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 : International audience
The Oisans Massif, located in the external zones of the western Alps, experienced significant shortening during the Alpine collision. While a series of major top-to-the west shear zones was recently described, the general low grade of the metamorphism has not attracted much petrological and geochronological studies. This paper provides combined temperature and age constraints on the evolution of the Oisans Massif. Temperature was estimated with the Raman Spectrometry of Carbonaceous Material (RSCM) method and chlorite geothermometry. Maximum temperature reached by the Mesozoic cover (Tmax) from Grenoble to the Galibier pass (E-W) and from Saint Jean de Maurienne to Embrun (N-S) yielded almost constant ca. 330 °C temperatures all through the Massif. Temperatures however strongly decrease either westward towards the top of the Vercors sedimentary sequence or eastward towards the Penninic Frontal Thrust. Age constraints were retrieved using 40Ar/39Ar in situ analyses performed on variously strained samples from Alpine shear zones. Over strain gradients, incipient Alpine recrystallizations progressively develop at the expense of former Variscan parageneses. A combined textural and EPMA approach permitted to identify newly formed chlorite and phengite that unequivocally grew in response to deformation or to low grade metamorphism. Chlorites recorded temperatures from ca. 350–150 °C during the activity of shear zones. In parallel, 40Ar/39Ar in situ experiments enabled dating deformation using both synkinematic phengites crystallized below the closure temperature of white-micas and former Variscan muscovite whose isotopic system have been, at least partially re-opened. Activity of top-to-the-west shear zones responsible for the shortening and thickening of the Oisans massif thus occurred between 34 and 33 and 25 Ma. Integrating these new age-constraints, Tmax estimates, and published geological data on the Oisans Massif and neighbouring areas allow proposing a new shortening scenario for the external zones. From ca. 34–33 Ma, the Oisans Massif was buried as a rigid block below more internal units and reached a temperature of ca. 330 °C. Shearing progressively localized along a series of top-to-the-W shear zones in the basement until 25 Ma. Deformation then localized along a major thrust at the base of the ECM massif and propagated along the basement-cover interface below the Vercors massif after 16 Ma.
ISSN: 0264-3707

Droits : info:eu-repo/semantics/OpenAccess
insu-01093878
https://hal-insu.archives-ouvertes.fr/insu-01093878
https://hal-insu.archives-ouvertes.fr/insu-01093878/document
https://hal-insu.archives-ouvertes.fr/insu-01093878/file/GEOD1326RA.pdf
DOI : 10.1016/j.jog.2014.09.004

Éditeur(s) : HAL CCSD
Résumé : Mon document "Titres et travaux" contient 5 articles au format éditeur.
Mes premiers travaux de recherche, me permettant de soutenir une thèse de doctorat en décembre 1999, ont été effectués au sein du laboratoire du professeur Bernard GRANDCHAMP (unité 409 de l'INSERM) sous la direction du docteur Marie-Christine LECOMTE. Mon travail s'est intégré dans l'étude fonctionnelle et structurale de certains domaines des spectrines érythroïdes et non érythroïdes, principalement le site de tétramérisation et le domaine SH3. Concernant la tétramérisation de la spectrine érythroïde j'ai identifié les régions minimales nécessaires et suffisantes pour former le tétramère puis j'ai mis en évidence une relation entre certaines mutations de la spectrine associées à des anomalies membranaires du globule rouge et la sévérité du défaut de formation du tétramère. J'ai ensuite identifié plusieurs ligands du domaine SH3 de la spectrine non érythroïde. L'un d'entre eux m'a permis de définir une régulation de la protéolyse ciblée de cette spectrine faisant intervenir un mécanisme de phosphorylation/déphosphorylation. Ma formation initiale fut donc celle d'un biochimiste que j'ai étendue peu à peu vers la biologie moléculaire et la biologie cellulaire.
Puis, souhaitant acquérir les connaissances nécessaires au développement de modèles murins, j'ai décidé d'effectuer mon stage post-doctoral à l'Institut COCHIN (unité 567 de l'INSERM) dans une équipe co-dirigée par le docteur Sophie VAULONT et le professeur Axel KAHN. Je me suis ainsi familiarisé avec la souris comme « outil » de recherche (gestion d'un élevage, établissement de nouvelles lignées, génotypage, phénotypage). Je travaillais initialement sur le métabolisme du glucose mais j'ai complètement réorienté ma thématique de recherche au bout d'un an pour finalement identifier et caractériser une hormone, l'hepcidine, contrôlant l'homéostasie du fer.
J'ai été nommé chargé de recherche de grade 2 dans l'unité 409 de l'INSERM en octobre 2002 pour y développer une souche de souris exprimant une spectrine non érythroïde résistante à des mécanismes de protéolyse ciblée. Il s'agit donc toujours d'appréhender certaines fonctions des spectrines mais dans un contexte in vivo. En janvier 2005 j'ai intégré l'unité 665 de l'INSERM dirigée par Yves COLIN afin de poursuivre ce projet. Aujourd'hui, je suis chargé de recherche de grade 1.
Le chapitre scientifique de ce mémoire est divisé en deux parties distinctes : la première traite de mon travail sur la spectrine tandis que la seconde porte sur l'hepcidine. Chaque partie est composée d'une introduction au sujet suivie d'un résumé des travaux que j'ai effectués et/ou dirigés.
https://tel.archives-ouvertes.fr/tel-00285035

Droits : info:eu-repo/semantics/OpenAccess
tel-00285035
https://tel.archives-ouvertes.fr/tel-00285035
https://tel.archives-ouvertes.fr/tel-00285035/document
https://tel.archives-ouvertes.fr/tel-00285035/file/HDR_Titre_et_travaux_-_Gael_Nicolas.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Mantle noble gases record important and ancient isotopic heterogeneities, which fundamentally influence our understanding of mantle geodynamics, yet these heterogeneities are difficult to fully interpret without understanding the basic mechanisms of noble gas storage and transport in mantle minerals. A series of annealing experiments that mimic mantle conditions (i.e. sub-solidus with natural, polycrystalline, texturally equilibrated olivines at low noble gas partial pressures) show that intergranular interfaces (grain boundaries) are major hosts for noble gases in the mantle, and that interfaces can dramatically fractionate noble gases from their radio-parents (U + Th and K). Therefore, noble gas isotopic heterogeneities in the mantle could result from grain size variations. Fine-grained lithologies (mylonites and ultramylonites, for example) with more grain boundaries will have lower U/3He ratios (compared to a coarse grained equivalent), which, over time, will preserve higher 3He/4He ratios. As predicted by theory of points defect diffusivity, these results show that noble gas diffusion along interfaces is different from those in the grain lattice itself at low temperatures. However, for grain size relevant of the Earth's mantle, the resulting effective correlated activation energies (Ea)(Ea) and pre-exponential factors (Do/a2)(Do/a2) produce similar diffusivities at mantle temperatures for interface- and lattice-hosted helium. Therefore, grain boundaries do not significantly affect helium transport at mantle conditions and length scales.
ISSN: 0012-821X

hal-01236013
https://hal.archives-ouvertes.fr/hal-01236013
DOI : 10.1016/j.epsl.2015.08.024

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy C - Option B
Résumé : International audience
We report the characterization of a DNA primase/ polymerase protein (PolpTN2) encoded by the pTN2 plasmid from Thermococcus nautilus. Sequence analysis revealed that this protein corresponds to a fusion between an N-terminal domain homologous to the small catalytic subunit PriS of heterodimeric archaeal and eukaryotic primases (AEP) and a C-terminal domain related to their large regulatory subunit PriL. This unique domain configuration is not found in other virus-and plasmid-encoded primases in which PriS-like domains are typically fused to different types of helicases. PolpTN2 exhibited primase, polymerase and nucleotidyl transferase activities and specifically incorporates dNTPs, to the exclusion of rNTPs. PolpTN2 could efficiently prime DNA synthesis by the T. nautilus PolB DNA polymerase, suggesting that it is used in vivo as a primase for pTN2 plasmid replication. The N-terminal PriS-like domain of PolpTN2 exhibited all activities of the full-length enzyme but was much less efficient in priming cellular DNA polymerases. Surprisingly, the N-terminal domain possesses reverse transcriptase activity. We speculate that this activity could reflect an ancestral function of AEP proteins in the transition from the RNA to the DNA world.
ISSN: 0305-1048

Droits : http://creativecommons.org/licenses/by/
hal-01332620
http://hal.upmc.fr/hal-01332620
http://hal.upmc.fr/hal-01332620/document
http://hal.upmc.fr/hal-01332620/file/Nucl.%20Acids%20Res.-2014-Gill-3707-19.pdf
DOI : 10.1093/nar/gkt1385

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In this contribution we present a reconstruction of the overall lithotectonic architecture, from inner zones to external ones, of the Paleoproterozoic Trans North China Orogen, within the North China Craton. Moreover, forward thermobarometrical modeling on a kyanite-bearing gneiss yields a reliable prograde P-T-t-D path. In addition, 40Ar/39Ar dating on rocks from distinct litho-tectonic units helps us to distinguish several tectono-metamorphic events during the orogenic development. Considering these results, we propose a geodynamic model involving three cratonic blocks, namely the Western, Fuping and Eastern Blocks, separated by two oceans, the Lüliang and Taihang Oceans. The opening of oceanic basins occurred around 2.2-2.3 Ga. After the westward subductions of oceanic lithosphere, the Trans-North-China Orogen was built up through a polyphase tectonic evolution within the period 1900-1800 Ma. The first event (D1) corresponded to the emplacement of lower and upper nappes herein called the Orthogneiss-and-Volcanites Unit (OVU) and the Low-Grade-and-Mafic Unit (LGMU), respectively. The syn-metamorphic D1 deformation (1880 ± 10 Ma) is characterized by a NW-SE stretching and mineral lineation with a top-to-the SE sense of shear. During ongoing compression of the thickening orogenic crust, a second deformation event D2 (1850 ± 10 Ma) was responsible for (1) syn-anatectic lateral flow and exhumation of the orogenic root and (2) folding of the middle and upper parts of the orogenic wedge that consequently acquired a fan-type geometry. The late D3 (1830 ± 10 Ma) and D4 (1810 ± 10 Ma) events are related to late-orogenic normal and strike-slip shearing, respectively. In our present state of knowledge, the Paleoproterozoic Trans-North China Orogen might be regarded as the assemblage of two continent-continent collisional belts, both of which are characterized by nappe stacking accommodated by top-to-the E/SE ductile shearing. Continental subduction, crustal thickening, partial melting of overthickened crust, exhumation of HP rocks and deposition of syn-orogenic detrital basins are typical features of modern collisional-type orogens.
ISSN: 0301-9268

Droits : info:eu-repo/semantics/OpenAccess
insu-00628119
https://hal-insu.archives-ouvertes.fr/insu-00628119
https://hal-insu.archives-ouvertes.fr/insu-00628119/document
https://hal-insu.archives-ouvertes.fr/insu-00628119/file/Trap-PrecambrianResearch-2011.pdf
DOI : 10.1016/j.precamres.2011.09.008

Éditeur(s) : HAL CCSD Springer/Terra Scientific Publishing Company
Résumé : International audience
The laboratory of paleomagnetism of Montpellier (France) has developed a new one-axis vibrating thermal magnetometer dedicated to the Study of physical properties of natural rocks remanence. Among its key characteristics, this apparatus allows both measurement or the magnetization moment on the interval from room temperature to 700 degrees C with a precision of 2 x 10(-9) A m(2) and acquisition of a total or a partial thermo-remanent magnetization using a steady field from - 100 up to 100 mu T. Another point that is worth noting is that one can apply a controlled atmosphere by means of argon flux to prevent oxidation of the studied sample during heating. We report here a technical description of this new instrument and review some specific applications in absolute paleointensity surveys.
ISSN: 1343-8832

hal-00413078
https://hal.archives-ouvertes.fr/hal-00413078
https://hal.archives-ouvertes.fr/hal-00413078/document
https://hal.archives-ouvertes.fr/hal-00413078/file/Poidras-CatVTM.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Mechanism and kinematics of the Late Mesozoic continental extension event of eastern Asia are still debated. In order to better constrain its evolution, two granodioritic plutons of the Jiaodong Peninsula have been chosen as targets for a time-constrained palaeomagnetic study. Indeed, plutons are devoid of visible deformation, did not experience rotation along horizontal axis and are precisely dated by U/Pb and 40Ar/39Ar methods. Multidomain (MD) magnetite has been identified as the principal magnetic remanent carrier. The interpolation of existing and new U/Pb and 40Ar/39Ar ages revealed that characteristic remanent magnetisation was acquired in a narrow range of 116 ± 2 Ma. Twenty out of 27 sites present stable magnetic directions calculated from high-temperature or high-coercive components. The observations of the solo normal magnetic polarity for this palaeomagnetic collection and of the magnetic remanent age consistent with the Cretaceous Normal Superchron (CNS) argue that the characteristic magnetic remanence may be considered as primary. Detailed field observations of the intrusive relationship between the plutons and country rocks and Anisotropy of Magnetic Susceptibility (AMS) study reveal the absence of the subsequent deformation of plutons, or rigid rotation of plutons along a horizontal axis. Two palaeomagnetic poles have been therefore calculated from these plutons. Among 12 out 15 Cretaceous palaeomagnetic poles, including the two new poles provided by this study, from the Jiaodong Peninsula and on both sides of Tan-Lu and Muping-Jimo faults are statistically consistent. As a result, the Jiaodong Peninsula behaved as a rigid block as internal deformation appears negligible. The remaining three derived poles are probably due to the secular variation or/and the vicinity of fault zones near of the palaeomagnetic sampling site. Thus, they can not be applied to the peninsula-scaled tectonics. Comparison of these time52 constrained Cretaceous palaeomagnetic results of the Jiaodong Peninsula with those of North China Block (NCB) indicate that the Jiaodong Peninsula was rigidly attached to NCB since, 3 at least, the Cretaceous as residual difference is clearly insignificant with respect to the error brackets. These new palaeomagnetic results confirm that the relative clockwise (CW) rotation of Eastern Liaoning-Korea Block (ELKB) with respect to NCB does not affect the Jiaodong Peninsula as a rigid block, nevertheless, some tectonic structures have been reactivated since Cenozoic and local rotations could be produced. This palaeomagnetic study reveals that the Late Mesozoic extension in Eastern Asia is heterogeneously expressed in time and space. The complete understanding of the mechanism(s) of this extensional event needs further multidisciplinary investigations.
ISSN: 0031-9201

insu-00599546
https://hal-insu.archives-ouvertes.fr/insu-00599546
https://hal-insu.archives-ouvertes.fr/insu-00599546/document
https://hal-insu.archives-ouvertes.fr/insu-00599546/file/Charles_et_al_PEPI2011.pdf
DOI : 10.1016/j.pepi.2011.05.006

Éditeur(s) : HAL CCSD American Geophysical Union (AGU)
Résumé : New structural, microstructural, and 40Ar/39Ar data from the NW Massif Central (France) provide additional constraints on the timing and tectonic setting of late Variscan granite magmatism. Previous studies had emphasized the role of late orogenic extension in the emplacement of granite plutons in the Limousin region. In contrast, the new data set is consistent with syntectonic emplacement of magma in a dextral simple shear active from 350 to 300 Ma in a transpressional regime. As an alternative hypothesis to late orogenic extension, we propose that magmas migrated into tensional bridges between active P shears associated with a lithospheric shear zone comparable to a pop-up structure. The Galician region, in the western end of the Ibero-Armorican tectonic arc, exhibits major left-lateral ductile shear zones which can be interpreted as conjugate structures to the Limousin and Armorican shear zones. Citation: Ge´belin, A., M. Brunel, P. Monie´, M. Faure, and N. Arnaud (2007), Transpressional tectonics and Carboniferous magmatism in the Limousin, Massif Central, France: Structural and 40Ar/39Ar investigations
ISSN: 0278-7407

hal-00104212
https://hal-insu.archives-ouvertes.fr/hal-00104212
https://hal-insu.archives-ouvertes.fr/hal-00104212/document
https://hal-insu.archives-ouvertes.fr/hal-00104212/file/2005TC001822.pdf
DOI : 10.1029/2005TC001822

Éditeur(s) : HAL CCSD Elsevier
Résumé : A Ar-40/Ar-39 geochronological study was performed on amphibole and biotite from some representative units of distinct tectonic domains of the southeastern Guiana Shield, north of the Amazonian Craton, the Amapa Block and the Carecuru Domain. In the AmapA Block, an Archean continental block involved in the Transamazonian orogenesis (2.26-1.95 Ga), the investigated minerals, from rocks of the Archean high-grade basement assemblage, give only Paleoproterozoic ages, indicating their complete resetting during the Transamazonian orogenic event. Amphibole ages vary from 2087 +/- 3 to 2047 +/- 20 Ma, and biotite ages spread mainly between 2079 +/- 18 and 2033 +/- 13 Ma. In the Carecuru Domain, in which the geodynamic evolution is related to Paleoproterozoic magmatic arc setting during the Transamazonian event, calc-alkaline granitoids yield amphibole age of 2074 +/- 17 Ma, and biotite ages of 1928 +/- 19 Ma and 1833 +/- 13 Ma. These data reinforce the importance of the Transamazonian orogenic cycle in the investigated area, and indicate that the rocks were not significantly affected by post-Transamazonian events. When coupled with available U-Th-Pb monazite and Pb-Pb zircon geochronological records and petro-structural observations, the new Ar-40/Ar-39 data delineate contrasting cooling and exhumation histories for the tectonic domains. In the AmapA Block, the data suggest nearly vertical T-t paths that reflect fast cooling rates, which indicate tectonically controlled exhumation, related to collisional stages of the Transamazonian event, between 2.10 and 2.08 Ga. Conversely, in the Carecuru Domain, low cooling rates suggest that the arc-related granitoids underwent slow and monotonous cooling since their emplacement until reaching the biotite isotopic closure temperature.
ISSN: 0895-9811

hal-00420075
https://hal.archives-ouvertes.fr/hal-00420075
DOI : 10.1016/j.jsames.2008.08.010

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Located on the margin of the west Alboran basin, the Gibraltar Arc (Betic-Rif mountain belt) displays post-Pliocene vertical movements evidenced by uplifted marine sedimentary basins and marine terraces. Quantification of vertical movements is an important clue to understand the origin of present-day relief generation in the Betic-Rif mountain chain together with the causes of the Messinian Salinity Crisis. In this paper, we present the results of a pluridisciplinary study combining an analysis of low temperature thermochronology and Pliocene basins evolution to constrain the exhumation history and surface uplift of internals units of the Rif belt (Northern Morocco). The mean (U-Th)/He apatite ages obtained from 11 samples are comprised between 14.1 and 17.8 Ma and display a wide dispersion, which could be explained by a great variability of apatite chemistries in the analyzed samples. No correlations between altitude and age have been found along altitudinal profile suggesting a rapid exhumation during this period. Thermal modeling using our (U-Th)/He apatite ages and geochronological data previously obtained in the same area (40Ar/39Ar and K/Ar data on biotite, zircon and apatite fission track) allow us to propose a cooling history. The rocks suffered a rapid cooling at 60-100 °C/Ma between 22.5 and 19 Ma, then cooled to temperatures around 40 °C between 19 and 18 Ma. They were re-heated at around 110 °C between 18 and 15 Ma then rapidly cooled and exhumed to reach the surface temperature at around 13 Ma. The re-heating could be related to a renewal in thrusting and burying of the inner zones. Between 15 and 13 Ma the cooling resumed at a rate of 50 °C/Ma indicating an exhumation rate of 0.8 mm/y considering an average 40 °C/km geothermal gradient. This exhumation may be linked to the extension in the Alboran Sea. Otherwise biostratigraphic and sedimentological analysis of Pliocene basins of the internal Rif provided informations on the more recent events and vertical movements. Pliocene deposits of the Rifian coast represent the passive infilling of palaeo-rias between 5.33 and 3.8 Ma. The whole coastal area was uplifted at slow average rates (0.01-0.03 mm/y) in relation with a northeastward tilting of 0.2-0.3° since the Lower-Pliocene. A late Pliocene to present extensional tectonics associated to uplift has been identified all along the coastal ranges of the Internal Zone of the Rif chain. This extension was coeval with the major late Pliocene to Pleistocene extensional episode of the Alboran Sea and appears to be still active nowadays. No significant late Messinian uplift was evidenced, thus calling into question the geodynamic models relating the closure of the marine gateways and the MSC to slab roll back.
ISSN: 0264-3707

hal-01053531
https://hal.archives-ouvertes.fr/hal-01053531
DOI : 10.1016/j.jog.2014.01.006

Éditeur(s) : HAL CCSD
Résumé : International audience
Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
ISSN: 2168-6211

hal-01258705
http://hal.univ-brest.fr/hal-01258705
PUBMED : 25621457
DOI : 10.1001/jamapediatrics.2014.3351

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
ISSN: 1098-3600

hal-01134364
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134364
DOI : 10.1038/gim.2015.29
PUBMED : 25790162

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
Type IB DNA topoisomerases can eliminate torsional stresses produced during replication and transcription. These enzymes are found in all eukaryotes and a short version is present in some bacteria and viruses. Among prokaryotes, the long eukaryotic version is only observed in archaea of the phylum Thau-marchaeota. However, the activities and the roles of these topoisomerases have remained an open question. Here, we demonstrate that all available thaumar-chaeal genomes contain a topoisomerase IB gene that defines a monophyletic group closely related to the eukaryotic enzymes. We show that the topIB gene is expressed in the model thaumarchaeon Ni-trososphaera viennensis and we purified the recom-binant enzyme from the uncultivated thaumarchaeon Candidatus Caldiarchaeum subterraneum. This enzyme is active in vitro at high temperature, making it the first thermophilic topoisomerase IB characterized so far. We have compared this archaeal type IB enzyme to its human mitochondrial and nuclear counterparts. The archaeal enzyme relaxes both negatively and positively supercoiled DNA like the eukaryotic enzymes. However, its pattern of DNA cleavage specificity is different and it is resistant to camptothecins (CPTs) and non-CPT Top1 inhibitors, LMP744 and lamellarin D. This newly described ther-mostable topoisomerases IB should be a promising new model for evolutionary, mechanistic and structural studies.
ISSN: 0305-1048

Droits : http://creativecommons.org/licenses/by/
hal-01327354
http://hal.upmc.fr/hal-01327354
http://hal.upmc.fr/hal-01327354/document
http://hal.upmc.fr/hal-01327354/file/Nucl.%20Acids%20Res.-2016-Dahmane-2795-805.pdf
DOI : 10.1093/nar/gkw097

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : Key message Molecular markers were used for paternity recovery in a maritime pine (Pinus pinasterAit.) polycross trial, facilitating forward selection. Different breeding strategies for seed orchard establishment were evaluated by comparing genetic gains and diversity. This work opens up new perspectives in maritime pine breeding.Context Polycross mating designs are widely used in forest tree breeding to evaluate parental breeding values for backward selection. Alternatively, polycross progeny trials may be used to select the best trees on the basis of individual breeding values and molecular pedigree analysis.Aims This study aimed to test such a forward selection strategy for the maritime pine breeding program.Methods In a maritime pine polycross trial, progeny with higher breeding values for growth and stem straightness was first preselected with or without relatedness constraints. After paternity recovery, the preselected trees were ranked on the basis of their breeding values, estimated from the recovered full pedigree. Finally, the best candidates were selected with three different strategies (forward, backward, mixed) and three levels of coancestry constraints to establish a virtual clonal seed orchard.Results Complete pedigrees were successfully recovered for most of the preselected trees. There was no major difference in expected genetic gains between the two preselection strategies which differed for relatedness constraints. Genetic gains were slightly higher for forward selection than for classical backward selection.Conclusion This seminal study opens up new perspectives for using forward selection within the French maritime pine breeding program.
ISSN: 1932-6203

hal-01601804
https://hal.archives-ouvertes.fr/hal-01601804
DOI : 10.1371/journal.pone.0049990
PRODINRA : 391860

Éditeur(s) : HAL CCSD IOP Publishing
Résumé : The Bureau International des Poids et Mesures (BIPM), Sevres, France, hosted the 7th International Comparison of Absolute Gravimeters (ICAG) and the associated Relative Gravity Campaign (RGC) from August to September 2005.;ICAG 2005 was prepared and performed as a metrological pilot study, which aimed:;(1) To determine the gravity comparison reference values;;(2) To determine the offsets of the absolute gravimeters; and;(3) As a pilot study to accumulate experience for the CIPM Key Comparisons.;This document presents a complete and extensive review of the technical protocol and data processing procedures. The 1st ICAG-RGC comparison was held at the BIPM in 1980-1981 and since then meetings have been organized every 4 years.;In this paper, we present an overview of how the meeting was organized, the conditions of BIPM gravimetric sites, technical specifications, data processing strategy and an analysis of the final results. This 7th ICAG final report supersedes all previously published reports.;Readings were obtained from participating instruments, 19 absolute gravimeters and 15 relative gravimeters. Precise levelling measurements were carried out and all measurements were performed on the BIPM micro-gravity network which was specifically designed for the comparison.
ISSN: 0026-1394

hal-00644529
https://hal.archives-ouvertes.fr/hal-00644529
DOI : 10.1088/0026-1394/48/5/003

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
: Context:Masculinization depends on the fetal testis. Exposure of the human fetus during pregnancy to paracetamol or/and to other mild-analgesics is associated with an increased risk of cryptorchidism.Objective:We aimed at determining whether mild analgesics disrupted the morphology and endocrine function of the human testis.Design:We used an in vitro system based on the culture of human fetal testes exposed or not to paracetamol, its metabolite AM404, aspirin, indomethacin, ketoconazole at 10(-4) M to 10(-7) M.Setting:The study was conducted at the University of Rennes I.Patients/Participants:Human fetal testes were from pregnant women following induced abortion, between 7 and 12 weeks of gestation (GW).Main Outcome Measures:Testosterone (radioimmunoassay: RIA), Anti-Müllerian Hormone (AMH; ELISA), insulin-like factor 3 (INSL3; RIA), prostaglandin D2 and E2 (PGD2 and PGE2, respectively; ELISA), were assayed in the media. Testicular cells were counted using histology and image analysis. The possible nuclear receptor-mediated activities of the analgesics were investigated using reporter cell lines expressing estrogen (ERs), androgen (AR) and peroxysome proliferator-activated γ ( PPARγ) receptors.Results:Indomethacin and aspirin stimulated testosterone production, particularly by the younger testes (8-9 GW vs 10-12 GW). Paracetamol, AM404 and ketoconazole decreased INSL3 levels. Aspirin stimulated, whereas ketoconazole inhibited AMH production. PGE2 levels were inhibited by paracetamol, and aspirin in the 7-12 GW testes, and by indomethacin but only in 7-9.86 GW old testes. The inhibitory trends seen for PGD2 were not statistically significant.Conclusions:Analgesics at concentrations relevant to human exposure cause endocrine disturbances in the fetal testis. We suggest that the fetal human testis displays slight critical age windows for sensitivity to direct exposure to aspirin, indomethacin and paracetamol. The analgesic-induced inhibition of INSL3 may be the mechanism by which analgesics increase the risk of cryptorchidism. Greater caution is required concerning consumption of analgesics during pregnancy.
ISSN: 0021-972X

inserm-00876125
http://www.hal.inserm.fr/inserm-00876125
DOI : 10.1210/jc.2013-2531
PUBMED : 24030937

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase C gamma 1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway could be an attractive therapeutic approach for SLE treatment.
ISSN: 1074-7613

hal-01359568
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359568
DOI : 10.1016/j.immuni.2016.06.028
PUBMED : 27438772