Résumé : La recevabilité est le cœur de la procédure judiciaire. Elle permet d’étudier la pénalisation de la vie internationale. Elle semble pouvoir rendre compte de la réponse judiciaire à la rancœur internationale au regard des grands faits criminels ; quel qu’en fut le territoire de commission.Cette thèse porte sur la notion de recevabilité devant la Cour pénale internationale. Avec la création de la CPI, la justice pénale internationale prend une dimension nouvelle. La pratique de la Cour est encore récente. L’étude est le prétexte pour examiner le fonctionnement de la Cour pénale internationale. Les Etats ont tenté de limiter la capacité de recevoir de la Cour. Ils l’ont ainsi fondée sur le principe de la complémentarité. Elle supplée l’inaction ou l’action défaillante des Etats, qui ont le devoir de poursuivre les auteurs de crimes internationaux. L’article 17 du Statut de Rome énonce les exceptions permettant de déclarer une affaire recevable devant la CPI. Ainsi, la recevabilité d’une affaire ayant fait l’objet d’une enquête ne sera retenue que s’il est prouvé que les Etats n’ont pas l’intention de mener véritablement à bien les poursuites. Et, que par ailleurs, le seuil de gravité de l’affaire est atteint. Le caractère universel de la compétence de la CPI est battu en brèche par les conditions de recevabilité. On analyse la recevabilité comme une condition de compétence à juste titre, car c’est bien le manquement de l’Etat à assurer l’effectivité des poursuites qui justifie que l’affaire soit déclarée, par la Cour elle-même, recevable. Les conditions requises pour que la Cour puisse agir, force est de constater l’implication du système de recevabilité tant sur l’organisation de la Cour que sur ses rapports avec les Etats. Celles-ci ne sont pas négligeables. De fait, le système de recevabilité est amené à évoluer. Il se caractérise par sa capacité à influencer le droit interne. Ainsi, la décision de recevoir doit amener les Etats à adapter leur droit interne. La viabilité de la Cour, à long terme, dépend du maintien d’une synergie de coopération avec les juridictions nationales, des États parties et d'autres Etats. Le système de recevabilité tend à mettre en évidence des indicateurs émergents dans la pratique de la Cour pénale internationale. C’est notamment le réalignement frappant des rôles des acteurs internationaux et la relation nouvelle qui s’instaure entre les Etats et la Cour. Le système de recevabilité de la Cour tend à éroder le principe de la souveraineté de l'Etat, sans être elle-même balayée par l'opposition catégorique des Etats souverains.
Admissibility is the heart of the judicial process. It studies the criminalization of international life. It seems to account for the judicial response to the international resentment against the great criminal acts, whatever was the territory of commission.This thesis deals with the notion of admissibility before the ICC. With the creation of the ICC, International Criminal Justice is a new dimension. The practice of the Court is still new. The study is an excuse to investigate the operation of the ICC. States have tried to limit the ability to receive from the Court. They did so based on the principle of complementarity. It compensates the action or inaction of failing states, which have a duty to prosecute international crimes. Article 17 RS sets out exceptions to declare a case admissible before the ICC. Thus, the admissibility of a case which is the subject of an investigation will be accepted only, if it is shown that States did not intend genuinely to carry out prosecutions. And that furthermore, the threshold of gravity of a case is reached. The universal nature of the jurisdiction of the ICC is undermined by the conditions of admissibility. Analyzing the admissibility of competence as a condition rightly, for it is the failure of the state to ensure effective prosecution to justify that the case will be declared by the Court itself, admissible. The requirements for the Court to act, it is clear involvement of the system of admissibility as on the organization of the Court that its relationship with the United States. These are not insignificant. In fact, the system will evolve admissibility. It is characterized by its ability to influence the law. Thus, the decision to receive should encourage States to adapt their domestic law. The viability of the Court, in the long run depends on maintaining a synergy of cooperation with national courts of States Parties and other States. The system of admissibility tends to highlight indicators emerging in the practice of the International Criminal Court. This is especially striking realignment of the roles of international actors and the new relationship established between the States and the Court. The system of admissibility of the Court tends to erode the principle of state sovereignty, without itself being swept by the opposition of sovereign states.

http://www.theses.fr/2011AGUY0468

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 (R2 < 0.50), suggesting that other determinants modulate microvascular blood flow and oxygenation, such as vascular geometry and vasomotor reserve.
ISSN: 1386-0291

inserm-01081701
http://www.hal.inserm.fr/inserm-01081701
http://www.hal.inserm.fr/inserm-01081701/document
http://www.hal.inserm.fr/inserm-01081701/file/2013%2C%20Waltz%20-%20Is%20there%20a%20relationship%20between%20the%20hematocrit-to-viscosity%20ratio%20and%20microvascular%20oxygenation%20in%20brain%20and%20muscle.pdf
PUBMED : 23719422

Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
ISSN: 0006-4971

inserm-00821109
http://www.hal.inserm.fr/inserm-00821109
http://www.hal.inserm.fr/inserm-00821109/document
http://www.hal.inserm.fr/inserm-00821109/file/De_Grandis_Blood_2013.pdf
DOI : 10.1182/blood-2012-07-440487

Éditeur(s) : HAL CCSD
Résumé : Semi-volatile organic compounds (SVOCs) are widely present in indoor environments and are suspected to be repro- or neurotoxic but little is known on the health impact on SVOC mixtures. The objective of this work is to derive cumulative toxicity indicators for SVOCs detected in French dwellings in carrying forward a cumulative health risk assessment. SVOCs were grouped according to their repro- and neurotoxic common modes of action (i.e. decrease in serum testosterone concentrations, decrease in neuronal viability). Benchmark doses (BMDs) were then estimated by modeling dose-response relationships from scientific literature (Hill models, PROAST, RIVM). Comparable BMDs were estimated only for 6 of the 19 reprotoxic SVOCs which are responsible to 10 or 50% decrease in testosterone in adult male rats orally exposed. Estimated relative potency factors (RPFs) from BMDs are similar according to the response level (from 1600 for the B(a)P to 0.1 for the BBP), excepted for bisphenol A moving from 7E+6 to 180. For in vitro neuronal death, BMDs were estimated for 13 neurotoxic SVOCs using data from different cell lines and species. BMDs equivalent to a 10% of response range from 0.07 (PCB-153) to 95 µM (diazinon). The originality of this work is the grouping of compounds from different chemical families which we are really exposed to. BMDs estimation from published data was possible but many methodological limitations lead us to put forward recommendations especially on the standardization of experimental protocols and the availability of results in adapted format for dose-response relationship modeling.
Les composés organiques semi volatils (COSV) sont largement présents dans les environnements intérieurs et sont suspectés d’être repro- ou neurotoxiques, mais peu de données sont disponibles quant à leur toxicité en mélanges. L’objectif de cette thèse est de proposer des indicateurs de toxicité cumulés pour les COSV détectés dans les logements français, dans un cadre d’évaluation des risques sanitaires cumulés. Les COSV ont été regroupés en fonction de leurs modes d’action communs, en lien avec les effets reprotoxiques (diminution de la concentration de testostérone sérique) et neurotoxiques (diminution de la viabilité neuronale). Des benchmark doses (BMD) ont ensuite été estimées par modélisation (modèle de Hill, PROAST, RIVM) des relations dose-réponse de la littérature décrivant la réponse d’intérêt. Des BMD comparables ont pu être estimées seulement pour 6 des 19 COSV reprotoxiques induisant une diminution de testostérone de 10 ou 50 % chez le rat adulte exposé par voie orale. Les facteurs de toxicité relatifs (RPF) estimés à partir des BMD sont sensiblement les mêmes en fonction du niveau de réponse (de 1600 pour le B(a)P à 0,1 pour le BBP), excepté pour le biphénol A qui passe de 7E+6 à 180. Considérant la mort neuronale in vitro, des BMD ont pu être estimées pour 13 COSV neurotoxiques, à partir de données provenant de différentes lignées et espèces. Les BMD équivalent à un niveau de réponse de 10 % s’échelonnent de 0,07 (PCB-153) à 95 µM (diazinon). L’originalité de ce travail repose sur le regroupement de composés de familles chimiques différentes qui constituent des contaminations réelles de notre environnement. Si l’estimation des quelques BMD a été possible à partir des données de la littérature, de nombreuses limites méthodologiques conduisent à émettre des recommandations en particulier sur la standardisation des protocoles expérimentaux et la disponibilité des résultats sous une forme adaptée à la modélisation de la relation dose-réponse.
https://tel.archives-ouvertes.fr/tel-01308535

NNT : 2015REN1B019
tel-01308535
https://tel.archives-ouvertes.fr/tel-01308535
https://tel.archives-ouvertes.fr/tel-01308535/document
https://tel.archives-ouvertes.fr/tel-01308535/file/Kevin_Fournier-.pdf

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Introduction: Drug transporters are now recognized as major players involved in pharmacokinetics and toxicology. Methods for assessing their activity are important to consider, particularly owing to regulatory requirements with respect to inhibition of drug transporter activity and prediction of drug–drug interactions. In this context, the use of fluorescent-dye-based transport assays is likely to deserve attention.Areas covered: This review provides an overview of the nature of fluorescent dye substrates for ATP-binding cassette and solute carrier drug transporters. Their use for investigating drug transporter activity in cultured cells and clinical hematological samples, drug transporter inhibition, drug transporter imaging and drug transport at the organ level are summarized.Expert opinion: A wide range of fluorescent dyes is now available for use in various aspects of drug transporter studies. The use of these dyes for transporter analyses may, however, be hampered by classic pitfalls of fluorescence technology, such as quenching. Transporter-independent processes such as passive diffusion of dyes through plasma membrane or dye sequestration into subcellular compartments must also be considered, as well as the redundant handling by various distinct transporters of some fluorescent probes. Finally, standardization of dye-based transport assays remains an important on-going issue
ISSN: 1742-5255

hal-01162381
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162381
DOI : 10.1517/17425255.2015.1053462
PUBMED : 26050735

Éditeur(s) : Université des Antilles Études caribéennes
Résumé : Le tourisme est souvent présenté comme l’un des instruments d’un développement durable, même s’il connaît une expansion difficilement maîtrisable, au détriment du patrimoine environnemental, insulaire et littoral en particulier, comme dans les DOM-TOM.Le tourisme a des impacts, culturels et sociaux notamment, sur l’environnement. Les ressources du patrimoine alimentent de leur côté la demande et l’offre touristiques. Un tourisme assis sur une gestion ad hoc des ressources du patrimoine constitue un facteur puissant de durabilité du développement local. La soumission de l’activité touristique aux exigences de protection, de conservation et de gestion reproductible de la biodiversité et du patrimoine naturel, dans les aires protégées de la Caraïbe française en particulier, génère des approches, des stratégies et des comportements nouveaux. La démarche écotouristique appelle une gestion participative et intégrée des ressources et des espaces, et constitue un défi pour les opérateurs du tourisme comme pour les acteurs de l’environnement, et une opportunité de « réappropriation » de leur milieu de vie par les populations locales. Il faut alors en clarifier le concept et les implications ; puis en analyser les objectifs et les enjeux dans une perspective de développement durable.
Tourism often appears as one a tool for a sustainable development, even if it is not easy to control, in the détriment of island and costal environment heritage, as in French overseas regions. Besides the cultural and social impacts of tourism upon environment, the heritage resources nuture the touristic request and offer. If based on an appropriate management of those resources, it may be a strong incentive for local sustainable development. The respect of protection, conservation and sustainable management of biodiversity and natural resources by tourism, especially in the overseas regions of French West Indies, produces new approaches, strategies and behaviours. The ecotourism approach, calling for a joint and integrated management of resources and areas, is a challenge for tour operators as for environment actors, and brings local population an opportunity to reappropriate their life environment. Its concept and implications must then be clarified, before analysing its aims and stakes regarding sustainable development
Caraïbes

Droits : info:eu-repo/semantics/openAccess
urn:doi:10.4000/etudescaribeennes.3560
http://journals.openedition.org/etudescaribeennes/3560

Éditeur(s) : HAL CCSD
Résumé : International audience
Migration of chemicals from packaging materials to foods may lead to human exposure. Polyfluoroalkyl substances (PFAS) can be used in technical mixtures (TMs) for use in food packaging of paper and board, and PFAS have been detected in human serum and umbilical cord blood. The specific structures of the PFAS in TMs are often unknown, but polyfluorinated alkyl phosphate esters (PAPs) have been characterized in TMs, food packaging, and in food. PAPs can be metabolized into fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Some PFAS have endocrine activities, highlighting the need to investigate these effects. Herein, we studied the endocrine activity of less characterized PFAS, including short-chain PFCAs and FTOHs, PAPs, and TMs of unknown chemical composition. Long-chain PFCAs were also included. We applied seven assays covering effects on estrogen, glucocorticoid, androgen, and peroxisome proliferator-activated receptor (PPAR) activity, as well as steroidogenesis in vitro and ex vivo. In general, PAPs, FTOHs, TMs, and long-chain PFCAs showed estrogenic activity through receptor activation and/or increasing 17β-estradiol levels. Furthermore, short- and long-chain PFCAs activated PPARα and PPARγ. Collectively, this means that (i) PAPs, FTOHs, and PFCAs exhibit endocrine activity through distinct and sometimes different mechanisms, (ii) two out of three tested TMs exhibited estrogenic activity, and (iii) short-chain FTOHs showed estrogenic activity and short-chain PFCAs generally activate both PPARα and PPARγ with similar potency and efficacy as long-chain PFCAs. In conclusion, several new and divergent toxicological targets were identified for different groups of PFAS. © 2016 American Society of Andrology and European Academy of Andrology
Andrology

hal-01367144
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367144
DOI : 10.1111/andr.12190
PUBMED : 27152447

Éditeur(s) : HAL CCSD ACSM
Résumé : International audience
PURPOSE AND METHODS: This study was designed to determine whether the physiological responses elicited during the run part of repeated bouts of cycle-run exercise are similar to those required during the run segment of a cycle-run succession. Thirteen male triathletes underwent four successive laboratory trials: 1) an incremental treadmill test, 2) an incremental cycle test, 3) 30 min of cycling followed by 20 min of running (C-R), and 4) five repeated bouts of 6 min of cycling and 4 min of running (X-CR). During the C-R and X-CR trials, venous blood samples were obtained to measure lactate, epinephrine and norepinephrine concentrations. During all trials, ventilatory data were collected every min using an automated breath-by-breath system. RESULTS: The results showed that 1) the cardiorespiratory responses observed during running were similar in the X-CR and C-R trials, 2) the lactate concentration was similar in both trials, 3) the epinephrine concentration was greater (277.9 +/- 11.9 vs 169.8 +/- 86.7 pg x mL(-1), P < 0.025) in X-CR than in C-R, and 4) the norepinephrine concentration was similar in both trials, except at the first cycle-run succession (T1) of X-CR. CONCLUSION: We concluded that 1) multi-block training is a good method to stimulate the specific adaptations required for the cycle-run succession, and particularly for the cycle-run transition, and 2) multi-block training seems to induce a greater catecholaminergic response, which may be due to a combination of an inherent effect of this type of training and the triathletes' relative lack of experience with it. In any case, the efficacy of the multi-block model needs to be more thoroughly evaluated over the course of a longer-term training program.
Medicine & Science in Sports & exercise

hal-00720475
https://hal.univ-antilles.fr/hal-00720475
https://hal.univ-antilles.fr/hal-00720475/document
https://hal.univ-antilles.fr/hal-00720475/file/Article_2_.pdf

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The retroviral genome consists of an intron-containing transcript that has essential cytoplasmic functions in the infected cell. This viral transcript can escape splicing, circumvent the nuclear checkpoint mechanisms and be transported to the cytoplasm by hijacking the host machinery. Once in the cytoplasm, viral unspliced RNA acts as mRNA to be translated and as genomic RNA to be packaged into nascent viruses. The murine leukemia virus (MLV) is among the first retroviruses discovered and is classified as simple Retroviridae due to its minimal encoding capacity. The oncogenic and transduction abilities of MLV are extensively studied, whereas surprisingly the crucial step of its nuclear export has remained unsolved until 2014. Recent work has revealed the recruitment by MLV of the cellular NXF1/Tap-dependent pathway for export. Unconventionally, MLV uses of Tap to export both spliced and unspliced viral RNAs. Unlike other retroviruses, MLV does not harbor a unique RNA signal for export. Indeed, multiple sequences throughout the MLV genome appear to promote export of the unspliced MLV RNA. We review here the current understanding of the export mechanism and highlight the determinants that influence MLV export. As the molecular mechanism of MLV export is elucidated, we will gain insight into the contribution of the export pathway to the cytoplasmic fate of the viral RNA
ISSN: 1547-6286

hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/file/Insights%20into%20the%20nuclear%20export%20of%20murine%20leukemia%20virus%20intron-containing%20RNA.pdf
DOI : 10.1080/15476286.2015.1065375

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Although TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) is a well-known apoptosis inducer, we have previously demonstrated that acidic extracellular pH (pHe) switches TRAIL-induced apoptosis to regulated necrosis (or necroptosis) in human HT29 colon and HepG2 liver cancer cells. Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-induced murine hepatitis. Pretreatment of HT29 or HepG2 with pharmacological inhibitors of RIPK1 or PARP-1 (Nec-1 or PJ-34, respectively), or transient transfection with siRNAs against RIPK1 or RIPK3, inhibited both TRAIL-induced necroptosis and PARP-1-dependent intracellular ATP depletion demonstrating that RIPK1 and RIPK3 were involved upstream of PARP-1 activation and ATP depletion. In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34. These data provide new insights into TRAIL-induced necroptosis with PARP-1 being active effector downstream of RIPK1/RIPK3 initiators and suggest that pharmacological inhibitors of RIPKs and PARP-1 could be new treatment options for immune-mediated hepatitis.
ISSN: 1350-9047

inserm-00871432
http://www.hal.inserm.fr/inserm-00871432
DOI : 10.1038/cdd.2012.90
PUBMED : 22814620

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Because of the metabolic changes induced by a physical activity, the hemorheological properties of patients with sickle cell anemia could be further impaired and increase the risks for vaso-occlusive complications. However, few studies suggest that moderate physical activity could be beneficial rather than harmful in patients with sickle cell anemia (SCA). However, the definition of what can be considered as a moderate physical activity in SCA patients is imprecise. The present study tested the effects of a short incremental cycling exercise test conducted until the first ventilatory threshold on different biomarkers. Hematological and hemorheological parameters were compared between 8 patients with SCA and 13 healthy subjects (CONT) before, immediately after the end of the exercise and at 12, 36 and 60 hours after the exercise. We observed no significant hematological or hemorheological alteration induced by the exercise in the two groups. However, the exercise resulted in a delayed improvement of the red blood cell disaggregation threshold at 36 and 60 hrs after exercise in the SCA group which was paralleled to the decrease in the platelet count in this group. The present study suggests that such an exercise might be beneficial for microcirculatory blood flow.
ISSN: 1386-0291

hal-01137567
https://hal.univ-antilles.fr/hal-01137567

Éditeur(s) : HAL CCSD
Résumé : The Green and Blue infrastructure (Trame verte et bleue ?TVB) is a new conservation policy tool based on the notions of ecological network and corridor. The TVB's implementation process establishes the connection of multi and nested decisional and action levels and needs permanent adjustment to change that is analyzed as adaptive governance mechanisms. The implementation of an adaptive governance is described as an mean to overpass those failures. The literature on adaptive governance gives learning process a central place as it permits to systematically improve policies and practices for an effective preservation of the environment. The aim of this article is to provide a critical perspective on learning processes in adaptive governance. We aim at reintroducing two blind spots. First, knowledge theory frequently forget to consider the strategic issue of knowledge. Second, knowledge theory implicitly recognizes that an actor acts but, it is often true that an actor can «be acted».
ESEE 2013 - Ecological Economics and Institutional Dynamics - 10th International Conference of the European Society for Ecological Economics
Lille, France

hal-01195358
https://hal.archives-ouvertes.fr/hal-01195358
PRODINRA : 226906

Éditeur(s) : HAL CCSD
Résumé : International audience
Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.
Physiological Reviews

hal-01533249
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533249
DOI : 10.1152/physrev.00024.2016
PUBMED : 28539435

Éditeur(s) : HAL CCSD
Résumé : International audience
Primary cultures of hepatocytes are powerful models in studying the sequence of events that are necessary for cell progression from a G0-like state to S phase. The models mimic the physiological process of hepatic regeneration after liver injury or partial hepatectomy. Many reports suggest that the mitogen-activated protein kinase (MAPK) ERK1/2 can support hepatocyte proliferation in vitro and in vivo and the MEK/ERK cascade acts as an essential element in hepatocyte responses induced by the EGF. Moreover, its disregulation has been associated with the promotion of tumor cell growth of a variety of tumors, including hepatocellular carcinoma. Whereas the strict specificity of action of ERK1 and ERK2 is still debated, the MAPKs may have specific biological functions under certain contexts and according to the differentiation status of the cells, notably hepatocytes. In this paper, we will focus on MEK1/2-ERK1/2 activations and roles in normal rodent hepatocytes in vitro and in vivo after partial hepatectomy and in human hepatocarcinoma cells. The possible specificity of ERK1 and ERK2 in normal and transformed hepatocyte will be discussed in regard to other differentiated and undifferentiated cellular models.
International Journal of Hepatology

Droits : info:eu-repo/semantics/OpenAccess
hal-00875664
https://hal.archives-ouvertes.fr/hal-00875664
https://hal.archives-ouvertes.fr/hal-00875664/document
https://hal.archives-ouvertes.fr/hal-00875664/file/TheMAPKMEK12-accepted.pdf
DOI : 10.1155/2012/328372

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Until recently, synonymous mutations (which do not change amino acids) have been much neglected. Some evidence suggests that this kind of mutations could affect mRNA secondary structure or stability, translation kinetics and protein structure. To explore deeper the role of synonymous mutations, we studied their consequence on the functional activity of the estrogen receptor alpha (ERα). The ERα is a ligand-inducible transcription factor that orchestrates pleiotropic cellular effects, at both genomic and non-genomic levels in response to estrogens. In this work we analyzed in transient transfection experiments, the activity of ERα carrying the synonymous mutation Ala87, a polymorphism involving about 5-10% of the population. In comparison to the wild type receptor, our results show that ERαA87 mutation reduces the transactivation efficiency of ERα on an ERE reporter gene while its expression level remains similar. This mutation enhances 4-OHT-induced transactivation of ERα on an AP1 reporter gene. Finally, the mutation affects the subcellular localization of ERα in a cell type specific manner. It enhances the cytoplasmic location of ERα without significant changes in non-genomic effects of E2. The functional alteration of the ERαA87 determined in this work highlights the relevance of synonymous mutations for biomedical and pharmacological points of view.
Journal of steroid biochemistry and molecular biology

inserm-01015532
http://www.hal.inserm.fr/inserm-01015532
DOI : 10.1016/j.jsbmb.2014.02.016
PUBMED : 24607813

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The tg(cyp19a1b-GFP) transgenic zebrafish expresses GFP (green fluorescent protein) under the control of the cyp19a1b gene, encoding brain aromatase. This gene has two major characteristics: (i) it is only expressed in radial glial progenitors in the brain of fish and (ii) it is exquisitely sensitive to estrogens. Based on these properties, we demonstrate that natural or synthetic hormones (alone or in binary mixture), including androgens or progestagens, and industrial chemicals induce a concentration-dependent GFP expression in radial glial progenitors. As GFP expression can be quantified by in vivo imaging, this model presents a very powerful tool to screen and characterize compounds potentially acting as estrogen mimics either directly or after metabolization by the zebrafish embryo. This study also shows that radial glial cells that act as stem cells are direct targets for a large panel of endocrine disruptors, calling for more attention regarding the impact of environmental estrogens and/or certain pharmaceuticals on brain development. Altogether these data identify this in vivo bioassay as an interesting alternative to detect estrogen mimics in hazard and risk assessment perspective.
ISSN: 1932-6203

hal-00877371
https://hal.archives-ouvertes.fr/hal-00877371
https://hal.archives-ouvertes.fr/hal-00877371/document
https://hal.archives-ouvertes.fr/hal-00877371/file/Screening_Estrogenic_Activities-accepted.pdf
DOI : 10.1371/journal.pone.0036069

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: HCV treatment uptake has drastically increased in HIV-HCV coinfected patients in France since direct-acting antiviral (DAA) treatment approval, resulting in HCV cure in 63% of all HIV-HCV patients by the end of 2015. We investigated the impact of scaling-up DAA on HCV prevalence in the whole HIV population and in various risk groups over the next 10 years in France using a transmission dynamic compartmental model.Methods: The model was based on epidemiological data from the French Dat’AIDS cohort. Eight risk groups wereconsidered, including high-risk (HR) and low-risk (LR) men who have sex with men (MSM) and male/female heterosexuals,intra-venous drug users, or patients from other risk groups. The model was calibrated on prevalence and incidence dataobserved in the cohort between 2012 and 2015.Results: On January 1, 2016, 156,811 patients were registered as infected with HIV in France (24,900 undiagnosedpatients) of whom 7938 (5.1%) had detectable HCV-RNA (722 undiagnosed patients). Assuming a treatmentcoverage (TC) rate of 30%/year (i.e., the observed rate in 2015), model projections showed that HCV prevalenceamong HIV patients is expected to drop to 0.81% in 2026. Sub-analyses showed a similar decrease of HIV-HCVprevalence in most risk groups, including LR MSM. Due to higher infection and reinfection rates, predicted prevalencein HR MSM remained stable from 6.96% in 2016 to 6.34% in 2026. Increasing annual TC rate in HR MSM to 50/70%would decrease HCV prevalence in this group to 2.35/1.25% in 2026. With a 30% TC rate, undiagnosed patients wouldaccount for 34% of HCV infections in 2026.Conclusions: Our model suggests that DAA could nearly eliminate coinfection in France within 10 years for most riskgroups, including LR MSM. Elimination in HR MSM will require increased TC.
ISSN: 1741-7015

Droits : info:eu-repo/semantics/OpenAccess
inserm-01685739
http://www.hal.inserm.fr/inserm-01685739
http://www.hal.inserm.fr/inserm-01685739/document
http://www.hal.inserm.fr/inserm-01685739/file/2017%2C%20Virlogeux%20-%20Modeling%20HIV-HCV%20coinfection.pdf
DOI : 10.1186/s12916-017-0979-1

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The brain of the adult teleost fish exhibits intense neurogenic activity and an outstanding capability for brain repair. Remarkably, the brain estrogen-synthesizing enzyme, aromatase B, is strongly expressed, particularly in adult fishes, in radial glial cells, which act as progenitors. Using zebrafish, we tested the hypothesis that estrogens affect adult neurogenesis and brain regeneration by modulating the neurogenic activity of radial glial cells. To investigate this, the estrogenic environment was modified through inhibition of aromatase activity, blockade of nuclear estrogen receptors, or estrogenic treatments. Estrogens significantly decreased cell proliferation and migration at the olfactory bulbs/telencephalon junction and in the mediobasal hypothalamus. It also appears that cell survival is reduced at the olfactory bulbs/telencephalon junction. We also developed a model of telencephalic lesion to assess the role of aromatase and estrogens in brain repair. Proliferation increased rapidly immediately after the lesion in the parenchyma of the injured telencephalon, while proliferation at the ventricular surface appeared after 48 h and peaked at 7 days. At this time, most proliferative cells express Sox2, however, none of these Sox2 positive cells correspond to aromatase B-positive radial glial cells. Interestingly, aromatase B expression was significantly reduced 48 h and 7 days after the injury, but surprisingly, at 72 h after lesion, aromatase B expression appeared de novo expressed in parenchyma cells, suggesting a role for this ectopic expression of aromatase in brain repair mechanisms. Altogether these data suggest that estrogens modulate adult, but not reparative neurogenesis, in zebrafish.
ISSN: 0018-506X

inserm-00831715
http://www.hal.inserm.fr/inserm-00831715
DOI : 10.1016/j.yhbeh.2012.04.003
PUBMED : 22521210

Éditeur(s) : HAL CCSD
Résumé : National audience
Objectives To define the different stages of spontaneous labour. To determine the indications, modalities of use and the effects of administering synthetic oxytocin. And to describe undesirable maternal and perinatal outcomes associated with the use of synthetic oxytocin. Method A systematic review was carried out by searching Medline database and websites of obstetrics learned societies until March 2016. Results The 1st stage of labor is divided in a latence phase and an active phase, which switch at 5 cm of cervical dilatation. Rate of cervical dilatation is considered as abnormal below 1 cm per 4 hour during the first part of the active phase, and blow 1 cm per 2 hours above 7 cm of dilatation. During the latent phase of the first stage of labor, i.e. before 5 cm of cervical dilatation, it is recommended that an amniotomy not be performed routinely and not to use oxytocin systematically. It is not recommended to expect the active phase of labor to start the epidural analgesia if patient requires it. If early epidural analgesia was performed, the administration of oxytocin must not be systematic. If dystocia during the active phase, an amniotomy is recommended in first-line treatment. In the absence of an improvement within an hour, oxytocin should be administrating. However, in the case of an extension of the second stage beyond 2 hours, it is recommended to administer oxytocin to correct a lack of progress of the presentation. If dynamic dystocia, it is recommended to start initial doses of oxytocin at 2 mUI/min, to respect at least 30 min intervals between increases in oxytocin doses delivered, and to increase oxytocin doses by 2 mUI/min intervals without surpassing a maximum IV flow rate of 20 mUI/min. The reported maternal adverse effects concern uterine hyper-stimulation, uterine rupture and postpartum haemorrhage, and those of neonatal adverse effects concern foetal heart rate anomalies associated with uterine hyper-stimulation, neonatal morbidity and mortality, neonatal jaundice, weak suck/poor breastfeeding latch and autism. Conclusion The widespread use of oxytocin during spontaneous labour must not be considered as simply another inoffensive prescription without any possible deleterious consequences for mother or foetus. Conditions for administering the oxytocin must therefore respect medical protocols. Indications and patient consent have to be report in the medical file. © 2016 Elsevier Masson SAS
Revue Sage - Femme

hal-01467543
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467543
DOI : 10.1016/j.sagf.2016.11.006

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
ABSTRACT: BACKGROUND: Climate change poses unprecedented challenges, ranging from global and local policy challenges to personal and social action. Heat-related deaths are largely preventable, but interventions for the most vulnerable populations need improvement. Therefore, the prior identification of high risk areas at the community level is required to better inform planning and prevention. We aimed to demonstrate a simple and flexible conceptual framework relying upon satellite thermal data and other digital data with the goal of easily reproducing this framework in a variety of urban configurations. RESULTS: The study area encompasses Rennes, a medium-sized French city. A Landsat ETM + image (60 m resolution) acquired during a localized heatwave (June 2001) was used to estimate land surface temperature (LST) and derive a hazard index. A land-use regression model was performed to predict the LST. Vulnerability was assessed through census data describing four dimensions (socio-economic status, extreme age, population density and building obsolescence). Then, hazard and vulnerability indices were combined to deliver a heatwave health risk index. The LST patterns were quite heterogeneous, reflecting the land cover mosaic inside the city boundary, with hotspots of elevated temperature mainly observed in the city center. A spatial error regression model was highly predictive of the spatial variation in the LST (R2 = 0.87) and was parsimonious. Three land cover descriptors (NDVI, vegetation and water fractions) were negatively linked with the LST. A sensitivity analysis (based on an image acquired on July 2000) yielded similar results. Southern areas exhibited the most vulnerability, although some pockets of higher vulnerability were observed northeast and west of the city. The heatwave health risk map showed evidence of infra-city spatial clustering, with the highest risks observed in a north--south central band. Another sensitivity analysis gave a very high correlation between 2000 and 2001 risk indices (r = 0.98, p < 10-12). CONCLUSIONS: Building on previous work, we developed a reproducible method that can provide guidance for local planners in developing more efficient climate impact adaptations. We recommend, however, using the health risk index together with hazard and vulnerability indices to implement tailored programs because exposure to heat and vulnerability do not require the same prevention strategies.
ISSN: 1476-072X

inserm-00762303
http://www.hal.inserm.fr/inserm-00762303
http://www.hal.inserm.fr/inserm-00762303/document
http://www.hal.inserm.fr/inserm-00762303/file/1476-072X-11-38.pdf
DOI : 10.1186/1476-072X-11-38