99 research outputs found

    Intracellular mechanisms underlying the nicotinic enhancement of LTP in the rat dentate gyrus

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    We have previously shown that activation of nicotinic acetylcholine receptors (nAChRs) enhanced long-term potentiation (LTP) in the rat dentate gyrus in vitro via activation of α7 nAChR. In the present studies, mechanisms underlying the acute and chronic nicotinic enhancement of LTP were examined. In particular, the involvement of activation of intracellular kinases was examined using selective kinase antagonists, and the effects of enhancing cholinergic function with positive allosteric modulators of the α7 nAChR and with acetylcholinesterase (AChE) inhibitors were also investigated. Activation of extracellular signal-regulated kinase (ERK) and cAMP-dependent protein kinase (PKA) was found to be involved in the induction of the acute nicotinic enhancement of LTP, although not control LTP. In contrast, activation of the tyrosine kinase Src, Ca2+-calmodulin-dependent protein kinase II, Janus kinase 2 and p38 mitogen-activated protein kinase was not involved in the acute nicotinic enhancement of LTP, although Src activation was necessary for control LTP. Moreover, activation of phosphoinositide 3-kinase was involved in the acute nicotinic enhancement of LTP to a much lesser extent than in control LTP. Chronic nicotine enhancement of LTP was found to be dependent on PKA, ERK and Src kinases. Acute nicotinic enhancement of LTP was occluded by chronic nicotine treatment. The positive allosteric modulator PNU-120596 was found to strongly reduce the threshold for nicotinic enhancement of LTP, an affect mediated via the α7 nAChR as it was blocked by the selective antagonist methyllycaconitine. The AChE inhibitors tacrine and physostigmine enhanced control LTP

    Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression

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    Previous studies have documented that the insulin-producing beta-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes beta-cells, leading to secretory defects reminiscent of those observed in type 2 diabetes. Since human islets differ in several respects from those of laboratory rodents, we have now screened human pancreas, and islets isolated thereof, for expression of a variety of connexin genes, tested whether the cognate proteins form functional channels for islet cell exchanges, and assessed whether this expression changes with beta-cell function in islets of control and type 2 diabetics. Here, we show that (i) different connexin isoforms are differentially distributed in the exocrine and endocrine parts of the human pancreas; (ii) human islets express at the transcript level different connexin isoforms; (iii) the membrane of beta-cells harbors detectable levels of gap junctions made of Cx36; (iv) this protein is concentrated in lipid raft domains of the beta-cell membrane where it forms gap junctions; (v) Cx36 channels allow for the preferential exchange of cationic molecules between human beta-cells; (vi) the levels of Cx36 mRNA correlated with the expression of the insulin gene in the islets of both control and type 2 diabetics. The data show that Cx36 is a native protein of human pancreatic islets, which mediates the coupling of the insulin-producing beta-cells, and contributes to control beta-cell function by modulating gene expression.The Swiss National Science Foundation (310000-122430 to P.Me), the Juvenile Diabetes Research Foundation (1-2005-1084 to V.C., 1-2007-158 to P.Me), the National Institute of Health (DK55183 to V.C.), the European Union (FP6-Integrated Project EuroDia LSHM-CT-2006-518153 to P.Ma; FP-7 BETAIMAGE 222980 to P.Me), Novo Nordisk (to P.Me) and The Larry L. Hillblom Foundation (to V.C.). Image analysis was performed at The National Center for Microscopy and Imaging Research (NIH grant RR4050 to M. Ellisman). Fresh human islets were provided by the Cell Isolation and Transplantation Cente

    Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression

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    Previous studies have documented that the insulin-producing β-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes β-cells, leading to secretory defects reminiscent of those observed in type 2 diabetes. Since human islets differ in several respects from those of laboratory rodents, we have now screened human pancreas, and islets isolated thereof, for expression of a variety of connexin genes, tested whether the cognate proteins form functional channels for islet cell exchanges, and assessed whether this expression changes with β-cell function in islets of control and type 2 diabetics. Here, we show that (i) different connexin isoforms are differentially distributed in the exocrine and endocrine parts of the human pancreas; (ii) human islets express at the transcript level different connexin isoforms; (iii) the membrane of β-cells harbors detectable levels of gap junctions made of Cx36; (iv) this protein is concentrated in lipid raft domains of the β-cell membrane where it forms gap junctions; (v) Cx36 channels allow for the preferential exchange of cationic molecules between human β-cells; (vi) the levels of Cx36 mRNA correlated with the expression of the insulin gene in the islets of both control and type 2 diabetics. The data show that Cx36 is a native protein of human pancreatic islets, which mediates the coupling of the insulin-producing β-cells, and contributes to control β-cell function by modulating gene expressio

    Nicotinic Receptors Underlying Nicotine Dependence: Evidence from Transgenic Mouse Models.

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    Nicotine underlies the reinforcing properties of tobacco cigarettes and e-cigarettes. After inhalation and absorption, nicotine binds to various nicotinic acetylcholine receptor (nAChR) subtypes localized on the pre- and postsynaptic membranes of cells, which subsequently leads to the modulation of cellular function and neurotransmitter signaling. In this chapter, we begin by briefly reviewing the current understanding of nicotine's actions on nAChRs and highlight considerations regarding nAChR subtype localization and pharmacodynamics. Thereafter, we discuss the seminal discoveries derived from genetically modified mouse models, which have greatly contributed to our understanding of nicotine's effects on the reward-related mesolimbic pathway and the aversion-related habenulo-interpeduncular pathway. Thereafter, emerging areas of research focusing on modulation of nAChR expression and/or function are considered. Taken together, these discoveries have provided a foundational understanding of various genetic, neurobiological, and behavioral factors underlying the motivation to use nicotine and related dependence processes, which are thereby advancing drug discovery efforts to promote long-term abstinence

    L'organisation du marché du poisson en Sardaigne

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    Charpantier Jean. L'organisation du marché du poisson en Sardaigne. In: Méditerranée, 8ᵉ année, n°4, 1967. pp. 283-299

    Les Comores : économie agricole et transports

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    The Comoro Islands : Transportation and Agriculture-Based Economy. The Comoro archipelago , composed of the Great Comoro, Anjouan, Mayotte and Moheli islands — 250,000 inhabitants and 2,333 sq. km. — and an overseas territory of the French Republic enjoying internal autonomy since 1961 — derives the major portion of its income from agriculture. The commercial crops — vanilla, copra, perfume fragrances — for the most part in the hands of plantation companies, are of preponderant importance. On the other hand, the food crops — rice, cassava and various root plants, vegetables, fruit and farm animals — are raised in insufficient quantity for domestic needs ; as a consequence, the islands are obliged to import large amounts of food products (30 % of all imports ). The weakness of the Comoros economy is apparent in the adverse balance of payments figures, which show a huge deficit (only about 55 % of expenditures are covered). Communication and transportation means play a vital role in the life of the archipelago. The road system, though modern, is insufficiently developed for the rapidly growing number of vehicles. Maritime traffic, either by coastal or by scheduled line service, is irregular and precarious ; the port systems, however, are in the process of being improved. Great hope is placed in the growth of air transportation. Each island possesses an airport, but only the one of Moroni has modern equipment, which is, nevertheless, inadequate for handling jets. Service with the interior of the islands is improving ; on the other hand, links with the outside are much less dependable and traffic must be routed via Madagascar.L'archipel des Comores, formé des îles de la Grande Comore, Anjouan, Mayotte et Mohéli — 250 000 habitants et 2 336 km 2 — territoire d'outre-mer de la République française jouissant de l'autonomie interne depuis 1961, tire de l'agriculture l'essentiel de ses revenus. Les cultures commerciales — vanille, coprah, essences à parfum — dans la plupart des cas aux mains de sociétés de plantation occupent une place prépondérante. Par contre, les cultures vivrières, riz, manioc et diverses racines, légumes, fruits, l'élevage, sont très insuffisants aux besoins locaux ; d'où la nécessité d'importer de grosses quantités de produits alimentaires (30 % des importations). La faiblesse de l'économie des Comores se manifeste par une balance des comptes lourdement déficitaire (couverture d'environ 55 %). Les moyens de communication et les transports ont un rôle fondamental dans la vie de l'archipel. Le réseau routier moderne est insuffisant bien que le nombre de véhicules s'accroisse rapidement. Le trafic maritime par cabotage ou de ligne est irrégulier et précaire ; cependant l'infrastructure portuaire est en cours d'amélioration. On met beaucoup d'espoir dans le développement des transports aériens. Chaque île possède un aéroport, mais seul celui de Moroni est doté d'un équipement moderne sans être toutefois accessible aux «jets ». Le trafic intérieur se développe, par contre les relations extérieures sont moins bien assurées et doivent transiter par Madagascar.Charpantier Jean. Les Comores : économie agricole et transports. In: Cahiers d'outre-mer. N° 94 - 24e année, Avril-juin 1971. pp. 158-184

    L'organisation du marché du poisson en Sardaigne

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    Charpantier Jean. L'organisation du marché du poisson en Sardaigne. In: Travaux de l'Institut Géographique de Reims, n°1, 1969. Mélanges. pp. 47-65

    Condiciones infantiles y laborales :el trabajo de los niños y niñas vendedoras y lustrabotas.

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    Los fenómenos que vive la niñez actualmente son cada vez más notorios y por lo tanto, es más imperativo tratarlos. El trabajo infantil es un hecho que ha ido mostrándose poco a poco en la sociedad, es cada vez más común mirar a niños y niñas en la calle ofreciendo servicios o vendiendo diferentes artículos. El trabajo infantil además trae consigo una serie de discusiones entre las instituciones que trabajan con niños y niñas. La forma de prevenirlo, la desvaloración, los efectos sobre la infancia, la familia y la escuela, la continuación del círculo de pobreza, de analfabetismo y consecuente exclusión, son temas que urgen tratar y que causan polémicas. Si por un lado los niños y niñas se los trata de hacer actores sociales, por otro lado se los intenta proteger al máximo sin dejar que hagan nada por sí solos. El trabajo que realizan los niños y niñas ha sido parte de la educación que una sociedad brinda a los más pequeños. En ocasiones utilizados para brindar respeto a la persona del niño o niña incluyéndole en tareas comunitarias y en otras utilizándola como mano de obra barata y fácil de manejar. Lo cierto es que en la actualidad el trabajo ha ido tomando formas que se desconocían antes, que en lugar de insertar al niño o niña dentro de la comunidad lo repele cada vez más de su núcleo familiar. El trabajo, suele ser un acompañamiento formativo de los niños y niñas en todos los aspectos del trabajo que realizan los adultos

    Vitalidad lingüística del TSA Fiki en tres comunidades Tsa´chila en los años 2018-2019

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    La pérdida de vitalidad de las lenguas indígenas es un problema que ocurre en todo el mundo, debido principalmente a su relación con lenguas prestigiosas que son dominantes en diversas sociedades, como el inglés, el español, el francés, el portugués, el chino, el árabe y otras. Este fenómeno ocurre también con respecto a la lengua Tsa´fiki, hablada por los miembros de la nacionalidad Tsa´chila, que habita en las proximidades de la ciudad de Santo Domingo de los Tsa´ chilas, al pie de la cordillera de los Andes, en Ecuador. Por medio de un análisis sociolingüístico de tipo cuantitativo, cualitativo y comparativo, esta investigación se enfoca sobre la situación actual de la lengua Tsa ´fiki en tres comunidades: Chigüilpe, Peripa y Otongo Mapalí. Los resultados obtenidos nos dan una visión bastante precisa del estado en el que se encuentra dicha lengua en estas tres comunidades, especialmente en el caso de los niños, adolescentes y adultos jóvenes, lo que nos permite reflexionar sobre las causas del uso y desuso del Tsa´fiki en relación con factores sociales y económicos en el contexto de su entorno vivencial
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