Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

In vitro evaluation of Mucuna pruriens (L.) DC. antioxidant activity

Mucuna pruriens (L). Dc is a plant of the Fabaceae family, commonly known as velvet bean, itchy bean, chiporro bean, mucuna, among others. This plant has several medicinal properties, including its potential to treat Parkinson's disease (PD). International studies have shown that this plant surpasses the benefits of the substance levodopa in the treatment of PD. Taking into account that nerve cells are highly sensitive to oxidative substances, this study evaluated the antioxidant activity of mucuna and compared it to that of levodopa. The plant seeds' phenolic concentration was quantified by using the Folin-Denis reagent and the antioxidant activity assays were performed by using three different methods: the reduction of the phosphomolybdenium complex, the reduction of radical 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and the formation of radical monocation ABTS•+, from the acid [2-2'-azinobis (3-ethylbenzothiazoline-6-sulfonate)]. Results showed that M. pruriens presents high antioxidant capacity, although not superior to isolated levodopa antioxidant capacity. Therefore, further studies should be performed to elucidate the activity of this plant in humans.A Mucuna pruriens (L). Dc é uma planta da família Fabaceae, conhecida popularmente como feijão-veludo, fava-coceira, feijão chiporro, mucuna, entre outros. Possui diversas propriedades medicinais, entre elas, o tratamento da doença de Parkinson (DP). Estudos internacionais vêm demonstrando que essa planta possui atividade superior à do fármaco levodopa para o tratamento da DP. O presente estudo avaliou a possibilidade da atividade antioxidante dessa planta auxiliar nesses resultados, uma vez que as células nervosas são altamente sensíveis às substâncias oxidativas. Para isto foi quantificada a concentração fenólica da semente da mucuna e os testes empregados para a avaliação da atividade antioxidante foram o teste de redução do complexo fosfomolibdênio, redução do radical 1,1-difenil-2-picril-hidrazil (DPPH•) e a formação do radical monocatiônico ABTS•+, proveniente do ácido [2-2'-azino-bis(3-etil-benzolina-6-sulfonado)]. Essa análise demonstrou que M. pruriens possui alta capacidade antioxidante, no entanto, não superior à levodopa isolada e, portanto, novos estudos devem ser realizados para a elucidação da atividade dessa planta em seres humanos

LES POTENTIELS EVOQUES AUDITIFS CHEZ LE CHIEN

L'enregistrement des potentiels évoqués auditifs permet l'exploration des voies auditives de l'oreille interne jusqu'aux premiers relais du tronc cérébral. Dans cette thèse, la méthode d'enregistrement, les résultats et les intérêts des potentiels évoqués auditifs sont décrits. Deux études ont été réalisées : l'une a porté sur la maturation des potentiels évoqués auditifs chez le chiot, l'autre a présenté une analyse descriptive de la population des chiens testés à l'Ecole Vétérinaire de Maisons-Alfort (de 1997 à 2002) Les résultats obtenus montrent que cet examen peut être utilisé en routine et démontrent sa fiabilité, en particulier pour la détection des surdités neurosensorielles congénitales, ainsi que son intérêt pour l'amélioration des races prédisposées aux surdités congénitales.MAISONS-ALFORT-Ecole Vétérin (940462302) / SudocSudocFranceF