L'abattage en Inde. Modalités techniques, recompositions spatiales et contestations politiques

Cet article interroge les reconfigurations spatiales et organisationnelles de l'abattage dans le monde indien. En s'appuyant sur des recherches menées entre 2011 et 2014 dans l'État du Tamil Nadu, il met en lumière les processus qui sous-tendent ces reconfigurations. En Inde, les configurations spatiales de l'organisation du travail dans les abattoirs municipaux diffèrent de celles à l'oeuvre dans les abattoirs industriels. Dans l'abattoir municipal de Chennai, la saignée, la dépouille, l'éviscération et la découpe se font dans un même lieu. Cependant, une frontière nette et hermétique sépare la section des caprinés de celle des bovinés : cette frontière peut être comprise comme l'inscription dans l'espace de l'abattoir d'une hiérarchie de l'impureté qui affecte les individus et les viandes. Plus généralement, les lieux d'abattage sont des arènes de mobilisation politique où prennent place des conflits opposant les bouchers traditionnels, les décideurs politiques, les groupes agro-industriels, les experts scientifiques, les militants écologistes ou animalistes et les partisans du nationalisme hindou. Cet article montre que les différentes logiques de localisation et configurations techno-spatiales des lieux d'abattage renvoient à différents régimes de régulation de l'impureté organique, morale ou religieuse à laquelle les groupes dominants associent la viande en Inde

Severe familial hypercholesterolaemia: Current and future management

SummaryFamilial hypercholesterolaemia is an inherited disorder, leading to accumulation of low-density lipoprotein (LDL) particles in plasma and premature cardiovascular disease. Although the phenotype of the rare homozygous form is always severe, the phenotypic expression of the common heterozygous familial hypercholesterolaemia can vary considerably. Beyond the magnitude of the LDL-cholesterol elevation and the type of mutation, additional genetic, metabolic and environmental cardiovascular risk factors lead to the substantial variations in the clinical manifestations and severity of atherosclerotic disease. Heterozygous familial hypercholesterolaemia is often under-diagnosed and under-treated, and there is an unmet need in terms of management of severe heterozygous forms. Homozygous and severe heterozygous familial hypercholesterolaemia should receive more intensive treatment and alternative therapeutic approaches are needed for these high-risk patients. In this article, we review the recommendations for diagnosis and treatment of severe familial hypercholesterolaemia and the agents currently available or under development

Modulation of host polyubiquitination by the ankb f-box protein of Legionella pneumophila.

Legionella pneumophila is a facultative intracellular pathogen that infects a wide array of protozoan hosts and human alveolar macrophages. L. pneumophila is dependent on a functional Dot/Icm type IVB secretion system that translocates bacterial effector proteins into the host cell cytosol. L. pneumophila genomes encode more than 250 effector proteins, many of which inhibit host cellular processes to form a favorable niche termed the Legionella-containing vacuole (LCV). The eukaryotic-like Dot/Icm translocated effector AnkB contains two eukaryotic-like ankyrin protein-protein interacting domains, one eukaryotic-like F- box domain and an eukaryotic C-terminal CaaX motif. Immediately following attachment of extracellular bacteria, AnkB is translocated into the host cell where it is rapidly farnesylated and anchored to the plasma membrane beneath the attached extracellular bacteria. AnkB recruits the host cell SCF1 E3 ubiquitin ligase machinery to the point of attachment and promotes the lysine48-linked polyubiquitination of the AnkB substrates. Interestingly, the proteasomal degradation of the lysine48-liked polyubiquitinated proteins increases the levels of intracellular free amino acids within 15 minutes of attachment of extracellular bacteria. This early increase in free cellular amino acids is needed to prevent a starvation response and inhibits differentiation into the non-replicative phase which facilitates intracellular replication. The polyubiquitinated proteins surrounding the LCV have a wide range of cellular functions, and include the amino acid transporters SLC1A4 and SLC3A2 and the sodium bicarbonate transporter SLC4A7. In addition the ubiquitinated proteome of the WT strain, the LCV contains proteins involved in the immune response, including interferon regulatory factor 7 and Interleukin-1 receptor-associated kinase 1a. The complete LCV proteome of the WT strain as well as the ankB mutant strain contained E2 ubiquitin-conjugation enzymes, E3 ubiquitin ligases and ubiquitin peptidases. Bioinformatic analysis determined the major metabolic networks within the LCV proteome, including the phosphatidylinositol 4,5 diphosphate pathway and multiple amino acid synthesis pathways. These data showed that AnkB is polyubiquitinated on lysine 67 through lysine11-linked polyubiquitination. While lysine11-linked polyubiquitination has been shown to target the modified protein for proteasomal degradation, stability of AnkB is not affected following ubiquitination. This highlights a novel example of an F-box effector protein that is modified though lysine11-linked polyubiquitination. Taken together, AnkB manipulates multiple eukaryotic cellular pathways to enable intra-vacuolar proliferation of L. pneumophila