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

hal-01647782
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647782
DOI : 10.1016/j.rmr.2017.07.017
PUBMED : 28939155

Éditeur(s) : HAL CCSD
Résumé : National audience
Des expériences dans un bassin de 30 m x 30 m ont été réalisées dans l'objectif de caractériser la dynamique d'un courant d'arrachement et les évolutions morphologiques associées. La plage de sable fin (diamètre médian 166 microns) couvrait la largeur du bassin (30 m en longshore ) pour un profil total de 20 m cross-shore . La formation de courants sagittaux a été forcée par une houle frontale (spectre de Jonswap) avec un déficit d'énergie au centre du bassin. Une séquence accrétive complète de plage intermédiaire à simple barre (selon classification de WRIGHT & SHORT, 1984) a été reproduite. La barre s'est progressivement tridimensionnalisée en forme de croissant puis s'est connectée au haut de plage avec la présence de deux chenaux profonds qui se sont ensuite comblés pour obtenir une plage à terrasse au bout de plusieurs dizaines d'heures. L'association des mesures hydrodynamiques et morphodynamiques montre que le comblement des chenaux est alimenté par le haut de plage.
XI èmes Journées Nationales Génie Côtier - Génie Civil
Sables d'Olonne, France

hal-00861953
https://hal.archives-ouvertes.fr/hal-00861953

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 Nature Publishing Group
Résumé : International audience
CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic disorder leading to the development of skin appendage tumours. It encodes a deubiquitinating enzyme that removes Lys63- or linear-linked ubiquitin chains. CYLD was shown to regulate cell proliferation, cell survival and inflammatory responses, through various signalling pathways. Here we show that CYLD localizes at centrosomes and basal bodies via interaction with the centrosomal protein CAP350 and demonstrate that CYLD must be both at the centrosome and catalytically active to promote ciliogenesis independently of NF-κB. In transgenic mice engineered to mimic the smallest truncation found in cylindromatosis patients, CYLD interaction with CAP350 is lost disrupting CYLD centrosome localization, which results in cilia formation defects due to impairment of basal body migration and docking. These results point to an undiscovered regulation of ciliogenesis by Lys63 ubiquitination and provide new perspectives regarding CYLD function that should be considered in the context of cylindromatosis.
ISSN: 2041-1723

hal-01063915
https://hal.archives-ouvertes.fr/hal-01063915
DOI : 10.1038/ncomms5585
PUBMED : 25134987

Éditeur(s) : Pergamon-elsevier Science Ltd
Résumé : The south-west lagoon of New Caledonia is a wide semi-open coral reef lagoon bounded by an intertidal barrier reef and bisected by numerous deep inlets. This paper synthesizes findings from the 2000-2008 French National Program EC2CO-PNEC relative to the circulation and the transport of suspended particles in this lagoon. Numerical model development (hydrodynamic, fine suspended sediment transport, wind-wave, small-scale atmospheric circulation) allowed the determination of circulation patterns in the lagoon and the charting of residence time, the later of which has been recently used in a series of ecological studies. Topical studies based on field measurements permitted the parameterisation of wave set-up induced by the swell breaking on the reef barrier and the validation of a wind-wave model in a fetch-limited environment. The analysis of spatial and temporal variability of suspended matter concentration over short and long time-scales, the measurement of grain size distribution and the density of suspended matter (1.27 kg 1(-1)), and the estimation of erodibility of heterogeneous (sand/mud, terrigenous/biogenic) soft bottoms was also conducted. Aggregates were shown to be more abundant near or around reefs and a possible biological influence on this aggregation is discussed. Optical measurements enabled the quantification of suspended matter either in situ (monochromatic measurements) or remotely (surface spectral measurements and satellite observations) and provided indirect calibration and validation of a suspended sediment transport model. The processes that warrant further investigation in order to improve our knowledge of circulation and suspended sediment transport in the New Caledonia lagoon as well as in other coral reef areas are discussed, as are the relevance and reliability of the numerical models for this endeavour.
Marine Pollution Bulletin (0025-326X) (Pergamon-elsevier Science Ltd), 2010 , Vol. 61 , N. 7-12 , P. 269-296

Droits : 2010 Elsevier Ltd All rights reserved.
http://archimer.ifremer.fr/doc/00014/12526/9401.pdf
DOI:10.1016/j.marpolbul.2010.06.023
http://archimer.ifremer.fr/doc/00014/12526/

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay. The compound 6E11, a natural product derivative, was characterized as a positive hit. Interestingly, this flavanone compound: inhibits necroptosis induced by death receptors ligands TNF-α (Tumor Necrosis Factor) or TRAIL (TNF-Related Apoptosis-Inducing Ligand); is an extremely selective inhibitor, among kinases, of human RIPK1 enzymatic activity with a nM Kd; has a non-ATP competitive mode of action and a novel putative binding site; is weakly cytotoxic towards human primary blood leukocytes or retinal pigment epithelial cells at effective concentrations; protects human aortic endothelial cells (HAEC) from cold hypoxia/reoxygenation injury more effectively than necrostatin-1 (Nec-1) and Nec-1s. Altogether, these data demonstrate that 6E11 is a novel potent small molecular inhibitor of RIPK1-driven necroptosis.
ISSN: 2045-2322

hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/file/s41598-017-12788-4.pdf
DOI : 10.1038/s41598-017-12788-4

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 Wiley
Résumé : International audience
Morphology can be misleading in the representation of phylogenetic relationships, especially in simple organisms like cnidarians and particularly in hydrozoans. These suspension feeders are widely distributed in many marine ecosystems, and the family Aglaopheniidae Marktanner-Turneretscher, 1890 is among the most diverse and visible, especially on tropical coral reefs. The taxonomy of this family is based on morphological characters with emphasis on reproductive structures for the identification of genera. This study is the most comprehensive molecular phylogeny of the Aglaopheniidae to date, including six genera and 38 species, of which 13 were investigated for the first time and sampled on tropical coral reefs throughout the Indo-Pacific region. For newly sampled individuals, we sequenced the 16S rRNA, the nuclear locus comprising the complete ITS1-5.8S rRNA gene-ITS2 and the first intron of the calmodulin nuclear gene. Phylogenetic analyses of the data revealed and confirmed a general polyphyly, or doubtful monophyly, of all sampled genera in tropical regions based on both the mitochondrial and nuclear markers. Our results revealed that several morphological characters used today are unsuited to resolve phylogenetic relationships between species and genera, as well as the high phyletic diversity within this family. Future revision of the classification of this family will require extensive geographic sampling and the use of an integrative approach.
ISSN: 0300-3256

hal-01253738
https://hal.archives-ouvertes.fr/hal-01253738
https://hal.archives-ouvertes.fr/hal-01253738/document
https://hal.archives-ouvertes.fr/hal-01253738/file/Phylogenetic%20relationships%20within%20Aglaopheniidae%20%28Cnidaria%2C._hal.pdf
DOI : 10.1111/zsc.12135

Éditeur(s) : HAL CCSD
Résumé : International audience
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis. © 2017 Federation of European Biochemical Societies
ISSN: 1742464X

hal-01616420
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616420
DOI : 10.1111/febs.14176
PUBMED : 28715128

Éditeur(s) : HAL CCSD
Résumé : International audience
Letter to the Editors
Journal of Neurology

hal-01372466
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01372466
PUBMED : 27416854
DOI : 10.1007/s00415-016-8216-y

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

hal-01647079
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647079
DOI : 10.1016/j.rmr.2017.07.019
PUBMED : 28939154

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