2,658 research outputs found

    Identification of transmembrane domains that regulate spatial arrangements and activity of prokineticin receptor 2 dimers

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    The chemokine prokineticin 2 (PK2) activates its cognate G protein-coupled receptor (GPCR) PKR2 to elicit various downstream signaling pathways involved in diverse biological processes. Many GPCRs undergo dimerization that can modulate a number of functions including membrane delivery and signal transduction. The aim of this study was to elucidate the interface of PKR2 protomers within dimers by analyzing the ability of PKR2 transmembrane (TM) deletion mutants to associate with wild type (WT) PKR2 in yeast using co-immunoprecipitation and mammalian cells using bioluminescence resonance energy transfer. Deletion of TMs 5-7 resulted in a lack of detectable association with WT PKR2, but could associate with a truncated mutant lacking TMs 6-7 (TM1-5). Interestingly, TM1-5 modulated the distance, or organization, between protomers and positively regulated Gαs signaling and surface expression of WT PKR2. We propose that PKR2 protomers form type II dimers involving TMs 4 and 5, with a role for TM5 in modulation of PKR2 function

    The Effects of Mental Health Stigma on Treatment Attitude within the Therapeutic Dyad: Therapist Beliefts in the Mental Health Recovery Process for Patients with Schizophrenia

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    OBJECTIVE: Stigma maintains a belief that a recovery process is infeasible for patients with schizophrenia. As clients internalize stigma and therapists maintain a conceptualization of non-recovery, their core beliefs about recovery may become treatment barriers. This study investigated clinicians’ attitudes towards recovery by evaluating the relationship between knowledge of schizophrenia, attitudes of stigma, and attitudes of tolerance held towards people with schizophrenia; included in the evaluation are years of experience working as a mental health professional. METHOD: This study is a cross-sectional survey design using a sample of 319 participants. The survey consisted of the following measures: knowledge of schizophrenia and attitudes (tolerance) held towards people with schizophrenia (SKAPS), attitudes (stigma) toward mental illness (MICA-4) and belief in the process of recovery (RKI). RESULTS: The findings of this study suggest that 1) stigma exists along with recovery beliefs, 2) attitudes of tolerance are associated with less stigma of mental illness, and 3) attitudes of tolerance are associated with less belief in the recovery process. In an exploratory analysis, having experience in providing treatment to those with severe mental illness did not influence the associations between knowledge, attitudes (stigma and tolerance), and recovery. Therefore, the findings were found to be comparable among clinicians regardless of experience level. CONCLUSIONS: This study has indicated the need for advocacy for patients with schizophrenia and also awareness of mental health stigma. Mental health stigma has complex roots in society and can become a hidden construct that complicates the process of recovery for patients

    The footprint of large scale cosmic structure on the ultra-high energy cosmic ray distribution

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    Current experiments collecting high statistics in ultra-high energy cosmic rays (UHECRs) are opening a new window on the universe. In this work we discuss a large scale structure model for the UHECR origin which evaluates the expected anisotropy in the UHECR arrival distribution starting from a given astronomical catalogue of the local universe. The model takes into account the main selection effects in the catalogue and the UHECR propagation effects. By applying this method to the IRAS PSCz catalogue, we derive the minimum statistics needed to significatively reject the hypothesis that UHECRs trace the baryonic distribution in the universe, in particular providing a forecast for the Auger experiment.Comment: 21 pages, 14 figures. Reference added, minor changes, matches published versio

    Suinocultura e meio ambiente em Santa Catarina: indicadores de desempenho e avaliação sócio-econômica.

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    bitstream/item/58223/1/doc120.pdfProjeto/Plano de Ação: 16.00.30004-0

    Are time preference and risk preference associated with cognitive intelligence and emotional intelligence?

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    The authors investigated whether cognitive intelligence (intelligence quotient [IQ]) and emotional intelligence (emotional quotient [EQ]) meaningfully correlate with time preference and risk preference, finding solid evidence in support. In the realm of time preference, high-EQ individuals are less subject to present (or future) bias and more patient. Further, high-IQ subjects tend to exhibit preferences that conform to expected utility maximization. While recent research on the relationship between cognitive ability and preferences has provided important insights, the results suggest that both cognitive intelligence and emotional intelligence matter

    Space-time symmetry restoration in cosmological models with Kalb--Ramond and scalar fields

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    We study symmetry of space-time in presence of a minimally coupled scalar field interacting with a Kalb--Ramond tensor fields in a homogeneous but initially anisotropic universe. The analysis is performed for the two relevant cases of a pure cosmological constant and a minimal quadratic, renormalizable, interaction term. In both cases, due to expansion, a complete spatial symmetry restoration is dynamically obtained.Comment: Latex, 7 pages, 3 eps figure

    Enhancer of zeste homolog 2 (EZH2) in pediatric soft tissue sarcomas: first implications.

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    Soft tissue sarcomas of childhood are a group of heterogeneous tumors thought to be derived from mesenchymal stem cells. Surgical resection is effective only in about 50% of cases and resistance to conventional chemotherapy is often responsible for treatment failure. Therefore, investigations on novel therapeutic targets are of fundamental importance. Deregulation of epigenetic mechanisms underlying chromatin modifications during stem cell differentiation has been suggested to contribute to soft tissue sarcoma pathogenesis. One of the main elements in this scenario is enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to the Polycomb group proteins. EZH2 catalyzes histone H3 methylation on gene promoters, thus repressing genes that induce stem cell differentiation to maintain an embryonic stem cell signature. EZH2 deregulated expression/function in soft tissue sarcomas has been recently reported. In this review, an overview of the recently reported functions of EZH2 in soft tissue sarcomas is given and the hypothesis that its expression might be involved in soft tissue sarcomagenesis is discussed. Finally, the therapeutic potential of epigenetic therapies modulating EZH2-mediated gene repression is considered

    Arginine 125 is an essential residue for the function of MRAP2

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    MRAP2 is a small simple transmembrane protein arranged in a double antiparallel topology on the plasma membrane. It is expressed in the paraventricular nucleus of the hypothalamus, where it interacts with various G protein-coupled receptors, such as the prokineticin receptors, and regulates energy expenditure and appetite. The aim of this work was to analyze the functional role of the specific arginine residue at position 125 of MRAP2, which affects protein conformation, dimer formation, and PKR2 binding. Results obtained with the MRAP2 mutants R125H and R125C, which are found in human patients with extreme obesity, and mouse MRAP2, in which arginine 125 is normally replaced by histidine, were compared with those obtained with human MRAP2. Understanding the mechanism by which MRAP2 regulates G protein-coupled receptors helps in elucidating the metabolic pathways involved in metabolic dysfunction and in developing new drugs as specific targets of the MRAP2-PKR2 complex
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