997 resultados para Charlot, Joseph-Auguste (1...-1874)


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BACKGROUND Interferon-α (IFN-α) treatment suppresses HIV-1 viremia and reduces the size of the HIV-1 latent reservoir. Therefore, investigation of the molecular and immunologic effects of IFN-α may provide insights that contribute to the development of novel prophylactic, therapeutic and curative strategies for HIV-1 infection. In this study, we hypothesized that microRNAs (miRNAs) contribute to the IFN-α-mediated suppression of HIV-1. To inform the development of novel miRNA-based antiretroviral strategies, we investigated the effects of exogenous IFN-α treatment on global miRNA expression profile, HIV-1 viremia, and potential regulatory networks between miRNAs and cell-intrinsic anti-HIV-1 host factors in vivo. METHODS Global miRNA expression was examined in longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated interferon-α/ribavirin therapy (IFN-α/RBV). We implemented novel hybrid computational-empirical approaches to characterize regulatory networks between miRNAs and anti-HIV-1 host restriction factors. RESULTS miR-422a was the only miRNA significantly modulated by IFN-α/RBV in vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive regulatory involvement of miR-422a in p53-dependent apoptotic and pyroptotic pathways. Based on sequence homology and inverse expression relationships, 29 unique miRNAs may regulate anti-HIV-1 restriction factor expression in vivo. CONCLUSIONS The specific reduction of miR-422a is associated with exogenous IFN-α treatment, and likely contributes to the IFN-α suppression of HIV-1 through the enhancement of anti-HIV-1 restriction factor expression and regulation of genes involved in programmed cell death. Moreover, our regulatory network analysis presents additional candidate miRNAs that may be targeted to enhance anti-HIV-1 restriction factor expression in vivo.

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Der vorliegende Beitrag geht der Frage nach, ob die schweizerische Demokratie bereits ab der Bundesstaatsgründung im Jahr 1848 eine ausgeprägte Konsensusdemokratie war. Zur Beantwortung dieser Fragestellung bedient sich die Studie des Konzepts von Arend Lijphart (2012) mit der Unterscheidung von Mehrheits- und Konsensusdemokratie. Anhand von Literatur- und Dokumentenanalysen wurden Lijpharts Indikatoren für den schweizerischen Bundesstaat von 1848–1874 codiert. Die Ergebnisse zeigen, dass das politische System der neu gegründeten Schweiz auf Lijpharts Demokratiekarte insbesondere auf der horizontalen Machtteilungsdimension wie erwartet sehr nahe an der Position der USA zu liegen kommt.

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von Max Freudenthal

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Mit Stempel: "Aus der Adam Späth'schen Sammlung zu Frankfurt a. M. der Stadtbibliothek gewidmet von Martin May"