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Exposure to Atmospheric Ultrafine Particles Induces Severe Lung Inflammatory Response and Tissue Remodeling in Mice
No full textInternational audienceExposure to particulate matter (PM) is leading to various respiratory health outcomes. Compared to coarse and fine particles, less is known about the effects of chronic exposure to ultrafine particles, despite their higher number and reactivity. In the present study, we performed a time-course experiment in mice to better analyze the lung impact of atmospheric ultrafine particles, with regard to the effects induced by fine particles collected on the same site. Trace element and PAH analysis demonstrated the almost similar chemical composition of both particle fractions. Mice were exposed intranasally to FF or UFP according to acute (10, 50 or 100 µg of PM) and repeated (10 µg of PM 3 times a week during 1 or 3 months) exposure protocols. More particle-laden macrophages and even greater chronic inflammation were observed in the UFP-exposed mice lungs. Histological analyses revealed that about 50% of lung tissues were damaged in mice exposed to UFP for three months versus only 35% in FF-exposed mice. These injuries were characterized by alveolar wall thickening, macrophage infiltrations, and cystic lesions. Taken together, these results strongly motivate the update of current regulations regarding ambient PM concentrations to include UFP and limit their emission
Exposure of marine mussels to diclofenac: modulation of prostaglandin biosynthesis
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Characterization of Children's Exposure to Extremely Low Frequency Magnetic Fields by Stochastic Modeling
No full textInternational audienceIn this study, children's exposure to extremely low frequency magnetic fields (ELF-MF, 40-800 Hz) is investigated. The interest in this thematic has grown due to a possible correlation between the increased risk of childhood leukemia and a daily average exposure above 0.4 µT, although the causal relationship is still uncertain. The aim of this paper was to present a new method of characterizing the children's exposure to ELF-MF starting from personal measurements using a stochastic approach based on segmentation (and to apply it to the personal measurements themselves) of two previous projects: the ARIMMORA project and the EXPERS project. The stochastic model consisted in (i) splitting the 24 h recordings into stationary events and (ii) characterizing each event with four parameters that are easily interpretable: the duration of the event, the mean value, the dispersion of the magnetic field over the event, and a final parameter characterizing the variation speed. Afterward, the data from the two databases were divided in subgroups based on a characteristic (i.e., children's age, number of inhabitants in the area, etc.). For every subgroup, the kernel density estimation (KDE) of each parameter was calculated and the p-value histogram of the parameters together was obtained, in order to compare the subgroups and to extract information about the children's exposure. In conclusion, this new stochastic approach allows for the identification of the parameters that most affect the level of children's exposure
TOXsIgN: a cross-species repository for toxicogenomic signatures
No full textInternational audienceMOTIVATION:At the same time that toxicologists express increasing concern about reproducibility in this field, the development of dedicated databases has already smoothed the path toward improving the storage and exchange of raw toxicogenomic data. Nevertheless, none provides access to analyzed and interpreted data as originally reported in scientific publications. Given the increasing demand for access to this information, we developed TOXsIgN, a repository for TOXicogenomic sIgNatures.RESULTS:The TOXsIgN repository provides a flexible environment that facilitates online submission, storage and retrieval of toxicogenomic signatures by the scientific community. It currently hosts 754 projects that describe more than 450 distinct chemicals and their 8491 associated signatures. It also provides users with a working environment containing a powerful search engine as well as bioinformatics/biostatistics modules that enable signature comparisons or enrichment analyses.AVAILABILITY AND IMPLEMENTATION:The TOXsIgN repository is freely accessible at http://toxsign.genouest.org. Website implemented in Python, JavaScript and MongoDB, with all major browsers supported
Aquifer recharge with stormwater runoff in urban areas: Influence of vadose zone thickness on nutrient and bacterial transfers from the surface of infiltration basins to groundwater
No full textInternational audienceStormwater in␣ltration systems (SIS) have been built in urban areas to reduce the environmental impacts of stormwater runoff. In␣ltration basins allow the transfer of stormwater runoff to aquifers but their abilities to retain contaminants de- pend on vadose zone properties. This study assessed the in␣uence of vadose zone thickness (VZT) on the transfer of inor- ganic nutrients (PO34␣, NO␣3 , NH+4 ), dissolved organic carbon (total -DOC- and biodegradable -BDOC-) and bacteria. A ␣eld experiment was conducted on three SIS with a thin vadose zone (b3 m) and three SIS with a thick vadose zone (N10 m). Water samples were collected at three times during a rainy period of 10 days in each in␣ltration basin (stormwater runoff), in the aquifer impacted by in␣ltration (impacted groundwater) and in the same aquifer but upstream of the in␣ltration area (non-impacted groundwater). Inorganic nutrients, organic matter, and dissolved oxygen (DO) were measured on all water samples. Bacterial community structures were investigated on water samples through a next-generation se- quencing (NGS) scheme of 16S rRNA gene amplicons (V5-V6). The concentrations of DO and phosphate measured in SIS-impacted groundwaters were signi␣cantly in␣uenced by VZT due to distinct biogeochemical processes occurring in the vadose zone. DOC and BDOC were ef␣ciently retained in the vadose zone, regardless of its thickness. Bacterial transfers to the aquifer were overall low, but data obtained on day 10 indicated a signi␣cant bacterial transfer in SIS with a thin va- dose zone. Water transit time and water saturation of the vadose zone were found important parameters for bacterial transfers. Most bacterial taxa (N60%) from impacted groundwaters were not detected in stormwater runoff and in non- impacted groundwaters, indicating that groundwater bacterial communities were signi␣cantly modi␣ed by processes as- sociated with in␣ltration (remobilization of bacteria from vadose zone and/or species sorting)
Theoretical impact of simulated workplace-based primary prevention of carpal tunnel syndrome in a French region
No full textInternational audienceBackground - Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy in the working-age population. The reduction of CTS incidence in the workforce is a priority for policy makers due to the human, social and economic costs. To assess the theoretical impact of workplace-based primary interventions designed to reduce exposure to personal and/or work-related risk factors for CTS. Methods - Surgical CTS were assessed using regional hospital discharge records for persons aged 20-59 in 2009. Using work-related attributable fractions (AFEs), we estimated the number of work-related CTS (WR-CTS) in high-risk jobs. We simulated three theoretical scenarios of workplace-based primary prevention for jobs at risk: a mono-component work-centered intervention reducing the incidence of WR-CTS arbitrarily by 10% (10%-WI), and multicomponent global interventions reducing the incidence of all surgical CTS by 5% and 10% by targeting personal and work risk factors. Results - A limited proportion of CTS were work-related in the region's population. WR-CTS were concentrated in nine jobs at high risk of CTS, amounting to 1603 [1137-2212] CTS, of which 906 [450-1522] were WR-CTS. The 10%-WI, 5%-GI and 10%-GI hypothetically prevented 90 [46-153], 81 [58-111] and 159 [114-223] CTS, respectively. The 10%-GI had the greatest impact regardless of the job. The impact of the 10%-WI interventions was high only in jobs at highest risk and AFEs (e.g. food industry jobs). The 10%-WI and 5%-GI had a similar impact for moderate-risk jobs (e.g. healthcare jobs). Conclusion - The impact of simulated workplace-based interventions suggests that prevention efforts to reduce exposure to work-related risk factors should focus on high-risk jobs. Reducing CTS rates will also require integrated strategies to reduce personal risk factors, particularly in jobs with low levels of work-related risk of CTS
Descriptive self-reporting survey of people with idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) : similarities and comparisons with previous studies
No full textInternational audienceContext : In France, cases of people self-reporting symptoms due to electromagnetic fields (EMF) or idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) have emerged over the past 10 years. Several self-help and action groups have claimed an increasing number of members. However, little is known about this population in France. Aim : Our primary objective was to describe the reported symptoms and the sources that may induce these symptoms through a questionnaire-based study. Secondly, we discussed our results alongside those obtained from the existing literature and provide an overview of this physical condition. Subjects and methods : From April to November 2014, a self-questionnaire survey was conducted in France. With 52 participants, the average age of respondents was 50 ± 11 years and the majority of participants at 79% were women. Results : Our study results in the French population were consistent with findings in the literature conducted in other countries and also highlighted a number of emerging EMF sources such as wireless area networks, to be perceived as possible causes of symptoms. Conclusions : Despite methodological differences, we summarized facts from previous comparable investigations. We also provided an overview of people claiming EMF effects and briefly discussed possible avenues of research
The Involvement of Aryl hydrocarbon receptor in myelination and in human nerve sheath tumorigenesis
No full textInternational audienceAryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in xenobiotic metabolism. Plexiform neurofibromas (PNFs) can transform into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to existing therapies. These tumors are primarily composed of Schwann cells. In addition to neurofibroma-tosis type 1 (NF1) gene inactivation, further genetic lesions are required for malignant transformation. We have quantified the mRNA expression levels of AHR and its associated genes in 38 human samples. We report that AHR and the biosynthetic enzymes of its en-dogenous ligand are overexpressed in human biopsies of PNFs and MPNSTs. We also detect a strong nuclear AHR staining in MPNSTs. The inhibition of AHR by siRNA or antagonists, CH-223191 and tri-methoxyflavone, induces apoptosis in human MPNST cells. Since AHR dysregulation is observed in these tumors, we investigate AHR involvement in Schwann cell physiology. Hence, we studied the role of AHR in myelin structure and myelin gene regulation in Ahr −/− mice during myelin development. AHR ablation leads to lo-comotion defects and provokes thinner myelin sheaths around the axons. We observe a dysregulation of myelin gene expression and myelin developmental markers in Ahr −/− mice. Interestingly, AHR does not directly bind to myelin gene promoters. The inhibition of AHR in vitro and in vivo increased β-catenin levels and stimulated the binding of β-catenin on myelin gene promoters. Taken together, our findings reveal an endogenous role of AHR in peripheral myeli-nation and in peripheral nerve sheath tumors. Finally, we suggest a potential therapeutic approach by targeting AHR in nerve tumors. AHR | myelin | nerve | MPNST | neurofibrom
Stochastic Dosimetry Based on Low Rank Tensor Approximations for the Assessment of Children Exposure to WLAN Source
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Adult male mice exposure to nonylphenol alters courtship vocalizations and mating
No full textInternational audienceThe neural circuitry processing male sexual behavior is tightly regulated by testosterone and its neural metabolite estradiol. The present study evaluated the effects of adult exposure to low doses of nonylphenol (NP), a widespread environmental contaminant, on the neuroendocrine regulation of testosterone and expression of sexual behavior. Oral exposure of C57BL/6J males to NP (0.5, 5 or 50 μg/kg/day) for 4 weeks did not affect circulating levels of testosterone or the kisspeptin system, a key regulator of the gonadotropic axis. In contrast, mice exposed to NP at 5 μg/kg/day emitted an increased number and duration of ultrasonic vocalizations, took longer to reach ejaculation and showed increased number of mounts, intromissions and thrusts. This was associated with normal olfactory preference and locomotor activity, and increased anxiety level. Analysis of the neural circuitry that underlies sexual behavior showed changes in the number of cells expressing androgen and estrogen receptors in males exposed to NP at 5 μg/kg/day. The neural circuitry underlying sexual behavior is thus highly sensitive to adult exposure to NP. Furthermore, almost all the observed effects were induced at 5 μg/kg/day of NP, indicating that this endocrine disrupter triggers a non-monotonic response in the adult male mouse brain