1000 resultados para Lakanal, Joseph, 1762-1845.


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Comprend : Déclaration de Pierre Calas. [À Châtelaine, 23 juillet 1762.]

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Machado-Joseph disease or Spinocerebellar ataxia type 3 is a progressive fatal neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Recent studies demonstrate that RNA interference is a promising approach for the treatment of Machado-Joseph disease. However, whether gene silencing at an early time-point is able to prevent the appearance of motor behavior deficits typical of the disease when initiated before onset of the disease had not been explored. Here, using a lentiviral-mediated allele-specific silencing of mutant ataxin-3 in an early pre-symptomatic cerebellar mouse model of Machado-Joseph disease we show that this strategy hampers the development of the motor and neuropathological phenotypic characteristics of the disease. At the histological level, the RNA-specific silencing of mutant ataxin-3 decreased formation of mutant ataxin-3 aggregates, preserved Purkinje cell morphology and expression of neuronal markers while reducing cell death. Importantly, gene silencing prevented the development of impairments in balance, motor coordination, gait and hyperactivity observed in control mice. These data support the therapeutic potential of RNA interference for Machado-Joseph disease and constitute a proof of principle of the beneficial effects of early allele-specific silencing for therapy of this disease.

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Recherches médiévales, 4, série Magistralia. Leçons et lectures, 1. Choix, notices et avant-propos d'Alain Corbellari

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The published daily journals of the transactions of the House of Representatives for the current legislative session and the official bound journals printed after adjournment for previous legislative sessions. Four consecutive volumes bound as one.

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The published daily journals of the transactions of the Senate for the current legislative session and the official bound journals printed after adjournment for previous legislative sessions.Four consecutive volumes bound as one.