Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The parasitic life cycle of Leishmania includes an extracellular promastigote stage that occurs in the gut of the insect vector. During that period, the sucrose metabolism and more specifically the first glycosidase of this pathway are essential for growth and survival of the parasite. We investigated the expression of the invertase BfrA in the promastigote and amastigote stages of three parasite species representative of the three various clinical forms and of various geographical areas, namely Leishmania major, L. donovani and L. braziliensis. Thereafter, we cloned, overexpressed and biochemically characterized this invertase BfrA from L. major, heterologously expressed in both Escherichia coli and L. tarentolae. For all species, expression levels of BfrA mRNA were correlated to the time of the culture and the parasitic stage (promastigotes > amastigotes). BfrA exhibited no activity when expressed as a glycoprotein in L. tarentolae but proved to be an invertase when not glycosylated, yet owing low sequence homology with other invertases from the same family. Our data suggest that BfrA is an original invertase that is located inside the parasite. It is expressed in both parasitic stages, though to a higher extent in promastigotes. This work provides new insight into the parasite sucrose metabolism
ISSN: 0008-6215

hal-01187142
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187142
DOI : 10.1016/j.carres.2015.07.001
PUBMED : 26279524

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
The sources of exposure during diseases due to Aspergillus fungi in cystic fibrosis patients are still poorly explored. We assessed home fungal exposure in patients suffering from cystic fibrosis and analysed its impact on the presence of Aspergillus biological markers, the colonisation of airways, as well as the sensitization and Aspergillus serology. Between March 2012 and August 2012, 34 patients benefited from a visit performed by a home environment medical adviser including sampling for mycological analysis. The number of colonies of Aspergillus was not significantly different in the various sampling sites (P = 0.251), but the number of non-Aspergillus colonies was much higher in the kitchen (P = 0.0045). Subsequently, home fungal exposure was compared between the groups “absence of Aspergillus-related markers” and “presence of Aspergillus-related markers”. Home exposure to Aspergillus (P = 0.453) and non-Aspergillus (P = 0.972) flora was not significant between the 2 groups. Within this series of 34 patients that should be expanded, we note an absence of clear relationship between home exposure and the Aspergillus-linked markers in patients suffering from cystic fibrosis. This result should be taken into account regarding too restrictive hygiene advices provided to families, given the fact that fungal exposure can also results from activities performed away from home.
La source d’exposition au cours des pathologies aspergillaires du patient atteint de mucoviscidose reste encore peu explorée. Nous avons évalué l’exposition fongique domiciliaire chez des patients atteints de mucoviscidose, et analysé son impact sur la présence de marqueurs biologiques aspergillaires, colonisation des voies aériennes, ainsi que sensibilisation et sérologie anti-aspergillaire. Trente-quatre patients ont bénéficié d’une visite par un conseiller médical en environnement intérieur entre mars et août 2012, comprenant des prélèvements à visée mycologique. Le nombre de colonies aspergillaires ne différait pas significativement d’un site de prélèvement à l’autre (p = 0,251), mais le nombre de colonies non aspergillaires était significativement plus important dans la cuisine (p = 0,0045). L’exposition fongique domiciliaire a ensuite été comparée entre les groupes « marqueurs aspergillaires absents » et « marqueurs aspergillaires présents ». L’exposition domiciliaire à une flore aspergillaire (p = 0,453) et non aspergillaire (p = 0,972) ne différait pas significativement entre les 2 groupes. Sur cette série de 34 patients qui mérite d’être élargie, on note une absence de lien évident entre l’exposition domiciliaire et la pathologie aspergillaire. Ce résultat doit rendre prudent sur des conseils d’hygiène parfois très contraignants donnés aux familles, l’exposition fongique étant également importante dans le cadre des activités extra-domiciliaires.
ISSN: 1156-5233

hal-01158660
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01158660
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01158660/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01158660/file/Exposition%20domiciliaire%20aux%20moisissures%20postprint%20MYCMED-S-14-00173.pdf
DOI : 10.1016/j.mycmed.2015.03.005

Éditeur(s) : HAL CCSD
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.
7th INTECOL International Wetland Conference
Utrecht, Netherlands

hal-01032381
https://hal.archives-ouvertes.fr/hal-01032381

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Humans may be exposed via their environment to multiple chemicals as a consequence of human activities and use of synthetic products. Little knowledge is routinely generated on the hazards of these chemical mixtures. The metabolomic approach is widely used to identify metabolic pathways modified by diseases, drugs, or exposures to toxicants. This review, based on the state of the art of the current applications of metabolomics in environmental health, attempts to determine whether metabolomics might constitute an original approach to the study of associations between multiple, low-dose environmental exposures in humans. Studying the biochemical consequences of complex environmental exposures is a challenge demanding the development of careful experimental and epidemiological designs, in order to take into account possible confounders associated with the high level of interindividual variability induced by different lifestyles. The choices of populations studied, sampling and storage procedures, statistical tools used, and system biology need to be considered. Suggestions for improved experimental and epidemiological designs are described. Evidence indicates that metabolomics may be a powerful tool in environmental health in the identification of both complex exposure biomarkers directly in human populations and modified metabolic pathways, in an attempt to improve understanding the underlying environmental causes of diseases. Nevertheless, the validity of biomarkers and relevancy of animal-to-human extrapolation remain key challenges that need to be properly explored.
ISSN: 1093-7404

hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/file/Potential_input_from_metabolomics_accepted.pdf
DOI : 10.1080/10937404.2013.860318

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.
ISSN: 0160-4120

hal-01107546
https://hal.archives-ouvertes.fr/hal-01107546
DOI : 10.1016/j.envint.2013.10.010
PUBMED : 24246238

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed. Significant interactions occur by inhibition or induction of CYP450 3A4 which is the main metabolic pathway of TKIs. However, minor metabolic pathways should also be paid attention to. Interactions involving efflux and influx transporters should also be considered occurring for some TKIs. Genetic polymorphism in drug metabolism as well as in drug transport is a factor of variability in drug exposure, which could modulate the magnitude of drug-drug interactions (DDIs). It should be noticed that TKIs can also be at the origin of drug interactions by altering the pharmacokinetics of coprescribed drugs. Since cancer patients are given many drugs either for supportive care or for the treatment of drug toxicity, and to the fact that the oldest patients are polymedicated, a clear understanding of DDIs with TKIs is of interest. The objectives of this review are to provide an overview of the mechanisms of DDIs with TKIs and to provide to physicians and pharmacists recommendations to manage these DDIs in their clinical practice.
ISSN: 0278-0232

hal-01616064
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616064
DOI : 10.1002/hon.2335
PUBMED : 27925256

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The Caribbean bivalves Codakia orbicularis (Linnée, 1758) and C. orbiculata (Montagu, 1808) live in seagrass beds of Thalassia testudinum and harbor intracellular sulfuroxidizing gamma-proteobacteria. These bacterial symbionts fix CO2 via the Calvin Benson cycle and provide organic compounds to the bivalve. During experimentally induced starvation, no reduced sulfur compounds and no organic particle food are available; the symbionts could be considered as the sole nutrient source of the host bivalve. A previous study has shown that the intracellular bacterial population decreased considerably during starvation and that bacterial endosymbionts were not released by the bivalves. In this study, the activity of two lysosomal marker enzymes (acid phosphatase and arylsulfatase) was detected using cytochemical experiments coupled with energy-dispersive X-ray transmission electron microscopy during sulfide and organic particle starvation. The degradation of bacterial endosymbionts began after 2 weeks of starvation in C. orbiculata and after 3 weeks in C. orbicularis. Degradation processes seem to be continuous over several months and could be responsible for the disappearance of the bacterial endosymbionts within the gills during starvation. These data suggest that the host use symbionts as a nutrient source to survive a hunger crisis. The carbon transfer from the symbionts to the host could be flexible and could consist in transfer of organic matter, “milking,” under normal feeding conditions and digestion of the symbionts under starved conditions.
ISSN: 1059-910X

Droits : info:eu-repo/semantics/OpenAccess
hal-01206367
https://hal.univ-antilles.fr/hal-01206367
https://hal.univ-antilles.fr/hal-01206367/document
https://hal.univ-antilles.fr/hal-01206367/file/revised%20version%20to%20be%20submitted%20to%20the%20editor3oct.pdf
DOI : 10.1002/jemt.22458

Éditeur(s) : HAL CCSD Royal Society
Résumé : Coral bleaching events are predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes depends on many factors, including the magnitude of thermal stress and irradiance. The interactions among these two factors, and in particular with ultra-violet radiation (UVR), the most harmful component of light, are more complex than assumed, and are not yet well understood. This paper explores the individual and combined effects of temperature and UVR on the metabolism of Acropora muricata, one of the most abundant coral species worldwide. Particulate and dissolved organic matter (POM/DOM) fluxes and organic matter (OM) degradation by the mucus-associated bacteria were also monitored in all conditions. The results show that UVR exposure exacerbated the temperature-induced bleaching, but did not affect OM fluxes, which were only altered by seawater warming. Temperature increase induced a shift from POM release and DOM uptake in healthy corals to POM uptake and DOM release in stressed ones. POM uptake was linked to a significant grazing of pico- and nanoplankton particles during the incubation, to fulfil the energetic requirements of A. muricata in the absence of autotrophy. Finally, OM degradation by mucus-associated bacterial activity was unaffected by UVR exposure, but significantly increased under high temperature. Altogether, our results demonstrate that seawater warming and UVR not only affect coral physiology, but also the way corals interact with the surrounding seawater, with potential consequences for coral reef biogeochemical cycles and food webs.
ISSN: 2046-6390

hal-01606454
https://hal.archives-ouvertes.fr/hal-01606454
DOI : 10.1242/bio.026757
PRODINRA : 406580
PUBMED : 28811302

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: We aimed to assess, for the first time, the nature of the indoor air contamination of hospitals. METHODS AND FINDINGS: More than 40 volatile organic compounds (VOCs) including aliphatic, aromatic and halogenated hydrocarbons, aldehydes, alcohols, ketones, ethers and terpenes were measured in a teaching hospital in France, from sampling in six sampling sites--reception hall, patient room, nursing care, post-anesthesia care unit, parasitology-mycology laboratory and flexible endoscope disinfection unit--in the morning and in the afternoon, during three consecutive days. Our results showed that the main compounds found in indoor air were alcohols (arithmetic means ± SD: 928±958 µg/m³ and 47.9±52.2 µg/m³ for ethanol and isopropanol, respectively), ethers (75.6±157 µg/m³ for ether) and ketones (22.6±20.6 µg/m³ for acetone). Concentrations levels of aromatic and halogenated hydrocarbons, ketones, aldehydes and limonene were widely variable between sampling sites, due to building age and type of products used according to health activities conducted in each site. A high temporal variability was observed in concentrations of alcohols, probably due to the intensive use of alcohol-based hand rubs in all sites. Qualitative analysis of air samples led to the identification of other compounds, including siloxanes (hexamethyldisiloxane, octamethyltrisiloxane, decamethylcyclopentasiloxane), anesthetic gases (sevoflurane, desflurane), aliphatic hydrocarbons (butane), esters (ethylacetate), terpenes (camphor, α-bisabolol), aldehydes (benzaldehyde) and organic acids (benzoic acid) depending on sites. CONCLUSION: For all compounds, concentrations measured were lower than concentrations known to be harmful in humans. However, results showed that indoor air of sampling locations contains a complex mixture of VOCs. Further multicenter studies are required to compare these results. A full understanding of the exposure of healthcare workers and patients to complex mixtures of chemical compounds can then be related to potential health outcomes.
ISSN: 1932-6203

hal-00874694
https://hal.archives-ouvertes.fr/hal-00874694
https://hal.archives-ouvertes.fr/hal-00874694/document
https://hal.archives-ouvertes.fr/hal-00874694/file/VOC_Contamination-accepted.pdf
DOI : 10.1371/journal.pone.0055535

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Deciphering the evolutionary processes driving nucleotide variation in multiallelic genes is limited by the number of genetic systems in which such genes occur. The complementary sex determiner (csd) gene in the honey bee Apis mellifera is an informative example for studying allelic diversity and the underlying evolutionary forces in a well-described model of balancing selection. Acting as the primary signal of sex determination, diploid individuals heterozygous for csd develop into females, whereas csd homozygotes are diploid males that have zero fitness. Examining 77 of the functional heterozygous csd allele pairs, we established a combinatorical criteria that provide insights into the minimum number of amino acid differences among those pairs. Given a data set of 244 csd sequences, we show that the total number of csd alleles found in A. mellifera ranges from 53 (locally) to 87 (worldwide), which is much higher than was previously reported (20). Using a coupon-collector model, we extrapolate the presence of in total 116-145 csd alleles worldwide. The hypervariable region (HVR) is of particular importance in determining csd allele specificity, and we provide for this region evidence of high evolutionary rate for length differences exceeding those of microsatellites. The proportion of amino acids driven by positive selection and the rate of nonsynonymous substitutions in the HVR-flanking regions reach values close to 1 but differ with respect to the HVR length. Using a model of csd coalescence, we identified the high originating rate of csd specificities as a major evolutionary force, leading to an origin of a novel csd allele every 400,000 years. The csd polymorphism frequencies in natural populations indicate an excess of new mutations, whereas signs of ancestral transspecies polymorphism can still be detected. This study provides a comprehensive view of the enormous diversity and the evolutionary forces shaping a multiallelic gene.
ISSN: 0737-4038

hal-01544758
https://hal.archives-ouvertes.fr/hal-01544758
DOI : 10.1093/molbev/mst207

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet.
ISSN: 0021-9258

hal-01074835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835/file/JBC-2013-525220v2-Kristiansen-POSTPRINT.pdf
DOI : 10.1074/jbc.M113.525220

Éditeur(s) : HAL CCSD
Résumé : International audience
Here, we synthesize conceptual frameworks, applied modeling approaches, and as case studies to highlight complex social-ecological system (SES) dynamics that inform environmental policy, conservation and management. Although a set of “good practices” about what constitutes a good SES study are emerging, there is still a disconnection between generating SES scientific studies and providing decision-relevant information to policy makers. Classical single variable/hypothesis studies rooted in one or two disciplines are still most common, leading to incremental growth in knowledge about the natural or social system, but rarely both. The recognition of human dimensions is a key aspect of successful planning and implementation in natural resource management, ecosystem-based management, fisheries management, and marine conservation. The lack of social data relating to human-nature interactions in this particular context is now seen as an omission, which can often erode the efficacy of any resource management or conservation action. There have been repeated calls for a transdisciplinary approach to complex SESs that incorporates resilience, complexity science characterized by intricate feedback interactions, emergent processes, non-linear dynamics and uncertainty. To achieve this vision, we need to embrace diverse research methodologies that incorporate ecology, sociology, anthropology, political science, economics and other disciplines that are anchored in empirical data. We conclude that to make SES research most useful in adding practical value to conservation planning, marine resource management planning processes and implementation, and the integration of resilience thinking into adaptation strategies, more research is needed on (1) understanding social-ecological landscapes and seascapes and patterns that would ensure planning process legitimacy, (2) costs of transformation (financial, social, environmental) to a stable resilient social-ecological system, (3) overcoming place-based data collection challenges as well as modeling challenges.
Ocean and Coastal Management

Droits : http://creativecommons.org/licenses/by-nc-nd/
hal-01224152
https://hal-univ-perp.archives-ouvertes.fr/hal-01224152
https://hal-univ-perp.archives-ouvertes.fr/hal-01224152/document
https://hal-univ-perp.archives-ouvertes.fr/hal-01224152/file/1-s2.0-S096456911500126X-main.pdf
DOI : 10.1016/j.ocecoaman.2015.04.018

Éditeur(s) : HAL CCSD American Society for Investigative Pathology (ASIP)
Résumé : International audience
Semen represents the main vector of HIV dissemination worldwide, yet the origin of HIV in semen remains unclear. Viral populations distinct from those found in blood have been observed in semen, indicating local viral replication within the male genital tract. The seminal vesicles, the secretions of which constitute more than 60% of the seminal fluid, could represent a major source of virus in semen. This study is the first to investigate the susceptibility of human seminal vesicles to HIV infection both in vitro and in vivo. We developed and characterized an organotypic culture of human seminal vesicles to test for target cells and HIV infection, and, in parallel, analyzed the seminal vesicle tissues from HIV-infected donors. In vitro, in contrast to HIV-1 X4, HIV-1 R5 exposure induced productive infection. Infected cells consisted primarily of resident CD163(+) macrophages, often located close to the lumen. In vivo, HIV protein and RNA were also detected primarily in seminal vesicle macrophages in seven of nine HIV-infected donors, some of whom were receiving prolonged suppressive highly active antiretroviral therapy. These results demonstrate that human seminal vesicles support HIV infection in vitro and in vivo and, therefore, have the potential to contribute virus to semen. The presence of infected cells in the seminal vesicles of treated men with undetectable viremia suggests that this organ could constitute a reservoir for HIV.
American Journal of Pathology

inserm-00626549
http://www.hal.inserm.fr/inserm-00626549
DOI : 10.1016/j.ajpath.2011.08.005
PUBMED : 21925468

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Facts -The capacity to exercise is markedly reduced in hot environments. -High humidity imposes further physiological strain on the body. -The combination of exercise and hot environments increases the risk of heat illness and heatstroke. Recommendations for players -Fluid intake should be sufficient to restrict body mass loss to o2% of the pre-exercise mass. -A minimum of 1-2 weeks of acclimatization should be undertaken before playing in a hot environment. Recommendations for organizers -Perform pre-participation screenings before competing in the heat. -Watch at-risk individual (e.g. sickle cell trait, vascular disease) and observe signs and symptoms if WBGT > 28°C. -Add additional fluid breaks and foresee medical coverage if WBGT > 30°C. -Reconsider event if WBGT > 32°C. Future research should investigate -The optimal cooling strategies prior and during sporting activities, i.e., halftime in football games. -The influence of acclimatization on football performance. -The impact of heat on decision making in players and match officials. -The impact of heat on spectators from cooler regions.
ISSN: 0905-7188

hal-00706256
https://hal.univ-antilles.fr/hal-00706256

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Risk assessment related to the exposure of humans to chemicals released into the environment is a major concern of our modern societies. In this context, toxicology plays a crucial role to characterize the effects of this exposure on health and identify the targets of these molecules. MALDI imaging mass spectrometry (IMS) is an enabling technology for biodistribution studies of chemicals. Although the majority of published studies are presented in a pharmacological context, the concepts discussed in this review can be applied to the toxicological evaluation of chemicals released into the environment. The major asset of IMS is the simultaneous localization and identification of a parent molecule and its metabolites without labeling and without any prior knowledge. Quantification methods developed in IMS are presented with application to an environmental pollutant. IMS is effective in the localization of chemicals and endogenous species. This opens unique perspectives for the discovery of molecular alterations in metabolites and protein biomarkers that could help for a better understanding of toxicity mechanisms. Distribution studies of agrochemicals in plants by IMS can contribute to a better understanding of their mode of action and to a more effective use of these chemicals, avoiding the current concern of environmental damage.
ISSN: 1874-3919

hal-01367141
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367141/file/Potential%20of%20MALDI%20imaging.pdf
DOI : 10.1016/j.jprot.2016.05.008

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Anti-Müllerian hormone (AMH) plays crucial roles in sexual differentiation and gonadal functions. However, the possible extragonadal effects of AMH on the hypothalamic-pituitary-gonadal axis remain unexplored. Here we demonstrate that a significant subset of GnRH neurons both in mice and humans express the AMH receptor, and that AMH potently activates the GnRH neuron firing in mice. Combining in vivo and in vitro experiments, we show that AMH increases GnRH-dependent LH pulsatility and secretion, supporting a central action of AMH on GnRH neurons. Increased LH pulsatility is an important pathophysiological feature in many cases of polycystic ovary syndrome (PCOS), the most common cause of female infertility, in which circulating AMH levels are also often elevated. However, the origin of this dysregulation remains unknown. Our findings raise the intriguing hypothesis that AMH-dependent regulation of GnRH release could be involved in the pathophysiology of fertility and could hold therapeutic potential for treating PCOS
ISSN: 2041-1723

hal-01259206
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259206
DOI : 10.1038/ncomms10055
PUBMED : 26753790

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings suggest that defects in dermo/epidermal interactions could contribute to BCC susceptibility in NBCCS patients.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01257867
http://hal.upmc.fr/hal-01257867
http://hal.upmc.fr/hal-01257867/document
http://hal.upmc.fr/hal-01257867/file/journal.pone.0145369.pdf
DOI : 10.1371/journal.pone.0145369

Éditeur(s) : HAL CCSD
Résumé : After a review of knowledge, attitudes and practices related to leishmaniasis in Amazonia, this work focused on the vegetal species used for its cure. Utilization of geographic and cultural diffusion index allowed to characterize Pan-Amazonian antileishmanial taxa and to investigate the mechanisms allowing for their diffusion. Consistency between traditional use and laboratory results were looked for. Two " knowledge, attitudes and practices " surveys were conducted amongst the Chayahuita (Peru) and along the upper and middle Oyapock river (French Guiana, Teko and Wayãpi groups). These allowed us to refine the knowledge and perception of the disease in these cultural groups, to define patterns in the therapeutic itinerary, and to make an inventory of antileishmanial plant species. Thirty one species used by the Chayahuita were collected and submitted to in vitro assays on axenic amastigotes of Leishmania amazonensis. Pseudoelephantopus spicatus (Asteraceae) is one of the most active and most frequently used plant. From this species, piptocarphol derivatives, very active against Leishmania in vitro, were isolated along with ursolic acid. Presence of these molecules justifies the use of this species as traditional antileishmanial remedy by the Chayahuita.
Après avoir dressé un inventaire des connaissances, attitudes et pratiques concernant les leishmanioses en Amazonie d'après la littérature, le présent travail s'est focalisé sur les espèces végétales connues et utilisées dans le traitement de ces maladies. L'utilisation d'indices de diffusion (géographique, culturelle) a permis de caractériser des taxons antileishmaniens panamazoniens et de définir certains mécanismes impliqués dans leur diffusion. Des cohérences entre usages traditionnels et résultats de laboratoire ont été recherchés. Deux enquêtes de type " connaissance, attitudes et pratiques " effectuées au sein du groupe chayahuita (Pérou), et sur le haut et moyen cours du fleuve Oyapock (Guyane, communautés teko et wayãpi) ont permis d'affiner les connaissances sur la perception de cette maladie dans ces différents groupes culturels, de comprendre les recours aux différentes thérapeutiques et de dresser un inventaire des espèces médicinales utilisées. Trente et une espèces collectées chez les Chayahuita ont été soumises à des essais in vitro sur amastigotes axéniques de Leishmania amazonensis. Pseudoelephantopus spicatus (Asteraceae) compte parmi les espèces les plus actives et les plus fréquemment utilisées, et des dérivés du piptocarphol très actifs sur les parasites in vitro ont été isolés conjointement à l'acide ursolique. La présence de ces molécules permet de justifier en partie l'usage de cette espèce comme antileishmanien traditionnel par les Chayahuita.
https://tel.archives-ouvertes.fr/tel-00590977

tel-00590977
https://tel.archives-ouvertes.fr/tel-00590977
https://tel.archives-ouvertes.fr/tel-00590977/document
https://tel.archives-ouvertes.fr/tel-00590977/file/ThA_se_Odonne_light.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
Introduction: Type 1 diabetes mellitus, a T cell-mediated autoimmune disease, is a complex process that results from the loss of tolerance to insulin and other beta-cell-specific antigens. Diabetes is associated with an increased risk of death from infectious disease. Hyperglycaemia, oxidative stress and inflammation have been identified as the main factor contributing to the development of diseases associated with diabetes mellitus. However, experimental evidence indicates individual susceptibility to develop complications of diabetes. Various genetic and environmental factors have been studied so far, but precise causation has yet to be established. Numerous studies in rodents and human subjects have been performed in order to elucidate the role of B and T cells, which determine the risk of development and progression of diabetes. Moreover, the therapy management of diabetes includes nutritional recommendations and exercise training. The effects of exercise training on glycemia, oxidative stress, inflammation and immune response are well known and favorable to limit the development of diabetes and its complications. More interestingly, ?-galacto-oligosaccharides (?-GOS) are prebiotics that selectively alter the composition of gut microbiota and exhibit strong antioxidant, anti- inflammatory and insulin-sensitive effects in vitro (Efstathiou and Fathi 2010) and in vivo (Boucher J et al. 2003). Thus, ? -GOS is a potential functional food for the treatment of diabetes. But, less is known about the effect of training and ? –GOS on immune response in diabetes. In this context, the aim of this work was to study the immune response in a streptozotocin-induced type 1 diabetes with two therapeutic means: training and ?-galacto-oligosaccharides (?-GOS) alone or combined. Methods: Forty-two male Wistar rats were divided into control placebo, streptozotocin-diabetic rat (STZ) groups supplemented or not with ?-GOS (20 mg/kg/day) for 8 weeks and/or following endurance training. The training program was individualized and consisted in a 1h/day, 5days/week running during 8 weeks on a motor-driven treadmill. At the end of the protocol, blood was obtained by venous puncture into heparin-containing tubes for further analyses (glucose, insulin, fructosamine and immune responses) Results: Relative to the control group, STZ rats exhibited hyperglycemia, insulin deficiency and a trend to higher plasma fructosamine levels, a marker of glycated proteins. They also exhibited a decrease in T and B cells and an increase in natural killers (NK). ?-GOS treatment reduced plasma fructosamine levels and increased B cells compared to STZ rats. Training induced a decrease in plasma glucose, T cells and an increase in B cells in STZ rats. The combined effect of ?-GOS and training didn’t potentiate the immune response on B and T cells but inhibited the effects of training on NK. Discussion: Our results suggest that training and ?-GOS alter positively plasma glucose and/or fructosamine and the immune response. But the effects of combined treatments only concern limited parameters. ? -GOS effects could be partly attributable to its immunomodulating activity. Keywords: ?-GOS, training, immune cells, diabetes. References Efstathiou, T. and D. Fathi. Sojasun Technologies. 2010 Boucher J et al. J Physiol Biochem. 59(3):169-73, 2003
18th Annual Congress of the European College of Sport Sciences, Barcelone, Spain, 26-29 juin.
Barcelone, Spain

hal-01159378
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01159378

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
A cross section of a human population (501 individuals) selected at random, and living in a Bolivian community, highly endemic for Chagas disease, was investigated combining together clinical, parasitological and molecular approaches. Conventional serology and polymerase chain reaction (PCR) indicated an active transmission of the infection, a high seroprevalence (43.3%) ranging from around 12% in < 5 years to 94.7% in > 45 years, and a high sensitivity (83.8%) and specificity of PCR. Abnormal ECG tracing was predominant in chagasic patients and was already present among individuals younger than 13 years. SAPA (shed acute phase antigen) recombinant protein and the synthetic peptide R-13 were used as antigens in ELISA tests. The reactivity of SAPA was strongly associated to Trypanosoma cruzi infection and independent of the age of the patients but was not suitable neither for universal serodiagnosis nor for discrimination of specific phases of Chagas infection. Anti-R-13 response was observed in 27.5% only in chagasic patients. Moreover, anti-R13 reactivity was associated with early infection and not to cardiac pathology. This result questioned previous studies, which considered the anti-R-13 response as a marker of chronic Chagas heart disease. The major clonets 20 and 39 (belonging to Trypanosoma cruzi I and T. cruzi II respectively) which circulate in equal proportions in vectors of the studied area, were identified in patients' blood by PCR. Clonet 39 was selected over clonet 20 in the circulation whatever the age of the patient. The only factor related to strain detected in patients' blood, was the anti-R-13 reactivity: 37% of the patients infected by clonet 39 (94 cases) had anti-R13 antibodies contrasting with only 6% of the patients without clonet 39 (16 cases).
ISSN: 0074-0276

hal-01256421
https://hal.archives-ouvertes.fr/hal-01256421
DOI : 10.1590/S0074-02762002000300002
IRD : fdi:010029219
PUBMED : 12048553