103 research outputs found

    COMMD1-Mediated Ubiquitination Regulates CFTR Trafficking

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    The CFTR (cystic fibrosis transmembrane conductance regulator) protein is a large polytopic protein whose biogenesis is inefficient. To better understand the regulation of CFTR processing and trafficking, we conducted a genetic screen that identified COMMD1 as a new CFTR partner. COMMD1 is a protein associated with multiple cellular pathways, including the regulation of hepatic copper excretion, sodium uptake through interaction with ENaC (epithelial sodium channel) and NF-kappaB signaling. In this study, we show that COMMD1 interacts with CFTR in cells expressing both proteins endogenously. This interaction promotes CFTR cell surface expression as assessed by biotinylation experiments in heterologously expressing cells through regulation of CFTR ubiquitination. In summary, our data demonstrate that CFTR is protected from ubiquitination by COMMD1, which sustains CFTR expression at the plasma membrane. Thus, increasing COMMD1 expression may provide an approach to simultaneously inhibit ENaC absorption and enhance CFTR trafficking, two major issues in cystic fibrosis

    Securing the Downside Up: Client and Care Factors Associated with Outcomes of Secure Residential Youth Care

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    Although secure residential care has the potential of reducing young people's behavioral problems, it is often difficult to achieve positive outcomes. Research suggests that there are several common success factors of treatment, of which the client's motivation for treatment and the quality of the therapeutic relationship between clients and therapists might be especially relevant and important in the context of secure residential care. The objective of the present study was to explore the association of these potential success factors with secure residential care outcomes. A repeated measures research design was applied in the study, including a group of adolescents in a secure residential care center that was followed up on three measurements in time. Interviews and questionnaires concerning care outcomes in terms of adolescents' behavior change during care were administered to 22 adolescents and 27 group care workers. Outcomes in terms of adolescents' treatment satisfaction were assessed by the use of questionnaires, which were completed by 51 adolescents. Adolescents reported some positive changes in their treatment motivation, but those who were more likely to be motivated at admission were also more likely to deteriorate in treatment motivation from admission to departure. Treatment satisfaction was associated with better treatment motivation at admission and with a positive adolescent-group care worker relationship. The results suggest that outcomes can be improved by a more explicit treatment focus on improving the adolescent's treatment motivation and the quality of the adolescent-care worker relationship during secure residential care

    Interrogating open issues in cancer precision medicine with patient-derived xenografts

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    Reactions in the systems Mo-Si3N4 and Ni-Si3N4

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    The reaction products, formed during annealing of porous powder mixts. of Si3N4 with nonnitride-forming metals like Ni or Mo, will depend on the partial pressure of N2 in the atm. In a diffusion couple, however, nitrogen has to be released at the Si3N4 interface during the formation of a metal silicide. It cannot escape easily and build up a higher pressure of nitrogen at this interface. Therefore, the reaction products are different from those in porous pellets. This has been verified for Ni-Si3N4 and Mo-Si3N4 couples. The role of traces of oxygen on these reactions is discussed. [on SciFinder (R)
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