PLUMES: Pression Littorale Urbaine : Modélisation, Environnement, Simulation

Le projet porte sur la pression urbaine qui s'exerce sur le littoral méditerranéen, et tout particulièrement sur celui de la région PACA. Or, si le terme " pression ", est systématiquement invoqué dans les diagnostics territoriaux et les analyses prospectives, sa définition précise est rarement donnée. D'une part, ses manifestations et ses impacts sont davantage étudiés que le processus en lui-même, d'autre part, le phénomène est généralement abordé à une seule échelle. L'optique est ici différente. L'attention est focalisée sur les mécanismes spatiaux qui induisent la pression, qui jouent à différentes échelles et se combinent en chaque lieu. La démarche est multi-scalaire, spatiale et prospective. L'objectif final est double, produire un indicateur composite de la pression littorale urbaine, et estimer au moyen de modèles et de simulations spatiales, la pression urbaine future. Le champ d'étude est une zone de forme rectangulaire, s'étendant de Fos à Toulon, et vers l'intérieur, du trait de côte à la région aixoise. Les analyses sont menées à l'échelle communale et infra-communale, sur un maillage de 200m x 200m. La recherche s'organise en trois grands volets : - Détermination d'un indice de pression urbaine potentielle, calculé pour chaque commune, puis attribué à chaque maille. - Quantification des changements d'occupation du sol et de leurs déterminants spatiaux, sur le maillage retenu. Puis modélisation par automate cellulaire, de la dynamique d'occupation du sol, dont la diffusion de l'habitat. - Mesure de l'incidence des attributs paysagers sur l'artificialisation, à l'échelle infra-communale, dans deux sous-ensembles littoraux. Élaboration d'un protocole de détection des zones de pression potentielle

The Amyotrophic Lateral Sclerosis M114T PFN1 Mutation Deregulates Alternative Autophagy Pathways and Mitochondrial Homeostasis

International audienceMutations in profilin 1 (PFN1) have been identified in rare familial cases of Amyotrophic Lateral Sclerosis (ALS). PFN1 is involved in multiple pathways that could intervene in ALS pathology. However, the specific pathogenic role of PFN1 mutations in ALS is still not fully understood. We hypothesized that PFN1 could play a role in regulating autophagy pathways and that PFN1 mutations could disrupt this function. We used patient cells (lymphoblasts) or tissue (post-mortem) carrying PFN1 mutations (M114T and E117G), and designed experimental models expressing wild-type or mutant PFN1 (cell lines and novel PFN1 mice established by lentiviral transgenesis) to study the effects of PFN1 mutations on autophagic pathway markers. We observed no accumulation of PFN1 in the spinal cord of one E117G mutation carrier. Moreover, in patient lymphoblasts and transfected cell lines, the M114T mutant PFN1 protein was unstable and deregulated the RAB9-mediated alternative autophagy pathway involved in the clearance of damaged mitochondria. In vivo, motor neurons expressing M114T mutant PFN1 showed mitochondrial abnormalities. Our results demonstrate that the M114T PFN1 mutation is more deleterious than the E117G variant in patient cells and experimental models and suggest a role for the RAB9-dependent autophagic pathway in ALS

The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation by cyclic AMP (cAMP). Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR gene mutation, and sweat chloride concentrations close to normal values. In vivo demonstration of abnormal CFTR protein function would be an important diagnostic aid in this situation. Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening. METHODS/DESIGN: We adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na(+)) transport in response to the Na(+ )channel inhibitor amiloride, and CFTR-mediated chloride (Cl(-)) secretion in response to isoproterenol, a β-agonist in a Cl(- )free solution. The study will include 20 children with CF and 20 healthy control children. CF children will be included only if they carry 2 CF-causing mutations in the CFTR gene or have sweat chloride concentrations > 60 mEq/L or both. The healthy children will be recruited among the siblings of the CF patients, after verification that they do not carry the familial mutation. DISCUSSION: A preliminary study of 3 adult control subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling

C9ORF72 knockdown triggers FTD-like symptoms and cell pathology in mice

The GGGGCC intronic repeat expansion within C9ORF72 is the most common genetic cause of ALS and FTD. This mutation results in toxic gain of function through accumulation of expanded RNA foci and aggregation of abnormally translated dipeptide repeat proteins, as well as loss of function due to impaired transcription of C9ORF72. A number of in vivo and in vitro models of gain and loss of function effects have suggested that both mechanisms synergize to cause the disease. However, the contribution of the loss of function mechanism remains poorly understood. We have generated C9ORF72 knockdown mice to mimic C9-FTD/ALS patients haploinsufficiency and investigate the role of this loss of function in the pathogenesis. We found that decreasing C9ORF72 leads to anomalies of the autophagy/lysosomal pathway, cytoplasmic accumulation of TDP-43 and decreased synaptic density in the cortex. Knockdown mice also developed FTD-like behavioral deficits and mild motor phenotypes at a later stage. These findings show that C9ORF72 partial loss of function contributes to the damaging events leading to C9-FTD/ALS

Supernatant from Bifidobacterium Differentially Modulates Transduction Signaling Pathways for Biological Functions of Human Dendritic Cells

International audienceBACKGROUND:Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn) could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen-activated protein kinases (MAPK), glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K) pathways on biological functions of human monocyte-derived DCs treated with BbC50sn.METHODOLOGY/PRINCIPAL FINDINGS:DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS) or Zymosan, with or without specific inhibitors of p38MAPK (SB203580), ERK (PD98059), PI3K (LY294002) and GSK3 (SB216763). We found that 1) the PI3K pathway was positively involved in the prolonged DC survival induced by BbC50sn, LPS and Zymosan in contrast to p38MAPK and GSK3 which negatively regulated DC survival; 2) p38MAPK and PI3K were positively involved in DC maturation, in contrast to ERK and GSK3 which negatively regulated DC maturation; 3) ERK and PI3K were positively involved in DC-IL-10 production, in contrast to GSK3 that was positively involved in DC-IL-12 production whereas p38MAPK was positively involved in both; 4) BbC50sn induced a PI3K/Akt phosphorylation similar to Zymosan and a p38MAPK phosphorylation similar to LPS.CONCLUSION/SIGNIFICANCE:We report for the first time that a fermentation product of a bifidobacteria can differentially activate MAPK, GSK3 and PI3K in order to modulate DC biological functions. These results give new insights on the fine-tuned balance between the maintenance of normal mucosal homeostasis to commensal and probiotic bacteria and the specific inflammatory immune responses to pathogen bacteria

Facteurs de risque cardiovasculaire, troubles de l’érection et dysfonction endothéliale

L’érection est un événement physiologique complexe qui, à la suite d’une stimulation sexuelle activant le système nerveux autonome, central et périphérique, fait intervenir plusieurs mécanismes endothélium-dépendants pour permettre la relaxation du muscle lisse des corps caverneux. La fonction endothéliale joue un rôle clé dans la physiologie locale de l’érection. La physiopathologie de l’insuffisance érectile (IE) suggère un lien étroit entre maladies cardiovasculaires et IE. Des données épidémiologiques et expérimentales concordantes suggèrent même que l’IE et la dysfonction endothéliale qui lui est souvent associée pourraient constituer un nouveau marqueur du risque cardiovasculaire. Ce concept devrait favoriser l’émergence de nouvelles stratégies thérapeutiques

Surveillance des bactériémies nosocomiales à partir du laboratoire de bactériologie dans le Groupe hospitalier Lariboisière - Fernand Widal d'octobre à décembre 1998

PARIS-BIUP (751062107) / SudocSudocFranceF