30,145 research outputs found
Exploiting Drosophila as a model system for studying REEP1-linked HSP in vivo
No full textHereditary Spastic Paraplegia (HSP) is a genetic group of neurodegenerative disorders characterized by progressive degeneration of corticospinal tracts. Mutations in the SPG31 gene, encoding REEP1, are the third most common cause of autosomal dominant form of HSP. Recent studies have reported that REEP1, an integral ER membrane protein, interacts with the microtubule cytoskeleton to coordinate ER shaping. However it precise molecular function is still unknown.
To better understand the function of REEP1, we generated a model (Drosophila melanogaster) for the in vivo analysis of the fly REEP1 homolog (D-REEP1). Drosophila and human REEP1 proteins display remarkable homology and conservation of domain organization. We analyzed D-REEP1 loss of function and gain of function transgenic lines as well as animals expressing pathological forms of the protein. Our in vivo data in Drosophila have shown a strong involvement of D-REEP1 in the regulation of lipid droplets (LDs) number and size in neuronal and non neuronal tissues. Loss of D-REEP1 results in larvae leaner and smaller than their wild type counterparts while endoplasmic reticulum membranes are elongated when compared to controls. These ER defects are associated with a decrease in lipid droplets number and low triglycerides content. On the contrary over expression of wild type D-REEP1 produces a reduction in the size of lipid droplets. The lack of animal models available for REEP1 studies and experimental data concerning the functional alteration caused by pathological mutations of REEP1 prompted to generate transgenic lines carrying D-REEP1 pathological mutations and to analyse the consequence of their expression in vivo. Two missense mutations (P19R, D56N) affecting the trans-membrane domains of REEP1 and a novel mutation (A132V) located in the C-terminal part of the protein have been assessed.The mutations in the trans membranes domains relocate REEP1 from the ER to the membrane of lipid droplets when expressed in mammalian cells. In vivo expression of Drosophila P19R caused oversized LDs in the brain and axons and increased levels of triacylgycerides.
LDs are believed to originate from the endoplasmic reticulum, although the exact molecular mechanisms of their biogenesis is still not known. Based on the findings described above and the knowledge about REEP family, we hypothesize that REEP1 probably play an important role in membrane remodelling and possibly affects the lipid droplets metabolism. While, pathological forms of REEP1 could perturb the biogenesis and/or turnover of lipid droplets and eventually produce an imbalance in neuronal lipid metabolis
Maria Bersani
No full textLa voce illustra la biografia e l'apporto letterario dato da Maria Bersani alla letteratura per l'infanziaThe headword explains the biography and the contribution of the author Maria Bersani to the children's literatur
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
A Drosophila loss of function model to study the effects of Atypical Antipsychotic drugs
No full textModulators of lysosomal functions rescue autophagy and lysosomal defects in SPG15 hereditary spastic paraplegia models
No full textO curso de licenciatura em educação física da Universidade Federal de Santa Catarina: suas concepções de ensino e de educação física
No full textDissertação (mestrado) - Universidade Federal de Santa Maria. Centro de Educação Fisica e Desporto
Identification of promising molecules for Hereditary Spastic Paraplegia treatment using predictive Drosophila models
No full textAtypical Antipsychotics induce lysosomal regeneration rescuing dysbindin-dependent astrocytes death
No full textExploiting pharmacological predictive fruit fly models for the identification of promising molecules in future Hereditary Spastic Paraplegia therapy
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