The Dichotomous Pattern of IL-12R and IL-23R Expression Elucidates the Role of IL-12 and IL-23 in Inflammation

IL-12 and IL-23 cytokines respectively drive Th1 and Th17 type responses. Yet, little is known regarding the biology of these receptors. As the IL-12 and IL-23 receptors share a common subunit, it has been assumed that these receptors are co-expressed. Surprisingly, we find that the expression of each of these receptors is restricted to specific cell types, in both mouse and human. Indeed, although IL-12Rβ2 is expressed by NK cells and a subset of γδ T cells, the expression of IL-23R is restricted to specific T cell subsets, a small number of B cells and innate lymphoid cells. By exploiting an IL-12- and IL-23-dependent mouse model of innate inflammation, we demonstrate an intricate interplay between IL-12Rβ2 NK cells and IL-23R innate lymphoid cells with respectively dominant roles in the regulation of systemic versus local inflammatory responses. Together, these findings support an unforeseen lineage-specific dichotomy in the in vivo role of both the IL-12 and IL-23 pathways in pathological inflammatory states, which may allow more accurate dissection of the roles of these receptors in chronic inflammatory diseases in humans

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

L’inégale répartition du pouvoir dans les communautés francophones minoritaires

Dans cet article, nous distinguons deux « étapes » au pouvoir francophone : la formulation de projets (qui relève de considérations sociales) et la mise en oeuvre de projets (considérations économiques). Nous concentrons davantage notre attention sur la dimension économique du pouvoir qui, selon nous, attire moins l’attention des chercheurs. Nos résultats dressent un portrait selon lequel les communautés francophones traditionnelles en situation minoritaire ont moins de moyens pour mener à bien leurs projets alors que les communautés francophones émergentes risquent d’orienter leurs ressources vers des dépenses qui ne concernent pas la francophonie. En conclusion, nous nous interrogeons sur les besoins spécifiques et sur la complémentarité des communautés francophones.In this paper, we distinguish two “steps” of Francophone power: project formulation (relating to social considerations) and project implementation (economic considerations). Our focus is on the economic dimension of power which, we believe, attracts less attention from researchers. Our results show that traditional Francophone communities have fewer resources to carry out their projects, while emerging Francophone communities might direct their resources toward expenses that do not concern the Francophonie. In conclusion, we discuss the specific and complementary needs of Francophone communities

Le modèle de mesure de la technologie expérimenté dans le secteur aéronautique

Le secteur dans son ensemble -- Intrants -- Procédés physiques -- Procédés physiques -- Procédés organisationnels -- Ressources humaines -- Extrants -- Les 3 sous-secteurs -- Ateliers d'usinage -- Les entreprises du domaine électrique -- Les autres entreprises

Des canadiens français aux québécois : se nommer à l’épreuve du territoire?

Le présent article propose une réflexion sur la territorialisation de l’identité au Québec. À partir d’un corpus de journaux parus au Québec de 1944 à 1970, il tente de déterminer si cette territorialisation s’est amorcée avant la Révolution tranquille, période où la plupart des auteurs situent l’origine du phénomène. Les termes désignant le territoire et ses habitants sont systématiquement recensés et analysés. L’article propose entre autres le concept de déprovincialisation pour expliquer le phénomène alors en cours, et situe son avènement, en fait, bien avant la Révolution tranquille. Il présente aussi des données inédites sur le moment du passage de Canadien français à Québécois (à la fois comme adjectif et comme nom), et cherche à déterminer si l’usage a varié au gré des évènements qui ont ponctué l’actualité pendant cette période importante de l’histoire du Québec.This article offers a reflection on the territorialization of identity in Quebec. Drawing from a corpus of newspapers published in Quebec from 1944 to 1970, it tries to determine whether this territorialization began before or rather during the Quiet Revolution, where most authors locate the origin of the phenomenon. For this, we systematically inventoried and analyzed the terms used to designate the territory and its inhabitants. The article proposes, among other things, the concept of “deprovincialization” to explain the phenomenon then underway and places its advent well before the Quiet Revolution. It also presents previously unpublished data on the moment of passage from French Canadian to Québécois (both as an adjective and as a noun) and seeks to determine whether usage has varied from one event to the next during this important period in the history of Quebec

Le modèle de mesure de la technologie expérimenté dans le secteur des fonderies

Questionnaire de l'évaluateur -- Modifications et renseignements sur le questionnaire relatifs au secteur de la fonderie -- Analyse des résultats -- Modifications et recommandations sur le questionnaire relatifs au secteur de la fonderie (après expérience) -- Mesure de la technologie -- Résultats sectoriels -- Cote technologique -- Profils sectoriels -- Histogrammes -- Statistiques générales du secteur -- Coefficients de corrélation des vecteurs pris deux à deux

Diriger en période de transformation /

Bibliogr.: p. 179-18

Reduced Fertility in Male Mice Deficient in the Zinc Metallopeptidase NL1

Members of the M13 family of zinc metalloendopeptidases have been shown to play critical roles in the metabolism of various neuropeptides and peptide hormones, and they have been identified as important therapeutic targets. Recently, a mouse NL1 protein, a novel member of the family, was identified and shown to be expressed mainly in the testis as a secreted protein. To define its physiological role(s), we used a gene targeting strategy to disrupt the endogenous murine Nl1 gene by homologous recombination and generate Nl1 mutant mice. The Nl1(−/−) mice were viable and developed normally, suggesting that zygotic expression of Nl1 is not required for development. However, Nl1(−/−) males produced smaller litters than their wild-type siblings, indicating specific male fertility problems. Reduced fertility may be explained by two impaired processes, decreased egg fertilization and perturbed early development of fertilized eggs. These two phenotypes did not result from gross anatomical modifications of the testis or from impaired spermatogenesis. Basic sperm parameters were also normal. Thus, our findings suggest that one of the roles of NL1 in mice is related to sperm function and that NL1 modulates the processes of fertilization and early embryonic development in vivo