ApoE−/− PGC-1α−/− Mice Display Reduced IL-18 Levels and Do Not Develop Enhanced Atherosclerosis

BACKGROUND: Atherosclerosis is a chronic inflammatory disease that evolves from the interaction of activated endothelial cells, macrophages, lymphocytes and modified lipoproteins (LDLs). In the last years many molecules with crucial metabolic functions have been shown to prevent important steps in the progression of atherogenesis, including peroxisome proliferator activated receptors (PPARs) and the class III histone deacetylase (HDAC) SIRT1. The PPARγ coactivator 1 alpha (Ppargc1a or PGC-1α) was identified as an important transcriptional cofactor of PPARγ and is activated by SIRT1. The aim of this study was to analyze total PGC-1α deficiency in an atherosclerotic mouse model. METHODOLOGY/PRINCIPAL FINDINGS: To investigate if total PGC-1α deficiency affects atherosclerosis, we compared ApoE(-/-) PGC-1α(-/-) and ApoE(-/-) PGC-1α(+/+) mice kept on a high cholesterol diet. Despite having more macrophages and a higher ICAM-1 expression in plaques, ApoE(-/-) PGC-1α(-/-) did not display more or larger atherosclerotic plaques than their ApoE(-/-) PGC-1α(+/+) littermates. In line with the previously published phenotype of PGC-1α(-/-) mice, ApoE(-/-) PGC-1α(-/-) mice had marked reduced body, liver and epididymal white adipose tissue (WAT) weight. VLDL/LDL-cholesterol and triglyceride contents were also reduced. Aortic expression of PPARα and PPARγ, two crucial regulators for adipocyte differentiation and glucose and lipid metabolism, as well as the expression of some PPAR target genes was significantly reduced in ApoE(-/-) PGC-1α(-/-) mice. Importantly, the epididymal WAT and aortic expression of IL-18 and IL-18 plasma levels, a pro-atherosclerotic cytokine, was markedly reduced in ApoE(-/-) PGC-1α(-/-) mice. CONCLUSIONS/SIGNIFICANCE: ApoE(-/-) PGC-1α(-/-) mice, similar as PGC-1α(-/-) mice exhibit markedly reduced total body and visceral fat weight. Since inflammation of visceral fat is a crucial trigger of atherogenesis, decreased visceral fat in PGC-1α-deficient mice may explain why these mice do not develop enhanced atherosclerosis

Improved system for heterologous expression of cytochrome c mutants in Escherichia coli

We improved an already existing cytochrome c expression system to a reliable, tightly controllable one to achieve a higher expression yield for single cysteine mutants of horse cytochrome c. The protein is heterologously overexpressed in E. coli together with the maturation coordinating enzyme heme lyase from yeast. Various plasmid constructs and host strains were tested for protein expression yield and routinely around 35 mg/L yield was achieved, which is a good result for a post-translationally modified enzyme. The purpose of producing cysteine mutants is to position accessible cysteine residues on the surface of cytochrome c which can be labeled with a photoactive redox dye, 8-thiouredopyrene-1,3,6-trisulfonate, TUPS. TUPS labeled proteins have been used for intramolecular and intermolecular electron transfer measurements. Here, we initiate the photoreduction of cytochrome c oxidase, the natural electron acceptor partner of cytochrome c by an appropriate cytochrome c mutant labeled with TUPS. The electron transfer from cytochrome c to the first cytochrome oxidase redox cofactor, copper A, is shown to be very fast

Illegal import of bushmeat and other meat products into Switzerland on commercial passenger flights.

Illegal imports of meat can present substantial risks to public and animal health. Several European countries have reported considerable quantities of meat imported on commercial passenger flights. The objective of this study was to estimate the quantity of meat illegally imported into Switzerland, with a separate estimation for bushmeat. Data were obtained by participation in intervention exercises at Swiss international airports and by analysing data on seizures during the four-year period 2008 to 2011. The study revealed that a wide array of animal species was imported into Switzerland. From the database, the average annual weight of meat seized during the period analysed was 5.5 tonnes, of which 1.4% was bushmeat. However, in a stochastic model the total annual inflow of illegal meat imports was estimated at 1,013 tonnes (95% CI 226 to 4,192) for meat and 8.6 tonnes (95% CI 0.8 to 68.8) for bushmeat. Thus, even for a small European country such as Switzerland the quantities of illegally imported meat and meat products are substantial and the consequences for public and animal health could be high. To reduce the risk, it is essential that surveillance at European airports is harmonised and that passenger information campaigns clarify the consequences of the illegal import of meat, particularly bushmeat

Le risque en pastoralisme : quelques considérations pour orienter les actions de développement

Le pastoralisme est plus qu'un système de production extensif exploitant le milieu naturel, c'est aussi un mode de vie. Souvent confiné à des régions subissant de fortes contraintes environnementales, il est soumis directement aux aléas du climat et des ressources. Le pasteur doit faire face, probablement plus que bien d'autres groupes socio-professionnels, à des risques divers en rapport avec le milieu. Il est aussi expose a certaines insécurités sociales ou politiques. S'y ajoute une faible sécurité foncière. La viabilité et la pérennité de son activité résulte de tout un jeu de stratégies de gestion de ces risques. Le troupeau étant son principal moyen de production, le pasteur lui consacre une grande part de ses efforts. Pour réduire les risques qu'il encourt, il applique une série de mesures qui garantissent jusqu'à un certain point aux animaux l'affouragement, l'abreuvement, la santé, la protection contre les prédateurs. Mais il accepte aussi une part de risque. A côté de cela, les institutions publiques et privées ainsi que les projets disposent de la faculté d'appuyer ou de soutenir certaines stratégies réduisant les risques encourus, soit ordinaires, soit en cas de catastrophes, et de prendre en compte la viabilité à long terme du système et de l'environnement. Sur le plan des méthodes, il convient de comprendre ce qui motive les comportements des pasteurs pour mettre en place, en concertation avec eux, des mesures atténuant les risques spécifiques à leur condition. (Résumé d'auteur