Évaluation de la gène et système de coordination des travaux de voirie

Les travaux sur la voirie urbaine dans la Communauté Urbaine de Lyon sont soumis, depuis mars 1978, à une procédure de coordination visant à synchroniser les ouvertures de chantiers. La gestion des autorisations de travaux, la commande des produits de réfection définitive et leur facturation aux concessionnaires à l'origine des travaux sont automatisées, dans le cadre du système Asphalte. Cette étude tente une analyse rétrospective sur un échantillon de déclarations, pour montrer la nature et l'évolution de ces interventions. En particulier, elle cherche à mettre en évidence la gène provoquée par ces travaux au niveau de l'utilisation de la voirie (emprises dans l'espace et dans le temps). Cette approche conduit à s'interroger sur le principe d'une coordination élargie à tous les " utilisateurs " de la voirie, notamment le service Circulation pour la régularisation du trafic. Dans ce cadre, le système actuel s'avère inadapté : les bases d'un nouveau système sont rapidement décrites, ainsi que les indicateurs nécessaires au calcul de la gène (indisponibilité, sensibilité à l'environnement, concentration, évolution,...), selon une méthode d'analyse de la nature des chantiers par opérations élémentaires

GM-CSF induces noninflammatory proliferation of microglia and disturbs electrical neuronal network rhythms in situ

Background!#!The granulocyte-macrophage colony-stimulating factor (GM-CSF) (or CSF-2) is involved in myeloid cell growth and differentiation, and, possibly, a major mediator of inflammation in body tissues. The role of GM-CSF in the activation of microglia (CNS resident macrophages) and the consequent impacts on neuronal survival, excitability, and synaptic transmission are widely unknown, however. Here, we focused on electrical neuronal network rhythms in the gamma frequency band (30-70 Hz). Gamma oscillations are fundamental to higher brain functions, such as perception, attention, and memory, and they are exquisitely sensitive to metabolic and oxidative stress.!##!Methods!#!We explored the effects of chronic GM-CSF exposure (72 h) on microglia in male rat organotypic hippocampal slice cultures (in situ), i.e., postnatal cortex tissue lacking leukocyte invasion (adaptive immunity). We applied extracellular electrophysiological recordings of local field potential, immunohistochemistry, design-based stereology, biochemical analysis, and pharmacological ablation of microglia.!##!Results!#!GM-CSF triggered substantial proliferation of microglia (microgliosis). By contrast, the release of proinflammatory cytokines (IL-6, TNF-α) and nitric oxide, the hippocampal cytoarchitecture as well as the morphology of parvalbumin-positive inhibitory interneurons were unaffected. Notably, GM-CSF induced concentration-dependent, long-lasting disturbances of gamma oscillations, such as slowing (beta frequency band) and neural burst firing (hyperexcitability), which were not mimicked by the T lymphocyte cytokine IL-17. These disturbances were attenuated by depletion of the microglial cell population with liposome-encapsulated clodronate. In contrast to priming with the cytokine IFN-γ (type II interferon), GM-CSF did not cause inflammatory neurodegeneration when paired with the TLR4 ligand LPS.!##!Conclusions!#!GM-CSF has a unique role in the activation of microglia, including the potential to induce neuronal network dysfunction. These immunomodulatory properties might contribute to cognitive impairment and/or epileptic seizure development in disease featuring elevated GM-CSF levels, blood-brain barrier leakage, and/or T cell infiltration

Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

Intermittent fasting (IF) is a dietary intervention often used as an alternative to caloric restriction (CR) and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart

Antioxidant enzyme activities.

<p>Values are means ± SEM and were compared using <i>t</i> tests (n = 4 animals).</p><p>* p<0.05 vs AL. AL indicates <i>ad libitum</i> feeding, IF indicates intermittent fasting.</p><p>Antioxidant enzyme activities.</p

IF induces an increase in respiratory capacity in liver, without bioenergetic changes in other tissues.

<p>Oxygen consumption in isolated mitochondria from (A) brain, (B) heart, (C) skeletal muscle and (D) liver in the presence of 5 mM pyruvate plus 3 mM malate (A, B and D) or 2 mM glutamate plus 2 mM malate (C). State 3 was induced by the addition of 1 mM ADP and state 4 was achieved using 0.5 μg/mL oligomycin. The insert in Panel D represents respiratory control ratios (RCR), or state 3/state 4. Data represent averages ± SEM and were compared using <i>t</i> tests (n = 4–6 animals). * p<0.05 vs AL in the same respiratory state.</p

IF changes oxidative damage to biomolecules in a tissue-specific manner.

<p>(A) Carbonyl signals were quantified as described in Materials and Methods. (B) Malondaldehyde (MDA) levels were measured by HPLC as described in Materials and Methods. (C) Representative dot blots of NO₂-tyr signals. (D) Average densitometric results for the dot blots presented in C. Data represent averages ± SEM and were compared using <i>t</i> tests (n = 4–5 animals). * p<0.05, ** p<0.01 vs AL.</p

IF promotes enhanced electron transport capacity in the liver.

<p>Oxygen consumption in isolated mitochondria from livers in the presence of (A) 1 mM succinate plus 1 μM rotenone or (B) 200 μM TMPD plus 2 mM ascorbate. State 3 and state 4 were induced by ADP and oligomycin as described for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120413#pone.0120413.g002" target="_blank">Fig. 2</a>. (C) COX-IV and NRF-1 levels measured as described in Materials and Methods. (D) Liver citrate synthase activity, determined as described in Materials and Methods. Data represent averages ± SEM and were compared using <i>t</i> tests (4–6 animals). * p<0.05, ** p<0.01 vs AL.</p

Reactive oxygen species production is not significantly altered by IF.

<p>(A) H₂O₂ release by isolated mitochondria in the presence of 1 mM ADP (state 3) and 5 mM pyruvate plus 3 mM malate (brain, heart and liver) or 2 mM glutamate plus 2 mM malate (skeletal muscle). (B) Ratio between H₂O₂ production and O₂ consumption by isolated mitochondria under the same conditions as panel A. Data represent averages ± SEM and were compared using <i>t</i> tests (n = 4–6 animals).</p

Intermittent fasting promotes lower body mass related to a mild reduction in caloric intake and lower energy conversion efficiency.

<p>(A) Average body weight per cage in (●) AL and (☐) IF animals after one month of treatment. (B) Cumulative food intake over one month of treatment. (C) Energy conversion efficiency. Data represent averages ± SEM and were compared using <i>t</i> tests (n = 7 cages). ** p<0.01 vs AL. AL indicates <i>ad libitum</i> feeding, IF indicates intermittent fasting.</p