37 research outputs found

    SIMONE: a realistic neural network simulator to reproduce MEA-based recordings

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    International audienceContemporary multielectrode arrays (MEAs) used to record extracellular activity from neural tissues can deliver data at rates on the order of 100 Mbps. Such rates require efficient data compression and/or preprocessing algorithms implemented on an application specific integrated circuit (ASIC) close to the MEA. We present SIMONE (Statistical sIMulation Of Neuronal networks Engine), a versatile simulation tool whose parameters can be either fixed or defined by a probability distribution. We validated our tool by simulating data recorded from the first olfactory relay of an insect. Different key aspects make this tool suitable for testing the robustness and accuracy of neural signal processing algorithms (such as the detection, alignment, and classification of spikes). For instance, most of the parameters can be defined by a probabilistic distribution, then tens of simulations may be obtained from the same scenario. This is especially useful when validating the robustness of the processing algorithm. Moreover, the number of active cells and the exact firing activity of each one of them is perfectly known, which provides an easy way to test accuracy

    Adénylyl cyclases et transdifférenciation des cellules musculaires lisses vasculaires : rôle dans le remodelage vasculaire pathologique

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    En réponse à différents types de stress vasculaires, les cellules musculaires lisses de la paroi vasculaire (CMLV) changent de phénotype et acquièrent la capacité de répondre à des signaux anormaux. Ce phénomène les prédispose à participer au développement de pathologies vasculaires majeures telles que l’athérosclérose et certaines complications post-angioplastie comme la resténose. La voie de l’adénosine monophosphate cyclique (AMPc) joue un rôle central dans l’intégration des stimuli environnants et dans l’élaboration des réponses cellulaires. La spécificité des signaux transmis est assurée par la compartimentation subcellulaire spatiale et temporelle de l’AMPc. Cette compartimentation tient à la diversité (i) des protéines régulant directement ou indirectement la synthèse, la dégradation, ou l’extrusion de l’AMPc; (ii) des effecteurs intracellulaires de l’AMPc; (iii) des isoformes de toutes ces protéines aux propriétés biochimiques et aux mécanismes de régulations uniques; (iv) de protéines d’échafaudage les rassemblant en complexes macromoléculaires. Cette revue illustre en quoi le changement du profil d’expression des adénylyl cyclases (AC) peut jouer un rôle critique dans l’intégration des signaux et la réponse des cellules musculaires et être associé`a un remodelage vasculaire pathologique. Elle illustre également pourquoi il est pertinent de considérer, à nouveau, les AC comme des cibles thérapeutiques d’intérêt

    The stellate vascular smooth muscle cell phenotype is induced by IL-1β via the secretion of PGE2 and subsequent cAMP-dependent protein kinase A activation

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    International audienceAtherosclerosis development is associated with morphological changes to intimal cells, leading to a stellate cell phenotype. In this study, we aimed to determine whether and how key pro-atherogenic cytokines present in atherosclerotic plaques (IL-1β, TNFα and IFNγ) could induce this phenotype, as these molecules are known to trigger the transdifferentiation of vascular smooth muscle cells (VSMCs). We found that, IL-1β was the only major inflammatory mediator tested capable of inducing a stellate morphology in VSMCs. This finding was confirmed by staining for F-actin and vinculin at focal adhesions, as these two markers were disrupted only by IL-1β. We then investigated the possible association of this IL-1β-dependent change in morphology with an increase in intracellular cAMP concentration ([cAMP]), using the FRET-based biosensor for cAMP TEpacVV. Experiments in the presence of IL-1β or medium conditioned by IL-1β-treated VSMCs and pharmacological tools demonstrated that the long-term increase in intracellular cAMP concentration was induced by the secretion of an autocrine/paracrine mediator, prostaglandin E2 (PGE2), acting through the EP4 receptor. Finally, by knocking down the expression of the regulatory subunit PKAR1α, thereby reproducing the effects of IL-1β and PGE2 on VSMCs, we demonstrated the contribution of PKA activity to the observed behavior of VSMCs

    Testis hormone-sensitive lipase expression in spermatids is governed by a short promoter in transgenic mice

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    A testicular form of hormone-sensitive lipase (HSLtes), a triacylglycerol lipase, and cholesterol esterase, is expressed in male germ cells. Northern blot analysis showed HSLtes mRNA expression in early spermatids. Immunolocalization of the protein in human and rodent seminiferous tubules indicated that the highest level of expression occurred in elongated spermatids. We have previously shown that 0.5 kilobase pairs of the human HSLtes promoter directs testis-specific expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice and determined regions binding nuclear proteins expressed in testis but not in liver (Blaise, R,, Grober, J,, Rouet, P., Tavernier, G., Daegelen, D., and Langin, D. (1999) J. Biol. Chem. 274, 9327-9334). Mutation of a SRY/Sox-binding site in one of the regions did not impair in vivo testis-specific expression of the reporter gene. Further transgenic analyses established that 95 base pairs upstream of the transcription start site were sufficient for correct testis expression. In gel retardation assays using early spermatid nuclear extracts, a germ cell-specific DNA-protein interaction was mapped between -46 and -29 base pairs. The DNA binding nuclear protein showed properties of zinc finger transcription factors. Mutation of the region abolished reporter gene activity in transgenic mice, showing that it is necessary for testis expression of HSLtes
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