Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background : Trichoderma reesei is the main industrial source of cellulases and hemicellulases required for the hydrolysis of biomass to simple sugars, which can then be used in the production of biofuels and biorefineries. The highly productive strains in use today were generated by classical mutagenesis. As byproducts of this procedure, mutants were generated that turned out to be unable to produce cellulases. In order to identify the mutations responsible for this inability, we sequenced the genome of one of these strains, QM9136, and compared it to that of its progenitor T. reesei QM6a.Results : In QM9136, we detected a surprisingly low number of mutagenic events in the promoter and coding regions of genes, i.e. only eight indels and six single nucleotide variants. One of these indels led to a frame-shift in the Zn2Cys6 transcription factor XYR1, the general regulator of cellulase and xylanase expression, and resulted in its C-terminal truncation by 140 amino acids. Retransformation of strain QM9136 with the wild-type xyr1 allele fully recovered the ability to produce cellulases, and is thus the reason for the cellulase-negative phenotype. Introduction of an engineered xyr1 allele containing the truncating point mutation into the moderate producer T. reesei QM9414 rendered this strain also cellulase-negative. The correspondingly truncated XYR1 protein was still able to enter the nucleus, but failed to be expressed over the basal constitutive level.Conclusion : The missing 140 C-terminal amino acids of XYR1 are therefore responsible for its previously observed auto-regulation which is essential for cellulases to be expressed. Our data present a working example of the use of genome sequencing leading to a functional explanation of the QM9136 cellulase-negative phenotype.
ISSN: 1471-2164

Droits : http://creativecommons.org/licenses/by/
hal-01149671
http://hal.upmc.fr/hal-01149671
http://hal.upmc.fr/hal-01149671/document
http://hal.upmc.fr/hal-01149671/file/Lichius_2015_Genome_sequencing.pdf
DOI : 10.1186/s12864-015-1526-0

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. METHODOLOGY/PRINCIPAL FINDINGS: A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. CONCLUSIONS/SIGNIFICANCE: Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.
ISSN: 1932-6203

inserm-00871491
http://www.hal.inserm.fr/inserm-00871491
http://www.hal.inserm.fr/inserm-00871491/document
http://www.hal.inserm.fr/inserm-00871491/file/Milk_Fermented_by_Propionibacterium_freudenreichii.accepted.pdf
DOI : 10.1371/journal.pone.0031892

Éditeur(s) : HAL CCSD
Résumé : Scope: TNF-Related Apoptosis-Inducing Ligand (TRAIL) induces apoptosis via the extrinsic death pathway in human colon cancer cells. Short Chain Fatty Acids (SCFA) by contrast induce apoptosis of cancer cells via the intrinsic death pathway. We have previously shown that food-grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via SCFA metabolites (propionate and acetate) acting on mitochondria. We investigate here the possible synergistic pro-apoptotic effect between Propionibacterium freudenreichii and TRAIL. Methods and results: Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial SCFA, in combination with TRAIL, increased pro-apoptotic gene expression (TRAIL-R2/DR5) and decreased anti-apoptotic gene expression (FLIPL, XIAP) in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on both death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and caspases (caspase-8, -9 and -3) activation, was lethal on cancer cells but not on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented by P. freudenreichii induced HT29 cells apoptosis and enhanced TRAIL cytotoxic activity, as did P. freudenreichii culture supernatants or its SCFA metabolites.Conclusion: The revealed synergy opens new applications for food-grade P. freudenreichii-containing products as new adjuvants to potentiate TRAIL-based cancer therapy in colorectal cancer.
International Scientific Conference on Probiotics and Prebiotics - IPC2016
Budapest, Hungary

hal-01286497
https://hal.archives-ouvertes.fr/hal-01286497
PRODINRA : 349367

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: The RH blood group system has many RHCE variant alleles that have arisen through gene conversion or nucleotide changes. Two probands, with red blood cells (RBCs) that were D+C+E-c+(w) e+ were sent to our laboratories to resolve the weak c expression. STUDY DESIGN AND METHODS: Hemagglutination tests were performed by automated and manual procedures. Genomic DNA analysis was performed by sequencing of Exons 1 to 10 of RHCE and RHD. RESULTS: The probands' RBCs did not react with standard monoclonal anti-E reagents from Bio-Rad, Diagast, DiaMed, Immucor, Ortho, and Quotient. The RBCs reacted variably with anti-c reagents from Diagast, DiaMed, Immucor, or Ortho and did not react with the Quotient anti-c reagent. Surprisingly, sequencing results of RHCE showed the presence of C/G at Position 676 (E/e polymorphism) and the association of the E polymorphism with a 734T>C transition in Exon 5 of the RHCE, encoding a Leu245Pro amino acid substitution in the mature RhcE polypeptide. Replacement of leucine 245 by proline in the eighth transmembrane domain of the RhcE protein may have a steric effect on the protein such that most anti-E reagents do not bind and the interaction between anti-c and c antigen is also affected. CONCLUSION: We report a novel RHCE*cE allele, RHCE*cE734C, which was assigned the provisional ISBT allele name RHCE*cE.14 or RHCE*03.14. It was found in two probands whose RBCs had weakened c expression and typed E- with conventional anti-E reagents. These data, once again, highlight the fact that the genotype does not always reflect the phenotype.
ISSN: 0041-1132

hal-00839022
https://hal.archives-ouvertes.fr/hal-00839022
DOI : 10.1111/j.1537-2995.2012.03860.x
PUBMED : 22958092

Éditeur(s) : HAL CCSD
Résumé : International audience
The presence of photosynthetic zooxanthellae (dinoflagellates) in the tissue of many cnidarians is the main reason for their ecological success (i.e. coral reefs). It could also be the main cause of their demise, as the worldwide bleaching of reef-building coral is nothing less than the breakdown of this symbiotic association. The stability of this relationship is the principal marker for the biomonitoring of cnidarian health. We have therefore developed a new, simple method to isolate zooxanthellae in a few steps using NaOH solution. The protocol was validated in three symbiotic cnidarian species: a sea anemone, a gorgonian and a coral. Our method allows the isolation of intact and viable zooxanthellae with better yields than classic methods, especially for species with a calcareous skeleton. Moreover, the isolated zooxanthellae were free of host nucleic contaminants, facilitating subsequent specific molecular analyses.
Journal of Experimental Biology

hal-01546180
https://hal.archives-ouvertes.fr/hal-01546180
DOI : 10.1242/jeb.074955

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.
ISSN: 0022-2593

inserm-00529272
http://www.hal.inserm.fr/inserm-00529272
DOI : 10.1136/jmg.2008.062612
PUBMED : 19357115

Éditeur(s) : HAL CCSD American Geophysical Union (AGU)
Résumé : International audience
Located east of Guadeloupe, the island of La Désirade exhibits the oldest rocks of the Lesser Antilles arc and the eastern Caribbean plate. An old magmatic basement is composed of (1) late Jurassic ophiolitic complex with meta-basaltic pillow lavas and interbedded radiolarites, (2) acid igneous complex comprising meta-quartz-diorite and meta-rhyolitic lavas flows, and (3) meta-diabasic/microdioritic dyke swarm complex. We present and discuss the discovery of synmetamorphic thrust tectonics in this island. Based on detailed structural analysis we evidenced two main compressive events. The first event (D1) is characterized by pervasive folding associated with thrust development. In the northeastern part of the island, a major thrust fault, the Grand Abaque Thrust, has been discovered which displaces for several kilometers the acid igneous complex onto the ophiolitic unit. The second deformation event (D2) is featured by a main pervasive cleavage S2 observed at the regional scale associated with upright folding (F2) and by the development of two sets of conjugated steeply dipping strike-slip shear zones, dextral 130°N and sinistral 20°N striking, respectively. Microstructural observations indicate that Greenschist facies metamorphism is clearly contemporaneous with the development of D1 and D2 superimposed tectonic structures. Ar/Ar geochronology was performed on two bulk of adularia minerals sampled in the northeast volcanic complex within a deformed zone related to a D2 event. These analyses yield well-defined and concordant plateau ages at 106.2 ± 1.7 Ma and 107.2 ± 1.8 Ma. Thus, shortening and thickening tectonics occurred during Lower Cretaceous (Albian). In the available framework of Caribbean geodynamics, the synmetamorphic thrust tectonics we discovered in the French Lesser Antilles is related to the collision between an Aptian-Albian oceanic plateau and the Andean-Cordilleran east-dipping subduction zone. Our results support subduction polarity reversal during Lower Cretaceous.
ISSN: 0278-7407

hal-00620555
https://hal.archives-ouvertes.fr/hal-00620555
DOI : 10.1029/2011TC002875

Éditeur(s) : Elsevier
Résumé : The distribution, partition and speciation of mercury (Hg) were studied along the redox gradient of an anthropogenically perturbed tropical estuary, the Sinnamary Estuary in French Guiana. This system is a partially mixed estuary characterized by an anoxic freshwater end-member, while the marine end member consists of the Amazon Plume. The set up of an artificial oxygenation system in the anoxic freshwater end-member generates sharp gradients of major chemical species (iron, sulfides, etc.) coupled with intense organic matter (OM) turnover. The coexistence of oxygenated waters and dissolved sulfides in an organic rich environment depicts the Upper Sinnamary Estuary (USE: part of Sinnamary Estuary under the tidal influence but upstream of the salt intrusion) as a potential site for Hg methylation. The concentrations of all mercurial species (HgT) in the unfiltered samples (HgTUNF), in the dissolved (HgTD) and particulate (HgTP) phases of the USE average 11 ± 3, 6 ± 2 and 5 ± 3 (i.e. 600 ± 200 pmol g-1) pmol L-1 respectively. Average concentrations of monomethylmercury (MMHg) in the unfiltered (MMHgUNF), dissolved (MMHgD) and particulate (MMHgP) phases were 3.7 ± 1.0, 2.0 ± 0.9 and 1.8 ± 1.2 (i.e. 220 ± 130 pmol g-1) pmol L-1 respectively. Water oxygenation and sulfides concentrations emerged to play a critical role in controlling MMHg levels. Additionally, iron cycling, acid-base mechanisms, and edoxdependent processes were involved in the MMHg partitioning between phases. Overall, the USE constitutes a biogeochemical reactor that gathers partitioning and methylation processes. Thepermanent MMHg inputs from the anoxic freshwater end-member combined with the intense endogenous Hg methylation ensures high MMHg levels in both dissolved and particulate phases. To illustrate, the USE exports 60 ± 20 % more MMHgUNF than it imports: 5.5 ± 0.7 vs. 3.5 ± 1.2 kg y-1.
Geochimica et Cosmochimica Acta (0016-7037) (Elsevier), 2008-07 , Vol. 72 , N. 22 , P. 5416-5430

Droits : 2008 Elsevier Ltd. All rights reserved
http://archimer.ifremer.fr/doc/2008/publication-4223.pdf
DOI:10.1016/j.gca.2008.08.021
http://archimer.ifremer.fr/doc/00000/4223/

Éditeur(s) : HAL CCSD Springer Verlag (Germany)
Résumé : International audience
A hybrid linear ion-trap Fourier-transform ion cyclotron resonance mass spectrometer was used for top-down characterization of the abundant human salivary Cystatins, including S, S1, S2, SA, SN, C, and D, using collisionally activated dissociation (CAD) after chromatographic purification of the native, disulfide intact proteins from saliva. Post-translational modifications and protein sequence polymorphisms arising from single nucleotide polymorphisms (SNPs) were assigned from precursor and product ion masses at a tolerance of 10 ppm allowing confident identification of individual intact mass tags. Cystatins S, S1, S2, SA and SN were cleaved of a N-terminal 20 amino-acid signal peptide, and Cystatin C a 26-residue peptide, to yield a generally conserved N-terminus. In contrast, Cystatin D isoforms with 24 and 28 amino-acid residue N-terminal truncations were found such that their N-termini were not conserved. Cystatin S1 was phosphorylated at Ser3, while S2 was phosphorylated at Ser1 and Ser3 of the mature protein, in agreement with previous work. Both Cystatin D isoforms carried the polymorphism C46R (SNP: rs1799841). The 14328 Da isoform of Cystatin SN previously assigned with polymorphism P31L due to a SNP (rs2070856) was found only in whole saliva. Parotid secretions contained no detectable Cystatins while whole saliva largely mirrored the contents of submandibular/sublingual (SMSL) secretions. Top-down high-resolution mass spectrometry is a powerful tool for the identification and characterization of potential protein biomarkers in saliva.
ISSN: 1044-0305

hal-00677483
https://hal.archives-ouvertes.fr/hal-00677483
DOI : 10.1016/j.jasms.2010.01.025

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
Although protists are critical components of marine ecosystems, they are still poorly characterized. Here we analysed the taxonomic diversity of planktonic and benthic protist communities collected in six distant European coastal sites. Environmental deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from three size fractions (pico-, nano- and micro/mesoplankton), as well as from dissolved DNA and surface sediments were used as templates for tag pyrosequencing of the V4 region of the 18S ribosomal DNA. Beta-diversity analyses split the protist community structure into three main clusters: picoplankton-nanoplankton-dissolved DNA, micro/mesoplankton and sediments. Within each cluster, protist communities from the same site and time clustered together, while communities from the same site but different seasons were unrelated. Both DNA and RNA-based surveys provided similar relative abundances for most class-level taxonomic groups. Yet, particular groups were overrepresented in one of the two templates, such as marine alveolates (MALV)-I and MALV-II that were much more abundant in DNA surveys. Overall, the groups displaying the highest relative contribution were Dinophyceae, Diatomea, Ciliophora and Acantharia. Also, well represented were Mamiellophyceae, Cryptomonadales, marine alveolates and marine stramenopiles in the picoplankton, and Monadofilosa and basal Fungi in sediments. Our extensive and systematic sequencing of geographically separated sites provides the most comprehensive molecular description of coastal marine protist diversity to date.
ISSN: 1462-2912

hal-01191731
http://hal.upmc.fr/hal-01191731
http://hal.upmc.fr/hal-01191731/document
http://hal.upmc.fr/hal-01191731/file/Massana_2015_Marine_protist.pdf
DOI : 10.1111/1462-2920.12955

Éditeur(s) : HAL CCSD Elsevier
Résumé : Remerciements :- Dr. Jacques Delabie- Andrea Yockey-Dejean- Geoff Brown- Jean-Pierre Andrieu
Background: Most ant venoms consist predominantly of small linear peptides, although some contain disulfide linked peptides as minor components. However, in striking contrast to other ant species, some Anochetus venoms are composed primarily of disulfide-rich peptides. In this study, we investigated the venom of the ant Anochetus emarginatus with the aim of exploring these novel disulfide-rich peptides.Methods: The venom peptidome was initially investigated using a combination of reversed-phase HPLC and mass spectrometry, then the amino acid sequences of the major peptides were determined using a combination of Edman degradation and de novo MS/MS sequencing. We focused on one of these peptides, U-1-PONTX-Ae1a (Ae1a), because of its novel sequence, which we predicted would form a novel 3D fold. Ae1a was chemically synthesized using Fmoc chemistry and its 3D structure was elucidated using NMR spectroscopy. The peptide was then tested for insecticidal activity and its effect on a range of human ion channels.Results: Seven peptides named poneritoxins (PONTXs) were isolated and sequenced. The three-dimensional structure of synthetic Ae1a revealed a novel, compact scaffold in which a C-terminal beta-hairpin is connected to the N-terminal region via two disulfide bonds. Synthetic Ae1a reversibly paralyzed blowflies and inhibited human L-type voltage-gated calcium channels (Ca(v)1).Conclusions: Poneritoxins from Anochetus emarginatus venom are a novel class of toxins that are structurally unique among animal venoms.General significance: This study demonstrates that Anochetus ant venoms are a rich source of novel ion channel modulating peptides, some of which might be useful leads for the development of biopesticides.
ISSN: 0304-4165

hal-01511987
https://hal.archives-ouvertes.fr/hal-01511987
https://hal.archives-ouvertes.fr/hal-01511987/document
https://hal.archives-ouvertes.fr/hal-01511987/file/2016_Touchard_Biochimica_Biophysica_%7B4B3BE6A3-AE83-4C6E-B678-BBFB5CC84AF7%7D.pdf
DOI : 10.1016/j.bbagen.2016.07.027

Résumé : L'espèce Ludwigia leptocarpa (Onagracées) présente dans le paysage antillais est méconnue par la population locale. Pourtant, au Nigéria, ses feuilles sont préconisées pour traiter les rhumatismes, la dysenterie et pour leurs vertus laxative et vermifuge. L'absence de données phytochimiques sur cette plante justifie le choix de notre étude. Un criblage phytochimique réalisé sur les extraits bmts de feuilles, de fruits et de tiges a mis en évidence la présence de terpénoïdes dans les extraits hexane et dichlorométhane et des acides phénoliques et flavonoïdes dans les extraits méthanol et eau. L'évaluation du potentiel biologique des extraits apolaires des feuilles a révélé des activités antibiotique (E. coli et S. aureus) et anti-inflammatoire intéressantes. Les extraits plus polaires présentent des potentiels antioxydant, antibiotique (E. coli et S. aureus), antifongique (c. albicans et C. tropica/is), et antiviral (HSV-l) significatifs. L'étude des fractions volatiles de feuilles, de tiges et des parties aériennes par microextraction en phase solide a conduit à l'identification de 54 composés. Les analyses GC/MS menées sur les extraits apolaires de feuilles et de fruits ont mis en évidence la présence d'acides gras, de triterpènes et de stéroïdes. Le fractionnement et la purification des extraits polaires de feuilles ont mené à l'isolation et l'identification de 8 composés phénoliques parmi lesquels 1 acide polyhydroxylé, 3 acides phénoliques, 2 flavonoïdes et 2 tanins galliques. L'apport de nouvelles données scientifiques sur 1. leptocarpa contribue à la valorisation de cette matière végétale locale et laisse entrevoir des perspectives de recherche et d'application
Ludwigia Leptocarpa species (Onagraceae) is present in Caribean landscape, it remains unknown by French West Indies population. However, in Nigeria the leaves are recommended to treat rheumatism, dysentery and as laxative or deworming. The lack of data phytochemical on this plant justifies our study choice. A phytochemical screening carried out on crude extracts from leaves, fruits and stems highlighted terpenoids presence in hexane and dichloromethane crude extracts and phenolic compounds (phenolic acids and flavonoids) in methanol and water cmde extracts. The biological potentials evaluation of apolar extracts showed interesting antibiotic (E. coli and S. aureus) and inflammatory activities. Polar extracts present antioxidant, antibiotic (E. coli and S. aureus), antifungal (C albicans and C tropicalis), and viral (HSV-l) potential. Volatile fraction study of lcave, stems and aerial parts by Solid Phase MicroExtraction (SPME) 100 to theidentification of 54 compounds. GCIMS analysis conducted on leaves and fruits apolar extracts underlined the presence of fatty acid, triterpenes and steroids. Leaves polar extract fractionnation and purification resulted to isolation and identification of 8 phenolic componuds including 1 polyhydroxylated acid, 3 phenolic acids, 2 flavonoids and 2 gallic tannins. The addition of new scientific data on L. /eptocarpa contributes to the enhancement of this local plant rnaterial and suggests many opportunities for research and application

http://www.theses.fr/2013AGUY0676/document

Éditeur(s) : HAL CCSD
Résumé : Background. Chlorine is the most widely used disinfectant for drinking water treatment. During treatment process, the natural organic matter present in water reacts with chlorine to form disinfection by-products (DBPs), such as trihalomethanes (THMs) and haloacetic acids (HAAs), the most occurring ones. Several identified DBPs were recognized carcinogens or fetotoxic in animals. We conducted two epidemiological studies to assess the health effects of human exposure to DBPs regarding cancer and reproduction. Association between THM exposure and the risk of bladder cancer: a pooled analysis of 3 European case-control studies. The study included 2381 cases and 3086 controls from 3 case-control studies (France, Finland, Spain). Environmental exposure to SPCs was measured by THM concentrations in water distribution systems, retrospectively estimated through the 40-year exposure window. Information about water uses (tap water ingestion, showers and baths, swimming-pool attendance) was available. An increased risk of bladder cancer was observed, in men only, with increasing THM concentrations in water systems and duration of exposure to chlorinated surface water. No association was observed with exposure through tap water ingestion. Exposure through showers, baths and swimming in pools (available in Spanish study only) was associated with an increased risk of bladder cancer. Three North-American case-control studies were joined to the three European ones into a meta-regression. No specific dose-response relationship was identified for European studies. A global dose-response relationship was consequently estimated, including 4351 cases and 7055 controls. Association between DBP exposure and the risk of preterm birth and Intra-Uterine Growth Retardation (IUGR). This study was conducted within the PELAGIE cohort (3400 pregnant women included in early pregnancy, in Brittany, France, between 2002 and 2006). Exposure during pregnancy was measured by 2 indicators: THM concentrations in water distribution systems and a biomarker of HAA ingestion, the level of trichloroacetic acid in maternal urine at inclusion (in a nested case-control study). The regulatory database SISE-Eaux was used to estimate THMs concentrations in the water distribution systems. Water uses during pregnancy (ingested tap water, swimming-pool attendance, showers and bath frequencies and duration) were collected with questionnaires. Our results suggest an association between prenatal exposure to DBPs (THMs and HAAs) and the risk of IUGR. No association was found with the risk of preterm birth.
Contexte. La chloration est le traitement le plus utilisé pour désinfecter l’eau distribuée à la population. Lors du traitement, des sous-produits de chloration (SPCs) se forment par réaction de la matière organique naturelle présente dans l’eau avec le chlore. Les produits les plus présents sont les trihalométhanes (THMs), les acides haloacétiques (HAAs). Des études toxicologiques (animales et in vitro) ont montré la génotoxicité et/ou carcinogénicité et la reprotoxicité de certains SPCs. Nous avons mené deux études évaluant les effets sur la santé humaine de l’exposition aux SPCs, dans le domaine du cancer et de la reproduction. Association entre exposition aux THMs et risque de cancer de la vessie : une analyse poolée de 3 études cas-témoins européennes. Cette analyse a inclus 2381 cas et 3086 témoins issus de 3 études cas-témoins (France, Espagne, Finlande). L’exposition environnementale aux SPCs a été mesurée par la concentration en THMs estimée rétrospectivement dans les réseaux de distribution d’eau au cours des 40 années de la fenêtre d’exposition. Les usages de l’eau connus sont l’ingestion, les douches et les bains, la fréquentation de piscine (étude espagnole seulement). Une relation croissante a été observée entre le niveau environnemental de THMs, la durée d’exposition à une eau de surface chlorée et le risque de cancer de la vessie, chez les hommes uniquement. Aucune association n’a été observée avec l’exposition via l’ingestion d’eau du robinet. L’exposition via les douches, les bains et la piscine est apparue liée au risque de cancer de la vessie. Trois études cas-témoins nord-américaines ont été intégrées dans une méta-régression. Aucune spécificité européenne de la relation dose-réponse n’a été mise en évidence. Une relation dose-réponse globale incluant 4351 cas et 7055 témoins a été estimée. Association entre exposition aux SPCs et risque de prématurité et de retard de croissance intra-utérin (RCIU). Cette étude est issue de la cohorte bretonne Pélagie (3400 femmes enceintes recrutées en début de grossesse entre 2002 et 2006). L’exposition pendant la grossesse a été mesurée à l’aide de 2 indicateurs : la concentration en THMs de l’eau distribuée dans les réseaux et le dosage d’un biomarqueur urinaire (acide trichloroacétique) pour un sous-échantillon de femmes (étude cas-témoins nichée). Les niveaux dans les réseaux proviennent de la base de données réglementaire SISE-Eaux. Les usages de l’eau du robinet par les femmes pendant la grossesse ont été collectés par questionnaire (quantité d’eau du robinet bue, fréquentation de la piscine, fréquence et durée des douches et des bains). Notre étude suggère une association entre l’exposition prénatale aux SPCs et le risque de RCIU. Aucune association n’est observée avec le risque de prématurité.
https://tel.archives-ouvertes.fr/tel-00927735

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B008
tel-00927735
https://tel.archives-ouvertes.fr/tel-00927735
https://tel.archives-ouvertes.fr/tel-00927735/document
https://tel.archives-ouvertes.fr/tel-00927735/file/COSTET_DEIBER_Nathalie4.pdf

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury. The zebrafish larva model was demonstrated to be fully relevant as membrane remodeling was maintained even after a 1-week exposure without any adaptation as usually reported in rodents and hepatocyte cultures. It was also proven to exhibit a high sensitivity as it discriminated various levels of cytotoxicity depending on the extent of changes in membrane remodeling. In this context, its sensitivity appeared higher than that of WIF-B9 hepatic cells, which is suited for analyzing this kind of hepatotoxicity. Finally, the protection afforded by a membrane stabilizer, ursodeoxycholic acid (UDCA), or by a lipid raft disrupter, pravastatin, definitely validated zebrafish larva as a reliable model to quickly assess membrane remodeling involvement in chemical-induced hepatotoxicity. In conclusion, this model, compatible with a high throughput screening, might be adapted to seek hepatotoxicants via membrane remodeling, and also drugs targeting membrane features to propose new preventive or therapeutic strategies in chemical-induced liver diseases.
ISSN: 0260-437X

hal-01526425
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425/file/Zebrafish%20larva%20as%20a%20reliable%20model-Podechard%20JAT%202016%20revised.pdf
DOI : 10.1002/jat.3421

Éditeur(s) : Gauthier-Villars
Résumé : Mud fields located In the inner part of shelves in front of large estuaries are preferential environments for the investigation of the mechanisms and evolution in time of the supply of such sedimentary bodies. The study of different constituents of the particulate organic matter trapped in the sediments of the West Gironde mud patch contributes to the knowledge of the input origins. This study was carried out with different techniques, including pyrolysis-gas chromatography-mass spectrometry and high performance liquid chromatography, on samples from a core collected in the centre of the mud field. At the bottom of the core, the increase of sugars, amino-sugars and some aromatic hydrocarbons may indicate a more marine character of organic components. The same appears to be the case at the top of the core, where, despite a finer sedimentation, biochemical characteristics could show a more pronounced marine influence than in the middle part. In the middle part of the core, on the other hand, the increase in phenols could result from an increase in lignin-derived. terrestrial inputs. The increase in pyrolysis-derived cyclopentenone may indicate the same terrestrial influence, because this component has its origin in aliphatic polycarboxylic acids resulting from sail leaching. The continental character of the sedimentation is also reflected in the increase of the silt-clay fractions representative of suspended matter originating in the Gironde estuary, associated with a slight carbonate decrease. The taxonomic significance of some phenols is noteworthy: this is especially the case of the cinnamyls which, in the middle part of the core, emphasize the input of herbaceous debris and of the hydroxybenzyls which, at the bottom, provide evidence of the algal origin of part of the organic material. Thus, by means of pyrolysis results and HPLC phenol analysis, it is possible to establish the more or less continental signature of organic components trapped in the ''Ouest-Gironde'' mud patch. This study of organic matter, which confirms earlier sedimentological and micropaleontological data, constitutes a new approach, adapted to the identification of the origin of carbon sources.
Oceanolica Acta (0399-1784) (Gauthier-Villars), 1997 , Vol. 20 , N. 5 , P. 687-695

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00093/20426/18093.pdf
http://archimer.ifremer.fr/doc/00093/20426/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The heterodimeric L-type amino acid transporter (LAT) 1/ CD98hc is overexpressed in lung cancers with a poor prognosis factor. Factors that contribute to LAT1/CD98hc overexpression in lung cells remain however to be determined, but the implication of atmospheric pollution can be suspected. The present study was therefore designed to analyze the effects of diesel exhaust particle (DEP) extract (DEPe) on LAT1/CD98hc expression in bronchial epithelial BEAS-2B cells. Exposure to DEPe up-regulated LAT1 and CD98hc mRNA levels in a concentration-dependent manner, with DEPe EC50 values (around 0.2 μg/mL) relevant to environmental situations. DEPe concomitantly induced LAT1/CD98hc protein expression and LAT1-mediated leucine accumulation in BEAS-2B cells. Inhibition of the aryl hydrocarbon receptor (AhR) pathway through the use of a chemical AhR antagonist or the siRNA-mediated silencing of AhR expression was next found to prevent DEPe-mediated induction of LAT1/CD98hc, indicating that this regulation depends on AhR, known to be activated by major chemical DEP components like polycyclic aromatic hydrocarbons. DEPe exposure was finally shown to induce mRNA expression and activity of matrix metalloproteinase (MMP)-2 in BEAS-2B cells, in a CD98hc/focal adhesion kinase (FAK)/extracellular regulated kinase (ERK) manner, thus suggesting that DEPe-mediated induction of CD98hc triggers activation of the integrin/FAK/ERK signaling pathway known to be involved in MMP-2 regulation. Taken together, these data demonstrate that exposure to DEPe induces functional overexpression of the amino acid transporter LAT1/CD98h in lung cells. Such a regulation may participate to pulmonary carcinogenic effects of DEPs, owing to the well-documented contribution of LAT1 and CD98hc to cancer development.
ISSN: 0041-008X

hal-01237095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095/file/Aryl%20hydrocarbon%20receptor-dependent%20up-regulation_accepted.pdf
DOI : 10.1016/j.taap.2015.11.014

Éditeur(s) : HAL CCSD
Résumé : Food-grade dairy propionibacteria are nutraceutical producers. They release short chain fatty acids (SCFAs), folic acid and cobalamin, which play a role in intestinal physiology. SCFAs induce apoptosis via the mitochondrial death pathway. We investigated the potential of dairy propionibacteria-fermented products to synergize with drugs used in gastric and colorectal cancer.Fermented milk contained high and viable populations of propionibacteria. This product, as well as its cell-free supernatant, were tested in vitro on gastric HGT-1 and colic HT-29 cells with respect to apoptosis and synergy with known anti-cancer molecules, camptothecin and the human cytokine TRAIL (TNF Related Apoptosis Inducing Ligand). Viability was monitored and apoptosis quantified by Hoescht staining, ROS production, mitochondrial membrane potential perturbation and caspases activity assay. A transcriptomic study on genome-wide microarray was performed in collaboration with the company Miltenyi.Fermented milk induced cell death in both gastric and colon cancer cells. Characterization of cells revealed cell cycle arrest, drop in intracellular ATP, depolarization of mitochondria, translocation of key apoptosis proteins, processing of caspases and fragmentation of the nucleus. Interestingly, the fermented milk was shown to potentiate the cytotoxic effect of molecules used in cancer chemotherapy, camptothecin and TRAIL. The observed synergistic pro-apoptotic effect between TRAIL and propionibacterial SCFAs depended on death receptors and on caspases, was more lethal on cancer cells than on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Transcriptomics revealed that propionibacterial metabolites boosted TRAIL-induced modulation of gene expression in human colon cancer cells.These results open new perspectives in the field of colon cancer cells prevention and/or treatment. The synergy with pro-apoptotic chemotherapy molecules suggests that such a fermented product, or the propionibacterium alone, may be proposed as a food supplement to enhance the effects of anticancer treatments.
The 2nd International conference on Cell Death In Cancer (CDIC)
La Baule, France

hal-01209622
https://hal.archives-ouvertes.fr/hal-01209622
PRODINRA : 261291

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed. Significant interactions occur by inhibition or induction of CYP450 3A4 which is the main metabolic pathway of TKIs. However, minor metabolic pathways should also be paid attention to. Interactions involving efflux and influx transporters should also be considered occurring for some TKIs. Genetic polymorphism in drug metabolism as well as in drug transport is a factor of variability in drug exposure, which could modulate the magnitude of drug-drug interactions (DDIs). It should be noticed that TKIs can also be at the origin of drug interactions by altering the pharmacokinetics of coprescribed drugs. Since cancer patients are given many drugs either for supportive care or for the treatment of drug toxicity, and to the fact that the oldest patients are polymedicated, a clear understanding of DDIs with TKIs is of interest. The objectives of this review are to provide an overview of the mechanisms of DDIs with TKIs and to provide to physicians and pharmacists recommendations to manage these DDIs in their clinical practice.
ISSN: 0278-0232

hal-01616064
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616064
DOI : 10.1002/hon.2335
PUBMED : 27925256

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Outbreaks of the corallivorous crown-of-thorns seastar Acanthaster planci (COTS) represent one of the greatest disturbances to coral reef ecosystems in the Indo-Pacific, affecting not only coral reefs but also the coastal communities which rely on their resources. While injection approaches are increasingly used in an attempt to control COTS densities, most of them display severe drawbacks including logistical challenges, high residual environmental impacts or low cost-effectiveness. We tested a new alternative control method based upon acidic injections of cheap, 100% natural products. We investigated the lethal doses, intra-and inter-specific disease transmission and immune responses of COTS when injected with fresh lime juice (extracted from local Citrus arantifolia) and white spirit vinegar. High COTS mortality was achieved with small volumes: 10–20 ml per seastar induced death in 89%/ 97% of injected specimens after an average 34.3 h/29.8 h for lime juice and vinegar respectively. Highest efficiency was reached for both solutions with double shots of (2 × 10 ml) in two different areas on the body: 100% mortality occurred within 12–24 h, which is similar or faster compared with other current injection methods. Multiple immune measures suggested that death was very likely caused by pH stress from the acidic solutions rather than a bacterial infection. Contagion to either conspecifics or a variety of other reef species was not observed, even at COTS densities 15 times higher than the highest naturally reported. 10 to 20 l lime juice/vinegar could kill up to a thousand COTS at a cost of less than 0.05 USD per specimen; no permits or special handling procedures are required. We conclude that injections of lime juice and vinegar offer great advantages when compared to current best practises and constitute a cheap and natural option for all reefs affected by COTS.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01208272
https://hal-univ-perp.archives-ouvertes.fr/hal-01208272
https://hal-univ-perp.archives-ouvertes.fr/hal-01208272/document
https://hal-univ-perp.archives-ouvertes.fr/hal-01208272/file/journal.pone.0137605.pdf
DOI : 10.1371/journal.pone.0137605

Éditeur(s) : HAL CCSD American Geophysical Union
Résumé : Results are reported for an acidic water flow-through experiment conducted in a fractured argillaceous limestone sample (73% carbonates). The change in fracture geometry and related parameters is reported for six data sets obtained from synchrotron X-ray microtomography experiments. High-resolution three-dimensional images of the sample allowed quantification of the changes in fracture morphology at a spatial resolution of 6 ;μm. Mineral mass loss and permeability changes in the sample were also determined. Several physico-chemical phenomena were identified during the experiment. Initial smooth fracture surfaces evolved rapidly toward rough surfaces with uneven clay coverage due to the preferential dissolution of carbonate minerals compared to clay minerals whose dissolution rate is about 106 slower. A microporous clay coating progressively developed at the fluid-rock interface during heterogeneous dissolution of the fracture, while the global dissolution rate of the fracture walls exponentially decreased. The increase in surface roughness and the presumed reorganization of clays caused a progressive reduction in permeability. During the last flow-through stage, a large decrease in sample permeability was attributed to the large removal of clay particles; this process was responsible for a dramatic collapse of the fracture walls near the sample inlet and led to the development of preferential flow pathways. The development of the clay coating also acted as a barrier to flow and mass transfer between calcite grains and bulk solution and affected transport processes within the fracture
ISSN: 0043-1397

hal-00405333
https://hal.archives-ouvertes.fr/hal-00405333
DOI : 10.1029/2006WR005379