Modulation of the c-Jun N-terminal kinase activity in the embryonic heart in response to anoxia-reoxygenation: involvement of the Ca2+ and mitoKATP channels

Whether the response of the fetal heart to ischemia-reperfusion is associated with activation of the c-Jun N-terminal kinase (JNK) pathway is not known. In contrast, involvement of the sarcolemmal L-type Ca2+ channel (LCC) and the mitochondrial KATP (mitoKATP) channel has been established. This work aimed at investigating the profile of JNK activity during anoxia-reoxygenation and its modulation by LCC and mitoKATP channel. Hearts isolated from 4-day-old chick embryos were submitted to anoxia (30min) and reoxygenation (60min). Using the kinase assay method, the profile of JNK activity in the ventricle was determined every 10min throughout anoxia-reoxygenation. Effects on JNK activity of the LCC blocker verapamil (10nM), the mitoKATP channel opener diazoxide (50μM) and the blocker 5-hydroxydecanoate (5-HD, 500μM), the mitochondrial Ca2+ uniporter (MCU) inhibitor Ru360 (10μM), and the antioxidant N-(2-mercaptopropionyl) glycine (MPG, 1mM) were determined. In untreated hearts, JNK activity was increased by 40% during anoxia and peaked fivefold relative to basal level after 30-40min reoxygenation. This peak value was reduced by half by diazoxide and was tripled by 5-HD. Furthermore, the 5-HD-mediated stimulation of JNK activity during reoxygenation was abolished by diazoxide, verapamil or Ru360. MPG had no effect on JNK activity, whatever the conditions. None of the tested pharmacological agents altered JNK activity under basal normoxic conditions. Thus, in the embryonic heart, JNK activity exhibits a characteristic pattern during anoxia and reoxygenation and the respective open-state of LCC, MCU and mitoKATP channel can be a major determinant of JNK activity in a ROS-independent manne

Design des levées de fonds pour la firme entrepreneuriale : Quand le crowdfunding co-investit avec les business angels

International audienceLe crowdfunding(CF)connaît un succès croissant. En France, les chiffres publiés par l’Association de Financement Participatif France1témoigne de ce succès. Par exemple, plus de 1,75 millions d’internautes ont participé à une opération de CF depuis la création des plateformes. On peut définir le crowdfundingcomme «an open call, essentially through internet, for the provision of financial resources either in form of donation or in exchange for some form of reward and /or voting rights in order to support initiatives for specific purposes» (Schwienbacher et Larralde, (2010)). Ainsi, si l’idée de faire financer un projet par la foule n’est pas nouvelleen soi, le développementde plateforme de négociation,l’intégration des techniques de communication liée auweb 2.0 et le développement du crowdsourcingtendent à donner à ce mode de financement une nouvelle dynamique

Crowdfunding et business angels : de nouvelles interactions en seed capital

International audienc

Design des levées de fonds pour la firme entrepreneuriale : Quand le crowdfunding co-investit avec les business angels

International audienceLe crowdfunding(CF)connaît un succès croissant. En France, les chiffres publiés par l’Association de Financement Participatif France1témoigne de ce succès. Par exemple, plus de 1,75 millions d’internautes ont participé à une opération de CF depuis la création des plateformes. On peut définir le crowdfundingcomme «an open call, essentially through internet, for the provision of financial resources either in form of donation or in exchange for some form of reward and /or voting rights in order to support initiatives for specific purposes» (Schwienbacher et Larralde, (2010)). Ainsi, si l’idée de faire financer un projet par la foule n’est pas nouvelleen soi, le développementde plateforme de négociation,l’intégration des techniques de communication liée auweb 2.0 et le développement du crowdsourcingtendent à donner à ce mode de financement une nouvelle dynamique

Les différences de performance financière entre les entreprises: résultats du marché français

The question of what drives firm profitability has been intriguing re-searchers for some time. At the heart of the debate lies the relative importance of the industry structure, corporate strategy, and firm heterogeneity on firm performance. The current paper reexamines this issue using the data from French publicly traded companies. The findings indicate some convergence [e.g. the role of industry and firm effects] and divergence [e.g. the role of diversification] with some of the studies that use data from the US market.firm diversity;industry;firm heterogeneity; diversification;financial performance; econometric analysis.

Normal and pathological development of subject–verb agreement in speech production: a study on French children

We report a study on the spoken production of subject–verb agreement in number by four age groups of normally developing children (between 5 and 8;5) and a group of 8 children with Specific Language Impairment (SLI; between 5;4 and 9;4), all French speaking. The production of verb agreement was experimentally elicited by asking children to complete sentence preambles containing a head noun and a potentially attracting ‘local noun’. In contrast to previous studies that focused on attraction with local nouns within the subject constituent (postmodifiers), we also studied attraction with local nouns in structures that are not part of the subject constituent (interpolated adjuncts). In normally developing children, we report that (1) attraction effects appear from early on; (2) singular is produced as the default number until age 7 included; (3) more errors are produced with adjunct structures than with postmodifiers, but only from age 8;5 on. In contrast, even the older SLI children showed no attraction effect, a predominance of the singular as default, no effect of syntactic structure and, more generally, persistent high error rates. The turning point observed between 7 and 8;5 in normal children, characterized by a reduced error rate and a significant effect of syntactic structure, is interpreted as an index of the automatization of agreement. The syntactic structure effect is discussed in terms of the interplay of structural and working memory factors in the computation of long-distance relationships

Modulation of the c-Jun N-terminal kinase activity in the embryonic heart in response to anoxia-reoxygenation: involvement of the Ca2+ and mitoKATP channels.

Whether the response of the fetal heart to ischemia-reperfusion is associated with activation of the c-Jun N-terminal kinase (JNK) pathway is not known. In contrast, involvement of the sarcolemmal L-type Ca2+ channel (LCC) and the mitochondrial KATP (mitoKATP) channel has been established. This work aimed at investigating the profile of JNK activity during anoxia-reoxygenation and its modulation by LCC and mitoK(ATP) channel. Hearts isolated from 4-day-old chick embryos were submitted to anoxia (30 min) and reoxygenation (60 min). Using the kinase assay method, the profile of JNK activity in the ventricle was determined every 10 min throughout anoxia-reoxygenation. Effects on JNK activity of the LCC blocker verapamil (10 nM), the mitoK(ATP) channel opener diazoxide (50 microM) and the blocker 5-hydroxydecanoate (5-HD, 500 microM), the mitochondrial Ca2+ uniporter (MCU) inhibitor Ru360 (10 microM), and the antioxidant N-(2-mercaptopropionyl) glycine (MPG, 1 mM) were determined. In untreated hearts, JNK activity was increased by 40% during anoxia and peaked fivefold relative to basal level after 30-40 min reoxygenation. This peak value was reduced by half by diazoxide and was tripled by 5-HD. Furthermore, the 5-HD-mediated stimulation of JNK activity during reoxygenation was abolished by diazoxide, verapamil or Ru360. MPG had no effect on JNK activity, whatever the conditions. None of the tested pharmacological agents altered JNK activity under basal normoxic conditions. Thus, in the embryonic heart, JNK activity exhibits a characteristic pattern during anoxia and reoxygenation and the respective open-state of LCC, MCU and mitoKATP channel can be a major determinant of JNK activity in a ROS-independent manner