[Illustrations de Le livre des prouffitz champestres.] / [Non identifié) ; Pierre de Crescens

Comprend : [Fig. au titre : Pierre de Crescent dictant ou enseignant la matière de son ouvrage.] [cote : microfilm m 11611/R 70185] ; [pl. en reg. folio Aii : scène de dédicace. Pierre de Crescent remettant son livre au Roi Charles V.] [cote : microfilm m 11611/R 70185] ; [Fig. folio Bi : scène de taille des arbres, de construction d'un édifice. Vue d'une cour de ferme. Scène de taille de la vigne. (Cette gravure est une reprise de l'édition de 1486. Elle est également réemployée dans la présente édition de ; [Fig. folio Cii : scène de taille des arbres, coupe et greffons. (Cette gravure est réemployée dans la présente édition de 1516 aux folios XIVI et CXXXV.)] [cote : microfilm m 11611/R 70185] ; [Fig. folio XXii : scène de semailles et de moissons. (Cette gravure est une reprise de l'édition de 1486.)] [cote : microfilm m 11611/R 70185] ; [Fig. folio FXVi verso : manières d'utiliser les plantes et les herbes. Séchage, distillation ou infusion, préparation et conditionnement à des fins médicinales.] [cote : microfilm m 11611/R 70185] ; [Fig. folio XCiii verso : animaux fabuleux ou exotiques : licorne, chameau, éléphant, cerf, lion, panthère, singe, hérisson et autres.] [cote : microfilm m 11611/R 70185] ; [Fig. folio LXViii : scène de chasse. Chasse au faucon avec une arbalète. (Cette gravure est une reprise de l'édition de 1486.)] [cote : microfilm m 11611/R 70185] ; [Fig. folio LXXXiii verso : calendrier des saisons et des mois. Activités agricoles selon les périodes de l'année.] [cote : microfilm m 11611/R 70185]

Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

SL(3,C) elementary instanton configurations

Several SL(3,C) self-dual instanton solutions of the Yang-Mills equations are presented which have very striking properties. While one of them is regular and SU(3) inside (outside) a sphere of arbitrarily large (small) radius, another one has all the characteristics of a meron solution (in particular its topological charge is concentrated at one point) although its Pontryagin number equals one. Their continuation to Minkowski space is also studied.

Batalin-Vilkovisky analysis of covariant and noncovariant actions

The equivalence between the covariant and the noncovariant versions of a constrained system is shown to hold after quantization in the framework of the field-antifield formalism. Our study covers the cases of electromagnetism and Yang-Mills fields and sheds light on some aspects of the Faddeev-Popov method, for both the covariant and noncovariant approaches, which have not been fully clarified in the literature.

The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes.

Cellular directional migration in an electric field (galvanotaxis) is one of the mechanisms guiding cell movement in embryogenesis and in skin epidermal repair. The epithelial sodium channel (ENaC), in addition to its function of regulating sodium transport in kidney, has recently been found to modulate cell locomotory speed. Here we tested whether ENaC has an additional function of mediating the directional migration of galvanotaxis in keratinocytes. Genetic depletion of ENaC completely blocks only galvanotaxis and does not decrease migration speed. Overexpression of ENaC is sufficient to drive galvanotaxis in otherwise unresponsive cells. Pharmacologic blockade or maintenance of the open state of ENaC also decreases or increases, respectively, galvanotaxis, suggesting that the channel open state is responsible for the response. Stable lamellipodial extensions formed at the cathodal sides of wild-type cells at the start of galvanotaxis; these were absent in the ENaC knockout keratinocytes, suggesting that ENaC mediates galvanotaxis by generating stable lamellipodia that steer cell migration. We provide evidence that ENaC is required for directional migration of keratinocytes in an electric field, supporting a role for ENaC in skin wound healing.

Murine alpha1-adrenoceptor subtypes. I. Radioligand binding studies.

Alpha1-adrenoceptors were identified in murine tissues by [3H]prazosin saturation binding studies, with a rank order of cerebral cortex > cerebellum > liver > lung > kidney > heart > spleen, with the spleen not exhibiting detectable expression. Competition binding studies were performed with 5-methylurapidil, BMY 7378, methoxamine, (+)-niguldipine, noradrenaline, SB 216469 and tamsulosin. On the basis of monophasic low-affinity competition by BMY 7378, alpha1D-adrenoceptors were not detected at the protein level in any tissue. On the basis of competition studies with the alpha1A/alpha1B-discriminating drugs, alpha1B-adrenoceptors appeared to be the predominant or even the sole subtype in murine liver, lung and cerebellum, whereas murine cerebral cortex and kidney contained approximately 30% and 50% of alpha1A-adrenoceptors, respectively. The affinities of the various competitors in the murine tissues were quite similar to those reported from other species. The ratio of high- and low-affinity sites for tamsulosin did not in all cases match the percentages of alpha1A- and alpha1B-adrenoceptors detected by the other competitors; however, the low-affinity component of the tamsulosin competition curves was abolished in the cerebral cortex of alpha1B-adrenoceptor knockout mice. Treatment with chloroethylclonidine (10 microM, 30 min, 37 degrees C) inactivated the alpha1-adrenoceptors in all tissues by >75%. When the concentration-dependent inactivation of tissue alpha1B-adrenoceptors (liver) and tissue alpha1A-adrenoceptors (cerebral cortex from alpha1B-adrenoceptor knockout mice) was compared, alpha1A-adrenoceptors were only slightly less sensitive toward chloroethylclonidine than alpha1B-adrenoceptors. We conclude that murine tissues express alpha1A- and alpha1B-adrenoceptors, which are largely similar to those in other species. However, the tissue-specific distribution of subtypes may differ from that of other species.

A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1.

Pseudohypoaldosteronism type 1 (PHA1) is a monogenic disorder of mineralocorticoid resistance characterized by salt wasting, hyperkalemia, high aldosterone levels, and failure to thrive. An autosomal recessive form (AR-PHA1) is caused by mutations in the epithelial sodium channel ENaC with usually severe and persisting multiorgan symptoms. The autosomal dominant form of PHA1 (AD-PHA1) is due to mutations in the mineralocorticoid receptor causing milder and transient symptoms restricted to the kidney. We identified a homozygous missense mutation in the SCNN1A gene (c.727T>C/p.Ser(243)Pro), encoding α-subunit of ENaC (α-ENaC) in a prematurely born boy with a severe salt-losing syndrome. The patient improved rapidly under treatment, and dietary salt supplementation could be stopped after 6 mo. Interestingly, the patient's sibling born at term and harboring the same homozygous Ser(243)Pro mutation showed no symptom of salt-losing nephropathy. In vitro expression of the αSer(243)Pro ENaC mutant revealed a slight but significant decrease in ENaC activity that is exacerbated in the presence of high Na(+) load. Our study provides the first evidence that ENaC activity is critical for the maintenance of salt balance in the immature kidney of preterm babies. Together with previous studies, it shows that, when the kidney is fully mature, the severity of the symptoms of AR-PHA1 is related to the degree of the ENaC loss of function. Finally, this study identifies a novel functional domain in the extracellular loop of ENaC.