Hiato: o espaço entre eu e você

Esse memorial aborda à construção do espetáculo Hiato, de Karla Muniz com direção de Daniella Fiaux desde a fase inicial do projeto até a finalização dele com as apresentações dias 10, 11 e 12 de dezembro de 2019. No início de 2019 comecei a elaborar o projeto que se desdobraria no meu espetáculo de formatura (PET -Projeto Experimental de Teatro). O primeiro passo foi estruturarmos a cada aula parte a parte do projeto a ser realizado. Para isso necessitava a escolha de um tema ou dramaturgia e, portanto, decidi utilizar meu espetáculo de formatura como a parte prática da minha pesquisa de iniciação científica “Autobiografia na cena contemporânea” a qual desenvolvo desde 2017. Nessa pesquisa investiguei espetáculos autobiográficos contemporâneos a partir de três eixos de análise: processo de criação, dramaturgia e espectador. Após a decisão de tornar minha PET a parte prática da pesquisa, entendi que seria interessante escolher um tema central que me atravessa de verdade ainda que eu não estivesse em cena. Refletindo sobre a minha existência percebi como a palavra “ausência” permeia a minha vida de diversas maneiras. Imbuída desses atravessamentos, optei pelo tema Ausência, pois a amplitude dessa temática me permitiria explorá-la a partir dos eixos citados, bem como caminhar em direção as respostas às perguntas da minha pesquisa de iniciação científica. Durante a elaboração do projeto fui orientada a aprofundar à temática principal, o que originou cinco subtemas: Abandono parental; Término de relacionamento; Alzheimer; Depressão e Morte. Um espetáculo autobiográfico é construído a partir das vivências dos envolvidos, podendo ser dos atores, diretor, dramaturgo ou qualquer outra pessoa envolvida na equipe

Development of new anticancer agents based on [alpha]-mannosidase inhibition

Enzymes that are involved in the synthesis and processing of oligosaccharides, such as glycosidases, are important catalysts for the specific assembly of oligosaccharide structures on proteins. Design and preparation of selective inhibitors of these enzymes are of high interest as these molecules can be used to modulate cellular functions. Moreover, they may provide potential drugs in new therapeutic strategies. In particular, swainsonine (Swa), a natural inhibitor of Golgi α-mannosidase II, reduces certain tumors and hematological dysfunctions. Nevertheless, some side effects resulted in limitations for the development of this compound in medicinal treatments. Recently, our laboratory has developed a new combinatorial methodology for the disclosure of glycosidase inhibitors based on the dihydroxypyrrolidine scaffold found in Swa. This method allowed the preparation of a new family of selective and competitive a-mannosidase inhibitors with inhibitory activities (Ki values) ranging from 3 µM to 135 nM for the best congeners toward α-mannosidase from jack bean, a reliable model enzyme for mammalian Golgi α-mannosidase II. The aim of the present work was to design and synthesise optimized inhibitors of α-mannosidases II based on a 2-aminomethyl-3,4-dihydroxypyrrolidine scaffold and to assess their potential as new anti cancer leads. In a first time, a structural study was carried out through the analysis of x-ray structures of the best inhibitors previously developed in our laboratory complexed to Golgi α-mannosidase II from Drosophila melanogaster (dGMII), which presents a high sequence identity with the human enzyme. The binding mode of these inhibitors could be thus established. This study combined with docking experiments allowed us to design inhibitors of α-mannosidase II, with improved efficacy. The best congener (3R,4R,5R)-3,4-dihydroxy-5-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)-1-methylpyrrolidin-2-one displayed an enhanced inhibitory potency against dGMII (IC50 = 0.5 µM vs 80 µM for the first generation inhibitor). Introduction of a polar substituent on the C(5) position of the pyrrolidine ring accounted for this improved activity as revealed by the x-ray structure of this new derivative complexed to dGMII which displayed additional interactions with active site residues. In a second time, these new α-mannosidase inhibitors have been evaluated as anti cancer agents and their effects were determined on human cancer cells from glioblastoma and melanoma, two tumors associated with a high proliferative and invasive potential, multiple resistance toward conventional chemotherapeutic agents, and poor prognosis. As these compounds were not able to inhibit cellular growth, probably due to a poor cellular uptake, derivatization of our inhibitors into more lipophilic esters, ethers and amides derivatives was envisaged. In particular, introduction of a 4-bromobenzoate moiety resulted in an improvement of cellular uptake, leading to a complete inhibition of cellular growth at 300 µM with inhibitors (2R)-2-({[(2R,3R,4S)-3,4-dihydroxypyrrolidin-2-yl]methyl}amino)-2-phenylethyl 4-bromobenzoate and (2R)-2-({[(2R,3R,4R)-3,4-dihydroxy-1-methyl-5-oxopyrrolidin-2-yl]methyl}amino)-2-phenylethyl 4-bromobenzoate. Under the same conditions, Swa didn't provide any significant growth inhibition. Moreover, exposure of human fibroblasts, as model of healthy cells, to our lead derivatives revealed some selectivity toward tumoral cells. It was hypothesized that cellular esterases were able to hydrolyse the ester moiety and thus release the more hydrophilic parent inhibitors within the tumoral cells. Finally, in order to get more insights into the mode of action of our derivatives, their inhibitory activity on α-mannosidases from human glioblastoma extracts was determined and compared to the activity of Swa. The first generation inhibitor presented a moderate inhibitory potency on α-mannosidases whereas the optimized derivative displayed potent inhibitory activity on human α-mannosidases (IC50 = 50 µM decreased to 0.5 µM). Nevertheless, Swa presented higher potency than our new lead (IC50 = 10-50 nM). It was also determined by gel filtration that the cellular α-mannosidases targeted by our pyrrolidine based inhibitors displayed apparent molecular weight of about 120 kD

Um estudo sobre a realidade da inclusão de pessoas com deficiência na educação superior no Paraná.

This study integrates the discussions shown in the Master's thesis in Education, in which it was analyzed the disabled students inclusion in the Higher Education, emphasizing the access, staying and learning  issues, seeking to understand the inclusion process of these students in Higher Education Institutions in Umuarama City, in Parana Northwest region. For study, enrolled students, concluding and dropout were interviewed, from 2008 to 2014. Analytical, descriptive, qualitative/quantitative research presuppositions were used to be considered appropriated in understanding the participants' life in their university routine, trying to identify, by analysis of data from interviews, the guidelines of this study. The bibliographic basis is of the authors who talk about disabled people education and the educational inclusion in Higher Education. The study shows as study meaning units the difficulties and challenges faced by disable people in Higher Education specially referring to the teaching and learning process, prejudiced situations and accessibility aspects, as well as, the importance of the family participation in academic life, like fundamental elements to the stay or dropout of these students in the Higher Education Institutions (HEI).Este estudo integra as discussões apresentadas na dissertação de Mestrado em Educação, as quais analisaram a inclusão dos estudantes com deficiência na Educação Superior, com ênfase na análise de questões de acesso, permanência e aprendizagem, buscando compreender o processo de inclusão dos mesmos em instituições de Educação Superior do município de Umuarama, na região Noroeste do Paraná. Para o estudo, foram entrevistados estudantes matriculados, concluintes e desistentes, no período de 2008 a 2014. Utilizaram-se os pressupostos da pesquisa qualitativa/quantitativa, descritiva, analítica por ser considerada adequada na compreensão da vida dos participantes em seu cotidiano universitário, buscando-se identificar, por meio da análise dos dados obtidos nas entrevistas, os eixos norteadores deste estudo. A base bibliográfica é de autores que discutem a educação das pessoas com deficiência e a inclusão educacional na Educação Superior. O estudo revela como unidades de significados 1- dificuldades e desafios encontrados pelas pessoas com deficiência na Educação Superior especialmente no que se refere ao processo de ensino e aprendizagem; 2- as situações de preconceito e 3- aspectos da acessibilidade e a importância da participação da família na vida acadêmica, como elementos fundamentais para permanência ou abandono desses estudantes nas IES. A análise dos dados revela que a permanência desses estudantes na Educação Superior ocorre em meio a dificuldades, como falta de materiais adequados e preconceito. Ações de responsabilidade das IES ficaram a cargo das famílias, que assumem papel relevante para que eles superem dificuldades impostas pela própria deficiência. A compreensão e estímulo de professores e de amigos são condições que auxiliam na permanência e conclusão do curso

NormAntibio : centre régional de conseil en antibiothérapie « Made in Normandie »

International audienc

Functionalized pyrrolidines as alpha-mannosidase inhibitors and growth inhibitors of human glioblastoma and melanoma cells

New substituted pyrrolidine-3,4-diol derivatives were prepared from D-(-)- and L-(+)-phenyl glycinol. The influence of the configuration and the substitution of the lateral side chain of these derivatives on the inhibition of 25 commercial glycosidases were determined. (2R,3R,4S)-2-({[(1R)-2-Hydroxy-1-phenylethyl]amino}methyl)pyrrolidine-3,4-diol ((+)-7a) was a potent and selective inhibitor of jack bean alpha-mannosidase (Ki = 135 nM). However, when evaluated on human tumor cells, 7a, and the reference compound swainsonine, did not efficiently inhibit the growth of glioblastoma cells. Further derivatization of the hydroxyl group with lipophilic groups to increase bioavailability improved their growth inhibitory properties for human glioblastoma and melanoma cells. In particular the 4-bromobenzoyl derivative 26 demonstrated high efficacy for human tumor cells whereas primary human fibroblasts were less sensitive to 26. Therefore functionalized pyrrolidines have the potential to inhibit the growth of tumor cells and display selectivity for tumor cells compared to normal cells

Modèle in vitro d'infection urinaire sur cathéter à Pseudomonas aeruginosa traitée par ciprofloxacine : rôle prépondérant de la persistance sur la résistance

International audienc

O lugar do psicanalista na escola

In this work we analyze the tension inherent to the educative action in its formal aspect, practiced at school, and in its informal aspect, practiced by the family, raising some questions ot impossibility that give rise to impotence and as a consequence the miscarriage of education. The miscarriage of school, considered one of the pathologies of our time, is being associated to the manipulation of the promises of pleasure associated to the political actions of Education, supported by an ethic of globalization and by the loss of ideals. These are questions that are brought to the psychoanalyst in intersection of the psychoanalysis and education.Este trabalho busca pensar a tensão inerente à ação educativa em seu aspecto formal, praticada pela escola, e no informal, ministrada pela família, levantando alguns pontos de impossibilidade que vêm se transformando em impotência e conseqüente fracasso da educação. O fracasso escolar, considerado uma das patologias de nosso tempo, vem sendo associado à manipulação das promessas de gozo inerentes às ações políticas da educação amparadas por uma ética da globalização e da queda de ideais. Estas questões interrogam o psicanalista na interseção psicanálise e educação

Patterns of recurrences in sinonasal cancers undergoing an endoscopic surgery-based treatment: Results of the MUSES* on 940 patients: *MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers

The improvements in survival with expansion of the survivors' population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence