Vers une gestion de la demande sur une nappe en accès libre : exploration des interactions ressource usages par les systèmes multi-agents : application à la nappe de Kairouan, Tunisie centrale

Pour enrayer la surexploitation des nappes en accès libre, une gestion de la demande en eau est de plus en plus préconisée. Jusqu'alors, la gestion des nappes a été étudiée par des modèles de fonctionnement du système physique, les usages étant modélisés simplement, sans tenir compte des comportements non marchands, des interactions locales entre usagers, et des investissements à long terme. Le présent travail, fondé sur le cas de la nappe de Kairouan, vise à tenir compte plus explicitement des comportements socio-économiques réels et à fournir un outil d'aide à la décision. Le modèle SINUSE repose ainsi sur l'hypothèse centrale d'importance des interactions locale sur la dynamique globale. Il représente des agents autonomes communiquant et agissant dans un environnement distribué et réactif. Après avoir permis de tester la validité de l'hypothèse centrale, les simulations sont consacrées à l'évaluation des impacts de certains outils techniques, économiques et réglementaires. Dans le contexte du modèle et parmi les scénarios testés, l'instauration d'un quota semble constituer la mesure la plus efficace pour limiter l'abaissement de la nappe et le coût social de l'intervention de gestion. Si les résultats des simulations doivent être interprétés avec prudence, SINUSE, en tant que formalisation conjointe des dynamiques les discussions entre chercheurs et acteurs sur la représentation du système et sur les effets de différentes interventions. (Résumé d'auteur

Gestion intégrée de l'eau au sein d'un bassin versant

L'objectif de ce papier est de montrer l'intérêt d'une modélisation pour explorer la gestion des nappes surexploitées, par une maîtrise de la demande. L'étude se base sur le cas de la nappe de Kairouan, en Tunisie Centrale. Considérée comme nécessaire dans un contexte de déséquilibre offre/demande, lorsque le développement de l'offre atteint ses limites, la gestion de la demande peut être mise en oeuvre grâce à plusieurs types d'outils, plus ou moins efficaces selon le contexte de l'intervention. La modélisation des interactions entre nappe et usages permet d'étudier les effets de ces interventions. Deux types de modèles sont utilisés, un simulateur agro-économique Olympe et un modèle multi-agents Sinuse, pour formaliser le système complexe nappe de Kairouan et ses usagers, explorer les liens entre ressource et usages à travers des simulations et étudier les évolutions du système sous diverses contraintes d'interventions. (Résumé auteur

Pseudo-acetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity

Tau is a microtubule-associated protein that is highly soluble and natively unfolded. Its dysfunction is involved in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD), where it aggregates within neurons. Deciphering the physiological and pathogenic roles of human Tau (hTau) is crucial to further understand the mechanisms leading to its dysfunction in vivo. We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo

Implicating Calpain in Tau-Mediated Toxicity In Vivo

Alzheimer's disease and other related neurodegenerative disorders known as tauopathies are characterized by the accumulation of abnormally phosphorylated and aggregated forms of the microtubule-associated protein tau. Several laboratories have identified a 17 kD proteolytic fragment of tau in degenerating neurons and in numerous cell culture models that is generated by calpain cleavage and speculated to contribute to tau toxicity. In the current study, we employed a Drosophila tauopathy model to investigate the importance of calpain-mediated tau proteolysis in contributing to tau neurotoxicity in an animal model of human neurodegenerative disease. We found that mutations that disrupted endogenous calpainA or calpainB activity in transgenic flies suppressed tau toxicity. Expression of a calpain-resistant form of tau in Drosophila revealed that mutating the putative calpain cleavage sites that produce the 17 kD fragment was sufficient to abrogate tau toxicity in vivo. Furthermore, we found significant toxicity in the fly retina associated with expression of only the 17 kD tau fragment. Collectively, our data implicate calpain-mediated proteolysis of tau as an important pathway mediating tau neurotoxicity in vivo

Understanding Human-Plasmodium falciparum Immune Interactions Uncovers the Immunological Role of Worms

BACKGROUND: Former studies have pointed to a monocyte-dependent effect of antibodies in protection against malaria and thereby to cytophilic antibodies IgG1 and IgG3, which trigger monocyte receptors. Field investigations have further documented that a switch from non-cytophilic to cytophilic classes of antimalarial antibodies was associated with protection. The hypothesis that the non-cytophilic isotype imbalance could be related to concomittant helminthic infections was supported by several interventions and case-control studies. METHODS AND FINDINGS: We investigated here the hypothesis that the delayed acquisition of immunity to malaria could be related to a worm-induced Th2 drive on antimalarial immune responses. IgG1 to IgG4 responses against 6 different parasite-derived antigens were analyzed in sera from 203 Senegalese children, half carrying intestinal worms, presenting 421 clinical malaria attacks over 51 months. Results show a significant correlation between the occurrence of malaria attacks, worm carriage (particularly that of hookworms) and a decrease in cytophilic IgG1 and IgG3 responses and an increase in non-cytophilic IgG4 response to the merozoite stage protein 3 (MSP3) vaccine candidate. CONCLUSION: The results confirm the association with protection of anti-MSP3 cytophilic responses, confirm in one additional setting that worms increase malaria morbidity and show a Th2 worm-driven pattern of anti-malarial immune responses. They document why large anthelminthic mass treatments may be worth being assessed as malaria control policies

Stable Mutated tau441 Transfected SH-SY5Y Cells as Screening Tool for Alzheimer’s Disease Drug Candidates

The role of hyperphosphorylation of the microtubule-associated protein tau in the pathological processes of several neurodegenerative diseases is becoming better understood. Consequently, development of new compounds capable of preventing tau hyperphosphorylation is an increasingly hot topic. For this reason, dependable in vitro and in vivo models that reflect tau hyperphosphorylation in human diseases are needed. In this study, we generated and validated an in vitro model appropriate to test potential curative and preventive compound effects on tau phosphorylation. For this purpose, a stably transfected SH-SY5Y cell line was constructed over-expressing mutant human tau441 (SH-SY5Y-TMHT441). Analyses of expression levels and tau phosphorylation status in untreated cells confirmed relevance to human diseases. Subsequently, the effect of different established kinase inhibitors on tau phosphorylation (e.g., residues Thr231, Thr181, and Ser396) was examined. It was shown with several methods including immunosorbent assays and mass spectrometry that the phosphorylation pattern of tau in SH-SY5Y-TMHT441 cells can be reliably modulated by these compounds, specifically targeting JNK, GSK-3, CDK1/5, and CK1. These four protein kinases are known to be involved in in vivo tau phosphorylation and are therefore authentic indicators for the suitability of this new cell culture model for tauopathies