200 research outputs found
ABC1, an ATP binding cassette transporter required for phagocytosis of apoptotic cells, generates a regulated anion flux after expression in Xenopus laevis oocytes.
Pharmacological therapy for cystic fibrosis: From bench to bedside
AbstractWith knowledge of the molecular behaviour of the cystic fibrosis transmembrane conductance regulator (CFTR), its physiological role and dysfunction in cystic fibrosis (CF), therapeutic strategies are now being developed that target the root cause of CF rather than disease symptoms. Here, we review progress towards the development of rational new therapies for CF. We highlight the discovery of small molecules that rescue the cell surface expression and defective channel gating of CF mutants, termed CFTR correctors and CFTR potentiators, respectively. We draw attention to alternative approaches to restore epithelial ion transport to CF epithelia, including inhibitors of the epithelial Na+ channel (ENaC) and activators of the Ca2+-activated Cl− channel TMEM16A. The expertise required to translate small molecules identified in the laboratory to drugs for CF patients depends on our ability to coordinate drug development at an international level and our ability to provide pertinent biological information using suitable disease models
Predicting CFTR activity with front-runner cystic fibrosis drugs
[Commentary] DOI of original article: http://dx.doi.org/10.1016/j.ebiom.2014.12.005International audienc
Poésies de F. Malherbe : accompagnées du Commentaire d'André Chénier (Nouv. éd.) / nouvelle édition, contenant la vie de Malherbe par Racan, des extraits de Tallemant des Réaux, de Balzac, etc., par L. Becq de Fouquières
Comprend : Vie de Malherb
MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells.
Chronic lung inflammation in cystic fibrosis (CF) is specifically characterized by predominant endobronchial neutrophil infiltrates, colonization by Pseudomonas aeruginosa, and elevated levels of cytokines and chemokines, first of all IL-8. The extensive inflammatory process in CF lungs is the basis of progressive tissue damage and is largely considered detrimental, making antiinflammatory approaches a relevant therapeutic target. This neutrophil-dominated inflammation seems to be related to an excessive proinflammatory signaling, originating from the same surface epithelial cells expressing the defective CF transmembrane conductance regulator (CFTR) protein, although the underlying mechanisms have not been completely elucidated. To investigate the relationship between defective CFTR and the inflammatory response to P. aeruginosa in CF airway cells, we studied the effect of the DeltaF508 CFTR corrector, benzo(c)quinolizinium (MPB)-07 (Dormer et al., J Cell Science 2001;114:4073-4081). CF bronchial epithelial IB3-1 and CuFi-1 cells overproduced the inflammatory molecules, IL-8 and intercellular adhesion molecule (ICAM)-1, in response to P. aeruginosa, compared with the wild-type, CFTR-expressing bronchial cells, S9, and NuLi-1 cells. In both IB3-1 and CuFi-1 cells, the corrector MPB-07 dramatically reduces the IL-8 and ICAM-1 mRNA expression elicited by P. aeruginosa infection. Correction of CFTR-dependent Cl- efflux was confirmed in MPB-07-treated IB3-1 and CuFi-1 cells. In conclusion, the DeltaF508 CFTR corrector MPB-07 produces an antiinflammatory effect in CF bronchial cells exposed to P. aeruginosa in vitro
MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells
Les arts poétiques en France au XVIIIe siècle
L'auteur définit les positions fondamentales de l'esthétique de Boileau comme «ouverture» et négation du système normatif (néoaristotélicien). L'incompréhension de cette esthétique et sa confusion avec une poétique normative à la La Harpe aboutirait à une diffamation du Stendhal «classiciste» et à une appréciation erronée de sa production de (fragments de) tragédies, comédies, épopées, considérée comme «ratée», et de sa production de «romans» et «contes» comme libération de la contrainte de l'esthétique classique. Or, Stendhal ne cessera jamais d'adhérer à l'esthétique innovatrice de Boileau, qui, unie à l'esthétique shakespearienne-cervantine, aboutit à la production de «textes fleuves» auxquels on a donné le nom de romans.The author regards the fundamental tenets of Boileau's aesthetic as a répudiation of the neo-Aristotelean normative System. A misunderstanding of this aesthetic and its misidentification as normative poetics by La Harpe conduce to a false vision of Stendhal as both a failed classicist (as writer of tragic, comic and epic fragments) and a successful creator of "novels" and "taies" (and as such delivered from the shackles of classical aesthetics). In fact, Stendhal never ceased to adhere to Boileau's innovative aesthetic. Combined with the aesthetics of Shakespeare and Cervantes, it leads him to produce the "textes fleuves" to which the name of novels has been given
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