Ex vivo analysis of T-cell responses to Epstein-Barr virus-encoded oncogene latent membrane protein 1 reveals highly conserved epitope sequences in virus isolates from diverse geographic regions

Epstein-Barr virus (EBV)-encoded oncogene latent membrane protein (LMP) 1, which is consistently expressed in multiple EBV-associated malignancies, has been proposed as a potential target antigen for any future vaccine designed to control these malignancies. However, the high degree of genetic variation in the LMP1 sequence has been considered a major impediment for its use as a potential immunotherapeutic target for the treatment of EBV-associated malignancies. In the present study, we have employed a highly efficient strategy, based on ex vivo functional assays, to conduct an extensive sequence-wide analysis of LMP1-specific T-cell responses in a large panel of healthy virus carriers of diverse ethnic origin and nasopharyngeal carcinoma patients. By comparing the frequencies of T cells specific for overlapping peptides spanning LMP1, we mapped a number of novel HLA class I- and class II-restricted LMP1 T-cell epitopes, including an epitope with dual HLA class I restriction. More importantly, extensive sequence analysis of LMP1 revealed that the majority of the T-cell epitopes were highly conserved in EBV isolates from Caucasian, Papua New Guinean, African, and Southeast Asian populations, while unique geographically constrained genetic variation was observed within one HLA A2 supertype-restricted epitope. These findings indicate that conserved LMP1 epitopes should be considered in designing epitope-based immunotherapeutic strategies against EBV-associated malignancies in different ethnic populations.

Localization of the Epstein-Barr virus protein LMP 1 to exosomes

The Epstein-Barr virus latent membrane protein (LMP 1) functions as a constitutively active signalling molecule and associates in lipid rafts clustered with other signalling molecules. Using immunofluorescent confocal microscopy, LMP 1 was shown to have an heterogeneous distribution among individual cells which was not related to the cell cycle stage. LMP 1 was shown to localize to intracellular compartments in cells other than the plasma membrane, Co-labelling of cells with both an LIMP 1 antibody and an antibody to the Golgi protein GS15 revealed that the intracellular LMP 1 partly co-localized with the Golgi apparatus. Further confirmation of intracellular LMP 1 localization was obtained by immunoelectron microscopy with rabbit polyclonal LIMP 1 antibodies and cryosectioning. As well as being present in intracellular foci, LMP 1 co-localized in part with MHC-II and was present on exosomes derived from a lymphoblastoid cell line. Preparations of LMP 1 containing exosomes were shown to inhibit the proliferation of peripheral blood mononuclear cells, suggesting that LIMP 1 could be involved in immune regulation. This may be of particular relevance in EBV-associated tumours such as nasopharyngeal carcinoma and Hodgkin's disease, as LMP 1-containing exosomes may be taken up by infiltrating T-lymphocytes, where LMP 1 could exert an anti-proliferative effect, allowing the tumour cells to evade the immune system.

Detecção do vírus Epstein-Barr em tonsilites recorrentes

As tonsilites recorrentes têm sido objeto de muitos estudos. Eventos considerados na predisposição e causa incluem a utilização errônea de antibióticos em crises agudas, alterações da microflora, mudanças estruturais nas criptas epiteliais tonsilares e infecções virais. A infecção pelo vírus Epstein-Barr (EBV) ocorre freqüentemente na infância persistindo em linfócitos de tonsilas, podendo causar tonsilites recorrentes. Pouco se conhece sobre a persistência e reativação do EBV em pacientes imunocompetentes. Alguns métodos como a hibridização in situ, a reação em cadeia da polimerase (PCR) e a imuno-histoquímica têm sido utilizados no estudo da patogenia do vírus. OBJETIVO: Para caracterizar a associação do vírus Epstein-Barr com tonsilites recorrentes examinamos a presença do EBV pela PCR e por imuno-histoquímica usando como alvo a proteína viral LMP-1. FORMA DE ESTUDO: Estudo transversal com análise de prevalência amostral. MATERIAL E MÉTODOS: Foram selecionados 24 blocos parafinados de tonsilas, provenientes do Serviço de Anatomia Patológica, removidas de crianças de 2 a 12 anos com diagnóstico de tonsilite recorrente. Resultados: O genoma do EBV foi detectado em 13 (54,1%) e a LMP-1 em 9 (37,5%) dos casos. CONCLUSÃO: As tonsilas das crianças podem ser colonizadas pelo EBV e este pode estar associado à patogenia das tonsilites recorrentes.

De Jean de Léry a Claude Lévi-Strauss: por uma arqueologia de Tristes trópicos

A comparação entre a História de Duas Viagens ao Brasil, de Jean de Léry, e Tristes trópicos, de Claude Lévi-Strauss, mostra entre os autores e suas narrativas acerca do Brasil numerosos paralelos. No modo de se relacionar com o Brasil, na descrição dos índios, na própria forma de construir seu texto, Léry aparece como um predecessor de Lévi-Strauss. Mais do que retomar a narrativa de Léry, Lévi-Strauss estabelece com ela um diálogo, no qual se pode também perceber as divergências de ponto de vista entre os autores, envoltas nas lembranças nostálgicas de ambos de suas estadas no Novo Mundo.

Soro-epidemiologia do virus de Epstein-Barr (VEB)

É feita revisão dos estudos soro-epidemiológicos do vírus de Epstein-Barr (vírus EB), mostrando a ubicuidade deste vírus, bem como sua relação com doenças malígnas e não malígnas do homem. O desenvolvimento de novas técnicas laboratoriais e o acúmulo, nos últimos 10 anos, de grande número de estudos soro-epidemiológicos, levaram à conclusão de que, além da associação etiológica com a mononucleose infecciosa, torna-se cada vez mais evidente a ligação do vírus EB com o linfoma de Burkitt e com o carcinoma do nasofaringe. Estas observações, além de sua extraordinária importância intrínseca, tem sido de grande utilidade para a melhor compreensão dos possíveis mecanismos e efeitos das infecções virais no homem.

Mutations du roman français depuis les années quatre-vingt : le parcours de Jean Echenoz

Artigo também disponível no PROA-UA: plataforma de revistas em open access da universidade de aveiro com o URI http://revistas.ua.pt/index.php/Carnets/article/view/808/742.

Traduction et invasion culturelle : Jean Echenoz en portugais et José Saramago en français

La traduction est un moyen d'invasion culturelle dont le pouvoir est souvent sous-estimé. Elle permet, pourtant, l'introduction, dans une culture nationale, d'éléments appartenant à une culture étrangère. Ce pouvoir de la traduction est toutefois potentiel. Pour qu'il y ait effectivement invasion culturelle par le biais de la traduction, il faut la contribution des entités du pays envahisseur (les organismes qui font la promotion de la littérature à l’étranger) et de celles du pays envahi (maisons d'édition, traducteurs et lecteurs). Les traductions de Je m'en vais de Jean Echenoz et de História do cerco de Lisboa de José Saramago, en portugais et en français respectivement, fonctionneront comme le point de départ pour une réflexion sur le rôle de la traduction dans le rapport entre le Portugal et la France à l'époque contemporaine.

14, de Jean Echenoz, un récit de guerre à l’épreuve du pathos

14 is a recently published novel by a French contemporary writer, Jean Echenoz. Having the First World War as its core subject, the text covers the main traditional themes of war novels. Its interest, however, does not lie in what it says about the war, but rather in how the war is told. In fact, 14 points out the main horrors of the war, without engaging in pathos. In order to do so, Echenoz resorts to two groups of techniques, whose main purpose is to lighten the dramatic effect of the war scenes depicted. Surprisingly, the result is a text which recounts the crude horrors of war.

O auteur a ver-se a si mesmo ao espelho: as alegorias do enunciador em Jean Cocteau

ABSTRACT - Jean Cocteau, French cinema auteur avant la lettre, has consecrated his uniqueness to the defense of the “poet” and the promotion of its artistic ideals, before the French Nouvelle Vague inspired the break away from the filmic tradition and ahead of the eulogistic tendency to consider the director the undisputed creative entity of the filmmaking process. The Orphic trilogy expresses Cocteau’s cinematic philosophy in action. In other words, it reveals the way by which the creative entity affirms itself as the major filmic enunciator, through an allegorical relationship with vision. Therefore, Cocteau’s self-reflexive metacinema conjoins, in a fertile attunement, the starting point and the ultimate goal, the creation and the reception. Without being exactly a cinema about the cinema, this artistic practice is, nonetheless, very much with the cinema, feeding as it does on its essence. The films Le Sang d’un poète (“The Blood of a Poet”, 1932), Orphée (“Orpheus”, 1950) and Le Testament d’Orphée, ou ne me demandez pas pourquoi! (“Testament of Orpheus”, 1960) recreate, in allegorical form, the double creative function: the look of the directing entity reflects the gaze of the observer, just as this one always restores the presence of the creator. In short: Cocteau’s films, more than anyone else’s, deliberately reflect its auteur as enunciator.

O casaco dourado de Jean Paul Gaultier (n.1952-): conservação de alta costura (MUDE - Colecção Francisco Capelo)

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Conservação e Restauro