Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BOI1 and BOI2 are paralogs important for the actin cytoskeleton andpolar growth. BOI1 encodes a meiotic transcript isoform with an extended5-untranslated region predicted to impair protein translation. It is,however, unknown how the isoform is repressed during mitosis, and ifBoi1 is present during sporulation. By interpreting microarray data fromMATa cells, MATa/ cells, a starving MAT/ control, and a meiosis-impairedrrp6 mutant, we classified BOI1's extended isoform as earlymeiosis-specific. These results were confirmed by RNA-Sequencing, andextended by a 5-RACE assay and Northern blotting, showing that meioticcells induce the long isoform while the mitotic isoform remainsdetectable during meiosis. We provide evidence via motif predictions, anin vivo binding assay and genetic experiments that the Rpd3/Sin3/Ume6histone deacetylase complex, which represses meiotic genes duringmitosis, also prevents the induction of BOI1's 5-extended isoform inmitosis by direct binding of Ume6 to its URS1 target. Finally, we findthat Boi1 protein levels decline when cells switch from fermentation torespiration and sporulation. The histone deacetylase Rpd3 is conserved,and eukaryotic genes frequently encode transcripts with variable 5-UTRs.Our findings are therefore relevant for regulatory mechanisms involvedin the control of transcript isoforms in multi-cellular organisms.
ISSN: 0950-382X

hal-01122120
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122120
DOI : 10.1111/mmi.12976
PUBMED : 25708805

Éditeur(s) : HAL CCSD
Résumé : International audience
Smoking is well-known to impair pharmacokinetics, through inducing expression of drug metabolizing enzymes. In the present study, we demonstrated that cigarette smoke condensate (CSC) also alters activity and expression of hepatic drug transporters, which are now recognized as major actors of hepatobiliary elimination of drugs. CSC thus directly inhibited activities of sinusoidal transporters such as OATP1B1, OATP1B3, OCT1 and NTCP as well as those of canalicular transporters like P-glycoprotein, MRP2, BCRP and MATE1, in hepatic transporters-overexpressing cells. CSC similarly counteracted constitutive OATP, NTCP and OCT1 activities in human highly-differentiated hepatic HepaRG cells. In parallel, CSC induced expression of BCRP at both mRNA and protein level in HepaRG cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B1, OATP2B1, OAT2, NTCP, OCT1 and BSEP, and enhanced that of MRP4. Such changes in transporter gene expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin, a reference activator of the aryl hydrocarbon receptor (AhR) pathway, and were counteracted, for some of them, by siRNA-mediated AhR silencing. This suggests that CSC alters hepatic drug transporter levels via activation of the AhR cascade. Importantly, drug transporter expression regulations as well as some transporter activity inhibitions occurred for a range of CSC concentrations similar to those required for inducing drug metabolizing enzymes and may therefore be hypothesized to be relevant for smokers. Taken together, these data established human hepatic transporters as targets of cigarette smoke, which could contribute to known alteration of pharmacokinetics and some liver adverse effects caused by smoking. © 2016 Elsevier Ireland Ltd
Toxicology

hal-01367143
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367143
DOI : 10.1016/j.tox.2016.07.011
PUBMED : 27450509

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
ISSN: 0003-6811

hal-01529548
https://hal.univ-antilles.fr/hal-01529548
DOI : 10.1080/00036811.2010.511474

Éditeur(s) : HAL CCSD
Résumé : In this thesis, we propose a method to solve some Cauchy problems with irregular or characteristic data by using the recent theories of generalized functions. We study a regular Cauchy problem and a regular Goursat problem in the first part with data on a monotonic curve. The second part is devoted to the setting up of an algebra adapted to the generalized Cauchy problem. In the third part, we give a meaning to a generalized Cauchy problem and we show that the problem admits a unique solution. We study a generalized Goursat problem in the same way. In the fourth part, we approach a characteristic Cauchy problem by a family of non-characteristic ones. The family of solutions is a representative of a generalized function we consider as the generalized solution of the problem in an appropriate algebra. We give a meaning to the characteristic Cauchy problem with irregular data by replacing it by a family of non-characteristic problems in an appropriate biparametric algebra. The first parameter permits to replace the given problem by a non-characteristic one, whereas the second parameter makes it regular. The family of solutions is a representative of a generalized function considered as the solution of the problem.
Dans cette thèse nous proposons une méthode pour résoudre certains problèmes de Cauchy à données irrégulières ou caractéristiques en utilisant les récentes théories des fonctions généralisées. Nous étudions dans la première partie un problème de Cauchy et un problème de Goursat réguliers avec des données sur une courbe monotone. La deuxième partie est consacrée à la mise en place d'une algèbre adaptée à la résolution du problème de Cauchy généralisé. Dans la troisième partie nous donnons un sens à un problème de Cauchy généralisé et nous montrons qu'il admet une unique solution. Nous étudions de même un problème de Goursat généralisé. Dans la quatrième partie nous approchons un problème de Cauchy caractéristique par une famille de problèmes non caractéristiques. La famille de solutions est un représentant d'une fonction généralisée que nous considérons comme la solution généralisée du problème dans une algèbre appropriée. Nous donnons un sens au problème de Cauchy caractéristique dans le cas de données irrégulières en le remplaçant par une famille de problèmes non caractéristiques dans une algèbre convenable dépendant de deux paramètres. Le premier paramètre permet de se ramener à un problème non caractéristique que le second rend régulier. La famille de solutions est un représentant d'une fonction généralisée que nous considérons comme la solution du problème.
https://tel.archives-ouvertes.fr/tel-00012098

Droits : info:eu-repo/semantics/OpenAccess
tel-00012098
https://tel.archives-ouvertes.fr/tel-00012098
https://tel.archives-ouvertes.fr/tel-00012098v2/document
https://tel.archives-ouvertes.fr/tel-00012098/file/These-Devoue-29-12-2006.pdf

Résumé : After a period of rapid development of the sites (an increase in both reared surface area and production), tropical shrimp aquaculture is currently being faced with critical problems due to economical and ecological constraints. In many countries with favourable conditions for shrimp aquaculture such as indonesia or Vietnam, sites are often badly selected and/or over-exploited. This conducts to sorne extent to decreases or collapses in the production due to the difficulty in predicting the maximum production capacity of the sites. Furthermore, it appears that production sustainability depends on many factors among which socio-economy and ecolo gy are of prime importance. The STD3 project titled « Assessment of tropical shrimp aquaculture impact on the environment in tropical countries using hydrobiology, ecology and remote sensing as helping tools for diagnosis )) was initiated in 1994, with the aim to study the sustainability of marine shrimp aquaculture in tropical areas, main! y Indonesia and Vietnam, through the following tasks: (i) improve site selection and study the impact of aquaculture on marine environments presenting a variable sensitivity to organic sewage, (ii) analyse the socio-economical aspects and profitability of the aquaculture industry and of common resources (iii) use remote sensing and geographical data bases for diagnosis and monitoring of site degradation (iv) reinforce the capacity of Asian scientists through training. Severa! aquaculture sites have been investigated in the Lampung region (South Sumatra, Indonesia), the Mekong delta (Vietnam) and on the West coast of New-Caledonia, providing a large range of typical ecosystems encountered in Asia and in the Pacifie, from coralline sites to coastal plains with mangrove and deltaic areas. The study concerned the spatial structure and seasonal influence of these ecosystems, the temporal variation during the course of the project (3 years) and the relation between the ecological structure and farm productions. Remote sensing provides a synoptic vision over large land expanses. Severa! scenes were processed for landuse mapping using conventional classification techniques. Concerning water quality assessment, a general relation for the Java sea was found between image and field data in terms of total suspended matter. Applying this relation to a new site in Sumatra has provided an initial approach to water type and, together with land use mapping, a preliminary assessment of the suitability of the area to shrimp aquaculture development. Socio-economic research has been focused on the identification ofneeds for collective action, including public policy, in the perspective of shrimp farming sustainability. The main concern is in the regulation of shrimp farming intensification and extensification at the scale of coastal ecosystemic entities in a common property resource management perspective. The common considered here is coastal water quality. Comparing the local development profiles and the institutional grounds for the design and implementation of collective management rules shows that variables such as land tenure system, farm owner socio-economic profile, social homogeneity or heterogeneity of the farmers are key factors to analyse the potential for sustainability. The defmition of water quality and the possible means to ensure its collective management are discussed. The main conclusion is that the economie incentives to farming development are strong but there is no significant difference among traditional, semi-intensive and intensive systems in terms of economie efficiency or wealth distribution. The description of the functioning of the different kinds of ecosystems make it possible to give an advice concerning the positioning of the activity inside the ecosystem, and furthermore to have a reference state in order to determine the impact of the activity on the coastal environnement. This impact can be summarized as an increase in the concentration of total suspended matt€?r, of particulate organic matter and of sulfate reducing bacterias. This organic ma~.er is either issued from rearing activities or from telluric origine, due to mangrove eradication when building the ponds. An evaluation of the relationship existing between productivity and characteristics of each ecosystem bas been conducted by correlating ecological indicators data (concentration of total suspended matter, particulate organic matter, chlorophyll, percentage of pheopigments in total pigments and cyanobacteria and sulfatereducing bacteria in water and sediments) with the average production of the farms. This comparison lead to the compilation of a scale of observed production integrating the range of these environmental parameters with shrimp production levels, bound to facilitate the positioning of shrimp farming in relation with the confmement leve! of each ecosystem. Lastly, ali geographie data originated from the various compartments of the study have been geo-referenced and loaded into a geographical information system. This allows to display any query made on spatial variables and their related statistical data, including the ir variations over the last few years and to reveal patterns and phenomena otherwise not obvious.
Le programme mis en oeuvre par la DRV (Paris, CREMA-L'Houmeau, DELIAO Brest, COP Tahiti, GIE/RA Nouvelle Calédonie), dans le cadre d'un projet européen STD3 «(Sciences et Technique au Service du Développement», en collaboration avec l'Université de Montpellier II, l'Ecole Nationale d'Agronomie de Rennes, l'ITC (Hollande), l'Institut Océanographique de Nha Trang (Vietnam), le BADC de Jepara et le BPPT de Jakarta (Indonésie), avait pour but la mise au point de méthodes permettant d'améliorer la sélection des sites ainsi que le suivi du développement et de l'impact de l'aquaculture des crevettes Péneides en milieu tropical pour éviter la surexploitation. Quatre axes de recherche ont été défmis : a) identifier la nature et quantifier les rejets de déchets issus de ce type d'aquaculture, b) définir les caractéristiques écologiques des écosystèmes susceptibles d'accueillir l'activité aquacole et suivre leur évolution sous l'influence des rejets, c) déterminer l'influence de la gestion des fermes et des ressources (aspects économiques) sur les performances de productivité, d) déterminer la capacité de la télédétection comme outil de diagnostic d'impact à l'échelle de la région, e) mener un programme de formation d'étudiants et jeunes chercheurs Vietnamiens et Indonésiens.

Droits : 1998 Ifremer
http://archimer.ifremer.fr/doc/00132/24357/22357.pdf
http://archimer.ifremer.fr/doc/00132/24357/

Résumé : Sea fish farms with production of more than 20 tons per year in France must obtain two operating licences: (i) one for Sea Farming (AECM), with the aim of ensuring that the granted site and use of the maritime public domain for exploitation will respect all restrictions of general interest; (ii) one for regulating Facilities Classified for the Protection of the Environment (ICPE). Although the first one requires a relatively simple licence request file, the second one demands a very complete file, which includes, beyond the notice of exploitation information, a complete impact study, as well as a hazards study and a health and safety notice. In this context, petitioners in Corsica (adjustment of status or new exploitation) are faced with the same difficulties, which highlighted the need for a methodological guide adapted to each region's specific situation, assembling in particular the necessary baseline data (legal, zootechnical, geographical, climatic, socio-economic, ecological...) as well as recognised methods for evaluating the potential effects of the farm on the environment. Development of this guide was supported by ADEC and supervised by a steering committee composed of representatives from the administrations concerned, fish farmers and scientific bodies. The significant aspects dealt with the effects of fish farming on Posidonie herbarium, a protected species very present in Corsica and with coordinating the two AECM and ICPE procedures. For each part of the ICPE file, the guide introduces the technical or scientific context and, depending upon the case, the state of the art, sources of available data, acquisition and methods of acquiring measurements and of assessing the potential effects, as well as practical editing recommendations. Finally, the guide is made complete by a model schedule of conditions designed to help petitioners to have a specialist research department incorporate all or part of the file. This guide primarily concerns first-time marine facilities for exploitation in Corsica, conceived of as in the open sea rather than in confined spaces. Nonetheless, any fish farmer or future fish farmer needing to process a request for an exploitation licence may find it useful.
Les piscicultures marines de plus de 20 t/an de production sont soumises en France à l'obtention de deux autorisations d'exploiter : (i) celle au titre des Cultures Marines (AECM), visant à s'assurer que le site concédé et l'usage du domaine public maritime pour l'exploitation permettent de respecter l'ensemble des contraintes d'intérêt général ; (ii) celle au titre de la réglementation des Installations Classées pour la Protection de l'Environnement (ICPE). Si la première nécessite un dossier de demande d'autorisation relativement simple, la seconde requiert un dossier très complet, qui comprend, outre une notice de renseignements sur l'exploitation, une étude d'impact complète, ainsi qu'une étude des dangers et une notice d'hygiène et de sécurité. Dans ce contexte, les demandeurs en Corse (régularisation ou exploitation nouvelle) sont confrontés aux mêmes difficultés, ce qui a mis en évidence le besoin d'un guide méthodologique adapté aux spécificités régionales, rassemblant en particulier les données de base nécessaires (juridiques, zootechniques, géographiques, climatiques, socio-économiques, écologiques...) ainsi que les méthodes reconnues de l'évaluation des effets potentiels de la ferme sur l'environnement. L'élaboration de ce guide a été soutenue par l'ADEC et suivie par un comité de pilotage composé de représentants des administrations concernées, des pisciculteurs et d'organismes scientifiques. Les aspects importants ont porté sur les effets de la pisciculture sur l'herbier de Posidonie, espèce protégée très présente en Corse et sur la coordination entre les deux procédures AECM et ICPE. Pour chaque partie du dossier ICPE, le guide présente le contexte technique ou scientifique et selon le cas, l'état de l'art, les sources de données disponibles, les méthodes d'acquisition des mesures et d'évaluation des effets potentiels, ainsi que des recommandations pratiques de rédaction. Enfin, le guide est complété par un cahier des charges type destiné à aider les demandeurs à confier à un bureau d'étude spécialisé la réalisation de tout ou partie de la constitution du dossier. Ce guide concerne prioritairement les installations marines de nouvelles exploitations en Corse, envisagées en mer ouverte plutôt que dans des espaces confinés. Néanmoins tout pisciculteur ou futur pisciculteur devant instruire une demande d'autorisation d'exploiter peut y trouver intérêt.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2004/rapport-2188.pdf
http://archimer.ifremer.fr/doc/00000/2188/

Éditeur(s) : Université Paul Sabatier, Toulouse III
Résumé : The marine phytoplankton in the ocean represents only less than 1% of global biomass. Phytoplankton performs half of all photosynthesis. This autotrophic biomass in ocean is then an essential element in the climate regulation through processes as carbon dioxide absorption during the photosynthesis. Therefore, we need to estimate precisely this biomass as well as the processes which affect it. Using remotely sensed data (altimetry and ocean colour) and a coupled physical/biogeochemical model (MERCATOR-OPA/NPZDDON), Rossby waves and their influence on phytoplankton biomass are specifically studied in the North Atlantic Ocean. Their features and their influences on surface chlorophyll concentrations were analysed. Through the different mechanisms identified, we estimated that these waves can induce local increases from 60% to 150% of the estimated primary production.
Même si l'océan ne représente que moins de 1% de la biomasse liée aux plantes sur la terre, il est responsable de près de la moitié de la photosynthèse nette de la biosphère. Cette biomasse est par conséquent un élément essentiel dans la régulation du climat à travers par exemple le cycle océanique du carbone. Il est donc nécessaire d'estimer correctement cette biomasse ainsi que les processus qui l'affectent. A l'aide de données satellites altimétriques et couleur de l'eau et d'un modèle couplé physique/biogéochimie (MERCATOR-OPA / NPZDDON), les ondes de Rossby et leur influence sur cette biomasse sont spécifiquement étudiées dans l'océan Atlantique Nord. Leurs propriétés et leur influence sur les concentrations en chlorophylle de surface sont analysées. Au travers des mécanismes mis en jeu identifiés, nous estimons que ces ondes peuvent entraîner une augmentation locale comprise entre 60% et 150% de la production primaire estimée.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2005/these-2454.pdf
http://archimer.ifremer.fr/doc/00000/2454/

Éditeur(s) : HAL CCSD National Institute of Environmental Health Sciences (NIEHS) National Institute of Environmental Health Sciences
Résumé : International audience
Long-term exposure to persistent pollutants with hormonal properties (endocrine-disrupting chemicals, EDCs) may contribute to the risk of prostate cancer (PCa). However, epidemiological evidence remains limited. We investigated the relationship between PCa and plasma concentrations of universally widespread pollutants, in particular p,p'-dichlorodiphenyl dichloroethene (DDE) and the non-dioxin like polychlorinated biphenyl congener 153 (PCB153). We evaluated before treatment 576 men with newly diagnosed PCa and 655 controls in Guadeloupe (French West Indies). Exposure was analyzed according to case-control status. Associations were assessed by unconditional logistic regression analysis, controlling for confounding factors. Missing data were handled by multiple imputation. We estimated a significant positive association between DDE and PCa (adjusted odds ratio [OR] 1.53; 95% CI 1.02, 2.30 for the highest versus lowest quintile of exposure; PTrend = 0.01). PCB153 was inversely associated with PCa (OR 0.30; 95% CI 0.19, 0.47 for the highest versus lowest quintile of exposure values; PTrend < 0.001). Also, PCB153 was more strongly associated to low-grade than high grade PCa. Associations of PCa with DDE and PCB153 were in opposite directions. This may reflect differences in the mechanisms of action of these EDCs, and although our findings need to be replicated in other populations, they are consistent with complex effects of EDCs on human health.
ISSN: 0091-6765

hal-01118553
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118553
DOI : 10.1289/ehp.1408407
PUBMED : 25493337

Éditeur(s) : HAL CCSD American Society for Cell Biology
Résumé : International audience
Based on its shedding and binding activities, the disintegrin and metalloprotease 12 (ADAM12) has been implicated in cell signaling. Here we investigate the intracellular protein interaction network of the transmembrane ADAM12L variant using an integrative approach. We identify the integrin-linked kinase (ILK) as a new partner for ADAM12L cellular functions. We demonstrate that ADAM12L coimmunoprecipitates with ILK in cells and that its cytoplasmic tail is required for this interaction. In human cultured hepatic stellate cells (HSCs), which express high levels of endogenous ADAM12L and ILK, the two proteins are redistributed to focal adhesions upon stimulation of a β1 integrin-dependent pathway. We show that down-regulation of ADAM12L in HSCs leads to cytoskeletal disorganization and loss of adhesion. Conversely, up-regulation of ADAM12L induces the Akt Ser-473 phosphorylation-dependent survival pathway via stimulation of β1 integrins and activation of phosphoinositide 3-kinase (PI3K). Depletion of ILK inhibits this effect, which is independent of ADAM12L proteolytic activity and involves its cytoplasmic domain. We further demonstrate that overexpression of ADAM12L promotes kinase activity from ILK immunoprecipitates. Our data suggest a new role for ADAM12L in mediating the functional association of ILK with β1 integrin to regulate cell adhesion/survival through a PI3K/Akt signaling pathway.
ISSN: 1059-1524

Droits : info:eu-repo/semantics/OpenAccess
inserm-00717429
http://www.hal.inserm.fr/inserm-00717429
http://www.hal.inserm.fr/inserm-00717429/document
http://www.hal.inserm.fr/inserm-00717429/file/MBoC_E11-11-0918R-A_LEYME_ET_AL.pdf
PUBMED : 22767580

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : Le cantonnement de pêche est un outil administratif et juridique français employé pour la gestion de la ressource halieutique et la réglementation de la pêche sur un site marin défini. Cet outil a été mis en place à la Martinique (Petites Antilles) en 1999, à la demande des marins-pêcheurs confrontés à la raréfaction des stocks de poissons au sein de la bande côtière. Les autorités compétentes sur le milieu marin ont installé ce dispositif sur huit zones réparties autour de l’île (de la côte Atlantique à la côte Caraïbes). Le cantonnement de pêche reste peu documenté scientifiquement à ce jour, en dehors d’inventaires ichtyologiques réalisés par des scientifiques-biologistes. Il est donc opportun de retracer les étapes de la mise en place de cet outil et d’analyser les premiers résultats et les enjeux.
Cantonment fishing is a French legal and administrative tool used to manage fisheries resources and the regulation of fishing on marine site defined. This tool was developed in Martinique (Lesser Antilles) in 1999, at the request of fishermen facing depletion of fish stocks in the coastal strip. The competent authorities on the marine environment have installed this device on eight areas spread around the island (the Atlantic coast to the Caribbean coast). Cantonment fishing is little scientifically documented to date, apart from fishery surveys conducted by scientists-biologists. It is therefore appropriate to retrace the steps of the development of this tool and analyze the first results and challenges.
Martinique

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.6800
http://journals.openedition.org/etudescaribeennes/6800

Éditeur(s) : HAL CCSD
Résumé : International audience
In vitro evaluation of P-glycoprotein (P-gp) inhibitory potential is now a regulatory issue during drug development, in order to predict clinical inhibition of P-gp and subsequent drug-drug interactions. Assays for this purpose, commonly based on P-gp-expressing cell lines and digoxin as a reference P-gp substrate probe, unfortunately exhibit high variability, raising thus the question of developing alternative or complementary tests for measuring inhibition of P-gp activity. In this context, the present study was designed to investigate the use of the fluorescent dye rhodamine 123 as a reference P-gp substrate probe for characterizing P-gp inhibitory potential of 16 structurally-unrelated drugs known to interact with P-gp. 14/16 of these P-gp inhibitors were found to increase rhodamine 123 accumulation in P-gp-overexpressing MCF7R cells, thus allowing the determination of their P-gp inhibitory potential, i.e., their half maximal inhibitor concentration (IC50) value towards P-gp-mediated transport of the dye. These IC50 values were in the range of variability of previously reported IC50 for P-gp and can be used for the prediction of clinical P-gp inhibition according to Food and Drug Administration (FDA) criteria, with notable sensitivity (80%). Therefore, the data demonstrated the feasibility of the use of rhodamine 123 for evaluating the P-gp inhibitory potential of drugs
Pharmaceutics

hal-01305488
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305488
DOI : 10.3390/pharmaceutics8020012
PUBMED : 27077878

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We show that a new definition of the asymptotic structure of the (C,E,P)-algebras (which are a refinement of the Colombeau Generalized Algebras) allows to define a natural topology on them. Furthermore, this topology can be mixed with functorial aspects of the construction in order to give extension principles, which give powerful tools to solve singular differential problems in this framework.
ISSN: 0022-247X

hal-01529551
https://hal.univ-antilles.fr/hal-01529551
DOI : 10.1016/j.jmaa.2009.05.046

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
The hematocrit-to-viscosity ratio (HVR) has been widely used has an estimate of red blood cell (RBC) oxygen transport effectiveness into the microvasculature or as an oxygen delivery index. However, no study investigated the possibility of HVR to truly reflect RBC oxygen transport effectiveness or to be an oxygen delivery index. We measured blood viscosity at high shear rate (225 s −1), hematocrit, HVR, as well as the microvascular oxyhemoglobin saturation (TOI; tissue oxygen index) by spatial resolved near-infrared spectroscopy (NIRS) at cerebral and muscle levels in three population known to have various degrees of hemorheological abnormalities: healthy subjects (AA), patients with sickle cell SC disease (SC) characterized by moderate anemia and patients with sickle cell anemia (SS) marked by severe anemia. At both the cerebral and muscle level, HVR was positively correlated with TOI (r = 0.28; p = 0.03 and r = 0.38; p = 0.003, at the cerebral and muscle level, respectively). These findings suggest that HVR probably play a key role in blood flow and hemodynamic regulation in the microvasculature, hence modulating the amount of oxygen available for tissues. Nevertheless, the strengths of the associations are weak (R 2 < 0.50), suggesting that other determinants modulate microvascular blood flow and oxygenation, such as vascular geometry and vasomotor reserve.
ISSN: 1386-0291

hal-01163460
https://hal.univ-antilles.fr/hal-01163460
DOI : 10.3233/CH-131742

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We use the low-regret notion of Lions for the control of a class of singular distributed systems: the ill-posed problems. A regularization approach is applied to the backwards heat equation, and we obtain a problem of incomplete data, for which the method of Nakoulima et al. is developed. Passing to the limit, a singular optimality system is obtained for the low-regret control of the original problem without any Slater hypothesis.
ISSN: 0893-9659

hal-00763938
https://hal.univ-antilles.fr/hal-00763938
DOI : 10.1016/j.aml.2003.04.006

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The regulatory mechanisms involved in the acquisition of thermal tolerance are unknown in insects. Reversible phosphorylation is a widespread post-translational modification that can rapidly alter proteins function(s). Here, we conducted a large-scale comparative screening of phosphorylation networks in adult Drosophila flies that were cold-acclimated versus control. Using a modified SIMAC method followed by a multiple MS analysis strategy, we identified a large collection of phosphopeptides (about 1600) and phosphoproteins (about 500) in both groups, with good enrichment efficacy (80%). The saturation curves from the four biological replicates revealed that the phosphoproteome was rather well covered under our experimental conditions. Acclimation evoked a strong phosphoproteomic signal characterized by large sets of unique and differential phosphoproteins. These were involved in several major GO superclusters of which cytoskeleton organization, positive regulation of transport, cell cycle, and RNA processing were particularly enriched. Data suggest that phosphoproteomic changes in response to acclimation were mainly localized within cytoskeletal network, and particularly within microtubule associated complexes. This study opens up novel research avenues for exploring the complex regulatory networks that lead to acquired thermal tolerance.
ISSN: 2045-2322

hal-01532256
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01532256
DOI : 10.1038/s41598-017-01974-z
PUBMED : 28490779

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The increased expression of the Disintegrin and Metalloprotease ADAM12 has been associated with human cancers, however its role remain unclear. We have previously reported that ADAM12 expression is induced by the transforming growth factor, TGF-β and promotes TGF-β-dependent signaling through interaction with the type II receptor of TGF-β. Here we explore the implication of ADAM12 in TGF-β-mediated epithelial to mesenchymal transition (EMT), a key process in cancer progression. We show that ADAM12 expression is correlated with EMT markers in human breast cancer cell lines and biopsies. Using a non-malignant breast epithelial cell line (MCF10A), we demonstrate that TGF-β-induced EMT increases expression of the membrane-anchored ADAM12L long form. Importantly, ADAM12L overexpression in MCF10A is sufficient to induce loss of cell-cell contact, reorganization of actin cytoskeleton, up-regulation of EMT markers and chemoresistance. These effects are independent of the proteolytic activity but require the cytoplasmic tail and are specific of ADAM12L since overexpression of ADAM12S failed to induce similar changes. We further demonstrate that ADAM12L-dependent EMT is associated with increased phosphorylation of Smad3, Akt and ERK proteins. Conversely, inhibition of TGF-β receptors or ERK activities reverses ADAM12L-induced mesenchymal phenotype. Together our data demonstrate that ADAM12L is associated with EMT and contributes to TGF-β-dependent EMT by favoring both Smad-dependent and Smad-independent pathways
ISSN: 1932-6203

hal-01207281
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207281
DOI : 10.1371/journal.pone.0139179
PUBMED : 26407179

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The TGF-β transforming growth factor is the most pleiotropic cytokine controlling a broad range of cellular responses that include proliferation, differentiation and apoptosis. The context-dependent multifunctional nature of TGF-β is associated with complex signaling pathways. Differential models describe the dynamics of the TGF-β canonical pathway, but modeling the non-canonical networks constitutes a major challenge. Here, we propose a qualitative approach to explore all TGF-β-dependent signaling pathways. RESULTS: Using a new formalism, CADBIOM, which is based on guarded transitions and includes temporal parameters, we have built the first discrete model of TGF-β signaling networks by automatically integrating the 137 human signaling maps from the Pathway Interaction Database into a single unified dynamic model. Temporal property-checking analyses of 15934 trajectories that regulate 145 TGF-β target genes reveal the association of specific pathways with distinct biological processes. We identify 31 different combinations of TGF-β with other extracellular stimuli involved in non-canonical TGF-β pathways that regulate specific gene networks. Extensive analysis of gene expression data further demonstrates that genes sharing CADBIOM trajectories tend to be co-regulated. CONCLUSIONS: As applied here to TGF-β signaling, CADBIOM allows, for the first time, a full integration of highly complex signaling pathways into dynamic models that permit to explore cell responses to complex microenvironment stimuli.
ISSN: 1752-0509

inserm-00978313
http://www.hal.inserm.fr/inserm-00978313
http://www.hal.inserm.fr/inserm-00978313/document
http://www.hal.inserm.fr/inserm-00978313/file/1752-0509-8-30.pdf
DOI : 10.1186/1752-0509-8-30

Éditeur(s) : HAL CCSD
Résumé : International audience
This paper deals with data structures within GIS. Continuous phenomenons are usually represented by raster structures for simplicity reasons. With such structures spatial repartitions of the data is not easily interpretable. Moreover, in an overlapping clustering context these structures remove the links between the data and the algorithms. We propose a vector representation of such data based on non-regular multi-rings polygons. The structure requires multipart nested polygons and new set operations. We present the formalism based on belief theory and uncertainty reasoning. We also detail the implementation of the structures and the set operations. The structures and the set operations are illustrated in the context of forest classification having diffuse transitions.
IF&GIS
Shangai, China

hal-01514239
https://hal.archives-ouvertes.fr/hal-01514239

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background : Trichoderma reesei is the main industrial source of cellulases and hemicellulases required for the hydrolysis of biomass to simple sugars, which can then be used in the production of biofuels and biorefineries. The highly productive strains in use today were generated by classical mutagenesis. As byproducts of this procedure, mutants were generated that turned out to be unable to produce cellulases. In order to identify the mutations responsible for this inability, we sequenced the genome of one of these strains, QM9136, and compared it to that of its progenitor T. reesei QM6a.Results : In QM9136, we detected a surprisingly low number of mutagenic events in the promoter and coding regions of genes, i.e. only eight indels and six single nucleotide variants. One of these indels led to a frame-shift in the Zn2Cys6 transcription factor XYR1, the general regulator of cellulase and xylanase expression, and resulted in its C-terminal truncation by 140 amino acids. Retransformation of strain QM9136 with the wild-type xyr1 allele fully recovered the ability to produce cellulases, and is thus the reason for the cellulase-negative phenotype. Introduction of an engineered xyr1 allele containing the truncating point mutation into the moderate producer T. reesei QM9414 rendered this strain also cellulase-negative. The correspondingly truncated XYR1 protein was still able to enter the nucleus, but failed to be expressed over the basal constitutive level.Conclusion : The missing 140 C-terminal amino acids of XYR1 are therefore responsible for its previously observed auto-regulation which is essential for cellulases to be expressed. Our data present a working example of the use of genome sequencing leading to a functional explanation of the QM9136 cellulase-negative phenotype.
ISSN: 1471-2164

Droits : http://creativecommons.org/licenses/by/
hal-01149671
http://hal.upmc.fr/hal-01149671
http://hal.upmc.fr/hal-01149671/document
http://hal.upmc.fr/hal-01149671/file/Lichius_2015_Genome_sequencing.pdf
DOI : 10.1186/s12864-015-1526-0

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study was designed to determine whether epinephrine may also target expression of main hepatic drug transporters, that play a major role in liver detoxification and are commonly coordinately regulated with drug detoxifying enzymes. Treatment of primary human hepatocytes with 10 mu M epinephrine for 24 h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP. Most of these changes in transporter mRNA levels were also found in epinephrine-exposed human highly-differentiated hepatoma HepaRG cells, which additionally exhibited reduced protein expression of OATP2B1 and MRP3, increased expression of P-glycoprotein and decreased transport activity of NTCP, OATPs and OCT1. Epinephrine effects towards transporter mRNA expression in human hepatocytes were next shown to be correlated to those of the selective beta 2-adrenoreceptor (ADR) agonist fenoterol, of the adenylate cyclase activator forskolin and of the cAMP analogue 8-bromo-cAMP. In addition, the non-selective beta-ADR antagonist carazolol and the selective beta 2-ADR antagonist ICI-118,551, unlike the alpha-ADR antagonist phentolamine, suppressed epinephrine -mediated repressions of transporter mRNA expression. Taken together, these data indicate that epinephrine regulates in vitro expression of main hepatic drug transporters in a beta 2-ADR/adenylate cyclase/cAMP-dependent manner. Hepatic drug transport appears therefore as a target of the beta 2-adrenergic system, which may have to deserve attention for drugs interacting with beta 2-ADRs.
ISSN: 0928-0987

hal-01578583
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578583
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578583/file/Mayati%20et%20al.%20-%20%CE%B22-adrenergic%20receptor-mediated%20in%20vitro%20regulatio.pdf
DOI : 10.1016/j.ejps.2017.06.010
PUBMED : 28603032