Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Purpose: Marine mangrove sediments in the Manche-à-Eau lagoon (Guadeloupe, Caribbean Sea) harbor locally extensive, white microbial mats. These mats cover the surface of reduced sediments near the roots of red mangrove trees, Rhizophora mangle, and are mainly composed of sulfur-oxidizing bacteria belonging to the Beggiatoaceae family, with some filamentous cyanobacteria. The goal of this study was to investigatethe possible influence of sediment characteristics on the presence of these microbial mats. Materials and methods: Four push cores were collected in April 2013, two from zones with microbial mats and two from zones without mats. Sediment characteristics (grain-size distribution, mineralogy, total organic carbon (TOC) and total nitrogen (TN) contents, atomic TOC/TN ratios, and organic matter (OM) δ13C values) were compared for all four cores.Results and discussion: Significant differences were observed between sediments below microbial mats and those without mats. Sediments with microbial mats contained greater amounts of clay, and higher TOC, TN, and TOC/TN ratios, with lower total carbonate content andδ13C values. The higher clay content most likely results from lower fluid flow velocity near to mangrove roots, while higher TOC/TN ratiosand lower δ13C values indicate higher inputs of OM from mangrove trees. These results are consistent with the fact that microbial mats were observed near the roots of mangrove trees, which trap OM from terrestrial vegetation and fine sediments.Conclusions: The grain-size distribution of sediment particles, the total carbonate content, and the δ13C values are the main parameters discriminating between zones with microbial mats and those without mats. Variations in total carbonate content, which is mainly of biogenic origin, result from conditions that are more favorable for benthic organisms in zones without microbial mats. Variations of the TOC/TN ratios are controlled by the presence of a non-negligible amount of inorganic nitrogen bound to surface clay mineral particles and/or by microbial processes.
ISSN: 1439-0108

hal-01682110
https://hal.univ-antilles.fr/hal-01682110
DOI : 10.1007/s11368-016-1555-6

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
ISSN: 0001-6322

hal-00875723
https://hal.archives-ouvertes.fr/hal-00875723
DOI : 10.1007/s00401-013-1084-y
PUBMED : 23400299

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
: We investigated the in vitro effects of four alkyl-galactofuranoside derivatives, i.e. octyl-β-D-galactofuranoside (1), 6-amino-β-D-galactofuranoside (2), 6-N-acetamido-β-D-galactofuranoside (3), and 6-azido-β-D-galactofuranoside (4) on Leishmania donovani. Their mechanism of action was explored using electron paramagnetic resonance spectroscopy (EPR) and nuclear magnetic resonance (NMR), and ultrastructural alterations by transmission electron microscopy (TEM). Compound 1 showed the most promising effects by inhibiting promastigote growth at IC50 8.96 ± 2.5 μM. All compounds exhibit low toxicity towards human macrophages. Compound 1 had a higher selectivity index than the comparative molecule used, i.e. miltefosine (159.7 versus 37.9, respectively). EPR showed that compound 1 significantly reduced membrane fluidity, compared to control promastigotes and to compound 3. The furanose ring was shown to support this effect since the isomer galactopyranose had no effect on parasite membrane fluidity or growth. NMR showed a direct interaction of all compounds (1>2>3>4) with the promastigote membrane, as well as with octyl-galactopyranose and octanol, providing evidence that the n-octyl chain was primarily involved in the anchoring with the parasite membrane, followed by the putative crucial role of furanose ring in the anti-leishmanial activity. A morphologic analysis of compound 1-treated promastigotes by TEM revealed profound alterations on parasite membrane and organelles, but not with compound 3. Quantification of annexinV binding by flow cytometry confirmed that compound 1 induced apoptosis in >90% promastigotes. The effect of compound 1 was also assessed on intra-macrophagic amastigotes, and showed a reduction in amastigote growth associated with an increase of ROS production, thus validating its promising effect.
ISSN: 0066-4804

hal-00941772
https://hal.archives-ouvertes.fr/hal-00941772
PUBMED : 24468785
DOI : 10.1128/AAC.01350-13

Éditeur(s) : HAL CCSD Humana Press
Résumé : International audience
The sodium-proton exchanger 1 (NHE-1) is a membrane transporter that exchanges Na(+) for H(+) ion across the membrane of eukaryotic cells. It is cooperatively activated by intracellular protons, and this allosteric regulation is modulated by the biophysical properties of the plasma membrane and related lipid environment. Consequently, NHE-1 is a mechanosensitive transporter that responds to osmotic pressure, and changes in membrane composition. The purpose of this study was to develop the relationship between membrane surface tension, and the allosteric balance of a mechanosensitive transporter such as NHE-1. In eukaryotes, the asymmetric composition of membrane leaflets results in a difference in surface tensions that is involved in the creation of a reservoir of intracellular vesicles and membrane buds contributing to buffer mechanical constraints. Therefore, we took this phenomenon into account in this study and developed a set of relations between the mean surface tension, membrane asymmetry, fluid phase endocytosis and the allosteric equilibrium constant of the transporter. We then used the experimental data published on the effects of osmotic pressure and membrane modification on the NHE-1 allosteric constant to fit these equations. We show here that NHE-1 mechanosensitivity is more based on its high sensitivity towards the asymmetry between the bilayer leaflets compared to mean global membrane tension. This compliance to membrane asymmetry is physiologically relevant as with their slower transport rates than ion channels, transporters cannot respond as high pressure-high conductance fast-gating emergency valves.
ISSN: 1085-9195

inserm-00871709
http://www.hal.inserm.fr/inserm-00871709
http://www.hal.inserm.fr/inserm-00871709/document
http://www.hal.inserm.fr/inserm-00871709/file/art_3A10.1007_2Fs12013-012-9340-7.pdf
DOI : 10.1007/s12013-012-9340-7

Éditeur(s) : HAL CCSD Wiley-VCH Verlag
Résumé : International audience
Deciphering the assembly history of the Milky Way is a formidable task, which becomes possible only if one can produce high-resolution chrono-chemo-kinematical maps of the Galaxy. Data from large-scale astrometric and spectroscopic surveys will soon provide us with a well-defined view of the current chemo-kinematical structure of the Milky Way, but will only enable a blurred view on the temporal sequence that led to the present-day Galaxy. As demonstrated by the (ongoing) exploitation of data from the pioneering photometric missions CoRoT, Kepler, and K2, asteroseismology provides the way forward: solar-like oscillating giants are excellent evolutionary clocks thanks to the availability of seismic constraints on their mass and to the tight age-initial-mass relation they adhere to. In this paper we identify five key outstanding questions relating to the formation and evolution of the Milky Way that will need precise and accurate ages for large samples of stars to be addressed, and we identify the requirements in terms of number of targets and the precision on the stellar properties that are needed to tackle such questions. By quantifying the asteroseismic yields expected from PLATO for red-giant stars, we demonstrate that these requirements are within the capabilities of the current instrument design, provided that observations are sufficiently long to identify the evolutionary state and allow robust and precise determination of acoustic-mode frequencies. This will allow us to harvest data of sufficient quality to reach a 10% precision in age. This is a fundamental pre-requisite to then reach the more ambitious goal of a similar level of accuracy, which will only be possible if we have to hand a careful appraisal of systematic uncertainties on age deriving from our limited understanding of stellar physics, a goal which conveniently falls within the main aims of PLATO's core science.
ISSN: 0004-6337

hal-01541393
https://hal.archives-ouvertes.fr/hal-01541393
ARXIV : 1706.3778
BIBCODE : 2017AN....338..644M
DOI : 10.1002/asna.201713385

Éditeur(s) : HAL CCSD Inter Research
Résumé : International audience
The main objective of the VULSACO (VULnerability of SAndy COasts to climate change and anthropic pressure) project was to investigate present day and potential future vulnerability of sandy coasts at the 2030 horizon, i.e. on a time scale related to climate variability. The method, based on a multidisciplinary approach bringing together geologists, geographers, physicists, social psychologists, engineers and stakeholders, was structured around 4 axes: field data analysis; numerical modelling; analysis of governance and stakeholder perceptions; and development of vulnerability indexes. This approach was designed to investigate vulnerability at a local scale and was applied to 4 contrasting beaches located in France: Sète Lido (Mediterranean Sea), Truc Vert and La Tresson beaches (Atlantic Ocean), and Dewulf (English Channel). The results focus on decadal and multi-annual beach trends at the Truc Vert beach site. There is almost no trend in beach volume at Truc Vert beach, although there is a variation in this parameter on a cycle of 2 to 3 yr, with variations related to wave energy and probably to indexes of climate variability. Numerical modelling identified the sensitivity of beach responses to changes in wave height and direction, especially in terms of subtidal morphology and the potential development of shoreline instability. Together with the observed offshore wave angle at the Biscay Buoy, these model results suggest that a potential change in wave angle due to climate variability could significantly modify the bars' morphology. The combination of data analysis and numerical modelling contributed to the development of vulnerability indexes designed for sandy coasts, which take into account climate-dependant variables such as waves. This allowed the differentiation of the sites in terms of vulnerability to erosion: Sète Lido and Truc Vert beach were the most and least vulnerable sites, respectively. These indexes help in identifying the dominant components of beach vulnerability, and provide potential for the study of how anthropogenic factors affect vulnerability. The study of stakeholder perceptions and decision-making with regard to climate-related risk also highlighted potential anthropogenic effects on beach vulnerability, and identified possible site-specific outcomes.
ISSN: 0936-577X

hal-00843946
https://hal-brgm.archives-ouvertes.fr/hal-00843946
DOI : 10.3354/cr01153

Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Revue Des Maladies Respiratoires

hal-01647076
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647076
DOI : 10.1016/j.rmr.2017.07.022
PUBMED : 28935495

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
We provide new constraints on the modes of mantle exhumation and denudation in the pre-orogenic Pyrenees by investigating the poorly known peridotites located east of the Lherz body, in eastern Ariè ge (Vicdessos, Urs, Bestiac, Caussou and Prades main peridotitic bodies). We show that: (1) numerous peridotite bodies, not described so far, are constituted by decametric to sub-metric outcrops scattered between and around the main outcrops identified by Monchoux (1970); (2) most of the peridotites form blocks and lenses of various sizes, from millimetric monocrystalline grains to hectometric olistoliths, embedded in debris flows involving mainly Mesozoic metasediments; these peridotites can therefore be linked to the S-type peridotites of Lagabrielle et al. (2010), and share similarities with the peridotites of Lherz region (Clerc et al., 2012). All originated from tectono-sedimentary processes associated with mantle exhumation in relation with extreme thinning and breakoff of the continental basement; (3) the various petrographic characters of these peridotites and their heterogeneity in serpentinisation degree imply a peculiar mode of exhumation, which merges mantle fragments inherited from different structural levels; (4) the lack of tectonic structures such as faults and shear planes associated with the ultramafic-rich breccia formation and the presence of neoformation of metamorphic minerals within the matrix preclude their origin as cataclasites related to the Latest Cretaceous and Tertiary Pyrenean contractional deformation. The peridotites of eastern Ariè ge are indisputable witnesses of the presence of an inverted hyper-extended Cretaceous passive margin forming the current North Pyrenean zone. The geometry of the extensional system was complex and probably associated with strike-slip faults and transcurrent motion. ß 2016 The Authors. Published by Elsevier Masson SAS on behalf of Acadé mie des sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
ISSN: 1631-0713

Droits : http://creativecommons.org/licenses/by-nc-nd/
insu-01280502
https://hal-insu.archives-ouvertes.fr/insu-01280502
https://hal-insu.archives-ouvertes.fr/insu-01280502/document
https://hal-insu.archives-ouvertes.fr/insu-01280502/file/1-s2.0-S1631071316000043-main.pdf
DOI : 10.1016/j.crte.2015.12.003

Éditeur(s) : HAL CCSD springer Link
Résumé : International audience
Experimental Astronomy

hal-01094521
https://hal.archives-ouvertes.fr/hal-01094521
BIBCODE : 2014ExA...tmp...41R
DOI : 10.1007/s10686-014-9383-4
ARXIV : 1310.0696

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 Springer Verlag
Résumé : International audience
Selected high-resolution seismic-reflection profiles and multibeam bathymetry acquired along the convergent Ecuador margin during the ATACAMES cruise on onboard the R/V L’Atalante (Jan.15–Feb.18, 2012) allow a preliminary evaluation of the neotectonic development and stratigraphic evolution of the margin based on the sismo-stratigraphic analysis of Quaternary sediment preserved on the margin shelf and upper slope. We present three major preliminary results. (1) The evolution of the Esmeraldas, Guayaquil and Santa Elena canyons. The head of the Esmeraldas canyon is the location of a continuous significant sediment transport. The Guayaquil canyon shows several episodes of deposition and incision. Aggrading sedimentation pattern in the canyon records several changes in relative sea-level. The subsidence of the Gulf of Guayaquil probably contributes to the good preservation of the canyon filling stages. The Santa Elena canyon is controlled by a SW–NE trending normal fault. (2) Variations of sediment accumulation and relative vertical motions are shown along-strike the shelf edge. Offshore the uplifted Manta peninsula, a pronounced subsidence of the shelf edge is documented by sedimentary clinoforms that have deposited in a morphological reentrant, and have migrated upslope testifying of a local subsidence meanwhile the adjacent La Plata Island area underwent uplift. In the Esmeraldas canyon area, a local uplift of the shelf is documented. (3) Two neotectonic fault systems with a possible transcurrent component are imaged across the shelf edge and upper margin slope offshore Jama, and Cape Galera. This possible transcurrent motion could be related to the reactivation of ancient faults of the upper plate by the subduction. These preliminary results indicate that the ATACAMES data set has a strong potential to evaluate the spatial and temporal contribution of tectonic and climate changes on the structural development and stratigraphic evolution of the Ecuador continental margin.
ISSN: 0025-3235

insu-01131151
https://hal-insu.archives-ouvertes.fr/insu-01131151
DOI : 10.1007/s11001-014-9231-y

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Polarization dependence second harmonic generation (P-SHG) microscopy is gaining increase popularity for in situ quantification of fibrillar protein architectures. In this report, we combine P-SHG microscopy, new linear least square (LLS) fitting and modeling to determine and convert the complex second-order non-linear optical anisotropy parameter ρ of several collagen rich tissues into a simple geometric organization of collagen fibrils. Modeling integrates a priori knowledge of polyhelical organization of collagen molecule polymers forming fibrils and bundles of fibrils as well as Poisson photonic shot noise of the detection system. The results, which accurately predict the known sub-microscopic hierarchical organization of collagen fibrils in several tissues, suggest that they can be subdivided into three classes according to their microscopic and macroscopic hierarchical organization of collagen fibrils. They also show, for the first time to our knowledge, intrahepatic spatial discrimination between genuine fibrotic and non-fibrotic vessels. CCl 4-treated livers are characterized by an increase in the percentage of fibrotic vessels and their remodeling involves peri-portal compaction and alignment of collagen fibrils that should contribute to portal hypertension. This integrated P-SHG image analysis method is a powerful tool that should open new avenue for the determination of pathophysiological and chemo-mechanical cues impacting collagen fibrils organization.
ISSN: 2045-2322

hal-01592192
https://hal.archives-ouvertes.fr/hal-01592192
https://hal.archives-ouvertes.fr/hal-01592192/document
https://hal.archives-ouvertes.fr/hal-01592192/file/s41598-017-12398-0.pdf
DOI : 10.1038/s41598-017-12398-0

Éditeur(s) : HAL CCSD
Résumé : National audience
Expositions environnementales et santé : évaluations, attentes et incertitudes. Applications à la présence des pesticides dans l’environnement et à la pollution de l’air urbain
Lyon, France

hal-01283641
https://hal.archives-ouvertes.fr/hal-01283641

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
ISSN: 1058-4838

hal-01118447
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118447
PUBMED : 25139963
DOI : 10.1093/cid/ciu659

Éditeur(s) : HAL CCSD
Résumé : National audience
Le littoral, caractérisé par une grande diversitéd’environnements (plages sableuses ou rocheuses, cordonsdunaires, falaises, lagunes, estuaires...) est une zone très mobile etévolutive du fait de forçages hydrodynamiques et météorologiquessouvent intenses. Cet environnement est fragile, car soumis àl’impact d’activités humaines qui ne cessent d’augmenter (urbanisation,aménagements...), mais aussi aux effets du changementclimatique (élévation du niveau de la mer, modification durégime de houles, inondations). Comprendre le fonctionnementhydromorpho-sédimentaire des environnements littoraux est crucialpour prédire leur évolution et celle des écosystèmes associés.Le Service National d’Observation labellisé par le CNRS, (SNO)DYNALIT, - Dynamique du Littoral et du Trait de Côte a pourbut de constituer une base de données hydromorphologiques sur lelong terme de 29 sites ateliers représentatifs des environnementslittoraux français (côtes sableuses, falaises et embouchures) afin :- De mesurer la cinématique de ces environnements et du trait decôte associé ;- De mieux comprendre les interactions entre les processushydrodynamiques-transport sédimentaires-réponse morphologiqueassociés à la dynamique du littoral ;- Utiliser les observations pour améliorer notre connaissance desréponses de la morphologie des littoraux dans différents contextesde forçages météo-marins ;- D’utiliser ces observations pour analyser l’importance relativedes facteurs anthropiques et naturels sur la dynamique littorale ;- De se positionner en interlocuteur pour les responsables de ladéfinition et la mise en oeuvre des politiques de gestion des risqueslittoraux.
RST 2016, livre des résumés
Caen, France

insu-01387873
https://hal-insu.archives-ouvertes.fr/insu-01387873

Éditeur(s) : HAL CCSD Taylor & Francis Open
Résumé : International audience
Our recent findings indicate that cells exposed to transmembrane (m-CD95L) or metalloprotease-cleaved CD95L (cl-CD95L) undergo a localized Ca(2+)entry that not only inhibits the initial steps of the CD95-mediated apoptotic signal but also promotes cell motility. Based on recent findings published on the non-apoptotic signals induced by CD95, we discuss how m-CD95L and cl-CD95L diverging by their stoichiometry could both contribute to the immune response by first recruiting activated T lymphocytes in the inflamed area and later by eliminating infected and transformed cells.
ISSN: 1942-0889

hal-00873761
https://hal.archives-ouvertes.fr/hal-00873761
https://hal.archives-ouvertes.fr/hal-00873761/document
https://hal.archives-ouvertes.fr/hal-00873761/file/The_CD95_signaling_pathway-accepted.pdf
DOI : 10.4161/cib.18888

Éditeur(s) : HAL CCSD Karger
Résumé : International audience
Cell Physiol Biochem
Tübingen, Germany

hal-01122597
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122597
DOI : 10.1159/000335868

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The etiology of congenital heart defect (CHD) combines environmental and genetic factors. So far, there were studies reporting on the screening of a single gene on unselected CHD or on familial cases selected for specific CHD types. Our goal was to systematically screen a proband of familial cases of CHD on a set of genetic tests to evaluate the prevalence of disease-causing variant identification. A systematic screening of GATA4, NKX2-5, ZIC3 and Multiplex ligation-dependent probe amplification (MLPA) P311 Kit was setup on the proband of 154 families with at least two cases of non-syndromic CHD. Additionally, ELN screening was performed on families with supravalvular arterial stenosis. Twenty-two variants were found, but segregation analysis confirmed unambiguously the causality of 16 variants: GATA4 (1 x), NKX2-5 (6 x), ZIC3 (3 x), MLPA (2 x) and ELN (4 x). Therefore, this approach was able to identify the causal variant in 10.4% of familial CHD cases. This study demonstrated the existence of a de novo variant even in familial CHD cases and the impact of CHD variants on adult cardiac condition even in the absence of CHD. This study showed that the systematic screening of genetic factors is useful in familial CHD cases with up to 10.4% elucidated cases. When successful, it drastically improved genetic counseling by discovering unaffected variant carriers who are at risk of transmitting their variant and are also exposed to develop cardiac complications during adulthood thus prompting long-term cardiac follow-up. This study provides an important baseline at dawning of the next-generation sequencing era.
ISSN: 1018-4813

hal-01404211
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01404211
DOI : 10.1038/ejhg.2015.105
PUBMED : 26014430

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) : HAL CCSD
Résumé : National audience
The Lesser Antilles subduction zone has produced no recent strong thrust earthquakes, making it difficult to quantify the seismic hazard from such events. The Lesser Antilles arc has a low subduction rate and an accretionary wedge that is very wide at its southern end. To investigate the effect of the wedge on seismogenesis, numerical models of forearc thermal structure were constructed along six transects perpendicular to the arc in order to determine the thermally predicted width of the seismogenic zone. The geometry of each section is constrained by published seismic profiles and crustal models derived from gravity and seismic data and by earthquake hypocenters at depth. A major constraint on the deep part of the model is that mantle temperature beneath the volcanic arc should achieve a temperature of 1,100°C to generate partial melts. Predicted surface heat flow is compared to the available heat flow observations. Thermal modeling results indicate a systematic southward increase in the width of the seismogenic zone, more than doubling in width from north to south and corresponding to a dramatic southward increase in forearc width (distance from the arc to the deformation front of the accretionary wedge). The minimum width of the seismogenic zone (distance between the intersections of the subduction interface with the 150°C and 350°C isotherms) increases from about 80 km, north of 16°N, to 230 km, at 13°N. The maximum width (between the 100°C and 450°C isotherms) ranges from about 150 km in the north to up to 320 km in the south. This large variation in the width of the seismogenic zone is a consequence of the increasing width of the accretionary wedge to the south, caused by the increased thickness of sediment on the subducting plate. There is good agreement between the thermally predicted seismogenic limits and the sparse distribution of recorded thrust earthquakes, which are observed only in the northern portion of the arc. Possible scenarios for mega-thrust earthquakes are discussed. Depending on the segment length (along-strike) of the rupture plane, the occurrence of an event of magnitude 8-9 cannot be excluded.
Bulletin Société Géologique de France

insu-00814056
https://hal-insu.archives-ouvertes.fr/insu-00814056
DOI : 10.2113/gssgfbull.184.1-2.47