2,077 research outputs found

    Extracellular ATP triggers proteolysis and cytosolic Ca²⁺ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites.

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    BACKGROUND: Plasmodium has a complex cell biology and it is essential to dissect the cell-signalling pathways underlying its survival within the host. METHODS: Using the fluorescence resonance energy transfer (FRET) peptide substrate Abz-AIKFFARQ-EDDnp and Fluo4/AM, the effects of extracellular ATP on triggering proteolysis and Ca²⁺ signalling in Plasmodium berghei and Plasmodium yoelii malaria parasites were investigated. RESULTS: The protease activity was blocked in the presence of the purinergic receptor blockers suramin (50 μM) and PPADS (50 μM) or the extracellular and intracellular calcium chelators EGTA (5 mM) and BAPTA/AM (25, 100, 200 and 500 μM), respectively for P. yoelii and P. berghei. Addition of ATP (50, 70, 200 and 250 μM) to isolated parasites previously loaded with Fluo4/AM in a Ca²⁺-containing medium led to an increase in cytosolic calcium. This rise was blocked by pre-incubating the parasites with either purinergic antagonists PPADS (50 μM), TNP-ATP (50 μM) or the purinergic blockers KN-62 (10 μM) and Ip5I (10 μM). Incubating P. berghei infected cells with KN-62 (200 μM) resulted in a changed profile of merozoite surface protein 1 (MSP1) processing as revealed by western blot assays. Moreover incubating P. berghei for 17 h with KN-62 (10 μM) led to an increase in rings forms (82% ± 4, n = 11) and a decrease in trophozoite forms (18% ± 4, n = 11). CONCLUSIONS: The data clearly show that purinergic signalling modulates P. berghei protease(s) activity and that MSP1 is one target in this pathway

    ARQUEOLOGIA, CULTURA MATERIAL E INCLUSÃO SOCIAL NO BRASIL

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    Patrimônio é um tema complexo. Pode ser considerado uma maneira de transmitir sabedorias ou ensimanento morais, mas também pode se tornar instrumento importante para desafiar ideias e práticas estabelecidas, provocando o pensamento crítico e a ação. Tudo depende de como entedemos o que é patrimônio. O objetivo central desse artigo é discutir exatamente essa questão, explorando os significados dessa segunda perspectiva: os autores discutirão três estudos de caso no Brasil para arugumentar que cultura material, quando entendida de maneira mais progressiva, pode promover inclusão social e empoderamento.Heritage is a most controversial subject. It may be considered a way of upholding received wisdom and traditional mores, but it may also be considered a potent way of challenging established ideas and practices and fostering critical thinking and action. It all depends on the stand we take about heritage. The aim of this paper is to discuss the second perspective: the authors focus on three case studies in Brazil to argue that material culture, when understood in a progressive way, can promote social inclusion and community empowerment.Le patrimoine est un sujet complexe. Il peut être considéré comme un moyen de transmettre des savoirs ou connaissances morales, tout comme il peut se révéler être un instrument de premier plan pour remettre en cause des pratiques et des idées toutes faites, générant dans le même temps une action et une pensée critique. Tout dépend de la manière dont on aborde le patrimoine. L’objectif principal de cet article est justement d’aborder cette question de diversité d’approches, en étudiant les significations de la seconde perspective sur le patrimoine : les auteurs y discutent trois études de cas au Brésil pour soutenir l’idée que la culture matérielle, quand elle est pensée de manière progressive, peut promouvoir l’inclusion sociale et l’empowerment

    Banisteriopsis Species: A Source of Bioactive of Potential Medical Application

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    In recent years, interest in further development of herbal or botanical drug products derived from traditional preparations has been increasing steadily. Plants have been used for thousands of years to treat health disorders and to prevent diseases including epidemics. Several research works have been developed to search for new natural products to be used in pharmaceutical products. Active compounds produced during secondary metabolism are responsible for the biological properties of the plant species and may be used to most diverse purposes, including treatment of several diseases. Banisteriopsis species has been described showing interesting activities by its use in popular medicine. The mainly use was described to production of the Ayahuasca, an Amazonian psychotropic plant tea obtained from Banisteriopsis caapi, which contains  betacarboline alkaloids, mainly harmine, harmaline and tetrahydroharmine. Other species of Banisteriopsis genus have been described with biological metabolites as antimicrobial, anticholinesterase, antianxiety and others. These biological activities were described chiefly by the presence of alkaloids, flavonoids, tannins. Thus, to stimulate the study into the Banisteriopsis genus, the purpose of the present review is to gather information on the use of the extracts and metabolites of Banisteriopsis species (Malpighiaceae) as a resource to diseases treatment or to pharmaceutical purposes

    Functional phage display of leech-derived tryptase inhibitor (LDTI): construction of a library and selection of thrombin inhibitors

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    The recombinant phage antibody system pCANTAB 5E has been used to display functionally active leech-derived tryptase inhibitor (LDTI) on the tip of the filamentous M13 phage, A limited combinatorial library of 5.2 x 10(4) mutants was created with a synthetic LDTI gene, using a degenerated oligonucleotide and the pCANTAB 5E phagemid. the mutations were restricted to the P1-P4' positions of the reactive site. Fusion phages and appropriate host strains containing the phagemids were selected after binding to thrombin and DNA sequencing. the variants LDTI-2T (K8R, I9V, S10, K11W, P12A), LDTI-5T (K8R, I9V, S10, K11S, P12L) and LDTI-10T (K8R, I9L, S10, K11D, P12I) were produced with a Saccharomyces cerevisiae expression system. the new inhibitors, LDTI-2T and -5T, prolong the blood clotting time, inhibit thrombin (Ki 302 nM and 28 nM) and trypsin (K-i 6.4 nM and 2.1 nM) but not factor Xa, plasma kallikrein or neutrophil elastase, the variant LDTI-10T binds to thrombin but does not inhibit it, the relevant reactive site sequences of the thrombin inhibiting variants showed a strong preference for arginine in position P1 (K8R) and for valine in P1' (I9V), the data indicate further that LDTI-5T might be a model candidate for generation of active-site directed thrombin inhibitors and that LDTI in general may be useful to generate specific inhibitors suitable for a better understanding of enzyme-inhibitor interactions. (C) 1999 Federation of European Biochemical Societies.UNIFESP, Dept Bioquim, EPM, BR-04044020 São Paulo, BrazilUniv Munich, Klinikum Innenstadt, Chirurg Klin & Poliklin, Klin Chem & Klin Biochem Abt, D-8000 Munich, GermanyUNIFESP, Dept Med, Disciplina Hematol, EPM, BR-04044020 São Paulo, BrazilUNIFESP, Dept Bioquim, EPM, BR-04044020 São Paulo, BrazilUNIFESP, Dept Med, Disciplina Hematol, EPM, BR-04044020 São Paulo, BrazilWeb of Scienc

    Clinical management for epidermolysis bullosa dystrophica

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    Epidermolysis bullosa (EB) consists of a group of genetic hereditary disorders in which patients frequently present fragile skin and mucosa that form blisters following minor trauma. More than 20 subtypes of EB have been recognized in the literature. Specific genetic mutations are well characterized for most the different EB subtypes and variants. The most common oral manifestations of EB are painful blisters affecting all the oral surfaces. Dental treatment for patients with EB consists of palliative therapy for its oral manifestations along with typical restorative and periodontal procedures. The aim of this article is to describe two dental clinical treatments of recessive dystrophic EB cases and their specific clinical manifestations. The psychological intervention required during the dental treatment of these patients is also presented

    GESTORES E AGENTES SOCIAIS DE ESPORTE E LAZER NA BAIXADA MARANHENSE: um estudo dos recursos humanos para o Sistema Nacional de Esporte e Lazer

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    O governo federal criou, em 1998, o Sistema Brasileiro do Esporte, que abrange o Ministério do Esporte, o Conselho Nacional do Esporte e o Sistema Nacional de Esporte, concebendo-o como objeto de política de estado.Este artigo refere-se a um projeto de pesquisa em desenvolvimento pelo Núcleo/UFMA do Centro de Desenvolvimento do Esporte Recreativo e do Lazer (REDE CEDES), financiado pelo MCT/FINEP/ME. Investiga o perfil dos sujeitos responsáveis pelo gerenciamento e execução direta das políticas públicas de esporte e lazer em dez municípios da baixada maranhense. Serão utilizadas entrevistas semi-estruturadas, aplicadas aos gestores públicos municipais e questionários aos agentes sociais de alguns segmentos da sociedade. Encontra-se na fase de pesquisa bibliográfica e das primeiras visitas ao campo. A conclusão será em 2008, quando apresentar-se-á o relatório final.Rede CEDE

    MIGRANTES TEMPORALES: RESIGNIFICACIÓN DE LAS NARRATIVAS

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     El objetivo de este texto es el análisis de las narrativas de campesinos migrantes temporales, procedentes de dos regiones de fuerte emigración en Brasil: el estado de Paraíba, (situado en el nordeste del país), y el norte de Minas Gerais (situado en la región sudeste), donde se localiza el Vale do Rio Jequitinhonha. El estado de São Paulo es el principal destino de estos campesinos migrantes a causa de los extensos cañaverales que, actualmente, cubren un área de más de cinco millones de hectáreas. Son utilizadas también las narrativas de campesinos migrantes para la ciudad de São Paulo y de Rio de Janeiro. La metodología se basa en la Historia Oral. El eje principal de las reflexiones sostiene la idea de que no hay una desaparición de las narrativas causada por las constantes migraciones, sino una resignificación de las mismas, a partir de la experiencia migratoria. Palabras clave: Trabajo, emigración, narrativas.   Abstract The aim of this article is to analyse the narratives of  the temporary peasant migrants  from two important emigration regions in Brazil:  the State of Paraiba (located in the Northeast region) and  Vale of Jequitinhonha River in the North of Minas Gerais (located in the southeast region). The  main destination of the peasant migrants  is the sugar cane fields in the State of São Paulo, which covers over five millions of hectares of land. The narratives of peasant  migrants who go to the cities of São Paulo and Rio de Janeiro are also analysed in the article. The methodology is grounded on oral history. The main idea of the analysis  is that the narrative has not disappeared due to the permanent migrations, but there has been a re-interpretation of the narratives throughout the migration experience. Keywords: Job, emigration, narratives

    Tumor slices as a model to evaluate doxorubicin in vitro treatment and expression of trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 in canine mammary gland cancer

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    <p>Abstract</p> <p>Background</p> <p>In women with breast cancer submitted to neoadjuvant chemotherapy based in doxorubicin, tumor expression of groups of three genes (PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2) have classified them as responsive or resistant. We have investigated whether expression of these trios of genes could predict mammary carcinoma response in dogs and whether tumor slices, which maintain epithelial-mesenchymal interactions, could be used to evaluate drug response <it>in vitro</it>.</p> <p>Methods</p> <p>Tumors from 38 dogs were sliced and cultured with or without doxorubicin 1 μM for 24 h. Tumor cells were counted by two observers to establish a percentage variation in cell number, between slices. Based on these results, a reduction in cell number between treated and control samples ≥ 21.7%, arbitrarily classified samples, as drug responsive. Tumor expression of PRSS11, MTSS1, CLPTM1 and SMYD2, was evaluated by real time PCR. Relative expression results were then transformed to their natural logarithm values, which were spatially disposed according to the expression of trios of genes, comprising PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. Fisher linear discrimination test was used to generate a separation plane between responsive and non-responsive tumors.</p> <p>Results</p> <p>Culture of tumor slices for 24 h was feasible. Nine samples were considered responsive and 29 non-responsive to doxorubicin, considering the pre-established cut-off value of cell number reduction ≥ 21.7%, between doxorubicin treated and control samples. Relative gene expression was evaluated and tumor samples were then spatially distributed according to the expression of the trios of genes: PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. A separation plane was generated. However, no clear separation between responsive and non-responsive samples could be observed.</p> <p>Conclusion</p> <p>Three-dimensional distribution of samples according to the expression of the trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 could not predict doxorubicin <it>in vitro </it>responsiveness. Short term culture of mammary gland cancer slices may be an interesting model to evaluate chemotherapy activity.</p

    Exegese Bíblica: vantagens, desvantagens, limites e contribuições na interpretação moderna da Bíblia

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    Resumo: o presente artigo procura tratar da contribuição da Exegese Bíblica para a Interpretação Moderna da Bíblia. Começa por definir a diferença entre Exegese e hermenêutica, iniciada no âmbito teológico, mas que logo se expandiu para a moderna Filologia, Fisologia e História. Prossegue traçando um breve itinerário histórico da exegese bíblica para desembocar na complexidade dos métodos atuais de interpretação da Bíblia, todos eles apresentando vantagens, desvantagens, limites e contribuições. Porém, se detém na contribuição do Método Hitórico-Crítico por colocar o estudo bíblico numa discussão secular. Embora o Método Histórico-Crítico seja bastante criticado é, no mínimo, um ponto de partida e não deve ser rejeitado. A importância da exegese bíblica, para não dizer de sua necessidade, reside no fato de que ela possibilita uma compreensão mais exata do sentido de um texto bíblico, e, por conseguinte, fornece bases para uma construção teológica melhor fundamentada. Palavras-chave: Bíblia. Exegese. Hermenêutica. Método histórico-crítico. Vida
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