Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: Phthalic acid esters are widely used in the manufacture of plastics. Numerous studies have shown that these phthalates impair testicular testosterone production in the rat. However, the scarce and contradictory data concerning humans have cast doubt over whether these compounds are also anti-androgenic in man. We therefore investigated the direct effects of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) on organo-cultured adult human testis and a human cell line. METHODS: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with DEHP or MEHP. The effects of ketoconazole, used as a reference molecule, were also assessed. RESULTS: In both models, DEHP and MEHP significantly inhibited testosterone production. The effects of both phthalates appeared to be specific for steroidogenesis, as INSL3 production by Leydig cells was not altered. Furthermore, the phthalates of interest had no effect on inhibin B production by Sertoli cells or on germ cell apoptosis. As only a small fraction of the phthalates added was found in the testis explants, and as these compounds were found to be metabolized, we estimate that the anti-androgenic effects observed occurred at concentrations of phthalates that are of the same order of magnitude as exposures reported in the literature for men. CONCLUSIONS: We provide the first evidence that DEHP and MEHP can inhibit testosterone production in the adult human testis. This is consistent with recent epidemiological findings of an inverse correlation between exposure to MEHP and testosterone concentrations.
ISSN: 0268-1161

hal-00876965
https://hal.archives-ouvertes.fr/hal-00876965
DOI : 10.1093/humrep/des069
PUBMED : 22402212

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Convergent plate margins typically experience a transition from subduction to collision dynamics as massive continental blocks enter the subduction channel. Studies of high-pressure rocks indicate that tectonic fragments are rapidly exhumed from eclogite facies to mid-crustal levels, but the details of such dynamics are controversial. To understand the dynamics of a subduction channel we report the results of a petrochronological study from the central Sesia Zone, a key element of the internal Western Alps. This comprises two polymetamorphic basement complexes (Eclogitic Micaschist Complex and Gneiss Minuti Complex) and a thin, dismembered cover sequence (Scalaro Unit) associated with pre-Alpine metagabbros and metasediments (Bonze Unit). Structurally controlled samples from three of these units (Eclogitic Micaschist Complex and Scalaro-Bonze Units) yield unequivocal petrological and geochronological evidence of two distinct high-pressure stages. Ages (U-Th-Pb) of growth zones in accessory allanite and zircon, combined with inclusion and textural relationships, can be tied to the multi-stage evolution of single samples. Two independent tectono-metamorphic 'slices' showing a coherent metamorphic evolution during a given time interval have been recognized: the Fondo slice (which includes Scalaro and Bonze rocks) and the Druer slice (belonging to the Eclogitic Micaschist Complex). The new data indicate separate stages of deformation at eclogite-facies conditions for each recognized independent kilometer-sized tectono-metamorphic slice, between ∼85 and 60 Ma, with evidence of intermittent decompression (ΔP ∼ 0*5 GPa) within only the Fondo slice. The evolution path of the Druer slice indicates a different P-T-time evolution with prolonged eclogite-facies metamorphism between ∼85 and 75 Ma. Our approach, combining structural, petrological and geochronological techniques, yields field-based constraints on the duration and rates of dynamics within a subduction channel.
ISSN: 0022-3530

hal-01054335
https://hal.archives-ouvertes.fr/hal-01054335
DOI : 10.1093/petrology/egu029

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : Publication Inra prise en compte dans l'analyse bibliométrique des publications scientifiques mondiales sur les Fruits, les Légumes et la Pomme de terre. Période 2000-2012. http://prodinra.inra.fr/record/256699
Background and Aims Plastic tree-shelters are increasingly used to protect tree seedlings against browsing animals and herbicide drifts. The biomass allocation in young seedlings of deciduous trees is highly disturbed by common plastic tree-shelters, resulting in poor root systems and reduced diameter growth of the trunk. The shelters have been improved by creating chimney-effect ventilation with holes drilled at the bottom, resulting in stimulated trunk diameter growth, but the root deficit has remained unchanged. An experiment was set up to elucidate the mechanisms behind the poor root growth of sheltered Prunus avium trees. Methods Tree seedlings were grown either in natural windy conditions or in tree-shelters. Mechanical wind stimuli were suppressed in ten unsheltered trees by staking. Mechanical stimuli (bending) of the stem were applied in ten sheltered trees using an original mechanical device. Key Results Sheltered trees suffered from poor root growth, but sheltered bent trees largely recovered, showing that mechano-sensing is an important mechanism governing C allocation and the shoot-root balance. The use of a few artificial mechanical stimuli increased the biomass allocation towards the roots, as did natural wind sway. It was demonstrated that there was an acclimation of plants to the imposed strain. Conclusions This study suggests that if mechanical stimuli are used to control plant growth, they should be applied at low frequency in order to be most effective. The impact on the functional equilibrium hypothesis that is used in many tree growth models is discussed. The consequence of the lack of mechanical stimuli should be incorporated in tree growth models when applied to environments protected from the wind (e.g. greenhouses, dense forests).
ISSN: 0305-7364

hal-01032056
https://hal.archives-ouvertes.fr/hal-01032056
DOI : 10.1093/aob/mcn054

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
It was recently reported that the sizes of many mRNAs change when budding yeast cells exit mitosis and enter the meiotic differentiation pathway. These differences were attributed to length variations of their untranslated regions. The function of UTRs in protein translation is well established. However, the mechanism controlling the expression of distinct transcript isoforms during mitotic growth and meiotic development is unknown. In this study, we order developmentally regulated transcript isoforms according to their expression at specific stages during meiosis and gametogenesis, as compared to vegetative growth and starvation. We employ regulatory motif prediction, in vivo protein-DNA binding assays, genetic analyses and monitoring of epigenetic amino acid modification patterns to identify a novel role for Rpd3 and Ume6, two components of a histone deacetylase complex already known to repress early meiosis-specific genes in dividing cells, in mitotic repression of meiosis-specific transcript isoforms. Our findings classify developmental stage-specific early, middle and late meiotic transcript isoforms, and they point to a novel HDAC-dependent control mechanism for flexible transcript architecture during cell growth and differentiation. Since Rpd3 is highly conserved and ubiquitously expressed in many tissues, our results are likely relevant for development and disease in higher eukaryotes.
ISSN: 0305-1048

Droits : http://creativecommons.org/licenses/by/
hal-01122128
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122128
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122128/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122128/file/The%20conserved%20histone%20deacetylase.pdf
DOI : 10.1093/nar/gku1185

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : This paper presents an inversion method using the interseismic velocity field to determine effective rigidity of the lithosphere. The method is based on the minimization of a cost function defined as the quadratic measure of the difference between measured and modelled velocity fields on a discrete set of points. The continuous mapping of the rigidity is fulfilled with a limited set of parameters and the forward solution is achieved using a plane stress finite element code. The computation of the cost function gradient in the parameters' space allows one to iteratively find the best parameters set through a suitable optimization algorithm.;We first design a benchmark including an abrupt rigidity variation that cannot be described by a continuous function. For such a case, we show that increasing the number of parameters is a way to accurately describe sharp variations of the rigidity map. Then, we use a dense GPS velocity field over the southwestern United States to estimate the corresponding rigidity variations for different spatial resolutions of the parameters' grid. We analyse the conceptual and practical difficulties associated with our methodology. Finally, rigidity maps obtained by our inversion method in southwestern United States and particularly across the San Andreas Fault System are reviewed and compared to current plate rigidity estimates and geophysical data over this area.
ISSN: 0956-540X

hal-00669897
https://hal.archives-ouvertes.fr/hal-00669897
DOI : 10.1111/j.1365-246X.2011.05192.x

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B - Oxford Open Option A
Résumé :  
absent
Journal of Experimental Botany

hal-01032195
https://hal.archives-ouvertes.fr/hal-01032195
DOI : 10.1093/jxb/erp276

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
ISSN: 1058-4838

hal-01118447
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118447
PUBMED : 25139963
DOI : 10.1093/cid/ciu659

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
We analyse temporal variations of gravity measured in southern Taiwan since November 2006 at 10 sites using absolute gravimeters and, since November 2008, at 70 sites using a relative gravimeter. We describe and apply methods to interpret the gravity changes in terms of local hydrological processes and vertical ground motions. The effect of land water is computed from local rainfall data and a model of rain accumulation and discharge in the ground. The effect of the vertical motions of the ground is estimated using time-series of permanent Global Positioning System (GPS) stations and the theoretical gravity to height ratio of −2 μGal cm−1. Unexpectedly, Morakot typhoon (2009 August), the strongest typhoon in Taiwan in 50 yr, was responsible for the highest gravity changes. Morakot triggered numerous large landslides and debris flow deposits. Their thicknesses are estimated from the gravity changes (up to ∼280 μGal) along with field observations and satellite images.
ISSN: 0956-540X

hal-00768216
https://hal.archives-ouvertes.fr/hal-00768216
DOI : 10.1093/gji/ggs019

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B - Oxford Open Option A
Résumé :  
The mechanism for tree orientation in angiosperms is based on the production of high tensile stress on the upper side of the inclined axis. In many species, the stress level is strongly related to the presence of a peculiar layer, called the G-layer, in the fibre cell wall. The structure of the G-layer has recently been described as a hydrogel thanks to N2 adsorption-desorption isotherms of supercritically dried samples showing a high mesoporosity (pores size from 2-50 nm). This led us to revisit the concept of the G-layer that had been, until now, only described from anatomical observation. Adsorption isotherms of both normal wood and tension wood have been measured on six tropical species. Measurements show that mesoporosity is high in tension wood with a typical thick G-layer while it is much less with a thinner G-layer, sometimes no more than normal wood. The mesoporosity of tension wood species without a G-layer is as low as in normal wood. Not depending on the amount of pores, the pore size distribution is always centred around 6-12 nm. These results suggest that, among species producing fibres with a G-layer, large structural differences of the G-layer exist between species.
Journal of Experimental Botany

hal-01032161
https://hal.archives-ouvertes.fr/hal-01032161
DOI : 10.1093/jxb/erp133

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B - Oxford Open Option B
Résumé : absent
ISSN: 0829-318X

hal-01031083
https://hal.archives-ouvertes.fr/hal-01031083

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
A network of 26 GPS sites was implemented in Iran and Northern Oman to measure displacements in this part of the Arabia–Eurasia collision zone. We present the GPS velocity field obtained from three surveys performed in 1999 September, 2001 October and 2005 September and the deduced strain tensor. This study refines previous studies inferred from only the two first surveys. Improvements are significant in NE Iran. The present-day shortening rate across the mountain belts of NE Iran is estimated to 5 ± 1 mm yr−1 at about N11°, 2 ± 1 mm yr−1 of NS shortening across the eastern Kopet Dag and 3 ± 1 mm yr−1 of NS shortening across Binalud and Kuh-e-Sorkh. Our GPS measurements emphasize the varying character of the Kopet Dag deformation between its southeastern part with prevailing thrusting at low rates and its northwestern part with dominant strike-slip activity at increasing rates. The principal axes of the horizontal strain tensor appears very homogeneous from the Zagros to the Alborz and the Kopet-Dag (N20°) and in eastern Iran (Makran and Lut block: N30°). Only NW Iran suffers a variable strain pattern which seems to wrap the Caspian basin. The strain tensor map underlines the existence of large homogeneous tectonic provinces in terms of style and amplitude of the deformation.
ISSN: 0956-540X

insu-00346744
https://hal-insu.archives-ouvertes.fr/insu-00346744
DOI : 10.1111/j.1365-246X.2007.03477.x

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
The activity of diethylcarbamazine (DEC) and suramin (S) on Litomosoides carinii filariasis was assessed by the study of microfilaraemia in 30 cotton-rats (Sigmodon hispidus). DEC (per os) and S (injected subcutaneously) were administered alone or in combination, at doses of 50 mg/kg/day for five consecutive days. 15 rats were treated at day 91 after infection and 15 others at day 184. The immediate but temporary efficacy observed with DEC was in contrast to the delayed and long-lasting effect of S. With combined therapy there was neither antagonism nor synergism. The demonstration of an apparently smaller reduction of parasitaemia in the rats treated with DEC before the plateau phase of the microfilaraemia was consistent with the lack of action of this drug on microfilariae outside the blood system.
ISSN: 0035-9203

hal-00717073
https://hal.univ-antilles.fr/hal-00717073
PUBMED : 7034313

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Background and Aims: In rain forests, sapling survival is highly dependent on the regulation of trunk slenderness (height/diameter ratio): shade-intolerant species have to grow in height as fast as possible to reach the canopy but also have to withstand mechanical loadings (wind and their own weight) to avoid buckling. Recent studies suggest that mechanosensing is essential to control tree dimensions and stability-related morphogenesis. Differences in species slenderness have been observed among rainforest trees; the present study thus investigates whether species with different slenderness and growth habits exhibit differences in mechanosensitivity. Methods: Recent studies have led to a model of mechanosensing (sum-of-strains model) that predicts a quantitative relationship between the applied sum of longitudinal strains and the plant's responses in the case of a single bending. Saplings of five different neotropical species (Eperua falcata, E. grandiflora, Tachigali melinonii, Symphonia globulifera and Bauhinia guianensis) were subjected to a regimen of controlled mechanical loading phases (bending) alternating with still phases over a period of 2 months. Mechanical loading was controlled in terms of strains and the five species were subjected to the same range of sum of strains. The application of the sum-of-strain model led to a dose-response curve for each species. Dose-response curves were then compared between tested species. Key Results: The model of mechanosensing (sum-of-strain model) applied in the case of multiple bending as long as the bending frequency was low. A comparison of dose-response curves for each species demonstrated differences in the stimulus threshold, suggesting two groups of responses among the species. Interestingly, the liana species B. guianensis exhibited a higher threshold than other Leguminosae species tested. Conclusions: This study provides a conceptual framework to study variability in plant mechanosensing and demonstrated interspecific variability in mechanosensing.
ISSN: 0305-7364

halsde-00454145
https://hal.archives-ouvertes.fr/halsde-00454145
DOI : 10.1093/aob/mcp286

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
IODP Expedition 352 cored igneous rocks from the Izu-Bonin-Mariana forearc crust. Cores from Sites U1440 and U1441 recovered Eocene basalts and related rocks and cores from Sites U1439 and U1442 recovered Eocene boninites and related rocks. We selected samples from Holes U1439C, U1440B and U1442A for palaeointensity measurements. Hysteresis measurements and high and low-temperature magnetization curves show that samples from Hole U1440B undergo magneto-chemical changes when heated and are mostly composed of single-domain (SD) or pseudo-single-domain (PSD) titanomaghemite. In contrast, the same measurements show that most selected samples from Holes U1439C and U1442A are thermally stable and are composed of either SD or PSD titanomagnetite with very little titanium content, or SD ferromagnetic grains with a large paramagnetic contribution. Thellier–Thellier palaeointensity experiments carried out on U1439C and U1442A samples give a good success rate of 25/60 and Virtual Dipole Moment (VDM) values between 1.3 and 3.5 × 1022 Am2. Multispecimen palaeointensity experiments with the domain-state corrected method carried out on 55 samples from Hole U1440B (divided into four groups) and 20 from Hole U1439C gave poor quality results, but indicated a VDM around 4–6 × 1022 Am2 in Hole U1440B forearc basalts. These results are in agreement with the few, low VDM values previously measured on Eocene rocks. However, they do not support an inverse relationship between field intensity and reversal rate for this period of time, since the Eocene reversal rate was low.
ISSN: 0956-540X

hal-01622775
https://hal.archives-ouvertes.fr/hal-01622775
https://hal.archives-ouvertes.fr/hal-01622775/document
https://hal.archives-ouvertes.fr/hal-01622775/file/carvalloGJI2017.pdf
DOI : 10.1093/gji/ggx208

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
The mechanism for tree orientation in angiosperms is based on the production of high tensile stress on the upper side of the inclined axis. In many species, the stress level is strongly related to the presence of a peculiar layer, called G-layer, in the fibre wall. The structure of G-layer has been recently described as a hydrogel thanks to N2 adsorption-desorption isotherms of supercritically dried samples showing a high mesoporosity (pores size from 2 to 50 nm). This led us to revisit the concept of G-layer that was until now only described from anatomical observation. Adsorption isotherms of both normal wood and tension wood have been measured on six tropical species. Measurements show that mesoporosity is high in tension wood with typical thick G-layer while it is much less with thinner G-layer, sometimes no more than normal wood. The mesoporosity of tension wood species without G-layer is as low as in normal wood. Not depending on the amount of pores, the pore sizes distribution are always centred around 6-12 nm. These results suggest that, among species producing fibres with G-layer, large structural differences of G-layer exist between species
ISSN: 0022-0957

hal-00387861
https://hal.archives-ouvertes.fr/hal-00387861
DOI : 10.1093/jxp/erp133

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B - Oxford Open Option B
Résumé : International audience
To recover verticality after disturbance, angiosperm trees produce " tension wood " allowing them to bend actively. The driving force of the tension has been shown to take place in the G-layer, a specific unlignified layer of the cell wall observed in most temperate species. However, in tropical rain forests, the G-layer is often absent and the mechanism generating the forces to reorient trees remains unclear. A study was carried out on tilted seedlings, saplings and adult Simarouba amara trees – a species known to not produce a G-layer. Microscopic observations were done on sections of normal and tension wood after staining or observed under UV light to assess the presence/absence of lignin. We showed that S. amara produces a cell-wall layer with all of the characteristics typical of G-layers, but that this G-layer can be observed only as a temporary stage of the cell-wall development because it is masked by a late lignification. Being thin and lignified, tension wood fibres cannot be distinguished from normal wood fibres in the mature wood of adult trees. These observations indicate that the mechanism generating the high tensile stress in tension wood is likely to be the same as that in species with a typical G-layer and also in species where the G-layer cannot be observed in mature cells.
ISSN: 0829-318X

hal-01229280
https://hal.archives-ouvertes.fr/hal-01229280
https://hal.archives-ouvertes.fr/hal-01229280/document
https://hal.archives-ouvertes.fr/hal-01229280/file/Roussel-Clair-2015-TreePhysiol-LateLignifGLayerSimarouba_preprintHAL.pdf
DOI : 10.1093/treephys/tpv082

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Although semen is the principal vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the infected leukocytes and free viral particles in this body fluid remain elusive. Here we review the accumulated evidence of the genital origin of HIV in semen from therapy naive individuals and men receiving suppressive highly active antiretroviral therapy (HAART), summarize the data on the detection and localization of HIV/SIV within the male genital tract, discuss the potential involvement of each genital tissue as a source of infected cells and virions in semen in the absence and presence of HAART, and suggest further studies. Deciphering the exact sources of HIV in semen will be crucial to improving HIV transmission prevention strategies.
ISSN: 0022-1899

hal-01121761
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121761
PUBMED : 25414416
DOI : 10.1093/infdis/jiu328

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Our knowledge and understanding of the 3-D lithospheric structure of the Himalayas and the Tibetan Plateau is still challenging although numerous geophysical studies have been performed in the region. The GOCE satellite mission has the ambitious goal of mapping Earth's gravity field with unprecedented precision (i.e. an accuracy of 1-2 mGal for a spatial resolution of 100 km) to observe the lithosphere and upper-mantle structure. Consequently, it gives new insights in the lithospheric structure beneath the Himalayas and the Tibetan Plateau. Indeed, the GOCE gravity data now allow us to develop a new strategy for joint gravimetry-seismology inversion. Combined with teleseismic data over a large region in a joint inversion scheme, they will lead to lithospheric velocity-density models constrained in two complementary ways. We apply this joint inversion scheme to the Hi-CLIMB (Himalayan-Tibetan Continental Lithosphere during Mountain Building) seismological network which was deployed in South Tibet and the Himalayas for a 3-yr period. The large size of the network, the high quality of the seismological data and the new GOCE gravity data set allow us to image the entire lithosphere of this active area in an innovative way. We image 3-D low velocity and density structures in the middle crust that fit the location of discontinuous low S-velocity zones revealed by receiver functions in previous geophysical studies. In the deeper parts of our velocity model we image a positive anomaly interpreted to be the heterogenous Indian lithosphere vertically descending beneath the centre of the Tibetan Plateau.
ISSN: 0956-540X

hal-00858024
https://hal.archives-ouvertes.fr/hal-00858024
DOI : 10.1093/gji/ggs110

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear. METHODS: We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression. RESULTS: During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment. CONCLUSIONS: Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.
ISSN: 0300-5771

hal-00875138
https://hal.archives-ouvertes.fr/hal-00875138
DOI : 10.1093/ije/dys164
PUBMED : 23148105

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10(-9)-10(-5) M for 24 or 48 h. Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10(-9) M; P < 0.05), BPB (10(-9) M; P < 0.05), BPS (10(-9) and 10(-8) M; P < 0.05) and BADGE (10(-5) M; P < 0.05) increased Leydig cell INSL3 production. By contrast, BPE dose dependently inhibited INSL3 (P = 0.0372). Conversely, Sertoli cell function (inhibin B) and germ cell viability were not significantly affected by either bisphenols. N/A. Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for testosterone secretion with n = 5). The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis.
ISSN: 0268-1161

hal-01578582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582/file/Parallel%20assessment%20of%20the%20effects%20of%20bisphenol%20A_accepted.pdf
DOI : 10.1093/humrep/dex093