1,247 research outputs found

    Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

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    This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe

    Short-term economic impact of the Zika virus outbreak

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    Summary Zika virus (ZIKV) is mainly transmitted by mosquitoes bites. However, transmission by sexual contacts has been reported in 11 non endemic countries. The rapid spread of ZIKV in Latin American and Caribbean Countries (LCR), person-to-person transmission and perceived risk on people’s well being can affect the emerging economies of LCR which historically dependent on truism. Here we present an analysis on economic outputs for assessing the current impact of ZIKV on markets. Our analysis show an unexpected resilience of LCR markets to international alerts. This positive response represents an opportunity to scale-up interventions for preventing the further spreading of the ZIKV epidemic

    Intact triacylglycerol profiles of fats and meats via thermal imprinting easy ambient sonic-spray ionization mass spectrometry

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    Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Thermal imprinting (TI) on a paper surface, using minimal solvent amounts, followed by direct analysis of the triacylglycerols (TAG) content via easy ambient sonic-spray ionization mass spectrometry (EASI-MS) is shown to provide a fast protocol to analyze TAG in meats and fats. The technique is simple, fast and eco-friendly requiring no hydrolysis, derivatization or chromatographic separation. The entire TI-EASI-MS protocol is performed in a few minutes and with minimal sample handling and solvent consumption. The TAG profiles obtained via TI-EASI-MS are shown to be quite similar to those obtained using GC and MALDI-MS analyses, and the imprinting and mailing of the imprinted paper in a sealed plastic bag is proposed for remote TI-EASI-MS analysis of meat and fat samples.41135513557Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financing Agency of Studies and Projects (FINEP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

    Interrelationship between implant and orthognathic surgery for the rehabilitation of edentulous cleft palate patients: a case report

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    A 43-year-old woman with a unilateral cleft lip and palate, presenting a totally edentulous maxilla and mandible with marked maxillomandibular discrepancy, attended the Prosthodontics section of the Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo for treatment. She could not close her mouth and was dissatisfied with her complete dentures. Treatment planning comprised placement of six implants in the maxilla, four in the mandible followed by prostheses installation and orthognathic surgery. The mandibular full arch prosthesis guided the occlusion for orthognathic positioning of the maxilla. The maxillary complete prosthesis was designed to assist the orthognathic surgery with a provisional prosthesis (no metal framework), allowing reverse treatment planning. Maxillary and mandibular realignment was performed. Three months later, a relapse in the position of the maxilla was observed, which was offset with a new maxillary prosthesis. This isa complex interdisciplinary treatment and two-year follow-up is presented and discussed. It should be considered that this type of treatment could also be applied in non-cleft patients

    Human aging and somatic point mutations in mtDNA: A comparative study of generational differences (grandparents and grandchildren)

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    The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop) of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years) and their 62 grandchildren (mean age: 15 ± 4.1 years), the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers and in a heteroplasmic state in an additional 13 grandmothers; no mutations were detected in the remaining 15 grandmothers. However, cloning followed by DNA sequencing in 12 grandmothers confirmed homoplasia in only one of the three mutations previously considered to be homoplasmic and did not confirm heteroplasmy in three out of nine grandmothers found to be heteroplasmic by direct sequencing. Thus, of 12 grandmothers in whom mtDNA was analyzed by cloning, eight were heteroplasmic for mutations not detected in their grandchildren. In this study, the use of genetically related subjects allowed us to demonstrate the occurrence of age-related (> 60 years old) mutations (homoplasia and heteroplasmy). It is possible that both of these situations (homoplasia and heteroplasmy) were a long-term consequence of mitochondrial oxidative phosphorylation that can lead to the accumulation of mtDNA mutations throughout life
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