Default in plasma and intestinal IgA responses during acute infection by Simian Immunodeficiency Virus.

International audienceABSTRACT: BACKGROUND: Conflicting results regarding changes in mucosal IgA production or in the proportions of IgA plasma cells in the small and large intestines during HIV-infection have been previously reported. Except in individuals repeatedly exposed to HIV-1 but yet remaining uninfected, HIV-specific IgA are frequently absent in mucosal secretions from HIV-infected patients. However, little is known about the organization and functionality of mucosal B-cell follicles in acute HIV/SIV infection during which a T-dependent IgA response should have been initiated. In the present study, we evaluated changes in B-cell and T-cell subsets as well as the extent of apoptosis and class-specific plasma cells in Peyer's Patches, isolated lymphoid follicles, and lamina propria. Plasma levels of IgA, BAFF and APRIL were also determined. RESULTS: Plasma IgA level was reduced by 46 percent by 28 dpi and no IgA plasma cells were found within germinal centers of Peyer's Patches and isolated lymphoid follicles. This lack of a T-dependent IgA response occurs although germinal centers remained functional with no sign of follicular damage, but a prolonged survival of follicular CD4+ T-cells and normal generation of IgG plasma cells is observed. Whereas the average plasma BAFF level was increased by 4.5-fold and total plasma cells were 1.7 to 1.9-fold more numerous in the lamina propria, the relative proportion of IgA plasma cells in this effector site was reduced by 19 percent (duodemun) to 35 percent (Ileum) at 28 dpi. CONCLUSION: Our data provide evidence that SIV is unable to initiate a T-dependent IgA response during the acute phase of infection and favors the production of IgG (ileum) or IgM (duodenum) plasma cells at the expense of IgA plasma cells. Therefore, an early and generalized default in IgA production takes place during the acute of phase of HIV/SIV infection, which might impair not only a virus-specific antibody response but also IgA responses to other pathogens and vaccines as well. Understanding the mechanisms that impair IgA production during acute HIV/SIV infection is crucial to improve virus-specific response in mucosa and control microbial translocation

Leptin Controls Parasympathetic Wiring of the Pancreas during Embryonic Life

The autonomic nervous system plays a critical role in glucose metabolism through both its sympathetic and parasympathetic branches, but the mechanisms that underlie the development of the autonomic innervation of the pancreas remain poorly understood. Here, we report that cholinergic innervation of pancreatic islets develops during mid-gestation under the influence of leptin. Leptin-deficient mice display a greater cholinergic innervation of pancreatic islets beginning in embryonic life, and this increase persists into adulthood. Remarkably, a single intracerebroventricular injection of leptin in embryos caused a permanent reduction in parasympathetic innervation of pancreatic β cells and long-term impairments in glucose homeostasis. These developmental effects of leptin involve a direct inhibitory effect on the outgrowth of preganglionic axons from the hindbrain. These studies reveal an unanticipated regulatory role of leptin on the parasympathetic nervous system during embryonic development and may have important implications for our understanding of the early mechanisms that contribute to diabetes

Assimilation de données de télédétection pour la mise à jour de modèles de culture

National audienc

Using a coupled canopy functioning and SVAT model in the ReSeDA experiment: Assimilation of SPOT/HRV observations into the model

National audienc

Development of Alternative Models to In Vivo Animal Human Experiments for Regional Aerosol Deposition

International audienc

MicroRNA Targeting of CoREST controls polarization of migrating cortical neurons

SummaryThe migration of cortical projection neurons is a multistep process characterized by dynamic cell shape remodeling. The molecular basis of these changes remains elusive, and the present work describes how microRNAs (miRNAs) control neuronal polarization during radial migration. We show that miR-22 and miR-124 are expressed in the cortical wall where they target components of the CoREST/REST transcriptional repressor complex, thereby regulating doublecortin transcription in migrating neurons. This molecular pathway underlies radial migration by promoting dynamic multipolar-bipolar cell conversion at early phases of migration, and later stabilization of cell polarity to support locomotion on radial glia fibers. Thus, our work emphasizes key roles of some miRNAs that control radial migration during cerebral corticogenesis

Périphéries gauche et droite

International audienceThis article describes a pilot French/English contrastive study of some peripheral expressions. A “peripheral expression” is understood as one which occurs at the beginning (“left-peripheral” (LP)) or at the end (“right-peripheral” (RP)) of an utterance which acts as its host and over which it has scope. (The nature of the formal link between the peripheral expression and its host is left open for the purposes of this article.) These peripheral slots are prime sites for the expression of speaker stance towards the idea expressed by the host unit, and for the expression of coherence relations between the idea in the host clause and the previous idea(s). They harbour a wide range of adverbial connectors, discourse particles and comment clauses.The pilot study establishes a basic framework, within a broadly functional approach, for the identification and analysis of peripherals that can serve for contrastive study of French and English. Within the framework, the study has two main goals. One is to test whether and how, for French and/or for English expressions that can occur at either periphery, position correlates with other features of the expressions in context: function, prosodic pattern, information status and syntactic status of the host (and potentially other features of the co-text); in particular, the aim is to discover, if position is not random, what the main motivations appear to be in each case. The other main goal, and the focus of this article, is contrastive: to examine the frequencies and distributions, based on the feature analysis, of comparable peripheral expressions across French and English, to identify what generalizations, if any, can be made across the two languages. Interspeaker variation is also monitored. The primary variables here are position (right vs. left) and language (French vs. English).Recent interest in the peripheries has focused on four main issues: defining the peripheries, including devising a model of syntax that adequately accounts for peripheral expressions; determining the order of expressions, where a periphery contains several; tracing the emergence of peripheral expressions through language change; and identifying potential correlations between position and function.The first two issues have been addressed in formal linguistics, where a cartographic model of the syntactic structure of the periphery has been developed (e.g. Speas & Tenny 2003; Haegeman & Hill 2013; Rizzi & Cinque 2016). Functional and cognitive linguists until recently tended to ignore the syntactic status of peripheral elements like discourse particles and connectors, which were often claimed to be “outside” of syntax (e.g. Kaltenböck et al. 2016; Brinton 2017). Some scholars identify clause-initial pragmatic-marker “slots” (e.g. Aijmer 1996). Others posit a special “discourse grammar” distinct from “sentence grammar” (e.g. Heine et al. 2013, Fernandez Vest 2015). It has also been suggested, for English, that RP particles now constitute a formal paradigm (Haselow 2013).Overall, the third and fourth issues have received greater attention. Diachronically, in European languages investigated so far, RP appears to be a relatively recent development that can be viewed as “further grammaticalization” (almost all forms occurring at RP occur also, and occurred earlier, in other positions). The potentially different synchronic functions linked to LP and RP have mainly been investigated from the pragmatic and discourse-analytic perspectives. One widely-cited hypothesis is that the LP is specialized for subjectivity (speaker stance), while the RP is specialized for intersubjectivity (speaker-hearer relations) (e.g. Degand and Fagard 2011; Beeching and Detges 2014a). Subsequent work across languages has been inconclusive, providing moderate support for this hypothesis along with some counter-evidence (Traugott 2012). Where peripheral expressions are connective, it has been suggested for English that at RP their main function is retrospective connectivity (Haselow 2012), tying the host closely to the previous idea and/or modifying the modal or illocutionary force of the previous idea, while at LP they express interpropositional relations more loosely and can scope over longer stretches of discourse. But little attention has been paid to the role of particles at either periphery in signalling prominence relations and information structure, and relatively few studies have focused on prosodic features (v. Wichmann 2001; Bertrand and Chanet 2005; Dehé and Wichmann 2010; Romero Trillo 2018). Discourse particles, especially at LP, are often assumed to have “comma intonation”, but this assumption rests on insufficient evidence and contradictory claims are found. English final particles, it is claimed, are prosodically integrated (Haselow 2016).Although work in different language varieties has started to clarify some of these issues, few constrastive-linguistic studies have so far been carried out.For this article the peripheral expressions chosen were French alors and English then. Both expressions have developed from their lexical roots into modal adverbs and then discourse particles and/or connectives. Alors and then are both temporal adverbs that have developed very similar non-temporal polysemies. And, relevantly for this study, both now occur as discourse particles of various kinds at both the left and the right peripheries.This corpus-based study first describes a pilot methodology for the contrastive analysis. Data sources are comparable selections of dialogue from spoken-language corpora. Occurrences (and their co-text) are coded for position and on the four parameters listed above (function, prosody, information structure, syntax). The data set is too small for extrapolation, but the study suggests differences in frequency, distribution and usage across the two languages for the comparable genres. It also suggests increased divergence between alors and then for the more abstract and interactional uses. The results of this pilot study can be used to refine the approach in preparation for further work on peripheral expressions based on larger corpora.Cet article décrit une étude contrastive pilote de quatre expressions de périphérie, deux françaises et deux anglaises. S’entend par “expression périphérique” une expression positionnée en début (périphérie gauche (PG)) ou à la fin (périphérie droite (PD)) d’un énoncé sur lequel elle porte et qui fonctionne comme hôte. (Nous laissons de côté, dans le contexte de cet article, la nature exacte du lien formel entre l’expression périphérique et son hôte.) Ces positions périphériques sont des sites privilégiés pour l’expression de l’attitude du locuteur envers l’idée contenue dans l’unité hôte et pour l’expression de relations de cohérence entre cette idée et la précédente. Elles accueillent un éventail de connecteurs adverbiaux et de particules discursives.L’étude pilote propose un cadre, dans une approche fonctionnelle, pour l’identification et l’analyse d’éléments périphériques dans le contexte de la linguistique contrastive (français/anglais). Ensuite l’étude a deux buts principaux. Le premier consiste à vérifier, pour les expressions se positionnant en PG et en PD et dans leurs contextes, si des corrélations existent entre position et fonction, prosodie, structure informationnelle ou la syntaxe de l’hôte (et éventuellement d’autres paramètres du co-texte). Il s’agit d’explorer, si la position s’avère ne pas être aléatoire, les possibles motivations dans chaque cas. Le deuxième but, et le focus de l’article, consiste à analyser les fréquences et les distributions dans une perspective contrastive français/anglais, pour identifier des généralisations éventuelles sur les deux langues. La variation interlocuteur est également contrôlée. Les variables principales sont donc la position (droite vs. gauche) et la langue (français vs. anglais).La recherche récente sur les périphéries s’est focalisée sur quatre questions majeures : la définition des périphéries, y compris l’élaboration d’un modèle syntaxique capable de rendre compte des expressions périphériques ; la détermination de l’ordre des expressions périphériques au cas où un énoncé en accueille deux ou plus ; le traçage de l’évolution des expressions périphériques en diachronie ; et l’identification d’éventuelles corrélations entre position et fonction.Les deux premières questions ont surtout été abordées en linguistique formelle, où un modèle cartographique de la structure syntaxique de la périphérie a été développé (par ex. Speas & Tenny 2003 ; Haegeman & Hill 2013 ; Rizzi & Cinque 2016). Jusqu’à tout récemment le statut syntaxique des éléments périphériques, comme les particules discursives et les connecteurs adverbiaux, a été peu étudié dans la tradition fonctionnelle, ces éléments étant considérés comme “en dehors” de la syntaxe (par ex. Kaltenböck et al. 2016 ; Brinton 2017). Certains chercheurs néanmoins posent un créneau syntaxique spécifique aux particules discursives en début d’énoncé (par ex. Aijmer 1996) ; d’autres encore posent qu’une grammaire du discours, différenciée de la grammaire de la phrase, doit rendre compte des périphériques (par ex. Heine et al. 2013, Fernandez Vest 2015). D’aucuns suggèrent, pour l’anglais, que les particules à la PD constituent un paradigme formel (Haselow 2013).Ce sont les deux dernières questions qui ont capté plus d’attention. En diachronie, à en juger par les résultats d’études sur des langues européennes, la PD serait un développement assez récent qui peut être considéré comme une “grammaticalisation poussée”, la plupart des formes occupant la PD étant attestées avant à la PG. Les différentes fonctions éventuelles associées à la PG et la PD ont été abordées en pragmatique et analyse du discours. L’hypothèse est très citée que la PG accueille la subjectivité (l’attitude du locuteur) alors que la PD accueille l’intersubjectivité (les relations entre le locuteur et son interlocuteur) (par ex. Degand et Fagard 2011 ; Beeching et Detges 2014a). Des études sur différentes langues pourtant ont révélé quelques confirmations et quelques contre-exemples sans arriver à des conclusions solides (Traugott 2012). Pour les éléments périphériques dont la fonction est connective, il a été proposé qu’à la PD soit ils expriment une connectivité rétrospective très étroite entre l’hôte et l’idée précédente (Haselow 2012) soit ils modifient la modalité de celle-ci, tandis qu’à la PD ils expriment une connectivité moins étroite et peuvent porter sur plusieurs segments du discours. Peu d’études ont abordé le rôle des périphériques, que ce soit à gauche ou à droite, dans la prominence ou dans la structure informationnelle. Peu d’études ont abordé la prosodie (v. Wichmann 2001 ; Bertrand et Chanet 2005 ; Dehé et Wichmann 2010 ; Romero Trillo 2018). L’idée est souvent citée que les particules discursives, surtout à la PG, manifestent une “intonation de virgule”, mais cette supposition repose sur peu de données concrètes et elle a été remise en cause. Il a été proposé pour l’anglais qu’à la PD les périphériques manifestent une prosodie intégrée (Haselow 2016).Si des études sur des langues variées ont commencé à éclaircir beaucoup de ces questions, peu d’études ont adopté une perspective contrastive.Deux expressions ont été retenues pour cet article : alors pour le français et then pour l’anglais. Ces expressions ont en commun que de leurs origines lexicales elles se sont développées en adverbes modaux puis en particules discursives et/ou en connecteurs. Alors et then sont des adverbes temporels qui ont évolué dans le même sens vers des polysémies non temporelles. Plus pertinent pour cette étude est leur positionnement tant à la PG qu’à la PD en tant que particules discursives de divers types.Cette étude sur corpus commence par décrire la méthodologie pilote pour l’analyse contrastive. Les données proviennent d’échantillons de dialogue comparables pris dans des corpus oraux. Sont codées les positions des occurrences (et leurs co-textes) ainsi que les quatre paramètres cités ci-dessus (fonction, prosodie, structure informationnelle, syntaxe). Les résultats des analyses révèlent des différences de fréquence, de distribution et d’usage sur les deux langues pour le genre comparable. Ils pointent également une différenciation accrue entre alors et then pour les fonctions plus abstraites et interactionnelles. Les résultats de cette étude pilote nous servent pour affiner l’approche en vue d’une étude quantitative sur des expressions périphériques à base de corpus plus grands

Nicotine delivery from the refill liquid to the aerosol via high-power e-cigarette device

International audienceTo offer an enhanced and well-controlled nicotine delivery from the refill liquid to the aerosol is a key point to adequately satisfy nicotine cravings using electronic nicotine delivery systems (ENDS). A recent high-power ENDS, exhibiting higher aerosol nicotine delivery than older technologies, was used. The particle size distribution was measured using a cascade impactor. The effects of the refill liquid composition on the nicotine content of each size-fraction in the submicron range were investigated. Nicotine was quantified by liquid chromatography coupled with tandem mass spectrometry. Particle size distribution of the airborne refill liquid and the aerosol nicotine demonstrated that the nicotine is equally distributed in droplets regardless of their size. Results also proved that the nicotine concentration in aerosol was significantly lower compared to un-puffed refill liquid. A part of the nicotine may be left in the ENDS upon depletion, and consequently a portion of the nicotine may not be transferred to the user. Thus, new generation high-power ENDS associated with propylene glycol/vegetable glycerin (PG/VG) based solvent were very efficient to generate carrier-droplets containing nicotine molecules with a constant concentration. Findings highlighted that a portion of the nicotine in the refill liquid may not be transferred to the user