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 : 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
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) : 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 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
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
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 Public Library of Science
Résumé : International audience
We studied the diversity within the former genus Gymnangium in the South West IndianOcean by using an integrative approach of both traditional (morphology-based) and modernmolecular taxonomy. Nine species were recorded in the material collected. A total of 97 16Smitochondrial DNA sequences and 54 Calmodulin nuclear sequences from eight Gymnangium/Taxella species were analyzed. We found both morphological and molecular differencesin the studied Gymnangium species that make it necessary to split the genus. It isproposed to revalidate the genus Taxella which is currently regarded as a synonym ofGymnangium. Two species of the genus Taxella (T. eximia and T. gracilicaulis), until nowregarded as distinct species based on morphological characteristics, cluster together in onephylogenetic clade. Possible explanations are discussed. Two species from Madagascarnew to science are herein described and rare species from the Indian Ocean islands are redescribed.
ISSN: 1932-6203

hal-01564043
https://hal-univ-perp.archives-ouvertes.fr/hal-01564043
DOI : 10.1371/journal.pone.0174244