Identificação de compostos que modulam a patogénese da doença de Machado-Joseph em C.elegans: autofagia como alvo terapêutico: identification of small compounds that modulate pathogenesis of Machado-Joseph disease in a C.elegans model: targeting autophagy

A doença de Machado-Joseph (DMJ) ou ataxia espinocerebelosa do tipo 3 (SCA3), conhecida por ser a mais comum das ataxias hereditárias dominantes em todo o mundo, é uma doença neurodegenerativa autossómica dominante que leva a uma grande incapacidade motora, embora sem alterar o intelecto, culminando com a morte do doente. Atualmente não existe nenhum tratamento eficaz para esta doença. A DMJ é resultado de uma alteração genética causada pela expansão de uma sequência poliglutamínica (poliQ), na região C-terminal do gene que codifica a proteína ataxina-3 (ATXN3). Os mecanismos celulares das doenças de poliglutaminas que provocam toxicidade, bem como a função da ATXN3, não são ainda totalmente conhecidos. Neste trabalho, usamos, pela sua simplicidade e potencial genético, um pequeno animal invertebrado, o nemátode C. elegans, com o objetivo de identificar fármacos eficazes para o combate contra a patogénese da DMJ, analisando simultaneamente o seu efeito na agregação da ATXN3 mutante nas células neuronais in vivo e o seu impacto no comportamento motor dos animais. Este pequeno invertebrado proporciona grandes vantagens no estudo dos efeitos tóxicos de proteínas poliQ nos neurónios, uma vez que a transparência das suas 959 células (das quais 302 são neurónios) facilita a deteção de proteínas fluorescentes in vivo. Para além disso, esta espécie tem um ciclo de vida curto, é económica e de fácil manutenção. Neste trabalho testámos no nosso modelo transgénico da DMJ com 130Qs em C.elegans dois compostos potencialmente moduladores da agregação da ATXN3 mutante e da resultante disfunção neurológica, atuando pela via da autofagia. De modo a validar a possível importância terapêutica da ativação da autofagia os compostos candidatos escolhidos foram o Litío e o análogo da Rapamicina CCI-779, testados independentemente e em combinação. A neuroproteção conferida pelo Litío e pelo CCI-779 independentemente sugere que o uso destes fármacos possa ser considerado uma boa estratégia como terapia para a DMJ, a testar em organismos evolutivamente mais próximos do humano. A manipulação da autofagia, segundo vários autores, parece ser benéfica e pode ser a chave para o desenvolvimento de novos tratamentos para várias doenças relacionadas com a agregação proteica e o envelhecimento.

The wedding of Prince Charles and Camilla Parker-Bowles: royal mediation and press mediatization

Bearing in mind the relationship between discourse and society at large, this article addresses the way the British monarchy represented Charles’s second marriage and the way the media constructed their accounts in the period from 10 February (announcement) until 9 April 2005 (wedding) in relation to wider issues such as power relations, newspaper economic structures and popular culture. Particular attention is paid to the multifunctional features of discourse (i.e. its ideational, interpersonal and textual functions), which requires a contextualized reading of a dual process of mediation: on the one hand, the staging of the ceremony by St. James’s Palace and its strategy for attaining monologic closure and, on the other hand, discursive representations by the British press open to a polyphony of voices and discursive frames

Henri Tintant face au problème "Science et Foi"

From an early age Henri Tintant was conforted with the problematic relationships between Science and Faith. After a traditional religious education, he took responsabilities within groups of teenagers and adults through scouting and the J. E. C. (an organisation of catholic students). In 1940 he was at Montpellier distributing unauthorised leaflets defending religious faith. But more significant is his intellectual contribution. He was an active and inspiring member of several workshops and in one in particumar initiated by the Catholic University of Lyon entitled : "From Naturalist to Theologians" where he would start a very fruitful and compelling intellectual collaboration with Father Gustave Martelet a jesuit theologian and a strong supporter of a permanent dialog with the scientists. Throughout the years they will gradually come to the conclusion of a necessary synergy between the scientific and the theologic approach when dealing with the mystery of religious faith . Even in the last months of his life, Henri Tintant was writing to his friendon the subject, with the same profound religious faith that brought him the serenity and the open mindness he has showed throughout his teaching and scientific career. His legacy will remain in two of his last thoughts: "Almost 50 years of scientific research have brought me a lot of pleausures and satisfactions but no answer to the essential questions. In my personal case, science and researching have not driven me away from my religious faith, on the contrary the helped me in my awareness of its utmost necessity". "Faithful to my religious belief, I am convinced that with the death, the inevitable human destiny, not everything disapears completely but another form of live, unimaginable for our limited minds, emerges, bearing in itself the perfect realization of all our hopes and desires".

Portuguese internet radio from 2006 to 2009: technical readiness and openness to interaction

[Extrat] The advent of thc internet raised questions about the role of radio in a fast-changing media environment. Many voices forecast its end but in the summer of 2008 the Swedish Radio and TV Authority published a study named 'The Future of Radio', which clearly opposed the pessimism of recent analysis. While the study anticipates the exhaustion of the FM model, it clearly broadens perspectives for DAB and internet radio, highlighting digitalization as the key element for the future relevance of radio. The Portuguese researcher and radio professional João Paulo Meneses states that 'the future of radio relies upon the internet', calling the broad service offerings of the net the pathway for the survival of radio from the threats to its two essential aspects: rnobility and accumulation (Meneses 2008). Accumulation is radio's capability to be used in a non­exclusive manner, which means that a listener can use the radio while performing other activities, like cooking, sewing, reading, writing or jogging.

Introduction [to "Citizen voices: performing public participation in science and environment communication"]

"ECREA series, ISSN 1742-9420"

Behavioral and psychological symptoms and cognitive decline in patients with amnestic MCI and mild AD: a two-year follow-up study.

BACKGROUND: Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and dementia. In many cases, MCI represents an early stage of developing cognitive impairment. Patients diagnosed with MCI do not meet the criteria for dementia as their general intellect and everyday activities are preserved, although minor changes in instrumental activities of daily living (ADL) may occur. However, they may exhibit significant behavioral and psychological signs and symptoms (BPS), also frequently observed in patients with Alzheimer's disease (AD). Hence, we wondered to what extent specific BPS are associated with cognitive decline in participants with MCI or AD. METHODS: Our sample consisted of 164 participants, including 46 patients with amnestic (single or multi-domain) MCI and 54 patients with AD, as well as 64 control participants without cognitive disorders. Global cognitive performance, BPS, and ADL were assessed using validated clinical methods at baseline and at two-year follow-up. RESULTS: The BPS variability over the follow-up period was more pronounced in the MCI group than in patients with AD: some BPS improve, others occur newly or worsen, while others still remain unchanged. Moreover, specific changes in BPS were associated with a rapid deterioration of the global cognitive level in MCI patients. In particular, an increase of euphoria, eating disorders, and aberrant motor behavior, as well as worsened sleep quality, predicted a decline in cognitive functioning. CONCLUSIONS: Our findings confirm a higher variability of BPS over time in the MCI group than in AD patients. Moreover, our results provide evidence of associations between specific BPS and cognitive decline in the MCI group that might suggest a risk of conversion of individuals with amnestic MCI to AD.

Matka serkamolaiseen teatteriin : kohti sanatonta kerrontaa

A travelogue to serkamoan theater deals, just like its name implies, with the molding process of one theater opinion. It has been influenced by both Aristotle's poetry and Bertold Brecht's epic theater. Side by side with theater goes dance, whose development the thesis also considers briefly. Of today's theater makers, Päivi Ketonen (playback theater), Juha Hurme and Nigel Charnock (dance theater) have had a definitive impact on the Serkamoan theater view. Their relation to theater and dance is clarified in the interviews conducted by the writer, which can be found in their entirety among the appendices of this thesis. Serkamoan theater has also been influenced by the writer's studies in Portuguese theater school in 2004. In Portugal the writer had a chance to work a theater piece in a new cultural environment where, for example, a novel and paintings were used as inspiration. The strongest legacy from Portugal however was the desire to do theater that can be understood without words. Serkamoan theater considers the combinations of theater and dance in performing arts, agreeing with, among others, Pina Bausch's footsteps. Serkamoan theater ladles its inspiration from theater, dance, human being, human body and movement. It is theater that cannot be understood through intellect but through the heart.

Like Man, Like Woman: Roman Women, Gender Qualities and Conjugal Relationships at the Turn of the First Century

Modern scholarship often discusses Roman women in terms of their difference from their male counterparts, frequently defining them as 'other'. This book shows how Roman male writers at the turn of the first century actually described women as not so different from men: the same qualities and abilities pertaining to the domains of parenthood, intellect and morals are ascribed by writers to women as well as to men. There are two voices, however: a traditional, ideal voice and an individual, realistic voice. This creates a duality of representations of women, which recurs across literary genres and reflects a duality of mentality. How can we interpret the paradoxical information about Roman women given by the male-authored texts? How does this duality of mentality inform us about gender roles and gender hierarchy? This work analyses well-known, as well as overlooked, passages from the writings of Pliny the Younger, Tacitus, Suetonius, Quintilian, Statius, Martial and Juvenal and sheds new light on Roman views of women and their abilities, on the notions of private and public and on conjugal relationships. In the process, the famous sixth satire of Juvenal is revisited and its topic reassessed, providing further insights into the complex issues of gender roles, marriage and emotions. By contrasting representations of women across a broad spectrum of literary genres, this book provides consistent findings that have wide significance for the study of Latin literature and the social history of the late first and early second centuries.

Raja-Yoga : Histoire et tradition. Vol 7 : Glossaire de culture indienne

Voici rassemblées en un ouvrage les philosophies, les origines et les filiations du Yoga, plus particulièrement du Raja-Yoga, dans une vision plurielle et chronologique. Le lecteur au fil des textes sélectionnés prend conscience des moyens extraordinaires et exigeants développés par les sages de l'Inde pour répondre aux questions universelles du sens de la vie et de sa finalité. À l'opposé de l'esprit occidental, qui s'appuie sur la dialectique pour explorer le monde, le Yoga se défie du seul intellect, et privilégie l'expérience de soi. Les témoignages et les révélations d'êtres spirituels, tels que Patanjali, Vivekananda ou Ram Chandra, montrent que le chemin de la connaissance passe par soi, le chercheur étant à la fois l'objet de l'expérience, l'observateur et la conscience transformée. S'adressant à chacun de nous dans sa quête de sens et de vérité, le Raja-Yoga est une science, une méthode de réalisation de soi vivante qui, tout en s'inscrivant dans une tradition religieuse et philosophique, reste libre d'évoluer et de répondre aux besoins de l'homme à chaque époque. Ce coffret a eu pour désir de mettre à disposition d'un public occidental la spiritualité de l'Inde vue par elle-même, sous l'angle du Raja-Yoga. L'intérêt porté par des universitaires occidentaux à cette démarche a contribué à mettre en valeur l'apport remarquable des chercheurs indiens, praticiens et érudits, autour d'un sujet sur lequel il n'existait pas d'étude approfondie. Pour la première fois, le Raja-Yoga révèle sa noblesse et son efficacité dans sa dimension de science spirituelle ouverte à tous.

Le veda : histoire d'une reconstruction

Voici rassemblées en un ouvrage les philosophies, les origines et les filiations du Yoga, plus particulièrement du Raja-Yoga, dans une vision plurielle et chronologique. Le lecteur au fil des textes sélectionnés prend conscience des moyens extraordinaires et exigeants développés par les sages de l'Inde pour répondre aux questions universelles du sens de la vie et de sa finalité. À l'opposé de l'esprit occidental, qui s'appuie sur la dialectique pour explorer le monde, le Yoga se défie du seul intellect, et privilégie l'expérience de soi. Les témoignages et les révélations d'êtres spirituels, tels que Patanjali, Vivekananda ou Ram Chandra, montrent que le chemin de la connaissance passe par soi, le chercheur étant à la fois l'objet de l'expérience, l'observateur et la conscience transformée. S'adressant à chacun de nous dans sa quête de sens et de vérité, le Raja-Yoga est une science, une méthode de réalisation de soi vivante qui, tout en s'inscrivant dans une tradition religieuse et philosophique, reste libre d'évoluer et de répondre aux besoins de l'homme à chaque époque. Ce coffret a eu pour désir de mettre à disposition d'un public occidental la spiritualité de l'Inde vue par elle-même, sous l'angle du Raja-Yoga. L'intérêt porté par des universitaires occidentaux à cette démarche a contribué à mettre en valeur l'apport remarquable des chercheurs indiens, praticiens et érudits, autour d'un sujet sur lequel il n'existait pas d'étude approfondie. Pour la première fois, le Raja-Yoga révèle sa noblesse et son efficacité dans sa dimension de science spirituelle ouverte à tous.

Catalan beauty and the transnational beast: Barcelona on screen

This article explores the case of Barcelona as paradigmatic global city in such transnational productions as Vicky Cristina Barcelona by Woody Allen (2008) and Biutiful by Alejandro González Iñárritu (2010). Allen"s film shows the extreme dilution that national and linguistic identity undergoes under foreign eyes in its rendition of a"hip Barcelona" for tourists"invaded" by transnational subjects in search of bourgeois pleasures. Maybe in pursuit of a more"real" city, Iñárritu"s Biutiful moves to the Barcelona of the immigrants and the undocumented, a transnational and paradoxical location inhabited by those who need to cross borders in order to survive. Through reference to the work of Manuel Castells, Saskia Sassen, Neil Smith and Michel De Certeau among others, we argue that neither of these representations of the city is more real or unreal than the other. In their drastically divergent ways, both films contribute their external perspectives to the imaginary construction of Barcelona as a fascinating global city and can be seen as a dyptich of a transnational Barcelona. Further, they contribute to the ongoing debate about the polarization between the local and the global, the construction of urban boarders inside cities through gentrification, the transformation of the places we (would like to) inhabit, and the translation of all these into visual terms.