other groups making the groups of workers behaviourally distinct. In some eusocial species, this has led to the evolution of a remarkable diversity of subcaste morphologies within the worker caste, and a division of labour amongst the subcastes. This caste polyethism is best represented in many species of ants where a smaller-bodied minor subcaste typically performs foraging duties while larger individuals of the major subcaste are tasked with nest defence. Recent work suggests that polyethism in the worker caste is influenced by an evolutionarily conserved, yet diversely regulated, gene called foraging (for), which encodes a cGMP-dependent protein kinase (PKG). Additionally, flexibility in the activity of this enzyme allows for workers from one task group to assist the workers of other task groups in times of need during the colony's life.

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 complexity.

Volochinov en contexte : essai d'épistémologie historique

Valentin N. Volochinov (1895-1936), un des amis de Mikhaïl Bakhtine, a longtemps été considéré par certains chercheurs du domaine des études bakhtiniennes comme le prête-nom de ce dernier ; les oeuvres de Volochinov et de Bakhtine ont souvent été reçues comme émanant d'un seul et même projet scientifique. Ce livre donne de Volochinov une image radicalement nouvelle. D'une part, on montre en quoi il est un auteur totalement indépendant de Bakhtine. D'autre part, on analyse les sources de ses textes - livres et articles - en les replaçant dans le contexte, peu connu du public francophone, de la vie intellectuelle russe d'avant et après la Révolution d'Octobre. Sont étudiés le type de sociologie et de critique marxiste de l'idéologie qui s'est diffusé en Russie avec Lénine, Plékhanov, Bogdanov et Boukharine, la réception du Cours de linguistique générale de Saussure et de la psychanalyse de Freud, les apports de la psychologie expérimentale et des travaux de De Roberty et de Sorokine en sciences humaines, que l'on retrouve à l'origine des premières théories de l'interaction verbale et de la parole dans la vie quotidienne. On rend ainsi à Volochinov, outre l'originalité et la cohérence de sa pensée, l'énergie roborative de son engagement scientifique, qui culminera en 1929 avec Marxisme et philosophie du langage

Genome-wide association study identifies eight loci associated with blood pressure.

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.