Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
Constitutive activation of the PI3K/mTOR signaling pathway contributes to carcinogenesis and metastasis in most, if not all, breast cancers. From a chromene backbone reported to inhibit class I PI3K catalytic subunits, several rounds of chemical syntheses led to the generation of a new collection of chromologues that showed enhanced ability to kill PI3K-addicted cancer cells and to inhibit Akt phosphorylation at serine 473, a hallmark of PI3K/mTOR activation. This initial screen uncovered a chromene designated DHM25 that exerted potent antitumor activity against breast tumor cell lines. Strikingly, DHM25 was shown to be a selective and covalent inhibitor of mTOR using biochemical and cellular analyses, modeling, and a large panel of kinase activity assays spanning the human kinome (243 kinases). Finally, in vivo, this novel drug was an efficient inhibitor of growth and metastasis of triple-negative breast cancer cells, paving the way for its clinical application in oncology
ISSN: 0022-2623

hal-01187307
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187307
DOI : 10.1021/acs.jmedchem.5b00991
PUBMED : 26237138

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
ISSN: 1935-2727

inserm-00919502
http://www.hal.inserm.fr/inserm-00919502
http://www.hal.inserm.fr/inserm-00919502/document
http://www.hal.inserm.fr/inserm-00919502/file/2013_Nacher_-_Disseminated_histo_in_hiv_in_south_america_a_neglected_killer_continues_on_its_rampage.pdf
DOI : 10.1371/journal.pntd.0002319

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 Nature Publishing Group
Résumé : International audience
Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na+/H+ exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways.
ISSN: 2045-2322

hal-01334067
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334067
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334067/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334067/file/Cleaved%20FAS%20ligand%20CC-BY.pdf
DOI : 10.1038/srep28008

Éditeur(s) : HAL CCSD Station Biologique
Résumé : International audience
This study deals with temporal variations in eel diet Anguilla anguilla sampled at each of the four seasons in the Languedocian Prévost lagoon (Gulf of Lion) from Autumn 1998 to Summer 1999. The following feeding indices were calculated based on observations of 12 categories of prey found in the contents of full stomachs: coefficient of vacuity CV, degree of fullness DR, occurrence frequency PP, relative abundance N (in %) and relative weight P (in %). The interpretation of results is also based on the Costello's method (1990) which combines PP and N. Anguilla anguilla mainly feeds on benthic organisms, primarily Gammarus gr. locusta, Polychaeta, insect larvae, small fish. Based on variations in eel diet, seasonal influence is illustrated by a decrease in feeding activity in summer which gradually increases during the following seasons. The good trophic quality available to eels in the Prévost lagoon depends on its hydrodynamics which is directly related to the movement of water entering and leaving lagoon by a short communication with the sea. This water movement accelerates the enrichment and production processes of this ecosystem. Changes observed during the four seasons illustrate an opportunistic type of feeding behaviour. Eels consume the most available benthic prey. They favour the importance of the prey at a given moment without using a particular feeding strategy like specialisation or generalisation. Thus, eel adapts its diet in adjusting available energy resources in the ecosystem. Because of this, the lagoon-resident species Anguilla anguilla is an obvious indirect bioindicator of the trophic capacity and present level of confinement in the brackish water lagoon ecosystem of Prévost.
ISSN: 0007-9723

hal-00753021
https://hal.univ-antilles.fr/hal-00753021

Éditeur(s) : HAL CCSD American Association for Cancer Research
Résumé : International audience
Triple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this risk is not understood. Here we report that serum levels of CD95L are higher in TNBC patients compared to other breast cancer patients. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility, due to formation of an unconventional CD95-containing receptosome termed the motility-inducing signaling complex. Formation of this complex was instrumental for Nox3-driven ROS generation. Mechanistic investigations revealed a Yes-Orai1-EGFR-PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a pro-metastatic function for metalloprotease-cleaved CD95L in triple-negative breast cancers, revisiting its role in carcinogenesis.
ISSN: 0008-5472

hal-00873634
https://hal.archives-ouvertes.fr/hal-00873634
PUBMED : 24072745
DOI : 10.1158/0008-5472.CAN-13-1794

Éditeur(s) : HAL CCSD Federation of American Society of Experimental Biology
Résumé : International audience
The innate immune system is able to detect bacterial LPS through the pattern recognition receptor CD14, which delivers LPS to various TLR signaling complexes that subsequently induce intracellular proinflammatory signaling cascades. In a previous study, we showed the overproduction of the soluble form of CD14 (sCD14) by macrophages from patients with cystic fibrosis (CF). CF is an autosomal recessive disorder that is caused by mutations in the gene that encodes the CFTR protein and is characterized by persistent inflammation. Macrophages play a significant role in the initial stages of this disease due to their inability to act as suppressor cells, leading to chronic inflammation in CF. In this work, we investigated the origin of sCD14 by human macrophages and studied the effect of sCD14 on the production of inflammatory cytokine/chemokine. Our data indicate that sCD14 stimulate proinflammatory cytokine/chemokine production in a manner that is independent of LPS but dependent on the TLR-4/CD14 membrane complex, NF-κB, and the inflammasome. Therefore, sCD14, overproduced by CF macrophages, originates primarily from the endocytosis/exocytosis process and should be considered to be a danger-associated molecular pattern. This elucidation of the origin and inflammation-induced mechanisms associated with sCD14 contributes to our understanding of maintained tissue inflammation.
ISSN: 0892-6638

hal-01526434
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526434/file/Soluble%20CD14%20acts%20as%20a%20DAMP%20in%20human-accepted.pdf
PUBMED : 28122919

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

Éditeur(s) : HAL CCSD Institute of Oceanography and Fisheries, Split
Résumé : International audience
This study deals with temporal variations in eel Anguilla anguilla diet, sampled seasonally in the Languedocian Mauguio lagoon (Gulf of Lion), from Autumn 1998 to Summer 1999. Eel mainly feeds on benthic organisms, primarily small Amphipoda, Crustacea (mainly Gammarus gr. locusta), Polychaeta, insect larvae (Chironomidae) and small fish. Based on variations in the eels feeding regime, seasonal influence is illustrated by decreased feeding activity in summer, which progressively increases during the following seasons. The trophic quality available to eels in the Mauguio lagoon depends more on allochtonous inputs from the catchment area than on its own hydrodynamics on which water of marine origin has little influence due to its long distance from the sea. Variations observed during the four seasons illustrate the opportunist type feeding behaviour of eels. They consume the most available benthic preys at a given moment without using a particular feeding strategy like specialisation or generalisation. Eel adapts its diet according to the available resources offered by the ecosystem. Because of this eel, as an amphihaline migrant species, can be characterised as an obvious indirect bioindicator of the trophic capacity and very marked level of confinement in the brackish lagoon ecosystem of Mauguio.
ISSN: 0001-5113

hal-00750416
https://hal.univ-antilles.fr/hal-00750416
https://hal.univ-antilles.fr/hal-00750416/document
https://hal.univ-antilles.fr/hal-00750416/file/Acta_Adriatica_2009_50_2_.pdf

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
The diagnosis of some infectious diseases is sometimes difficult to make and new diagnostic tools have been regularly assessed to that end. 18fluoro-deoxyglucose ((18)FDG) positron-emission tomography (PET) coupled with computed tomography (CT) is one of these new procedures. It has been evaluated for numerous infectious diseases with uneven results. A literature review allowed drawing some conclusions. First, (18)FDG-PET/CT is not currently a first-line procedure for infectious diseases. Second, it has proved useful for the evaluation of patients presenting with fever of unknown origin (FUO). Its negative predictive value is 100%: the symptoms of patients experiencing FUO with negative first-line investigations and a negative (18)FDG-PET/CT will almost always spontaneously disappear. Third, (18)FDG-PET/CT also seems to be contributive for the diagnosis of vascular prosthesis infections or osteomyelitis. Fourth, it has promising results for patients presenting with infective endocarditis, especially for secondary infectious foci, or for patients presenting with suspected infection of pacemakers or implanted defibrillator; but results are still preliminary and must be confirmed. Finally(18)FDG-PET/CT cannot be recommended yet for other infectious diseases due to lack of published data.
ISSN: 0399-077X

hal-01064982
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01064982
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01064982/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01064982/file/Contributionsur 18Fluoro_deoxyglucose_PETCT_accepted.pdf
DOI : 10.1016/j.medmal.2014.04.007

Éditeur(s) : HAL CCSD Station Biologique
Résumé : International audience
This study focuses on the diet of the eel Anguilla anguilla, sampled during one month of each of the four seasons from autumn 1998 to summer 1999 in the Languedocian Ingril Lagoon (Gulf ot Lion). The following feeding indices were calculated based on observations of 11 categories of prey found in the contents of full stomachs: coefficient of vacuity (CV), degree of fullness (DR), occurrence frequency (PP, in %), relative abundance (N, in %) and relative weight (P, in %). A parallel monitoring of the benthic macrofauna was conducted in autumn and spring. The interpretation of the results is based on the degree III of the scale of confinement established by Guélorget & Perthuisot (1983) and on the Costello et al. (1990) method, which combines PP and N. A. anguilla mainly feeds on benthic organisms, primarily amphipods crustaceans, polychaetes, insect larvae and small fish. The eel's feeding activity is very low in November and February and usually increases during May. The trophic quality available to the eel population in the Ingril Lagoon depends on its hydrodynamic variables, which are directly related to its close communication with the sea. Changes observed in the eel's diet over this year long study illustrate an opportunist type of feeding behaviour that reflects the typical composition of the macroinvertebrate species assemblage at a given point in time. Eels consume the type of benthic prey that is most available at a given moment without using a particular feeding strategy (e.g., specialisation or generalisation). The eels adapt by shifting their diet according to the energetic resources available in the ecosystem, which vary depending on hydrological regime. Thus, the facultative catadromous migrant species Anguilla anguilla could be used as a bioindicator of changes in the biological zonation and in the available food resources in the brackish ecosystem of Ingril Lagoon during its lagoon-resident ecophase.
ISSN: 0007-9723

hal-00753020
https://hal.univ-antilles.fr/hal-00753020

Éditeur(s) : HAL CCSD
Résumé : International audience
The environmental uncertainty leads SMEs to adopt collective strategies in order to supplement their inadequate resources. The longitudinal study of the Pic Saint-Loup union of wine producers provides an understanding of how SMEs can develop collective strategies. The case study is based on several time of data collection from mainly forty five semi-structured interviews. Our findings are twofold. We identify the stages of SMEs collective strategies development and the role of stakeholders. Then, we highlight the tertius strategies of SMEs owner-managers and the positive influence of their combination.
Les PME, plus vulnérables aux forces de l'environnement, cherchent à compléter l'insuffisance de leurs ressources en adoptant des stratégies collectives afin de réduire cette incertitude. L'étude longitudinale du syndicat de producteurs de vin du Pic Saint-Loup, qui s'appuie sur plusieurs temps de collecte et quarante-cinq entretiens semi-directifs, permet de comprendre la façon dont des PME peuvent développer des stratégies collectives. Nous identifions les phases du développement de la stratégie collective ainsi que le rôle joué par les parties prenantes. Puis, nous soulignons les stratégies de tertius des dirigeants de PME et leur combinaison favorisant le développement de ces stratégies collectives. Mots clés : Stratégie collective, PME, étude longitudinale, parties prenantes, tertius. *Remerciements Ce papier bénéficie du soutien de la chaire Entrepreneuriat et Innovation du 'Labex Entreprendre' de Montpellier en France. Ce " laboratoire d'excellence " est reconnu et soutenu par le gouvernement français pour la qualité de ses recherches dans les sciences humaines et sociales.
Management International / International Management / Gestión Internacional

hal-01588177
http://hal.univ-smb.fr/hal-01588177
http://hal.univ-smb.fr/hal-01588177/document
http://hal.univ-smb.fr/hal-01588177/file/MI-710%20-%20GRANATA%20DA%20FONSECA%20MARQU%C3%88S%20G%C3%89RAUDEL.pdf