Biomedical subjects

Christophe Blanchet

Publications and source records attributed to Christophe Blanchet.

6 recordsLinked to original sources

PubMed2006

Secured distributed service to manage biological data on EGEE grid.

Biological data are most times published and then become public ones. They, then, do not need to be isolated or encrypted. But, in some cases, these data stemed from patients or are analyzed with, for instance, pharmaceutical or agronomics goals. Also in simple ways , these data, before to become public, have to be kept confidential while researchers haven't been able to publish their work or to register them. So they are a lot of cases where the integrity and the confidentiality of biological data have to be protected against unauthorized accesses. But, as these private data are also large datasets, they need high-throughput computing and huge data storage to processed, such as ones produced by complete genome projects. These requirements are enhanced in the context of a Grid such EGEE, where the computing and storage resources are distributed across a large-scale platform. We have developed a secured distributed service to manage biological data on grid: the EncFile encrypted files management system. We have deployed it on the production platform of the EGEE grid project. Thus we provided grid users with a user-friendly component that doesn't require any user privileges. And we have integrated into a bioinformatics grid portal associated to encrypted representative biological resources: world-famous databases and programs.

Computational Biology↗

PubMed2006

GPS@ bioinformatics portal: from network to EGEE grid.

Bioinformatics analysis of data produced by complete genome sequencing projects is one of the major challenges of the current years. Integrating up-to-date databanks and relevant algorithms is a clear requirement of such analysis. Grid computing would be a viable solution to distribute data, algorithms, computing and storage resources for Genomics. Providing bioinformaticians with a good interface to grid infrastructure, such as the one provided by the EGEE European project, is also a challenge to take up. The GPS@ web portal, "Grid Protein Sequence Analysis", aims to provide such a user-friendly interface for these grid genomic resources on the EGEE grid.

Computational Biology↗

PubMed2005

Short-term regulation of information processing at the corticoaccumbens synapse.

In relation to expectation and delivery of reward, pyramidal neurons of the prefrontal cortex either switch from a single spiking mode to transient phasic bursting, or gradually increase their sustained tonic activity. Here, we examined how switching between firing modes affects information processing at the corticoaccumbens synapse. We report that increasing presynaptic firing frequency in a tonic manner either depresses or facilitates synaptic transmission, depending on initial probability of release. In contrast, repeated bursts of stimulation of cortical afferents trigger a new form of short-term potentiation of synaptic transmission (RB-STP) in the nucleus accumbens (NAc). RB-STP involves the regulation of axonal excitability mediated by 4-AP-sensitive potassium channels in afferent cortical neurons. Thus, in a tonic mode, information flow is tightly controlled by regulatory mechanisms at the level of presynaptic terminals, whereas switching to a bursting mode reliably enhances efficacy of information processing for all cortical afferents to NAc neurons.

Animals↗

PubMed2003

Integrated databanks access and sequence/structure analysis services at the PBIL.

The World Wide Web server of the PBIL (Pôle Bioinformatique Lyonnais) provides on-line access to sequence databanks and to many tools of nucleic acid and protein sequence analyses. This server allows to query nucleotide sequence banks in the EMBL and GenBank formats and protein sequence banks in the SWISS-PROT and PIR formats. The query engine on which our data bank access is based is the ACNUC system. It allows the possibility to build complex queries to access functional zones of biological interest and to retrieve large sequence sets. Of special interest are the unique features provided by this system to query the data banks of gene families developed at the PBIL. The server also provides access to a wide range of sequence analysis methods: similarity search programs, multiple alignments, protein structure prediction and multivariate statistics. An originality of this server is the integration of these two aspects: sequence retrieval and sequence analysis. Indeed, thanks to the introduction of re-usable lists, it is possible to perform treatments on large sets of data. The PBIL server can be reached at: http://pbil.univ-lyon1.fr.

Databases, Genetic↗

PubMed2003

Two distinct forms of desensitization of G-protein coupled inwardly rectifying potassium currents evoked by alkaloid and peptide mu-opioid receptor agonists.

Mu-opioid receptors (MORs) activate G-protein coupled inwardly rectifying potassium (GIRK) channels. The peptide agonist [D-Ala(2), NMe-Phe(4), Gly(5)-ol]enkephalin (DAMGO), but not the alkaloid morphine (MS), leads to acute desensitization of this response. Furthermore, DAMGO, as opposed to MS, triggers rapid internalization of MORs. Given this dichotomy, we probed the relationship between receptor internalization and GIRK current desensitization in neurons of the locus coeruleus (LC) using acute rat brain slices. Interfering with MOR recycling by selective impairment of dynamin-dependent endocytosis left GIRK current desensitization unchanged. Conversely, coapplication of MS with a low concentration of DAMGO, a cocktail reported to enhance MOR internalization, revealed competition between the two agonists and normal desensitization. We also examined the case of methadone (MD), an alkaloid that has been reported to strongly trigger endocytosis. Interestingly, MD and other alkaloids agonists did induce GIRK current desensitization, but only at suprasaturating concentrations. Furthermore, responses to alkaloids were blunted in LC neurons and the same agonists inhibited GIRK currents in cells that do not express MORs. Our results indicate that two distinct forms of MOR-evoked GIRK current desensitization exist. Peptide agonists induce receptor-mediated desensitization while alkaloid agonists lead to apparent desensitization by receptor-independent inhibition of GIRK channels.

Alkaloids↗

PubMed2002

Desensitization of mu-opioid receptor-evoked potassium currents: initiation at the receptor, expression at the effector.

Many G protein-coupled receptor-mediated responses desensitize within minutes. Sustained stimulation of mu-opioid receptors (MORs), which primarily signal through G(i/o) proteins, leads to activation and subsequent desensitization of G protein-coupled inwardly rectifying potassium (GIRK) currents. We observed that in neurons of the locus coeruleus, which express among the highest levels of MORs in the brain, the degree of desensitization depended on the intensity of receptor stimulation, indicating that the process is initiated at the receptor. Interestingly, while GIRK-mediated postsynaptic inhibition substantially desensitized within 15 min, presynaptic inhibition of afferent transmission, which involves other effector systems, remained constant, suggesting that the postsynaptic desensitization we observed is expressed at the effector. We show that desensitized GIRK currents can gradually be reactivated by additional G protein signals of increasing intensity and present evidence that desensitization is a G protein-mediated process. Finally, desensitization of MOR-induced GIRK currents had heterologous effects on responses mediated by other G protein-coupled receptors converging onto the same population of GIRK channels. Taken together, our results provide evidence for a form of desensitization mediated by a slowly developing G protein-dependent pathway, initiated at the MORs and leading to competitive inhibition of GIRK channel activation. This implies that MORs exert a bidirectional action on GIRK channels.

Animals↗