Éditeur(s) : HAL CCSD Cambridge University Press (CUP)
Résumé : International audience
We extend the theory of distributional kernel operators to a framework of generalized functions, in which they are replaced by integral kernel operators. Moreover, in contrast to the distributional case, we show that these generalized integral operators can be composed unrestrictedly. This leads to the definition of the exponential, and more generally entire functions, of a subclass of such operators.
ISSN: 0305-0041

hal-01530755
https://hal.univ-antilles.fr/hal-01530755

Éditeur(s) : HAL CCSD
Résumé : International audience
Studies report that foetal exposure to paracetamol by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (non-pharmaceutical) sources such as metabolic conversion from the ubiquitous industrial compound aniline. In this study we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that foetal hormone signalling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Foetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum foetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life
Toxicological Sciences

hal-01259211
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259211
DOI : 10.1093/toxsci/kfv332
PUBMED : 26732887

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The formation of ovarian follicles is a finely tuned process that takes place within a narrow time-window in rodents. Multiple factors and pathways have been proposed to contribute to the mechanisms triggering this process but the role of endocrine factors, especially estrogens, remains elusive. It is currently hypothesized that removal from the maternal hormonal environment permits follicle formation at birth. However, experimentally-induced maintenance of high 17β-estradiol (E2) levels leads to subtle, distinct, immediate effects on follicle formation and oocyte survival depending on the species and dose. In this study, we examined the immediate effects of neonatal E2 exposure from post-natal day (PND) 0 to PND2 on the whole organism and on ovarian follicle formation in rats. Measurements of plasma E2, estrone and their sulfate conjugates after E2 exposure showed that neonatal female rats rapidly acquire the capability to metabolize and clear excessive E2 levels. Concomitant modifications to the mRNA content of genes encoding selected E2 metabolism enzymes in the liver and the ovary in response to E2 exposure indicate that E2 may modify the neonatal maturation of these organs. In the liver, E2 treatment was associated with lower acquisition of the capability to metabolize E2. In the ovary, E2 depleted the oocyte pool in a dose dependent manner by PND3. In 10 µg/day E2-treated ovaries, apoptotic oocytes were observed in newly formed follicles in addition to areas of ovarian cord remodeling. At PND6, follicles without any visible oocyte were present and multi-oocyte follicles were not observed. Our study reveals a major species-difference. Indeed, neonatal exposure to E2 depletes the oocyte pool in the rat ovary, whereas in the mouse it is well known to increase oocyte survival.
ISSN: 1932-6203

hal-00936582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00936582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00936582/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00936582/file/Systemic_Compensatory_Response-accepted.pdf
DOI : 10.1371/journal.pone.0082175

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5-17.5 days post-coitum) and humans (8-12 gestational weeks) and under different culture conditions. BPA concentrations of 10-8M and 10-5M for 72h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48h in both strains. BPA at 10-7-10-5M for 72h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10-8M, 10-7M, and 10-5M for 72h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.
ISSN: 1932-6203

hal-01121759
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121759
PUBMED : 25706302
DOI : 10.1371/journal.pone.0117226

Éditeur(s) : HAL CCSD
Résumé : International audience
Revista Investigacion Operacional

hal-01312465
https://hal.archives-ouvertes.fr/hal-01312465

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development.
ISSN: 1553-7390

hal-01063929
https://hal.archives-ouvertes.fr/hal-01063929
DOI : 10.1371/journal.pgen.1004340
PUBMED : 24784881

Éditeur(s) : HAL CCSD
Résumé : International audience
Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.
European Respiratory Journal

hal-01647080
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647080
DOI : 10.1183/13993003.00716-2017
PUBMED : 29074543

Éditeur(s) : HAL CCSD
Résumé : International audience
In this paper, via the algebra of generalized functions, we investigate the generalized Riemann's problem associated to conservation laws with analytical coefficients. This allows us to transform the problem into a system of ordinary differential equations. In some particular cases, such that Burgers' and conservative Richard's equation, approximated solutions are obtained by the truncation of the so called Hugoniot-Maslov's chain and numerical simulations are also presented in the case of equations with polynomial coefficients.
Novi Sad Journal of Mathematics

hal-00771405
https://hal.archives-ouvertes.fr/hal-00771405

Éditeur(s) : HAL CCSD Bulgarian Academy of Sciences
Résumé : International audience
ISSN: 1310-1331

hal-01443821
https://hal.archives-ouvertes.fr/hal-01443821

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications - the synthetic pyrethroid cypermethrin (CYP) - on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from gestation to postnatal day 15. Behavioral analyses were performed during the offspring's early life and during adulthood. Postnatal analyses revealed that perinatal exposure to CYP disturbed motor development without modifying sensory and communicative skills. We found that later in life, CYP-exposed offspring expressed maladaptive behaviors in response to highly challenging tasks and abnormal sociability. Transcriptomic analyses performed in the offspring's brain at the end of the exposure, highlighted mitochondrial dysfunction as a relevant pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved in proteostasis maintenance were also shown to be dysregulated suggesting that alterations in biogenesis, folding, trafficking and degradation of proteins may significantly contribute to CYP-related DNT. From a regulatory perspective, this study highlights that behavioral and transcriptomic analyses are complementary tools providing useful direction for better DNT characterization, and as such, should be used together more systematically.
ISSN: 1932-6203

hal-01616489
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616489
DOI : 10.1371/journal.pone.0184475
PUBMED : 29020013

Éditeur(s) : HAL CCSD
Résumé : International audience
Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolised to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here we show through steroidogenic profiling that exposure to aniline led to increased levels of the Δ4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity. We confirm that aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance in mice, a sensitive marker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into anti-androgenic paracetamol, impairs male reproductive development
Toxicological Sciences: An Official Journal of the Society of Toxicology

hal-01187305
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187305
DOI : 10.1093/toxsci/kfv179
PUBMED : 26259604

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

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
OBJECTIVES:Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown.MATERIALS AND METHODS:Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients.RESULTS:Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age.CONCLUSION:The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01669747
https://hal.univ-antilles.fr/hal-01669747
DOI : 10.1371/journal.pone.0158182
PUBMED : 27355589
PUBMEDCENTRAL : PMC4927160

Éditeur(s) : HAL CCSD
Résumé : 25 pages, Equipe AANL
We extend the theory of distributional kernel operators to a framework of generalized functions, in which they are replaced by integral kernel operators. Moreover, in contrast to the distributional case, we show that these generalized integral operators can be composed unrestrictedly. This leads to the definition of the exponential, and more generally entire functions, of a subclass of such operators.
https://hal.archives-ouvertes.fr/hal-00004888

hal-00004888
https://hal.archives-ouvertes.fr/hal-00004888
https://hal.archives-ouvertes.fr/hal-00004888/document
https://hal.archives-ouvertes.fr/hal-00004888/file/Article5.pdf
ARXIV : math/0505126

Éditeur(s) : HAL CCSD
Résumé : To appear in the Proceeding of GF2004 in ITSF (8 pages).
We extend the theory of distributional kernel operators to a framework of generalized functions, in which they are replaced by integral kernel operators. Moreover, in contrast to the distributional case, we show that these generalized integral operators can be composed unrestrictedly. This leads to the definition of the exponential of a subclass of such operators.
https://hal.archives-ouvertes.fr/hal-00004897

hal-00004897
https://hal.archives-ouvertes.fr/hal-00004897
https://hal.archives-ouvertes.fr/hal-00004897/document
https://hal.archives-ouvertes.fr/hal-00004897/file/GF04BernardDelcroixColombeauNov01.pdf
ARXIV : math.GM/0505179

Éditeur(s) : HAL CCSD
Résumé : To appear in TOPOLOGICAL METHODS IN NONLINEAR ANALYSIS (16 pages).
In the last two decades, many algebras of generalized functions have been constructed, particularly the so-called generalized Sobolev algebras. Our goal is to study the latter and some of their main properties. In this framework, we pose and solve a nonlinear degenerated Dirichlet problem with irregular data such as Dirac generalized functions.
https://hal.archives-ouvertes.fr/hal-00004903

Droits : info:eu-repo/semantics/OpenAccess
hal-00004903
https://hal.archives-ouvertes.fr/hal-00004903
https://hal.archives-ouvertes.fr/hal-00004903/document
https://hal.archives-ouvertes.fr/hal-00004903/file/sb_psn_pjm.pdf
ARXIV : math.GM/0505228

Éditeur(s) : HAL CCSD Elsevier Elsevier Masson
Résumé : New field and micropalaeontological investigations have been conducted in four of the Pliocene rias of the internal zone of the Rif in Morocco, on the southern margin of the Alboran Sea. We found that marine sediments outcropping in these rias were deposited mainly during the Early Zanclean, between 5.04 and 3.8 Ma. After a transgressive episode that led to the deposition of terrestrial to marine conglomerates, dark clays deposited first at shallow palaeo-depths and then at bathyal palaeo-depths. The rias were then infilled with a shallowing upward succession comprising marine clays and sandstone and, locally, terrestrial sediments that indicate their final emersion. No Gilbert-deltas were observed in these rias. The presence of transgressive deposits at the bottom of the rias, also identified in other basins of the external zone of the Rif, and the absence of Gilbert deltas question a catastrophic reflooding after the Messinian Salinity Crisis in this area.
ISSN: 1631-0713

hal-01115243
https://hal.archives-ouvertes.fr/hal-01115243
DOI : 10.1016/j.crte.2014.03.002

Éditeur(s) : HAL CCSD
Résumé : International audience
Generalized functions 2004
Novi Sad, Serbia

hal-01535463
https://hal.univ-antilles.fr/hal-01535463

Éditeur(s) : HAL CCSD
Résumé : International audience
Investigacion Operacionnal

hal-01185666
https://hal.univ-antilles.fr/hal-01185666

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The aim of this paper is to prove that the framework of generalized functions of Sobolev type is more suitable to pose and solve some PDEs problems with very irregular data, than the one introduced by J.-F. Colombeau, when ${mathcal{C}}^{infty}$ estimates are not available or out of reach. In such type of algebras, one shows the existence and some qualitative properties of solutions for problems appearing in the mathematical modelisation of oil activities.
Journal of Mathematical Analysis and applications

hal-00685042
https://hal.archives-ouvertes.fr/hal-00685042
DOI : 10.1016/j.jmaa.2011.07.063