Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development

Epidermal growth factor receptor pathway substrate clone 15 (Eps15) is a protein implicated in endocytosis, endosomal protein sorting, and cytoskeletal organization. Its role is, however, still unclear, because of reasons including limitations of dominant-negative experiments and apparent redundancy with other endocytic proteins. We generated Drosophila eps15-null mutants and show that Eps15 is required for proper synaptic bouton development and normal levels of synaptic vesicle (SV) endocytosis. Consistent with a role in SV endocytosis, Eps15 moves from the center of synaptic boutons to the periphery in response to synaptic activity. The endocytic protein, Dap160/intersectin, is a major binding partner of Eps15, and eps15 mutants phenotypically resemble dap160 mutants. Analyses of eps15 dap160 double mutants suggest that Eps15 functions in concert with Dap160 during SV endocytosis. Based on these data, we hypothesize that Eps15 and Dap160 promote the efficiency of endocytosis from the plasma membrane by maintaining high concentrations of multiple endocytic proteins, including dynamin, at synapses.

Microbicide Vaginal Rings: Technological Challenges and Clinical Development

Vaginal rings (VRs) are flexible, torus-shaped, polymeric devices designed to sustain delivery of pharmaceutical drugs to the vagina for clinical benefit. Following first report in a 1970 patent application, several steroid-releasing VR products have since been marketed for use in hormone replacement therapy and contraception. Since 2002, there has been growing interest in the use of VR technology for delivery of drugs that can reduce the risk of sexual acquisition of human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Although no vaginally-administered product has yet been approved for HIV reduction/prevention, extensive research efforts are continuing and a number of VR devices offering sustained release of so-called ‘HIV microbicide’ compounds are currently being evaluated in late-stage clinical studies. This review article provides an overview of the published scientific literature within this important field of research, focusing primarily on articles published within peer-reviewed journal publications. Many important aspects of microbicide-releasing VR technology are discussed, with a particular emphasis on the technological, manufacturing and clinical challenges that have emerged in recent years.

Finance, social economics and community development

The last three decades have seen social enterprises in the United Kingdom pushed to the forefront of welfare delivery, workfare and area-based regeneration. For critics, this is repositioning the sector around a neoliberal politics that privileges marketization, state roll-back and disciplining community groups to become more self-reliant. Successive governments have developed bespoke products, fiscal instruments and intermediaries to enable and extend the social finance market. Such assemblages are critical to roll-out tactics, but they are also necessary and useful for more reformist understandings of economic alterity. The issue is not social finance itself but how it is used, which inevitably entangles social enterprises in a form of legitimation crises between the need to satisfy financial returns and at the same time keep community interests on board. This paper argues that social finance, how it is used, politically domesticated and achieves re-distributional outcomes is a necessary component of counter-hegemonic strategies. Such assemblages are as important to radical community development as they are to neoliberalism and the analysis concludes by highlighting the need to develop a better understanding of finance, the ethics of its use and tactical compromises in scaling it as an alternative to public and private markets.

Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development

Transdermal drug delivery offers a number of advantages for the patient, due not only its non-invasive and convenient nature, but also factors such as avoidance of first pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedle arrays can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below. Microneedles have been extensively investigated in recent decades for drug and vaccine delivery as well as minimally invasive patient monitoring/diagnosis. This review focuses on a range of critically important aspects of microneedle technology, namely their material composition, manufacturing techniques, methods of evaluation and commercial translation to the clinic for patient benefit and economic return. Microneedle research and development is finally now at the stage where commercialisation is a realistic possibility. However, progress is still required in the areas of scaled-up manufacture and regulatory approval.

English picturebook illustrations and language development in early years education

Este estudo investiga a influência da interação imagem-texto de três álbuns ilustrados de língua inglesa no desenvolvimento do repertório linguístico de crianças pré-leitoras. Numa metodologia de estudo de caso, adotando uma abordagem qualitativa e socio construtivista num contexto real de educação pré-escolar, três grupos de crianças portuguesas foram filmados ao longo de várias sessões de leitura repetida em voz alta e em inglês, e de sessões de recontos trabalhados em pequenos grupos. Após a transcrição das gravações, o corpus resultante foi analisado com base numa teoria fundamentada de compreensão literária e em escalas de leitura emergente. Os resultados mostraram que as crianças adotaram uma postura fortemente analítica face aos álbuns, direcionando as suas respostas para as ilustrações e usando-as como apoio na construção de significados. Os resultados mostraram também que cada interanimação visual e verbal ofereceu diversas oportunidades para o uso das línguas em presença, o português e o inglês, tendo o formato e a estrutura inerentes a cada álbum contribuído de forma muito relevante para as respostas das crianças. Contudo, os álbuns com uma dinâmica imagem-texto mais complexa proporcionaram um maior envolvimento das crianças, provocando mais discussão em torno das ilustrações e criando mais oportunidades para mediação do uso da segunda língua. Os resultados revelaram ainda a importância da interação durante as leituras repetidas, na compreensão e na análise narrativa, num processo de desenvolvimento da linguagem. Com base nestes resultados, apontam-se conclusões, com implicações para os contextos educativos, quer ao nível da língua materna, quer ao nível da segunda língua, nomeadamente em relação: à seleção de álbuns e à valorização das ilustrações e ainda à importância de leituras repetidas em voz alta e à discussão realizada pelas crianças.

Autistic Functioning and Language Development

This thesis is a retrospective qualitative study based on psychotherapy sessions with children presenting autistic features who use language in atypical ways. The aim was to understand, through the transferential relationship, what psychological context in terms of anxieties and defences prevents the child from using language efficiently. Hypotheses concerning children‘s use of language in the context of their emotional oscillation and evolution during the course of treatment were noted and checked against subsequent developments. They were also triangulated with the outcome of a grounded theory analysis. The grounded theory analysis led to the emergence of higher-level themes that were compared within and across cases and allowed factors surrounding the children‘s use of language to be conceptualized. The grounded theory method was used in parallel with the usual process of evaluation of the dynamics of each session and patient used by psychoanalysts a posteriori and which is part of the researcher‘s background. This procedure was enhanced by the use of Bion‘s Grid, here in a version adapted to the aims of the research. This approach is discussed in detail in the Methodology chapter. The psychoanalytic theoretical background that supported the research was mainly based on the tradition of Object-Relations Theory, particularly the evolution of Kleinian thinking represented by Bion‘s works, and as far as autism is concerned, by Frances Tustin and Donald Meltzer‘s formulations. Concerning the subject of language development, Meltzer‘s explorations on the necessary conditions for its development and the philosopher Wittgenstein‘s investigations on the social function of language were the main influences of this work. The evolution of the children‘s use of language in parallel with their emotional development in the context of their psychotherapies was analyzed and some hypotheses about the oscillations in their emotional and mental functioning were made. The oscillation in the children‘s emotional state, language use and thinking processes was also studied in terms of a general fluctuation between different mental states that was considered to be present in different degrees and quality in mental life and more strongly when there are limitations in communication skills and social interaction. A few excerpts from notes on adolescent and adult cases with autistic features were included in the Discussion Chapters to briefly illustrate this aspect.

Avaliação energética de um sistema fotovoltaico para bombagem

Dissertação de Mestrado, Energias Renováveis e Gestão de Energia, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Mothers, Fathers, Families and Child Development

Summary This chapter reviews the main tenets of attachment theory—one of the most popular and traditional approaches to conceptualising the relationship between caregivers and child development—in the light of recent research evidence. It highlights the limitations of attachment theory in achieving a holistic understanding of child development in current societal structures and considers the advantages of taking an ecological approach to the development of practice and policy. An ecological perspective that is child-centred contributes to a holistic understanding of how families, in all their variety of forms, influence child development and support child-centred practice and policy. The quality of the family environment is a key factor for the healthy adjustment, development and wellbeing of children.