Éditeur(s) : HAL CCSD
Résumé : The Franceville Basin (2.1 Ga) in southeastern Gabon, hosts a black shale series well preserved (FB Formation) which represents an exceptional example of unmetamorphised Paleoproterozoic sediment strata. This basin includes the protore of one of the largest Mn-oxide laterite ore worldwide, mined by Eramet-Comilog. The aim of this this work is to determine formation conditions of this protore and to characterize the global sedimentary evolution of the FB Formation which include the protore. This 75 m thick protore is constituted of Mn carbonate-rich black shales which represent a potential ore deposit for the future. It was drilled, on the Bangombé plateau, during a recent campaign of 24 boreholes with an average depth of 125 m.Through multidisciplinary study on these cores and key outcrops of the basin, this work focuses on : i) the depositional environment of the Mn-protore and FB Formation ; ii) the processes of formation of the Mn-carbonates at 2.1 Ga and iii) the architecture and distribution of Mn-rich levels of the protore on the Bangombé Plateau.A detailed sedimentological and petrological study allowed us to redefine the division of the FB into nine units, named U1 to U9 from the base to the top. These units show a fine upward cycle up to U5 and a reverse coarse loop until U9. This division leads to a new interpretation to propose an evolution from a shoreface depositional environment controlled by deltaic currents (U1) to an offshore depositional environment with anoxic conditions (U2). In this basin, a system of submarine fan is developed, feeding a network of sand injections (injectites) covering the Bangombé plateau (70 km²) and with a thickness of 150 m affecting U4 to U7, including the Mn-protore. The protore depositional environment formed below the wave base limit (U4, U5 and U6) in a starved basin, controlled by biochemical sedimentation allowed the formation of Mn-carbonates. The end of starved basin, would allow the re-opening of the detrital input into the offshore basin (U7). This basin is then filled by storm bar deposits intersected by deltaic sub-aquatic channels (U8). The U9 unit corresponds to a quiet lagoon environment, allowing the multicellular organism development for the first time on the planet.A geochemical study allowed the characterization of the depositional environment of Mn-carbonates as an anoxic to sub-oxic and alkaline environment. For the first time, we showed that the manganese carbonates, present as bacteriomorph forms, are precipitated from the seawater by the mediated photosynthetic cyanobacterial activity, which allows CO2 / HCO3 depression of the environment and a local increase of pH. The cyanobacterial activity is controlled by the absence of bottom currents, which increase the detrital input. This would stop the activity of the cyanobacteria and thus would lead to the decrease of the Mn-concentration along the protore.Finally, well-log and a sequential correlation analyses allowed us to detail spatial and timing repartition of FB Formation deposit, controlled by a tectono-sedimentary model. We propose two- tectono-sedimentary phases. A first syn-tectonic phase (U1 to U3) controls the depocentres and sedimentation gaps. Turbidite coarse deposits are located in the most subsident part, clay deposits rather on the slope and carbonates on shoals. A second post-tectonic phase (U4 to U7) allows isopach deposits. The Mn-protore formed during the post-tectonic phase. However, it shows a variable thickness due to subsidence to the north of the Bangombé plateau. So, on the Bangombé plateau, Mn-contents increase towards the south, whereas the protore thickness increases towards the NNE. Moreover sand injectites decrease Mn-content in the eastern part of the Bangombé plateau and impact on the economic evaluation of the Mn-carbonates. Currently, the protore is structured by post-sedimentary faults, which lead to a non-continuity of the high Mn levels on the Bangombé plateau.
Le Bassin de Franceville situé au SE du Gabon présente une série de black shales (Formation FB) d'âge Paléoprotérozoïque (2,1 Ga) surmontant les grès de la Formation FA. Ce bassin peu déformé et non métamorphique représente une archive exceptionnelle des processus de dépôt de cette période de l’histoire de la Terre où la vie commence à se développer. En particulier, la Formation FB contient le protore d'un gisement mondial d'oxydes de manganèse exploité par la société Eramet-Comilog. L’objectif de ce travail est de préciser les conditions de formation de ce protore et de le replacer dans l’histoire du remplissage du bassin. Ce protore d'une épaisseur moyenne de 75 m est constitué de carbonates de manganèse ; il a fait l'objet d'une récente campagne de 24 forages carottés d'une profondeur moyenne de 125 m sur le plateau de Bangombé.A travers une approche pluridisciplinaire comprenant l'étude de ces forages et des affleurements clefs du bassin, ce travail porte sur la caractérisation i) de l'environnement de dépôt du protore et des séries qui l'encadrent (du toit du FA au toit du FB) ; ii) du mode de formation des carbonates de Mn à 2,1 Ga et iii) de l'architecture et de la répartition des hautes teneurs en Mn du protore qui représente un gisement potentiel du futur.L’étude pétro-sédimentaire détaillée a permis de distinguer neuf unités (U1 à U9) au sein de la Formation FB organisées suivant un cycle rétrogradant jusqu’à U5 puis progradant jusqu’à U9. Ce découpage montre une évolution du milieu de dépôt depuis un domaine de shoreface contrôlé par des courants deltaïques (U1) évoluant vers des dépôts d’offshore restreint (U2). Ce bassin enregistre ensuite un système de chenaux-levées turbiditiques (U3) qui alimentent un réseau d'injectites reconnu sur l’ensemble du Pl. de Bangombé et qui traverse 150 m de série (U4 à U7) en affectant le protore et ainsi les teneurs en Mn. L'environnement de dépôt du protore (U5 et U6) marque l’isolement du bassin qui devient affamé et contrôlé par une sédimentation biochimique à l’origine du dépôt des carbonates de Mn. L'Unité 7 correspond à la réouverture des apports détritiques en domaine d'offshore supérieur puis en domaine de shoreface dominé par des dépôts de tempêtes et de chenaux sous-aquatiques deltaïques (U8), et enfin lagunaire (U9) dans lequel apparaissent les premiers métazoaires de l’histoire de la planète, suivant une séquence régressive.Une étude géochimique a permis de préciser les conditions de dépôt du protore qui se forme en milieu alcalin anoxique à sub-oxique. Dans ce milieu, nous montrons pour la première fois une précipitation directe des carbonates de Mn sous forme bactériomorphe induite par l'activité photosynthétique des cyanobactéries qui consomment le CO2/HCO3 et conduisent à une augmentation du pH favorable à la formation des carbonates de Mn. L'activité cyanobactérienne est conditionnée par l’absence de courants de fond qui augmentent la turbidité du milieu et stoppent cette dernière.Les corrélations diagraphiques et séquentielles permettent de préciser la répartition spatiale et temporelle du FB permettant ainsi de replacer le protore dans l’histoire tectono-sédimentaire du bassin. Une première phase syn-tectonique (U1 à U3) contrôle l’épaisseur et la mise en place de dépôts turbiditiques dans les parties subsidentes, de dépôts argileux sur les pentes et de dépôt de carbonates sur les hauts-fonds. La seconde phase post tectonique (U4 à U7) permet la mise en place de dépôts relativement isopaques, bien que le protore enregistre une subsidence plus importante au nord du Pl. de Bangombé. On observe ainsi, sur le Plateau de Bangombé, des teneurs en Mn qui augmentent vers le sud alors que l’épaisseur du protore augmente vers le NNE. Postérieurement au dépôt du FB, le protore est structuré par des failles qui le compartimentent en touches de piano limitant ainsi sa continuité sur le Plateau de Bangombé.
https://hal.archives-ouvertes.fr/tel-01621460

tel-01621460
https://hal.archives-ouvertes.fr/tel-01621460
https://hal.archives-ouvertes.fr/tel-01621460/document
https://hal.archives-ouvertes.fr/tel-01621460/file/these_Dubois2017-MnGabon.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
This study analyzes the active tectonics within the northwestern and southeastern extensions of the Pambak-Sevan-Syunik fault (PSSF), a major right-lateral strike-slip fault cutting through Armenia. Quantifying the deformations in terms of geometry, kinematics, slip rates and earthquake activity, using cosmogenic 3He, OSL/IRSL and radiocarbon dating techniques, reveal different behaviors between the two regions. Within the northwestern extension, in the region of Amasia, the PSSF bends to the west and splits into two main WNW–ESE trending reverse faults defining a compressional pop-up structure. We estimate an uplift rate and a shortening rate of 0.5 ± 0.1 mm/y and 1.4 ± 0.6 mm/y, respectively. This suggests that most of the ∼2 mm/y right lateral movement of the PSSF seems to be absorbed within the Amasia pop-structure. Within the southeastern extension, the PSSF shows signs of dying out within the Tsghuk Volcano region at the southernmost tip of the Syunik graben. There, the tectonic activity is characterized by a very slow NS trending normal faulting associated with a slight right-lateral movement. Slip rates analyses (i.e. vertical slip rate, EW stretching rate at 90° to the fault, and right-lateral slip rate of ∼0.2 mm/y, ∼0.1 mm/y and ∼0.05 mm/y, respectively) lead to the conclusion that the right lateral movement observed further north along the PSSF is mainly transferred within other active faults further west within the Karabagh (Hagari fault or other structures further northwestwards). Comparing our slip rates with those estimated from GPS data suggests that most of the deformation is localized and seismic, at least within the Tsghuk region. The geometrical and kinematic pattern observed within the two terminations of the PSSF suggests that the fault and its surrounding crustal blocks are presently rotating anticlockwise, as also observed within the GPS velocity field. This is consistent with the recent kinematic models proposed for the Caucasus-Kura-South Caspian region and brings a new insight into the present geodynamics of Armenia.
ISSN: 1040-6182

hal-01307342
https://hal.archives-ouvertes.fr/hal-01307342
DOI : 10.1016/j.quaint.2015.05.021

Éditeur(s) : American Geophysical Union
Résumé : We use seismic reflection and rock sample data to propose that the first-order physiography of New Caledonia Trough and Norfolk Ridge formed in Eocene and Oligocene time and was associated with the onset of subduction and back-arc spreading at the Australia-Pacific plate boundary. Our tectonic model involves an initial Cretaceous rift that is strongly modified by Cenozoic subduction initiation. Hence, we are able to explain (1) complex sedimentary basins of inferred Mesozoic age; (2) a prominent unconformity and onlap surface of middle Eocene to early Miocene age at the base of flat-lying sediments beneath the axis of New Caledonia Trough; (3) gently dipping, variable thickness, and locally deformed Late Cretaceous strata along the margins of the trough; (4) platform morphology and unconformities on either side of the trough that indicate a phase of late Eocene to early Miocene uplift to near sea level, followed by rapid Oligocene and Miocene subsidence of similar to 1100-1800 m; and (5) seismic reflection facies tied to boreholes that suggest absolute tectonic subsidence at the southern end of New Caledonia Trough by 1800-2200 m since Eocene time. The Cenozoic part of the model involves delamination and subduction initiation followed by rapid foundering and rollback of the slab. This created a deep (>2 km) enclosed oceanic trough, similar to 2000 km long and 200-300 km across, in Eocene and Oligocene time as the lower crust detached, with simultaneous uplift and local land development along basin flanks. Disruption of Late Cretaceous and Paleogene strata was minimal during this Cenozoic phase and involved only subtle tilting and local reverse faulting or folding. Basin formation was possible through the action of at least one detachment fault that allowed the lower crust to either be subducted into the mantle or exhumed eastward into Norfolk Basin. We suggest that delamination of the lithosphere, with possible mixing of the lower crust back into the mantle, is more widespread than previously thought and may be commonly associated with subduction initiation, such as Cenozoic events in the Mediterranean and western Pacific.
Tectonics (0278-7407) (American Geophysical Union), 2010-03 , Vol. 29 , N. TC2004 , P. 1-16

Droits : Copyright 2010 by the American Geophysical Union.
http://archimer.ifremer.fr/doc/00001/11271/9283.pdf
DOI:10.1029/2009TC002476
http://archimer.ifremer.fr/doc/00001/11271/

Éditeur(s) : Elsevier Science Bv
Résumé : A Lagrangian approach based on a physical-biogeochemical modeling was used to compare the potential transfer of cadmium (Cd) from natural and anthropogenic sources to plankton communities (Cd-uptake) in the NorthWest African upwelling. In this region, coastal upwelling was estimated to be the main natural source of Cd while the most significant anthropogenic source for marine ecosystem is provided by phosphate industry. In our model experiment, Cd-uptake (natural or anthropogenic) in the North-West African upwelling is the result of an interplay between the Cd dispersion (by advection processes) and the simulated biological productivity. In the Moroccan waters, advection processes limit the residence time of water masses resulting in a low natural Cd-uptake by plankton communities while anthropogenic Cd-uptake is high. As expected, the situation is reversed in the Senegalo-Mauritanian upwelling where natural Cd-uptake is higher than anthropogenic Cd-uptake. Based upon an estimate of Cd sources, our modeling study shows, unexpectedly, that the anthropogenic signal of potential Cd-bioaccumulation in the Moroccan upwelling is of the same order of magnitude as the natural signal mainly present in the Senegalo-Mauritanian upwelling region. A comparison with observed Cd levels in mollusk and fishes, which shows overall agreement with our simulations, is confirming our estimates.
Science Of The Total Environment (0048-9697) (Elsevier Science Bv), 2015-02 , Vol. 505 , P. 870-888

Droits : 2014 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/00252/36310/35200.pdf
DOI:10.1016/j.scitotenv.2014.10.045
http://archimer.ifremer.fr/doc/00252/36310/

Résumé : Le fluide chaud produit par les forages de la centrale géothermique de Bouillante (Guadeloupe) est enrichi en espèces dissoutes telles que la silice qui peuvent précipiter sous forme de dépôts solides lors de son refroidissement et gêner fortement la production électrique. L’un des principaux objectifs de ce travail de thèse a donc été d’améliorer l’état des connaissances sur les conditions physiques, chimiques et cinétiques de la précipitation de la silice amorphe à Bouillante. Après une étude des caractéristiques physico-chimiques des fluides et des dépôts associés au champ de Bouillante, des expériences sur la cinétique de précipitation de la silice, sur site, pour une large gamme de température (25 - 90°C) et de pH (4 - 12) ont été menées et analysées en détail.Pour l’ensemble de ces expériences, seule la polymérisation (réversible) de la silice dissoute, sous forme de suspensions colloïdales très stables en solution, a été observée. La modélisation des données expérimentales de cinétique montre que la vitesse de polymérisation de la silice suit une loi d’ordre 2 vis-à-vis de la silice dissoute jusqu’à l’équilibre en accord avec une dimérisation de la silice. Par contre, durant l’étape initiale de la réaction, une loi d’ordre 4 semble mieux adaptée, suggérant des réactions de polymérisation plus complexes avec formation de tétramères. La température a un effet limité sur la cinétique de polymérisation de la silice comparé à l’effet du pH qui est beaucoup plus important. L’énergie d’activation de la réaction globale est de 41 - 54 kJ pour des pH compris entre 5 et 8.La caractérisation de la silice précipitée a mis en évidence des différences notables entre la structure poreuse de la silice solide prélevée sur les installations de surface et celle de la silice colloïdale obtenue par polymérisation lors des expériences de cinétique, ce qui semble indiquer que des mécanismes différents interviennent dans ces deux contextes de précipitation de la silice dissoute.Le deuxième objectif de cette thèse était d’évaluer la possibilité de valoriser la silice extraite de l’eau géothermale de Bouillante dans un procédé de traitement des eaux naturelles par adsorption. Pour cela, les propriétés d’adsorption de la silice géothermale brute et fonctionnalisée par le poly(ethylèneimine) (ou PEI) ont été étudiées pour deux polluants : un colorant, le bleu de méthylène et un métal lourd, le plomb. Les résultats obtenus montrent que la silice brute possède une grande capacité d’adsorption vis-à-vis du bleu de méthylène. En outre, la fonctionnalisation de la silice par le PEI permet d’améliorer sa capacité d’adsorption vis-à-vis du plomb en solution, en accord avec un modèle cinétique du pseudo-second ordre suggérant une chimisorption. Le modèle d’isotherme de Redlich-Peterson est également en très bon accord avec les données expérimentales.
The hot geothermal fluid produced by the geothermal power plant of Bouillante (Guadeloupe) contains various dissolved components such as silica that can precipitate as solid deposits during their cooling and cause serious problems on the electricity generation. One of the aim of this study is to improve the understanding on the physical, chemical and kinetics conditions of the amorphous silica precipitation in the Bouillante geothermal field. After a study on the physical and chemical characteristics of the Bouillante fluids and deposits which can form during their exploitation, experiments on the kinetics of silica precipitation, on site, under a large range of temperature (25 – 90°C) and pH (4 – 12) have been carried out and analyzed in detail.During on site kinetics experimentations only dissolved silica polymerization (reversible) as colloidal gel, very stable in solution, was observed. Modeling of the experimental data showed that the kinetics polymerization is characterized by a 2-order kinetic law relative to dissolved silica until the equilibrium that is consistent with silica dimerization. On the other side, the initial stage of the reaction is better characterized by a 4-order kinetic law that suggested more complex polymerization reactions with tetramers formation.Temperature has a little effect on the polymerization kinetics compared with the pH which has an effect more important. The activation energy of silica precipitation calculated between 25 and 90°C, is about 41 - 54 kJ for pH ranging to 5 - 8.The characterization of the silica precipitate reveals significant differences in the porous structure of the silica collected on the surface installations and the one obtained from kinetic experiments that suggests different precipitation mechanisms. The second objective of this thesis was to evaluate the possibility to promote geothermal silica for the treatment of natural waters containing contaminants by adsorption. Adsorption properties of the untreated and functionalized by poly(ethylèneimine) (ou PEI) geothermal silica have been investigated for two pollutants: a colorant, the methylene blue and a heavy metal, the lead.Results showed that untreated silica has a great adsorption capacity concerning the methylene blue. Besides, silica functionalization by the PEI allows improving the adsorption capacity for lead in solution. The adsorption kinetics curves followed a pseudo-second order model consistent with a chimisorption. The isotherm model of Redlich-Peterson fitted well the experimental data.

http://www.theses.fr/2014AGUY0698/document

Éditeur(s) : HAL CCSD Springer Verlag (Germany) Springer Verlag
Résumé : International audience
We report here U-series and trace element data for an olivine-melilitite lava flow, erupted in 1957 in the Virunga volcanic field and known as the Mugogo eruption. Petrological and geochemical data show that the Mugogo magma represents a primary mantle melt, derived from a low degree of melting of a metasomatised mantle source. It is highly enriched in very incompatible trace elements (e.g. more than 300-fold compared to primitive mantle for Th), with a distinctly lower enrichment in Rb, Ba and Sr. The high Th/U and low (230Th/232Th) ratios (4.4 and 0.750, respectively, with a (230Th/238U) ratio of 1.09) are close to the values found for the Nyamuragira basanites. But the most striking feature is the very low (226Ra/230Th) ratio of 0.48, the lowest ever measured in a mafic volcanic rock. The most probable origin of this Ra deficit is the presence of phlogopite (having a high Ra partition coefficient) in the lithospheric mantle, either as a residual phase during low-degree isobaric melting (in batch-melting or a diffusion-controlled melting models), or in a phlogopite-bearing upper mantle through which the melt migrates and equilibrates (in an equilibrium porous flow model commonly used to describe adiabatic melting). The disequilibrium pattern (230Th) > (238U) > (210Pb) ≫ (226Ra), reversed compared to the pattern observed in the Oldoinyo Lengai natrocarbonatite, suggests that a carbonatite melt might have been involved to explain the Ra deficit. We thus discuss the possibility of an early separation of a Ra-enriched carbonate melt either from the olivine-melilitite melt or from a carbonated mantle source, followed by the production of a low-degree melt of olivine-melilitite composition, but the lack of available experimental, petrological and geochemical evidences makes this process somewhat speculative at present. Further studies of recent (<5 ky) olivine-melilitites are needed to check whether the large Ra deficit is a general characteristic of this type of magma that can be used to constrain models of its formation.
ISSN: 0010-7999

hal-01174173
https://hal.archives-ouvertes.fr/hal-01174173
DOI : 10.1007/s00410-015-1124-9

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Phase equilibrium data pertaining to melting of simplified carbonated peridotite in the systems CaO-MgO-SiO2-CO2 and CaO-MgO-Al2O3-SiO2-CO2 at pressures of 10-26 GPa, corresponding to similar to 300-750 km depths in the Earth, are presented. In both the studied systems, liquid compositions, with changing crystalline phase assemblage, are carbonatitic throughout the studied pressure range. In the system CMS-CO2, melting phase relations are isobarically invariant; liquid is in equilibrium with forsterite + clinoenstatite + clinopyroxene + magnesite, forsterite + majorite + clinopyroxene + magnesite, wadsleyite + majorite + clinopyroxene + magnesite, ringwoodite + majorite + calcium-silicate perovskite + magnesite, magnesium-silicate perovskite + periclase + calcium-silicate perovskite + magnesite at 12, 14, 16, 20, and 26 GPa, respectively. In the system CMAS-CO2, a phase assemblage consisting of forsterite + orthopyroxene + clinopyroxene + magnesite + garnet + melt from 10 to 14 GPa is isobarically invariant. However, owing to the disappearance of orthopyroxene at pressures greater than 14 GPa, from 16 and up to at least 26 GPa, the solidus of simplified carbonated peridotite spans a divariant surface in pressure-temperature space. The liquid coexists with wadsleyite + clinopyroxene + garnet + magnesite, ringwoodite + calcium-silicate perovskite + garnet + magnesite, and magnesium-silicate perovskite + periclase + calcium-silicate perovskite + magnesite at 16, 20, and 26 GPa, respectively. A curious, and as yet unexplained, feature of our study is an abrupt drop in the solidus temperature between 14 and 16 GPa that causes a small amount of melting of carbonated mantle in the Transition Zone of the Earth. In the systems CMS-CO2 and CMAS-CO2 liquid compositions at 16 and 20 GPa are highly calcic bona fide carbonatites; however, these liquids revert to being magnesiocarbonatites at 10-14 and 26 GPa. In the system CMS-CO2, at 16 GPa we locate an isobaric invariant point consisting of wadsleyite + clinopyroxene + anhydrous B + magnesite + melt. The presence of anhydrous B at 16 GPa and 1475 degrees C is interesting, as it lies outside the composition space of the mantle peridotite analog we have studied. However, despite the presence of two highly magnesian silicate crystalline phases, wadsleyite and anhydrous B, at 16 GPa and 1475 degrees C, the liquid composition remains calcic with molar Ca-number [Ca/(Ca + Mg) x 100] of about 63. The melting reactions at 16 and 20 GPa (with or without anhydrous B) show that lime-bearing crystalline silicates play a fairly large part in generating and controlling the composition of the liquids. At 16 GPa, in the system CMS-CO2, we also report an experimental run at 1575 degrees C, in which liquid coexists with only wadsleyite and majorite. The liquid composition is less calcic (Ca-number 54) than that for other runs at lower temperatures, but is still more calcic than liquids at 10-14 and 26 GPa in both the studied systems. At present, the likely cause for these changes in the reported phase relations is not known. For normally assumed mantle temperatures, melting in the Transition Zone of the Earth, owing to the presence of carbonate, is probably unavoidable. The depth range of the drop in the carbonated peridotite solidus closely matches that of commonly observed low seismic velocities at similar to 400-600 km depth in the Earth.
ISSN: 0022-3530

hal-00669945
https://hal.archives-ouvertes.fr/hal-00669945
DOI : 10.1093/petrology/egr048

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background: Influenza is an important cause of serious illness and death, particularly in elderly and high-risk groups. Objectives Aim of this study was to identify factors associated with poor outcomes among adults hospitalized in France for laboratory-confirmed seasonal influenza. Study design Patients hospitalized for influenza were identified in a prospective, multicenter study carried out in French hospitals during three consecutive influenza seasons (2012–2015). Influenza virus infection was confirmed by reverse transcription polymerase chain reaction. Sociodemographic and clinical variables were compared according to the virus type and subtype. Risk factors for complications, intensive care unit (ICU) admission and death were analyzed by backward stepwise logistic regression. Results The study population consisted of 566 patients, of whom 56% were older than 65 years and 82% had underlying chronic illnesses. Type A influenza viruses infected 422 patients (75%), including subtype H3N2 in 239 patients (57%). The prior vaccine coverage rate was 38%. Complications occurred in 255 patients (45%), consisting mainly of pneumonia (n = 143, 30%) and respiratory failure (n = 116, 20%). Eighty-three patients (15%) were admitted to an ICU, and the in-hospital mortality rate was 4% (n = 21). Sixty-six patients (12%) received oseltamivir. Age over 65 years was the only identified risk factor for complications. Risk factors for ICU admission were an absence of vaccination, no oseltamivir administration before admission, pre-existing chronic respiratory disease, and current smoking. Age over 65 years and ICU admission were risk factors for death. Conclusions Older individuals and patients with underlying conditions are most at risk of influenza complications. Vaccination and early oseltamivir administration, both of which are recommended for these patients, appear to reduce ICU admissions
ISSN: 1386-6532

hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/file/Factors%20associated%20with%20poor%20outcomes.pdf
DOI : 10.1016/j.jcv.2016.04.005

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 Mary Ann Liebert
Résumé : International audience
Little information is available on the molecular epidemiologic profile of HIV-1 in French Guiana, the French department with the highest HIV/AIDS incidence. To follow the evolution of HIV-1 diversity, we carried out a molecular analysis of HIV-1 isolates from 305 treatment-naive patients between 2006 and 2012. Protease and reverse-transcriptase sequences were obtained for subtype characterization, polymorphism analysis, and identification of drug resistance mutations. Of 305 HIV-1 strains, 95.1% were subtype B viruses. The overall prevalence of transmitted drug-resistance mutations (TDRMs) was 4.6% (14/305), ranging from 1.9% to 7.1% depending on the year. This study shows a low level of HIV-1 genetic diversity and a moderate prevalence of TDRMs with no evidence of an increasing trend over the study period. Nevertheless, the strong genetic polymorphism observed on both genes may be of concern for long-term treatment of people living with HIV-1 and thus deserves continuous monitoring.
ISSN: 0889-2229

pasteur-01583613
https://hal-riip.archives-ouvertes.fr/pasteur-01583613
https://hal-riip.archives-ouvertes.fr/pasteur-01583613/document
https://hal-riip.archives-ouvertes.fr/pasteur-01583613/file/2016%20Darcissac%20et%20al.%20ARHR.pdf
DOI : 10.1089/aid.2016.0048

Éditeur(s) : Wiley-blackwell
Résumé : Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). While a number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received substantial scientific attention recently is fisheries-induced evolution (FIE). Increasing evidence indicates that intensive fishing has the potential to exert strong directional selection on life-history traits, behaviour, physiology, and morphology of exploited fish. Of particular concern is that reversing evolutionary responses to fishing can be much more difficult than reversing demographic or phenotypically plastic responses. Furthermore, like climate change, multiple agents cause FIE, with effects accumulating over time. Consequently, FIE may alter the utility derived from fish stocks, which in turn can modify the monetary value living aquatic resources provide to society. Quantifying and predicting the evolutionary effects of fishing is therefore important for both ecological and economic reasons. An important reason this is not happening is the lack of an appropriate assessment framework. We therefore describe the evolutionary impact assessment (EvoIA) as a structured approach for assessing the evolutionary consequences of fishing and evaluating the predicted evolutionary outcomes of alternative management options. EvoIA can contribute to EAF by clarifying how evolution may alter stock properties and ecological relations, support the precautionary approach to fisheries management by addressing a previously overlooked source of uncertainty and risk, and thus contribute to sustainable fisheries.
Fish And Fisheries (1467-2960) (Wiley-blackwell), 2014-03 , Vol. 15 , N. 1 , P. 65-96

Droits : 2012 John Wiley & Sons Ltd
http://archimer.ifremer.fr/doc/00124/23522/21409.pdf
DOI:10.1111/faf.12007
http://archimer.ifremer.fr/doc/00124/23522/

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis.
ISSN: 0022-538X

hal-01390974
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390974/file/Mouse%20Hepatitis%20Virus%20Infection_accepted.pdf
DOI : 10.1128/JVI.01069-16

Éditeur(s) : HAL CCSD
Résumé : When the upper crust below the mountain ranges shows crustal extension with a direction collinear to the convergence direction, it is generally accepted that it is the result of gravitational collapse. However, recent studies challenge this paradigm by showing that erosion induces uplift and extension in the central part of the low convergent mountain ranges. In this study, we investigate the impact of denudation on the seismotectonic regime of mountain ranges.In order to identify a relationship between seismotectonic regime and erosion, the first part of this work presents a compilation of data in the mountain ranges. Based on these observations, a simple kinematic model is proposed to predict the seismotectonic regime of the study ranges.For low convergence rate and moderate mean elevation ranges, this model predicts an extension regime when the denudation rate is 15% higher than the convergence rate.The second part is devoted to the development of thermomechanical 2D finite element models to study the impact of surface processes on the deformation of the Pyrenees. The results show that the isostatic response to erosion reactivates pre-existing structures. The kinematics of an inherited fault plane can be predicted due to the gradient of the horizontal surface velocity profile. Thus, a plane located in the eroded zone is reactivated in normal fault when near the border of the erosion area, this same plane is reactivated in reverse fault. These results suggest that the current deformation in the North Pyrenean Zone could be the result of surface processes.Given the small number of studies quantifying erosion rates in the Pyrenees, the models developed in the second part suffer from high uncertainty. To remedy this, we study the central Pyrenees through a study that combines two types of data : watershed denudation rates from cosmogenic isotopes concentration, and incision rates from sediments buried in the karst. These results are presented in chapter 3. Denudation profiles obtained are consistent with reactivation of a normal fault plane located in the North Zone of the Central Pyrenees.From our study in the Pyrenees, a good correlation appears between the value of the rate of erosion and the glacier occupation. Given that the glaciers where more developed in the Alps, it raises the question of the impact of the late-würmian deglaciation on the present deformation of this range. A numerical model detailing this relationship is presented in the fourth chapter. Theresults show that deglaciation of the western Alps is controlled by the rheological heterogeneity of the crust. Some of our models predict uplift rates consistent with those highlighted by geodesy.
Lorsque l’extension de la croûte sous les parties hautes des chaînes de montagnes est colinéaire à la direction de convergence, il est traditionnellement admis que le moteur est l’effondrement gravitaire. Pourtant, des études récentes remettent en cause ce paradigme en montrant que l’érosion induit un soulèvement et de l’extension dans la partie centrale des chaînes de montagne à faible taux de convergence. L’objectif de notre étude est d’étudier l’impact de la dénudation de la topographie sur le régime sismo-tectonique des chaînes de montagnes.La première partie de ce travail présente une compilation de données dans les chaînes de montagnes afin de dégager des relations entre régime sismo-tectonique et érosion. Sur la base de ces observations, un modèle cinématique simple permettant de prévoir le régime de la chaîne est proposé. Ainsi, pour les chaînes à faible taux de convergence et d’élévation moyenne, ce modèleprédit de l’extension lorsque le taux de dénudation est 15% plus élevé que le taux de convergence.La deuxième partie est consacrée au développement d’un modèle thermo-mécanique 2D en éléments finis pour étudier l’impact des processus de surface sur la déformation des Pyrénées.Les résultats montrent que la réponse isostatique à l’érosion permet de réactiver des structurespré-existantes. La cinématique d’un plan de faille hérité peut être prédite grâce au gradient du profil des vitesses de surface horizontales. Ainsi, un plan situé dans la zone d’érosion est réactivé en faille normale alors qu’en bordure de cette zone une faille est réactivée en régime inverse. Ces résultats suggèrent que la déformation actuelle des Pyrénées pourrait être la conséquence d’unprocessus d’érosion.Compte tenu du faible nombre d’études quantifiant les taux d’érosion dans les Pyrénées, les modèles développés dans la deuxième partie souffrent d’une forte incertitude. Pour y remédier, nous avons cherché à les quantifier dans les Pyrénées Centrales grâce à une étude qui combine deux types de données : taux de dénudation des bassins versants à partir des isotopes cosmogéniques, et vitesses d’incision à partir des sédiments piégés dans les karsts. Ces résultats sontprésentés dans la troisième partie. Les profils de dénudation obtenus sont compatibles avec unrejeu en faille normale d’un plan situé dans la Zone Nord Pyrénéenne des Pyrénées Centrales.Notre étude dans les Pyrénées, montre une bonne corrélation entre la valeur du taux d’érosion et la cartographie de l’occupation glaciaire. Les glaciers ayant été plus développés dans les Alpes, cela pose la question de l’impact de la déglaciation tardi-Wurmienne sur la déformation actuelle de cette chaîne. Un modèle numérique détaillant cette relation est présenté dans le quatrième chapitre. Les résultats montrent que la déglaciation des Alpes occidentales est contrôléepar l’hétérogénéité rhéologique de la croute. Certains de nos modèles prédisent des vitesses de surrection compatibles avec celles mises en évidence par la géodésie.
https://hal.archives-ouvertes.fr/tel-01262333

tel-01262333
https://hal.archives-ouvertes.fr/tel-01262333
https://hal.archives-ouvertes.fr/tel-01262333/document
https://hal.archives-ouvertes.fr/tel-01262333/file/these-Genti-2015-postjury.pdf

Éditeur(s) : Soc General Microbiology
Résumé : The Plasmodium falciparum kinome includes a family of four protein kinases (Pfnek-1 to -4) related to the NIMA (never-in-mitosis) family, members of which play important roles in mitosis and meiosis in eukaryotic cells. Only one of these, Pfnek-1, which we previously characterized at the biochemical level, is expressed in asexual parasites. The other three (Pfnek-2, -3 and -4) are expressed predominantly in gametocytes, and a role for nek-2 and nek-4 in meiosis has been documented. Here we show by reverse genetics that Pfnek-1 is required for completion of the asexual cycle in red blood cells and that its expression in gametocytes in detectable by immunofluorescence in male (but not in female) gametocytes, in contrast with Pfnek-2 and Pfnek-4. This indicates that the function of Pfnek-1 is non-redundant with those of the other members of the Pfnek family and identifies Pfnek-1 as a potential target for antimalarial chemotherapy. A medium-throughput screen of a small-molecule library provides proof of concept that recombinant Pfnek-1 can be used as a target in drug discovery.
Microbiology-sgm (1350-0872) (Soc General Microbiology), 2011-10 , Vol. 157 , P. 2785-2794

Droits : 2011 SGM Printed in Great Britain / This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
http://archimer.ifremer.fr/doc/00175/28578/26965.pdf
DOI:10.1099/mic.0.049023-0
http://archimer.ifremer.fr/doc/00175/28578/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
From outcrops located in Provence (South-East France), we describe the distribution, the microstructures, and the petrophysical properties of deformation band networks related to both contractional and extensional tectonic events. In contraction, pervasively distributed networks of reverse-sense compactional shear bands are observed in all folded sand units of the foreland, whereas localized networks of clustered reverse-sense shear bands are only observed close to a large-scale thrust. In extensional setting, networks of clustered normal-sense shear bands are generally observed adjacent to map-scale faults (100 m–10 km scale), although some randomly distributed bands are also observed between these faults. Normal-sense cataclastic faults, i.e. zone of deformation bands containing a localized slip-surface, are also observed to be restricted to sand units, suggesting that faults initiated in the sands during extension, but not during contraction. Shear bands and faults show cataclastic microstructures with high-permeability reduction whereas compactional shear bands show crush microbreccia or protocataclastic microstructures with moderate permeability reduction. This basin-scale analysis underlines the major role of tectonic settings (thrust-fault versus normal-fault andersonian-stress regime) and the influence of inherited large-scale faults on the formation/localization of low-permeability shear bands. We also provide a geometrical analysis of the band network properties (spacing, thickness, shear/compaction ratio, degree of cataclasis, petrophysical properties) with respect to the median grain size, porosity and grain sorting of host sand. This analysis suggests that grain size, although less important than stress-state conditions and the presence of large-scale faults, has a non-negligible effect on band network geometry. No correlations are observed between the grain sorting, porosity and band network geometry.
ISSN: 0264-8172

hal-01116421
https://hal.archives-ouvertes.fr/hal-01116421
DOI : 10.1016/j.marpetgeo.2013.12.020

Éditeur(s) : Elsevier Science Bv
Résumé : On the Mediterranean continental shelves the post-glacial transgressive succession is a complex picture composed by seaward progradations, related to sea level stillstands and/or increased sediment supply to the coasts, and minor flooding surfaces, associated to phases of enhanced rates of sea level rise. Among Late Pleistocene examples, major mid-shelf progradations have been related to the short-term climatic reversal of the Younger Dryas event, a period during which the combination of increased sediment supply from rivers and reduced rates of sea level rise promoted the formation of progradations up to tens-meter thick. While the documentation of coastal and subaqueous progradations recording the Younger Dryas interval are widely reported in the literature, the model of compound progradation within transgressive deposits is not proposed so far. Here we present the documentation of a deltaic system where both delta front sands and related fine-grained subaqueous progradations (prodeltaic to shallow marine) have been preserved. The Paleo Gargano Compound Delta (PGCD) formed offshore the modern Gargano Promontory (southern Adriatic Sea), and is composed by a coastal coarse-grained delta of reduced thickness and a muddy subaqueous clinoform, up to 30 meters thick. The PGCD, probably the first worldwide documentation of a compound delta within the transgressive record, provides the opportunity to investigate the processes controlling the formation of a compound delta system during an overall sea level rise and the factors that allowed its preservation. The finding of the PGCD provides the opportunity of a comparison with modern worldwide compound systems.
Marine Geology (0025-3227) (Elsevier Science Bv), 2015-04 , Vol. 362 , P. 43-59

Droits : 2015 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/00250/36158/34714.pdf
DOI:10.1016/j.margeo.2015.01.010
http://archimer.ifremer.fr/doc/00250/36158/

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
The Taleghan fault (TF) is a major active fault of the Central Alborz mountain range in Iran. Located 50 km northwestwards of Tehran, this 80-km-long fault represents one of the major structures threatening 15 million people living in the capital of Iran and the surrounding cities (e.g. Karaj). The TF could be the source of some of the strongest historical earthquakes recorded in the Tehran region, notably the 958 AD event (estimated magnitude M 7.7). To characterize the kinematics and activity of the fault, we carried out a detailed morphological and palaeoseismological study combining aerial photographs, digital elevation models and fieldwork. We show that, unliked described so far, the TF is not a reverse fault but a left-lateral strike-slip fault with a normal component. Its strike, dip and rake within its eastern part are 105, 60 and -20/-40, respectively. Our palaeoseismological analysis shows that a sequence of 2-3 events with magnitudes M-w >= 7 occurred during the past 5300 years. If we consider a three-event scenario, the average recurrence interval is similar to 2000 years, and the most recent event is younger than 80 AD. If we consider a two-event scenario, the time interval between the second and the first events ranges between 3760 and 830 years, and the elapsed time since the last event ranges between 3529 and 1599 years. Combined with morphotectonics data, our palaeoseismological analysis allows estimating a minimum horizontal slip rate of 0.6-1.6 mm yr(-1) and a minimum vertical slip rate of similar to 0.5 mm yr(-1). Taking the similar to 450-m total vertical displacement observed across the fault, we conclude that the kinematical change along the TF (from reverse to left-lateral + normal) occurred similar to 1 Ma.
ISSN: 0956-540X

hal-00420896
https://hal.archives-ouvertes.fr/hal-00420896
https://hal.archives-ouvertes.fr/hal-00420896v2/document
https://hal.archives-ouvertes.fr/hal-00420896/file/narariGJI2009.pdf
DOI : 10.1111/j.1365-246X.2009.04173.x

Éditeur(s) : Springer
Résumé : The light response curve methodology for microphytobenthic biofilms was studied by comparing the two most usual approaches used in pulse amplitude modulated (PAM) fluorometry. The non-sequential light curve (N-SLC) method is characterized by independent measures of the photosynthetic activity across a light gradient whereas the rapid light curve (RLC) method consists of successive measures on the same sample exposed to a stepwise increase of light intensities. Experiments were carried out on experimental microphytobenthic biofilms prepared from natural assemblages and acclimated to dark conditions. In preliminary experiments, N-SLCs were constructed from fluorescence induction curves performed at 12 different photon flux densities (PFDs). A minimum of 50 s of illumination was necessary to reach a stable light response curve; shorter illumination times resulted in underestimating the physiological parameters (alpha the light utilization coefficient in light-limited conditions and rETR(max) the maximum rate of photosynthesis efficiency) of the light response curve. For the comparison between N-SLCs and RLCs, the same time of illumination (50 s) was used for each light step of RLCs so that N-SLCs differed from RLCs only by the way the amount of light was delivered, i.e., a light dose accumulation for RLC. The experimental results showed the difference between the two photobiological response curves. In the lower range of PFDs, RLCs exhibited a larger value of alpha; in this light-limited part of the response curve the incremental increase of PFDs limited the development of NPQ and resulted in a better optimization of electron transport rate for RLC. In the higher range of PFDs, the trend was reversed and the RLC showed a lower value of rETR(max) than the N-SLC did; this is attributed to the light dose accumulation which likely led to a more efficient dispersion of energy, as illustrated by a higher non-photochemical quenching (NPQ). In conclusion, these results confirm that parameters derived from both methods differ in their value and do not bear the same physiological information.
Marine Biology (0025-3162) (Springer), 2007-11 , Vol. 153 , N. 1 , P. 91-101

Droits : 2007 Springer
http://archimer.ifremer.fr/doc/2007/publication-3331.pdf
DOI:10.1007/s00227-007-0787-9
http://archimer.ifremer.fr/doc/00000/3331/

Éditeur(s) : HAL CCSD
Résumé : International audience
Cumulative human impacts have led to the degradation of marine ecosystems and thedecline of biodiversity in the European and contiguous seas. Effective conservationmeasures are urgently needed to reverse these trends. Conservation must entail societalchoices, underpinned by human values and worldviews that differ between the countriesbordering these seas. Social, economic and political heterogeneity adds to the challenge ofbalancing conservation with sustainable use of the seas. Comprehensive macro-regionalcoordination is needed to ensure effective conservation of marine ecosystems andbiodiversity of this region. Under the European Union Horizon 2020 framework programme,the MarCons COST action aims to promote collaborative research to support marinemanagement, conservation planning and policy development. This will be achieved bydeveloping novel methods and tools to close knowledge gaps and advance marineconservation science. This action will provide support for the development of macro-regional and national policies through six key actions: to develop tools to analysecumulative human impacts; to identify critical scientific and technical gaps in conservationefforts; to improve the resilience of the marine environment to global change and biologicalinvasions; to develop frameworks for integrated conservation planning across terrestrial,freshwater, and marine environments; to coordinate marine conservation policy acrossnational boundaries; and to identify effective governance approaches for marine protectedarea management. Achieving the objectives of these actions will facilitate the integration ofmarine conservation policy into macro-regional maritime spatial planning agendas for theEuropean and contiguous seas, thereby offsetting the loss of biodiversity and ecosystemservices in this region.
Research Ideas and Outcomes

hal-01474085
https://hal-univ-perp.archives-ouvertes.fr/hal-01474085
https://hal-univ-perp.archives-ouvertes.fr/hal-01474085/document
https://hal-univ-perp.archives-ouvertes.fr/hal-01474085/file/RIO_article_11884.pdf
DOI : 10.3897/rio.3.e11884

Éditeur(s) : HAL CCSD American Society for Pharmacology and Experimental Therapeutics (ASPET)
Résumé : International audience
Most human hepatocyte cell lines lack a substantial set of liver-specific functions, especially major cytochrome P450 (P450)-related enzyme activities, making them unrepresentative of in vivo hepatocytes. We have used the HepaRG cells, derived from a human hepatocellular carcinoma, which exhibit a high differentiation pattern after 2 weeks at confluency to determine whether they could mimic human hepatocytes for drug metabolism and toxicity studies. We show that when passaged at low density, these cells reversed to an undifferentiated morphology, actively divided, and, after having reached confluency, formed typical hepatocyte-like colonies surrounded by biliary epithelial-like cells. By contrast, when seeded at high density, hepatocyte-like clusters retained their typical differentiated morphology. Transcripts of various nuclear receptors (aryl hydrocarbon receptor, pregnane X receptor, constitutive androstane receptor, peroxisome proliferator-activated receptor alpha), P450s (CYP1A2, 2C9, 2D6, 2E1, 3A4), phase 2 enzymes (UGT1A1, GSTA1, GSTA4, GSTM1), and other liver-specific functions were estimated by reverse transcriptase-quantitative polymerase chain reaction and were found to be expressed, for most of them, at comparable levels in both confluent differentiated and high-density differentiated HepaRG cells and in cultured primary human hepatocytes. For several transcripts, the levels were strongly increased in the presence of 2% dimethyl sulfoxide. Measurement of basal activities of several P450s and their response to prototypical inducers as well as analysis of metabolic profiles and cytotoxicity of several compounds confirmed the functional resemblance of HepaRG cells to primary cultured human hepatocytes. In conclusion, HepaRG cells constitute the first human hepatoma cell line expressing high levels of the major P450s involved in xenobiotic metabolism and represent a reliable surrogate to human hepatocytes for drug metabolism and toxicity studies.
ISSN: 0090-9556

hal-00702085
https://hal.archives-ouvertes.fr/hal-00702085
DOI : 10.1124/dmd.105.006759
PUBMED : 16204462