3,015 research outputs found

    Knocking Down Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) Reverts Chemoresistance through Inactivation of Src and Bcr-Abl Proteins

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    The development of multidrug resistance (MDR) limits the efficacy of continuous chemotherapeutic treatment in chronic myelogenous leukemia (CML). Low molecular weight protein tyrosine phosphatase (LMW-PTP) is up-regulated in several cancers and has been associated to poor prognosis. This prompted us to investigate the involvement of LMW-PTP in MDR. In this study, we investigated the role of LMW-PTP in a chemoresistant CML cell line, Lucena-1. Our results showed that LMW-PTP is highly expressed and 7-fold more active in Lucena-1 cells compared to K562 cells, the non-resistant cell line. Knocking down LMW-PTP in Lucena-1 cells reverted chemoresistance to vincristine and imatinib mesylate, followed by a decrease of Src and Bcr-Abl phosphorylation at the activating sites, inactivating both kinases. On the other hand, overexpression of LMW-PTP in K562 cells led to chemoresistance to vincristine. Our findings describe, for the first time, that LMW-PTP cooperates with MDR phenotype, at least in part, through maintaining Src and Bcr-Abl kinases in more active statuses. These findings suggest that inhibition of LMW-PTP may be a useful strategy for the development of therapies for multidrug resistant CML

    DEP–DM: Uma Abordagem baseada em Ensemble Regression para o Diagnóstico de Problemas Educacionais

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    Este artigo apresenta a abordagem DEP-DM, baseada em modelos Ensemble Regression para o diagnóstico do problema do desempenho escolar dos estudantes das escolas públicas de Pernambuco. O estudo baseou-se em informações do SAEB do ano de 2013. O conhecimento foi extraído por meio da abordagem proposta, sendo possível identificar os fatores associados e estabelecer as relações de causa e efeito com o problema do desempenho escolar. Por fim, foram aplicados modelos de regressão paramétricos e não paramétricos para a previsão desse desempenho. Os resultados e diagnóstico apresentam que os fatores relacionados a infraestrutura da escola, ensino e familiares, exercem forte influência sobre o desempenho escolar

    Strong relationships between soil and vegetation in reference ecosystems of a riparian atlantic rainforest in the upper Doce River watershed, southeastern Brazil

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    Habitat loss and fragmentation have been impacting ecosystem services essential for human survival. The Brazilian Atlantic rainforest, a biodiversity hotspot, has suffered from historical deforestation and, more recently, from an environmental disaster caused by the Fundão dam collapse that released ore tailings drastically affecting a large territory in the Doce River watershed. This work aims to assess the relationships between soil properties and vegetation in a reference ecosystem to provide guidelines for restoration projects in areas affected by the dam collapse. We conducted phytosociological (vegetation characteristic) and soil quality studies in three distinct natural sites and studied different vegetation strata to better understand plant species composition in reference sites along the impacted Doce River and their potential role in community structuring and functioning. We recorded 140 species, 78 in the tree stratum, and 90 in the sapling stratum. Furthermore, our results highlight the influence of soil on floristic composition in the Atlantic rainforest. Smallscale edaphic variation influenced species composition in both sapling and tree strata. We also identified species of the same genus with strong association with the extremes of the edaphic gradient. Therefore, we highlight that studies in various regions along the Doce River watershed are of utmost importance to evaluate the association between species and soils. The particularities of the species are crucial to the effectiveness of restoration processes since this plant-soil correlation should not be extrapolated even within the same genus. This knowledge is of strategic relevance to provide scientificbased guidance for restoring these environments, aiming at the recovery of biodiversity and ecosystem services.Fil: Ramos, Letícia. Universidade Federal de Minas Gerais; BrasilFil: Negreiros, Daniel. Universidade Federal de Minas Gerais; BrasilFil: Ferreira, Bárbara S. Silva. Universidade Federal de Minas Gerais; BrasilFil: Figueiredo, João Carlos Gomes. Universidade Estadual de Montes Claros; BrasilFil: Paiva, Dario C.. Florida International University; Estados UnidosFil: Oki, Yumi. Universidade Federal de Minas Gerais; BrasilFil: De Souza Justino, Wénita. Universidade Federal de Minas Gerais; BrasilFil: Dos Santos, Rubens Manoel. Universidade Federal de Lavras; BrasilFil: Aguilar, Ramiro. Universidade Federal de Minas Gerais; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Nunes, Yule Roberta Ferreira. Universidade Estadual de Montes Claros; BrasilFil: Fernandes, G Wilson. Universidade Federal de Minas Gerais; Brasi

    The Combined Use of Melatonin and an Indoleamine 2,3-Dioxygenase-1 Inhibitor Enhances Vaccine-Induced Protective Cellular Immunity to HPV16-Associated Tumors

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    Immunotherapy has become an important ally in the fight against distinct types of cancer. However, the metabolic plasticity of the tumor environment frequently influences the efficacy of therapeutic procedures, including those based on immunological tools. In this scenario, immunometabolic adjuvants arise as an alternative toward the development of more efficient cancer therapies. Here we demonstrated that the combination of melatonin, a neuroimmunomodulator molecule, and an indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-DL-tryptophan, DL-1MT) improves the efficacy of an immunotherapy (gDE7) targeting human papillomavirus (HPV)-associated tumors. Melatonin or IDO inhibitors (D-1MT and DL-1MT) directly reduced proliferation, migration, adhesion and viability of a tumor cell line (TC-1), capable to express the HPV-16 E6 and E7 oncoproteins, but could not confer in vivo antitumor protection effects. Nonetheless, combination of gDE7 with melatonin or D-1MT or DL-1MT enhanced the antitumor protective immunity of gDE7-based vaccine in mice. Notably, expression of IDO1 in stromal cells and/or immune cells, but not in tumor cells, inhibited the antitumor effects of the gDE7, as demonstrated in IDO1-deficient mice. Finally, co-administration of gDE7, melatonin and DL-1MT further improved the protective antitumor effects and the numbers of circulating E7-specific CD8+ T cells in mice previously transplanted with TC-1 cells. The unprecedented combination of melatonin and IDO inhibitors, as immunometabolic adjuvants, thus, represents a new and promising alternative for improving the efficacy of immunotherapeutic treatments of HPV-associated tumors

    Digital tools for supporting climate-informed agroecological transition in beef production in Brazil

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    KEY MESSAGES ◼ Despite many available digital tools in the digital ecosystem, many neglect smallholders’ ranching. Also, they focus solely on performance indicators, lacking climate-informed agroecological features. ◼ Mitigation features are included only by performance assessment tools, although only by half of them. ◼ Adaptation features in digital tools include mitigation recommendations, access to pest and disease information or early warning, and product diversification. ◼ Of the digital tools providing performance assessment (6 total), all include agroecological principles, three included adaptation, and all mitigation indicators on average per tool. ◼ Social inclusion and co-design features are related to data protection for farmers, direct farmer contributions (on the improvement of the digital tools), and safety measures, especially amongst women. ◼ Tools with socially inclusive communication features are limited. Most of the tools reviewed here have more than one way of engaging farm users (IVR, SMS, etc.), and allow the integration of other tools

    Dengue Virus Type 4 Phylogenetics in Brazil 2011: Looking beyond the Veil

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    Dengue Fever and Dengue Hemorrhagic Fever are diseases affecting approximately 100 million people/year and are a major concern in developing countries. In the present study, the phylogenetic relationship of six strains of the first autochthonous cases of DENV-4 infection occurred in Sao Paulo State, Parana State and Rio Grande do Sul State, Brazil, 2011 were studied. Nucleotide sequences of the envelope gene were determined and compared with sequences representative of the genotypes I, II, III and Sylvatic for DEN4 retrieved from GenBank. We employed a Bayesian phylogenetic approach to reconstruct the phylogenetic relationships of Brazilian DENV-4 and we estimated evolutionary rates and dates of divergence for DENV-4 found in Brazil in 2011. All samples sequenced in this study were located in Genotype II. The studied strains are monophyletic and our data suggest that they have been evolving separately for at least 4 to 6 years. Our data suggest that the virus might have been present in the region for some time, without being noticed by Health Surveillance Services due to a low level of circulation and a higher prevalence of DENV-1 and DENV- 2

    Circulation of Different Lineages of Dengue Virus 2, Genotype American/Asian in Brazil: Dynamics and Molecular and Phylogenetic Characterization

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    The American/Asian genotype of Dengue virus type 2 (DENV-2) was introduced into the Americas in the 80′s. Although there is no data showing when this genotype was first introduced into Brazil, it was first detected in Brazil in 1990. After which the virus spread throughout the country and major epidemics occurred in 1998, 2007/08 and 2010. In this study we sequenced 12 DENV-2 genomes obtained from serum samples of patients with dengue fever residing in São José do Rio Preto, São Paulo (SJRP/SP), Brazil, in 2008. The whole open reading frame or envelope sequences were used to perform phylogenetic, phylogeographic and evolutionary analyses. Isolates from SJRP/SP were grouped within one lineage (BR3) close to isolates from Rio de Janeiro, Brazil. Isolates from SJRP were probably introduced there at least in 2007, prior to its detection in the 2008 outbreak. DENV-2 circulation in Brazil is characterized by the introduction, displacement and circulation of three well-defined lineages in different times, most probably from the Caribbean. Thirty-seven unique amino acid substitutions were observed among the lineages, including seven amino acid differences in domains I to III of the envelope protein. Moreover, we dated here, for the first time, the introduction of American/Asian genotype into Brazil (lineage BR1) to 1988/89, followed by the introduction of lineages BR2 (1998–2000) and BR3 (2003–05). Our results show a delay between the introduction and detection of DENV-2 lineages in Brazil, reinforcing the importance and need for surveillance programs to detect and trace the evolution of these viruses. Additionally, Brazilian DENV-2 differed in genetic diversity, date of introduction and geographic origin and distribution in Brazil, and these are important factors for the evolution, dynamics and control of dengue.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq Grant )Fundação de Amparo à Pesquisa do Estado de São PauloFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG grant
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