998 resultados para Joseph, Nez Percés chief, 1840-1904
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Donateur : Bonaparte, Roland (1858-1924)
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Donateur : Davidsard (18..-18.. ; marquis)
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Machado-Joseph disease is the most frequently found dominantly-inherited cerebellar ataxia. Over-repetition of a CAG trinucleotide in the MJD1 gene translates into a polyglutamine tract within the ataxin 3 protein, which upon proteolysis may trigger Machado-Joseph disease. We investigated the role of calpains in the generation of toxic ataxin 3 fragments and pathogenesis of Machado-Joseph disease. For this purpose, we inhibited calpain activity in mouse models of Machado-Joseph disease by overexpressing the endogenous calpain-inhibitor calpastatin. Calpain blockage reduced the size and number of mutant ataxin 3 inclusions, neuronal dysfunction and neurodegeneration. By reducing fragmentation of ataxin 3, calpastatin overexpression modified the subcellular localization of mutant ataxin 3 restraining the protein in the cytoplasm, reducing aggregation and nuclear toxicity and overcoming calpastatin depletion observed upon mutant ataxin 3 expression. Our findings are the first in vivo proof that mutant ataxin 3 proteolysis by calpains mediates its translocation to the nucleus, aggregation and toxicity and that inhibition of calpains may provide an effective therapy for Machado-Joseph disease.
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Aquest llibre va lligat a l'estudi que un dels seus autors, el doctor Vallribera i Puig, havia fet prèviament sobre els 145 treballs que restaven inèdits i que havien estat presentats al concurs de Topografies Mèdiques a la Reial Acadèmia de Medicina de Catalunya, on restaven conservats. Aquí es recupera un d'aquest treballs, datat el 1904 i aquí atribuït a Segimon Salgot i Baucells. Aquest treball centra el seu estudi a les topografies mèdiques a la comarca del Baix Llobregat.
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This study was written by John J. Louis and reprinted from volume II, numbers 1 and 2 of the Iowa journal of history and politics [Jan.-Apr.1904]. It examines the component society of Shelby County with reference to its social structure.