Éditeur(s) : HAL CCSD
Résumé : International audience
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis. © 2017 Federation of European Biochemical Societies
ISSN: 1742464X

hal-01616420
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616420
DOI : 10.1111/febs.14176
PUBMED : 28715128

Éditeur(s) : HAL CCSD Society for the Study of Reproduction
Résumé : International audience
Matrix-assisted laser desorption/ionization (MALDI) tissue imaging mass spectrometry is particularly promising among the numerous applications of mass spectrometry. It is used for probing and analyzing the spatial arrangement of a wide range of molecules, including proteins, peptides, lipids, drugs, and metabolites, directly in thin slices of tissue. In the field of proteomics, the technology avoids tedious and time-consuming extraction and fractionation steps classically required for sample analysis. MALDI imaging mass spectrometry is increasingly recognized as a powerful method for clinical proteomics, particularly in cancer research. The technology has particular potential for the discovery of new tissue biomarker candidates, classification of tumors, early diagnosis or prognosis, elucidating pathogenesis pathways, and therapy monitoring. Over recent years, MALDI imaging mass spectrometry has been used for molecular profiling and imaging directly in male and female reproductive tissues. This review will consider some of the recent publications in the field, addressing a range of issues covering embryo development, gene expression product profiling during gametogenesis, and seeking and identifying biomarkers of reproductive cancers. The wealth of advances in mass spectrometry imaging will inevitably attract biologists and clinicians as the advantages and power of this technology become more widely known. This review will also discuss bottlenecks and the many technical issues that remain to be resolved before laboratories in the field can adopt the technology. We foresee that MALDI imaging mass spectrometry will have a major impact in reproductive research by opening new avenues to the understanding of various molecular mechanisms and the diagnosis of reproductive pathologies.
ISSN: 0006-3363

hal-00877851
https://hal.archives-ouvertes.fr/hal-00877851
DOI : 10.1095/biolreprod.111.094896
PUBMED : 22156474

Éditeur(s) : HAL CCSD IRD
Résumé : International audience
The number of satellites and remote sensing sensors devoted to earth observation becomes increasingly high, providing more and more data and especially images. In the same time the access to such a data and to the tools to process them has been considerably improved. In the presence of such data flow - and regarding the necessity to follow up and predict environmental and societal changes in highly dynamic socio-environmental contexts - we need automatic image interpretation methods. This could be accomplished by exploring some strengths of artificial intelligence. Our main idea consists in inducing classification rules that explicitly take into account structural knowledge, using Aleph, an Inductive Logic Programming (ILP) system. We applied our proposed methodology to three land cover/use maps of the French Guiana littoral. One hundred and forty six classification rules were induced for the 39 land-cover classes of the maps. These rules are expressed in first order logic language which make them intelligible and interpretable by non-experts. A ten-fold cross validation gave average values for classification accuracy, specificity and sensibility equal to, respectively, 98.82 %, 99.65% and 70%. The proposed methodology could be valuably exploited to automatically classify new objects and/or help operators using object-based classification procedures.
Symposium of the Latin American Society for Remote Sensing and Spatial Information Systems (SELPER)
Cayenne, French Guiana

ird-00797337
http://hal.ird.fr/ird-00797337
http://hal.ird.fr/ird-00797337/document
http://hal.ird.fr/ird-00797337/file/Bayoudh_et_al_2012_FP_SELPER-086.pdf
IRD : fdi:010058343

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : In French Guiana, the population growth will result in an increase in demand for agricultural products and thus, will lead to an increase in the amount of tropical forests converted into cropland or pasture. Impacts of different agricultural systems on greenhouse gas (GHG) fluxes have not been studied in French Guiana. In this context, the fire-free chop-and-mulch method was used to convert a tropical forest site to agriculture. This study focused on soil nitrous oxide (N2O) emissions and we compared four land uses: (1) the undisturbed tropical forest, (2) recently converted grassland and recently converted croplands (fertilized soybean/maize rotation) with either (3) disk tillage or (4) no tillage.N2O measurements were obtained through the chamber technique and conducted over a 1-year period (measurements began 19 months after the forest was cleared). N2O fluxes were related to soil parameters measured at each sampling date: nitrate and ammonium contents, gravimetric water content (GWC) and temperature.Through the entire period, the mean (±standard error) and median N2O fluxes were 3.8 ± 0.5 and 2.7 g N ha−1 day−1, respectively for undisturbed tropical forest and 2.4 ± 0.9 and 0.8 g N ha−1 day−1, respectively for grassland (mowed Brachiaria ruziziensis). For croplands, no significant difference was found for N2O emissions between both agricultural practices. The mean (±standard error) and median N2O fluxes were 8.5 ± 1.2 and 4.0 g N ha−1 day−1, respectively for disk tillage plots and 8.5 ± 1.3 and 3.6 g N ha−1 day−1, respectively for no tillage plots. Nitrogen inputs (due to the application of fertilizer or due to the mineralization of crop residues) led to higher N2O fluxes, resulting in significantly higher mean N2O emissions from croplands compared to the forest, when only considering land use effect on N2O fluxes in a statistical model. The soil nitrate content, GWC and temperature had a significant positive effect on N2O fluxes. Taking into account these soil parameters in another statistical model, N2O emissions from croplands were not higher than the natural N2O emissions from tropical forest soils. Our results suggest that, if more forest will have to be converted in the course of the expected population growth in French Guiana, it could have low impact on the soil N2O fluxes (similar to natural fluxes from forest) with the improving of farming techniques (for example modification of the splitting of N-fertilizer) in the cropping plots.
ISSN: 0167-8809

hal-01204228
https://hal.archives-ouvertes.fr/hal-01204228
DOI : 10.1016/j.agee.2015.04.004
PRODINRA : 307607

Éditeur(s) : HAL CCSD Wiley-VCH Verlag
Résumé : International audience
Proteomic profiling plays a decisive role in the elucidation of molecular signatures representative of a specific clinical context. MuStem cell-based therapy represents a promising approach for clinical applications to cure Duchenne Muscular Dystrophy (DMD). To expand our previous studies collected in the clinically relevant DMD animal model, we decided to investigate the skeletal muscle proteome four months after systemic delivery of allogenic MuStem cells. Quantitative proteomics with isotope-coded protein labelling (ICPL) was used to compile quantitative changes in the protein expression profiles of muscle in transplanted Golden Retriever Muscular Dystrophy (GRMD) dogs as compared to GRMD dogs. A total of 492 proteins were quantified, including 25 that were overrepresented and 46 that were underrepresented after MuStem cell transplantation. Interestingly, this study demonstrates that somatic stem cell therapy impacts on the structural integrity of the muscle fascicle by acting on fibres and its connections with the extracellular matrix. We also show that cell infusion promotes protective mechanisms against oxidative stress and favours the initial phase of muscle repair. This study allows us to identify putative candidates for tissue markers that might be of great value in objectively exploring the clinical benefits resulting from our cell-based therapy for DMD.
ISSN: 1615-9853

Droits : info:eu-repo/semantics/OpenAccess
hal-01332030
https://hal.archives-ouvertes.fr/hal-01332030
https://hal.archives-ouvertes.fr/hal-01332030/document
https://hal.archives-ouvertes.fr/hal-01332030/file/Quantitative%20proteome%20profiling%20of%20dystrophic%20dog%20skeletal%20muscle_accepted.pdf
DOI : 10.1002/pmic.201600002

Éditeur(s) : HAL CCSD INVS
Résumé : National audience
Context – Cervical cancer is the second most frequent cancer of women in French Guiana. Studies have shown that populations living in remote villages in the interior of the territory have early sexual relations and that multiple sexual partnerships are frequent. Hence, the main objective of the study was to determine the prevalence of Human Papilloma Virus (HPV) in these areas.Methods – This multicentric cross sectional study was conducted in women aged 20 to 65 years, living in theremote villages along the Maroni and Oyapock rivers. Women were included on a voluntary basis after beinginformed of the study team schedule through radio address and key opinion leaders.The search for HPV and cytologic examinations were performed on each sample. HPV infection was defined bythe detection of viral DNA using the Greiner Bio One® kit. Cytologic analyses were performed using the 2001Bethesda classification.Results – Overall, 643 women were included in the study. Age-standardized HPV prevalence was 35%. Theprevalence curve by age group showed a U-shaped pattern: women over 50 years had the highest risk of being infected by HPV, followed by women aged 20-29 years. In addition, 26.1% of women with a normal smear test had HPV infection. The most frequent genotypes were HPV52, HPV58, and HPV16. On interpretable smears 1.16% of women had high grade superficial intra-epithelial (HSIL) lesions.Conclusions – The standardized prevalence of HPV in French Guiana is among the highest in the world. HSILcytological lesions were nearly 4 times more frequent than in the Île-de-France region. Given the importance of the incidence of cervical cancer in French Guiana, these results suggest it may be preferable to use HPV testing than cytology. Vaccination against HPV, preferably with the new nonavalent vaccine seems an appropriate prevention measure. However, this intervention will be a challenge to implement in this region where a significant proportion of the population is not covered by health insurance.
Contexte – Le cancer du col de l’utérus est le deuxième cancer féminin le plus fréquent en Guyane française.Des études ont montré que les populations résidant dans les communes isolées de l’intérieur du départementdébutent leur vie sexuelle de façon précoce et que le multipartenariat sexuel y est fréquent. Dans ce contexte, l’objectif principal de cette étude était de déterminer la prévalence de l’infection à papillomavirus humains (HPV) dans ces zones.Méthodes – Cette étude transversale multicentrique a été conduite auprès des femmes âgées de 20 à 65 ansrésidant dans les communes isolées des fleuves Maroni et Oyapock. Les femmes étaient incluses sur la basedu volontariat après avoir été informées du passage de l’équipe de l’étude via la radio locale et par les leadersd’opinion. La recherche d’infection à HPV et les analyses cytologiques ont été réalisées sur chaque prélèvement. L’infection à HPV était définie par la détection d’ADN viral par le kit de dépistage Greiner Bio One®. Les analyses cytologiques ont été décrites selon la classification de Bethesda 2001.Résultats – Au total, 643 femmes ont été incluses. La prévalence de l’infection à HPV, standardisée sur l’âge,était de 35%. La courbe de prévalence par classe d’âge présentait une forme en U : les femmes de plus de50 ans avaient le plus haut risque d’être infectées par HPV, suivies par les femmes âgées de 20 à 29 ans.Par ailleurs, 26,1% des femmes ayant un frottis normal étaient infectées par le HPV. Les génotypes les plusfréquents étaient HPV52, HPV58 et HPV16. Sur les frottis interprétables, 1,16% des femmes avaient des lésions de haut grade (type HSIL).Conclusions – Le taux standardisé de prévalence de l’infection par le HPV en Guyane est parmi les plus élevésau monde. Les lésions cytologiques de type HSIL étaient près de 4 fois plus fréquentes qu’en Île-de-France.Étant donné l’importance de l’incidence du cancer du col de l’utérus en Guyane, ces résultats montrent qu’il est peut être préférable d’utiliser le test HPV plutôt que la cytologie. La vaccination anti-HPV, de préférence avec le nouveau vaccin nonavalent, semble être une mesure de prévention appropriée. Pour autant, cela reste un challenge de mettre en oeuvre ces interventions dans cette région où une part importante de la population n’a pas d’assurance maladie.
ISSN: 1953-8030

Droits : info:eu-repo/semantics/OpenAccess
inserm-01407222
http://www.hal.inserm.fr/inserm-01407222
http://www.hal.inserm.fr/inserm-01407222/document
http://www.hal.inserm.fr/inserm-01407222/file/2016%2C%20Dufit%20et%20al.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Risk assessment related to the exposure of humans to chemicals released into the environment is a major concern of our modern societies. In this context, toxicology plays a crucial role to characterize the effects of this exposure on health and identify the targets of these molecules. MALDI imaging mass spectrometry (IMS) is an enabling technology for biodistribution studies of chemicals. Although the majority of published studies are presented in a pharmacological context, the concepts discussed in this review can be applied to the toxicological evaluation of chemicals released into the environment. The major asset of IMS is the simultaneous localization and identification of a parent molecule and its metabolites without labeling and without any prior knowledge. Quantification methods developed in IMS are presented with application to an environmental pollutant. IMS is effective in the localization of chemicals and endogenous species. This opens unique perspectives for the discovery of molecular alterations in metabolites and protein biomarkers that could help for a better understanding of toxicity mechanisms. Distribution studies of agrochemicals in plants by IMS can contribute to a better understanding of their mode of action and to a more effective use of these chemicals, avoiding the current concern of environmental damage.
ISSN: 1874-3919

hal-01367141
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141/file/Potential%20of%20MALDI%20imaging.pdf
DOI : 10.1016/j.jprot.2016.05.008