Photoactivation of butyric acid from 6-aminobenzocoumarin cages

A new benzocoumarin bearing an amino group is proposed as a photocleavable protecting group for carboxylic acids. The novel heterocycle, 6-amino-4-chloromethyl-2-oxo-2H-naphtho[1,2-b]pyran was used in the preparation of ester conjugates of butyric acid, and of the corresponding mono- and di-methylated or ethylated derivatives. The photolability of the ester conjugates was studied by irradiation at selected wavelengths in methanol/HEPES buffer (80:20) solutions, and the release of butyric acid was followed with HPLC/UV and 1H NMR monitoring. Release of the carboxylic acid was faster for the monoalkylated derivatives (approximately within 20 min), at the longer wavelengths of irradiation (350 and 419 nm). The photophysics of the heterocyclic conjugates was also evaluated by both steady state and time-resolved methods.

Desenvolvimento de competências no âmbito da educação sexual: uma investigação-ação com professores e alunos

De acordo com a lei portuguesa, a Educação Sexual (ES) é obrigatória desde o 1.º Ciclo do Ensino Básico (CEB) até ao Ensino Secundário. No entanto, muitos projetos de ES em meio escolar não consideram as necessidades do seu público-alvo, o que limita a sua eficácia. Assim, esta investigação-ação procurou averiguar necessidades e conceções de professores e alunos sobre ES em meio escolar e, a partir destas, desenvolver as competências dos professores para abordar a ES de modo a promover a vivência de uma sexualidade saudável por parte dos alunos. A investigação desenrolou-se em três fases: diagnóstico, intervenção e avaliação. Para a fase de diagnóstico construímos um questionário, validado por meio de um estudo piloto, que aplicámos a professores de 1.º, 2.º e 3.º CEB de escolas do concelho do Porto. O questionário foi preenchido on-line e os dados obtidos foram tratados com o programa SPSS. A mesma metodologia foi utilizada para analisar as conceções de alunos de 2.º e 3.º CEB de uma escola do Porto. Na fase de intervenção começamos por um focus group com professores para clarificar as suas opiniões e registar reações à imposição legal da ES. Seguiram-se sessões de formação para professores e a implementação de um conjunto de ações estruturadas com os alunos. A avaliação efetuou-se com novo focus group com os professores intervenientes e através de um questionário aplicado aos alunos das turmas alvo de intervenção. Os resultados revelaram que, depois da intervenção, os professores se sentiam mais confiantes, com mais conhecimentos e mais estratégias para implementar projetos de ES. Os alunos ampliaram o seu conceito de sexualidade, demonstraram uma atitude mais favorável face ao papel da ES no seu desenvolvimento, aumentaram a sua confiança na escola como agente educativo nesta temática, aumentaram os seus conhecimentos sobre sexualidade e atenuaram-se algumas diferenças de género.

Conceções de alunos do 1.º ciclo do ensino básico sobre sexualidade e educação sexual

Nesta investigação procuramos averiguar as conceções e necessidades de alunos do 1.ºCEB sobre sexualidade e educação sexual (ES), como ponto de partida para delinear intervenções adequadas. Construímos e validámos um questionário, que aplicámos a alunos de 3.º e 4.º anos de escolaridade de um agrupamento de escolas do concelho do Porto. Responderam 96 alunos (45 raparigas e 51 rapazes), cuja média de idades foi de 8.95 anos. Destes, 52 frequentavam o 3.º ano e 44 o 4.º ano. Os dados obtidos foram tratados e analisados com o programa SPSS. Sobre o papel que a ES pode desempenhar no desenvolvimento das crianças, a maioria dos alunos considerou que: “conhecer o corpo é importante para crescer saudável”; “conhecermo-nos a nós e aos outros ajuda a sermos mais amigos”; “nem sempre os meus amigos sabem o que é melhor para mim”; “conhecer o corpo torna-nos mais responsáveis”. As raparigas concordaram mais com esta afirmação. Verificámos que os alunos atribuem importância ao papel da escola na ES, pois, na sua maioria, consideraram que: “a escola é um local onde posso fazer perguntas sobre o corpo e o nascimento dos bebés à vontade”, “os professores sabem responder às minhas perguntas sobre o corpo e o nascimento dos bebés” e “gostava de participar em mais atividades sobre o corpo e o nascimento de bebés na escola”. Foram os alunos de 3.º ano que mais concordaram com estas afirmações. A maioria dos alunos (81%) referiu que gostaria que fossem os professores a falar sobre o corpo e o nascimento dos bebés, em detrimento dos amigos, pai e psicólogo escolar. Os alunos do 3.º ano concordaram mais com os professores como responsáveis pela ES e as raparigas concordaram menos com o pai. Estes resultados devem ser considerados na elaboração de projetos de ES, para conseguirmos intervenções eficazes junto do público-alvo.

Digital manipulatives as scaffolds for preschoolers’ language development

The study reported here aims at contributing to a deeper understanding of the educational possibilities offered by digital manipulatives in preschool contexts. It presents a study carried with a digital manipulative to enhance the development of lexical knowledge and language awareness, which are relevant language abilities for formal literacy learning. The study took place in a Portuguese preschool, with a class of 20 five-year-olds in collaboration with the teacher. The digital manipulative supported the construction of multiple fictional worlds, motivating children's verbal interactions, and the playing of words and sound games, thus contextualizing the learning of an extensive collection of vocabulary and language awareness abilities. The degree of engagement and involvement that the manipulative provided in supporting children’s imaginative play as well as the imitation, in their own play, of the playful pedagogical interventions that the teacher had designed, shows the importance of well- designed materials that support a child-centered learning model. As such, it sustains a discussion on the potential of digital manipulatives to enhance fundamental language development in the preschool years. Further, the study highlights the importance of multidisciplinary teams in the creation of innovative pedagogical materials.

Effector memory CD4+ T cells are associated with cognitive performance in a senior population

Objective: Immunosenescence and cognitive decline are common markers of the aging process. Taking into consideration the heterogeneity observed in aging processes and the recently described link between lymphocytes and cognition, we herein explored the possibility of an association between alterations in lymphocytic populations and cognitive performance. Methods: In a cohort of cognitively healthy adults (n = 114), previously characterized by diverse neurocognitive/psychological performance patterns, detailed peripheral blood immunophenotyping of both the innate and adaptive immune systems was performed by flow cytometry. Results: Better cognitive performance was associated with lower numbers of effector memory CD4(+) T cells and higher numbers of naive CD8(+) T cells and B cells. Furthermore, effector memory CD4(+) T cells were found to be predictors of general and executive function and memory, even when factors known to influence cognitive performance in older individuals (e.g., age, sex, education, and mood) were taken into account. Conclusions: This is the first study in humans associating specific phenotypes of the immune system with distinct cognitive performance in healthy aging.

Exploring female mice interstrain differences relevant for models of depression

Depression is an extremely heterogeneous disorder. Diverse molecular mechanisms have been suggested to underlie its etiology. To understand the molecular mechanisms responsible for this complex disorder, researchers have been using animal models extensively, namely mice from various genetic backgrounds and harboring distinct genetic modifications. The use of numerous mouse models has contributed to enrich our knowledge on depression. However, accumulating data also revealed that the intrinsic characteristics of each mouse strain might influence the experimental outcomes, which may justify some conflicting evidence reported in the literature. To further understand the impact of the genetic background, we performed a multimodal comparative study encompassing the most relevant parameters commonly addressed in depression, in three of the most widely used mouse strains: Balb/c, C57BL/6, and CD-1. Moreover, female mice were selected for this study taken into account the higher prevalence of depression in women and the fewer animal studies using this gender. Our results show that Balb/c mice have a more pronounced anxious-like behavior than CD-1 and C57BL/6 mice, whereas C57BL/6 animals present the strongest depressive-like trait. Furthermore, C57BL/6 mice display the highest rate of proliferating cells and brain-derived neurotrophic factor (Bdnf) expression levels in the hippocampus, while hippocampal dentate granular neurons of Balb/c mice show smaller dendritic lengths and fewer ramifications. Of notice, the expression levels of inducible nitric oxide synthase (iNos) predict 39.5% of the depressive-like behavior index, which suggests a key role of hippocampal iNOS in depression. Overall, this study reveals important interstrain differences in several behavioral dimensions and molecular and cellular parameters that should be considered when preparing and analyzing experiments addressing depression using mouse models. It further contributes to the literature by revealing the predictive value of hippocampal iNos expression levels in depressive-like behavior, irrespectively of the mouse strain.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice

Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8?weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

Um modelo de programação inteira para a otimização da distribuição do serviço docente

Dissertação de mestrado em Engenharia Industrial

Social entrepreneurship: does institutional environment make a difference?

The purpose of this paper is to contribute to a better understanding of the link between social entrepreneurs and institutional environment in Portugal. A quantitative approach is used in the study, and primary data were collected through an online survey. A questionnaire was emailed to, both, Portuguese Non-Governmental organizations and projects available on the Portuguese social stock exchange. In the analysis of the data were used descriptive statistics, factorial analysis and t-student tests to validate (or not) the research hypotheses. The results show that a favorable institutional environment has a low importance in the decision to develop social initiatives. This conclusion supports the idea that many social entrepreneurs can emerge even in developing regions where the institutional environment is weak. Therefore, social entrepreneurship could be an instrument of regional development and contribute to attenuate the social and economic differences among Portuguese regions.

Intermetallic layer formation and influence in solder joints reliability

Dissertação de mestrado integrado em Materials Engineering

The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.

Polymicrobial interactions in infections: the case Pseudomonas aeruginosa and Candida albicans in ventilator-associated pneumonia

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clinica)

Peptaibolin analogues by incorporation of α,α-dialkylglycines: synthesis and study of their membrane permeating ability

Analogues of Peptaibolin, a peptaibol with antibiotic activity, incorporating α,α-dialkylglycines (Deg, Dpg, and Ac6c) at selected positions were synthesised by MW-SPPS and fully characterized. A control analogue incorporating L-alanine was also prepared. The native peptide and the analogues were studied by fluorescence spectroscopy for their membrane permeating activity. Small unilamellar vesicles (SUVs) of egg phosphatidylcholine/ cholesterol (70:30) containing an encapsulated fluorescence probe (6-carboxyfluorescein) were used as membrane models. The assays of carboxyfluorescein release from SUVs upon peptide addition showed that Peptaibolin-Dpg and Peptaibolin-Ac6c are the most active peptides. These results indicate that the structure of the α,α-dialkylglycines is crucial for the membrane permeating ability of these Peptaibolin analogues.

Pró-fármacos fotoativáveis do péptido AAPV: síntese e avaliação da libertação controlada por luz

Dissertação de mestrado em Bioquímica Aplicada (área de especialização em Biomedicina)

Libertação fotocontrolada de moléculas bioativas a partir de conjugados de cumarinas

Dissertação de mestrado em Química Medicinal