Éditeur(s) : HAL CCSD
Résumé : International audience
Antiviral proteins that recognize pathogen-specific or aberrantly located molecular motifs are perfectly positioned to act as pattern-recognition receptors and signal to the immune system. Here we investigated whether the interferon-induced viral restriction factor tetherin (CD317/BST2), which is known to inhibit HIV-1 particle release by physically tethering virions to the cell surface, has such a signaling role. We find that upon restriction of Vpu-defective HIV-1, tetherin acts as a virus sensor to induce NFκB-dependent proinflammatory gene expression. Signaling requires both tetherin's extracellular domain involved in virion retention and determinants in the cytoplasmic tail, including an endocytic motif, although signaling is independent of virion endocytosis. Furthermore, recruitment of the TNF-receptor-associated factor TRAF6 and activation of the mitogen-activated protein kinase TAK1 are critical for signaling. Human tetherin's ability to mediate efficient signaling may have arisen as a result of a five amino acid deletion that occurred in hominids after their divergence from chimpanzees.
ISSN: 1934-6069

hal-01121777
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121777
PUBMED : 23159053
DOI : 10.1016/j.chom.2012.10.007
PUBMEDCENTRAL : PMC3556742

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Amelotin (AMTN) is an ameloblast-secreted protein that belongs to the secretory calcium-binding phosphoprotein (SCPP) family, which originated in early vertebrates. In rodents, AMTN is expressed during the maturation stage of amelogenesis only. This expression pattern strongly differs from the spatiotemporal expression of other ameloblast-secreted SCPPs, such as the enamel matrix proteins (EMPs). Furthermore, AMTN was characterized in rodents only. In this study, we applied various approaches, including in silico screening of databases, PCRs and transcriptome sequencing to characterize AMTN sequences in sauropsids and amphibians, and compared them to available mammalian and coelacanth sequences. Results: We showed that (i) AMTN is tooth (enamel) specific and underwent pseudogenization in toothless turtles and birds, and (ii) the AMTN structure changed during tetrapod evolution. To infer AMTN function, we studied spatiotemporal expression of AMTN during amelogenesis in a salamander and a lizard, and compared the results with available expression data from mouse. We found that AMTN is expressed throughout amelogenesis in non-mammalian tetrapods, in contrast to its expression limited to enamel maturation in rodents. Conclusions: Taken together our findings suggest that AMTN was primarily an EMP. Its functions were conserved in amphibians and sauropsids while a change occurred early in the mammalian lineage, modifying its expression pattern during amelogenesis and its gene structure. These changes likely led to a partial loss of AMTN function and could have a link with the emergence of prismatic enamel in mammals.
ISSN: 1471-2148

Droits : http://creativecommons.org/licenses/by/
hal-01212821
http://hal.upmc.fr/hal-01212821
http://hal.upmc.fr/hal-01212821/document
http://hal.upmc.fr/hal-01212821/file/s12862-015-0329-x.pdf
DOI : 10.1186/s12862-015-0329-x

Éditeur(s) : Elsevier
Résumé : Total (T-Hg) and organic (O-Hg) mercury concentrations and tissue distribution were examined in 20 species of cephalopods (n = 278) from the north eastern Atlantic waters, i.e. from the Bay of Biscay to the Faroe Islands. Concentrations of T-Hg in whole cephalopods showed elevated variations among species, i.e. from 40 to 3560ng g(-1) dwt, but a low variability within each species (mean CV%=39%). With the exception of oceanic squids, the digestive gland globally displayed higher T-Hg concentrations than the remaining tissues. In contrast, O-Hg concentrations determined in selected species were generally higher in the remaining tissues. Despite higher T-Hg concentrations, the digestive gland weakly contributed to the total body burden of both T-Hg and O-Hg (< 25% and < 15%, respectively). In fact, from 75% to 95% of the T-Hg and O-Mg were contained in the muscular remaining tissues. Therefore, O-Hg may have a strong affinity to proteins in cephalopods. Sex and size only significantly influenced the bioaccumulation of Hg for the Loliginidae family. T-Hg and O-Hg concentrations were also influenced by geographical origin: Celtic Sea > Bay of Biscay > Faroe Islands, corresponding to the seawater Hg concentrations in these areas. In the Faroe Islands and the Celtic Sea, benthic cephalopods contained significant higher Hg concentrations compared to pelagic ones. This suggests that diet is not the main pathway of Hg uptake in cephalopods as pelagic species were expected to be more exposed to O-Hg through fish consumption than benthic ones. (c) 2006 Elsevier B.V. All rights reserved.
The Science of The Total Environment (0048-9697) (Elsevier), 2006-09 , Vol. 368 , N. 2-3 , P. 585-596

Droits : 2006 Elsevier
http://archimer.ifremer.fr/doc/2006/publication-1873.pdf
DOI:10.1016/j.scitotenv.2006.01.038
http://archimer.ifremer.fr/doc/00000/1873/

Éditeur(s) : Nature Publishing Group
Résumé : Vibrio nigripulchritudo is an emerging pathogen of farmed shrimp in New Caledonia and other regions in the Indo-Pacific. The molecular determinants of V. nigripulchritudo pathogenicity are unknown; however, molecular epidemiological studies have suggested that pathogenicity is linked to particular lineages. Here, we performed high-throughput sequencing-based comparative genome analysis of 16 V. nigripulchritudo strains to explore the genomic diversity and evolutionary history of pathogen-containing lineages and to identify pathogen-specific genetic elements. Our phylogenetic analysis revealed three pathogen-containing V. nigripulchritudo clades, including two clades previously identified from New Caledonia and one novel clade comprising putatively pathogenic isolates from septicemic shrimp in Madagascar. The similar genetic distance between the three clades indicates that they have diverged from an ancestral population roughly at the same time and recombination analysis indicates that these genomes have, in the past, shared a common gene pool and exchanged genes. As each contemporary lineage is comprised of nearly identical strains, comparative genomics allowed differentiation of genetic elements specific to shrimp pathogenesis of varying severity. Notably, only a large plasmid present in all highly pathogenic (HP) strains encodes a toxin. Although less/non-pathogenic strains contain related plasmids, these are differentiated by a putative toxin locus. Expression of this gene by a non-pathogenic V. nigripulchritudo strain resulted in production of toxic culture supernatant, normally an exclusive feature of HP strains. Thus, this protein, here termed 'nigritoxin', is implicated to an extent that remains to be precisely determined in the toxicity of V. nigripulchritudo.
Isme Journal (1751-7362) (Nature Publishing Group), 2013-10 , Vol. 7 , N. 10 , P. 1985-1996

Droits : 2013 International Society for Microbial Ecology All rights reserved 1751-7362/13
http://archimer.ifremer.fr/doc/00160/27117/28369.pdf
DOI:10.1038/ismej.2013.90
http://archimer.ifremer.fr/doc/00160/27117/

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.
ISSN: 0007-1048

hal-01668325
https://hal.univ-antilles.fr/hal-01668325
DOI : 10.1111/bjh.14476

Éditeur(s) : HAL CCSD
Résumé : Benzophenone derivatives (BPs) are used as UV filters in many different products. These lipophilic compounds were recently described as ubiquitous contaminant of different compartiments of aquatic systems, including fish. In this study, we evaluated estrogenic activity of ten BPs in a model fish species, the zebrafish (Danio rerio), by combining newly developed in vitro and in vivo models. In vitro, three specific zebrafish reporter gene models expressing zebrafish estrogen receptors (ZfERs) in zebrafish hepatic cell line (ZFL) were used.Estrogenic activity of BPs was quantify in vivo by using a newly developed transgenic zebrafish line that expresses green fluorescent protein (GFP) under the control of the cyp19a1b promoter. The cyp19a1b gene codes for the brain aromatase B that is under the control of estrogens. Vitellogenin (Vtg), a marker of estrogenic compound, was used to assess the potential estrogenic effect of certain BPs in male fish. Five of 10 BPs induced an estrogenic activity on the three models: BP2, THB, BP1, 4BP, while BP and 234 BP were non active. We noted diffrence in BPs ranking depending on the zfER subtypes suggesting ?/? receptor selectivity by certain BPs. By quantifying GFP expression in live zebrafish, we confirm the estrogenic activity of some BP, i.e., BP1, THB, 4BP and 44'BP, as shown by their ability to induce GFP in a concentration-dependent manner. However, the ranking of BPs as a function of their estrogenic activity assay is different between models. For instance, 4BP was the most estrogenic compound in vivo but not in vitro. Differences were also noticed regarding the estrogenic activity of BP2. In vitro, BP2 has strong activity but had no effect on GFP in cyp19a1b-GFP embryo. However, BP2 induced strongly Vtg in male. The lack of estrogenic activity of BP2 in embryo may be related to difference of biodisponibility and/or metabolisation of this compound between embryo and adult fish. Our approach allows to characterize the estrogenic potency of emerging pollutants, using innovative in vitro and in vivo assays within a unique model fish species. The differences observed between assays deserve further studies to characterize the behavior of compounds in the different biological models in term of biodisponibility and metabolism.
1. European Conference on the Replacement, Reduction and Refinement of Animal Experiments in Ecotoxicology
Dübendorf, Switzerland

ineris-00971019
https://hal-ineris.archives-ouvertes.fr/ineris-00971019
INERIS : EN-2012-243

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.
ISSN: 1061-4036

hal-01544763
https://hal.archives-ouvertes.fr/hal-01544763
DOI : 10.1038/ng.2601

Éditeur(s) : Proceedings of 3rd East-West Fisheries conference; 24-26 Nov. 1998; Copenhagen, Denmark
Résumé : The demand for fish products, from freshwater and from the sea, is globally increasing ail over the world. This major trend can be explained by the development of mankind, not only in quantity (one billion people more in the last 15 years) but also because food consumption habits are changing: for southern countries, fish products consumption is first a diversification of protein sources. For northern countries, it is a new style of eating with diet, tasteful and original products coming from the attractive « new frontier » symbolised by the sea. Global/y speaking, the aquatic product consumption raised from 9 to 13 kg./unhab./year during the last 30 years. It is now clear that catches from ail fisheries cannot match this steady increase of the demand as data collected from al/ countries reveal the stagnation of the world production since the beginning of the nineties. The reasons are now well-known: over-capacity of fishing fleets, over-fishing of many stocks, poor management of harvested species which results in about 20 millions of tons of waste while the same amount is processed into fishmeal and oil, out of direct human consumption.

Droits : Ifremer
http://archimer.ifremer.fr/doc/00041/15181/12518.pdf
http://archimer.ifremer.fr/doc/00041/15181/

Éditeur(s) : HAL CCSD Ferrata Storti Foundation
Résumé : International audience
BACKGROUND: Abnormal interactions between red blood cells, leukocytes and endothelial cells play a critical role in the occurrence of the painful vaso-occlusive crises associated with sickle cell disease. We investigated the interaction between circulating leukocytes and red blood cells which could lead to aggregate formation, enhancing the incidence of vaso-occlusive crises. DESIGN AND METHODS: Blood samples from patients with sickle cell disease (n=25) and healthy subjects (n=5) were analyzed by imaging and classical flow cytometry after density gradient separation. The identity of the cells in the peripheral blood mononuclear cell layer was determined using antibodies directed specifically against white (anti-CD45) or red (anti-glycophorin A) blood cells. RESULTS: Aggregates between red blood cells and peripheral blood mononuclear cells were visualized in whole blood from patients with sickle cell disease. The aggregation rate was 10-fold higher in these patients than in control subjects. Both mature red blood cells and reticulocytes were involved in these aggregates through their interaction with mononuclear cells, mainly with monocytes. The size of the aggregates was variable, with one mononuclear cell binding to one, two or several red blood cells. Erythroid Lu/basal cell adhesion molecule and α(4)β(1) integrin were involved in aggregate formation. The aggregation rate was lower in patients treated with hydroxycarbamide than in untreated patients. CONCLUSIONS: Our study gives visual evidence of the existence of circulating red blood cell-peripheral blood mononuclear cell aggregates in patients with sickle cell disease and shows that these aggregates are decreased during hydroxycarbamide treatment. Our results strongly suggest that erythroid Lu/basal cell adhesion molecule proteins are implicated in these aggregates through their interaction with α(4)β(1) integrin on peripheral blood mononuclear cells.
ISSN: 0390-6078

inserm-00821120
http://www.hal.inserm.fr/inserm-00821120
http://www.hal.inserm.fr/inserm-00821120/document
http://www.hal.inserm.fr/inserm-00821120/file/1841.full.pdf
DOI : 10.3324/haematol.2010.026294

Éditeur(s) : HAL CCSD Society for the Study of Reproduction
Résumé : International audience
Spermmotility notably depends on the structural integrity of the flagellum and the regulation ofmicrotubule dynamics. Although researchers have started to use " omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined. In this study, we defined a core set of 116 gene products associated with the human sperm microtubulome (including products potentially involved in abnormal ciliary phenotypes and male infertility disorders). To this end, we designed and applied an integrated genomics workflow and combined relevant proteomics, transcriptomics, and interactomics datasets to reconstruct a dynamic interactome map. By further integrating phenotypic information, we defined a disease-interaction network; this enabled us to highlight a number of novel factors potentially associated with altered sperm motility and male fertility. Lastly, we experimentally validated the expression pattern of two candidate genes (CUL3 and DCDC2C) that had never previously been associated with male germline differentiation. Our analysis suggested that CUL3 and DCDC2C's products have important roles in the sperm flagellum. Taken as a whole, our results demonstrate that an integrated genomics strategy can highlight relevant molecular factors in specific sperm components. This approach could be easily extended by including other " omics" data (from asthenozoospermic men, for example) and identifying other critical proteins from the human sperm microtubulome. Summary Sentence Although researchers have started to use "omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined.
ISSN: 0006-3363

hal-01515563
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01515563
DOI : 10.1095/biolreprod.116.143479
PUBMED : 28395323

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 Oxford University Press (OUP)
Résumé : International audience
Hepatocellular carcinoma treatment by arterial infusion of cis-diamminedichloroplatinum-II (cisplatin) exhibits certain therapeutic efficacy. However, optimizations are required and the mechanisms underlying cisplatin proapoptotic effect remain unclear. The mitogen-activated protein kinase (MAPK) pathway plays a key role in cell response to cisplatin and the functional specificity of the isoform MAPK/ERK kinase 1 and 2 (MEK1/2) and ERK1/2 could influence this response. The individual contribution of each kinase on cisplatin-induced death was thus analyzed after a transient or stable specific inhibition by RNA interference in the human hepatocellular carcinoma cells Huh-7 or in knockout mice. We demonstrated here that ERK1 played a predominant role over ERK2 in cisplatin-induced death, whereas MEK1 and MEK2 acted in a redundant manner. Indeed, at clinically relevant concentrations of cisplatin, ERK1 silencing alone was sufficient to protect cells from cisplatin-induced death both in vitro, in Huh-7 cells and ERK1(-/-) hepatocytes, and in vivo, in ERK1-deficient mice. Moreover, we showed that ERK1 activity correlated with the induction level of the proapoptotic BH3-only protein Noxa, a critical mediator of cisplatin toxicity. On the contrary, ERK2 inhibition upregulated ERK1 activity, favored Noxa induction and sensitized hepatocarcinoma cells to cisplatin. Our results point to a crucial role of ERK1 in cisplatin-induced proapoptotic signal and lead us to propose that ERK2-specific targeting could improve the efficacy of cisplatin therapy by increasing ERK1 prodeath functions.
ISSN: 0143-3334

inserm-00814096
http://www.hal.inserm.fr/inserm-00814096
DOI : 10.1093/carcin/bgs317
PUBMED : 23042098

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The symbiotic interaction between cnidarians, such as corals and sea anemones, and the unicellular algae Symbiodinium is regulated by yet poorly understood cellular mechanisms, despite the ecological importance of coral reefs. These mechanisms, including host-symbiont recognition and metabolic exchange, control symbiosis stability under normal conditions, but also lead to symbiosis breakdown (bleaching) during stress. This study describes the repertoire of the sterol-trafficking proteins Niemann-Pick type C (NPC1 and NPC2) in the symbiotic sea anemone Anemonia viridis. We found one NPC1 gene in contrast to the two genes (NPC1 and NPC1L1) present in vertebrate genomes. While only one NPC2 gene is present in many metazoans, this gene has been duplicated in cnidarians, and we detected four NPC2 genes in A. viridis. However, only one gene (AvNPC2-d) was upregulated in symbiotic relative to aposymbiotic sea anemones and displayed higher expression in the gastrodermis (symbiont-containing tissue) than in the epidermis. We performed immunolabelling experiments on tentacle cross sections and demonstrated that the AvNPC2-d protein was closely associated with symbiosomes. In addition, AvNPC1 and AvNPC2-d gene expression was strongly downregulated during stress. These data suggest that AvNPC2-d is involved in both the stability and dysfunction of cnidarian-dinoflagellate symbioses.
ISSN: 0962-1083

hal-01546166
https://hal.archives-ouvertes.fr/hal-01546166
DOI : 10.1111/mec.12876

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Amelotin (AMTN) is an ameloblast-secreted protein that belongs to the secretory calcium-binding phosphoprotein family, which also includes the enamel matrix proteins amelogenin, ameloblastin and enamelin. Although AMTN is supposed to play an important role in enamel formation, data were long limited to the rodents, in which it is expressed during the maturation stage. Recent comparative studies in sauropsids and amphibians revealed that (i) AMTN was expressed earlier, i.e. as soon as ameloblasts are depositing the enamel matrix, and (ii) AMTN structure was different, a change which mostly resulted from an intraexonic splicing in the large exon 8 of an ancestral mammal. The present study was performed to know whether the differences in AMTN structure and expression in rodents compared to non-mammalian tetrapods dated back to an early ancestral mammal or were acquired later in mammalian evolution. We sequenced, assembled and screened the jaw transcriptome of a neonate opossum Monodelphis domestica, a marsupial. We found two AMTN transcripts. Variant 1, representing 70.8% of AMTN transcripts, displayed the structure known in rodents, whereas variant 2 (29.2%) exhibited the nonmammalian tetrapod structure. Then, we studied AMTN expression during amelogenesis in a neonate specimen. We obtained similar data as those reported in rodents. These findings indicate that more than 180 million years ago, before the divergence of marsupials and placentals, changes occurred in AMTN function and structure. The spatiotemporal expression was delayed to the maturation stage of amelogenesis and the intraexonic splicing gave rise to isoform 1, encoded by variant 1 and lacking the RGD motif. The ancestral isoform 2, housing the RGD, was initially conserved, as demonstrated here in a marsupial, then secondarily lost in the placental lineages. These findings bring new elements towards our understanding of the non-prismatic to prismatic enamel transition that occurred at the onset of mammals.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01233552
https://hal.archives-ouvertes.fr/hal-01233552
https://hal.archives-ouvertes.fr/hal-01233552/document
https://hal.archives-ouvertes.fr/hal-01233552/file/journal.pone.0133314.pdf
DOI : 10.1371/journal.pone.0133314

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers
Résumé : International audience
: A new set-up for exposure of human cells in vitro at 37°C to pulse-modulated 300 MHz and 500 MHz signals of future magnetic resonance imaging (MRI) systems is designed, built up, and characterized. Two dipole antennas, specifically designed for ultra high field MRI, are used as radiating structures. The electromagnetic (EM) field distribution inside the incubator containing the cells is computed, and it is shown to be in a good agreement with measurements. The electric field at the cell level is quantified numerically. Local, 1g average, and averaged over the culture medium volume SAR are provided along with the standard deviation values for each well. Temperature increments are measured inside the culture medium during the exposure using an optical fiber thermometer. Then we identify the pulse parameters corresponding to the thermal threshold of 1°C, usually considered as a threshold for thermally-induced biological effects. For these parameters, the induction of heat shock proteins is assessed to biologically verify a potential thermal response of cells. The data demonstrate that, under the considered experimental conditions, exposure to pulsemodulated radiations emulating typical ultra high field MRI signals, corresponding to temperature increments below 1°C, does not trigger any heat shock response in human brain cells.
ISSN: 0018-9294

hal-00874329
https://hal.archives-ouvertes.fr/hal-00874329
DOI : 10.1109/TBME.2013.2270371
PUBMED : 23799680

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The Hippo pathway regulates growth rate and organ size in fly and mouse, notably through control of cell proliferation. Molecular interactions at the heart of this pathway are known to have originated in the unicellular ancestry of metazoans. They notably involve a cascade of phosphorylations triggered by the kinase Hippo, with sub‑ sequent nuclear to cytoplasmic shift of Yorkie localisation, preventing its binding to the transcription factor Scalloped, thereby silencing proliferation genes. There are few comparative expression data of Hippo pathway genes in non‑ model animal species and notably none in non‑bilaterian phyla.Results: All core Hippo pathway genes could be retrieved from the ctenophore Pleurobrachia pileus and the hydro‑ zoan cnidarian Clytia hemisphaerica, with the important exception of Yorkie in ctenophore. Expression study of the Hippo, Salvador and Scalloped genes in tentacle " cellular conveyor belts " of these two organisms revealed striking differences. In P. pileus, their transcripts were detected in areas where undifferentiated progenitors intensely prolifer‑ ate and where expression of cyclins B and D was also seen. In C. hemisphaerica, these three genes and Yorkie are expressed not only in the proliferating but also in the differentiation zone of the tentacle bulb and in mature tentacle cells. However, using an antibody designed against the C. hemiphaerica Yorkie protein, we show in two distinct cell lineages of the medusa that Yorkie localisation is predominantly nuclear in areas of active cell proliferation and mainly cytoplasmic elsewhere.Conclusions: This is the first evidence of nucleocytoplasmic Yorkie shift in association with the arrest of cell prolifera‑ tion in a cnidarian, strongly evoking the cell division‑promoting role of this protein and its inhibition by the activated Hippo pathway in bilaterian models. Our results furthermore highlight important differences in terms of deployment and regulation of Hippo pathway genes between cnidarians and ctenophores.
ISSN: 2041-9139

Droits : http://creativecommons.org/licenses/by/
hal-01286578
http://hal.upmc.fr/hal-01286578
http://hal.upmc.fr/hal-01286578/document
http://hal.upmc.fr/hal-01286578/file/comparative.pdf
DOI : 10.1186/s13227-016-0041-y

Éditeur(s) : HAL CCSD American Society for Cell Biology
Résumé : International audience
Based on its shedding and binding activities, the disintegrin and metalloprotease 12 (ADAM12) has been implicated in cell signaling. Here we investigate the intracellular protein interaction network of the transmembrane ADAM12L variant using an integrative approach. We identify the integrin-linked kinase (ILK) as a new partner for ADAM12L cellular functions. We demonstrate that ADAM12L coimmunoprecipitates with ILK in cells and that its cytoplasmic tail is required for this interaction. In human cultured hepatic stellate cells (HSCs), which express high levels of endogenous ADAM12L and ILK, the two proteins are redistributed to focal adhesions upon stimulation of a β1 integrin-dependent pathway. We show that down-regulation of ADAM12L in HSCs leads to cytoskeletal disorganization and loss of adhesion. Conversely, up-regulation of ADAM12L induces the Akt Ser-473 phosphorylation-dependent survival pathway via stimulation of β1 integrins and activation of phosphoinositide 3-kinase (PI3K). Depletion of ILK inhibits this effect, which is independent of ADAM12L proteolytic activity and involves its cytoplasmic domain. We further demonstrate that overexpression of ADAM12L promotes kinase activity from ILK immunoprecipitates. Our data suggest a new role for ADAM12L in mediating the functional association of ILK with β1 integrin to regulate cell adhesion/survival through a PI3K/Akt signaling pathway.
ISSN: 1059-1524

Droits : info:eu-repo/semantics/OpenAccess
inserm-00717429
http://www.hal.inserm.fr/inserm-00717429
http://www.hal.inserm.fr/inserm-00717429/document
http://www.hal.inserm.fr/inserm-00717429/file/MBoC_E11-11-0918R-A_LEYME_ET_AL.pdf
PUBMED : 22767580

Éditeur(s) : Academic Press Ltd- Elsevier Science Ltd
Résumé : Extracellular products (ECPs) of the pathogenic Vibrio aestuarianus 01/32 were previously reported to display lethality in Crassostrea gigas oysters and to cause morphological changes and immunosuppression in oyster hemocytes. To identify the source of this toxicity, biochemical and genetic approaches were developed. ECP protease activity and lethality were shown to be significantly reduced following incubation with metal chelators, suggesting the involvement of a zinc metalloprotease. An open reading frame of 1836 bp encoding a 611-aa metalloprotease (designated yam) was identified. The deduced protein sequence showed high homology to other Vibrio metalloproteases reported to be involved in pathogenicity. To further confirm the role of this enzyme in ECP toxicity, a plasmid carrying the yarn gene under the control of an araC-P-BAD expression cassette was transferred to a Vibrio splendidus related strain, LMC20012(T), previously characterized as non-pathogenic to oysters. Expression of Vam conferred a toxic phenotype to LMG20012(T) ECPs in vivo and cytotoxicity to oyster hemocytes in vitro. Collectively, these data suggest that the Vam metalloprotease is a major contributor to the toxicity induced by V aestuarianus ECPs and is involved in the impairment of oyster hemocyte functions. (C) 2010 Elsevier Ltd. All rights reserved.
Fish & Shellfish Immunology (1050-4648) (Academic Press Ltd- Elsevier Science Ltd), 2010-11 , Vol. 29 , N. 5 , P. 753-758

Droits : 2010 Elsevier Ltd All rights reserved.
http://archimer.ifremer.fr/doc/00015/12649/9588.pdf
DOI:10.1016/j.fsi.2010.07.007
http://archimer.ifremer.fr/doc/00015/12649/

Éditeur(s) : HAL CCSD
Résumé : ABSTRACT Infectious complications are a leading cause of morbidity and mortality in patients with sickle cell disease. The exact reasons of the propensity of sickle cell patients to infection are not clear and are matter of debate. Besides, there is a striking variability of the clinical course of the disease between patients. This drew many scientists' attention. Genetic factors have been investigated as potential factor risks for infection in sickle cell patients, for example: HLA system; genes encoding Fc Human Immunoglobulin G receptor IIA, mannose-binding protein, and myeloperoxidase. Associations have been found, but all scientists agree that investigations have to be furthered. We investigated an association between HLA DRB1 and DQB1 polymorphism and infectious complications in sickle cell patients. Genotype frequencies were different between cases and controls for DRB1 locus. Indeed, HLA-DRB1*11 frequency was significantly higher in patients without infections than in patients with infections (χ² = 5.02; p = 0.025).
https://hal.archives-ouvertes.fr/hal-00387082

hal-00387082
https://hal.archives-ouvertes.fr/hal-00387082
https://hal.archives-ouvertes.fr/hal-00387082/document
https://hal.archives-ouvertes.fr/hal-00387082/file/MO_JOANNES_et_al_HLA_and_SCD.pdf

Éditeur(s) : HAL CCSD Cancer Research UK
Résumé : International audience
BACKGROUND: Cancer cell killing might be achieved by the combined use of available drugs. Statins are major anti-hypercholesterolemia drugs, which also trigger apoptosis of many cancer cell types, while docetaxel is a potent microtubule-stabilising agent. METHODS: Here, we looked at the combined effects of lovastatin and docetaxel in cancer cells. RESULTS: Whole transcriptome microarrays in HGT-1 gastric cancer cells demonstrated that lovastatin strongly suppressed expression of genes involved in cell division, while docetaxel had very little transcriptional effects. Both drugs triggered apoptosis, and their combination was more than additive. A marked rise in the cell-cycle inhibitor p21, together with reduction of aurora kinases A and B, cyclins B1 and D1 proteins was induced by lovastatin alone or in combination with docetaxel. The drug treatments induced the proteolytic cleavage of procaspase-3, a drop of the anti-apoptotic Mcl-1 protein, Poly-ADP-Ribose Polymerase and Bax. Strikingly, docetaxel-resistant HGT-1 cell derivatives overexpressing the MDR-1 gene were much more sensitive to lovastatin than docetaxel-sensitive cells. CONCLUSION: These results suggest that the association of lovastatin and docetaxel, or lovastatin alone, shows promise as plausible anticancer strategies, either as a direct therapeutic approach or following acquired P-glycoprotein-dependent resistance.
ISSN: 0007-0920

hal-00684528
https://hal.archives-ouvertes.fr/hal-00684528
DOI : 10.1038/bjc.2012.6
PUBMED : 22294184