8 research outputs found

    The Obama administration and the Egyptian Muslim Brotherhood in the Arab Revolutions. Taming political Islam?

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    This article deals with US policy towards the Egyptian Muslim Brotherhood. How has the leading world state power been dealing with the main Islamist movement, especially in the aftermath of the Arab upheavals? What is the intellectual approach to political Islam, specifically within the Obama administration? Has the anti-US potential been tamed or not? In light of the discourse held by US leaders and diplomats, I highlight the difficulties in addressing the Muslim Brotherhood. More specifically, I shed light on the way US policy of engagement towards the Islamist movement has been conducted

    Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

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    : Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including seven recurrent variants in 30 individuals) and six individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function of the Drosophila orthologs, U2af50 and Prp19, led to lethality, abnormal mushroom body (MB) patterning, and social deficits, differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50 deficient flies. Upon re-analysis of negative clinical exomes followed by data sharing, we further identified six NDD patients carrying RBFOX1 missense variants which, by in vitro testing, showed loss of function. Our study implicates three splicing factors as NDD causative genes and establishes a genetic network with hierarchy underlying human brain development and function
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