Éditeur(s) : Université des Antilles et de la Guyane Agence des 50 pas géométriques Université des Antilles et de la Guyane Agence des 50 pas géométriques
Extrait de : 3e forum Bodlanmè. "Une zone de croissance durable ?", les 6 et 7 juin 2013. Université des Antilles et de la Guyane
Description : L'adjoint au maire de Schoelcher, M. Gommier, ouvre ce forum Bodlanmè dédié aux liens entre les zones littorales et l'économie. Sont présentes diverses personnalités du monde politique et de l'environnement, dont Ralph Monplaisir (président de l'agence des pas géométriques de la Martinique), Marie-Lucile BRESLAU (présidente de l'agence des 50 pas géométriques de la Guadeloupe), Jean-François Rapin (président de l'Association Nationale des Elus du Littoral), Daniel Chaumet (président de la commission environnement du conseil régional de la Martinique) et Laurent Prévost (préfet de région).
Siècle(s) traité(s) : 21
Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V13167
V13167
V13167
V13167

Éditeur(s) : Université des Antilles et de la Guyane. Service commun de la documentation
Description : L'association "Tchok en doc" organise du 4 novembre au 3 décembre 2011 le mois du film documentaire en Martinique autour de la thématique : "Retour vers soi". La bibliothèque universitaire du campus de Schoelcher s'associe à cette manifestation autour d'un débat intéressant sur la démarche et l'esthétique du cinéma documentaire avec Gilles-Elie-dit-Cosaque, Marie-Claude Céleste, Laurent Cadoux et Nathalie Glaudon. Ils échangeront autour des pratiques documentaires en Outre-mer, du documentaire comme témoin de la réalité et de leurs perceptions en tant que réalisateurs.
Siècle(s) traité(s) : 21
Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V12134
V12134

Éditeur(s) : Université des Antilles
Description : Dans les années 1970, l'échec scolaire est particulièrement élevé en Martinique comparativement à la France hexagonale. Le système scolaire est de plus en plus ouvertement qualifié d'inadapté, de colonialiste et assimilationniste. A partir des années 1980, des intellectuels, des organisations de parents d'élèves, des enseignants, des syndicats, des partis politiques et des associations vont revendiquer d'abord l'adaptation des programmes d'enseignement au vécu et à l'environnement des jeunes Martiniquais puis, assez rapidement, l'introduction de la langue créole à l?école. Ce mémoire de DEA retrace ces mouvements puis s'intéresse en particulier à la position des enseignants martiniquais face à la question de l?adaptation des programmes, aux demandes d'adaptations, aux revendications. La méthodologie s'appuie sur le dépouillement de sources complété par une série d'entretiens.
Siècle(s) traité(s) : 20
Droits : Ce document est protégé par le droit d'auteur. Il ne peut en aucun cas être utilisé sans l'autorisation de l'auteur et des ayant droits
Permalien : http://www.manioc.org/recherch/T20029
T20029

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0003-4975

hal-01563338
http://hal.univ-brest.fr/hal-01563338
DOI : 10.1016/j.athoracsur.2016.03.093
PUBMED : 27262916

Éditeur(s) : HAL CCSD
Résumé : International audience
Conférence MISTRALS PAELOMEX
Montpellier, France

hal-01683548
https://hal-univ-tlse2.archives-ouvertes.fr/hal-01683548

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
ISSN: 0959-8049

hal-01666517
https://hal.univ-lorraine.fr/hal-01666517
DOI : 10.1016/j.ejca.2015.11.024

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The release of polycyclic aromatic hydrocarbons (PAHs) into the environment has increased very substantially over the last decades. PAHs are hydrophobic molecules which can accumulate in high concentrations in sediments acting then as major secondary sources. Fish contamination can occur through contact or residence nearby sediments or though dietary exposure. In this study, we analyzed certain physiological traits in unexposed fish (F1) issued from parents (F0) exposed through diet to three PAH mixtures at similar and environmentally relevant concentrations but differing in their compositions. For each mixture, no morphological differences were observed between concentrations. An increase in locomotor activity was observed in larvae issued from fish exposed to the highest concentration of a pyrolytic (PY) mixture. On the contrary, a decrease in locomotor activity was observed in larvae issued from heavy oil mixture (HO). In the case of the third mixture, light oil (LO), a reduction of the diurnal activity was observed during the setup of larval activity. Behavioral disruptions persisted in F1-PY juveniles and in their offspring (F2). Endocrine disruption was analyzed using cyp19a1b:GFP transgenic line and revealed disruptions in PY and LO offspring. Since no PAH metabolites were dosed in larvae, these findings suggest possible underlying mechanisms such as altered parental signaling molecule and/or hormone transferred in the gametes, eventually leading to early imprinting. Taken together, these results indicate that physiological disruptions are observed in offspring of fish exposed to PAH mixtures through diet.
ISSN: 0944-1344

hal-01121865
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121865
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121865/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121865/file/Exposures%20of%20zebrafish_accepted.pdf
DOI : 10.1007/s11356-015-4157-8

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
We assessed the occurrence of algae in five species of tank-bromeliads found in contrasting environmental sites in a Neotropical, primary rainforest around the Nouragues Research Station, French Guiana. The distributions of both algal abundance and biomass were examined based on physical parameters, the morphological characteristics of bromeliad species and with regard to the structure of other aquatic microbial communities held in the tanks. Algae were retrieved in all of the bromeliad species with mean densities ranging from ∼10(2) to 10(4) cells/mL. Their biomass was positively correlated to light exposure and bacterial biomass. Algae represented a tiny component of the detrital food web in shaded bromeliads but accounted for up to 30 percent of the living microbial carbon in the tanks of Catopsis berteroniana, located in a highly exposed area. Thus, while nutrient supplies are believed to originate from wind-borne particles and trapped insects (i.e., allochtonous organic matter), our results indicate that primary producers (i.e., autochtonous organic matter) are present in this insectivorous bromeliad. Using a 24-h incubation of size-fractionated and manipulated samples from this plant, we evaluated the impact of mosquito foraging on algae, other microorganisms and rotifers. The prey assemblages were greatly altered by the predation of mosquito larvae. Grazing losses indicated that the dominant algal taxon, Bumilleriopsis sp., like protozoa and rotifers, is a significant part of the diet of mosquito larvae. We conclude that algae are a relevant functional community of the aquatic food web in C. berteroniana and might form the basis of a complementary non-detrital food web.
ISSN: 1932-6203

hal-00819161
https://hal.archives-ouvertes.fr/hal-00819161
https://hal.archives-ouvertes.fr/hal-00819161/document
https://hal.archives-ouvertes.fr/hal-00819161/file/Brouard2011_AreAlgae.pdf
DOI : 10.1371/journal.pone.0020129

Éditeur(s) : Elsevier France-editions Scientifiques Medicales Elsevier
Résumé : The essential characteristics of the vegetation dynamics of tropical Africa remain only partially known. This study assesses the succession of vegetation-types over Central Africa during the last two glacial/interglacial cycles. Analysis of core KZai 02, which contains pollen from the Zaire River watershed (latitudes 9°N-13°S), allows the investigation of long-term patterns of plant ecosystem development and their climatic causes. Core KZai 02 (18.20 m long) was recovered from 6°24.20′S/9°54.10′E in the uppermost axial edifice of the Zaire deep sea fan. The chronology of this sedimentary archive was established using nannofossils and correlations of pollen and total organic carbon signals with the nearby core GeoB1008. The pollen record indicates that: (i) glacials (MIS 6, 4, 2) are marked by the development of afromontane (Podocarpus) forest at high altitudes when central basin lowlands were occupied by Cyperaceae marshes and savannah; (ii) during interglacials (MIS 1, 5) lowland forests were developed, marked by the successive expansion of pioneer, warm-temperate, rain forests, and mangrove indicating sea-level rise; (iii) glacial-interglacial transitions (MIS 6/5, 2/1) display similar vegetation dynamics. The strong evidence of afromontane forest and the opening of the vegetation during glacials suggest a reduced latitudinal distribution of rainfall by the strengthening of the trade wind system. West African monsoon systems were enhanced during interglacials, allowing the progressive development of lowland forests. The development of rain and pioneer forests during glacial Heinrich stadials suggests an enhancement of water availability in tropical Africa associated with these high latitude events. However, no augmentation of wind activity, described by previous studies, is evidenced by our pollen record. Similar vegetation successions during glacial/interglacial transitions suggest the diachronous and stepped intervention of CO2 (emphasizing the influence of temperature on plant ecosystems) and water availability.
Geobios (0016-6995) (Elsevier France-editions Scientifiques Medicales Elsevier), 2014-07 , Vol. 47 , N. 4 , P. 183-198

Droits : 2014 Elsevier Masson SAS. All rights reserved.
http://archimer.ifremer.fr/doc/00199/31031/29436.pdf
DOI:10.1016/j.geobios.2014.06.002
http://archimer.ifremer.fr/doc/00199/31031/

Éditeur(s) : HAL CCSD
Résumé : International audience
Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
ISSN: 2168-6211

hal-01258705
http://hal.univ-brest.fr/hal-01258705
PUBMED : 25621457
DOI : 10.1001/jamapediatrics.2014.3351

Éditeur(s) : HAL CCSD International Medical Press
Résumé : International audience
BACKGROUND: Psychiatric disorders are relatively common among HIV-infected patients. However, there are few studies about their potential risk factors. This analysis aimed to measure the incidence of severe psychiatric events (PE) among patients receiving combination antiretroviral therapy (cART) of the French APROCO-COPILOTE (ANRS CO8) cohort, and to identify the medical and socio-behavioural correlates of their first episode of depression, suicide or suicide attempt (D/S/SA). METHODS: APROCO-COPILOTE is a cohort of patients started on a protease inhibitor regimen between 1997 and 1999, with prospective medical standardized records and self-administered questionnaires collecting socio-demographic and socio-behavioural data. This analysis included all 11-year follow-up visits for 1,095 patients having completed baseline self-administered questionnaires. A proportional hazard Cox model was used to identify the correlates of a first D/S/SA event. RESULTS: The overall prevalence of severe PE remained low: 50 patients experienced 67 events (incidence rate [95% CI] =1.04 [0.82, 1.32] per 100 person-years). Depression (n=16), suicides (n=5) and suicide attempts (n=14) were the most frequently diagnosed PE (0.54 [0.39, 0.76] per 100 person-years) among 25 patients. Multivariate results showed that unemployment, unstable housing, detectable viral load and smoking more than 20 cigarettes/day were independently associated with D/S/SA. CONCLUSIONS: Although the incidence of severe PE remained relatively low among the patients of APROCO-COPILOTE cohort, this study's results underline a clinically important problem in HIV-infected patients receiving cART. Furthermore, our findings not only emphasize the importance of comprehensive care, especially for socially vulnerable patients, but may also help future studies designed to assess the effectiveness of interventions in reducing the risk of PE during cART.
ISSN: 1359-6535

hal-00875183
https://hal.archives-ouvertes.fr/hal-00875183
DOI : 10.3851/IMP2102
PUBMED : 22544079

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00130/24093/22087.pdf
http://archimer.ifremer.fr/doc/00130/24093/22088.pdf
http://archimer.ifremer.fr/doc/00130/24093/22089.pdf
http://archimer.ifremer.fr/doc/00130/24093/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0012-8252

hal-01671832
https://hal-univ-rochelle.archives-ouvertes.fr/hal-01671832
DOI : 10.1016/j.earscirev.2016.12.005

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development.
ISSN: 1553-7390

hal-01063929
https://hal.archives-ouvertes.fr/hal-01063929
DOI : 10.1371/journal.pgen.1004340
PUBMED : 24784881

Éditeur(s) : IEEE
Résumé : Bathymetric estimation using remote sensing images has previously been applied to high spatial resolution imagery such as CASI, Ikonos, or SPOT but not on medium spatial resolution images (i.e., MERIS). This choice can be justified when there is a need to map the bathymetry on large areas. In this letter, we present the results of the bathymetry estimation over a large known area, the Gulf of Lion (France), expanding over 270 x 180 km.
Geoscience and Remote Sensing Letters, IEEE (1545-598X) (IEEE), 2007-04 , Vol. 4 , N. 2 , P. 274-277

Droits : 2007 IEEE
http://archimer.ifremer.fr/doc/2007/publication-2597.pdf
DOI:10.1109/LGRS.2007.890548
http://archimer.ifremer.fr/doc/00000/2597/

Éditeur(s) : HAL CCSD
Résumé : International audience
High Pressure - Low Temperature (HP-LT) rocks testify for burying and exhumation of crustal material in subduction zones. The question of their exhumation is nevertheless still unclear. The Aegean domain offers several HP-LT belts. Especially, the Attic-Cycladic Blueschist unit (ACBU) is an example of a HP-LT unit exhumed in a convergent and then in a divergent context. It actually appears in metamorphic core complexes (MCCs) formed in the back-arc of the subduction. The syn-convergence "message" is however difficult to read because of the post-convergence structural and thermal overprint that accompanied the formation of the MCCs. Particularly, the geometry, the timing and the amount of the syn-orogenic exhumation remain unclear. We investigate theses questions with metamorphic petrology (Andros and Ios islands) and phengite population, single grain and in situ 40Ar-39Ar geochronology (Andros, Tinos, Syros and Ios islands). Based on these new constraints and a synthesis of published data, we are able to refine the geometry, the timing and the modes of the exhumation of the ACBU. Data from the whole Cyclades exhibit little differences in the age and P-T conditions at the successive stages of syn-orogenic exhumation. The peak of pressure (500±50 °C-18±1 kbar) has been reached at 50-55 Ma. The onset of the exhumation occurred at 40-45 Ma in blueschist facies conditions, between a basal thrust and a summital detachment. The following decompression was accompanied by cooling until 30-35 Ma (400±50 °C-8±1 kbar). At that time, the boundary conditions switched to extension. The change in boundary conditions is recorded by slowing of the exhumation and isobare heating. The conditions of post-orogenic exhumation differ from an island to another. The onset of post-orogenic exhumation is dated around 30 Ma in the northern Cyclades and 25 Ma in the southern Cyclades. It is related to top-to-the-North deformation in all the studied domain. The end of ductile deformation below the detachments is also diachronous (21 Ma in the North and 18 Ma in the South). Finally, we propose a model for the final steps of the exhumation related to the intrusion of granitic bodies around 14 Ma.
American Geophysical Union, Fall Meeting
San Francisco, United States

insu-00860510
https://hal-insu.archives-ouvertes.fr/insu-00860510
BIBCODE : 2010AGUFM.T23C2301L

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
ISSN: 0001-6322

hal-00875723
https://hal.archives-ouvertes.fr/hal-00875723
DOI : 10.1007/s00401-013-1084-y
PUBMED : 23400299

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Little is known of how linkage patterns between species change along environmental gradients. The small, spatially discrete food webs inhabiting tank-bromeliads provide an excellent opportunity to analyse patterns of community diversity and food-web topology (connectance, linkage density, nestedness) in relation to key environmental variables (habitat size, detrital resource, incident radiation) and predators: prey ratios. We sampled 365 bromeliads in a wide range of understorey environments in French Guiana and used gut contents of invertebrates to draw the corresponding 365 connectance webs. At the bromeliad scale, habitat size (water volume) determined the number of species that constitute food-web nodes, the proportion of predators, and food-web topology. The number of species as well as the proportion of predators within bromeliads declined from open to forested habitats, where the volume of water collected by bromeliads was generally lower because of rainfall interception by the canopy. A core group of microorganisms and generalist detritivores remained relatively constant across environments. This suggests that (i) a highly-connected core ensures food-web stability and key ecosystem functions across environments, and (ii) larger deviations in food-web structures can be expected following disturbance if detritivores share traits that determine responses to environmental changes. While linkage density and nestedness were lower in bromeliads in the forest than in open areas, experiments are needed to confirm a trend for lower food-web stability in the understorey of primary forests.
PLoS ONE

hal-00913931
https://hal.archives-ouvertes.fr/hal-00913931
https://hal.archives-ouvertes.fr/hal-00913931/document
DOI : 10.1371/journal.pone.0071735
OATAO : 10204

Éditeur(s) : HAL CCSD
Résumé : International audience
This article describes a previously unreported mutation at position 210 (C210T) of the mitochondrial large subunit ribosomal RNA (mtLSUrRNA) gene of Pneumocystis jirovecii, which led to a false-negative result of a real-time polymerase chain reaction (PCR) assay. Since the aforementioned real-time PCR assay is widely used in France, a French multicenter study was conducted to estimate the mutation frequency and its potential impact on the routine diagnosis of Pneumocystis pneumonia (PCP). Through analysis of data obtained from eight centers, the mutation frequency was estimated at 0.28%. This low frequency should not call into question the routine use of this PCR assay. Nonetheless, the occurrence of the false-negative PCR result provides arguments for maintaining microscopic techniques combined to PCR assays to achieve PCP diagnosis.
Medical Mycology

hal-01477200
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477200
DOI : 10.1093/mmy/myw051
PUBMED : 27489302

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Binding of ligand FasL to its receptor Fas triggers apoptosis via the caspase cascade. FasL itself is homotrimeric, and a productive apoptotic signal requires that FasL be oligomerized beyond the homotrimeric state. We generated a series of FasL chimeras by fusing FasL to domains of the Leukemia Inhibitory Factor receptor gp190 which confer homotypic oligomerization, and analyzed the capacity of these soluble chimeras to trigger cell death. We observed that the most efficient FasL chimera, called pFasL, was also the most polymeric, as it reached the size of a dodecamer. Using a cellular model, we investigated the structure-function relationships of the FasL/Fas interactions for our chimeras, and we demonstrated that the Fas-mediated apoptotic signal did not solely rely on ligand-mediated receptor aggregation, but also required a conformational adaptation of the Fas receptor. When injected into mice, pFasL did not trigger liver injury at a dose which displayed anti-tumor activity in a model of human tumor transplanted to immunodeficient animals, suggesting a potential therapeutic use. Therefore, the optimization of the FasL conformation has to be considered for the development of efficient FasL-derived anti-cancer drugs targeting Fas.
ISSN: 1932-6203

hal-00873684
https://hal.archives-ouvertes.fr/hal-00873684
https://hal.archives-ouvertes.fr/hal-00873684/document
https://hal.archives-ouvertes.fr/hal-00873684/file/Functional_Characterization-accepted.pdf
DOI : 10.1371/journal.pone.0054000