Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study was designed to determine whether epinephrine may also target expression of main hepatic drug transporters, that play a major role in liver detoxification and are commonly coordinately regulated with drug detoxifying enzymes. Treatment of primary human hepatocytes with 10 mu M epinephrine for 24 h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP. Most of these changes in transporter mRNA levels were also found in epinephrine-exposed human highly-differentiated hepatoma HepaRG cells, which additionally exhibited reduced protein expression of OATP2B1 and MRP3, increased expression of P-glycoprotein and decreased transport activity of NTCP, OATPs and OCT1. Epinephrine effects towards transporter mRNA expression in human hepatocytes were next shown to be correlated to those of the selective beta 2-adrenoreceptor (ADR) agonist fenoterol, of the adenylate cyclase activator forskolin and of the cAMP analogue 8-bromo-cAMP. In addition, the non-selective beta-ADR antagonist carazolol and the selective beta 2-ADR antagonist ICI-118,551, unlike the alpha-ADR antagonist phentolamine, suppressed epinephrine -mediated repressions of transporter mRNA expression. Taken together, these data indicate that epinephrine regulates in vitro expression of main hepatic drug transporters in a beta 2-ADR/adenylate cyclase/cAMP-dependent manner. Hepatic drug transport appears therefore as a target of the beta 2-adrenergic system, which may have to deserve attention for drugs interacting with beta 2-ADRs.
ISSN: 0928-0987

hal-01578583
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578583
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578583/file/Mayati%20et%20al.%20-%20%CE%B22-adrenergic%20receptor-mediated%20in%20vitro%20regulatio.pdf
DOI : 10.1016/j.ejps.2017.06.010
PUBMED : 28603032

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
A hallmark of living systems is the management and the storage of information through genetic and epigenetic mechanisms. Although the notion of epigenetics was originally given to any regulation beyond DNA sequence, it has often been restricted to chromatin modifications, supposed to behave as cis-markers, specifying the sets of genes to be expressed or repressed. This definition does not take into account the initial view of epigenetics, based on nonlinear interaction networks whose "attractors" can remain stable without need for any chromatin mark. In addition, most chromatin modifications are the steady state resultants of highly dynamic modification and de-modification activities and, as such, seem poorly appropriate to work as long-term memory keepers. Instead, the basic support of epigenetic memory could remain the attractors, to which chromatin modifications belong as do many other components. The influence of chromatin modifications in memory is highly questionable when envisioned as static structural marks, but can be recovered under the dynamic circuitry perspective, thanks to their self-templating properties. Beside their standard repressive or permissive functions, chromatin modifications can also influence transcription in multiple ways such as: (1) by randomizing or inversely stabilizing gene expression, (2) by mediating cooperativity between pioneer and secondary transcription factors, and (3) in the hysteresis and the ultrasensitivity of gene expression switches, allowing the cells to take unambiguous transcriptional decisions.
ISSN: 1420-682X

hal-01063617
https://hal.archives-ouvertes.fr/hal-01063617
DOI : 10.1007/s00018-012-0923-7
PUBMED : 22331281

Éditeur(s) : HAL CCSD SPRINGER
Résumé : International audience
A key question in evolutionary biology is the reproducibility of adaptation. This question can now be quantitatively analyzed using experimental evolution coupled to whole genome sequencing (WGS). With complete sequence data, one can assess convergence among replicate populations. In turn, convergence reflects the action of natural selection and also the breadth of the field of possible adaptive solutions. That is, it provides insight into how many genetic solutions or adaptive paths may lead to adaptation in a given environment. Convergence is both a property of an adaptive landscape and, reciprocally, a tool to study that landscape. In this chapter we present the links between convergence and the properties of adaptive landscapes with respect to two types of microbial experimental evolution. The first tries to reconstruct a full adaptive landscape using a handful of carefully identified mutations (the reductionist approach), while the second uses WGS of replicate experiments to infer properties of the adaptive landscape. Reductionist approaches have highlighted the importance of epistasis in shaping the adaptive landscape, but have also uncovered a wide diversity of landscape architectures. The WGS approach has uncovered a very high diversity of beneficial mutations that affect a limited set of genes or functions and also suggests some shortcomings of the reductionist approach. We conclude that convergence may be better defined at an integrated level, such as the genic level or even at a phenotypic level, and that integrated mechanistic models derived from systems biology may offer an interesting perspective for the analysis of convergence at all levels.
ECOLOGICAL GENOMICS: ECOLOGY AND THE EVOLUTION OF GENES AND GENOMES

ISBN : 978-94-007-7347-9; 978-94-007-7346-2
hal-01544757
https://hal.archives-ouvertes.fr/hal-01544757
DOI : 10.1007/978-94-007-7347-9__11

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Formaldehyde (FA) is a volatile organic compound (VOC), considered as a major indoor air pollutant and suspected to favor the development of inflammatory lung diseases. The present study was aimed at identifying cytokines/chemokines targeted by FA in human lung cells. This VOC was demonstrated to up-regulate interleukin-11 (IL-11) mRNA and secretion levels in a dose-dependent manner in cultured lung epithelial BEAS-2B cells. It concomitantly induced mRNA expression of transforming growth factor (TGF)-β1, a fibrogenic marker regulated by IL-11. FA was also found to trigger an early phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinases (MAPKs) in BEAS-2B cells, whose inhibition by ERK and p38 MAPK chemical inhibitors (U0126 and SB203580, respectively) counteracted FA-mediated induction of IL-11. In addition, FA increased phosphorylation of cAMP response element binding protein (CREB) and the use of small-interfering RNA targeting CREB demonstrated that this transcription factor was required for the up-regulation of IL-11 by FA. Implication of protein kinase C (PKC) in FA-induced IL-11 expression was moreover demonstrated by using RO-31-8220, a PKC inhibitor. We finally showed using SB203580 and RO-31-8220 that phosphorylation of CREB and CREB-promoter activity induced by FA are under the control of both p38 MAPK and PKC. Taken together, the results showed that FA uses different pathways to induce IL-11 expression in lung BEAS-2B cells. IL-11, well-known to contribute to lung inflammatory diseases, appears thus as a molecular target of FA, which could be involved in putative deleterious inflammatory and fibrogenic pulmonary effects of this VOC.
ISSN: 0300-483X

hal-00682486
https://hal.archives-ouvertes.fr/hal-00682486
DOI : 10.1016/j.tox.2011.11.011
PUBMED : 22138297

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Clin Microbiol Infect ABSTRACT: Atypical Toxoplasma gondii strains, unrelated to archetypal clonal lineages (I, II, III), have been reported more frequently over the last decade in areas other than Europe and North America. A newly described form of toxoplasmosis, 'Amazonian toxoplasmosis' (AT), has been reported since 2002 in French Guiana. It is characterized by severe cases and atypical strains linked to a neotropical forest-based cycle. We report on the cases of AT that required intensive care management. We performed a prospective observational study on hospitalized adults in the Intensive Care Unit (ICU) from 2002 to 2008. Clinical and laboratory data, microbiological findings and outcomes were recorded. Data, including the ICU simplified acute physiology score and the pneumonia severity index, were calculated. Epidemiological risk factors for AT were assessed through questionnaires. Eleven non-immunodeficient patients were admitted to the ICU in Cayenne for life-threatening pneumonia associated with disseminated toxoplasmosis. Mechanical ventilation was necessary in seven patients, four of whom required immediate orotracheal intubation. Cardiac and ophthalmological abnormalities were found in five and four patients, respectively. One patient died from multiple organ failure. The genetic characterization of Toxoplasma DNA using six microsatellite markers revealed unique and atypical genotypes in eight patients. All patients presented epidemiological risk factors for AT. In French Guiana, significant T. gondii-related infectious syndrome associated with the lungs, a high level of LDH activity and the reported risk factors for AT was strongly suggestive of disseminated toxoplasmosis with a possible trend toward life-threatening pneumonia.
ISSN: 1198-743X

hal-00678752
https://hal-unilim.archives-ouvertes.fr/hal-00678752
DOI : 10.1111/j.1469-0691.2011.03648.x
PUBMED : 21958195

Éditeur(s) : HAL CCSD IWA Publishing
Résumé : International audience
Anti-cancer drugs are an important class of pharmaceutical products. Methotrexate (MTX) is a folic acid antagonist used in high doses as antimetabolite in anti-cancer treatment as well as in low doses for the treatment of rheumatoid arthritis and adults' psoriasis. In the past, several anti-cancer drugs, including methotrexate, have been found in the environment. Their presence in water, especially if used for the production of drinking water, is even in low concentrations of particular interest, due to the risk to retrieve them in the consumed water and their high activity and grave effects. But prior to usage as drinking water, raw waters are treated and chlorination is a common practice in several countries. As such a treatment can lead to the formation of organochlorine in water, the study of the fate of MTX during chlorination in a batch trial was carried out. The reaction was monitored by dissolved organic carbon (DOC) and by fluorescence and UV spectroscopy. Investigation of by-products formed was done with liquid chromatography/mass spectrometry (LC/MS). Under the given experimental conditions, Methotrexate was eliminated rapidly (t1/2 around 21 min). However, DOC elimination was incomplete. Monitoring with LC-MS showed the formation of a monochlorinated transformation product of MTX. In silico analysis of the proposed transformation products for different carcinogenic, mutagenic and genotoxic endpoints with different software platforms provided no clear evidence that the possible transformation products after chlorination might be more toxic than the parent compound. However, since a number of alerts is altered after chlorination, it cannot be excluded that the toxicity of these transformation products might be modulated compared with the parent compound.
ISSN: 0043-1354

hal-01016617
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01016617
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01016617/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01016617/file/Monitoringsur methotrexate_final.pdf
DOI : 10.1016/j.watres.2014.03.008

Éditeur(s) : HAL CCSD Springer Verlag
Résumé :  
A closed depression is defined as a geomorphologic element where a sediment depository is encircled by hillslopes. Despite the fact that closed depressions are often the only stagnant water points in many European landscapes, few ecological researches on their plant assemblages have been done. The main goal of this study was to give first results of the environmental factors responsible for the vegetation composition, richness and rarity in the closed depressions of the Lorraine biogeographical district (Belgium, France and grand-duche de Luxembourg). We surveyed for plant presence 85 forest and 77 grassland closed depressions. For each site, wetland area, local environmental factors and regional connectivities registered. For each species, the Ellenberg values were compiled. To investigate the main source of variation in species composition and in species richness (including richness in rare species), Non-metric Multidimensional Scaling analyses and Generalized Linear Models were respectively used. Species pools in forest (forest and preforest species) and in grassland (bog plants, pioneers, helophytes) were quite different. In both landscapes, a gradient from plants typical of basic high-productive soils to plants typical of acid low-productive soils reflects a shared successional gradient. The accumulation of organic matter allowed the establishment of Sphagnum spp., which slowly acidified the soil and thus acted as ecosystem engineers for the arrival of bog plants. Moreover, the species composition was additionally driven by the plant light tolerance in forests and by the plant water requirements in grasslands. Mechanisms of species accumulation (increase in species richness) were different in forests and in grasslands: respectively related to the plant light tolerance and to the wetland area. At the regional level, the averaged soil productivity was negatively related to the richness in rare species. Indeed, perennial highly-competitive plants such as Glyceria spp., Iris pseudacorus or Urtica dioica impeded the establishment of smaller and rarer species. At the habitat level, isolated closed depressions (due to either low connectivity or low grazing pressure) have more habitat rare species, giving evidences of dispersal limitation in plant assemblages of closed depressions.
ISSN: 0960-3115

hal-01032125
https://hal.archives-ouvertes.fr/hal-01032125
DOI : 10.1007/s10531-007-9227-x

Éditeur(s) : HAL CCSD ACM
Résumé : International audience
Environmental resources (e.g., air quality, water quantity) are needed to understand fundamental questions such as global change. Such resources are often collected from sensors, including humans acting as sensors. Tools have emerged to manage such data in the form of time series and, in particular, the Sensor Observation Service (SOS) which offers a framework based on predefined relational database schema. Environmental observatories can be built using such frameworks, allowing to address specific key scientific questions by collecting and sharing large-scale environmental data. However, the strict schema of SOS database makes it difficult to integrate some data that cannot be directly mapped to the schema. Guidelines and best practices are offered in the literature in order to reuse standards from the Semantic Web but they do not cover all needs. In particular, they do not help to reflect the fact that a single environmental database can lead to several SOS models. Since being aware of these multiple possibilities is crucial for a better use of the observatories, we argue that some extensions of the existing works are required. In this paper, we thus propose an extension of existing vocabularies to achieve this goal. Our contribution is illustrated on the real case of the Lebanese-French O-LiFE environmental observatory.
6th ACM International Conference on Web Intelligence, Mining and Semantics
Nimes, France

lirmm-01381082
https://hal-lirmm.ccsd.cnrs.fr/lirmm-01381082
https://hal-lirmm.ccsd.cnrs.fr/lirmm-01381082/document
https://hal-lirmm.ccsd.cnrs.fr/lirmm-01381082/file/presentationwims_s1_2.pdf
DOI : 10.1145/2912845.2912856

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
More than half the pregnant women in the Western world report taking mild analgesics. These pharmaceutical compounds have been associated with congenital cryptorchidism in humans, the best-known risk factor for low semen quality and testicular germ cell cancer. Furthermore, some of these mild analgesics exert potent anti-androgenic effects in the male rat and several endocrine-disrupting compounds, known to alter masculinization, have also been shown to be potent inhibitors of prostaglandin (PG) synthesis similar to mild analgesics. Using a 3-day ex vivo organotypic model system based on gestational day 14.5 rat testes, we herein show that testosterone production was inhibited by paracetamol, at doses of 0.1 μm to 100 μm. Similar results were obtained for aspirin (1-100 μm) and indomethacin (10 μm). The production of the other Leydig cell hormone, Insl3, was not disrupted by exposure to paracetamol. Investigations of the gross anatomy of the testis as well as Leydig cells number and rate of gonocyte apoptosis after the 3 days of ex vivo differentiation showed no significant effect of the analgesics tested compared with controls. These data indicate therefore that mild analgesics specifically inhibit testosterone production in rat foetal testes in vitro and that these compounds had no effect on gonocyte survival. Parallel determinations of prostaglandin D2 (PGD2) production indicated that the effects of paracetamol and aspirin on PGD2 and testosterone were not connected, whereas the effects of indomethacin were correlated. We conclude that mild analgesics exert direct and specific anti-androgenic effects in rat foetal testis in our experimental setup and that the mechanism of action is probably uncoupled from the inhibition of PG synthesis.
ISSN: 0105-6263

hal-00876956
https://hal.archives-ouvertes.fr/hal-00876956
DOI : 10.1111/j.1365-2605.2012.01282.x
PUBMED : 22612476

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Herbicides are generally the most extensively used of the pesticides applied to agricultural crops. However, the literature contains little evidence useful in assessing the potential sources of the general population's exposure to herbicides, including by residential proximity to crops. The objective of this study was to take advantage of data from the PELAGIE mother-child cohort to identify the main determinants of the body burden of exposure to the chloroacetanilide and triazine herbicides commonly used on corn crops in Brittany, France, before 2006. Urine samples from a randomly selected subcohort of women in the first trimester of pregnancy (n=579) were assayed for herbicide metabolites. The residential exposure resulting from proximity to corn crops was assessed with satellite-image-based scores combined with meteorological data. Data on diet, drinking tap water (from the public water supply), occupations, and household herbicide use were collected by questionnaires. Herbicides were quantified in 5.3% to 39.7% of urine samples. Alachlor and acetochlor were found most frequently in the urine of women living in rural areas. The presence of dealkylated triazine metabolites in urine samples was positively associated with residential proximity to corn crops (OR=1.38, 95% CI: 1.05-1.80). Urinary metabolites of both atrazine and dealkylated triazine were correlated with tap water consumption (OR=2.94, 1.09-7.90, and OR=1.82, 1.10-3.03, respectively); hydroxylated triazine metabolites were correlated with fish intake (OR=1.48, 1.09-1.99). This study reinforces previous results that suggest that environmental contamination resulting from agricultural activities may contribute to the general population's exposure to herbicides.
Environment International

hal-00966842
https://hal.archives-ouvertes.fr/hal-00966842
https://hal.archives-ouvertes.fr/hal-00966842/document
DOI : 10.1016/j.envint.2013.10.010
PUBMED : 24246238

Éditeur(s) : HAL CCSD
Résumé : International audience
In two swordtail species of the genus Xiphophorus, the onset of puberty has been shown to be modulated at the P locus by sequence polymorphism and gene copy-number variation affecting the type 4 melanocortin hormone receptor Mc4r. The system works through the interaction of two allelic types, one encoding wild type and the other dominant-negative receptors. We have analyzed the structure and evolution of the P locus in the platyfish Xiphophorus maculatus, where as many as nine alleles of P determining the onset of sexual maturity in males and females, fecundity in females, and adult size in males are located on both the X and Y chromosomes in a region linked to the master sex-determining locus. In this species, mc4r has been amplified to up to 10 copies on both the X and Y chromosomes through recent large serial duplications. Subsequently, mc4r paralogues have diverged considerably into many different subtypes. Certain copies have acquired new untranslated regions through genomic rearrangements, and transposable element insertions and other mutations have accumulated in promoter regions, possibly explaining observed deviations from the classical mc4r transcriptional pattern. In the mc4r-coding sequence, in-frame insertions and deletions as well as nonsense and missense mutations have generated a high diversity of Mc4r-predicted proteins. Most of these variants are expressed in embryos, adults, and/or tumors. Functional receptor characterization demonstrated major divergence in pharmacological behavior for Mc4r receptors encoded by different copies of platyfish mc4r, with differences in constitutive activity as well as binding and stimulation by hormones. The high degree of allelic and copy-number variation observed between individuals can explain the high level of polymorphism for sexual maturation, fecundity, and body size in the platyfish: multiple combinations of Mc4r variants with different biochemical properties might interact to modulate the melanocortin signaling that regulates the hypothalamus-pituitary-gonadal axis.
GENETICS

hal-01544912
https://hal.archives-ouvertes.fr/hal-01544912
DOI : 10.1534/genetics.113.155952

Éditeur(s) : HAL CCSD Springer-Verlag Berlin Heidelberg
Résumé : International audience
The main biological function of reaction wood is to act as " muscle " for trees, enabling them to control their posture. The key property to achieve this function is the development of high mechanical stress during the formation of reaction wood cells, called " maturation strains ". Actually, reaction wood formation is basically the asymmetric formation of wood around the tree circumference, with higher maturation strains on the side where reaction wood is formed than on the opposite side. This asymmetry enables stems to bend upward or to compensate for the downward bending induced by gravity. At the cross section level, the performance in this biological function is linked not only to the magnitude of this asymmetry but also to an effect of the cross-sectional size (diameter) of the stem. Eccentric growth and variations in wood mechanical stiffness are second order effects that can modify this performance. Differences in maturation strains between reaction and non-reaction woods are related to their specific cell wall structure and composition. The swelling of the cell wall matrix during maturation and the effect of microfibril angle explain the differences in maturation strains between normal and compression wood. However, this mechanism fails in explaining the high maturation shrinkage of tension wood, and several hypotheses at the molecular levels are still under debate. How trees perceive their gravitational disequilibrium is also an open question for physiologists. Integrative biomechanical modelling (from the polymer level to the cell wall, cross section and whole tree levels) enables defining key variables that explain the performance of reaction wood as a system that insures the stem motricity. Maturation strains can be precisely measured only in recently formed wood at the tree surface, but their changes during the whole tree life can also be estimated by retrospective dendrochronological analysis through structural markers of reaction wood. Lastly, wood in living trees ensures general storage, defence, vascular and skeletal functions, that ask general questions about synergies and trade-offs as the structural characteristics of reaction wood can affect all these functions.
The Biology of Reaction Wood

ISBN : 978-3-642-10813-6
hal-01452085
https://hal.archives-ouvertes.fr/hal-01452085
https://hal.archives-ouvertes.fr/hal-01452085/document
https://hal.archives-ouvertes.fr/hal-01452085/file/Chap_Gril_al_Biomechanical_action_biological_functions_2014.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life. OBJECTIVES: Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals. METHODS: We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10-12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures. RESULTS: We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose-response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight. CONCLUSIONS: Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life. https://doi.org/10.1289/EHP1014.
Environmental Health Perspectives

hal-01579609
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579609
DOI : 10.1289/EHP1014
PUBMED : 28796631

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : International audience
Plant responses to natural enemies include formation of secondary metabolites acting as direct or indirect defenses. Volatile terpenes represent one of the most diverse groups of secondary metabolites. We aimed to explore evolutionary patterns of volatile terpene emission. We measured the composition of damage-induced volatile terpenes from 202 Amazonian tree species, spanning the angiosperm phylogeny. Volatile terpenes were extracted with solid-phase micro extraction and desorbed in a gas chromatography–mass spectrometry for compound identification. The chemical diversity of the terpene blend showed a strong phylogenetic signal as closely related species emitted a similar number of compounds. Closely related species also tended to have compositionally similar blends, although this relationship was weak. Meanwhile, the ability to emit a given compound showed no significant phylogenetic signal for 200 of 286 compounds, indicating a high rate of diversification in terpene synthesis and/or great variability in their expression. Three lineages (Magnoliales, Laurales, and Sapindales) showed exceptionally high rates of terpene diversification. Of the 70 compounds found in >10% of their species, 69 displayed significant correlated evolution with at least one other compound. These results provide insights into the complex evolutionary history of volatile terpenes in angiosperms, while highlighting the need for further research into this important class of compounds.
ISSN: 2045-7758

Droits : http://creativecommons.org/licenses/by/
hal-01296640
http://hal.upmc.fr/hal-01296640
http://hal.upmc.fr/hal-01296640/document
http://hal.upmc.fr/hal-01296640/file/ece31810.pdf
DOI : 10.1002/ece3.1810

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
BACKGROUND: Addressing vulnerability to heat-related mortality is a necessary step in the development of policies dictated by heat action plans. We aimed to provide a systematic assessment of the epidemiologic evidence regarding vulnerability to heat-related mortality. METHODS: Studies assessing the association between high ambient temperature or heat waves and mortality among different subgroups and published between January 1980 and August 2014 were selected. Estimates of association for all the included subgroups were extracted. We assessed the presence of heterogeneous effects between subgroups conducting Cochran Q tests. We conducted random effect meta-analyses of ratios of relative risks (RRR) for high ambient temperature studies. We performed random effects meta-regression analyses to investigate factors associated with the magnitude of the RRR. RESULTS: Sixty-one studies were included. Using the Cochran Q test, we consistently found evidence of vulnerability for the elderly ages extgreater85 years. We found a pooled RRR of 0.99 (95% confidence interval [CI] = 0.97, 1.01) for male sex, 1.02 (95% CI = 1.01, 1.03) for age extgreater65 years, 1.04 (95% CI = 1.02, 1.07) for age extgreater75 years, 1.03 (95% CI = 1.01, 1.05) for low individual socioeconomic status (SES), and 1.01 (95% CI = 0.99, 1.02) for low ecologic SES. CONCLUSIONS: We found strongest evidence of heat-related vulnerability for the elderly ages extgreater65 and extgreater75 years and low SES groups (at the individual level). Studies are needed to clarify if other subgroups (e.g., children, people living alone) are also vulnerable to heat to inform public health programs
ISSN: 1044-3983

hal-01197347
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197347
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197347/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197347/file/Vulnerability%20to%20Heat-related%20Mortality%20A%20Systematic%20Review%2C%20Meta-analysis%2C%20and%20Meta-regression%20Analysis..pdf
DOI : 10.1097/EDE.0000000000000375

Éditeur(s) : HAL CCSD John Libbey Eurotext
Résumé : International audience
Prostate cancer is the most frequent cancer affecting men in most Western countries. Certain risk factors have been identified (age, family history, ethnic origin), but the aetiology of this cancer remains largely unknown. However, a role for environmental factors is strongly suspected. Questions have been raised concerning the role of the chemical substances generated by human activities in the occurrence of this disease. Diverse studies have consistently demonstrated a higher risk of prostate cancer in agricultural populations than in the general population. The hypothesis that this higher risk is linked to the use of pesticides has been tested in a number of studies, mostly in North America and Europe. However, to date, with a few possible exceptions, it has been impossible to demonstrate a significant association between exposure to pesticides or a chemical family of pesticides and prostate cancer. In the face of these uncertainties, rigorous studies are required, with objective measurements of exposure, taking into account confounding factors and individual risk factors, making it possible to assess gene-environment interactions.
ISSN: 0007-4551

inserm-00504733
http://www.hal.inserm.fr/inserm-00504733
DOI : 10.1684/bdc.2008.0812
PUBMED : 19258224

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Synkinematic phyllosilicates in fault zones can be used to deduce the deformation mechanisms and the conditions of fault activity, as their chemical composition, crystal structure and texture can record the different stages of deformation and fluid-rock interactions. The Pic de Port Vieux, a second-order thrust related to the major Gavarnie thrust in the southern central part of the Pyrenees Axial Zone, juxtaposes Triassic pelites of the hanging wall and Cretaceous limestones of the footwall. In order to investigate the mineralogical and geochemical changes and constrain the deformation conditions of thrusting, characterization of phyllosilicates was performed along a transect in the fault hanging wall pelites. The Triassic pelites are mainly composed of quartz, calcite, phyllosilicates (chlorite and K-white mica) and ± hematite. The core fault zone thickness is estimated to be about one meter of intensively foliated green pelites, whereas the damage zone is composed of several meters of red pelites. XRD data demonstrated that the difference in color is related to hematite which is only present in the damage zone. Phyllosilicates of the damage zone are mainly inherited/diagenetic K-white mica and chlorite. In the core zone, newly formed chlorite is abundant and preferentially located in veins. It is enriched in Fe compared to the chlorite of the red pelites. The well-defined foliation in the core zone is overlaid by preferentially oriented muscovite grains which have homogeneous compositions, with less Na and relatively more Fe than mica from the red pelites. Newly formed chlorite and muscovite in the core zone are synkinematic to the fault activity. They are both related to deformation processes and fluid rock interactions. Kübler index measurements and chlorite thermometry show that synkinematic phyllosilicates have registered a temperature of 270°C ± 23°C for the damage zone and 285°C ± 28°C for the core zone which are corresponding to lower-anchizone/epizone grade conditions. Numerical modelling with the geochemical modelling program PhreeqC was performed to determine the favorable conditions for the mineralogical change between red and green pelites. It suggests that the main critical parameter favoring hematite dissolution and chlorite precipitation in the core zone, is the redox conditions. According to the model, the chemical changes in the core zone occurred due to interactions with highly reductive fluids. In addition, the hematite dissolution maybe the source of iron for newly formed phyllosilicates in the core zone that are more iron rich compared to those from the red pelites.
ISSN: 0169-1317

hal-01536006
https://hal.archives-ouvertes.fr/hal-01536006
DOI : 10.1016/j.clay.2017.05.008

Éditeur(s) : HAL CCSD Wiley-VCH Verlag
Résumé : International audience
Proteomic profiling plays a decisive role in the elucidation of molecular signatures representative of a specific clinical context. MuStem cell-based therapy represents a promising approach for clinical applications to cure Duchenne Muscular Dystrophy (DMD). To expand our previous studies collected in the clinically relevant DMD animal model, we decided to investigate the skeletal muscle proteome four months after systemic delivery of allogenic MuStem cells. Quantitative proteomics with isotope-coded protein labelling (ICPL) was used to compile quantitative changes in the protein expression profiles of muscle in transplanted Golden Retriever Muscular Dystrophy (GRMD) dogs as compared to GRMD dogs. A total of 492 proteins were quantified, including 25 that were overrepresented and 46 that were underrepresented after MuStem cell transplantation. Interestingly, this study demonstrates that somatic stem cell therapy impacts on the structural integrity of the muscle fascicle by acting on fibres and its connections with the extracellular matrix. We also show that cell infusion promotes protective mechanisms against oxidative stress and favours the initial phase of muscle repair. This study allows us to identify putative candidates for tissue markers that might be of great value in objectively exploring the clinical benefits resulting from our cell-based therapy for DMD.
ISSN: 1615-9853

Droits : info:eu-repo/semantics/OpenAccess
hal-01332030
https://hal.archives-ouvertes.fr/hal-01332030
https://hal.archives-ouvertes.fr/hal-01332030/document
https://hal.archives-ouvertes.fr/hal-01332030/file/Quantitative%20proteome%20profiling%20of%20dystrophic%20dog%20skeletal%20muscle_accepted.pdf
DOI : 10.1002/pmic.201600002

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks
ISSN: 0013-7227

hal-01187409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187409
DOI : 10.1210/EN.2015-1350
PUBMED : 26241067

Éditeur(s) : HAL CCSD De Gruyter
Résumé : COST Action E35 : Fracture mechanics and micromechanics of wood and wood composites with regard to wood machining
The data available in the literature concerning wood cutting forces permits to build models or to simulate the main wood machining processes ( milling, sawing, peeling, etc.). This approach contributes to a better understanding of formation of wood surfaces and chips and the data may be helpful to optimise cutting geometry, reduce tool wear, improve tool material, and to size tool-machines. The models may also be useful for industrial application in two ways: ( 1) providing data to optimise the settings for a given operation ( batch approach), and ( 2) building predictive models that could be the basis of an online control system for the machining processes ( interactive approach). A prerequisite for this is that numerous machining tests on different wood materials are performed based on experiences with different kind of tools and experimental devices. With a focus on potential industrial applications, the emphasis of this review was on the wood peeling process, which is a very demanding special case of wood cutting. Although not so many industrial machines are equipped with expensive force sensors, there is a lot of high quality information available about cutting forces which may be useful to improve the scientific or technological knowledge in wood machining. Alternative parameters, such as vibration or sound measurements, appear to be promising substitutes in the praxis, particularly to feed online control systems of any wood cutting process.
ISSN: 0018-3830

hal-01032121
https://hal.archives-ouvertes.fr/hal-01032121
DOI : 10.1515/HF.2009.014