Stretch-Activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries

In intrapulmonary artery (IPA), endothelial cells (EC) respond to mechanical stimuli by releasing vasoactive factors to set the vascular tone. Piezo1, a stretch-activated calcium permeable channel is a sensor of mechanical stress in EC. The present study was undertaken to investigate the implication of Piezo1 in the endothelium-dependent regulation of IPA tone and its potential involvement in pulmonary hypertension, the main disease of this circulation. IPA tone was quantified by means of a myograph in control Piezo1+/+ mouse and in mouse lacking endothelial Piezo1 (EC-Piezo1-/-). Endothelial intracellular calcium concentration ([Ca2+]i) and nitric oxide (NO) production were measured, in mouse or human EC, with fluo-4 and DAF-fm probes, respectively. Immunofluorescence labeling and patch-clamp experiments revealed the presence of Piezo1 channels in EC. Yoda1, a Piezo1 agonist, induced an endothelium-dependent relaxation that was significantly reduced in pulmonary arteries in EC-Piezo1-/- compared to Piezo1+/+ mouse. Yoda1 as well as mechanical stimulation (by osmotic stress) increased [Ca2+]i in mouse or human EC. Consequently, both stimuli increased the production of NO. NO and [Ca2+]i increases were reduced in EC from Piezo1-/- mouse or in the presence of Piezo1 inhibitors. Furthermore, deletion of Piezo1 increased alpha-adrenergic mediated contraction. Finally, in chronically hypoxic mice, a model of pulmonary hypertension, Piezo1 still mediated arterial relaxation and deletion of this channel did not impair the development of the disease. The present study thus demonstrates that endothelial Piezo1 contributes to intrapulmonary vascular relaxation by controlling endothelial [Ca2+]i and NO production and that this effect is still present in pulmonary hypertension

Innovativeness in British and French construction: the evidence from Transmanche-Link

This paper addresses the 'innovativeness' (the extent to which the design of the organization facilitates or inhibits innovation) of French and British project organizations. Following a review of the literature on organization design and innovativeness, data from a comparative organizational assessment of the British and French approaches to managing the Channel Tunnel construction project by Transmanche-Link are presented. These show that the British approach could well have less capacity for innovation than the French. The available evidence on the relative levels of innovation on the two sides of the Channel Tunnel are reviewed, showing that the predicted effects are found.French Construction British Construction Channel Tunnel Major Projects Construction Innovation,

: Préface de J. Lang

International audienceUn des leaders mondiaux de l’industrie pharmaceutique vient de consacrer plus d’un milliard de francs suisses à la construction d’un centre de recherche scientifique à Bâle. Il a notamment fait appel aux architectes les plus réputés qui ont proposé des projets très ambitieux. De même, plusieurs œuvres d’art ont été acquises pour être disposées sur le site. L’idée est simple : associer création scientifique et artistique, création de connaissances situées et de valeur. La notion centrale de création renvoie à diverses formes organisationnelles originales supposant l’expression d’interactions nouvelles entre des acteurs jadis catalogués comme ingénieurs, gestionnaires ou encore artistes. Si le processus de décloisonnement observé suscite de nombreux questionnements dans les disciplines de gestion, d’économie ou de sociologie, il importe de mieux appréhender sa mise en œuvre, ses effets ainsi que les modalités de son évaluation. Une illustration renouvelée des logiques dédiées à l’action collective est proposée dans cet ouvrage à partir d’une sélection de communications scientifiques interdisciplinaires présentées lors du quatrième colloque Métamorphose des organisations