Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0003-4975

hal-01563338
http://hal.univ-brest.fr/hal-01563338
DOI : 10.1016/j.athoracsur.2016.03.093
PUBMED : 27262916

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
ISSN: 0959-8049

hal-01666517
https://hal.univ-lorraine.fr/hal-01666517
DOI : 10.1016/j.ejca.2015.11.024

Éditeur(s) : Amer Geophysical Union
Résumé : In this study, we undertook a reconnaissance study of sediments provenance in the Gulf of Lions focusing over the last 16 ka. We used geochemical and isotopic tracers to determine the source of sediments and give insight into the weathering conditions prevailing. Sediments samples were selected both onshore and offshore from the western, eastern, and central part of the Gulf of Lions. We analyzed bulk sediments, coarse and fine silt, and clay fractions. Elemental and Nd isotope compositions appeared to differ from one grain size fraction to another one. These are interpreted in terms of zircon addition in the coarse silt fraction for the elemental concentrations and variable sources influences for the Nd isotope compositions. Our results indicate that sediments in the Gulf of Lions mainly originated from the Rhone River watershed although a contribution of Saharan dust is seen in one sample. Influence of Pyrenean small rivers is minor in these samples. Some Sr isotope compositions shifts are interpreted as reflecting variable amounts of chemical weathering that are consistent with published paleoclimatic reconstructions.
Geochemistry Geophysics Geosystems (1525-2027) (Amer Geophysical Union), 2011-08 , Vol. 12 , N. Q08006 , P. 20 p.

Droits : 2011 by the American Geophysical Union
http://archimer.ifremer.fr/doc/00043/15376/12734.pdf
DOI:10.1029/2011GC003523
http://archimer.ifremer.fr/doc/00043/15376/

Éditeur(s) : Elsevier
Résumé : Emplacement of post-glacial turbidites is commonly controlled by rapid changes in sea level or by seismicity. On the continental rise of the Gulf of Lions (Western Mediterranean), an aseismic area, we identified turbiditic beds deposited during the rising stage and highstand of sea level. Swath bathymetry, sediment cores, in situ Cone Penetrating Tests (CPTU), heavy mineral associations and radiocarbon dating determined the source, composition, distribution and age of the turbiditic beds. Turbidites are composed of homogeneous to positively graded silts to medium sand with quartz (up to 90%), shell debris and shelfal benthic faunas. Their distribution on the sea floor is very patchy and controlled by abundant inherited erosional bedforms. Their source is found in relict regressive sands at the outershelf. Their deposition occurred just after the onset of the post-glacial sea level rise and the concomitant sediment starvation of the Rhone deep sea turbiditic system until recently. Whilst canyons are fed with sand by strong seasonal hydro-sedimentary dynamics on the outershelf, the emplacement of post-glacial turbidites is not controlled by sea level changes but probably by the periodic flushing of the canyons. Our study revealed that this low energy aseismic margin undergoes significant transport of sand, down to the base of slope, during the sea-level rise and the Holocene highstand.
Marine Geology (0025-3227) (Elsevier), 2009-02 , Vol. 257 , N. 1-4 , P. 65-86

Droits : 2009 Published by Elsevier Ltd.
http://archimer.ifremer.fr/doc/2009/publication-6316.pdf
DOI:10.1016/j.margeo.2008.10.013
http://archimer.ifremer.fr/doc/00000/6316/

Éditeur(s) : Elsevier Science Bv
Résumé : The modern Rhone delta in the Gulf of Lions (NW Mediterranean) is a typical wave-dominated delta that developed after the stabilization of relative sea level following the last deglacial sea-level rise. Similar to most other deltas worldwide, it displays several stacked parasequences and lobes that reflect the complex interaction between accommodation, sediment supply and autogenic processes on the architecture of a wave-dominated delta. The interpretation of a large set of newly acquired very high-resolution seismic and sedimentological data, well constrained by 14C dates, provides a refined three-dimensional image of the detailed architecture (seismic bounding surfaces, sedimentary facies) of the Rhone subaqueous delta, and allows us to propose a scenario for delta evolution during the last deglaciation and Holocene. The subaqueous delta consists of “parasequence-like” depositional wedges, a few meters to 20–30 m in thickness. These wedges first back-stepped inland toward the NW in response to combined global sea-level rise and overall westward oceanic circulation, at a time when sediment supply could not keep pace with rapid absolute (eustatic) sea-level rise. At the the Younger Dryas-Preboreal transition, more rapid sea-level rise led to the formation of a major flooding surface (equivalent to a wave ravinement surface). After stabilization of global sea level in the mid-Holocene, accommodation became the leading factor controlling delta architecture. An eastward shift of depocenters occurred, probably favoured by higher subsidence rate within the thick Messinian Rhone valley fill. The transition between transgressive (backstepping geometry) and regressive (prograding geometry) (para)sequences resulted in creation of a Maximum Flooding Surface (MFS) that differs from a “classical” MFS described in the literature. It consists of a coarse-grained interval incorporating reworked shoreface material within a silty clay matrix. This distinct lithofacies results from condensation/erosion, which appears as an important process even within supply-dominated deltaic systems, due to avulsion of distributaries. The age of the MFS varies along-strike between ca. 7.8-5.6 kyr cal. BP in relation to the position of depocenters and climatically-controlled sediment supply. The last rapid climate change of the Holocene, the Little Ice Age (1250–1850 AD), had a distinct stratigraphic influence on the architecture and lithofacies of the Rhone subaqueous delta through the progradation of two deltaic lobes. In response to changes in sediment supply linked to rapid climate changes (and to anthropic factors), the Rhone delta evolved from wave-dominated to fluvial dominated, and then wave dominated again.
Sedimentary Geology (0037-0738) (Elsevier Science Bv), 2014-05 , Vol. 305 , P. 35-53

Droits : 2014 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/00179/29017/27445.pdf
DOI:10.1016/j.sedgeo.2014.02.004
http://archimer.ifremer.fr/doc/00179/29017/

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development.
ISSN: 1553-7390

hal-01063929
https://hal.archives-ouvertes.fr/hal-01063929
DOI : 10.1371/journal.pgen.1004340
PUBMED : 24784881

Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : Elsevier
Résumé : The fining upward trend commonly described on levees of turbidite systems can be either attributed to changes in the sediment supply (external forcing = allocyclic) or changes in the spillover processes related to the growth of the levee (internal forcing = autocyclic). However the real causes remain speculative and difficult to demonstrate. Knowledge of vertical change in flow velocity (or grain size) in turbidity currents, of the turbidity current's height, as well as the growth rate of a levee are theoretically sufficient to describe the evolution of the grain size of a leveed turbidite sequence deposited by spillover processes. A piston core (MD99-2344) retrieved on the right levee of the Petit-Rhone neofan, sampled an 8.50 m long turbidite sequence containing more than one hundred turbidite beds and showing a marked fining upward trend. With the help of two profiles describing respectively the vertical velocity [Stacey, M. and Bowen, A.J., 1988b. The vertical structure of turbidity currents and a necessary condition for self-maintenance, Journal of Geophysical Research, pp. 3543-3553.] and the vertical grain size [Migeon, S., 2000. Dunes geantes et levees sedimentaires en domaine marin profond: approche morphologique, sismique et sedimentologique. PhD Thesis, Universite Bordeaux 1, Talence, France, 288 pp.] of a turbidity current, and a simple graphical method, we test several hypotheses on the height of the turbidity current and on the grain size at the bottom of the turbidity current and we attempt to reproduce the vertical fining upward trend. Our results show that the fining upward trend of the turbidite facies can be explained by the aggradation of the turbidite levee and the gradual confinement of the turbidity currents in the channel. This is, therefore, an autocyclical phenomenon. However a high frequency variability of the grain size overprinted on the trend cannot be explained by internal forcing and is believed to be allocyclical, depending on changes to the sediment input. The vertical grain-size profile allows more realistic flow conditions to be determined and shows that the vertical velocity profile does not describe the ability of turbidity current to transport sediment. This simple graphical method allows a better understanding and quantification of the forcing on turbidite deposits and improves description of the characteristics of the turbidity currents from the grain size of the deposits.
Marine Geology (0025-3227) (Elsevier), 2006-12 , Vol. 234 , N. 1-4 , P. 191-213

Droits : 2006 Elsevier
http://archimer.ifremer.fr/doc/2006/publication-2311.pdf
DOI:10.1016/j.margeo.2006.09.019
http://archimer.ifremer.fr/doc/00000/2311/

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Androgen signaling, via the androgen receptor (AR), is crucial in mediating prostate cancer (PCa) initiation and progression. Identifying new downstream effectors of the androgens/AR pathway will allow a better understanding of these mechanisms and could reveal novel biomarkers and/or therapeutic agents to improve the rate of patient survival. We compared the microRNA expression profiles in androgen-sensitive LNCaP cells stimulated or not with 1 nM R1881 by performing a high-throughput reverse transcriptase-quantitative PCR and found that miR-135a was upregulated. After androgen stimulation, we showed that AR directly activates the transcription of miR-135a2 gene by binding to an androgen response element in the promoter region. Our findings identify miR-135a as a novel effector in androgens/AR signaling. Using xenograft experiments in chick embryos and adult male mice, we showed that miR-135a overexpression decreases in vivo invasion abilities of prostate PC-3 cells. Through in vitro wound-healing migration and invasion assays, we demonstrated that this effect is mediated through downregulating ROCK1 and ROCK2 expression, two genes that we characterized as miR-135a direct target genes. In human surgical samples from prostatectomy, we observed that miR-135a expression was lower in tumoral compared with paired adjacent normal tissues, mainly in tumors classified with a high Gleason score (⩾8). Moreover, miR-135a expression is lower in invasive tumors, showing extraprostatic extension, as compared with intraprostatic localized tumors. In tumor relative to normal glands, we also showed a more frequently higher ROCK1 protein expression determined using a semi-quantitative immunohistochemistry analysis. Therefore, in tumor cells, the lower miR-135a expression could lead to a higher ROCK1 protein expression, which could explain their invasion abilities. The highlighted relationship between miR-135a expression level and the degree of disease aggressiveness suggests that miR-135a may be considered as a prognostic marker in human PCa.Oncogene advance online publication, 28 July 2014; doi:10.1038/onc.2014.222.
ISSN: 0950-9232

hal-01063902
https://hal.archives-ouvertes.fr/hal-01063902
https://hal.archives-ouvertes.fr/hal-01063902/file/Androgen-regulated%20microRNA-135a.pdf
DOI : 10.1038/onc.2014.222
PUBMED : 25065599

Éditeur(s) : HAL CCSD
Résumé : International audience
ISSN: 1937-7835

hal-01391676
https://hal-univ-perp.archives-ouvertes.fr/hal-01391676

Éditeur(s) : HAL CCSD
Résumé : International audience
Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.
Eur Respir Rev

hal-01063982
https://hal.archives-ouvertes.fr/hal-01063982
DOI : 10.1183/09059180.00001814
PUBMED : 24881074

Éditeur(s) : Elsevier Science Bv
Résumé : The timing, routing and processes of sediment transfer from the continents to the oceans at millennial time-scale are still largely unknown. The potential of turbidite systems (dominantly deposited during sea-level lowstands) to record global or regional environmental fluctuations is usually under-exploited because of the difficulty to obtain robust chronostratigraphic constraints in turbiditic deposits, and therefore to tie changes in sedimentary processes to environmental fluctuations. We were able to obtain a millennial-scale chronostratigraphy based on oxygen isotopes of the scarce foraminifera preserved in turbiditic deposits of the Rhone Turbidite System within the Western Mediterranean. Our results show that 1) objective criteria can be defined for the selection of foraminifera preserved within the pelagic intervals between the turbiditic sequences, in order to obtain a reliable isotope stratigraphy; 2) Turbidites triggered by hyperpycnal currents are described for the first time within the Rhone Turbidite System. They are related to the periods of direct fluvial connection with the canyon head (during the sea-level lowstand and early rise), and to a period of high sediment flux in relation with the massive recession of the Rhone glaciers in the Alps; 3) The lithofacies change passing from hyperpycnal to “Bouma-type” is dated at ca 19 cal. ka BP, which might correspond to an acceleration of sea-level rise (19-ka Meltwater Pulse,).
Sedimentary Geology (0037-0738) (Elsevier Science Bv), 2015-06 , Vol. 323 , P. 148-166

Droits : 2015 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/00266/37712/35730.pdf
DOI:10.1016/j.sedgeo.2015.04.009
http://archimer.ifremer.fr/doc/00266/37712/

Éditeur(s) : HAL CCSD Elsevier
Résumé : absent
ISSN: 0034-4257

hal-01019844
https://hal.archives-ouvertes.fr/hal-01019844
DOI : 10.1016/j.rse.2012.03.012

Éditeur(s) : HAL CCSD Elsevier
Résumé : Eperua falcata (Aublet), a late-successional species in tropical rainforest and one of the most abundant tree in French Guiana, has developed an original strategy concerning N-acquisition by largely preferring nitrate, rather than ammonium (H. Schimann, S. Ponton, S. Hattenschwiler, B. Ferry, R. Lensi, A.M. Domenach, J.C. Roggy, Differing nitrogen use strategies of two tropical rainforest tree species in French Guiana: evidence from N-15 natural abundance and microbial activities, Soil Biol, Biochem. 40 (2008) 487-494). Given the preference of this species for nitrate, we hypothesized that root exudates would promote nitrate availability by (a) enhancing nitrate production by stimulating ammonium oxidation or (b) minimizing nitrate losses by inhibiting denitrification. Root exudates were collected in situ in monospecific planted plots. The phytochemical analysis of these exudates and of several of their corresponding root extracts was achieved using UHPLC/DAD/ESI-QTOF and allowed the identification of diverse secondary metabolites belonging to the flavonoid family. Our results show that (i) the distinct exudation patterns observed are related to distinct root morphologies, and this was associated with a shift in the root flavonoid content, (ii) a root extract representative of the diverse compounds detected in roots showed a significant and selective metabolic inhibition of isolated denitrifiers in vitro, and (iii) in soil plots the abundance of nirK-type denitrifiers was negatively affected in rhizosphere soil compared to bulk. Altogether this led us to formulate hypothesis concerning the ecological role of the identified compounds in relation to N-acquisition strategy of this species. (C) 2013 Elsevier Masson SAS. All rights reserved.
ISSN: 0981-9428

hal-01032437
https://hal.archives-ouvertes.fr/hal-01032437
DOI : 10.1016/j.plaphy.2013.05.003

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2α), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1β), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility.
ISSN: 0888-8809

hal-01146846
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146846
DOI : 10.1210/me.2014-1356
PUBMED : 25710594

Éditeur(s) : HAL CCSD E Schweizerbart Science Publishers
Résumé : The occurrence and preservation of aragonite in eclogite-facies rocks of north-eastern Corsica is linked to an uncommon microtexture. Aragonite exclusively occurs as oriented fibres in garnet crystals of a graphitic, more or less siliceous marble that immediately overlies a serpentinite body of the meta-ophiolitic unit. The arrangement of the fibres is grossly radial, but more clearly sectoral in subhedral garnet, the fibres growing perpendicular to the garnet/matrix interface. Raman mapping reveals that the carbonate is calcite in the matrix and in poikiloblastic garnet cores, and that the fibres in the garnet mantle are aragonite alone in the case of a carbonate matrix, and both aragonite and quartz (in distinct fibres) in a quartz–carbonate matrix. These features are interpreted as prograde intergrowths, the result of garnet nucleation and growth in a calcite and then aragonite matrix (±quartz). Upon further heating and/or decompression, the aragonite matrix transformed back to calcite while the carbonates included in garnet retained their original structure, in spite of the relatively high temperature attained (ca. 500 °C). These aragonite relics are one more example of the preservation of a high-pressure polymorph through mechanical shielding of inclusions in a rigid host. The aragonite–garnet intergrowths are similar to quartz–garnet intergrowths described in amphibolite-facies graphitic schists. They are evidence that oriented inclusions in garnet are not necessarily precipitates (‘exsolutions'). Unlike precipitates, their orientation is controlled more by the shape of the garnet growth front than by symmetry constraints.
ISSN: 0935-1221

hal-00411136
https://hal.archives-ouvertes.fr/hal-00411136
DOI : 10.1127/0935-1221/2008/0020-1892

Éditeur(s) : HAL CCSD
Résumé : International audience
Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824
Journal of Medical Genetics

hal-01272929
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01272929
DOI : 10.1136/jmedgenet-2015-103302
PUBMED : 26502894

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Epithelial-to-mesenchymal transition (EMT) promotes cell motility, which is important for the metastasis of malignant cells, and blocks CD95-mediated apoptotic signaling triggered by immune cells and chemotherapeutic regimens. CD95L, the cognate ligand of CD95, can be cleaved by metalloproteases and released as a soluble molecule (cl-CD95L). Unlike transmembrane CD95L, cl-CD95L does not induce apoptosis but triggers cell motility. Electron paramagnetic resonance was used to show that EMT and cl-CD95L treatment both led to augmentation of plasma membrane fluidity that was instrumental in inducing cell migration. Compaction of the plasma membrane is modulated, among other factors, by the ratio of certain lipids such as sphingolipids in the membrane. An integrative analysis of gene expression in NCI tumor cell lines revealed that expression of ceramide synthase-6 (CerS6) decreased during EMT. Furthermore, pharmacological and genetic approaches established that modulation of CerS6 expression/activity in cancer cells altered the level of C16-ceramide, which in turn influenced plasma membrane fluidity and cell motility. Therefore, this study identifies CerS6 as a novel EMT-regulated gene that has a pivotal role in the regulation of cell migration.Oncogene advance online publication, 17 March 2014; doi:10.1038/onc.2014.55.
ISSN: 0950-9232

hal-01063558
https://hal.archives-ouvertes.fr/hal-01063558
https://hal.archives-ouvertes.fr/hal-01063558/file/Down-regulation%20of%20ceramide_accepted.pdf
DOI : 10.1038/onc.2014.55
PUBMED : 24632610

Éditeur(s) : American Geophysical Union
Résumé : Thick forced regressive units on the wide continental shelf of the Gulf of Lions (western Mediterranean) recorded the composite effect of sea level changes during the Quaternary. They are mostly composed of coastal siliciclastic and bioclastic wedges showing clinoform geometry. These deposits have been intensively explored through high-resolution seismic investigations, but only recently it was possible to ground truth seismic interpretations, based on a long (100 m) borehole that crossed the succession and recovered a large part of the mainly sandy deposits (similar to 84% recovery). A multiproxy analysis of the sedimentary succession shows that (1) the stratal architecture of the shelf margin is defined by major bounding surfaces that are polygenic erosion surfaces associated with coarse-grained material incorporating abundant and diverse shells, including cold-water fauna (presently absent from the Mediterranean Sea). Between each surface, coarsening upward units with steep (up to 5 degrees) foresets are made of massive (more than 20 m thick) sands with possible swaley and hummocky cross-stratification, passing seaward to sands with muddy intervals and, further offshore, alternating highly boiturbated sands and silts. Each prograding wedge corresponds to a forced-regressive shoreface (or delta front/prodelta), deposited during the overall sea level falls occurring at (relatively slow) interglacial/glacial transition and therefore represents the record of 100 ka cyclicity. Higher-frequency Milankovitch cyclicities are also probably represented by distinct shoreface/delta front wedges; (2) detailed examination of the architecture and chronostratigraphy of the most recent sequence shows that minor bounding surfaces, corresponding to abrupt shallowing of sedimentary facies, separate downward stepping parasequences within the last 100 ka sequence. These events are in phase with millennial-scale glacial climatic and sea level variability, the downward shift surfaces corresponding to the falls during the coldest stadials. These deposits provide a comprehensive and well-constrained Pleistocene analog to the numerous shoreface deposits attributed to falling-stage systems tracts recognized in ancient stratigraphic records, studied at the outcrop scale.
Geochemistry Geophysics Geosystems - G3 (1525-2027) (American Geophysical Union), 2008-11 , Vol. 9 , N. Q11R05 , P. NIL_40-NIL_66

Droits : 2008 American Geophysical Union
http://archimer.ifremer.fr/doc/2008/publication-4929.pdf
DOI:10.1029/2007GC001854
http://archimer.ifremer.fr/doc/00000/4929/

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Although they are famous among Earth scientists, the Lherz peridotites are exposed within geological formations of the North Pyrenean Zone (NPZ) still lacking detailed investigations. Our study focuses on the metasediments of the Aulus basin hosting the Lherz peridotite body and associated ultramafic fragments of smaller size. The new data set comprises of structural analysis and detailed geological mapping of the massive Mesozoic marbles that form the prerift sequence typical of the NPZ and of the ultramafic-rich clastic breccia formations surrounding the peridotite bodies. The massive marbles display an evolution from hot and ductile to cold and brittle deformation, indicative of an exhumation process ending with the sedimentary reworking of both the deformed Mesozoic metasediments and the exhumed ultramafic rocks. Crystal Preferred Orientations (CPO) measured in the marbles support a deformation mechanism by dislocation creep of calcite, which is dominant between 400 8C and 600 8C; these deformation temperatures are within the range determined earlier by Clerc et al. (2015), using RSCM (Raman Spectroscopy of Carbonaceous Material) geothermometry. As a consequence, we better describe the transition from ductile to brittle deformation in the prerift marbles and clarify the origin of the syn-rift breccias. Due to continuous exhumation along detachments' faults, the brecciated metamorphic carbonates of the prerift NPZ sedimentary cover were passively uplifted towards shallower levels and progressively unroofed, while transported passively on the back of the exhumed ultramafic footwall. These results are consistent with the recent interpretations of the North Pyrenean peridotites as remnants of subcontinental mantle rocks exhumed within the pre-Pyrenean rift system. We emphasize the importance of tectonic decoupling between the Mesozoic sedimentary cover and the Palaeozoic basement, which leads to the juxtaposition of metamorphosed and deformed Mesozoic Please cite this article in press as: Lagabrielle Y, et al. Very high geothermal gradient during mantle exhumation recorded in mylonitic marbles and carbonate breccias from a Mesozoic Pyrenean palaeomargin (Lherz area, North Pyrenean Zone, France). C. R. Geoscience (2016), http://dx.
ISSN: 1631-0713

Droits : http://creativecommons.org/licenses/by-nc-nd/
insu-01285079
https://hal-insu.archives-ouvertes.fr/insu-01285079
https://hal-insu.archives-ouvertes.fr/insu-01285079/document
https://hal-insu.archives-ouvertes.fr/insu-01285079/file/1-s2.0-S1631071315002060-main.pdf
DOI : 10.1016/j.crte.2015.11.004