29 research outputs found

    Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity

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    Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the MAP3K14 gene encoding NIK (NF- B-inducing kinase). Loss of kinase activity of mutant NIK, predicted by in silico analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF- B signalling. Patients with mutated NIK exhibit B-cell lymphopenia, decreased frequencies of class-switched memory B cells and hypogammaglobulinemia due to impaired B-cell survival, and impaired ICOSL expression. Although overall T-cell numbers are normal, both follicular helper and memory T cells are perturbed. Natural killer (NK) cells are decreased and exhibit defective activation, leading to impaired formation of NK-cell immunological synapses. Collectively, our data illustrate the non-redundant role for NIK in human immune responses, demonstrating that loss-of-function mutations in NIK can cause multiple aberrations of lymphoid immunity

    Music, Singing and Stage Practice in the Cinemas of Upper Silesia During the 1920s

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    National, transnational, or supranational cinema? Rethinking European film studies

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    This article discusses critical parameters and historical perceptions that have dominated the academic study of European cinema since the 1990s. The main argument is that what has been frequently ignored is the supranational dimension of the term ‘European’. Thus, while the field of European film studies has witnessed a number of significant shifts in emphasis (most pertinently the refocusing from art cinema towards popular film genres), the core debate still primarily centres on national cinemas. The article then suggests engaging in areas that exemplify interconnectedness between national cinemas. These include patterns of inter-European migration and issues of multiculturalism; industrial practices such as co-productions; as well as localized strategies of receiving foreign films through mechanisms of translation and adaptation
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