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) : Actes de Colloque: Avancées et nouvellles technologies en toxinologie, éditeurs: Julien BARBIER, Evelyne BENOIT, Pascale MARCHOT, César MATTEI, Denis SERVENT
Résumé : Over the past seven years, methods available for the detection of phycotoxins have been extensively reviewed in a number of international expert committees, such as the consultations organised by FAO/IOC/WHO and EFSA, as well as by individual scientists. These reviews have shown that the methods available have severe limitations for the use in official control, either due to their limited scope and detection capability or due to a lack of calibration standards, reference materials and validation efforts. The present review focuses on recent developments in the detection of phycotoxins in several areas of applied research. Not being able to exhaustively describe all recent developments, the review focussed on three areas of interest to the authors: (i) detection of ultra-trace amounts of toxins, (ii) metabolism of toxins and their localisation in biological tissues, and (iii) approaches to detect unknown toxins or analogues of known toxins. Miniaturisation in combination with physico-chemical techniques appears to be a very efficient approach to detect low trace amounts of individual toxin analogues. In particular, the detection of azaspiracids and okadaic acid and analogues, using micro-filtration and on-line pre-concentration techniques, has shown to be useful for the characterisation of various algal and shellfish species. In the area of interactions of toxins with shellfish and mammalian systems, it is noted that several studies on biomarkers reveal either protein biomarkers of exposure to toxins or potential pathways of metabolism of the toxins themselves. A particular focus is given to recent findings in the areas of brevetoxin metabolism and biomarkers as well as azaspiracid localisation and metabolism. Finally, the detection of novel compounds is a particularly challenging area. The interest in this area has risen over the past years following cases of unexplained mouse toxicity such as the UK cockle toxicity and the French atypical toxicity in mussels and oysters from the Atlantic and Mediterranean coasts. Some attention is given to immuno-, functional and cellular bio-assays for the identification of bioactive agents in shellfish.
Durant les sept dernières années, les méthodes disponibles pour la détection des phycotoxines ont été abondamment revues dans de nombreux groupes internationaux d’expertises, tels que les consultations organisées par FAO/IOC/WHO et EFSA ainsi que dans de nombreux articles scientifiques de synthèse. Ces revues ont démontré que, vis-à-vis des systèmes de régulations officiels, les méthodes disponibles présentent des limites d’utilisation importantes. Soit elles ont un périmètre réduit et des limites de détection trop élevées, soit il y a un manque d’étalons, de matériaux de référence ou d’efforts de validation. La présente revue focalise sur les développements récents dans la détection de phycotoxines en recherche appliquée. Sans vouloir décrire de manière exhaustive tous les développements récents, la revue examine trois domaines d’intérêt pour les auteurs : (i) la détection de quantités ultra-traces de toxines, (ii) la métabolisation et la localisation des toxines dans des tissus biologiques, et (iii) les approches pour la détection de toxines non-répertoriées ou des analogues de toxines connues. La miniaturisation en combinaison avec les techniques physico-chimiques constitue apparemment une approche efficace pour la détection de faibles traces d’analogues individuels des toxines. En particulier, la micro-filtration et des techniques de pré-concentration en ligne se sont montrées utiles pour la détection des azaspiracides et des toxines du groupe de l’acide okadaïque dans la caractérisation de diverses espèces d’algues et de coquillages. Dans le domaine des interactions des toxines avec les coquillages et des systèmes vivants de mammifères, nous avons noté que plusieurs études sur les bio-marqueurs révèlent soit des marqueurs protéiniques d’exposition aux toxines, soit des marqueurs du métabolisme des toxines elles-mêmes. Un intérêt spécifique a été trouvé dans les résultats d’étude sur le métabolisme des brévétoxines et des azaspiracides. La détection des composés bioactifs non-répertoriés constitue un défi particulièrement difficile. Ce domaine a trouvé plus d’intérêt dû à plusieurs cas de toxicités inexpliquées dans le test souris telles que les toxicités observées dans les coques en provenance de Grande-Bretagne ou encore dans les moules et huîtres des côtes méditerranéennes et atlantiques françaises. Une attention particulière a été consacrée à l’identification d’agents bioactifs par les essais cellulaires ou fonctionnels ou basés sur la détection immuno-chimique.

Droits : 2010 SFET
http://archimer.ifremer.fr/doc/00019/12975/9949.pdf
http://archimer.ifremer.fr/doc/00019/12975/

Éditeur(s) : Springer
Résumé : Because of their characteristic living environments, marine organisms produce a variety of lipids. Fatty acids constitute the essential part of triglycerides and wax esters, which are the major components of fats and oils. Nevertheless, phospholipids and glycolipids have considerable importance and will be taken into account, especially the latter compounds that excite increasing interest regarding their promising biological activities. Thus, in addition to the major polyunsaturated fatty acids (PUFA) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, a great number of various fatty acids occur in marine organisms, e.g. saturated, mono- and diunsaturated, branched, halogenated, hydroxylated, methoxylated, non-methylene-interrupted. Various unprecedented chemical structures of fatty acids, and lipid-containing fatty acids, have recently been discovered, especially from the most primitive animals such as sponges and gorgonians. This review of marine lipidology deals with recent advances in the field of fatty acids since the end of the 1990s. Different approaches will be followed, mainly developing biomarkers of trophic chains in marine ecosystems and of chemotaxonomic interest, reporting new structures, especially those with biological activities or biosynthetic interest. An important part of this review will be devoted to the major PUFA, their relevance to health and nutrition, their biosynthesis, their sources (usual and promising) and market.
Marine Biotechnology I (0724-6145) (Springer), 2005 , Vol. 96 , P. 49-125

Droits : 2005 Springer-Verlag
http://archimer.ifremer.fr/doc/2005/publication-937.pdf
DOI:10.1007/b135782
http://archimer.ifremer.fr/doc/00000/937/

Éditeur(s) : HAL CCSD
Résumé : International audience
Leishmania parasites induce an immunomodulation by subverting the host immune response towards a CD4(+) Th2 lymphocytic cell response that favors parasite persistence. Here, we report that after successful treatment of visceral leishmaniasis due to Leishmania infantum, an immune reconstitution syndrome revealing hip septic arthritis was associated with a switch from Th2 towards a Th1 cytokine profile, and a decrease in the level of immunomodulating factors, such as soluble HLA-G and indoleamine 2,3-dioxygenase (IDO) activity. We then measured IDO activity in a cohort of 39 patients and uninfected control subjects. Results showed significantly enhanced IDO activity in patients with visceral Leishmania infection, compared with uninfected control subjects (P < 0.001), but also compared with treated patients (P < 0.05). A decrease in IDO activity could constitute a relevant biomarker for the restoration of the immune response during visceral leishmaniasis.
Innate Immunity

inserm-00818884
http://www.hal.inserm.fr/inserm-00818884
DOI : 10.1177/1753425912473170
PUBMED : 23413147

Éditeur(s) : Elsevier
Résumé : Regardless of the degree of closure of a recirculation system, effluents are produced and replacement water is needed, which limits the possibility of locating a seawater production system away from the shoreline. At the Palavas Ifremer station, in the south of France, a High Rate Algal Pond (HRAP) was operated during several years to treat the effluent from a recirculating aquaculture system before reusing it. The effect of the HRAP-treated water on the recirculation system and on the fish was investigated and the optimal algae growing conditions were defined. The experiments were carried out in three rearing systems: one flow through, one recirculating and one recirculating with a HRAP. The water flow rate, temperature, pH and salinity conditions were similar in all systems. The effect of reusing the HRAP-treated water is very limited (1) on the functioning of the recirculation system and (2) on fish performance, but it allows a significant reduction of the dissolved inorganic nitrogen and phosphorus concentration in the rearing water. HRAP treatment reduced metal accumulation in muscle and liver of RAS fish, except for chromium and arsenic. All biomarkers presented no significant difference between systems, except for Superoxide Dismutase (SOD) and EROD, which showed a higher concentration in RAS and in both recirculating system respectively. (c) 2005 Elsevier B.V. All rights reserved.
Aquaculture (0044-8486) (Elsevier), 2006-03 , Vol. 252 , N. 1 , P. 92-101

Droits : 2005 Elsevier
http://archimer.ifremer.fr/doc/2006/publication-2306.pdf
DOI:10.1016/j.aquaculture.2005.11.053
http://archimer.ifremer.fr/doc/00000/2306/

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: Cancer/Testis (CT) genes are expressed in male gonads, repressed in most healthy somatic tissues and de-repressed in various somatic malignancies including prostate cancers (PCa). Because of their specific expression signature and their associations with tumor aggressiveness and poor outcomes, CT genes are considered to be useful biomarkers and they are also targets for the development of new anti-cancer immunotherapies. The aim of this study was to identify novel CT genes associated with hormone-sensitive prostate cancer (HSPC), and castration-resistant prostate cancer (CRPC). METHODS: To identify novel CT genes we screened genes for which transcripts were detected by RNA profiling specifically in normal testis and in either HSPC or CRPC as compared to normal prostate and 44 other healthy tissues using GeneChips. The expression and clinicopathological significance of a promising candidate-NR6A1-was examined in HSPC, CRPC, and metastatic site samples using tissue microarrays. RESULTS: We report the identification of 98 genes detected in CRPC, HSPC and testicular samples but not in the normal controls. Among them, cellular levels of NR6A1 were found to be higher in HSPC compared to normal prostate and further increased in metastatic lesions and CRPC. Furthermore, increased NR6A1 immunoreactivity was significantly associated with a high Gleason score, advanced pT stage and cancer cell proliferation. CONCLUSIONS: Our results show that cellular levels of NR6A1 are correlated with disease progression in PCa. We suggest that this essential orphan nuclear receptor is a potential therapeutic target as well as a biomarker of PCa aggressiveness. Prostate © 2013 Wiley Periodicals, Inc.
ISSN: 0270-4137

inserm-00821963
http://www.hal.inserm.fr/inserm-00821963
DOI : 10.1002/pros.22659
PUBMED : 23532770

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Estrogen receptors (ER) α and β are found in both women and men in many tissues, where they have different functions, including having roles in cell proliferation and differentiation of the reproductive tract. In addition to estradiol (E2), a natural hormone, numerous compounds are able to bind ERs and modulate their activities. Among these compounds, phytoestrogens such as isoflavones, which are found in plants, are promising therapeutics for several pathologies. Glyceollins are second metabolites of isoflavones that are mainly produced in soybean in response to an elicitor. They have potentially therapeutic actions in breast cancer by reducing the proliferation of cancer cells. However, the molecular mechanisms driving these effects remain elusive. METHODS: First, to determine the proliferative or anti-proliferative effects of glyceollins, in vivo and in vitro approaches were used. The length of epithelial duct in mammary gland as well as uterotrophy after treatment by E2 and glyceollins and their effect on proliferation of different breast cell line were assessed. Secondly, the ability of glyceollin to activate ER was assessed by luciferase assay. Finally, to unravel molecular mechanisms involved by glyceollins, transcriptomic analysis was performed on MCF-7 breast cancer cells. RESULTS: In this study, we show that synthetic versions of glyceollin I and II exert anti-proliferative effects in vivo in mouse mammary glands and in vitro in different ER-positive and ER-negative breast cell lines. Using transcriptomic analysis, we produce for the first time an integrated view of gene regulation in response to glyceollins and reveal that these phytochemicals act through at least two major pathways. One pathway involving FOXM1 and ERα is directly linked to proliferation. The other involves the HIF family and reveals that stress is a potential factor in the anti-proliferative effects of glyceollins due to its role in increasing the expression of REDD1, an mTORC1 inhibitor. CONCLUSION: Overall, our study clearly shows that glyceollins exert anti-proliferative effects by reducing the expression of genes encoding cell cycle and mitosis-associated factors and biomarkers overexpressed in cancers and by increasing the expression of growth arrest-related genes. These results reinforce the therapeutic potential of glyceollins for breast cancer.
ISSN: 1478-811X

hal-01560288
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560288
DOI : 10.1186/s12964-017-0182-1
PUBMED : 28666461

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
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
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 National Institute of Environmental Health Sciences
Résumé : International audience
Safe drinking water is essential for well-being. Although microbiological contamination remains the largest cause of water-related morbidity and mortality globally, chemicals in water supplies may also cause disease, and evidence of the human health consequences is limited or lacking for many of them. We aimed to summarize the state of knowledge, identify gaps in understanding, and provide recommendations for epidemiological research relating to chemicals occurring in drinking water. Assessing exposure and the health consequences of chemicals in drinking water is challenging. Exposures are typically at low concentrations, measurements in water are frequently insufficient, chemicals are present in mixtures, exposure periods are usually long, multiple exposure routes may be involved, and valid biomarkers reflecting the relevant exposure period are scarce. In addition, the magnitude of the relative risks tends to be small. Research should include well-designed epidemiological studies covering regions with contrasting contaminant levels and sufficient sample size; comprehensive evaluation of contaminant occurrence in combination with bioassays integrating the effect of complex mixtures; sufficient numbers of measurements in water to evaluate geographical and temporal variability; detailed information on personal habits resulting in exposure (e.g., ingestion, showering, swimming, diet); collection of biological samples to measure relevant biomarkers; and advanced statistical models to estimate exposure and relative risks, considering methods to address measurement error. Last, the incorporation of molecular markers of early biological effects and genetic susceptibility is essential to understand the mechanisms of action. There is a particular knowledge gap and need to evaluate human exposure and the risks of a wide range of emerging contaminants.
ISSN: 0091-6765

hal-01118530
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118530
PUBMED : 24380896
DOI : 10.1289/ehp.1206229
PUBMEDCENTRAL : PMC3948022

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial EIA (Bordier Affinity Products) with those of the Bio-Rad and VirionSerion EIAs. This assay is novel in the association of two recombinant antigens with somatic and metabolic antigens of A. fumigatus. In a prospective multicentre study, 436 serum samples from 147 patients diagnosed with CPA (136 sera/104 patients) or ABPA (94 sera/43 patients) and from 205 controls (206 sera) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad and VirionSerion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (p < 0.01), which was itself more sensitive than the VirionSerion kit (p=0.04). The Bordier and Bio-Rad kits had similar specificities (p=0.8), both higher than that of the VirionSerion kit (p=0.02). The areas under the ROC curves confirmed the superiority of the Bordier kit over the Bio-Rad and the VirionSerion kits (0.977, 0.951 and 0.897, respectively; p < 0.01 for each comparison). In a subset analysis of 279 sera tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; p=0.10).The use of recombinant, somatic and metabolic antigens in a single EIA improved the balance between sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.
ISSN: 0095-1137

hal-01282328
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328/file/Prospective%20evaluation%20of%20a%20new%20Aspergillus.pdf
DOI : 10.1128/JCM.03261-15

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Several studies suggest that exposure to organophosphate insecticides (OP) during pregnancy impairs neurodevelopment in children. OBJECTIVES: We evaluated associations between biomarkers of prenatal and postnatal OP exposure and cognitive function of 6-year-olds in a French longitudinal birth cohort. METHODS: In 2002-2006, the PELAGIE mother-child cohort enrolled pregnant women from Brittany. For a random subcohort, we measured nonspecific dialkylphosphate metabolites (DAP) of OP in one maternal urine sample, collected before 19 weeks' gestation, and in one urine sample collected from their 6-year-old children. Six subtests of the Wechsler Intelligence Scale for Children-4th edition (WISC-IV) was administered at 6 years to evaluate cognitive function (n=231). Linear regression models controlling for factors including maternal intelligence and the Home Observation for Measurement of the Environment score were used. RESULTS: WISC-IV scores were not significantly associated with prenatal or childhood total DAP metabolites. WISC verbal comprehension score was significantly higher in association with the highest maternal urinary concentrations of diethylphosphate metabolites (DE) (5.5; 95% CI: 0.8, 10.3 for extgreater 13.2 nmol/L versus extlessLOQ), while WISC working memory score was significantly lower in association with the highest urinary concentrations of DE metabolites at age 6 years (-3.6; 95% CI: -7.8, -0.6 for extgreater 11.1 nmol/L versus extlessLOD). CONCLUSION: This study found no evidence that prenatal OP exposure adversely affected cognitive function in 6-year-olds, perhaps because of the higher population's socioeconomic status than in previous studies though other causal and non-causal explanations are also possible. The negative association between WISC score and concurrent DE urinary concentrations requires replication by longitudinal studies investigating childhood OP exposure
Environmental Health Perspectives

hal-01207282
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207282
DOI : 10.1289/ehp.1409472
PUBMED : 26394442

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Pyrethroids are insecticides frequently used in agriculture and in the home; exposure occurs through dietary and non-dietary pathways, including indoor and outdoor environmental contamination. Our objective was to study the potential determinants of pyrethroid metabolite concentrations measured in children's urine samples and in the dust of their homes. Specifically, we measured urinary metabolites from morning spot samples of 245 six-year- old children living in Brittany (France) in 2009-2012 and from dust vacuumed from the floor of their homes. Mothers reported home insecticide use, dietary habits, sociodemographic data; residential and school proximity to agricultural crops was assessed with spatialized data. The metabolites cis-DBCA, trans-DCCA, cisDCCA, 3-PBA, and F-PBA were detected in 84, 95, 64, 63, and 16% of the urine samples, respectively. Permethrin, cypermethrin, cyfluthrin, deltamethrin, and tetramethrin pyrethroids were detected in 100, 56, 9, 15, and 26% of the dust samples, respectively. Multiple regression analysis suggested diet plays a role in children's exposure, in particular, the food groups "pasta, rice or semolina" (for cis-DCCA and F-PBA), fruit (3-PBA), "breakfast cereals and whole grain bread" (cis-DBCA), and the global proportion of organic food in diet (for cis-DBCA, trans-DCCA). Children with a parent occupationally exposed to pesticides were about 3-times more likely to have higher urinary concentrations of 3-PBA (OR = 2.8, 95% CI [1.2; 6.5]). Dust content was correlated mainly with household insecticide use: higher mean concentrations of permethrin (beta = 0.8 [0.3; 1.3], in mu g/g) and an increased risk of a detectable level of cyfluthrin (OR = 4.7 [1.7; 12.9]) were observed in home dust, for indoor use of at least twice a year. Outdoor insecticide use at least once a year was associated with detection in dust of cypermethrin (OR = 3.0 [1.3; 6.7]) and tetramethrin (OR = 3.7 [1.6; 8.3]). Three positive and one negative correlations (out of 11) between urinary metabolite concentrations and home dust contents of their possible corresponding parent compounds were observed. The strength of this study lies in its concurrent use of biomarkers, environmental measurements, and potential sources of exposure. Its limitations include the use of a single urine sample and imprecise data about pyrethroid use in local agriculture.
ISSN: 0160-4120

hal-01560147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560147
DOI : 10.1016/j.envint.2017.04.007
PUBMED : 28453973

Éditeur(s) : Gauthier-Villars
Résumé : Preparative pyrolysis followed by liquid chromatographic separation and gas chromatography of hydrocarbons (Pyrolysis-LC-GC) were used to study the participation of terrestrial and/or aquatic compounds in the formation of humic substances in sediments. Analyses performed on humic substances from recent sediments sampled in the Elorn river estuary (France) show that these substances are similar in many respects to other lacustrine or marine humic substances, with regard, for instance, to their high nitrogen and sulphur content and their low aromaticity. Mass balances on pyrolysis products and group composition of the C-14+ fraction of the pyrolysates were performed. The distribution of the total alkane and alkene fraction, isocyclo alkanes and alkenes from these humic acid pyrolysates was compared to that of various reference humic acid pyrolysates. The biomarker study (distribution and hopanes/steranes ratios from humic acid pyrolysates) confirms the participation throughout the estuary of algal precursors in the formation of the studied compounds, irrespective of the location of the sampling zone (upstream, median or downstream part of the estuary).
Oceanologica Acta (0399-1784) (Gauthier-Villars), 1994 , Vol. 17 , N. 1 , P. 43-53

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00099/21029/18655.pdf
http://archimer.ifremer.fr/doc/00099/21029/

Éditeur(s) : Elsevier
Résumé : The aim of this study was to distinguish between sources of the complex variety of Marennes-Oléron Bay suspended particulate organic matter (SPOM) contributing to the tropho-dynamics of the Marennes-Oléron oyster farming bay. Basic biomarkers (Chl a, C/N and POC/Chl a ratios), carbon and nitrogen stable isotopes from SPOM were analyzed and the microalgae community was characterized. The sampling strategy was bimonthly from March 2002 to December 2003; samples were taken from an intertidal mudflat. Four main sources contributed to the SPOM pool: terrigenous input from rivers, neritic phytoplankton, resuspended microphytobenthos and periodic inputs from intertidal Zostera noltii meadows. Seasonal fluctuations were observed in both years of the study period: (1) SPOM collected in the spring of 2002 (δ13C = −250/00 to −230/00) was mainly composed of fresh estuarine inputs; (2) SPOM from the summer and fall of 2002 and 2003 was predominantly neritic phytoplankton (δ13C = − 220/00 to −190/00); (3) SPOM from the winter of 2002, spring of 2003 and winter of 2003 (δ13C = −21 to −230/00) was composed of a mixture of decayed terrigenous river inputs and pelagic phytoplankton, which was predominantly resuspended microphytobenthos. In the summer of 2003—the warmest summer on record in southern France and Europe—SPOM was particularly enriched for 13C, with δ13C values ranging from −140/00 to −120/00. Pulses in δ13C values, indicative of 13C-enriched decaying materials, extended into the fall. These were attributed to benthic intertidal inputs, including both resuspended microphytobenthos and Z. noltii detritus. Changes in SPOM sources in Marennes-Oléron Bay may lead to differences in the quality of the trophic environment available for reared oysters.
Estuarine, Coastal and Shelf Science (0272-7714) (Elsevier), 2008-07 , Vol. 78 , N. 3 , P. 576-586

Droits : 2008 Elsevier Ltd All rights reserved.
http://archimer.ifremer.fr/doc/2008/publication-4313.pdf
DOI:10.1016/j.ecss.2007.11.001
http://archimer.ifremer.fr/doc/00000/4313/

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers Inc.
Résumé : International audience
An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy. The results indicate that high-field (4.7T) MRI parameters (T2-weighted; T2-quantitative) allow to detect the gradual neuro-anatomical changes that occur during epileptogenesis while electrophysiological parameters (number and duration of Hippocampal Paroxysmal Discharges) allow to assess the dysfunctional changes through the quantification of epileptiform activity. We found a strong correlation between EEG-based markers (invasive recording) and MRI-based parameters (non-invasive) periodically computed over the 'latent period' that spans over two weeks, on average. These results indicated that both structural and functional changes occur in the considered epilepsy model and are considered as biomarkers of the installation of epilepsy. Additionally, such structural and functional changes can also be observed in human temporal lobe epilepsy. Interestingly, MRI imaging parameters could be used to track early (day-7) structural changes (gliosis, cell loss) in the lesioned brain and to quantify the evolution of epileptogenesis after traumatic brain injury. © 2016 IEEE.
38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2016
Unknown, Unknown or Invalid Region

hal-01467552
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467552
DOI : 10.1109/EMBC.2016.7591605

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The potential interest of antifungal treatment of non-immunocompromized patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown. It represents three-quarters of antifungals prescribed in Intensive Care Units. It may allow early treatment of invasive fungal infection in the incubation phase but expose patients to unnecessary antifungal treatments with subsequent cost and fungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered to be insufficient, the potential interest in this strategy needs to be demonstrated. METHODS: This prospective multicenter, double blind, randomized-controlled trial is conducted in 23 French Intensive Care Units. All adult patients, mechanically ventilated for more than four days with sepsis of unknown origin and with at least one extradigestive fungal colonization site and multiple organ failure are eligible for randomization. Patients with proven invasive candidiasis are not included. After a complete mycological screening, patients are allocated to receive micafungin 100 mg intravenously once a day or placebo for 14 days. We plan to enroll 260 patients. The main objective is to demonstrate that micafungin increases survival of patients without invasive candidiasis at day 28 as compared to placebo. Other outcomes include day 28 and 90 survival and organ failure evolution. Additionally, pharmacokinetics of micafungin in enrolled patients will be measured and evolution of fungal biomarkers and susceptibility profiles of infecting fungi will also be followed. DISCUSSION: This study will help to provide guidelines for treating non-immunocompromized patients with fungal colonization multiple organ failure and sepsis of unknown origin.Trial registration: Clinicaltrials.gov number NCT01773876.
ISSN: 1745-6215

inserm-00913515
http://www.hal.inserm.fr/inserm-00913515
http://www.hal.inserm.fr/inserm-00913515/document
http://www.hal.inserm.fr/inserm-00913515/file/1745-6215-14-399.pdf
PUBMED : 24261608

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
Childhood absence epilepsy is a prototypic form of generalized nonconvulsive epilepsy characterized by short impairments of consciousness concomitant with synchronous and bilateral spike-and-wave discharges in the electroencephalogram. For scientists in this field, the BS/Orl and BR/Orl mouse lines, derived from a genetic selection, constitute an original mouse model "in mirror" of absence epilepsy. The potential of MALDI imaging mass spectrometry (IMS) for the discovery of potential biomarkers is increasingly recognized. Interestingly, statistical analysis tools specifically adapted to IMS data sets and methods for the identification of detected proteins play an essential role. In this study, a new cross-classification comparative design using a combined discrete wavelet transformation-support vector machine classification was developed to discriminate spectra of brain sections of BS/Orl and BR/Orl mice. Nineteen m/z ratios were thus highlighted as potential markers with very high recognition rates (87-99%). Seven of these potential markers were identified using a top-down approach, in particular a fragment of Synapsin-I. This protein is yet suspected to be involved in epilepsy. Immunohistochemistry and Western Blot experiments confirmed the differential expression of Synapsin-I observed by IMS, thus tending to validate our approach. Functional assays are being performed to confirm the involvement of Synapsin-I in the mechanisms underlying childhood absence epilepsy.
ISSN: 1535-3893

hal-00877728
https://hal.archives-ouvertes.fr/hal-00877728
DOI : 10.1021/pr3006974
PUBMED : 22994238

Éditeur(s) : HAL CCSD
Résumé : The trophic endosymbiosis interaction between a cnidarian host and its photosynthetic dinoflagellatessymbionts form the basis of coral reef ecosystems. Cnidarians host their symbionts in gastrodermis cells, in a phagocytosis-derived vacuole. Establishment and maintenance of the symbiotic interaction depend on an intimate molecular communication between the two partners. However, environmental and/or anthropogenic disturbances can lead to the breakdown of the symbiotic association, which is responsible for the worldwide decline of coral reefs. The main objectives of my research project are to improve the knowledge regarding symbiosis maintenance and disruption mechanisms, but also to define the molecular key players involved at the symbiotic interface in the sea anemone, Anemonia viridis. First, we have described the cellular mechanisms involved in the different types of symbiosis breackdown. Meanwhile, the characterization of npc1 and npc2 genes (involved in endosomal sterol transport), showed a duplication and a sub-functionalization of the npc2d gene. Both NPC1 and NPC2 proteins are expressed around symbionts. We therefore suggest that the duplicated protein NPC2-d is a biomarker of symbiosis health and that NPC1 protein is a marker of the perisymbiotic membrane. We then developed a protocol to characterize the proteome of the symbiotic interface between the two symbiotic partners. The newly-identified symbiotic key players will increase the general knowledge on the symbiotic interaction and its regulation during both stable and bleaching conditions.
L’endosymbiose trophique établie entre un hôte Cnidaire et ses symbiotes Dinoflagellés photosynthétiques est à l’origine du succès évolutif des écosystèmes coralliens. Les symbiotes sont internalisés par un mécanisme de phagocytose et maintenus dans les cellules du gastroderme de l'hôte. La symbiose est régie par un dialogue moléculaire intime entre les deux partenaires, interrompu lors de perturbations environnementales ou anthropiques, responsables du déclin mondial des récifs coralliens. Les objectifs de mon projet de recherche sont de définir les acteurs moléculaires localisés à l’interface symbiotique chez l’anémone de mer, Anemonia viridis. Premièrement, nous avons étudié les mécanismes cellulaires impliqués dans différents types de rupture de la symbiose et mis en évidence des phénomènes d’apoptose, nécrose et symbiophagie. Parallèlement, nous avons caractérisé chez l’anémone les gènes npc1 et npc2, impliqués chez les vertébrés dans le transport endosomal de stérols, et dont l’expression est modulée par l’état symbiotique. Nous avons pu montrer que le gène npc2d est issus d’une duplication et vraisemblablement d’une sub-fonctionnalisation et que les protéines NPC1 et NPC2 sont exprimées au voisinage des symbiotes. Nous proposons donc que la protéine NPC2-d soit utilisée comme marqueur de l’état de santé des Anthozoaires symbiotiques et que la protéine NPC1 soit un marqueur de la membrane périsymbiotique. Nous avons également développé un protocole afin d’identifier les protéines associées à l’interface symbiotique entre les deux partenaires. A terme, les cibles identifiées permettront une meilleure compréhension des mécanismes qui régulent la relation symbiotique.
https://tel.archives-ouvertes.fr/tel-01673491

NNT : 2015NICE4105
tel-01673491
https://tel.archives-ouvertes.fr/tel-01673491
https://tel.archives-ouvertes.fr/tel-01673491/document
https://tel.archives-ouvertes.fr/tel-01673491/file/2015NICE4105.pdf