Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Can protein biomarkers of the male genital tract be identified in human seminal plasma? SUMMARY ANSWER: We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. WHAT IS KNOWN ALREADY: The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract. STUDY DESIGN, SIZE, DURATION: This study combines proteomic analyses of normal seminal plasma together with transcriptomic gene expression profiling of human healthy tissues. MATERIALS, SETTING, METHODS: Non-liquefied seminal plasma proteins from a healthy donor were prefractionated using two sequential Proteominer™ libraries. Eight subproteome fractions were collected, trypsin digested and subjected to three successive mass spectrometry analyses for peptide characterization. The list of identified proteins was compared with and merged with other available data sets of the human seminal plasma proteome. The expression of corresponding genes was then investigated using tissue transcriptome profiles to determine where, along the male reproductive tract, these proteins were produced. Finally, tissue specificity of a selected subset of biomarker candidates was validated on human tissues. MAIN RESULTS AND THE ROLE OF CHANCE: We first performed a proteomic analysis of the human seminal plasma and identified 699 proteins. By comparing our protein list with other previous proteomic data sets, we found that 2545 unique proteins have been described so far in the human seminal plasma. We then profiled their expression at the gene level and identified 83 testis, 42 epididymis, 7 seminal vesicle and 17 prostate candidate protein markers. For a subset of testis-specific candidates, i.e. TKTL1, LDHC and PGK2, we further validated their germ cell expression and demonstrated that such markers could distinguish between semen from fertile and infertile men. LIMITATIONS, REASONS FOR CAUTION: While some of the markers we identified are well-known tissue-specific products, further dedicated studies to validate the biomarker status of new candidates will be required. Additionally, whether or not the abundance of these proteins is indeed decreased in some specific pathological situations remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: Using an integrative genomics approach, we identified biomarker candidates for each of the organs participating in the seminal plasma production. In this study, we essentially focused on germ cell markers and their potential application for the diagnosis of male infertility. Other types of markers also deserve a focused attention given their potential predictive value for various reproductive disorders, notably for prostate cancers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Proteomics Core Facility at Biogenouest and was funded by Conseil Régional de Bretagne, IBiSA and Agence de la Biomédecine grants. The authors declare that there exists a competing financial interest in this work that is related to a patent application on the use of identified germ cell-specific proteins in an antibody-based assay (Fertichip™) to predict the successful testicular biopsy outcomes in human non-obstructive azoospermia.
ISSN: 0268-1161

inserm-00814146
http://www.hal.inserm.fr/inserm-00814146
DOI : 10.1093/humrep/des360
PUBMED : 23024119

Éditeur(s) : HAL CCSD
Résumé : The present study addresses the question of increasing need in water supply. One line of research consists in investigating karst aquifers that represent significant water supplies for the areas around the Mediterranean. This work aims at developing a methodology of predictive evaluation of karst distribution and karst thickness within the carbonate massifs. It is based on the study of the Tethysian carbonate platform from the area of Montpellier, South of France. This area underwent a polyphased, complex, tectonic evolution, involving successive karst forming events. The approach is based on the relationships between eustacy and geodynamics, on one hand, and base-level variation recorded within palaeokarsts, on the other hand. Sedimentary fill of palaeokarsts allows to identify distinct karstification phases and sometimes to date them. It is a marker of base-level variations, which we attempt to quantify, that is responsible for karst formation and karst filling and sealing. For three palaeokarsts of regional extent, we analyze : karst sedimentary-fill, the distribution along upstream-downstream profile, the vertical extension of palaeokarsts, indicative of the base-level lowering. - The " Bauxite palaeokarst " results from the two-stage evolution of the " Isthme Durancien " : i) Bauxitic weathering of the Neocomian cover over the southern Massif Central , related to an inversion during Barremian ; ii) ≥1600 m uplift and exhumation during Aptian-Albian, inducing erosion of alterites, upstream, and deposition of detrital bauxites, downstream. - The " Early Paleocene palaeokarsts with marine sedimentary-fill " indicate base level variations of more than 350m in the upstream area. It is suggested here that such base-level variations, exceeding eustacy and recorded in tabular undeformed series, result from desiccation-flooding events in an endoreic silled basin. - The " Miocene palaeokarst with Cevennes-sourced sediment-fill " records a Serravalian-Tortonian base-level drop, depicted by canyon incision in the hinterland of the Gulf of Lion Margin. Uplift values of ≥ 400m upstream, about 250m in an intermediate area and 10's of m downstream, are measured. The present 3D geometry and distribution of carbonate massifs (exposed and covered) are modeled in the study area, from the Cevennes to the Mediterranean. The 3D geological model integrates seismic reflection, borehole and gravimetric data. Tectonic restoration of a N-S section, extracted from the 3D model, allows to reconstruct paleo-base-levels with respect with the carbonate massifs, at different stages of deformation and successive phases of karstification. The 3D paleo-flows through carbonates across the study area, are thus constrained, especially during the Messinian desiccation stage. Application of the results to hydrogeology leads to the following : - Uplift of upstream hinterland (Cretaceous, Miocene) produces large amplitude karsts, but they do not make significant reservoirs. - Karstification responsible for the development of important and deep karst reservoirs is related to desiccation of endoreic basins (early Paleocene and Messinian). - Theses two events have produced two main deep karst reservoirs, with a gravimetric signature : (1) Upstream of Montpellier Thrust, between Pic St Loup, Les Matelles Fault and Hérault Basin, a deep karsts developed over 900m thickness in the Malm limestone, during Paleocene. (2) Downstream (south) of Montpellier Thrust, the coastal karsts extend offshore over more than 10km, they are sealed by a thick Miocene to Quaternary cover, and they result from the Messinian event.
Cette étude s'inscrit dans un contexte de demande croissante en ressources en eau, conduisant à mieux contraindre et estimer la distribution des aquifères karstifiés qui représentent une ressource importante, notamment sur le pourtour méditerranéen. Le but de ce travail est d'élaborer une méthode prédictive de la distribution de la karstification et de l'épaisseur de massifs carbonatés karstifiés, notamment pour les karsts profonds. La méthodologie est développée à partir de l'étude des karsts de la plateforme carbonatée téthysienne du Languedoc montpelliérain; région qui a subi une histoire tectonique complexe et polyphasée, entrainant des phases de karstification successives. Elle est basée sur la compréhension des relations entre eustatisme, géodynamique et niveau de base, enregistrées par les paléokarsts de la région. Le remplissage sédimentaire des paléokarsts permet d'identifier les épisodes de karstification et de les dater ; c'est un marqueur des variations -que l'on cherche à quantifier- du niveau de base local responsable de la formation et du comblement des karsts. On analyse 3 paléokarsts d'extension régionale dont on peut étudier : le remplissage karstique, la distribution le long de profils amont-aval et l'extension verticale indicatrice de l'amplitude de l'abaissement du niveau de base dont il est issu. On en déduit les causes géodynamiques à l'origine de leur formation: - Le " paléokarst des bauxites " à remplissage caractéristique, résulte de l'évolution en 2 phases de " l'Isthme Durancien " : altération bauxitique de la couverture néocomienne sur le sud du Massif Central, liée à une inversion au Barrémien, suivi d'une surrection ≥ 1600m à l'Aptien-Albien, causant l'érosion des altérites en amont et le dépôt des bauxites détritiques en aval. - Le " paléokarst à remplissage marin paléocène inférieur " indique des variations du niveau de base local ≥350m dans la zone amont sud-cévenole. On propose que ces variations de niveau de base d'amplitude très supérieures aux variations eustatiques et dans une zone faiblement déformée, résultent d'assèchements et d'ennoiements d'un bassin endoréique à seuil. - Le " paléokarst à remplissage détritique d'origine cévenole ", enregistre la chute du niveau de base au Serravalien-Tortonien, qui se traduit par l'incision de canyons dans l'arrière-pays de la marge du Golfe du Lion. On détermine une surrection de plus de 400 mètres à l'amont, près de 250m dans les blocs faillés intermédiaires et quelques dizaines de mètres dans la zone avale. En parallèle, on établit la géométrie et la distribution actuelles des massifs carbonatés dans la zone d'étude (y compris sous couverture), en construisant un modèle géologique 3D, des Cévennes à la Méditerranée. On intègre les données de sismique réflexion, de forages et les données gravimétriques. La restauration tectonique séquentielle d'une coupe Nord-Sud extraite du modèle géologique permet d'appréhender la position des paléo-niveaux de base par rapport aux massifs carbonatés, pour chaque époque de karstification. On déduit l'organisation 3D des paléo-écoulements à travers la géométrie complexe des massifs carbonatés languedociens, notamment pendant l'évènement messinien. En terme d'évaluation de la ressource en eau, on déduit que: - Les surrections de l'arrière-pays (Crétacé " moyen ", Miocène) produisent des karsts de grande amplitude, mais ne constituent pas de réservoirs significatifs. - La karstification à l'origine de réservoirs exploitables importants et profonds est créée par l'assèchement de bassins endoréiques, qui ont affecté la région au Paléocène inférieur et au Messinien . - Ces deux évènements sont à l'origine de deux principaux réservoirs karstiques profonds qui ont une signature gravimétrique : (1) En amont du chevauchement de Montpellier, entre le Pic Saint Loup, la faille des Matelles et le bassin de l'Hérault, le karst profond se développe sur une épaisseur atteignant 900m, et est attribuée à l'événement du Paléocène. (2) Au Sud du chevauchement de Montpellier les karsts côtiers s'étendent jusqu'à plus de 10 km au large, scellés par une épaisse couverture Miocène et Plio-Quaternaire, et résultent de l'événement Messinien.
https://tel.archives-ouvertes.fr/tel-00936257

tel-00936257
https://tel.archives-ouvertes.fr/tel-00936257
https://tel.archives-ouvertes.fr/tel-00936257/document
https://tel.archives-ouvertes.fr/tel-00936257/file/thA_se_husson_couleurs.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (>/=F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.
Journal of gastroenterology and hepatology

hal-01477209
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477209
DOI : 10.1111/jgh.13338
PUBMED : 26992056

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Challenging evaluation of tropical forest biodiversity requires the reporting of taxonomic diversity but also the systematic characterization of wood properties in order to discover new promising species for timber industry. Among wood properties, the dimensional stability is regarded as a major technological characteristic to validate whether a wood species is adapted to commercial uses. Cell structure and organization are known to influence the drying shrinkage making wood density and microfibrils angle markers of choice to predict wood dimensional stability. On the contrary the role of wood extractive content remains unclear. This work focuses on the fast-growing tropical species Bagassa guianensis and we report herein a correlation between heartwood drying shrinkage and extractive content. Chemical extractions and shrinkage experiments were performed on separate wood twin samples to better evaluate correctly how secondary metabolites influence the wood shrinkage behaviour. Extractive content were qualitatively and quantitatively analysed using HPLC and NMR spectroscopy. We found that B guianensis heartwood has a homogeneous low shrinkage along its radius that could not be explained only by its basic density. In fact the low drying shrinkage is correlated to the high extractive content and a corrected model to improve the prediction of wood dimensional stability is presented. Additionally NMR experiments conducted on sapwood and heartwood extracts demonstrate that secondary metabolites biosynthesis occurs in sapwood thus revealing B. guianensis as a Juglans-Type heartwood formation. This work demonstrates that B. guianensis, a fast-growing species associated with high durability and high dimensional stability, is a good candidate for lumber production and commercial purposes.
ISSN: 1932-6203

hal-01392725
https://hal.archives-ouvertes.fr/hal-01392725
https://hal.archives-ouvertes.fr/hal-01392725/document
https://hal.archives-ouvertes.fr/hal-01392725/file/2016_BossuBeaucheneEstevezDuplaisClair_PlosOne_WoodDimentionalStabilityAndSecondaryMetabolites.pdf
DOI : 10.1371/journal.pone.0150777.s005

Éditeur(s) : Springer
Résumé : The great fecundity and very high larval mortality of most marine invertebrates and fish make possible substantial variance in the number of offspring contributed by adults to subsequent generations. The reproductive success of such organisms may thus resemble a sweepstakes lottery, in which a minority of progenitors succeeds in replacing an entire population, while the majority fails to procreate. One specific prediction of this hypothesis, that genetic diversity of newly settled cohorts should be less than that of the adult population, is tested in the present study. Microsatellite DNA markers were examined in naturally spawned juvenile European flat oysters Ostrea edulis (L.), collected over a 12-day period in 1993 from the western Mediterranean Sea, near Sete, France (43 degrees 32'N, 3 degrees 56'E) and grown out for a period of up to 10 months. Variation in these juveniles was compared to that in a pooled sample of adults collected in 1994 from two locations (Thau Lagoon and Port St. Louis) that had statistically homogeneous allelic frequencies. Though nearly twice as large as the pooled adult sample, the juvenile sample had only 60% of the adult allelic diversity. Analyses of linkage disequilibrium and kinship, as well as estimation of the effective number of parents, suggested that 10-20 adults produced this juvenile cohort. This observation supports the hypothesis of sweepstakes reproductive success and suggests that partial inbreeding may occur even in species with large populations and dispersing planktonic larvae.
Marine Biology (0025-3162) (Springer), 2007-03 , Vol. 150 , N. 6 , P. 1173-1182

Droits : 2007 Springer
http://archimer.ifremer.fr/doc/2007/publication-2616.pdf
DOI:10.1007/s00227-006-0441-y
http://archimer.ifremer.fr/doc/00000/2616/

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

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

Éditeur(s) : HAL CCSD
Résumé : International audience
Among infertile couples, approximately half have to face with male infertility. In men with non-obstructive azoospermia, surgical retrieval testicular sperm extraction (TESE) of spermatozoa can be attempted, but with low success rates. A specific biomarker that could predict residual spermatogenesis would obviously be of interest before performing TESE. Thus, our aim was to identify biomarkers of residual spermatogenesis in seminal plasma of patients with non-obstructive azoospermia (NOA) using an isotope-coded protein label (ICPL)-based proteomic strategy coupled with conventional protein assay. This retrospective study was conducted in 40 men with NOA at the University Hospital of Nantes and Proteomics Core facility Biogenouest - Inserm U1085 - IRSET, Rennes, France. Comparative ICPL proteomic screening of frozen seminal plasma and correlation with TESE outcome allowed the identification of some differentially expressed proteins. Among them, lectin galactoside-binding, soluble 3 binding protein (LGALS3BP) expression was further confirmed using conventional protein assay, and its interest as a predictor of TESE outcome was then evaluated and compared with conventional clinical and hormonal markers of residual spermatogenesis. Among the 12 differentially expressed proteins identified with comparative ICPL proteomic strategy, seminal LGALS3BP expression was found to be significantly higher in men with successful TESE. Finally, comparative ICPL proteomic screening of seminal plasma appears to be a promising approach for the identification of biomarkers of residual spermatogenesis. LGALS3BP, associated with clinical and hormonal markers, could potentially be used as a predictive marker of successful TESE outcome in patients with NOA.
Andrology

inserm-00818514
http://www.hal.inserm.fr/inserm-00818514
DOI : 10.1111/j.2047-2927.2012.00059.x
PUBMED : 23427166

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: To better select for patients who most likely will benefit from cardiac surgery among those with infective endocarditis (IE), we aimed to identify preoperative markers associated with poor outcome after cardiac surgery for IE, and to evaluate the accuracy of European System for Cardiac Operative Risk Evaluation (EuroSCORE) II to predict mortality. METHODS: We enrolled all adult patients who underwent cardiac surgery during the acute phase of definite IE (Duke Criteria) in two referral centres for cardiac surgery. Patients were identified through intensive care unit (ICU) electronic databases, and data were collected from medical charts on standardized questionnaire. RESULTS: Between 2002 and 2013, 149 patients (117 males), with a median age of 64 years [interquartile range 52-73], fulfilled the inclusion criteria. Main complications before surgery were left ventricular dysfunction (23%), central nervous system symptomatic events (34%) and septic shock (24%). Most patients (95%) presented with valve regurgitation, and 49% had perivalvular abscess. Surgery was performed with a median delay of 12 days [5-24] after IE diagnosis, and mean EuroSCORE II was 15.8 (13.4-18.1). In-hospital mortality was 21%. Preoperative variables associated with mortality in multivariate analysis were obesity [odds ratio (OR) 3.67 [1.10-12.19], P = 0.03], vegetation extgreater15 mm (OR 6.72 [1.46-30.98], P = 0.01), septic shock (OR 4.87 [1.67-14.28], P = 0.004) and mechanical prosthetic valve IE (OR 4.99 [1.72-28.57], P = 0.007). EuroSCORE II underestimated mortality in patients with predicted mortality over 10%. CONCLUSION: Factors independently predictive of mortality after cardiac surgery for IE are obesity, septic shock, large vegetation and a mechanical prosthetic valve IE. EuroSCORE II underestimates post-cardiac surgery mortality in patients with IE
ISSN: 1010-7940

hal-01169802
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169802
DOI : 10.1093/ejcts/ezv223
PUBMED : 26116921

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.
ISSN: 2045-2322

hal-01518808
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808/file/Hardonni%C3%A8re%20et%20al%202017.pdf
DOI : 10.1038/s41598-017-00269-7

Éditeur(s) : HAL CCSD
Résumé : National audience
Endometriosis is a common gynecological estrogen-dependent disorder, affecting more than 10 % of women in reproductive age. This disease results in chronic pelvic pain and infertility and is characterized by the presence of functional endometrial tissue outside of uterine cavity. To date, the diagnosis of endometriosis takes many years because of the lack of non-invasive diagnostic tools. Interestingly, "Omics" technologies demonstrated their relevance for the search, identification and characterization of potential disease biomarkers with significant achievements in many areas in the field of human health. Use a panel of Omics approaches seems to be a good way to improve our knowledge about endometriosis. Despite several studies on the subject, the potential biomarkers obtained are still not used in the clinical practice, as it calls for large-scale validation. Combined approaches based on strong interdisciplinary collaborations should improve our knowledge of endometriosis, and allow the identification of specific predictive markers, thus leading to the development of therapeutic solutions for a non-invasive and early diagnosis of this debilitating disease. Copyright © 2017 John Libbey Eurotext.
Medecine Therapeutique Medecine de la Reproduction, Gynecologie et Endocrinologie

hal-01467551
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467551
DOI : 10.1684/mte.2016.0632

Éditeur(s) : HAL CCSD
Résumé : Today, one of the main challenges in the oil industry is the exploitation of new resources in naturally fractured reservoirs often located in structurally complex areas such as plate boundaries, mountain ranges or near salt structures. While numerical models of rock deformation based on continuum mechanics are becoming industry standard in providing efficient means for modelling natural fractures in reservoirs, the knowledge of past perturbed stress fields, which is referred as the type (normal, wrench or reverse), orientation and magnitude of the regional or local tectonic stresses that needs to be applied as boundary condition in numerical simulations, is often unknown or approximated.The essence of this thesis is to improve the recovery of the paleostress field needed to constrain numerical simulations. I first described and discuss through a comprehensive mechanically-based multi-parametric study how far we can rely on the commonly used paleostress inversion methods based on fault slip data and the Wallace and Bott assumptions. I then compared this method with a new generation technique based on geomechanics using field observations. Since slip markers on faults are hardly observed in core or image log, I used observed natural fracture data as main drivers for the inversion of the paleostress using geomechanically-based method. I demonstrated, through various outcrop and subsurface examples, how this can efficiently be done. Finally, I aimed at addressing the problem of polyphase fracture data sets with unknown mechanical type (joints, faults, stylolites ...) and expanded the mechanical stress inversion to the separation of tectonic phases.
Aujourd'hui, l'un des principaux défis dans l'industrie pétrolière est l'exploitation de nouvelles ressources dans les réservoirs naturellement fracturés souvent situés dans des zones structurellement complexes tels que les frontières de plaques, les chaînes de montagnes ou les structures de proches des dômes de sel. Alors que les modèles numériques de déformation des roches basée sur la mécanique des milieux continus fournissant des moyens efficaces pour la modélisation de fractures naturelles dans les réservoirs, sont devenus la norme dans l'industrie, les paléo-contraintes régionales ou locales appliquées comme condition aux limites dans les simulations numériques, définies par le régime (normal, décrochant ou inverse), l'orientation, et la magnitude des contraintes tectoniques, sont souvent inconnues ou approximées.L'essence de cette thèse est d'améliorer la prédiction du champ de paléo-contrainte nécessaire pour contraindre les simulations numériques. J’ai décrit dans un premier temps à travers une étude comparative multi-paramétrique complète basée sur la mécanique, dans quelle mesure nous pouvions compter sur les méthodes d'inversion des paléo-contraintes basées sur les hypothèses de Wallace et Bott et les données de glissement sur les failles. J’ai ensuite comparé ces méthodes avec une technique d’inversion de nouvelle génération basée sur la géomécanique en utilisant les observations de terrain. Puisque les marqueurs de glissement sur les failles sont rarement observés le long du forage, j’ai utilisé l’inversion géomécanique des contraintes pour les données de fractures naturelles observées. J’ai alors démontré, l’efficacité de cette technique à travers divers exemples d'affleurements et de subsurface. Enfin, j’ai proposé une solution afin de résoudre le problème des données de fractures polyphasées à type cinématique inconnu (joints, failles, stylolites ...) et étendu l’inversion de contrainte basée sur la géomécanique à la séparation des phases tectoniques.
https://hal.archives-ouvertes.fr/tel-01324110

tel-01324110
https://hal.archives-ouvertes.fr/tel-01324110
https://hal.archives-ouvertes.fr/tel-01324110/document
https://hal.archives-ouvertes.fr/tel-01324110/file/theselejri.pdf

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVE: To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009. DESIGN: Prospective study of 1046 patients at 47 French clinical sites. METHODS: Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure. RESULTS: Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when ≥50 years), overweight (hazard ratio = 1.91 for a BMI 25-29 kg/m(2), hazard ratio = 2.85 >30 kg/m(2)), waist-to-hip ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes. CONCLUSIONS: In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients.
ISSN: 0269-9370

hal-00875222
https://hal.archives-ouvertes.fr/hal-00875222
DOI : 10.1097/QAD.0b013e32834e8776
PUBMED : 22089377

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Microbial genetic diversity is often investigated via the comparison of relatively similar 16S molecules through multiple alignments between reference sequences and novel environmental samples using phylogenetic trees, direct BLAST matches, or phylotypes counts. However, are we missing novel lineages in the microbial dark universe by relying on standard phylogenetic and BLAST methods? If so, how can we probe that universe using alternative approaches? We performed a novel type of multi-marker analysis of genetic diversity exploiting the topology of inclusive sequence similarity networks. Results: Our protocol identified 86 ancient gene families, well distributed and rarely transferred across the 3 domains of life, and retrieved their environmental homologs among 10 million predicted ORFs from human gut samples and other metagenomic projects. Numerous highly divergent environmental homologs were observed in gut samples, although the most divergent genes were over-represented in non-gut environments. In our networks, most divergent environmental genes grouped exclusively with uncultured relatives, in maximal cliques. Sequences within these groups were under strong purifying selection and presented a range of genetic variation comparable to that of a prokaryotic domain. Conclusions: Many genes families included environmental homologs that were highly divergent from cultured homologs: in 79 gene families (including 18 ribosomal proteins), Bacteria and Archaea were less divergent than some groups of environmental sequences were to any cultured or viral homologs. Moreover, some groups of environmental homologs branched very deeply in phylogenetic trees of life, when they were not too divergent to be aligned. These results underline how limited our understanding of the most diverse elements of the microbial world remains, and encourage a deeper exploration of natural communities and their genetic resources, hinting at the possibility that still unknown yet major divisions of life have yet to be discovered.
ISSN: 1745-6150

Droits : http://creativecommons.org/licenses/by/
hal-01257771
http://hal.upmc.fr/hal-01257771
http://hal.upmc.fr/hal-01257771/document
http://hal.upmc.fr/hal-01257771/file/s13062-015-0092-3.pdf
DOI : 10.1186/s13062-015-0092-3

Éditeur(s) : HAL CCSD BioMed Central
Résumé : [b]Background[/b][br/] [br/] The Amazonian rainforest is predicted to suffer from ongoing environmental changes. Despite the need to evaluate the impact of such changes on tree genetic diversity, we almost entirely lack genomic resources.[br/] [br/] [b]Results[/b][br/] [br/] In this study, we analysed the transcriptome of four tropical tree species (Carapa guianensis, Eperua falcata, Symphonia globulifera and Virola michelii) with contrasting ecological features, belonging to four widespread botanical families (respectively Meliaceae, Fabaceae, Clusiaceae and Myristicaceae). We sequenced cDNA libraries from three organs (leaves, stems, and roots) using 454 pyrosequencing. We have developed an R and bioperl-based bioinformatic procedure for de novo assembly, gene functional annotation and marker discovery. Mismatch identification takes into account single-base quality values as well as the likelihood of false variants as a function of contig depth and number of sequenced chromosomes. Between 17103 (for Symphonia globulifera) and 23390 (for Eperua falcata) contigs were assembled. Organs varied in the numbers of unigenes they apparently express, with higher number in roots. Patterns of gene expression were similar across species, with metabolism of aromatic compounds standing out as an overrepresented gene function. Transcripts corresponding to several gene functions were found to be over- or underrepresented in each organ. We identified between 4434 (for Symphonia globulifera) and 9076 (for Virola surinamensis) well-supported mismatches. The resulting overall mismatch density was comprised between 0.89 (S. globulifera) and 1.05 (V. surinamensis) mismatches/100 bp in variation-containing contigs.[br/] [br/] [b]Conclusion[/b][br/] [br/] The relative representation of gene functions in the four transcriptomes suggests that secondary metabolism may be particularly important in tropical trees. The differential representation of transcripts among tissues suggests differential gene expression, which opens the way to functional studies in these non-model, ecologically important species. We found substantial amounts of mismatches in the four species. These newly identified putative variants are a first step towards acquiring much needed genomic resources for tropical tree species.
ISSN: 1471-2164

hal-01032439
https://hal.archives-ouvertes.fr/hal-01032439
https://hal.archives-ouvertes.fr/hal-01032439/document
https://hal.archives-ouvertes.fr/hal-01032439/file/art_10-1186_1471-2164-15-238.pdf
DOI : 10.1186/1471-2164-15-238

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Properly assessing the extent and magnitude of fault ruptures associated with large earthquakes is critical for understanding fault behavior and associated hazard. Submarine faults can trigger tsunamis, whose characteristics are defined by the geometry of seafloor displacement, studied primarily through indirect observations (e.g., seismic event parameters, seismic profiles, shipboard bathymetry, coring) rather than direct ones. Using deep-sea vehicles, we identify for the first time a marker of coseismic slip on a submarine fault plane along the Roseau Fault (Lesser Antilles), and measure its vertical displacement of ∼0.9 m in situ. We also map recent fissuring and faulting of sediments on the hangingwall, along ∼3 km of rupture in close proximity to the fault's base, and document the reactivation of erosion and sedimentation within and downslope of the scarp. These deformation structures were caused by the 2004 M w 6.3 Les Saintes earthquake, which triggered a subsequent tsunami. Their characterization informs estimates of earthquake recurrence on this fault and provides new constraints on the geometry of fault rupture, which is both shorter and displays locally larger coseismic displacements than available model predictions that lack field constraints. This methodology of detailed field observations coupled with near-bottom geophysical surveying can be readily applied to numerous submarine fault systems, and should prove useful in evaluating seismic and tsunamigenic hazard in all geodynamic contexts.
ISSN: 0012-821X

insu-01557932
https://hal-insu.archives-ouvertes.fr/insu-01557932
https://hal-insu.archives-ouvertes.fr/insu-01557932/document
https://hal-insu.archives-ouvertes.fr/insu-01557932/file/EPSL-2006-escartin.pdf
DOI : 10.1016/j.epsl.2016.06.024

Éditeur(s) : HAL CCSD
Résumé : International audience
Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (ATL). Such complications are seen frequently in L.guyanensis infections where patients respond variously to first-line anti-leishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently ,: we reported that a dsRNA virus (LRV1) nested within L.guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyper-inflammatory response. This report investigates the prevalence of LRV1 in human L.guyanensis infection and its effect on treatment efficacy as well as its correlation to symptomatic relapses after the first-line treatment. In our cohort of 75 patients diagnosed with primary-localised ATL, the prevalence of LRV1+ infection was elevated to 58%. All patients infected with LRV1-negative L.guyanensis were cured after one (22/31 i.e.71%) or two (31/31 i.e.100%) doses of pentamidine. Oppositely, 12 out of the 44 LRV1-positive patients presented with persistent infection and symptomatic relapse required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in intra-lesional inflammatory markers. In conclusion, LRV1 status in L.guyanensis infection is significantly predictive (p=0.0009) of first-line treatment failure and symptomatic relapse, and could stand to guide therapeutic choices in ATL
Journal of Infectious Diseases

hal-01175528
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01175528
DOI : 10.1093/infdis/jiv355
PUBMED : 26123564

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The objective of the study was to evaluate the distribution of methotrexate (MTX) in cerebrospinal fluid (CSF) lateral ventricles and in cisterna magna after 3rd intraventricular CSF administration in a rabbit model.MTX or gadolinium chelate (Gd-DOTA) was administered in the 3rd ventricle with a local microdialysis to study the pharmacokinetics at the site of administration and with a simultaneous magnetic resonance imaging (MRI) acquisition in the 3rd ventricle, the lateral ventricles and in the cisterna magna. A specific CSF Physiologically Based Pharmacokinetic (PBPK) model was then extrapolated for MTX from Gd-DOTA data.The relative contribution of elimination and distribution processes to the overall disposition of MTX and Gd-DOTA in the 3rd ventricle was similar (i.e., around 60% for CLE and 40% for CLI) suggesting that Gd-DOTA was a suitable surrogate marker for MTX disposition in ventricular CSF. The PBPK predictions for MTX both in CSF of the 3rd ventricle and in plasma were in accordance with the in vivo results.The present study showed that the combination of local CSF microdialysis with MRI acquisition of the brain ventricles and a PBPK model could be a useful methodology to estimate the drug diffusion within CSF ventricles after direct brain CSF administration. Such a methodology would be of interest to clinicians for a rationale determination and optimization of drug dosing parameters in the treatment of leptomeningeal metastases.
ISSN: 0939-6411

hal-01335562
https://hal.archives-ouvertes.fr/hal-01335562
https://hal.archives-ouvertes.fr/hal-01335562/document
https://hal.archives-ouvertes.fr/hal-01335562/file/PBPK%20model%20of%20methotrexate%20in%20cerebrospinal%20fluid.pdf
DOI : 10.1016/j.ejpb.2016.04.012

Éditeur(s) : HAL CCSD
Résumé : International audience
The Chromosome-Centric Human Proteome Project (C-HPP) aims to identify "missing" proteins in the neXtProt knowledgebase. We present an in-depth proteomics analysis of the human sperm proteome to identify testis-enriched missing proteins. Using protein extraction procedures and LC-MS/MS analysis, we detected 235 proteins (PE2-PE4) for which no previous evidence of protein expression was annotated. Through LC-MS/MS and LC-PRM analysis, data mining, and immunohistochemistry, we confirmed the expression of 206 missing proteins (PE2-PE4) in line with current HPP guidelines (version 2.0). Parallel reaction monitoring acquisition and sythetic heavy labeled peptides targeted 36 ≪one-hit wonder≫ candidates selected based on prior peptide spectrum match assessment. 24 were validated with additional predicted and specifically targeted peptides. Evidence was found for 16 more missing proteins using immunohistochemistry on human testis sections. The expression pattern for some of these proteins was specific to the testis, and they could possibly be valuable markers with fertility assessment applications. Strong evidence was also found of four "uncertain" proteins (PE5); their status should be re-examined. We show how using a range of sample preparation techniques combined with MS-based analysis, expert knowledge, and complementary antibody-based techniques can produce data of interest to the community. All MS/MS data are available via ProteomeXchange under identifier PXD003947. In addition to contributing to the C-HPP, we hope these data will stimulate continued exploration of the sperm proteome. © 2016 American Chemical Society.
Journal of Proteome Research

hal-01406074
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01406074
DOI : 10.1021/acs.jproteome.6b00400
PUBMED : 27444420