N-acétyltransférase lysosomale : organisation, fonctionnement et défauts moléculaires chez les patients atteints du syndrome de Sanfilippo type C

L’acétylation des résidus de glucosamine terminaux par la N-acétyltransférase lysosomale (HGSNAT) est une étape essentielle de la dégradation catabolique de l’héparan sulfate. Des défauts dans cette réaction causent une maladie de surcharge lysosomale autosomale récessive rare : le désordre de Sanfilippo type C (SFC). À ce jour, 54 mutations ont été rapportées chez des patients SFC, incluant 13 mutations des sites d’épissage, 11 insertions et délétions, 8 mutations non-sens, 18 mutations faux-sens et 4 polymorphismes, avec différentes manifestations phénotypiques. Nous avons identifié 10 d’entre elles et effectué une étude exhaustive portant sur l’éventail des mutations SFC, leur distribution dans la population de patients, ainsi que leur impact potentiel sur la structure de la HGSNAT. Les erreurs d’épissage, les mutations non-sens, les insertions et les délétions devraient toutes entraîner un ARN non fonctionnel qui est rapidement dégradé par des mécanismes de contrôle qualité cellulaire. Les 4 polymorphismes identifiés sont des changements d'acides aminés qui ne modifient pas l'activité enzymatique, la glycosylation ou la localisation et n'ont donc pas de signification au niveau clinique. Au niveau des enzymes, les polymorphismes sont des changements d’acides aminés qui n’affectent pas la fonction, mais dans un contexte d’acides nucléiques ils peuvent être considérés comme des mutations faux-sens. Les dix-huit mutations faux-sens qui ont été exprimées ont produit des protéines inactives, en raison d'erreurs dans leur repliement. Ceci expliquerait donc la progression sévère de la maladie chez les personnes porteuses de ces mutations. Les protéines mutantes mal repliées sont anormalement glycosylées et conservées dans le réticulum endoplasmique. La thérapie par amélioration de l’activité enzymatique par des chaperonnes est une option thérapeutique potentielle, spécifiquement conçue pour exploiter l'activité enzymatique résiduelle de mutants mal repliés, afin d’éliminer les substrats stockés. Nous avons démontré que le traitement de plusieurs lignées de fibroblastes de patients SFC avec le chlorhydrate de glucosamine, un inhibiteur spécifique de la HGSNAT, a partiellement restauré l’activité de l'enzyme mutante, fournissant une preuve de l’utilité future de la thérapie par des chaperonnes dans le traitement de la maladie de SFC.

Pogge -vs- Sen on Global Poverty and Human Rights

This Paper is part of a broader project examining the ways in which Amartya Sen’s “capability approach” provides a framework for thinking about global poverty as a denial or a violation of basic human rights. The Paper compares the “capability approach” as a basis for thinking about global poverty and human rights with the alternative framework developed by Thomas Pogge. Both the “capability approach” and Pogge’s theory of “severe poverty as a violation of negative duties” support the idea of “freedom from severe poverty as a basic human right”. However, there are important differences. The Paper examines the limitations of Pogge’s “apparent minimalism” and establishes the ways in which Sen’s treatment of the “capability approach” and human rights moves beyond a “minimalist normative position” whilst avoiding Pogge’s charge of “implausibility”.

Companies’ practices and social responsibility: cases of companies in the French tourist sector

This article examines the firms’practices in the French tourist sector. By confronting the concepts defined in the literature on the social responsibility and what really happens in companies, the current research shows that the studied firms implement a minimal social responsibility which remains well below the expectation level of some stakeholders. This situation is explained by several factors, namely structural. Finally, the paper suggests ways to improve the concept of social responsibility.

Religion and Clothing: the Capabilities Approach Considered

Proponents of the capabilities approach claim that it should be used to give guidance for the implementation of good constitutional laws. This suggests that it also gives us grounds to support attempts to create or protect constitutions based on something like the capabilities approach. The Turkish Republic claims that in order to protect secularism and the equal status of women, it needs to keep certain Islamic practices away from the public domain. The wearing of the headscarf has been singled out as such a practice, and the Turkish Republic has therefore legislated against headscarf wearing in schools, universities, and government buildings. In consequence many women are forced to choose between religion over education and politics in a way that curtails central human capabilities. Nussbaum claims that the best way to help states resolve the dilemma presented by the conflict between religious choice and other central capabilities is to refer to principles embodied in to the US Religious Freedom Restoration Act 1993, which states that a law can burden a person's exercise of religion only when the burden is a furtherance of a compelling state interest. In this paper I consider how this advice partly vindicates the Turkish case and how the solution it yields is in many ways more satisfactory than that of more traditional approaches in political philosophy.

Censure.cn : Google s’attaque au marché chinois

Étude de cas

The Money Question and the Good Life

This paper proposes a theory of the good life for use in answering the question how much money the rich should spend on fighting poverty. The paper moves from the abstract to the concrete. To begin with, it investigates various ways to get an answer to the question what is good, and finds itself drawn to objective theories of the good. It then develops, taking Bernard Williams and Martha Nussbaum as its guides, a broad outline of a theory of the good. It holds that something evil happens to people if they do not have a real choice from a reasonable number of projects that realize most of their key capacities to a certain degree, and in connection to this it points to the great importance of money. The paper goes on specifically to consider what criticisms of Nussbaum's version of the capability approach are implied in this outline of a theory of the good. Next, it gets more specific and asks how much money the rich can give -and how they can be restricted in spending their money- without suffering any evil. It does three suggestions: the tithe suggestion, the ecological (or footprint) suggestion, and the fair trade suggestion. To conclude, the paper returns to the question how much money the rich should spend on fighting poverty.

Working Children: their Agency and self-organization

In recent years, ‘agency’ has appeared in academic writings as a new way of referring to active involvement from below in development interventions. The concept of ‘agency’ starts from the assumption that people are actually agents themselves, continuously acting in and reacting to circumstances. In child labour activism, this concept has been applied to working children in the understanding that, in order to improve their working conditions, children should be organised in organizations that are exclusively for and (ideally) run by working children. This paper aims to evaluate the extent to which child labourers can become agents of change through their own organizations. The paper will draw on two studies carried out by the IREWOC foundation. In 2002 a study was undertaken in Bolivia to give practical meaning to the concept of child agency. Secondly, in 2004/2005 an investigation was carried out on the functioning and impact of children’s organizations in Peru, Bolivia and Brazil. The applied research methods were mainly anthropological and used participant observation, (semi-) informal interviews and group interviewing with working children, their parents and adult representatives of the working children’s organizations. Both investigations show that in focussing on children as active participants, the structural constraints under which children have to live also need to be highlighted. One needs to understand how material poverty, mental deprivation and disempowerment help to shape resilience and defiance, but also anger, distrust and marginalisation.

Travail des enfants, enfants des rues et approche par les capabilités : Liens méthodologiques et implications pour les politiques

Le débat sur le travail des enfants a pris une ampleur considérable ces vingt dernières années. Les politiques se sont majoritairement orientées vers la promotion de l’éducation. Pourtant, le débat n’a guère fait de place à la question des enfants des rues. Intégrer cette catégorie d’enfants au débat pose de nouvelles questions. En particulier, l’éducation doit prendre une forme non violente et des espaces de travail doivent être ouverts pour les enfants des rues.

Une approche géographique du « travail » des enfants des rues

Cet article propose de décrire le quotidien des enfants des rues de Yaoundé (Cameroun) et d’Antananarivo (Madagascar) en mettant l’accent sur les activités générant des revenus. Quels espaces de travail émergent au sein de la ville, suivant quelles logiques? Ce questionnement nous permet de dessiner les contours, incertains, de l’univers de la rue. Il ouvre aussi la réflexion sur le devenir des enfants et leur capacité à s’insérer au sein de la société urbain. Nous prenons en compte les actions de l’Etat, des ONG et les représentations des habitants.