Analysis of susceptibility to human immunodeficiency virus 1 (HIV-1) by comparative genetics

Summary [résumé français voir ci-dessous] From the beginning of the 20th century the world population has been confronted with the human immune deficiency virus 1 (HIV-1). This virus has the particularity to mutate fast, and could thus evade and adapt to the human host. Our closest evolutionary related organisms, the non-human primates, are less susceptible to HIV-1. In a broader sense, primates are differentially susceptible to various retrovirus. Species specificity may be due to genetic differences among primates. In the present study we applied evolutionary and comparative genetic techniques to characterize the evolutionary pattern of host cellular determinants of HIV-1 pathogenesis. The study of the evolution of genes coding for proteins participating to the restriction or pathogenesis of HIV-1 may help understanding the genetic basis of modern human susceptibility to infection. To perform comparative genetics analysis, we constituted a collection of primate DNA and RNA to allow generation of de novo sequence of gene orthologs. More recently, release to the public domain of two new primate complete genomes (bornean orang-utan and common marmoset) in addition of the three previously available genomes (human, chimpanzee and Rhesus monkey) help scaling up the evolutionary and comparative genome analysis. Sequence analysis used phylogenetic and statistical methods for detecting molecular adaptation. We identified different selective pressures acting on host proteins involved in HIV-1 pathogenesis. Proteins with HIV-1 restriction properties in non-human primates were under strong positive selection, in particular in regions of interaction with viral proteins. These regions carried key residues for the antiviral activity. Proteins of the innate immunity presented an evolutionary pattern of conservation (purifying selection) but with signals of relaxed constrain if we compared them to the average profile of purifying selection of the primate genomes. Large scale analysis resulted in patterns of evolutionary pressures according to molecular function, biological process and cellular distribution. The data generated by various analyses served to guide the ancestral reconstruction of TRIM5a a potent antiviral host factor. The resurrected TRIM5a from the common ancestor of Old world monkeys was effective against HIV-1 and the recent resurrected hominoid variants were more effective against other retrovirus. Thus, as the result of trade-offs in the ability to restrict different retrovirus, human might have been exposed to HIV-1 at a time when TRIM5a lacked the appropriate specific restriction activity. The application of evolutionary and comparative genetic tools should be considered for the systematical assessment of host proteins relevant in viral pathogenesis, and to guide biological and functional studies. Résumé La population mondiale est confrontée depuis le début du vingtième siècle au virus de l'immunodéficience humaine 1 (VIH-1). Ce virus a un taux de mutation particulièrement élevé, il peut donc s'évader et s'adapter très efficacement à son hôte. Les organismes évolutivement le plus proches de l'homme les primates nonhumains sont moins susceptibles au VIH-1. De façon générale, les primates répondent différemment aux rétrovirus. Cette spécificité entre espèces doit résider dans les différences génétiques entre primates. Dans cette étude nous avons appliqué des techniques d'évolution et de génétique comparative pour caractériser le modèle évolutif des déterminants cellulaires impliqués dans la pathogenèse du VIH- 1. L'étude de l'évolution des gènes, codant pour des protéines impliquées dans la restriction ou la pathogenèse du VIH-1, aidera à la compréhension des bases génétiques ayant récemment rendu l'homme susceptible. Pour les analyses de génétique comparative, nous avons constitué une collection d'ADN et d'ARN de primates dans le but d'obtenir des nouvelles séquences de gènes orthologues. Récemment deux nouveaux génomes complets ont été publiés (l'orang-outan du Bornéo et Marmoset commun) en plus des trois génomes déjà disponibles (humain, chimpanzé, macaque rhésus). Ceci a permis d'améliorer considérablement l'étendue de l'analyse. Pour détecter l'adaptation moléculaire nous avons analysé les séquences à l'aide de méthodes phylogénétiques et statistiques. Nous avons identifié différentes pressions de sélection agissant sur les protéines impliquées dans la pathogenèse du VIH-1. Des protéines avec des propriétés de restriction du VIH-1 dans les primates non-humains présentent un taux particulièrement haut de remplacement d'acides aminés (sélection positive). En particulier dans les régions d'interaction avec les protéines virales. Ces régions incluent des acides aminés clé pour l'activité de restriction. Les protéines appartenant à l'immunité inné présentent un modèle d'évolution de conservation (sélection purifiante) mais avec des traces de "relaxation" comparé au profil général de sélection purifiante du génome des primates. Une analyse à grande échelle a permis de classifier les modèles de pression évolutive selon leur fonction moléculaire, processus biologique et distribution cellulaire. Les données générées par les différentes analyses ont permis la reconstruction ancestrale de TRIM5a, un puissant facteur antiretroviral. Le TRIM5a ressuscité, correspondant à l'ancêtre commun entre les grands singes et les groupe des catarrhiniens, est efficace contre le VIH-1 moderne. Les TRIM5a ressuscités plus récents, correspondant aux ancêtres des grands singes, sont plus efficaces contre d'autres rétrovirus. Ainsi, trouver un compromis dans la capacité de restreindre différents rétrovirus, l'homme aurait été exposé au VIH-1 à une période où TRIM5a manquait d'activité de restriction spécifique contre celui-ci. L'application de techniques d'évolution et de génétique comparative devraient être considérées pour l'évaluation systématique de protéines impliquées dans la pathogenèse virale, ainsi que pour guider des études biologiques et fonctionnelles

Cantant entre guerres : música coral per a veus blanques a França i Catalunya a principis del segle XX

Aquest treball busca definir algunes característiques comunes d'obres musicals escrites a principis del segle XX per compositors francesos i catalans per a cor de veus blanques, mitjançant l'estudi de les seves biografies i l'anàlisi de les pròpies obres. Aquestes peces, compostes en llocs i moments diferents, convergeixen però en alguns punts estilístics, transcendint les fronteres per contribuir a l'elaboració d'un llenguatge propi d'un entorn cultural més ampli, de París a Barcelona.

The effect of divorce laws on divorce rates in Europe

This paper analyzes a panel of 18 European countries spanning from 1950 to 2003 toexamine the extent to which the legal reforms leading to easier divorce that took placeduring the second half of the 20th century have contributed to the increase in divorce rates across Europe. We use a quasi-experimental set-up and exploit the different timing of the reforms in divorce laws across countries. We account for unobserved country-specificfactors by introducing country fixed effects, and we include country-specific trends tocontrol for time-varying factors at the country level that may be correlated with divorcerates and divorce laws, such as changing social norms or slow moving demographictrends. We find that the reforms were followed by significant increases in divorce rates.Overall, we estimate that the introduction of no-fault, unilateral divorce increased thedivorce rate by about 1, a sizeable effect given the average rate of 4.2 divorces per 1,000married people in 2002.

A influência do e-learning no capital humano

Na Europa e nas últimas décadas do Século XX, a emergência da Sociedade de Informação veio impor às organizações a necessidade de que, para além das inovações tecnológicas, haja uma preocupação relativamente aos bens intangíveis como a informação, as novas metodologias de trabalho e o know how (Batista, 2002). Paralelamente a estas inovações, as Instituições de Ensino Superior têm contribuído para a evolução do Capital Humano, como ativo intangível intrínseco ao Homem. Em Portugal e no contexto do Ensino/Formação a Distância parecem continuar a existir, ainda, em algumas instituições, problemas de identificação, e de descriminação das vantagens no que concerne à estrutura aberta e flexível, com o estudante/formando a ter algumas dificuldades em adaptar o seu perfil e interesses profissionais ao tipo de aprendizagem que mais se lhe adequa. O e-learning surge como um método de Ensino/Formação a Distância, só possível com a especificidade dos processos pedagógicos e em complementaridade com as Tecnologias de Informação e Comunicação (TIC), uma vez que são estas que lhe dão o suporte necessário à sua concretização. O e-learning ao proporcionar novas formas de comunicação, de interação e de confronto de ideias, permite uma aprendizagem baseada na partilha de saberes, tendo em consideração as experiências e os objetivos profissionais dos formandos. Dentro destes pressupostos, achámos importante fazer uma investigação a partir de Instituições de Ensino Superior Portuguesas, de modo a percebermos qual o papel e a influência que o e-learning desempenha nos objetivos das organizações académicas em geral e no Capital Humano dos seus Estudantes/Formandos em particular. A partir da questão da investigação foram definidos os objetivos e hipóteses de investigação de modo a que ao ser enunciada uma metodologia esta englobe fatores que foquem os elementos necessários à confirmação, ou não, dos pressupostos enunciados. Foi analisada documentação diversa, criado um questionário e conduzidas entrevistas, de modo a obter e potenciar a informação necessária e suficiente para o efeito. A recolha de dados para posterior análise e os resultados depois de interpretados, permitirão responder aos propósitos expressos desde o início da investigação.

Did colonization matter for growth? An empirical exploration into the historical causes of Africa's underdevelopment

We investigate the impact of 20th--century European colonizationon growth in Africa. We find that in the 1960--88 period growth has beenfaster for dependencies than for colonies; for British and Frenchcolonies than for Portuguese, Belgian and Italian ones; and for countrieswith less economic penetration during the colonial period. On average,African growth accelerates after decolonization. Proxies for colonialheritage add explanatory power to growth regressions and make indicatorsfor human capital, political and ethnic instability lose significance.Colonial variables capture the same effects of a sub--Saharan dummy andreduce its significance when jointly included in a cross sectionalregression with 98 countries.

Managing by values in the next milenium: Cultural redesign for strategic organizational change

The system of beliefs and values, that shaped the model for management and organizations during the 20th century, is just not good enough today. In order to keep a business functioning well and competing successfully in markets that are increasingly more global, complex, professionally demanding, constantly changing and oriented towards quality and customer satisfaction a new model is needed. In this paper, we will propose that both Management by Instructions (MBI) and Management by Objectives (MBO) today give notoriously inadequate results. By contrast, description of a new approach labeled: Management by Values (MBV), seem to be emerging as a strategic leadership tool. The paper outlines this approach and discusses the implementation of MBV as a tool to redesign culture in organizations and prepare them for the next millenium.

Signal analysis of Ney performances

Ney is an end-blown flute which is mainly used for Makam music. Although from the beginning of 20th century a score representation based on extending the Western musicis used, because of its rich articulation repertoire, actualNey music can not be totally represented by written score.Ney is still taught and transmitted orally in Turkey. Becauseof that the performance has a distinct and importantrole in Ney music. Therefore signal analysis of ney performancesis crucial for understanding the actual music.Another important aspect which is also a part of the performanceis the articulations that performers apply. In Makam music in Turkey none of the articulations are taught evennamed by teachers. Articulations in Ney are valuable for understanding the real performance. Since articulations are not taught and their places are not marked in the score, the choice and character of the articulation is unique for eachperformer which also makes each performance unique.Our method analyzes audio files of well known Turkish Ney players. In order to obtain our analysis data, we analyzed audio files of 8 different performers vary from 1920to 2000.

Conceptos y métodos fundamentales en ecología del paisaje (landscape ecology). Una interpretación desde la geografía

L'ecologia del paisatge neix en una vinculació ben estreta amb la geografia i viu un espectacular desenvolupament a partir de la segona meitat del segle XX. En l’actualitat, és una perspectiva científica transdisciplinària, consolidada i reconeguda, que intenta comprendre i ajudar a resoldre els principals reptes ambientals contemporanis pel que fa a la conservació del patrimoni natural i cultural. En aquestes pàgines, es repassa de forma sintètica els conceptes clau i els mètodes, eminentment quantitatius, emprats per l’ecologia del paisatge per analitzar la situació i l’evolució dels paisatges

Le regard d'un psychiatre sur les écrits de la folie : la carrière de Hans Steck à l'Asile psychiatrique de Cery (1920-1960)

Quelles représentations de la schizophrénie les psychiatres vont-ils construire à travers l'étude des écrits asilaires des patients et des scientifiques dans la première moitié du XXème siècle? Le psychiatre helvétique Hans Steck (1891-1980), qui a travaillé à l'Asile psychiatrique de Cery de 1920 à 1960 et qui s'est fait connaître du public grâce à l'oeuvre d'Aloïse Corbaz, reconnue comme auteure d'art brut par Jean Dubuffet en 1945, constitue le fil rouge de la thèse. Dans le contexte des mouvements tels que Γ "art psychopathologique" et Γ "art brut", Steck étudie les théories de "la mentalité primitive et les peintures magiques des schizophrènes". En 1927, il se tourne vers les théories évolutionnistes de la régression et les premières études de Lévy-Bruhl pour avancer l'idée qu'il existe un "parallélisme schizo-primitif'. Puis il développe des explications de la pensée délirante, à partir des théories exposées lors du Premier Congrès International de Psychiatrie en 1950. Enfin, adoptant la perspective phénoménologique, il explique que "la fonction de l'art et la fonction du délire visent à reconstituer un monde viable pour le malade". En ce sens, l'expression artistique, bien que n'entrant pas dans le champ de la psychothérapie, fournit des indicateurs de l'état psychique du malade en même temps qu'elle contribue à son bien-être. Sont abordés les problèmes concernant la reconnaissance de Γ "auteur" interné, dont les oeuvres appartiennent soit aux archives médicales, soit au musée. La pérennité des critères qui définissent les oeuvres d'"art psychopathologique" ou d'"art brut" est également mise en question. Enfin, le rôle essentiel de l'écriture à l'hôpital, tant pour les patients que pour les soignants, fait l'objet de nombreux développements. - What representations of schizophrenia have psychiatrists been constructing when studying writings by patients and scientists in mental asylums in the first half of the 20th century? The Swiss psychiatrist Hans Steck (1891-1980) is the protagonist of this dissertation. From 1920 to 1960, he has been working at the "Asile psychiatrique de Cery" near Lausanne. Steck is known thanks to the paintings of Aloïse Corbaz, an artist recognized by Jean Dubuffet as belonging to the "art brut" movement in 1945. In the context of movements like "art psychopathologique" and "art brut," Steck studies theories of "primitive character and magic paintings of schizophrenics." In 1927, Steck engages with theories of regression and Lévy-Bruhl's early studies in order to push the idea of a "parallelism schizo-primitif." On the occasion of the First International Congress of psychiatry held in Paris in 1950, Steck develops explanations for the "pensée délirante." Finally, turning to a phenomenological point of view, he explains, "the function of art and the function of the delusion help the patient to reconstruct a viable environment for the sick person." In this way, artistic expression is not thought of as a psychotherapeutical means, but provides insight into the state of mind of a mentally sick person at the same time as contributing to his well-being. The dissertation discusses whether the "author's" work belongs in medical archives or museums. The continuity of "psychopathological art" and "art brut" criteria will be discussed. Finally, the essential role that writing played in the hospital for the patients as well as for the medical staff is presented.

El Trienio Liberal en el Virreinato peruano: los ayuntamientos constitucionales de Arequipa, Cusco y Huamanga, 1820-1824

El artículo profundiza en aspectos desconocidos de lo que fue la reimplantación del gobierno representativo en el Virreinato del Perú durante el Trienio Liberal. Para ello se seleccionan tres ciudades, el Cusco, Huamanga y Arequipa, que se mantuvieron hasta muy tarde leales a la Corona. La consulta de documentación generada por las tres corporaciones ha permitido reconstruir tres ejemplos de poder local a través de los procesos electorales, la composición de los ayuntamientos y el análisis de sus competencias. Se demuestra que el virrey La Serna gobernó según la Constitución de 1812 y se pone de manifiesto que existieron cambios y continuidades entre ayuntamientos españoles y municipalidades peruanas, porque permanecieron algunos actores y fórmulas de las instituciones hispanas