17,754 research outputs found

    Impacts from initialization techniques – An optimal computational resource allocation problem

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    Multiple criteria data envelopment analysis for full ranking units associated to environment impact assessment

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    Author name used in this publication: Chun-Tian ChengAuthor Gang LI, Department of Civil Engineering, Dalian University of Technology, Dalian.2006-2007 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

    New tricks for KDEL receptors

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    Tankyrase Inhibitors Target YAP by Stabilizing Angiomotin Family Proteins

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    SummaryAs the key effector in the Hippo pathway, YAP was identified as an oncoprotein whose expression is elevated in various human cancers. However, the development of potentially therapeutic compounds targeting YAP has been slow and limited. Here, we find that tankyrase inhibitors suppress YAP activity. This effect is mediated by anigomotin (AMOT) family proteins. Tankyrases associate with AMOT family proteins and promote their degradation through E3 ligase RNF146. By antagonizing tankyrase activity, tankyrase inhibitors stabilize AMOT family proteins, thereby suppressing YAP oncogenic functions. Together, our studies not only demonstrate the tankyrase-RNF146-AMOT axis as an upstream pathway regulating YAP but also reveal a therapeutic opportunity in targeting YAP for cancer treatment

    Class II ADP-ribosylation factors are required for efficient secretion of Dengue viruses

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    This article is available open access through the publisher’s website.Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins.Research Fund for Control of Infectious Diseases of Hong Kong and BNP Paribas Corporate and Investment Banking

    The clinical course of polymyalgia rheumatica in Chinese

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    Polymyalgia rheumatica (PMR) is diagnosed based on clinical features that may overlap with other rheumatic conditions like rheumatoid arthritis (RA). Furthermore, a proportion of PMR patients may subsequently evolve into RA. The aim of this study was to examine the clinical characteristics of PMR patients in a Chinese cohort compared to a Caucasian series. Patients diagnosed to have PMR during 1997-2008 were reviewed for clinical features and compared to a reported Caucasian series. Rheumatoid factor (RF) and anticyclic citrullinated peptide (CCP) antibodies were determined by immunonephelometry and enzyme-linked immunosorbent assay, respectively. Forty-four patients of southern Chinese origin were diagnosed to have PMR according to specialist opinion. Seventy-five percent of patients (n = 33) were >65 years of age at diagnosis (mean ± standard deviation, 75.8 ± 9.6 years). The commonest feature at disease onset was elevated erythrocyte sedimentation rate >40 mm/h (100% vs. 95.7%; p = 0.17) and bilateral shoulder pain or stiffness (95.5% vs. 90.8%; p = 0.31), comparable in frequency to the Caucasian cohort. However, Chinese patients had significantly longer duration of symptoms before diagnosis (p < 0.001) but less bilateral upper arm tenderness (p < 0.001) and generalized stiffness (p = 0.01). Twelve (27.3%) patients evolved into RA after a median duration of 2 months from onset of PMR. RF and anti-CCP antibodies were positive in 66.7% and 60% of these patients compared to 9.4% and 6.2%, respectively, among those who did not evolve into RA during the period observed. Chinese patients with PMR have modestly different clinical profile compared to the Caucasian counterpart. RF and anti-CCP antibodies were more likely to be present in those who subsequently developed into RA. © 2009 Clinical Rheumatology.postprin

    Aortic Coarctation Following Aortic Valve Replacement: Problem Solving with Multimodality Cardiac Imaging

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