Opposite regulation of metabotropic glutamate receptor 3 and metabotropic glutamate receptor 5 by inflammatory stimuli in cultured microglia and astrocytes.

Metabotropic glutamate receptors (mGluRs) were previously shown to modulate several essential functions in glial cells, including cell proliferation, glutamate uptake, neurotrophic support, and inflammatory responses. As these receptors are regularly proposed as promising targets for the treatment of a wide range of neurological disorders, we herein examined the reciprocal modulation of glial mGluRs by inflammation. Such regulation of mGluRs was also studied in cultures from an experimental model of amyotrophic lateral sclerosis (ALS). Indeed, ALS is characterized by increased neuroinflammation, and glial cell cultures derived from the animal model (rat expressing hSOD1(G93A)) show enhanced glial reactivity. Within 72 h, the pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) induced an increase in mGluR3 and a decrease in mGluR5 gene expression. A similar regulation of these receptors was observed in microglia 48 h after an initial 4-h exposure to lipopolysaccharide. In hSOD1(G93A)-derived glial cultures, the gene up-regulation of mGluR3 (but not the gene down-regulation of mGluR5) was found to be enhanced in both astrocytes and microglia. Together, these results indicate that an inflammatory environment triggers an opposite regulation in the gene expression of the two predominant mGluR subtypes found in glial cells, and that these regulations were particularly robust in hSOD1(G93A) glial cultures. As neuroinflammation commonly occurs in several nervous diseases, its influence on mGluR expression should be taken into account when considering these receptors as future drug targets

Synthesis of large-scale source apportionment of oxidative potential at 15 sites in France

International audienceAtmospheric ambient particulate matter (PM) is linked to diverse health outcomes such as asthma, cardiovascular disease and increased cancer risk. Although PM present a wide span of size, shape, chemical composition and so sanitary impacts, epidemiological studies usually focus on PM mass concentrations only. The oxidative potential (OP) of PM has been proposed as a new proxy for air quality in order to better estimate the population exposure since it integrates the different PM characteristic and is closely linked to the inflammatory response of the body to the oxidative stress induced by PM. However, long time-series of OP measurement are still limited in the literature and no standardized assays has emerged. Moreover, very few source apportionment studies of OP have been conducted yet

Centreafrique/Afrique centrale : ressources et conflits armés

Ce numéro des Cahiers d’Outre-Mer traite d’une question classique de géographie politique, la relation entre ressources et conflits armés, dans un contexte original, celui de la République centrafricaine (RCA). Afin d’introduire les textes qui composent ce dossier, il s’agit d’abord de situer le cas centrafricain par rapport aux principales approches développées dans les sciences sociales sur la thématique des conflits et des ressources, et de trier celles qui semblent le plus opératoires pour éclairer l’imbroglio centrafricain… [En savoir +

A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning

International audienceRecent events demonstrated that organophosphorus nerve agents are a serious threat for civilian and military populations. The current therapy includes a pyridinium aldoxime reactivator to restore the enzymatic activity of acetylcholinesterase located in the central nervous system and neuro-muscular junctions. One major drawback of these charged acetylcholinesterase reactivators is their poor ability to cross the blood–brain barrier. In this study, we propose to evaluate glucoconjugated oximes devoid of permanent charge as potential central nervous system reactivators. We determined their in vitro reactivation efficacy on inhibited human acetylcholinesterase, the crystal structure of two compounds in complex with the enzyme, their protective index on intoxicated mice, and their pharmacokinetics. We then evaluated their endothelial permeability coefficients with a human in vitro model. This study shed light on the structural restrains of new sugar oximes designed to reach the central nervous system through the glucose transporter located at the blood–brain barrier

Coexistence des mondes ruraux et des agricultures

Bien que dans le monde la population urbaine soit devenue majoritaire (54 % en 2015), il n’y a jamais eu autant de ruraux qu’aujourd’hui (3,4 milliards en 2015) d’après la Banque mondiale. La population rurale devient minoritaire parce que le nombre des urbains augmente beaucoup plus vite. Cette civilisation urbaine croissante et dominante confinerait-elle le rural à la marge du monde ? Non. Les questions alimentaires, en particulier celles de l’alimentation des villes, les imbrications de plus en plus complexes entre les systèmes de revenus de ménages s’appuyant sur des membres et des activités éclatés dans l’espace et dans le temps, montrent combien mondes ruraux et mondes urbains sont étroitement associés et liés à de nombreuses échelles… [En savoir +

Devenirs de(s) villes nouvelles dans les Suds

Au fil du temps, le modèle ville nouvelle s’est diffusé sur l’ensemble des continents, dans une variété de contextes territoriaux : Chine, Inde, Kazakhstan, Côte d’Ivoire, Nigeria, Myanmar, Venezuela, Algérie, Maroc, Égypte, Émirats arabes unis, Russie, Angola, Corée du Sud, Pologne, etc. La liste, non-exhaustive – il faudrait plus d’une page pour énumérer les seules centaines de projets chinois –, est représentative d’une forte circulation du modèle à l’échelle mondiale : autrement dit, d’une mondialisation de la new town à travers les politiques et les pratiques professionnelles d’aménagement du territoire et d’urbanisme. [En savoir +