Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Screening the mutagenic activities of coomonly used antiparasite drugs by the Simultest, a simplified Salmonella/microsome plate incorporation assay Rastreamento de atividade mutagênica de drogas anti-parasitárias de uso comum pelo Simultest, uma versão simplificada do teste Salmonella/fração microssomal

The mutagenic activities of 16 anti-parasite drugs were screened by the Simultest in both qualitative (spot test) and quantitative (plate incorporation) assays with a Salmonella typhimurium pool composed by the indicator strains TA97, TA 98, TA100 and TA102. Four anti Chagas' disease drugs (nifurtimox, benznidazole, CL 64,855, and MK 436) and two anti-amebae drugs (metronidazole and tinidazole) gave positive results in qualitative tests and incorporation of rat liver microsomes did not alter the results. Comparative dose response curves of the mutagenic activities of CL 64,855, metronidazole and benznidazole obtained by the simultest and by individual Salmonella indicator strains demonstrated that both approachs have similar sensitivities. The results corroborate the validity of the Simultest, as a simplified, fast and economic version of the Ames test in preliminary screening of potential mutagenic drugs.<br>As atividades mutagênicas de 16 drogas com ação anti-parasitária foram avaliadas pelo Simultest em ensaios qualitativos (spot testes) e quantitativos (incorporação em placa) com uma mistura das linhagens indicadoras de Salmonella typhimurium TA97, TA98, TA100 e TA102. Quatro drogas anti-doença de Chagas (nifurtimox, benzonidazol, CL 64,855 e MK 436) e duas drogas anti-amebiase (metronidazol e tinidazol) deram resultados positivos em testes qualitativos e a incorporação de fração microssomal de fígado de rato não alterou os resultados. Curvas comparadas de efeito da dose da atividade mutagênica do metronidazol, benzonidazol e CL 64,855 detectadas pelo Simultest e linhagens indicadoras individuais demonstraram que as duas abordagens possuem sensibilidades semelhantes. Os resultados corroboram a validade do Simultest como uma versão simplificada, rápida e econômica do teste de Ames no rastreamento preliminar de drogas potencialmente mutagênicas