Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.
ISSN: 0007-1048

hal-01668325
https://hal.univ-antilles.fr/hal-01668325
DOI : 10.1111/bjh.14476

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Morphology can be misleading in the representation of phylogenetic relationships, especially in simple organisms like cnidarians and particularly in hydrozoans. These suspension feeders are widely distributed in many marine ecosystems, and the family Aglaopheniidae Marktanner-Turneretscher, 1890 is among the most diverse and visible, especially on tropical coral reefs. The taxonomy of this family is based on morphological characters with emphasis on reproductive structures for the identification of genera. This study is the most comprehensive molecular phylogeny of the Aglaopheniidae to date, including six genera and 38 species, of which 13 were investigated for the first time and sampled on tropical coral reefs throughout the Indo-Pacific region. For newly sampled individuals, we sequenced the 16S rRNA, the nuclear locus comprising the complete ITS1-5.8S rRNA gene-ITS2 and the first intron of the calmodulin nuclear gene. Phylogenetic analyses of the data revealed and confirmed a general polyphyly, or doubtful monophyly, of all sampled genera in tropical regions based on both the mitochondrial and nuclear markers. Our results revealed that several morphological characters used today are unsuited to resolve phylogenetic relationships between species and genera, as well as the high phyletic diversity within this family. Future revision of the classification of this family will require extensive geographic sampling and the use of an integrative approach.
ISSN: 0300-3256

hal-01253738
https://hal.archives-ouvertes.fr/hal-01253738
https://hal.archives-ouvertes.fr/hal-01253738/document
https://hal.archives-ouvertes.fr/hal-01253738/file/Phylogenetic%20relationships%20within%20Aglaopheniidae%20%28Cnidaria%2C._hal.pdf
DOI : 10.1111/zsc.12135

Éditeur(s) : HAL CCSD Elsevier
Résumé : Field isolates of Toxoplasma gondii in Europe and North America have been grouped into three clonal lineages that display different virulence in mice. Whether the genetic structure of the parasite is related to clinical expression in humans has not yet been demonstrated. We developed an enzyme-linked immunosorbent assay which uses lineage-specific, polymorphic polypeptides derived from the dense granule antigens, GRA5 and GRA6. Our goal was to compare serotypical patterns observed in asymptomatic versus symptomatic (ocular disease and severe infection in human immunodeficiency virus (HIV)-positive patients) infections among patients from Europe and South America. Independent of the clinical presentation of the disease, serotypes differed according to geographical origin, with a homogeneous distribution of serotype II in Europe and of serotypes I and III in South America. We conclude that GRA5-GRA6 serotyping is an interesting tool to study serotype prevalence in populations but it is not an accurate marker of pathogenicity of Toxoplasma infection in humans.
ISSN: 1286-4579

hal-00306841
https://hal.archives-ouvertes.fr/hal-00306841
DOI : 10.1016/j.micinf.2008.04.001
PUBMED : 18539501

Résumé : La distribution actuelle des espèces d’arbres des forêts tropicales humides amazoniennes est le résultat de processus dynamiques sur lesquels les perturbations passées, d’origine climatique ou anthropique, peuvent avoir jouées un rôle majeur. Des outils génétiques actuels associés à des méthodes d’analyses puissantes permettent d’inférer et de dater l’empreinte génomique des évènements démographiques subits par les populations naturelles. Le but de cette thèse est de contribuer à une vision d’ensemble de l’évolution démographique de la forêt tropicale humide du plateau des Guyanes pendant le Quaternaire. J’ai d’abord étudié les propriétés des microsatellites (répétitions simple de séquences, SSR) et les limites de leurs applications en tant que marqueurs moléculaires en phylogéographie. Plusieurs allèles SSR contenu dans diverses populations de trois genres d’arbres différents ont été séquencés et le polymorphisme, porté par chaque partie des fragments ADN contenant des SSR, a été étudié. J’ai observé que la quantité de variation génétique était aussi importante dans les régions encadrant le microsatellite que dans le SSR lui-même. Ces régions ont contribué significativement à l’information phylogénétique et ont parfois été la principale source de différenciation entre les individus et les populations. Cette expérience m’a permis de choisir la meilleure stratégie à adopter pour traiter les données de variation génétique des SSR dans des modèles démographiques. J’ai ensuite utilisé ces marqueurs SSR et des méthodes ABC pour étudier l’impact local des occupations humaines précolombiennes sur les forêts en Guyane française. Les changements démographiques subis par des populations de quatre espèces d’arbres ont été comparés entre cinq sites occupés et quatre sites non perturbés. Les perturbations naturelles et induites par l’homme ont contribué à la mise en place de la diversité observée actuellement, comme le suggère des signatures d’effet fondateur détectées sur les sites perturbés ou non. Néanmoins, la taille des populations fondatrices semble être proportionnelle à l’impact humain estimé, indiquant que les perturbations anthropique ont induit un remplacement des populations plus important que les processus écologiques naturels. Pour terminer, j’ai mené une étude de démographie comparative d’espèces d’arbres tropicaux à l’échelle régionale de la Guyane française. Cinq scénarios démographiques ont été testés pour neuf populations de huit espèces en utilisant des microsatellites nucléaires et des séquences chloroplastiques. Les changements démographiques les plus récents détectés convergent vers une signature générale d’expansion de la forêt humide depuis probablement la dernière glaciation. Cela peut suggérer, soit que la composition des forêts du plateau des Guyanes était différente, ou que le couvert forestier était moins étendu. Ce résultat constitue le premier indice de changement passé, probablement d’origine climatique, subi par les communautés forestières du plateau des Guyanes ; qui n’avait jusque-là pas pu être testé avec des méthodes standards en raison d’un manque de fossiles. En conclusion, j’ai recueilli des preuves génétiques que les perturbations, à différents échelles de temps, ont marqué la structure et la composition génétique des forêts du plateau des Guyanes. L’application de ces méthodes à d’autres régions Néotropicales pourrait contribuer, à l’avenir, à reconstruire l’histoire écologique de la forêt amazonienne de façon détaillée.
The current tree species distribution in Amazonian tropical rainforests is the outcome of dynamic processes in which past perturbations, climatic or anthropogenic, may have played a major role. Currently available genetic tools associated with powerful analytical methods allow inferring and dating the genomic imprint of demographic events undergone by natural populations. The aim of my thesis is to contribute to an overview of the demographic evolution of the tropical rainforest in the Guiana shield during the Quaternary. I have first studied the properties of microsatellites or Simple sequence repeat (SSR) and the limits in their applications as molecular markers in phylogeography. Several SSR alleles in multiple populations of three divergent tree genera have been sequenced and the sources of polymorphisms, carried by each portion of SSR-containing DNA amplicons, have been broken apart. I have observed that the amount of variation was as large in flanking regions as in the SSR itself. The former contributed significantly to the phylogenetic information and sometimes was the main source of differentiation among individuals and populations. This experiment allowed me to choose the best strategy to treat SSR variation in demographic modeling. I have subsequently used SSR markers and ABC methods to study the impact of pre-Columbian human settlements at the local level on rainforests in French Guiana. Demographic changes undergone by populations of four tree species were compared between five settled and four undisturbed sites. Both natural turnover and human-induced disturbances appeared as shaping currently observed genetic diversity, with signatures of founder effect both at disturbed and undisturbed sites. Nevertheless, the size of founding populations appeared to be proportional to the estimated human impact, suggesting that human-made disturbance caused deeper population turnover than background ecological processes. Finally, I have conducted a comparative demography study of tropical tree species at the regional level across French Guiana. Five demographic scenarios have been tested for nine populations from eight species using both nuclear microsatellites and chloroplastic sequences. The most recent demographic signals detected converge on a global signature of expansion of the rainforest since probably the last glaciation. This finding can suggest either that the composition of the Guiana shield rainforests was different, or that its global extent was smaller, during earlier epochs of the Pleistocene than today. This result is the first firm indication of changes undergone by the forest communities of the Guiana shield in the distant climatic past – something which could not be tested with standard methods due to almost complete lack of fossil evidence. In conclusion, I have gathered genetic evidence that disturbances, both in historical and geological times, have marked the structure and composition of forests in the Guiana shield.The extensive application of these methods to other regions of the Neotropics maycontribute, in the future, to the detailed reconstruction of the ecological history ofAmazonian forests.

http://www.theses.fr/2012AGUY0568/document

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We explore the relationships within Serraniformes (Li et al., 2009) using a dense taxon sampling and seven nuclear markers. Six had already used been for teleost phylogeny (IRBP, MC1R, MLL4, Pkd1, Rhodopsin, and RNF213) at other scales, and one (MLL2) is new. The results corroborate the composition of Serraniformes described in previous publications (some Gasterosteiformes, Perciformes and Scorpaeniformes). Within the clade, Notothenioidei and Zoarcoidei are each monophyletic. Cottoidei was not monophyletic due to placement of the genus Ebinania (Psychrolutidae). Our independent data confirm the sister-group relationship of Percophidae and Notothenioidei as well as the division of Platycephaloidei in four different groups (Bembridae, Platycephalidae, Hoplichthyidae and Peristediidae with Triglidae). Within Cottoidei, Liparidae and Cyclopteridae formed a clade associated with Cottidae, the genus Cottunculus (Psychrolutidae), and Agonidae. Serranidae and Scorpaenidae are not monophyletic, with the Serranidae divided in two clades (Serraninae and Epinephelinae/Anthiinae) and Scorpaenidae including Caracanthidae and the genus Ebinania (Psychrolutidae). We discuss some morphological characters supporting clades within the Scorpaenidae.
ISSN: 1055-7903

hal-01544909
https://hal.archives-ouvertes.fr/hal-01544909
DOI : 10.1016/j.ympev.2012.12.020

Éditeur(s) : HAL CCSD
Résumé : The Tyrrhenian Sea is usually interpreted to be a Neogene back-arc basin that opened by continental rifting and oceanic spreading caused by the eastward migration of the Apennine subduction system from Tortonian to Pliocene times. Rifting of the Tyrrhenian Sea started first along the Eastern Sardinian margin during the Tortonian-Messinian times. The " METYSS " project aims at better constraining the relations between crustal tectonics, salt tectonics and sedimentation from Messinian times to present-day. The " METYSS 1 " cruise (2009, R/V "Téthys II"-INSU) allowed us to obtain about 1200 km of high-resolution seismic reflection profiles along the SE Corsican margin, and along the upper and middle parts of the Eastern Sardinian margin, Western Tyrrhenian. This new dataset clearly illustrates that this area has been highly dissected during the rifting stage by N-S trending normal faults delineating ridges and basins, as previously described. The Messinian seismic markers (UU and MU) locally display fan-shaped stratal geometries, but the mechanism responsible for such geometries, i.e., salt tectonics or rifting, has yet to be carefully deciphered. We also mapped the spatial distribution of the mobile salt (MU). The highly variable thickness of the confined salt basins may be related to the initial pre-Messinian basin geometry or to the fact that sediment deposition was syn-rift. Southeastward, salt tectonics appears highly vigorous. More surprisingly, our data demonstrate that some of the major faults have been significantly reactivated during the post-rift period, up to late Quaternary time. Such recent fault activity has been recorded by bathymetric scarps and associated footwall debris flows. Moreover, some of this post-rift deformation can be evidenced within the Plio-Quaternary sequence by a regional unconformity. The post-Miocene deformation style varies greatly between different areas of the margin, and can also be strongly influenced by the presence or absence of mobile Messinian evaporites (MU).
13ème Congrès Français de Sédimentologie
Dijon, France

hal-00657310
https://hal-brgm.archives-ouvertes.fr/hal-00657310

Éditeur(s) : Canadian Science Publishing, Nrc Research Press
Résumé : Examining the genetic structure of species allows an estimate of the level of evolutionary connectivity between localities; this information is important for marine biodiversity protection, in particular, for the delineation of marine protected areas. In this context, a total of 601 Lutjanus kasmira (Forsskal, 1775) were sampled in 16 localities of the western Indian Ocean and analyzed with both mitochondrial cytochrome b sequencing and eight microsatellite loci genotyping. Both genetic markers indicate that differentiation was not significant even between samples separated by more than 4000 km. This absence of genetic differentiation among samples was favored by ecological plasticity of the species and is now ensured by resultant high levels of dispersal. Nevertheless, some significant genetic structure was detected for the areas of Mauritius and Moroni, as well as within populations in all localities, which will have to be explained by additional studies on local processes.
Canadian Journal Of Fisheries And Aquatic Sciences (0706-652X) (Canadian Science Publishing, Nrc Research Press), 2012-05 , Vol. 69 , N. 5 , P. 842-853

Droits : 2012 Published by NRC Research Press
http://archimer.ifremer.fr/doc/00079/19044/16647.pdf
DOI:10.1139/F2012-012
http://archimer.ifremer.fr/doc/00079/19044/

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Among persisting questions on bone calcification, a major one is the link between protein expression and mineral deposition. A cell culture system is here proposed opening new integrative studies on biomineralization, improving our knowledge on the role played by non-collagenous proteins in bone. This experimental in vitro model consisted in human primary osteoblasts cultured for 60 days at the surface of a 3D collagen scaffold mimicking an osteoid matrix. Various techniques were used to analyze the results at the cellular and molecular level (adhesion and viability tests, histology and electron microscopy, RT-and qPCR) and to characterize the mineral phase (histological staining, EDX, ATG, SAED and RMN). On long term cultures human bone cells seeded on the osteoid-like matrix displayed a clear osteoblast phenotype as revealed by the osteoblast-like morphology, expression of specific protein such as alkaline phosphatase and expression of eight genes classically considered as osteoblast markers, including BGLAP, COL1A1, and BMP2. Von Kossa and alizarine red allowed us to identify divalent calcium ions at the surface of the matrix, EDX revealed the correct Ca/P ratio, and SAED showed the apatite crystal diffraction pattern. In addition RMN led to the conclusion that contaminant phases were absent and that the hydration state of the mineral was similar to fresh bone. A temporal correlation was established between quantified gene expression of DMP1 and IBSP, and the presence of hydroxyapatite, confirming the contribution of these proteins to the mineralization process. In parallel a difference was observed in the expression pattern of SPP1 and BGLAP, which questioned their attributed role in the literature. The present model opens new experimental possibilities to study spatio-temporal relations between bone cells, dense collagen scaffolds, NCPs and hydroxyapatite mineral deposition. It also emphasizes the importance of high collagen density environment in bone cell physiology.
ISSN: 1932-6203

hal-01142641
http://hal.upmc.fr/hal-01142641
http://hal.upmc.fr/hal-01142641/document
http://hal.upmc.fr/hal-01142641/file/Silvent_2013_Collagen.pdf
DOI : 10.1371/journal.pone.0057344

Éditeur(s) : HAL CCSD Wiley/Blackwell
Résumé : International audience
This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis (Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle,Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium albo-atrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species.
ISSN: 1755-098X

hal-01094222
https://hal-agroparistech.archives-ouvertes.fr/hal-01094222
DOI : 10.1111/j.1755-0998.2010.02916.x

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We present results of a geomorphological and morphotectonic analysis of the northeastern part of the Rif. We show that the present day kinematics of the Rif is characterized by active deformation along the Trougout and Nekor faults in the North-East. Digital Elevation Models of offset drainage features (streams, fluvial terraces) allow determining a normal-left-lateral motion along the Trougout fault and a left-lateral strike-slip motion along the Nekor fault. Preliminary 3He cosmogenic dates of tectonic markers yield vertical and horizontal slip rates of ∼0.9 mm/yr and ∼0.5 mm/yr, respectively along the Trougout fault. The present-day localized transtension seen in the north-eastern Rif morphology (Ras Tarf) is coeval with uplifted marine terraces near the Al Hoceima Bay. U/Th dating of shells yield an average uplift rate of ∼0.2 mm/yr during the past 500 ka. These data show that active transtension in the northeastern Rif is also associated with uplift. These new morphotectonic constraints are consistent with the GPS measurements showing southwestward overall motion of most of the Rif belt with respect to stable Africa.
ISSN: 0264-3707

hal-01053492
https://hal.archives-ouvertes.fr/hal-01053492
DOI : 10.1016/j.jog.2014.01.004

Éditeur(s) : HAL CCSD
Résumé : Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma. Therapeutic treatment against the virus has been recently improved by a tritherapy including pegylated interferon, ribavirin and antiviral protease. Nevertheless, the importance of side effects and the emergence of resistant mutants require the development of new antivirals. In this context, our team has recently discovered that Type III phosphatidylinositol 4-kinases (PI4KIIIα and PI4KIIIβ) are essential for the propagation of the virus in a human hepatic cell line at the entry and replication steps. To further characterize these potential therapeutic targets, we investigate the implication of these kinases during the HCV entry, using primary human hepatocytes, a model closer to the in vivo conditions. Two lines of research were developed: Verification of the importance of the kinase activity of PI4KIIIs during HCV entry in primary human hepatocytes, through a chemical approach; Validation of the involvement of these kinases and their enzymatic activity during viral entry through a genetic approach based on RNA interference and phenotype rescue. In parallel, we studied the expression of PI4KIIIα in liver diseases. Our results suggest the involvement of PI4KIIIα in HCV entry; the involvement of PI4KIIIIβ needs to be confirmed. The analysis of PI4KIIIα expression in hepatocellular carcinoma led us to propose this kinase as a new molecular marker, which could improve the already established prognosis models and could lead to the development of new therapeutic approaches.
Le virus de l’hépatite C (VHC) est l’un des principaux facteurs étiologiques du carcinome hépatocellulaire. Le traitement des hépatites virales C a été récemment amélioré grâce à une trithérapie (interféron, ribavirine et anti-protéase virale). Néanmoins l’importance des effets secondaires et l’émergence de mutants résistants nécessitent de découvrir de nouveaux antiviraux. Dans ce contexte, notre équipe a récemment découvert que les phosphatidylinositol 4-kinases de type III (PI4KIIIα et PI4KIIIβ) étaient indispensables à la propagation du virus dans une lignée hépatique humaine, et ce, à 2 étapes de son cycle biologique : l’entrée et la réplication. L’objectif du présent travail était de poursuivre la validation de ces nouvelles cibles thérapeutiques potentielles, en approfondissant nos connaissances sur la dépendance du virus à l’égard de ces kinases au cours de son entrée. Pour cela, nous avons utilisé le modèle des hépatocytes humains primaires, système in vitro plus proche du contexte physiologique que les modèles utilisés jusqu’à présent et qui étaient basés sur l’exploitation de lignées. Deux axes ont été développés : Vérification de l’importance de l’activité kinase des PI4KIIIs au cours de l’entrée du VHC dans les hépatocytes humains primaires, à travers une approche chimique ; Validation de l’implication de ces kinases et de leur activité enzymatique au cours de l’entrée virale grâce à une approche génétique basée sur l’ARN interférence et la restauration de phénotype. En parallèle, nous avons étudié l’expression de PI4KIIIα au cours de pathologies hépatiques. Nos résultats suggèrent une implication de PI4KIIIα au cours de l’entrée du VHC dans les hépatocytes humains primaires, mais restent à confirmer quant à l’implication de PI4KIIIβ. Par ailleurs, l’analyse de l’expression de PI4KIIIα dans le carcinome hépatocellulaire (CHC) conduit à proposer cette kinase comme un nouveau marqueur moléculaire, qui pourrait améliorer les modèles de pronostic déjà établis et pourrait conduire au développement de nouvelles approches thérapeutiques pour les patients atteints d’un CHC, quelque soit l’étiologie.
https://tel.archives-ouvertes.fr/tel-00950335

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B006
tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335/document
https://tel.archives-ouvertes.fr/tel-00950335/file/ILBOUDOAdeodat.pdf

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : Key message Molecular markers were used for paternity recovery in a maritime pine (Pinus pinasterAit.) polycross trial, facilitating forward selection. Different breeding strategies for seed orchard establishment were evaluated by comparing genetic gains and diversity. This work opens up new perspectives in maritime pine breeding.Context Polycross mating designs are widely used in forest tree breeding to evaluate parental breeding values for backward selection. Alternatively, polycross progeny trials may be used to select the best trees on the basis of individual breeding values and molecular pedigree analysis.Aims This study aimed to test such a forward selection strategy for the maritime pine breeding program.Methods In a maritime pine polycross trial, progeny with higher breeding values for growth and stem straightness was first preselected with or without relatedness constraints. After paternity recovery, the preselected trees were ranked on the basis of their breeding values, estimated from the recovered full pedigree. Finally, the best candidates were selected with three different strategies (forward, backward, mixed) and three levels of coancestry constraints to establish a virtual clonal seed orchard.Results Complete pedigrees were successfully recovered for most of the preselected trees. There was no major difference in expected genetic gains between the two preselection strategies which differed for relatedness constraints. Genetic gains were slightly higher for forward selection than for classical backward selection.Conclusion This seminal study opens up new perspectives for using forward selection within the French maritime pine breeding program.
ISSN: 1932-6203

hal-01601804
https://hal.archives-ouvertes.fr/hal-01601804
DOI : 10.1371/journal.pone.0049990
PRODINRA : 391860

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Mechanical forces influence the growth and shape of virtually all tissues and organs. Recent studies show that increased cell contractibility, growth and differentiation might be normalized by modulating cell tensions. Particularly, the role of these tensions applied by the extracellular matrix during liver fibrosis could influence the hepatocarcinogenesis process. The objective of this study is to determine if 3D stiffness could influence growth and phenotype of normal and transformed hepatocytes and to integrate extracellular matrix (ECM) stiffness to tensional homeostasis. We have developed an appropriate 3D culture model: hepatic cells within three-dimensional collagen matrices with varying rigidity. Our results demonstrate that the rigidity influenced the cell phenotype and induced spheroid clusters development whereas in soft matrices, Huh7 transformed cells were less proliferative, well-spread and flattened. We confirmed that ERK1 played a predominant role over ERK2 in cisplatin-induced death, whereas ERK2 mainly controlled proliferation. As compared to 2D culture, 3D cultures are associated with epithelial markers expression. Interestingly, proliferation of normal hepatocytes was also induced in rigid gels. Furthermore, biotransformation activities are increased in 3D gels, where CYP1A2 enzyme can be highly induced/activated in primary culture of human hepatocytes embedded in the matrix. In conclusion, we demonstrated that increasing 3D rigidity could promote proliferation and spheroid developments of liver cells demonstrating that 3D collagen gels are an attractive tool for studying rigidity-dependent homeostasis of the liver cells embedded in the matrix and should be privileged for both chronic toxicological and pharmacological drug screening.
ISSN: 0730-2312

hal-01196600
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01196600/file/Increasing%203D%20Matrix%20Rigidity_accepted.pdf
DOI : 10.1002/jcb.25356

Éditeur(s) : HAL CCSD
Résumé : absent
Actes du BRG

hal-01031523
https://hal.archives-ouvertes.fr/hal-01031523

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The mycotoxin enniatin B (EnnB) is predominantly produced by species of the Fusarium genera, and often found in grain. The cytotoxic effect of EnnB has been suggested to be related to its ability to form ionophores in cell membranes. The present study examines the effects of EnnB on cell death, differentiation, proliferation and pro-inflammatory responses in the murine monocyte-macrophage cell line RAW 264.7. Exposure to EnnB for 24 h caused an accumulation of cells in the G0/G1-phase with a corresponding decrease in cyclin D1. This cell cycle-arrest was possibly also linked to the reduced cellular ability to capture and internalize receptors as illustrated by the lipid marker ganglioside GM1. EnnB also increased the number of apoptotic, early apoptotic and necrotic cells, as well as cells with elongated spindle-like morphology. The Neutral Red assay indicated that EnnB induced lysosomal damage; supported by transmission electron microscopy (TEM) showing accumulation of lipids inside the lysosomes forming lamellar structures/myelin bodies. Enhanced levels of activated caspase-1 were observed after EnnB exposure and the caspase-1 specific inhibitor ZYVAD-FMK reduced EnnB-induced apoptosis. Moreover, EnnB increased the release of interleukin-1 beta (IL-1β) in cells primed with lipopolysaccharide (LPS), and this response was reduced by both ZYVAD-FMK and the cathepsin B inhibitor CA-074Me. In conclusion, EnnB was found to induce cell cycle arrest, cell death and inflammation. Caspase-1 appeared to be involved in the apoptosis and release of IL-1β and possibly activation of the inflammasome through lysosomal damage and leakage of cathepsin B.
ISSN: 0041-008X

inserm-00871698
http://www.hal.inserm.fr/inserm-00871698
DOI : 10.1016/j.taap.2012.03.014
PUBMED : 22483798

Éditeur(s) : HAL CCSD American Geophysical Union
Résumé : International audience
We analyze the kinematics of fault tip folding at the front of a fold-and-thrust wedge using a sandbox experiment. The analog model consists of sand layers intercalated with low-friction glass bead layers, deposited in a glass-sided experimental device and with a total thickness h = 4.8 cm. A computerized mobile backstop induces progressive horizontal shortening of the sand layers and therefore thrust fault propagation. Active deformation at the tip of the forward propagating basal décollement is monitored along the cross section with a high-resolution CCD camera, and the displacement field between pairs of images is measured from the optical flow technique. In the early stage, when cumulative shortening is less than about h/10, slip along the décollement tapers gradually to zero and the displacement gradient is absorbed by distributed deformation of the overlying medium. In this stage of detachment tip folding, horizontal displacements decrease linearly with distance toward the foreland. Vertical displacements reflect a nearly symmetrical mode of folding, with displacements varying linearly between relatively well defined axial surfaces. When the cumulative slip on the décollement exceeds about h/10, deformation tends to localize on a few discrete shear bands at the front of the system, until shortening exceeds h/8 and deformation gets fully localized on a single emergent frontal ramp. The fault geometry subsequently evolves to a sigmoid shape and the hanging wall deforms by simple shear as it overthrusts the flat ramp system. As long as strain localization is not fully established, the sand layers experience a combination of thickening and horizontal shortening, which induces gradual limb rotation. The observed kinematics can be reduced to simple analytical expressions that can be used to restore fault tip folds, relate finite deformation to incremental folding, and derive shortening rates from deformed geomorphic markers or growth strata.
ISSN: 2169-9313

hal-00138061
https://hal.archives-ouvertes.fr/hal-00138061
https://hal.archives-ouvertes.fr/hal-00138061/document
https://hal.archives-ouvertes.fr/hal-00138061/file/Bernard_et_al-2007-Journalsur Geophysical_Research__Solid_Earth_%281978-2012%29.pdf
DOI : 10.1029/2005JB004149

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Studies focusing on the effect of invasive species on the genetic diversity of native marine invertebrates remain scant. Here we report diversity among French populations of the intertidal gastropod Ocenebra erinacea (Linnaeus, 1758) sampled in the presence and absence of the invasive Ocenebra inornata (Recluz, 1851). Between 1999 and 2004, a total of 352 individuals of O. erinacea was collected from 15 sites, five of which had the invasive present, and genotyped at the mitochondrial locus cox1. No statistical difference was observed between polymorphism levels recorded within native populations exposed to the invasive, compared with populations sampled in the absence of O. inornata. No sign of native population decline was detected in response to the invader. While significant shifts in native O. erinacea population sizes have previously been reported in the literature, genetic effects may take longer to accumulate, or may be undetectable without a larger panel of genetic markers. By contrast, large genetic distances and significant population differentiation were recorded between Atlantic and Mediterranean O. erinacea samples, suggesting that these populations have distinct evolutionary histories. Comparison of genetic divergence within the closely related genus Nucella suggests that the Atlantic populations of O. erinacea and those from Thau Lagoon in the Mediterranean may belong to different species or subspecies.
ISSN: 0173-9565

hal-01064464
https://hal.archives-ouvertes.fr/hal-01064464
https://hal.archives-ouvertes.fr/hal-01064464/document
https://hal.archives-ouvertes.fr/hal-01064464/file/Ocenebra_revision_submission_to_MarEcol.pdf
DOI : 10.1111/maec.12208

Éditeur(s) : HAL CCSD American Society of Nephrology
Résumé : International audience
Since the recent publication of data showing favorable outcomes for patients with HIV-1 and ESRD, kidney transplantation has become a therapeutic option in this population. However, reports have documented unexplained reduced allograft survival in these patients. We hypothesized that the unrecognized infection of the transplanted kidney by HIV-1 can compromise long-term allograft function. Using electron microscopy and molecular biology, we examined protocol renal transplant biopsies from 19 recipients with HIV-1 who did not have detectable levels of plasma HIV-1 RNA at transplantation. We found that HIV-1 infected the kidney allograft in 68% of these patients. Notably, HIV-1 infection was detected in either podocytes predominately (38% of recipients) or tubular cells only (62% of recipients). Podocyte infection associated with podocyte apoptosis and loss of differentiation markers as well as a faster decline in allograft function compared with tubular cell infection. In allografts with tubular cell infection, epithelial cells of the proximal convoluted tubules frequently contained abnormal mitochondria, and both patients who developed features of subclinical acute cellular rejection had allografts with tubular cell infection. Finally, we provide a novel noninvasive test for determining HIV-1 infection of the kidney allograft by measuring HIV-1 DNA and RNA levels in patients' urine. In conclusion, HIV-1 can infect kidney allografts after transplantation despite undetectable viremia, and this infection might influence graft outcome.
ISSN: 1046-6673

hal-01121764
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121764
DOI : 10.1681/ASN.2013050564
PUBMED : 24309185
PUBMEDCENTRAL : PMC3904571

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Clin Microbiol Infect ABSTRACT: Atypical Toxoplasma gondii strains, unrelated to archetypal clonal lineages (I, II, III), have been reported more frequently over the last decade in areas other than Europe and North America. A newly described form of toxoplasmosis, 'Amazonian toxoplasmosis' (AT), has been reported since 2002 in French Guiana. It is characterized by severe cases and atypical strains linked to a neotropical forest-based cycle. We report on the cases of AT that required intensive care management. We performed a prospective observational study on hospitalized adults in the Intensive Care Unit (ICU) from 2002 to 2008. Clinical and laboratory data, microbiological findings and outcomes were recorded. Data, including the ICU simplified acute physiology score and the pneumonia severity index, were calculated. Epidemiological risk factors for AT were assessed through questionnaires. Eleven non-immunodeficient patients were admitted to the ICU in Cayenne for life-threatening pneumonia associated with disseminated toxoplasmosis. Mechanical ventilation was necessary in seven patients, four of whom required immediate orotracheal intubation. Cardiac and ophthalmological abnormalities were found in five and four patients, respectively. One patient died from multiple organ failure. The genetic characterization of Toxoplasma DNA using six microsatellite markers revealed unique and atypical genotypes in eight patients. All patients presented epidemiological risk factors for AT. In French Guiana, significant T. gondii-related infectious syndrome associated with the lungs, a high level of LDH activity and the reported risk factors for AT was strongly suggestive of disseminated toxoplasmosis with a possible trend toward life-threatening pneumonia.
ISSN: 1198-743X

hal-00678752
https://hal-unilim.archives-ouvertes.fr/hal-00678752
DOI : 10.1111/j.1469-0691.2011.03648.x
PUBMED : 21958195

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Objectives To investigate the association between priapism in men with sickle cell anemia (SCA) and hemorheological and hemolytical parameters. Materials and Methods Fifty-eight men with SCA (median age: 38 years) were included; 28 who had experienced priapism at least once during their life (priapism group) and 30 who never experienced this complication (control group). Twenty-two patients were treated with hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC) deformability at 30 Pa (ektacytometry) and RBC aggregation properties (laser backscatter versus time). Blood viscosity was measured at a shear rate of 225 s(-1) using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), total bilirubin (BIL) levels and reticulocyte (RET) percentage) to calculate a hemolytic index. Results Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01), LDH (p = 0.03), RET (p = 0.03) levels and hemolytic indices (p = 0.02). Higher RBC aggregates strength (p = 0.01) and lower RBC deformability (p = 0.005) were observed in patients with priapism compared to controls. After removing the hydroxycarbamide-treated patients, RBC deformability (p = 0.01) and RBC aggregate strength (p = 0.03) were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01) than controls. Conclusion Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.
ISSN: 1932-6203

hal-01390971
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390971
DOI : 10.1371/journal.pone.0154866
PUBMED : 27145183