3 research outputs found
Role of Lipid Rafts and GM1 in the Segregation and Processing of Prion Protein
Get PDFThe prion protein (PrPC) is highly expressed within the nervous system. Similar to other GPI-anchored proteins, PrPC is found in lipid rafts, membrane domains enriched in cholesterol and sphingolipids. PrPC raft association, together with raft lipid composition, appears essential for the conversion of PrPC into the scrapie isoform PrPSc, and the development of prion disease. Controversial findings were reported on the nature of PrPC-containing rafts, as well as on the distribution of PrPC between rafts and non-raft membranes. We investigated PrPC/ganglioside relationships and their influence on PrPC localization in a neuronal cellular model, cerebellar granule cells. Our findings argue that in these cells at least two PrPC conformations coexist: in lipid rafts PrPC is present in the native folding (α-helical), stabilized by chemico-physical condition, while it is mainly present in other membrane compartments in a PrPSc-like conformation. We verified, by means of antibody reactivity and circular dichroism spectroscopy, that changes in lipid raft-ganglioside content alters PrPC conformation and interaction with lipid bilayers, without modifying PrPC distribution or cleavage. Our data provide new insights into the cellular mechanism of prion conversion and suggest that GM1-prion protein interaction at the cell surface could play a significant role in the mechanism predisposing to pathology
Contemporary pedagogical dilemmas: a study of vocational guidance in schools
No full textO objetivo desta pesquisa é abordar o tema da orientação vocacional em escolas, precisamente, em projetos destinados a alunos do ensino médio. A partir da experiência da autora em um projeto de orientação vocacional em uma escola particular da Grande São Paulo, observou-se que a escolha de uma profissão migrou do ambiente familiar para o escolar. Analisando essa mudança, o trabalho procura evidenciar significativas alterações sócio-econômico-culturais que concorreram para transformar a Orientação Vocacional num projeto (psico) pedagógico. A metodologia utilizada para investigar estas alterações consistiu no levantamento de ideias e ideais que ao circularem discursivamente tem definido ações no campo da educação. Assumiu-se como definição de discurso a proposta por Jacques Lacan, segundo a qual o discurso é condição para que haja laço social. O estudo constata que o discurso capitalista, aliado ao da ciência em sua versão tecnocientificista , tem, por um lado, legitimado a transferência de responsabilidades que outrora eram das famílias para as escolas e, por outro, transformado a educação escolar em mais uma mercadoria disponível ao consumo. Após a descrição pormenorizada do projeto que inspirou esta pesquisa, elencam-se alguns elementos que, diante dessa temática, podem nortear o trabalho do psicanalista em escolas. A conclusão deste estudo propõe que às escolas caberia a função de delimitar a abrangência com a qual o projeto de Orientação Vocacional tem sido proposto. A partir da teoria psicanalítica, não se propõe a definição de outros projetos como sendo melhores ou mais completos, em vez disso, reitera-se que a escolha de uma profissão é mais uma dentre as muitas escolhas com as quais o adolescente se verá confrontado, e, como toda escolha, será determinada pela posição fantasmática de cada um. Então, na escola, o aluno até poderá ser instruído sobre cursos e carreiras, mas não se aconselha a adoção de projetos que se proponham a instituir um outro que se prontifique a responder sobre o desejo dos adolescentes.The objective of this study is to address vocational guidance in schools, more precisely, projects designed for high-school students. From the experience of the author in a vocational guidance project in a private school in the metropolitan area of São Paulo, Brazil, we observed that the choice of a career has migrated from the family environment to the school environment. By analyzing this change, this study highlights significant social, economic and cultural alterations that have contributed to transform Vocational Guidance in a (psycho) pedagogical project. The methodology used to investigate these alterations consisted of gathering ideas and ideals which by circulating discursively have defined actions in the fields of education. We assumed as the definition of discourse the one proposed by Jacques Lacan, according to which discourse is the condition for the existence of social bond. In this study we verify that the capitalist discourse, with the scientific discourse in its techno-scientistic version , has, on the one hand, legitimated transferring to the schools responsibilities that formerly belonged the family and, on the other hand, has transformed education in another commodity available for consumption. After thorough description of the project which inspired this study, we list some elements that, in the face of this theme, can guide the work of psychoanalysts in schools. In the conclusion of this study we propose that the schools limit the scope with which the Vocational Guidance project has been proposed. From the psychoanalytic theory, we do not propose a definition of other projects as being better or more complete on the contrary, it is emphasized that career choice is one choice amongst many which the adolescent will face and, as with all choices, it will be determined by the phantasmic position of the person. Therefore, in school, the student can even be instructed on courses and careers, but the adoption of projects to institute an other to give answers about the desires of the adolescents is not advised
Biomolecular studies in Alzheimer’s Disease models: investigations in vitro and in vivo
No full textThe Alzheimer’s disease (AD), the most prevalent form of age-related dementia, is a multifactorial and heterogeneous neurodegenerative disease. The molecular mechanisms underlying the pathogenesis of AD are yet largely unknown. However, the etiopathogenesis of AD likely resides in the interaction between genetic and environmental risk factors. Among the different factors that contribute to the pathogenesis of AD, amyloid-beta peptides and the genetic risk factor apoE4 are prominent on the basis of genetic evidence and experimental data. ApoE4 transgenic mice have deficits in spatial learning and memory associated with inflammation and brain atrophy. Evidences suggest that apoE4 is implicated in amyloid-beta accumulation, imbalance of cellular antioxidant system and in apoptotic phenomena. The mechanisms by which apoE4 interacts with other AD risk factors leading to an increased susceptibility to the dementia are still unknown. The aim of this research was to provide new insights into molecular mechanisms of AD neurodegeneration, investigating the effect of amyloid-beta peptides and apoE4 genotype on the modulation of genes and proteins differently involved in cellular processes related to aging and oxidative balance such as PIN1, SIRT1, PSEN1, BDNF, TRX1 and GRX1. In particular, we used human neuroblastoma cells exposed to amyloid-beta or apoE3 and apoE4 proteins at different time-points, and selected brain regions of human apoE3 and apoE4 targeted replacement mice, as in vitro and in vivo models, respectively. All genes and proteins studied in the present investigation are modulated by amyloid-beta and apoE4 in different ways, suggesting their involvement in the neurodegenerative mechanisms underlying the AD. Finally, these proteins might represent novel potential diagnostic and therapeutic targets in AD
