A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2. HER2 targeting by antibodies inhibited growth in association with persistent generation of reactive oxygen species (ROS), glutathione (GSH) depletion, reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell lines. The combination of antibodies produced more potent effects than single alone; downregulated NRF2 substrates by repressing the Antioxidant Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We showed the antibody combination produced increased methylation at the NRF2 promoter consistent with repression of NRF2 antioxidant function, as HDAC and methylation inhibitors reversed such produced transcriptional effects. These findings demonstrate a novel mechanism and role for NRF2 in mediating the response of cancer cells to the combination of Trastuzumab and Pertuzumab and reinforce the importance of NRF2 in drug resistance and as a key anticancer target.

Educação intercultural no 1º Ciclo do Ensino Básico: parcerias envolvendo a escola e a comunidade

Este estudo tem como finalidade compreender o processo de constituição de uma parceria educativa envolvendo escolas do 1.º Ciclo do Ensino Básico e outras instituições da comunidade para a promoção da educação intercultural e analisar a influência do trabalho desenvolvido por essa parceria nas práticas, atitudes, competências e conhecimentos de todos os participantes. Situa-se, por um lado, num entendimento de educação intercultural enquanto abordagem educativa fundamental para todos os alunos, assente na valorização da diversidade e na promoção de atitudes e competências de relacionamento interpessoal (como o respeito e a solidariedade), tendo em vista a formação de cidadãos responsáveis e participativos na construção de sociedades mais justas e coesas. Por outro, justifica o potencial das parcerias educativas para o desenvolvimento pessoal, profissional e institucional dos parceiros, assim como para o desenvolvimento da competência intercultural de todos os participantes (parceiros, alunos e comunidade envolvente). O desenho investigativo delineado, de natureza predominantemente qualitativa, encontra-se na interseção de três métodos investigativos: estudo de caso, estudo etnográfico e investigação-ação. Num primeiro momento (ano letivo 2008/2009) efetuou-se um estudo exploratório que visou conhecer as práticas de educação intercultural e de trabalho em parceria de professores a lecionar em escolas do 1.º CEB do concelho de Aveiro. O objetivo deste estudo era reunir sugestões de atividades e de instituições a contactar para a constituição de um grupo de parceiros com vista ao desenvolvimento posterior de um projeto sobre educação intercultural. Os dados recolhidos por meio da aplicação de um inquérito por questionário a 228 professores do 1º CEB do distrito de Aveiro (dos quais 114 foram respondidos) permitiram concluir que as práticas educativas a este nível, e no contexto em causa, são ainda escassas ou pouco divulgadas. Passou-se, então, à constituição de um grupo de parceiros educativos que contou com um total de 13 elementos: a investigadora, enquanto parceira representante da Universidade de Aveiro, seis professoras do 1.º CEB, duas professoras de Música das Atividades de Enriquecimento Curricular, um representante de uma associação de imigrantes, um representante de uma associação cultural, um representante de uma CERCI e um representante da Câmara e Biblioteca Municipal. Ao longo do ano escolar 2010/2011, o grupo de parceiros desenvolveu colaborativamente um projeto de intervenção sobre educação intercultural para alunos do 1.º CEB. Este projeto proporcionou-lhes momentos de formação sobre educação intercultural e jogos colaborativos e permitiu-lhes partilhar as suas dúvidas e experiências relativas à temática em causa, propor estratégias e metodologias e disponibilizar recursos para a conceção e implementação das atividades. Os dados foram recolhidos em diferentes momentos: antes de se dar início ao projeto de intervenção, efetuou-se uma entrevista inicial a cada um dos parceiros; durante o decorrer do projeto realizou-se um focus group e registaram-se em formato áudio todas as sessões de trabalho entre os parceiros; após a conclusão do projeto de intervenção, teve lugar uma nova entrevista individual a cada um deles. Estes dados foram transcritos e analisados de acordo com a técnica de análise de conteúdo. Para além disso, todos os documentos elaborados pela investigadora durante a gestão da parceria, os portfólios das professoras participantes e os registos fotográficos das atividades implementadas constituíram-se como dados secundários. Os resultados mostraram que a participação neste projeto: i) conduziu a que ocorresse uma alteração das representações dos parceiros sobre interculturalidade e educação intercultural; ii) permitiu a todos os participantes (parceiros, alunos e comunidade) desenvolverem a sua competência intercultural; iii) proporcionou situações de trabalho colaborativo que contribuíram para o desenvolvimento pessoal, profissional e institucional de todos os parceiros; iv) motivou os parceiros a darem continuidade ao trabalho aqui desenvolvido. Este estudo permitiu, ainda, refletir sobre a importância da formação de formadores em educação intercultural e da necessidade de sensibilização para o desenvolvimento de trabalho colaborativo entre escola, comunidade e investigadores académicos.

Novos saberes e novas competências dos professores. A Supervisão pedagógica no contexto de uma escola pública

Trabalho de Projeto apresentado à ESEPF para obtenção do grau de Mestre em Ciências da Educação Área de especialização em Supervisão Pedagógica

Action-Emotion Style, Learning Approach and Coping Strategies, in Undergraduate University Students

Action-Emotion Style (AES) is an affective-motivational construct that describes the achievement motivation that is characteristic of students in their interaction with stressful situations. Using elements from the Type-A Behavior Pattern (TABP), characteristics of competitiveness and overwork occur in different combinations with emotions of impatience and hostility, leading to a classification containing five categories of action-emotion style (Type B, Impatient-hostile type, Medium type, Competitive-Overworking type and Type A). The objective of the present research is to establish how characteristics of action-emotion style relate to learning approach (deep and surface approaches) and to coping strategies (emotion-focused and problem-focused). The sample was composed of 225 students from the Psychology degree program. Pearson correlation analyses, ANOVAs and MANOVAs were used. Results showed that competitiveness-overwork characteristics have a significant positive association with the deep approach and with problem-focused strategies, while impatience-hostility is thus related to surface approach and emotion-focused strategies. The level of action-emotion style had a significant main effect. The results verified our hypotheses with reference to the relationships between action-emotion style, learning approaches and coping strategies.

Joint Action CHRODIS Work Package 5 - Good practices in the field of health promotion and chronic disease prevention across the life cycle: outcomes at a glance

Associated Partners in the Work Package 5: National Health Institute Doutor Ricardo Jorge (INSA), Portugal (Luciana Costa)

O Modelo de gestão participativa do Plano Nacional do Turismo (PNT-2003/2007): a atuação do CONETUR/RN

To implement policies and plans at the tourist sector involve disposition to the establishment of parceries among government and private initiative, space to the action of studious, researchers and professionals of several areas of knowledge and formation, able of to give new courses no only at the tourism, but to the economy how a every, seen which the tourism had a effect multiplicator, reaching 52 sectors of the economy. At this sense, the Brazil came pruning for a new phase of politic actuation at the touristy activity. Until the year 2002, the tourism politic in the Brazil no had detail, because herself treated of isolated actions and many without continuity. However, at to start 2003, several actions were developed in order to contribute for the national touristy planning. The principal was the creation of Ministério do Turismo, accompanied of the formulation and implementation of the Plano Nacional do Turismo (2003/2007). This work pretend to understand the implementation at the Rio Grande do Norte of the model of participative administration extolled by Plano Nacional do Turismo. The your centre detail the action of the Conselho Estadual de Turismo do Rio Grande do Norte (CONETUR), to promote the participation at the tourism public policies. The bibliographical research contemplated diverse sources in order to compile knowledge of credential authors in the quarrel of inherent subjects to the participation and to the tourism public policies, especially at the Brazil. A qualitative perspective the case study was adapted as research method and for attainment of the data interviews with the members of the Conselho had been carried through beyond consultation the referring documents the dynamics of functioning of the Conselho. The principal actuations of the CONETUR, the directives tourism public policies already made and directed to implementation, the type of participation at made decision, the principal difficulties of the implementation of the participative administration model of the Plano Nacional do Turismo and the degree of participation of the members of the Conselho at the reunions had been identified. The results had shown that exist some difficulties at the implementation of the participation at the Conselho Estadual de Turismo do Rio Grande do Norte, knowledge of the Conselheiros of CONETUR function, the presence of bodies which doesn t directly connected at the touristy activity; the absence of time of the Conselheiros to be presents at reunions; the discontinuity of the presidency of the Conselho; among others. So, the CONETUR show himself how a Conselho with participative characteristics, but with some adapted needs.

Design as a critical research

Historically the imaginary and the hegemonic thinking, in the Western globe north, has been marked by the epistemology and capitalists archetypes. Notwithstanding the design seem as a practice and discipline shielded on a simplistic discourse of functional / communicative efficiency, wandering through by multiple aestheticism apparently neutral in relation to the symbolic, but in fact they never are, because what really hapens is that the aesthetic appearance of the generated forms will always be a review of the powers ruling. We start from the understanding that the act of creating an aesthetic artifact, will also be a movement of inscription in a discursive platform (that precedes it), is in itself an narrative act and that fact represent a certain take place in relation to certain symbolic reality. On reflection shown if it sees design as a discipline and / or an instrument of action, whose operational relevance tends to question and simultaneously rehearsing a response, in which more than why interests answer to why. Apparently the design is a content mediator, but also, it is structure, is body, is idea. We think a design praxis as discipline and enrollment tool of critical thought and social transformation. For guiding research in this text, we propose the following question: Can the Design want for themselves an engagement with the symbolic in order to be an active part in the production of critical thinking in the place where it belongs? Methodologically our argument will be present in two differents moments: 1. a first, exploratory nature where we rescue the draw issues in the practice of design and 2. a second analytical nature concerning the subject issues (graphic and / or utility ) design and how it incorporates formal rites, political events and social practices of contemporary everyday life. We consider the praxis of design as a discipline and critical thinking enrollment tool as agents of social transformation. With this study we seek for contribute phenomenology design by studying the artifacts of configuration as well as the possible messages they convey and what impact they may have on the social network.

Relatório de estágio em educação pré-escolar

No âmbito do Mestrado em Educação Pré-Escolar surge este relatório de estágio, que apresenta uma reflexão acerca da prática pedagógica desenvolvida nos contextos de estágio de creche e educação pré-escolar, bem como do processo de construção e desenvolvimento profissional de competências da mestranda. Assim, foi através de processos inerentes à metodologia de investigaçãoação que, a mestranda desenvolveu a sua prática recorrendo a estratégias de observação, planificação, ação, avaliação e reflexão que lhe permitiram desenvolver atitudes questionadoras e críticas. Este desenvolvimento de atitudes foi permitido não só pelas estratégias utilizadas, mas também pela colaboração das orientadoras cooperantes, da supervisora institucional e do par pedagógico, que, conjuntamente, refletiam com a mestranda na, para e sobre a ação, articulando a prática e teoria na ação desenvolvida. Considerando a prática desenvolvida, a mestranda terá ainda oportunidade de refletir sobre as aprendizagens desenvolvidas, bem como o percurso realizado ao longo do ano letivo, nunca esquecendo que esta é uma prática que tem o intuito de a emancipar mediante o desenvolvimento dos seus saberes e das suas capacidades de acção educativa e a sua postura crítico-reflexiva face aos contextos profissionais em que se insere (Vieira, 2006).Deste modo, ao refletir sobre as suas ações e desenvolvimento, a mestranda explanará também as oportunidades de aprendizagem proporcionadas aos grupos de crianças, tendo em conta a imagem de criança como um ser com agência, competente e participativo (Oliveira-Formosinho & Araújo, 2013).

Metodologias de serviços públicos de ATER: estudo em instituições do Rio Grande do Norte

Due to the appreciation of family farming by the Brazilian Federal Government, the Technical Assistance and Rural Extension was induced to restructure and act in a more participative way, culminating in the National Policy of Technical Assistance and Rural Extension (PNATER), changing the profile of technology transfer and knowledge (diffusionism) for an action that uses participatory methodologies focused on exchange of knowledge between farmers and technicians. The process of discussion of the trends of ATER brought the New ATER , with the recognition of agroecology as the main guidance. This research aimed to analyze methods of public ATER developed by institutions of Rio Grande do Norte, under the guidance of New ATER. The research is qualitative. Secondary data were collected through documental research and literature. Primary data were collected through a set of interviews applied to representatives of public institutions ATER, namely EMATER-RN, Diaconia and AACC and representatives of organizations that receive public ATER. The research showed the difficulties of EMATER-RN in implementing of New ATER due to lack of infrastructure and low adherence of the new form of technical assistance and rural extension. It was shown also that the AACC and Diaconia act with ATER through projects with implementation deadlines set, often interrupting ATER while communities are still in need of assistance

Action and perception: Neural indices of learning in infants

Early human development offers a unique perspective in investigating the potential cognitive and social implications of action and perception. Specifically, during infancy, action production and action perception undergo foundational developments. One essential component to examine developments in action processing is the analysis of others’ actions as meaningful and goal-directed. Little research, however, has examined the underlying neural systems that may be associated with emerging action and perception abilities, and infants’ learning of goal-directed actions. The current study examines the mu rhythm—a brain oscillation found in the electroencephalogram (EEG)—that has been associated with action and perception. Specifically, the present work investigates whether the mu signal is related to 9-month-olds’ learning of a novel goal-directed means-end task. The findings of this study demonstrate a relation between variations in mu rhythm activity and infants’ ability to learn a novel goal-directed means-end action task (compared to a visual pattern learning task used as a comparison task). Additionally, we examined the relations between standardized assessments of early motor competence, infants’ ability to learn a novel goal-directed task, and mu rhythm activity. We found that: 1a) mu rhythm activity during observation of a grasp uniquely predicted infants’ learning on the cane training task, 1b) mu rhythm activity during observation and execution of a grasp did not uniquely predict infants’ learning on the visual pattern learning task (comparison learning task), 2) infants’ motor competence did not predict infants’ learning on the cane training task, 3) mu rhythm activity during observation and execution was not related to infants’ measure of motor competence, and 4) mu rhythm activity did not predict infants’ learning on the cane task above and beyond infants’ motor competence. The results from this study demonstrate that mu rhythm activity is a sensitive measure to detect individual differences in infants’ action and perception abilities, specifically their learning of a novel goal-directed action.

Analysing intention and action in mobile banking services

Technological advances at the level of mobile devices are transforming the world. Banking users are able to conduct banking services at any place, and at any time, with m-banking. The purpose of this research is to analyse intention and action in m-banking services. A research model was developed and PLS was used to test the causalities in the proposed model. Our proposal extends the existing models with an assessment of the actual usage of m-banking and of how behavioural intention translates into action. This study found that the main determinants of behavioural intention for m-banking are social influence and relative advantage. Furthermore, perceived risk, lack of information and usage barriers have a negative effect on m- banking behavioural intention. Perceived risks, e-banking use, and behaviour intention are found to be significant antecedents of m-banking use. Gender has a positive and significant influence on m-banking usage, but not on the construction of behavioural intention.

Antitumor effect and mechanism of action of polysaccharides extracted from Polygonum perfoliatum L whole plant in human lung carcinoma A549 cell line

Purpose: To optimize the extraction conditions of polysaccharides from Polygonum perfoliatum L. (PSDP) and to evaluate their anti-tumor activities on A549 cell line. Methods: Extraction of PSDP was optimized using Box-Behnken design (BBD). Three factors of response surface methodology (RSM) including extraction time, ratio of water to raw material and number of extractions were employed to optimize the yield of PSDP. The cytotoxic effect of PSDP on human lung carcinoma A549 cell line was evaluated in vivo, while its effects on expressions of caspase3, caspase-9, Bcl-2 and Bax were determined by western blot assay. Result: BBD was significant and applicable to PSDP extraction. Based on the contour plots, response surface plots and variance analysis, it predicted that the optimum conditions for PSDP extraction were: 1.58 h (extraction time); 30.18 mL/g (ratio of water to raw material); and 2.02 (number of extractions). PSDP had significant inhibitory effect on the growth of A549 cells in a concentration- and timedependent manner (p < 0.05). After treatment with PSDP, caspase-3, caspase-9 and Bax were significantly up-regulated (p < 0.05), whereas Bcl-2 was down-regulated, all concentration-dependently. Conclusion: RSM analysis is an appropriate method to optimize PSDP extraction. The results also indicate that PSDP has significant anti-tumor effect against A549 cells, most likely via inducing mitochondria-mediated apoptosis.

Anticonvulsant and sedative effect of Fufang Changniu pills and probable mechanism of action in mice

Purpose: To investigate the anticonvulsant and sedative effects of Fufang Changniu Pills (FCP) and its probable mechanism of action in mice. Methods: The water decoction of FCP was prepared and the main constituents were determined by high performance liquid chromatography (HPLC). The anticonvulsant activities of FCP were evaluated by maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in mice. Pentobarbital sodium-induced sleeping time and locomotor activity measurements were performed to evaluate the sedative effects of FCP in mice. Finally, PTZ-induced chronic seizures were established, and expressions of gamma-aminobutyric acid A receptor (GABA-A) and glutamic acid decarboxylase 65 (GAD65) in the brains of the mice were assayed by western blot in order to explore the probable mechanisms of action of the drug. Results: Gallic acid, liquiritin, cinnamyl alcohol, cinnamic acid and glycyrrhizic acid were detected in FCP decoction. FCP (50, 100 and 200 mg/kg) showed significant anticonvulsant and sedative effects on epileptic mice induced by MES (p < 0.05) and PTZ (p < 0.05). Moreover, pentobarbital sodium-induced sleeping time and locomotor activity tests showed that FCP possesses sedative effect (p < 0.05). Western blot data indicate that FCP significantly up-regulated GABA-A and GAD 65 in the brains of chronic epileptic rats (p < 0.05). Conclusion: FCP has significant anticonvulsant and sedative effects, and the mechanism of its action may be related to the up-regulation of GABA-A and GAD 65 in mice brain.

Antiviral activity and mechanism of action of arbidol against Hantaan virus infection

Purpose: To investigate the activity and mechanism of action of arbidol against Hantaan virus (HTNV) activity by modulating inflammation via TLR-4 pathway. Methods: HUVEC cells infected with HTNV 76-118 were treated with serially diluted arbidol solutions at -2h (2 h before viral infection, pre-treatment mode), 0 h (at the same time as viral infection, simultaneous treatment mode) or 2 h (2 h after viral infection, post-treatment mode). The transcript levels of TLR4 were detected by semi-quantitative reverse transcription-PCR (RT-PCR) at 6, 12, 18, and 24 h later. The levels of iNOS and TNF-α were examined using enzyme-linked immunosorbent assay (ELISA). Results: Pre-treatment with arbidol, rather than simultaneous treatment or post-treatment, effectively inhibited up-regulation of cellular TLR4 expression (up to 40 ± 6.1 % inhibition) and activity of supernatant iNOS induced by HTNV infection(up to 44.1 ± 9.4 % inhibition), as well as in a LPSstimulated inflammatory endothelial cell. Arbidol decreased the elevated TNF-α levels induced by LPS stimulation. Conclusion: These results are the first evidence that arbidol modulates viral PRRs signaling and its consequential inflammatory cytokine/chemokine response during hantavirus infection.