Éditeur(s) : HAL CCSD
Résumé : International audience
The SOX8 and SOX9 transcription factors are involved in, among others, sex differentiation, male gonad development and adult maintenance of spermatogenesis. Sox8(-/-) mice lacking Sox9 in Sertoli cells fail to form testis cords and cannot establish spermatogenesis. Although genetic and histological data show an important role for these transcription factors in regulating spermatogenesis, it is not clear which genes depend upon them at a genome-wide level. To identify transcripts that respond to the absence of Sox8 in all cells and Sox9 in Sertoli cells we measured mRNA concentrations in testicular samples from mice at 0, 6 and 18 days post-partum. In total, 621 and 629 transcripts were found at decreased or increased levels, respectively, at different time points in the mutant as compared to the control samples. These mRNAs were categorized as preferentially expressed in Sertoli cells or germ cells using data obtained with male and female gonad samples and enriched testicular cell populations. Five candidate genes were validated at the protein level. Furthermore, we identified putative direct SOX8 and SOX9 target genes by integrating predicted SOX-binding sites present in potential regulatory regions upstream of the transcription start site. Finally, we used protein network data to gain insight into the effects on regulatory interactions that occur when Sox8 and Sox9 are absent in developing Sertoli cells. The integration of testicular samples with enriched Sertoli cells, germ cells and female gonads enabled us to broadly distinguish transcripts directly affected in Sertoli cells from others that respond to secondary events in testicular cell types. Thus, combined RNA profiling signals, motif predictions and network data identified putative SOX8/SOX9 target genes in Sertoli cells and yielded insight into regulatory interactions that depend upon these transcription factors. In addition, our results will facilitate the interpretation of genome-wide in vivo SOX8 and SOX9 DNA binding data.
Andrology

hal-00877013
https://hal.archives-ouvertes.fr/hal-00877013
DOI : 10.1111/j.2047-2927.2012.00049.x
PUBMED : 23315995

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The origin of replication complex subunit ORC1 is important for DNA replication. The gene is known to encode a meiotic transcript isoform (mORC1) with an extended 5′-untranslated region (5′-UTR), which was predicted to inhibit protein translation. However, the regulatory mechanism that controls the mORC1 transcript isoform is unknown and no molecular biological evidence for a role of mORC1 in negatively regulating Orc1 protein during gametogenesis is available. By interpreting RNA profiling data obtained with growing and sporulating diploid cells, mitotic haploid cells, and a starving diploid control strain, we determined that mORC1 is a middle meiotic transcript isoform. Regulatory motif predictions and genetic experiments reveal that the activator Ndt80 and its middle sporulation element (MSE) target motif are required for the full induction of mORC1 and the divergently transcribed meiotic SMA2 locus. Furthermore, we find that the MSE-binding negative regulator Sum1 represses both mORC1 and SMA2 during mitotic growth. Finally, we demonstrate that an MSE deletion strain, which cannot induce mORC1, contains abnormally high Orc1 levels during post-meiotic stages of gametogenesis. Our results reveal the regulatory mechanism that controls mORC1, highlighting a novel developmental stage-specific role for the MSE element in bi-directional mORC1/SMA2 gene activation, and correlating mORC1 induction with declining Orc1 protein levels. Because eukaryotic genes frequently encode multiple transcripts possessing 5′-UTRs of variable length, our results are likely relevant for gene expression during development and disease in higher eukaryotes. © 2016 Taylor & Francis Group, LLC.
ISSN: 1547-6286

hal-01367153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367153
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367153/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367153/file/Ndt80%20activates%20the%20meiotic%20ORC1%20transcript.pdf
PUBMEDCENTRAL : PMC5013992

Éditeur(s) : HAL CCSD
Résumé : International audience
Earthquake, volcanic eruption, cyclone, flood, tsunami, the Caribbean are particularly vulnerable to many natural hazards. Citizen Education to hazard mitigation is much more important in French West Indies than in Paris. With national, curriculum, evaluation and textbooks, how science education in French West Indies manage the challenge to take account this particularity of our territories? Based on this example and others, the aim of this communication is to present a science education theoretical background focus on contexts studies. During science teaching, learning effects due to different context like social, cultural or language could be described as contextual effects. But others micro-didactic effects of contexts could also be identified as linked with specificity of natural environment. These effects manifest a strain between a goal of teaching or learning and its implementation, when this stain is due in the educational process in different contexts involved.To ensure the quality of education, reference and quantify the effects of educational context seems to be necessary. it should be interested in the process leading to the emergence of these contexts. We propose a simplified model of these processes initially described as meetings of mechanisms operating within a network of transposition of designs. Then we question these processes by degree or forms of contextualization (low to high) and crossed these two approaches, giving an initial typology of contextualisation process. It then emerges the idea that these processes are constrained by resistances. We retain the following three: epistemological, social and educational. As these constraints are expressed in different ways according to disciplines, the data suggest the existence of disciplinary contextualization profiles. All these three approaches (network implementation, degree of contextualization, disciplinary profiles) are three tools for analyzing contextual phenomena which remain to test the robustness and operational character for the training analysis context.
Biennial Conference of Caribbean Academy of Sciences
Barbados, Barbados

hal-01539482
https://hal.univ-antilles.fr/hal-01539482

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : Combined petrographic study and apatite fission track analysis (apatite FTA) across the Gres d'Annot basin document maximum temperatures reached by this turbiditic sandstone formation, from around 60 degrees C at the SW basin margin up to around 200 degrees C below the Penninic frontal thrust, in relation to burial below the front of Alpine nappes. Increasing diagenetic grade across the basin is primarily expressed by the development of silica transfer by pressure solution and correlated porosity loss. We infer the nappe thickness profile, from the nappe front in the SW up to around 8-10 km in the NE. Apatite FTA dates exhumation of the Gres d'Annot during the Late Miocene, in relation to thrusting of the underlying Argentera and Barrot Palaeozoic massifs. This study illustrates the influence of thrust front propagation on foreland basin diagenesis and exhumation, and highlights potential implications for the evolution of sediment reservoir properties in this context.
ISSN: 0954-4879

hal-00411860
https://hal.archives-ouvertes.fr/hal-00411860
DOI : 10.1111/j.1365-3121.2008.00793.x

Éditeur(s) : HAL CCSD American Society for Pharmacology and Experimental Therapeutics (ASPET)
Résumé : International audience
Most human hepatocyte cell lines lack a substantial set of liver-specific functions, especially major cytochrome P450 (P450)-related enzyme activities, making them unrepresentative of in vivo hepatocytes. We have used the HepaRG cells, derived from a human hepatocellular carcinoma, which exhibit a high differentiation pattern after 2 weeks at confluency to determine whether they could mimic human hepatocytes for drug metabolism and toxicity studies. We show that when passaged at low density, these cells reversed to an undifferentiated morphology, actively divided, and, after having reached confluency, formed typical hepatocyte-like colonies surrounded by biliary epithelial-like cells. By contrast, when seeded at high density, hepatocyte-like clusters retained their typical differentiated morphology. Transcripts of various nuclear receptors (aryl hydrocarbon receptor, pregnane X receptor, constitutive androstane receptor, peroxisome proliferator-activated receptor alpha), P450s (CYP1A2, 2C9, 2D6, 2E1, 3A4), phase 2 enzymes (UGT1A1, GSTA1, GSTA4, GSTM1), and other liver-specific functions were estimated by reverse transcriptase-quantitative polymerase chain reaction and were found to be expressed, for most of them, at comparable levels in both confluent differentiated and high-density differentiated HepaRG cells and in cultured primary human hepatocytes. For several transcripts, the levels were strongly increased in the presence of 2% dimethyl sulfoxide. Measurement of basal activities of several P450s and their response to prototypical inducers as well as analysis of metabolic profiles and cytotoxicity of several compounds confirmed the functional resemblance of HepaRG cells to primary cultured human hepatocytes. In conclusion, HepaRG cells constitute the first human hepatoma cell line expressing high levels of the major P450s involved in xenobiotic metabolism and represent a reliable surrogate to human hepatocytes for drug metabolism and toxicity studies.
ISSN: 0090-9556

hal-00702085
https://hal.archives-ouvertes.fr/hal-00702085
DOI : 10.1124/dmd.105.006759
PUBMED : 16204462

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Thermal acclimation drastically alters thermotolerance of ectotherms, but the mechanisms determining this plastic response are not fully understood. The present study investigates the proteomic response (2D-DIGE) of adult Drosophila melanogaster acclimated at 11, 25 or 31 C. As expected 11 C-acclimation improved cold tolerance and 31 C-acclimation improved heat tolerance. We hypothesized that the marked organismal responses to acclimation could be detected at the proteomic level assuming that changes in the abundance of specific proteins are linked to the physiological changes underlying the phenotypic response. The 31 C-acclimated flies displayed a particular divergent proteomic profile where molecular chaperones made up a large number of the proteins that were modulated during heat acclimation. Many other proteins showed significant modulation during acclimation including proteins involved in iron ion and cell redox homeostasis, carbohydrate and energy metabolism, chromatin remodeling and translation, and contractile machinery. Interestingly the changes in protein abundance were often unrelated to transcriptional activity of the genes coding for the proteins, except for the most strongly expressed proteins (e.g. Hsp70). The 11 C-acclimation evoked weak proteomic response despite the marked effect on the organismal phenotype. Thus the acquired cold tolerance observed here may involve regulatory process such as posttranslational regulation rather than de novo protein synthesis.
ISSN: 0965-1748

hal-00826939
https://hal.archives-ouvertes.fr/hal-00826939
DOI : 10.1016/j.ibmb.2013.01.006
PUBMED : 23416132

Éditeur(s) : HAL CCSD Wiley
Résumé : Publication Inra prise en compte dans l'analyse bibliométrique des publications scientifiques mondiales sur les Fruits, les Légumes et la Pomme de terre. Période 2000-2012. http://prodinra.inra.fr/record/256699
International audience
Potato can be severely affected by various pathogens, including Pectobacterium atrosepticum, the cause of bacterial soft rot on tubers and of blackleg on stems. To date, no complete resistance to P.similar to atrosepticum is available, so that only cultivars exhibiting partial resistance can be found. The mechanistic basis of this type of resistance is still poorly understood. A proteomic approach was thus developed to identify pathways specifically activated during the interaction between potato tubers and P.similar to atrosepticum. Protein profiles on silver-stained gels in the 58 similar to pH range were obtained from healthy and infected tubers from two cultivars differing for resistance level and analyzed by 2-DE and nano-LC-MS/MS. Thirteen proteins were differentially up-regulated in the partially resistant cv. Kerpondy; by contrast, no significant differences in protein profiles of inoculated and control tubers were observed in the susceptible cv. Bintje. Mass spectrometry and database searching showed that these proteins are involved in energetic metabolism (glyceraldehyde-3-phosphate dehydrogenase, 2-phosphoglycerate dehydratase or enolase, fructose biphosphate aldolase and ATPase a subunit), cytoskeleton structure (actin), protein catabolism (cysteine protease inhibitor) and patatins or patatin precursors. Their involvement in defence responses of cv. Kerpondy to P.similar to atrosepticum is discussed. Proteomic appears as an efficient approach to have insight into the mechanisms and pathways leading to potato resistance against P.similar to atrosepticum.
ISSN: 0931-1785

hal-01208654
https://hal.archives-ouvertes.fr/hal-01208654
PRODINRA : 213002
DOI : 10.1111/j.1439-0434.2012.01950.x

Éditeur(s) : HAL CCSD
Résumé : International audience
Clear cell renal cell carcinoma (ccRCC) has a poor prognosis with a 50% risk of metastases. Little is known about the phenotypic and molecular profiles of metastases regarding their corresponding primary tumors. This study aimed to screen phenotypic and genotypic differences between metastases and their corresponding primary tumors. We selected four cases with available frozen material. The histological, immunohistochemical (VEGFA, CD31, SMA, Ki67, p53, PAR-3), FISH (VHL gene), next-generation sequencing (VHL and c-MET genes), multiplex ligation-dependent probe amplification, and array-(comparative genomic hybridization) CGH analyses were realized. Metastases were nodal, hepatic (synchronous), adrenal, and pulmonary (metachronous). High-grade tumor cells were significantly more frequent in metastases (p = 0.019). Metastases and high-grade zones of primary tumors shared similar characteristics compared to low-grade zones: a lower microscopic vascular density (43.5 vs 382.5 vessels/mm(2); p = 0.0027), a higher expression of VEGF (73 vs 10%, p = 0.045), Ki67 (37.6 vs 8.3%; p = 0.011), and p53 (54 vs 10.6%; p = 0.081), and a cytoplasmic and membranous PAR-3 staining. Metastases exhibited more chromosomal imbalances than primary tumors in total (18.75 ± 6.8; p = 0.044) with more genomic gains (13.5 ± 7; p = 0.013). The loss of chromosome 9 and gain of Xq were found in both primary tumors and metastases but gains of loci or chromosomes 2p, 3q, 5, 8q, 12, and 20 were only found in metastases. The VHL gene status was similar in each tumor couple. Although metastases and primary tumors share common histological features, this study highlights chromosomal differences specific to metastases which could be involved in ccRCC metastatic evolution.
Virchows Archiv

hal-01560281
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560281
DOI : 10.1007/s00428-017-2124-0
PUBMED : 28488172

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : Nucleotide diversity was assessed within nine candidate genes (in total 4.6 kb) for the time of bud burst in nine sessile oak (Quercus petraea) populations distributed in central and northern Europe. The sampled populations were selected on the basis of their contrasting time of bud burst observed in common garden experiments (provenance tests). The candidate genes were selected according to their expression profiles during the transition from quiescent to developing buds and/or their functional role in model plants. The overall nucleotide diversity was large (pi(tot) - 6.15 x 10(-3); pi(silent) - 11.2 x 10(-3)), but population differentiation was not larger than for microsatellites. No outlier single-nucleotide polymorphism (SNP), departing from neutral expectation, was found among the total of 125 SNPs. These results contrasted markedly with the significant associations that were observed between the candidate genes and bud burst in segregating populations. Quantitative trait loci (QTLs) for bud burst were identified for 13 year*site seasonal observations in a cloned mapping pedigree. Nineteen QTLs were detected, and QTLs located on linkage groups 2, 5 and 9 contributed repeatedly to more than 12% of the phenotypic variation of the trait. Eight genes were polymorphic in the two parents of the pedigree and could be mapped on the existing genetic map. Five of them located within the confidence intervals of QTLs for bud burst. Interestingly, four of them located within the three QTLs exhibiting the largest contributions to bud burst.
ISSN: 0018-067X

hal-01032156
https://hal.archives-ouvertes.fr/hal-01032156
DOI : 10.1038/hdy.2009.170

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Modern measures of diversity satisfy reasonable axioms, are parameterized to produce diversity profiles, can be expressed as an effective number of species to simplify their interpretation, and come with estimators that allow one to apply them to real-world data. We introduce the generalized Simpson’s entropy as a measure of diversity and investigate its properties. We show that it has many useful features and can be used as a measure of biodiversity. Moreover, unlike most commonly used diversity indices, it has unbiased estimators, which allow for sound estimation of the diversity of poorly sampled, rich communities.
ISSN: 1932-6203

hal-01276738
https://hal-agroparistech.archives-ouvertes.fr/hal-01276738
https://hal-agroparistech.archives-ouvertes.fr/hal-01276738v2/document
https://hal-agroparistech.archives-ouvertes.fr/hal-01276738/file/Grabchak%20et%20al.%20-%202017%20-%20The%20Generalized%20Simpson%27s%20Entropy%20is%20a%20Measure%20of%20Biodiversity.pdf
DOI : 10.1371/journal.pone.0173305

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The stratigraphy of the last deglaciation sequence is investigated in Lake Saint-Jean (Québec Province, Canada) based on 300 km of echo-sounder two dimensional seismic profiles. The sedimentary archive of this basin is documented from the Late Pleistocene Laurentidian ice-front recession to the present-day situation. Ten seismic units have been identified that reflect spatio-temporal variations in depositional processes characterizing different periods of the Saint-Jean basin evolution. During the postglacial marine flooding, a high deposition rate of mud settling, from proglacial glacimarine and then prodeltaic plumes in the Laflamme Gulf, produced an extensive, up to 50 m thick mud sheet draping the isostatically depressed marine basin floor. Subsequently, a closing of the water body due to glacio-isostatic rebound occurred at 8.5 cal. ka BP, drastically modifying the hydrodynamics. Hyperpycnal flows appeared because fresh lake water replaced dense marine water. River sediments were transferred towards the deeper part of the lake into river-related sediment drifts and confined lobes. The closing of the water body is also marked by the onset of a wind-driven internal circulation associating coastal hydrodynamics and bottom currents with sedimentary features including shoreface deposits, sediment drifts and a prograding shelf-type body. The fingerprints of a forced regression are well expressed by mouth-bar systems and by the shoreface-shelf system, the latter unexpected in such a lacustrine setting. In both cases, a regressive surface of lacustrine erosion (RSLE) has been identified, separating sandy mouth-bar from glaciomarine to prodeltaic muds, and sandy shoreface wedges from the heterolithic shelf-type body, respectively. The Lake Saint-Jean record is an example of a regressive succession driven by a glacio-isostatic rebound and showing the transition from late-glacial to post-glacial depositional systems.
ISSN: 0300-9483

hal-00984683
https://hal.archives-ouvertes.fr/hal-00984683
DOI : 10.1111/bor.12039

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : International audience
Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
ISSN: 1757-4676

hal-01118028
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118028
PUBMED : 25214462
PUBMEDCENTRAL : PMC4287935
DOI : 10.15252/emmm.201404112