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) : HAL CCSD Frontiers
Résumé : International audience
Estrogens can induce rapid, short-lived physiological and behavioral responses, in addition to their slow, but long-term, effects at the transcriptional level. To be functionally relevant, these effects should be associated with rapid modulations of estrogens concentrations. 17β-estradiol is synthesized by the enzyme aromatase, using testosterone as a substrate, but can also be degraded into catechol-estrogens via hydroxylation by the same enzyme, leading to an increase or decrease in estrogens concentration, respectively. The first evidence that aromatase activity (AA) can be rapidly modulated came from experiments performed in Japanese quail hypothalamus homogenates. This rapid modulation is triggered by calcium-dependent phosphorylations and was confirmed in other tissues and species. The mechanisms controlling the phosphorylation status, the targeted amino acid residues and the reversibility seem to vary depending of the tissues and is discussed in this review. We currently do not know whether the phosphorylation of the same amino acid affects both aromatase and/or hydroxylase activities or whether these residues are different. These processes provide a new general mechanism by which local estrogen concentration can be rapidly altered in the brain and other tissues.
ISSN: 1662-4548

Droits : http://creativecommons.org/licenses/by/
hal-01142062
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01142062
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01142062/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01142062/file/fnins-09-00083.pdf
PUBMED : 25852459

Éditeur(s) : HAL CCSD Cambridge University Press (CUP)
Résumé : International audience
This paper presents a synthetic view of the geodynamic evolution of the Zagros orogen within the frame of the Arabia-Eurasia collision. The Zagros orogen and the Iranian plateau preserve a record of the long-standing convergence history between Eurasia and Arabia across the Neo-Tethys, from subduction/obduction processes to present-day collision (from ~ 150 to 0 Ma). We herein combine the results obtained on several geodynamic issues, namely the location of the oceanic suture zone, the age of oceanic closure and collision, the magmatic and geochemical evolution of the Eurasian upper plate during convergence (as testified by the successive Sanandaj-Sirjan, Kermanshah and Urumieh-Dokhtar magmatic arcs), the P-T-t history of the few Zagros blueschists, the convergence characteristics across the Neo-Tethys (kinematic velocities, tomographic constraints, subduction zones and obduction processes), together with a survey of recent results gathered by others. We provide lithospheric-scale reconstructions of the Zagros orogen from ~ 150 to 0 Ma across two SW-NE transects. The evolution of the Zagros orogen is also compared to those of the nearby Turkish and Himalayan orogens. In our geotectonic scenario for the Zagros convergence, we outline three main periods/regimes: (1) the Mid to Late Cretaceous (115-85 Ma) corresponds to a distinctive period of perturbation of subduction processes and interplate mechanical coupling marked by blueschist exhumation and upper-plate fragmentation, (2) the Paleocene-Eocene (60-40 Ma) witnesses slab break-off, major shifts in arc magmatism and distributed extension within the upper plate, and (3) from the Oligocene onwards (~ 30-0 Ma), collision develops with a progressive SW migration of deformation and topographic build-up (Sanandaj-Sirjan Zone: 20-15 Ma, High Zagros: ~12-8 Ma; Simply Folded Belt: 5-0 Ma) and with partial slab tear at depths (~10 Ma to present). Our reconstructions underline the key role played by subduction throughout the whole convergence history. We finally stress that such a long-lasting subduction system with changing boundary conditions also makes the Zagros orogen an ideal natural laboratory for subduction processes.
ISSN: 0016-7568

insu-00616582
https://hal-insu.archives-ouvertes.fr/insu-00616582
https://hal-insu.archives-ouvertes.fr/insu-00616582/document
https://hal-insu.archives-ouvertes.fr/insu-00616582/file/692.full.pdf
DOI : 10.1017/S001675681100046X

Éditeur(s) : HAL CCSD American College of Physicians
Résumé : International audience
BACKGROUND: Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. OBJECTIVE: To identify the optimal CD4 cell count at which cART should be initiated. DESIGN: Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. SETTING: HIV clinics in Europe and the Veterans Health Administration system in the United States. PATIENTS: 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. MEASUREMENTS: Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. RESULTS: Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations: CD4 cell count at cART initiation was not randomized. Residual confounding may exist. CONCLUSION: Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.
ISSN: 0003-4819

hal-00875307
https://hal.archives-ouvertes.fr/hal-00875307
PUBMED : 21502648
DOI : 10.7326/0003-4819-154-8-201104190-00001

Éditeur(s) : HAL CCSD Frontiers Media
Résumé : The disease, Heartwater, caused by the Anaplasmataceae E. ruminantium, represents a major problem for tropical livestock and wild ruminants. Up to now, no effective vaccine has been available due to a limited cross protection of vaccinal strains on field strains and a high genetic diversity of Ehrlichia ruminantium within geographical locations. To address this issue, we inferred the genetic diversity and population structure of 194 E. ruminantium isolates circulating worldwide using Multilocus Sequence Typing based on lipA, lipB, secY, sodB, and sucA genes. Phylogenetic trees and networks were generated using BEAST and SplitsTree, respectively, and recombination between the different genetic groups was tested using the PHI test for recombination. Our study reveals the repeated occurrence of recombination between E. ruminantium strains, suggesting that it may occur frequently in the genome and has likely played an important role in the maintenance of genetic diversity and the evolution of E. ruminantium. Despite the unclear phylogeny and phylogeography, E. ruminantium isolates are clustered into two main groups: Group 1 (West Africa) and a Group 2 (worldwide) which is represented by West, East, and Southern Africa, Indian Ocean, and Caribbean strains. Some sequence types are common between West Africa and Caribbean and between Southern Africa and Indian Ocean strains. These common sequence types highlight two main introduction events due to the movement of cattle: from West Africa to Caribbean and from Southern Africa to the Indian Ocean islands. Due to the long branch lengths between Group 1 and Group 2, and the propensity for recombination between these groups, it seems that the West African clusters of Subgroup 2 arrived there more recently than the original divergence of the two groups, possibly with the original waves of domesticated ruminants that spread across the African continent several thousand years ago.
ISSN: 2235-2988

hal-01594501
https://hal.archives-ouvertes.fr/hal-01594501
https://hal.archives-ouvertes.fr/hal-01594501/document
https://hal.archives-ouvertes.fr/hal-01594501/file/paper_MLST_ER_2016_%7B51027B58-C2C7-41C8-9746-BD8A9F387C87%7D.pdf
DOI : 10.3389/fcimb.2016.00111

Éditeur(s) : HAL CCSD
Résumé : International audience
To assess prognostic factors for survival and describe Model for End-Stage liver disease (MELD) dynamics in human immunodeficiency virus+/hepatitis C virus+ (HIV+/HCV+) patients after an initial episode of hepatic decompensation.An HIV+/HCV+ cohort of patients experiencing an initial decompensation episode within the year preceding enrollment were followed prospectively. Clinical and biological data were collected every 3 months. Predictors for survival were identified using Kaplan-Meier curves and Cox models. A 2-slope-mixed linear model was used to estimate MELD score changes as a function of survival.Sixty seven patients were included in 32 centers between 2009 and 2012 (72% male; median age: 48 years [interquartile ratio (IQR):45-52], median follow-up: 22.4 months [range: 0.5-65.3]). Overall survival rates were 86%, 78%, and 59% at 6, 12, and 24 months, respectively. Under multivariate analysis, the MELD score at initial decompensation was predictive of survival, adjusted for age, type of decompensation, baseline CD4 counts, and further decompensation during follow-up as a time-dependent variable. The adjusted hazard ratio of death was 1.32 for a score 3 points higher (95% CI: [1.06-1.63], P = 0.012). MELD score kinetics within the 6 months after initial decompensation differed significantly between non-deceased and deceased patients, with a decreased (-0.49/month; P = 0.016), versus a flat (+0.06/month, P = 0.753) mean change in score.MELD is an effective tool to predict survival in HIV+/HCV+ patients with decompensated cirrhosis. A non-decreasing MELD score within 6 months following this initial decompensation episode may benefit from privileged access to liver transplantation in this poor prognosis population
Medicine

hal-01205351
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01205351
DOI : 10.1097/MD.0000000000001239
PUBMED : 26222860

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