A new portal for the analysis of human splicing variants

Understanding alternative splicing is crucial to elucidate the mechanisms behind several biological phenomena, including diseases. The huge amount of expressed sequences available nowadays represents an opportunity and a challenge to catalog and display alternative splicing events (ASEs). Although several groups have faced this challenge with relative success, we still lack a computational tool that uses a simple and straightforward method to retrieve, name and present ASEs. Here we present SPLOOCE, a portal for the analysis of human splicing variants. SPLOOCE uses a method based on regular expressions for retrieval of ASEs. We propose a simple syntax that is able to capture the complexity of ASEs.

Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study

Background: The purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families. Methods: The data set consisted of 1,694 individuals enrolled in the Baependi Heart Study. The heritability and the heterogeneity in genetic and environmental variance components by gender were estimated from variance components approaches, using the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package. The mixed-effects Cox model was used for the genetic analysis of the age-at onset of regular cigarette use. Results: The heritability estimates were high (> 50%) for smoking initiation and were intermediate, ranging from 23.4 to 31.9%, for smoking persistence and quantity. Significant evidence for heterogeneity in variance components by gender was observed for smoking initiation and age-at-onset of regular cigarette use. Genetic factors play an important role in the interindividual variation of these phenotypes in females, while in males there is a predominant environmental component, which could be explained by greater social influences in the initiation of tobacco use. Conclusions: Significant heritabilities were observed in smoking phenotypes for both males and females from the Brazilian population. These data add to the literature and are concordant with the notion of significant biological determination in smoking behavior. Samples from the Baependi Heart Study may be valuable for the mapping of genetic loci that modulate this complex biological trait.

Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury

de Araujo CC, Silva JD, Samary CS, Guimaraes IH, Marques PS, Oliveira GP, do Carmo LGRR, Goldenberg RC, Bakker-Abreu I, Diaz BL, Rocha NN, Capelozzi VL, Pelosi P, Rocco PRM. Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury. J Appl Physiol 112: 1206-1214, 2012. First published January 19, 2012; doi:10.1152/japplphysiol.01061.2011.-Physical activity modulates inflammation and immune response in both normal and pathologic conditions. We investigated whether regular and moderate exercise before the induction of experimental sepsis reduces the risk of lung and distal organ injury and survival. One hundred twenty-four BALB/c mice were randomly assigned to two groups: sedentary (S) and trained (T). Animals in T group ran on a motorized treadmill, at moderate intensity, 5% grade, 30 min/day, 3 times a week for 8 wk. Cardiac adaptation to exercise was evaluated using echocardiography. Systolic volume and left ventricular mass were increased in T compared with S group. Both T and S groups were further randomized either to sepsis induced by cecal ligation and puncture surgery (CLP) or sham operation (control). After 24 h, lung mechanics and histology, the degree of cell apoptosis in lung, heart, kidney, liver, and small intestine villi, and interleukin (IL)-6, KC (IL-8 murine functional homolog), IL-1 beta, IL-10, and number of cells in bronchoalveolar lavage (BALF) and peritoneal lavage (PLF) fluids as well as plasma were measured. In CLP, T compared with S groups showed: 1) improvement in survival; 2) reduced lung static elastance, alveolar collapse, collagen and elastic fiber content, number of neutrophils in BALF, PLF, and plasma, as well as lung and distal organ cell apoptosis; and 3) increased IL-10 in BALF and plasma, with reduced IL-6, KC, and IL-1 beta in PLF. In conclusion, regular and moderate exercise before the induction of sepsis reduced the risk of lung and distal organ damage, thus increasing survival.

Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats

Objective: To investigate, in male Wistar rats, the effects of long-term moderate red wine (RW) consumption (equivalent to similar to 0.15 mg% resveratrol RS), or RS in low (L, 0.15 mg%) or high (H, 400 mg%) doses in chow. Background: Both RW and RS exhibit cardioprotection. RS extends lifespan in obese rats. It is unclear whether RW consumption or low-dose RS delay vascular aging and prolong life span in the absence of overt risk factors. Methods: Endpoints were aerobic performance, exercise capacity, aging biomarkers (p53,p16,p21, telomere length and telomerase activity in aortic homogenates), vascular reactivity. Data were compared with controls (C) given regular chow. Results: Expressions of p53 decreased similar to 50% similar to with RW and LRS (p < 0.05 vs. C), p16 by similar to 29% with RW (p < 0.05 vs. C) and p21 was unaltered. RW and LRS increased telomere length >6.5-fold vs. C, and telomerase activity increased with LRS and HRS. All treatments increased aerobic capacity (C 32.5 +/- 1.2, RW 38.7 + 1.7, LRS 38.5 + 1.6, HRS 38.3 + 1.8 mlO2 min(-1) kg(-1)), and RW or LRS also improved time of exercise tolerance vs. C (p < 0.05). Endothelium-dependent relaxation improved with all treatments vs. C. Life span, however, was unaltered with each treatment vs. C = 673 +/- 30 days, p = NS. Conclusions: RW and LRS can preserve vascular function indexes in normal rats, although not extending life span. These effects were translated into better aerobic performance and exercise capacity. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Photoconduction action spectra of regio-regular poly(3-hexylthiopene):TiO2 diodes

The development of polymer-based photovoltaic devices brings the promise of low-cost and lightweight solar energy conversion systems. This technology requires new materials and device architectures with enhanced efficiency and lifetime, which depends on the understanding of charge-transport mechanisms. Organic films combined with electronegative nanoparticles may form systems with efficient dissociation of the photogenerated excitons, thus increasing the number of carriers to be collected by the electrodes. In this paper we investigate the steady-state photoconductive action spectra of devices formed by a bilayer of regio-regular poly(3-hexylthiophene) (RRP3HT) and TiO2 sandwiched between ITO and aluminum electrodes (ITO/TiO2:RRP3HT/Al). Photocurrents were measured for distinct bias voltages with illumination from either side of the device. Heterojunction structures were prepared by spin coating a RRP3HT film on an already deposited TiO2 layer on ITO. Symbatic and antibatic curves were obtained and a model for photocurrent action spectra was able to fit the symbatic responses. The quantum yield increased with the electric field, indicating that exciton dissociation is a field-assisted process as in an Onsager mechanism. Furthermore, the quantum yield was significantly higher when illumination was carried out through the ITO electrode onto which the TiO2 layer was deposited, as the highly electronegative TiO2 nanoparticles were efficient in exciton dissociation.

Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria

Abstract Background The development of protective immunity against malaria is slow and to be maintained, it requires exposure to multiple antigenic variants of malaria parasites and age-associated maturation of the immune system. Evidence that the protective immunity is associated with different classes and subclasses of antibodies reveals the importance of considering the quality of the response. In this study, we have evaluated the humoral immune response against Plasmodium falciparum blood stages of individuals naturally exposed to malaria who live in endemic areas of Brazil in order to assess the prevalence of different specific isotypes and their association with different malaria clinical expressions. Methods Different isotypes against P. falciparum blood stages, IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on the analysis of different clinical expressions of malaria (complicated, uncomplicated and asymptomatic) and factors related to prior malaria exposure such as age and the number of previous clinical malaria attacks. The occurrence of the H131 polymorphism of the FcγIIA receptor was also investigated in part of the studied population. Results The highest levels of IgG, IgG1, IgG2 and IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant among individuals with complicated malaria. Individuals reporting more than five previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3 antibodies, while IgM, IgA and IgE antibodies predominated among individuals reporting five or less previous clinical malaria attacks. Among individuals with uncomplicated and asymptomatic malaria, there was a predominance of high-avidity IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism was found in 44.4% of the individuals, and the highest IgG2 levels were observed among asymptomatic individuals with this allele, suggesting the protective role of IgG2 in this population. Conclusion Together, the results suggest a differential regulation in the anti-P. falciparum antibody pattern in different clinical expressions of malaria and showed that even in unstable transmission areas, protective immunity against malaria can be observed, when the appropriated antibodies are produced.

Inclusão de crianças com deficiência na escola regular numa região do município de São Paulo: conhecendo estratégias e ações

A inclusão de alunos com necessidades educacionais especiais no ensino regular depende da preparação da comunidade escolar para promover a participação de todos os alunos. Foi objetivo deste estudo conhecer, do ponto de vista do professor do ensino fundamental da rede pública municipal, as estratégias pedagógicas que utilizavam para a inclusão de crianças com deficiência na classe comum. Para isso foram realizadas entrevistas semiestruturadas individuais e, posteriormente, grupais com 11 professores de cinco escolas, um representante do Centro de Formação e Acompanhamento à Inclusão e um coordenador pedagógico. As entrevistas foram gravadas e transcritas. Após diversas leituras foi possível identificar como temáticas principais: sentidos e imaginários do professor sobre a deficiência, formação do professor para efetivação do processo de inclusão, bem como a utilização de estratégias pedagógicas diferenciadas e formação de rede de apoio na escola. Os entrevistados utilizavam estratégias gerais como aula expositiva, debates, e específicas como: avaliação dos alunos, adaptação do material, atividades em duplas, parceria com o professor da sala de apoio e acompanhamento à inclusão. Parte dos entrevistados trouxe uma visão com relação aos alunos com deficiência permeada de possibilidades, acreditando no potencial de aprendizagem dos mesmos, enquanto para outros, o discurso centrou-se, sobretudo, na impossibilidade da aprendizagem. Os docentes identificaram a necessidade de apoio institucional para seu trabalho, incluindo possibilidades de formação a partir das demandas cotidianas. Responder às necessidades levantadas é parte dos desafios para implementar a Educação Inclusiva na perspectiva da Educação para Todos, para a efetivação dos direitos de crianças com necessidades educacionais especiais.

Impacto da orientação para a prática regular de atividade física dois anos após o parto

OBJETIVOS: avaliar as modificações na prática de atividade física (AF) e as barreiras para adoção de um estilo de vida saudável em mulheres que receberam orientações nutricionais e de AF durante a gestação e no primeiro ano após o parto. MÉTODOS: estudo de coorte com 57 mulheres (Grupo Controle = 29 e Grupo Intervenção = 28), e idade média igual a 28 (±6) anos. As informações foram obtidas através de entrevistas em visita domiciliar (durante a intervenção) e inquérito telefônico (um ano após o término da intervenção), utilizou-se questionário de AF. Para análise das barreiras foi realizada uma entrevista semiestruturada com questões abertas, as quais foram codificadas e agrupadas para análise dos dados. Foram realizados testes de qui-quadrado, Mann-Whitney U e Friedman. RESULTADOS: aos seis meses, apenas 30% das mulheres do grupo Intervenção realizavam AF no lazer pelo menos 120 minutos por semana, contra 10% do grupo Controle, reduzindo para 18% e 4%, respectivamente, dois anos após o parto. As principais barreiras à prática de AF regular foram: falta de tempo (44%), cuidado com os filhos (37%), trabalho (21%), afazeres domésticos (21%) e comodismo (26%). CONCLUSÕES: futuros programas devem priorizar a aquisição de conhecimento, visando à adoção de um estilo de vida ativo no pós-parto, considerando as barreiras maternas.

Inclusão do portador de necessidades especiais no ensino regular: revisão da literatura

OBJETIVOS: Analisar criticamente a inclusão do portador de necessidades especiais no ensino regular brasileiro, considerando aspectos sociais e jurídicos, por meio de revisão de literatura. ESTRATÉGIA DE PESQUISA: A pesquisa bibliográfica foi conduzida em bases de dados de acesso público: LILACS, SciELO, Portal Cochrane e IUSDATA, sendo esta última da Biblioteca da Faculdade de Direito da Universidade de São Paulo, considerando todos os artigos publicados até o mês de dezembro de 2010. Como estratégia de busca foram utilizados os seguintes termos livres: educação inclusiva, educação especial, proposta inclusiva e portador de necessidades especiais. CRITÉRIOS DE SELEÇÃO: Durante a busca, foram avaliados e selecionados apenas os estudos cujo resumo ou corpo do artigo tivesse relação com o objetivo proposto. ANÁLISE DE DADOS : Os artigos potencialmente relevantes para a revisão foram apresentados em uma ficha protocolar contendo critérios de elegibilidade do estudo, métodos utilizados, características do grupo de artigos analisado, tipo de intervenção realizada e resultados obtidos no estudo. Os artigos classificados como opinião de especialistas, apesar de apresentarem baixo nível de evidência científica, foram incluídos no trabalho, pois são frequentemente encontrados na literatura sobre o assunto. RESULTADOS: Foram encontrados 1.399 artigos, e após leitura dos resumos foram selecionados 120 artigos potencialmente relevantes considerando-se o objetivo da pesquisa. Destes, 67 artigos foram citados em mais de uma base de dados, o que resultou em 53 artigos para serem lidos na íntegra. Após a leitura dos 53 artigos, foram excluídos 15 que não se enquadravam nos critérios de inclusão. Desta forma, 38 estudos foram incluídos e analisados. CONCLUSÃO: Após a análise crítica da literatura da área conclui-se que, até o momento, de maneira geral, a escola recebe, mas há muito a percorrer para incluir os alunos portadores de necessidades especiais, embora o país possua o escopo da inclusão. Assim, faz-se necessário o estabelecimento de diretrizes e ações políticas visando uma inclusão efetiva.