655 research outputs found

    Trusting the messenger because of the message: feedback dynamics from information quality to source evaluation

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    Published Online: 28 August 2013International audienceInformation provided by a source should be assessed by an intelligent agent on the basis of several criteria: most notably, its content and the trust one has in its source. In turn, the observed quality of information should feed back on the assessment of its source, and such feedback should intelligently distribute among different features of the source--e.g., competence and sincerity. We propose a formal framework in which trust is treated as a multi-dimensional concept relativized to the sincerity of the source and its competence with respect to specific domains: both these aspects influence the assessment of the information, and also determine a feedback on the trustworthiness degree of its source. We provide a framework to describe the combined effects of competence and sincerity on the perceived quality of information. We focus on the feedback dynamics from information quality to source evaluation, highlighting the role that uncertainty reduction and social comparison play in determining the amount and the distribution of feedback

    A Study on Binary Asteriod System Deflection

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    The study of asteroids, its composition and trajectories, has been a persistent interest in the space exploration community. In addition, they are also perceived as a great threat to life on Earth, considering the possibility of an impact with our planet. A considerable portion, around 15%, of the asteroid population are believed to be part of a double or triple asteroid system

    Molybdenum Induces the expression of a protein containing a new heterometallic Mo-Fe cluster in desulfoVibrio alaskensis

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    Biochemistry. 2009 Feb 10;48(5):873-82. doi: 10.1021/bi801773t.The characterization of a novel Mo-Fe protein (MorP) associated with a system that responds to Mo in Desulfovibrio alaskensis is reported. Biochemical characterization shows that MorP is a periplasmic homomultimer of high molecular weight (260 +/- 13 kDa) consisting of 16-18 monomers of 15321.1 +/- 0.5 Da. The UV/visible absorption spectrum of the as-isolated protein shows absorption peaks around 280, 320, and 570 nm with extinction coefficients of 18700, 12800, and 5000 M(-1) cm(-1), respectively. Metal content, EXAFS data and DFT calculations support the presence of a Mo-2S-[2Fe-2S]-2S-Mo cluster never reported before. Analysis of the available genomes from Desulfovibrio species shows that the MorP encoding gene is located downstream of a sensor and a regulator gene. This type of gene arrangement, called two component system, is used by the cell to regulate diverse physiological processes in response to changes in environmental conditions. Increase of both gene expression and protein production was observed when cells were cultured in the presence of 45 microM molybdenum. Involvement of this system in Mo tolerance of sulfate reducing bacteria is proposed

    Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming

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    Funding Information: Funding. This research was supported by Funda??o para a Ci?ncia e Tecnologia (FCT) (Ph.D. ProRegeM program, Ref: PD/BD/105893/2014; FCT individual Ph.D. fellowship Ref: 2020.06956.BD) and iNOVA4 Health (Project 4 and Project 21). iNOVA4Health-UID/Multi/04462/2013 is a program financially supported by Funda??o para a Ci?ncia e Tecnologia/ Minist?rio da Educa??o e Ci?ncia, through national funds. The authors would like to acknowledge the Instituto Portugu?s de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. Publisher Copyright: © Copyright © 2021 Nunes, Ramos, Santos, Mendes, Silva, Vicente, Pereira, Félix, Gonçalves and Serpa.Among gynecologic malignancies, ovarian cancer is the third most prevalent and the most common cause of death, especially due to diagnosis at an advanced stage together with resistance to therapy. As a solid tumor grows, cancer cells in the microenvironment are exposed to regions of hypoxia, a selective pressure prompting tumor progression and chemoresistance. We have previously shown that cysteine contributes to the adaptation to this hypoxic microenvironment, but the mechanisms by which cysteine protects ovarian cancer cells from hypoxia-induced death are still to be unveiled. Herein, we hypothesized that cysteine contribution relies on cellular metabolism reprogramming and energy production, being cysteine itself a metabolic source. Our results strongly supported a role of xCT symporter in energy production that requires cysteine metabolism instead of hydrogen sulfide (H2S) per se. Cysteine degradation depends on the action of the H2S-synthesizing enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and/or 3-mercaptopyruvate sulfurtransferase (MpST; together with cysteine aminotransferase, CAT). In normoxia, CBS and CSE inhibition had a mild impact on cysteine-sustained ATP production, pointing out the relevance of CAT + MpST pathway. However, in hypoxia, the concomitant inhibition of CBS and CSE had a stronger impact on ATP synthesis, thus also supporting a role of their hydrogen sulfide and/or cysteine persulfide-synthesizing activity in this stressful condition. However, the relative contributions of each of these enzymes (CBS/CSE/MpST) on cysteine-derived ATP synthesis under hypoxia remains unclear, due to the lack of specific inhibitors. Strikingly, NMR analysis strongly supported a role of cysteine in the whole cellular metabolism rewiring under hypoxia. Additionally, the use of cysteine to supply biosynthesis and bioenergetics was reinforced, bringing cysteine to the plateau of a main carbon sources in cancer. Collectively, this work supports that sulfur and carbon metabolism reprogramming underlies the adaptation to hypoxic microenvironment promoted by cysteine in ovarian cancer.publishersversionpublishe

    Purification, characterization and structural determination of UDP-N-acetylglucosamine pyrophosphorylase produced by Moniliophthora perniciosa

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    The enzyme UDP-N-acetylglucosamine pyrophosphorylase (PyroMp) from Moniliophthora perniciosa (CCMB 0257), a pathogenic fungal strain and the causative agent of the witches' broom disease in Theobroma cacao, was partially purified by precipitation with ammonium sulfate and gel filtration on Sephacryl S-200. The buffer for enzyme extraction was sodium phosphate, 0.050 mol L-1, pH 7.0, containing 1.0 mol L-1 NaCl. Response surface methodology (RSM) was used to determine the optimum pH and temperature conditions. Four different isoenzymes (PyroMp I, PyroMp II, PyroMp III and PyroMp IV) were obtained with optimal pH ranging from 6.9-8.4 and optimum temperature ranging from 28 to 68 °C. The 3D structure of pyrophosphorylase of M. perniciosa was determined by comparative modeling. The model obtained showed a good quality, possessing 78.6% of amino acids in energetically allowed regions. The model was then submitted for DM simulation and showed a good geometric quality (91.1% Ramachandran plot). The active site of the enzyme was found to be extremely well conserved. This model will be useful for developing new inhibitors against witches' broom disease.A enzima UDP-N-acetilglicosamina pirofosforilase de Moniliophthora perniciosa (CCMB 0257), o fungo patogênico causador da doença vassoura-de-bruxa do Theobroma cacao, foi parcialmente purificada por precipitação com sulfato de amônio e cromatografia de gel filtração em Sephacryl S-200. O tampão de extração da enzima foi o fosfato de sódio, 0,050 mol L-1, pH 7,0, contendo 1,0 mol L-1 de NaCl. A metodologia de superfície de resposta (MSR) foi usada para a obtenção do pH e temperatura ótima. Os resultados mostraram quatro diferentes isoenzimas (PyroMp I, PyroMp II, PyroMp III e PyroMp IV) que apresentaram pH ótimo na faixa de 6,9-8,4 e temperatura ótima variando entre 28 a 68 °C. A estrutura 3D de pirofosforilase de M. perniciosa foi obtida por modelagem comparativa. O modelo obtido mostrou uma boa qualidade, possuindo 78,6% de aminoácidos nas regiões energeticamente favoráveis. O modelo foi então submetido a simulações de dinâmica molecular (DM). O modelo apresentou uma boa qualidade geométrica após as simulações de DM (91,1% -gráfico de Ramachandran). A procura pelo sítio ativo da enzima mostrou que este é mantido extremamente conservado. Este modelo pode ser útil para desenvolvimento de inibidores contra a doença vassoura de bruxa.FINEPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNPqFAPESBFIOCRUZ - Programa de Pós-Graduação em Biotecnologia UEF

    Purification, characterization and structural determination of UDP-N-acetylglucosamine pyrophosphorylase produced by Moniliophthora perniciosa

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    The enzyme UDP-N-acetylglucosamine pyrophosphorylase (PyroMp) from Moniliophthora perniciosa (CCMB 0257), a pathogenic fungal strain and the causative agent of the witches' broom disease in Theobroma cacao, was partially purified by precipitation with ammonium sulfate and gel filtration on Sephacryl S-200. The buffer for enzyme extraction was sodium phosphate, 0.050 mol L-1, pH 7.0, containing 1.0 mol L-1 NaCl. Response surface methodology (RSM) was used to determine the optimum pH and temperature conditions. Four different isoenzymes (PyroMp I, PyroMp II, PyroMp III and PyroMp IV) were obtained with optimal pH ranging from 6.9-8.4 and optimum temperature ranging from 28 to 68 °C. The 3D structure of pyrophosphorylase of M. perniciosa was determined by comparative modeling. The model obtained showed a good quality, possessing 78.6% of amino acids in energetically allowed regions. The model was then submitted for DM simulation and showed a good geometric quality (91.1% Ramachandran plot). The active site of the enzyme was found to be extremely well conserved. This model will be useful for developing new inhibitors against witches' broom disease22610151023CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DA BAHIA - FAPESBFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãoA enzima UDP-N-acetilglicosamina pirofosforilase de Moniliophthora perniciosa (CCMB 0257), o fungo patogênico causador da doença vassoura-de-bruxa do Theobroma cacao, foi parcialmente purificada por precipitação com sulfato de amônio e cromatografia de gel filtração em Sephacryl S-200. O tampão de extração da enzima foi o fosfato de sódio, 0,050 mol L-1, pH 7,0, contendo 1,0 mol L-1 de NaCl. A metodologia de superfície de resposta (MSR) foi usada para a obtenção do pH e temperatura ótima. Os resultados mostraram quatro diferentes isoenzimas (PyroMp I, PyroMp II, PyroMp III e PyroMp IV) que apresentaram pH ótimo na faixa de 6,9-8,4 e temperatura ótima variando entre 28 a 68 °C. A estrutura 3D de pirofosforilase de M. perniciosa foi obtida por modelagem comparativa. O modelo obtido mostrou uma boa qualidade, possuindo 78,6% de aminoácidos nas regiões energeticamente favoráveis. O modelo foi então submetido a simulações de dinâmica molecular (DM). O modelo apresentou uma boa qualidade geométrica após as simulações de DM (91,1% -gráfico de Ramachandran). A procura pelo sítio ativo da enzima mostrou que este é mantido extremamente conservado. Este modelo pode ser útil para desenvolvimento de inibidores contra a doença vassoura de brux

    Estudo comparativo entre as técnicas de aglutinação em látex e de imunoturbidimetria para a detecção de fator reumatoide

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    INTRODUCTION: The rheumatoid factor (RF) is the most common antibody found in patients with rheumatoid arthritis. It is an inflammatory chronic disease characterized by articular involvement, inflammation of synovial fluid, tissue infiltration by leucocytes and joint destruction, which ultimately determine articular deformities. The rheumatoid factor is found in 70%-80% of the adult population and in 10% of the young population. OBJECTIVE: The aim of this research was to compare immunoturbidimetric and latex agglutination methods for the detection of RF in serum. RESULTS: The immunoturbidimetric method displayed sensitivity (95.2%), specificity (89.4%) and high positive correlation (R² = 0,8077) with the latex agglutination method in positive serum samples. CONCLUSION: The study allowed to demonstrate that both immunoturbidimetric and latex agglutination methods equally discriminate between negative and positive serum samples for RF.INTRODUÇÃO: O fator reumatoide (FR) é o autoanticorpo mais comum encontrado em pacientes com artrite reumatoide, uma doença crônica inflamatória caracterizada pelo envolvimento articular com inflamação do líquido sinovial, infiltração de tecido por leucócitos e destruição das articulações, que acaba por determinar deformidades articulares. O FR é encontrado em 70%-80% da população adulta e em 10% da população juvenil. OBJETIVO: Comparar os métodos de imunoturbidimetria e aglutinação (prova do látex) para a determinação de FR em soro. RESULTADO: Foi possível observar que o método imunoturbidimétrico apresenta sensibilidade (95,2%), especificidade (89,4%) e correlação positiva elevada (R² = 0,8077) com o método de aglutinação pelo látex em amostras de soro positivas. CONCLUSÃO: O estudo permitiu demonstrar que o método imunoturbidimétrico e o método de aglutinação pelo látex são igualmente capazes de discriminar amostras negativas e positivas para FR.Faculdade de Medicina do ABCInstituto Paulista de Ensino e Saúde de São PauloFaculdade de Medicina do ABC clinical laboratory analystUniversidade de São Paulo Faculdade de Medicina clinical laboratory biologisHospital Emílio RibasUniversidade PaulistaUSP Instituto de QuímicaUniversidade Federal de São Paulo (UNIFESP) Department of Biological SciencesUniversidade Federal de São Paulo (UNIFESP) Department of Biological SciencesUNIFESP, Department of Biological SciencesUNIFESP, Department of Biological SciencesSciEL

    Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

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    Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma
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