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) : National Shellfisheries Association
Résumé : The subcellular fractionation of the digestive gland cells of the common cuttlefish Sepia officinalis was performed to investigate the distribution of metals between organelles and cytosol and the different cytosolic fractions separated by gel-filtration chromatography. Total metal concentrations vary over 3 orders of magnitude, ranging from dwt for Pb to dwt for Zn. With the exception of Cd, Co, and Cu, metals were mostly bound to the organelles. Whereas no specific organelle compartment was found for Mn, Ph, and Zn, Fe was mainly associated with nucleus, brown body, and "boule" fraction (i.e., 52%) and 44% of the total Ag was contained in the lysosomal and mitochondria enriched fraction. The link of metals with hydrosoluble proteins in the cytosolic fraction was investigated at 254 and 280 not. Direct relationship between cytosolic metal and metallothioneins could only be established for Ag and Cu, whereas Cd and Zn seem to mainly bind high (> 70 kDa) and low (< 4 kDa) molecular weight proteins.
The Journal of Shellfish Research (0730-8000) (National Shellfisheries Association), 2006-12 , Vol. 25 , N. 3 , P. 987-993

Droits : 2006 NSA
http://archimer.ifremer.fr/doc/2006/publication-2532.pdf
http://archimer.ifremer.fr/doc/00000/2532/

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
ISSN: 2045-7758

hal-01204216
https://hal.archives-ouvertes.fr/hal-01204216
DOI : 10.1002/ece3.1303
PRODINRA : 280886

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
o abstract
ISSN: 0168-8278

hal-01519257
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519257
DOI : 10.1016/S0168-8278(16)00178-1

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: Cancer/Testis (CT) genes are expressed in male gonads, repressed in most healthy somatic tissues and de-repressed in various somatic malignancies including prostate cancers (PCa). Because of their specific expression signature and their associations with tumor aggressiveness and poor outcomes, CT genes are considered to be useful biomarkers and they are also targets for the development of new anti-cancer immunotherapies. The aim of this study was to identify novel CT genes associated with hormone-sensitive prostate cancer (HSPC), and castration-resistant prostate cancer (CRPC). METHODS: To identify novel CT genes we screened genes for which transcripts were detected by RNA profiling specifically in normal testis and in either HSPC or CRPC as compared to normal prostate and 44 other healthy tissues using GeneChips. The expression and clinicopathological significance of a promising candidate-NR6A1-was examined in HSPC, CRPC, and metastatic site samples using tissue microarrays. RESULTS: We report the identification of 98 genes detected in CRPC, HSPC and testicular samples but not in the normal controls. Among them, cellular levels of NR6A1 were found to be higher in HSPC compared to normal prostate and further increased in metastatic lesions and CRPC. Furthermore, increased NR6A1 immunoreactivity was significantly associated with a high Gleason score, advanced pT stage and cancer cell proliferation. CONCLUSIONS: Our results show that cellular levels of NR6A1 are correlated with disease progression in PCa. We suggest that this essential orphan nuclear receptor is a potential therapeutic target as well as a biomarker of PCa aggressiveness. Prostate © 2013 Wiley Periodicals, Inc.
ISSN: 0270-4137

inserm-00821963
http://www.hal.inserm.fr/inserm-00821963
DOI : 10.1002/pros.22659
PUBMED : 23532770

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-α) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-α-dependent signaling pathway. We took advantage of two different deficient mouse lines, the RIPK1 kinase dead knock-in mice (Ripk1K45A) and the conditional knockout mice lacking RIPK1 only in liver parenchymal cells (Ripk1LPC-KO), to characterize the role of RIPK1 and TNF-α in hepatitis induced by concanavalin A (ConA). Our results show that RIPK1 is dispensable for liver homeostasis under steady-state conditions but in contrast, RIPK1 kinase activity contributes to caspase-independent cell death induction following ConA injection and RIPK1 also serves as a scaffold, protecting hepatocytes from massive apoptotic cell death in this model. In the Ripk1LPC-KO mice challenged with ConA, TNF-α triggers apoptosis, responsible for the observed severe hepatitis. Mechanism potentially involves both TNF-independent canonical NF-κB activation, as well as TNF-dependent, but canonical NF-κB-independent mechanisms. In conclusion, our results suggest that RIPK1 kinase activity is a pertinent therapeutic target to protect liver against excessive cell death in liver diseases. © The Author(s) 2016.
ISSN: 2041-4889

hal-01414916
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01414916
DOI : 10.1038/cddis.2016.362
PUBMED : 27831558

Éditeur(s) : Oxford university press
Résumé : The results of a survey on fishers' perceptions of recent changes in the eastern English Channel ecosystem carried out in 2006 were compared with fishery and bottom-trawl survey data. A hypothesis-testing framework was used, testing the null hypothesis that fishers' statements were true, which permitted evaluation of both agreement and disagreement. Overall good agreement between fishers' statements and scientific data was found, and both sources suggested that the fish community in the Channel is undergoing large changes, among which are decreases in some commercially important species; in addition, a number of human pressures impact the ecosystem. Fishers had an accurate perception of changes and their time-frames, but not necessarily of their causes. They had a greater power than survey data to detect recent changes, showing that fishers' perceptions have great potential as early warning signals.
ICES Journal of Marine Science (1054-3139) (Oxford university press), 2008-09 , Vol. 65 , N. 6 , P. 1057-1068

Droits : 2008 International Council for the Exploration of the Sea. Published by Oxford Journals.
http://archimer.ifremer.fr/doc/2008/publication-4474.pdf
DOI:10.1093/icesjms/fsn062
http://archimer.ifremer.fr/doc/00000/4474/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Diploid budding yeast undergoes rapid mitosis when it ferments glucose, and in the presence of a non-fermentable carbon source and the absence of a nitrogen source it triggers sporulation. Rich medium with acetate is a commonly used pre-sporulation medium, but our understanding of the molecular events underlying the acetate-driven transition from mitosis to meiosis is still incomplete. We identified 263 proteins for which mRNA and protein synthesis are linked or uncoupled in fermenting and respiring cells. Using motif predictions, interaction data and RNA profiling we find among them 28 likely targets for Ume6, a subunit of the conserved Rpd3/Sin3 histone deacetylase-complex regulating genes involved in metabolism, stress response and meiosis. Finally, we identify 14 genes for which both RNA and proteins are detected exclusively in respiring cells but not in fermenting cells in our sample set, including CSM4, SPR1, SPS4 and RIM4, which were thought to be meiosis-specific. Our work reveals intertwined transcriptional and post-transcriptional control mechanisms acting when a MATa/α strain responds to nutritional signals, and provides molecular clues how the carbon source primes yeast cells for entering meiosis. Our integrated genomics study provides insight into the interplay between the transcriptome and the proteome in diploid yeast cells undergoing vegetative growth in the presence of glucose (fermentation) or acetate (respiration). Furthermore, it reveals novel target genes involved in these processes for Ume6, the DNA binding subunit of the conserved histone deacetylase Rpd3 and the co-repressor Sin3. We have combined data from an RNA profiling experiment using tiling arrays that cover the entire yeast genome, and a large-scale protein detection analysis based on mass spectrometry in diploid MATa/α cells. This distinguishes our study from most others in the field-which investigate haploid yeast strains-because only diploid cells can undergo meiotic development in the simultaneous absence of a non-fermentable carbon source and nitrogen. Indeed, we report molecular clues how respiration of acetate might prime diploid cells for efficient spore formation, a phenomenon that is well known but poorly understood.
ISSN: 1874-3919

hal-01122122
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122122
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122122/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122122/file/Integrated%20RNA-%20and%20protein%20profiling%20of%20fermentation.pdf
DOI : 10.1016/j.jprot.2015.01.015

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background & Aims: The severity of liver diseases is exacerbated by the death of hepatocytes, which can be induced by the sensing of pathogen associated molecular patterns (PAMPs) derived from the gut microbiota. The molecular mechanisms regulating these cell death pathways are poorly documented. In this study, we investigated the role of the receptor interacting protein kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-induced hepatitis. Methods: Hepatitis was induced in mice by independent injections of two different bacterial PAMPs: lipopolysaccharide (LPS) and unmethylated CpG oligodeoxynucleotide (CpG-DNA) motifs. The role of RIPK1 was evaluated by using mice specifically lacking RIPK1 in liver parenchymal cells (Ripk1(LPC-KO)). Administration of liposome-encapsulated clodronate served to investigate the role of Kupffer cells in the establishment of the disease. Etanercept, a tumor necrosis factor (TNF)-decoy receptor, was used to study the contribution of TNF-alpha during LPS-mediated liver injury. Results: Whereas RIPK1 deficiency in liver parenchymal cells did not trigger basal hepatolysis, it greatly sensitized hepatocytes to apoptosis and liver damage following a single injection of LPS or CpG-DNA. Importantly, hepatocyte death was prevented by previous macrophage depletion or by TNF inhibition. Conclusions: Our data highlight the pivotal function of RIPK1 in maintaining liver homeostasis in conditions of macrophage-induced TNF burst in response to PAMPs sensing. Lay summary: Excessive death of hepatocytes is a characteristic of liver injury. A new programmed cell death pathway has been described involving upstream death ligands such as TNF and downstream kinases such as RIPK1. Here, we show that in the presence of LPS liver induced hepatic injury was due to secretion of TNF by liver macrophages, and that RIPK1 acts as a powerful protector of hepatocyte death. This newly identified pathway in the liver may be helpful in the management of patients to predict their risk of developing acute liver failure. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
ISSN: 0168-8278

hal-01532060
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01532060
DOI : 10.1016/j.jhep.2017.01.005
PUBMED : 28088582

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The Iranian plateau is a flat ~ 1.5–2 km high plateau thought to result from the collision between the Arabian and Eurasian plates since ~ 30 ± 5 Ma, and may represent a young analogue to the so far better studied Tibetan plateau. In order to constrain the exhumation history of the internal Zagros and of the Iranian plateau, we herein present apatite (U-Th)/He (AHe) and apatite (AFT) and zircon fission-track (ZFT) data on plutonic rocks from the Sanandaj–Sirjan Zone (SSZ), Urumieh–Dokhtar magmatic arc (UDMA), Central Iran and Kopet Dagh. Thermochronologic data show that the SSZ was exhumed early in the collision process (essentially before 25–20 Ma), with a likely acceleration of cooling during the late Eocene, from 0.04 to 0.3 mm/year. Results suggest that cooling of the internal Zagros migrated from the SSZ to the UDMA during a more mature stage of the continental collision, after ~ 17 Ma (i.e., coeval with the outward propagation of deformation and topography fronts in the external Zagros). Constant exhumation rates in the UDMA (~ 0.3 mm/year) suggest that no significant variation of erosion rates occurred since the onset of continental collision. In Central Iran, the overlap of ZFT, AFT and AHe ages from gneissic samples points to rapid cooling during the late Eocene (~ 42 °C/Myr), which is consistent with previous reports on the formation of Eocene metamorphic core-complexes.
ISSN: 0024-4937

hal-01115691
https://hal.archives-ouvertes.fr/hal-01115691
DOI : 10.1016/j.lithos.2014.07.021

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Saccharomyces cerevisiae is an established model organism for the molecular analysis of fundamental biological processes. The genomes of numerous strains have been sequenced, and the transcriptome and proteome ofmajor phases during the haploid and diploid yeast life cycle have been determined. However, much less is known about dynamic changes of the proteome when cells switch from mitotic growth to meiotic development. We report a quantitative protein profiling analysis of yeast cell division and differentiation based on mass spectrometry. Information about protein levels was integrated with strand-specific tiling array expression data. We identified a total of 2366 proteins in at least one condition, including 175 proteins showing a statistically significant > 5-fold change across the sample set, and 136 proteins detectable in sporulating but not respiring cells. We correlate protein expression patterns with biological processes and molecular function by Gene Ontology term enrichment, chemoprofiling, transcription interference and the formation of double stranded RNAs by overlapping sense/antisense transcripts. Our work provides initial quantitative insight into protein expression in diploid respiring and differentiating yeast cells. Critically, it associates developmentally regulated induction of antisense long noncoding RNAs and double stranded RNAs with fluctuating protein concentrations during growth and development.
ISSN: 1874-3919

hal-01485858
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01485858
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01485858/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01485858/file/Becker%20et%20al.%20-%20The%20protein%20expression%20landscape%20of%20mitosis%20and%20me.pdf
DOI : 10.1016/j.jprot.2016.12.016

Éditeur(s) : Elsevier
Résumé : To better understand the recent motion of the Pacific plate relative to the Rivera plate and to better define the limitations of the existing Rivera-Pacific plate motion models for accurately predicting this motion, total-field magnetic data, multibeam bathymetric data and sidescan sonar images were collected during the BART and FAMEX campaigns of the N/O L'Atalante conducted in April and May 2002 in the area surrounding the Moctezuma Spreading Segment of the East Pacific Rise, located offshore of Manzanillo, Mexico, at 106 degrees 16'W, between 17.8 degrees N and 18.5 degrees N. Among the main results are: (1) the principle transform displacement zone of the Rivera Transform is narrow and well defined east of 107 degrees 15'W and these azimuths should be used preferentially when deriving new plate motion models, and (2) spreading rates along the Moctezuma Spreading Segment should not be used in plate motion studies as either seafloor spreading has been accommodated at more than one location since the initiation of seafloor spreading in the area of the Moctezuma Spreading Segment, or this spreading center is not a Rivera-Pacific plate boundary as has been previously assumed. Comparison of observed transform azimuths with those predicted by the best-fit poles of six previous models of Rivera-Pacific relative motion indicate that, in the study area, a significant systematic bias is present in the predictions of Rivera-Pacific motion. Although the exact source of this bias remains unclear, this bias indicates the need to derive a new Rivera-Pacific relative plate motion model.
Tectonophysics (0040-1951) (Elsevier), 2008-06 , Vol. 454 , N. 1-4 , P. 70-85

Droits : 2008 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/2008/publication-4486.pdf
DOI:10.1016/j.tecto.2008.04.013
http://archimer.ifremer.fr/doc/00000/4486/

Éditeur(s) : HAL CCSD
Résumé : International audience
Two opposing visions of the Aegean backarc tectonics implicitly contain contrasting images of the rheological behaviour of the lihosphere, supported by different sets of observations. The propagation of the NAF and extension in the Corinth Rift suggest a strongly localising rheology whereas the formation of MCC in the Cyclades and the Rhodope suggests instead a more viscous behaviour. This paradox was the seminal question addressed by the ANR-EGEO programme (2007-2010) that leads to the following conclusions: (1) The exhumation of the Cycladic MCC's is accommodated by the N-dipping North Cycladic Detachment System (NCDS) that partly reworks the Vardar suture and at the base by a series of thrusts, including the basal contact of the Cycladic Blueschists (CBS) over the Cycladic Basement (CB). The activity of LANF is due to the reactivation of pre-existing discontinuities such as thrusts or earlier detachments and much less to the interaction with granitic plutons. (2) Exhumation in the Cyclades has proceeded in two stages: (a) Eocene syn-orogenic exhumation within the subduction lower/upperplate interface while the post-orogenic Rhodope MCC formed further north, (b) Oligo-Miocene post-orogenic extension in an MCC mode coeval with syn-orogenic exhumation in Crete and the Peloponnese. (3) Both stages were associated with slab retreat, as early as the Eocene with an acceleration at 30-35 Ma. (4) The localisation of the presently active steeply-dipping normal faults on the southern margin of the Corinth Rift may have been preceded by a partial reworking of thrusts and syn-orogenic detachments by shallow-dipping decollements. (5) The localisation of the NAF in the Marmara Sea region and the Northern Aegean Sea is now accurately dated between 5.3 and 5 Ma Ma using the erosion and deposition surfaces that mark the Messinian salinity Crisis and nannofossils ages. (6) The formation of MCCs in the Cyclades resulted in the draining of the low viscosity lower crust from the northern Aegean Sea and led to an easier coupling between upper mantle and upper crust, easing the localisation and propagation of the NAF. (7) A comparison between crustal and mantle finite strain suggests that mantle flow due to slab retreat controls the stretching of the crust. Our model involves progressive slab retreat and mantle flow below the overriding plate inducing the observed succession of tectonic episodes with a progressive localisation of extension due to several slab tearing events. There is no paradox in the tectonic history and rheological behaviour of the Aegean lithosphere but an evolution of the kinematic boundary conditions due to slab deformation at depth.
American Geophysical Union
San Francisco, United States

insu-00860518
https://hal-insu.archives-ouvertes.fr/insu-00860518
BIBCODE : 2010AGUFM.T13G..04J

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Hepatocyte death is a central event during liver disease progression, in which immune cells play key roles by activating members of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF), including TNFR1 (TNFRSF1A), Fas (TNFRSF6) and TRAIL-R2 (TNFRSF10B). Receptor Interacting Protein Kinase 1 (RIPK1) emerged as a signaling node downstream of these receptors. In the case of TNFR1, RIPK1 has been demonstrated to paradoxically serve as a scaffold to promote the survival of hepatocytes and as a kinase to kill them. To evaluate whether RIPK1 also protects hepatocytes from death in response to FasL or TRAIL, we took advantage of liver parenchymal cell-specific Ripk1 knockout mice (Ripk1 (LPC-KO)). We found that Ripk1 (LPC-KO) mice, as well as primary hepatocytes derived from them, were more susceptible to Fas-mediated apoptosis than their respective WT counterparts. Fas-induced hepatocyte death was independent of TNF-α signaling. Interestingly, while TRAIL administration did not induce hepatitis in Ripk1 (LPC-KO) mice or in their WT counterparts, its combination with IFN-γ only induced TNF-α dependent apoptosis in the Ripk1 (LPC-KO) mice. Together, our data demonstrate the protective role of RIPK1 downstream of Fas and highlight the general protective function of RIPK1 in hepatocytes exposed to inflammatory conditions, where TNF-α, FasL and/or TRAIL are present.
ISSN: 2045-2322

hal-01579612
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579612
DOI : 10.1038/s41598-017-09789-8
PUBMED : 28835677