Effets d un polyphénol naturel, le Resvératrol, dans des lignées cellulaires exprimant la protéine CFTR (vers une nouvelle piste thérapeutique de la mucoviscidose ?)

La mucoviscidose est la plus fréquente des maladies génétiques potentiellement létales dans la population caucasienne. La mutation la plus fréquente est une délétion de Phenylalanine en position 508, qui aboutit à une protéine fonctionnelle mais retenue dans le réticulum et rapidement dégradée. Une piste thérapeutique consiste donc à rechercher les possibilités d adressage de delF508CFTR à la membrane. Les travaux réalisés au cours de ma thèse ont permis d étudier l effet de dérivés oestrogéniques (en particulier le dérivé naturel 17 beta oestradiol et un phyto-oestrogène, le Resvératrol) sur l expression et la localisation de CFTR. L analyse de l expression (protéine et ARNm) sur différentes lignées cellulaires à CFTR normale (MDCK) ou mutée delF508 (CFPAC) a montré une augmentation de l expression de CFTR dans les cellules traitées avec le Resveratrol et l Estradiol. Nous avons montré également la restauration d un transport anionique AMPc-dépendant dans les cellules CFPAC après traitement, suggérant une correction de la fonction de delF508CFTR. Un adressage de cette protéine à la membrane a été confirmé par immunocytochimie sur ces cellules, avec une localisation péri-membranaire de delF508CFTR dans les cellules traitées.Ces résultats nous ont mené à conduire des expériences complémentaires d une part sur le mécanisme d action de ce phytoestrogène et d autre part à tester l effet du Resveratrol in vivo par mise au point d un protocole de traitement de souris delF508/delF508 avec Resveratrol. Les résultats préliminaires sont prometteurs. Dans leur ensemble, ces résultats nous permettent de suggérer une correction de la mutation delF508 avec le Resveratrol.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Evolution and Functional Characterization of the RH50 Gene from the Ammonia-Oxidizing Bacterium Nitrosomonas europaea▿ †

The family of ammonia and ammonium channel proteins comprises the Amt proteins, which are present in all three domains of life with the notable exception of vertebrates, and the homologous Rh proteins (Rh50 and Rh30) that have been described thus far only in eukaryotes. The existence of an RH50 gene in bacteria was first revealed by the genome sequencing of the ammonia-oxidizing bacterium Nitrosomonas europaea. Here we have used a phylogenetic approach to study the evolution of the N. europaea RH50 gene, and we show that this gene, probably as a component of an integron cassette, has been transferred to the N. europaea genome by horizontal gene transfer. In addition, by functionally characterizing the Rh50Ne protein and the corresponding knockout mutant, we determined that NeRh50 can mediate ammonium uptake. The RH50Ne gene may thus have replaced functionally the AMT gene, which is missing in the genome of N. europaea and may be regarded as a case of nonorthologous gene displacement

Comparative Evaluation of Biogas Yield and Physicochemical Properties of Three-Phase and Traditional Olive Oil Mill Wastes – The Most Suitable Choice for Efficient Anaerobic Digestion

Olive oil mill waste is characterized by its high organic matter content, especially fatty acids, polyphenols, sugars, and proteins. These nutrients can be used as a source of energy for biogas production. However, olive oil mill waste can also contain heavy metals such as lead, cadmium, copper, and zinc that can be absorbed by plants. In addition, very high concentrations of heavy metals can also inhibit the anaerobic digestion process by affecting the methanogenic bacteria involved in biogas production The aim of this research is to determine the composition of solid and liquid rejections from traditional and continuous three-phase crushing systems, by analyzing samples from different oil mills in the eastern region of Morocco. We also applied the technology of anaerobic digestion of solid and liquid waste forms of oil mills, to make a link between the biogas yield and the physicochemical characteristics of these wastes. The results suggest that traditional oil mill wastewater (Discontinuous OMWW) has high organic matter, nutrients, and heavy metals content and a low concentration of phenolic compounds, which can increase its biogas production potential with a production of 10.02 Nml/ g VS, while three-phase wastewater (Continuous OMWW) has limited biogas production potential (3.83 Nml/ g VS) due to the low organic matter and nutrients content, and high concentration of phenolic compounds. Three-phase olive pomace (Continuous OMSW) has a higher biogas production (9.28 Nml/ g VS) than traditional olive pomace (Discontinuous OMSW) with 5.91 Nml/ g VS. In fact, the lower content of phenolic compounds and volatile fatty acids favors their anaerobic digestion and improves their biogas production. In conclusion, the selection of the type of waste adapted for biogas production must be based on the physicochemical and microbiological characteristics of these wastes

c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes.

International audienceThe mechanisms of podocyte disorders in cases of idiopathic nephrotic syndrome (INS) are complex and remain incompletely elucidated. The abnormal regulation of NF-κB may play a key role in the pathophysiology of these podocyte diseases, but at present, NF-κB has not been thoroughly investigated. In this study, we report that induction of c-mip in podocytes of patients with INS is associated with a down-regulation of RelA, a potent antiapoptotic factor that belongs to the NF-κB family. Overexpression of c-mip in differentiated podocytes promotes apoptosis by inducing caspase-3 activity and up-regulating the proapoptotic protein Bax, whereas the overall levels of the antiapoptotic protein Bcl-2 was concomitantly decreased. The associated overexpression of RelA prevented the proapoptotic effects of c-mip. In addition, the targeted induction of c-mip in podocytes in vivo inhibited the expression of the RelA protein and increased the Bax/Bcl-2 ratio. The expression of both c-mip and active caspase-3 increased in focal and segmental glomerulosclerosis biopsies, and both proteins displayed a close spatial relationship. These results suggest that alterations in NF-κB activity might result from the up-regulation of c-mip and are likely to contribute to podocyte disorders in cases of INS

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy