Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Persistent organic pollutants may affect the immune and respiratory systems, but available evidence is based on small study populations. We studied the association between prenatal exposure to dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyl 153 (PCB 153) and children's respiratory health in European birth cohorts. METHODS: We included 4608 mothers and children enrolled in 10 birth cohort studies from 7 European countries. Outcomes were parent-reported bronchitis and wheeze in the first 4 years of life. For each cohort, we performed Poisson regression analyses, modeling occurrences of the outcomes on the estimates of cord-serum concentrations of PCB 153 and DDE as continuous variables (per doubling exposure) and as cohort-specific tertiles. Summary estimates were obtained through random-effects meta-analyses. RESULTS: The risk of bronchitis or wheeze (combined variable) assessed before 18 months of age increased with increasing DDE exposure (relative risk [RR] per doubling exposure = 1.03 [95% confidence interval = 1.00-1.07]). When these outcomes were analyzed separately, associations appeared stronger for bronchitis. We also found an association between increasing PCB 153 exposure and bronchitis in this period (RR per doubling exposure = 1.06 [1.01-1.12]) but not between PCB 153 and wheeze. No associations were found between either DDE or PCB 153 and ever-wheeze assessed after 18 months. Inclusion of both compounds in the models attenuated risk estimates for PCB 153 tertiles of exposure, whereas DDE associations were more robust. CONCLUSION: This large meta-analysis suggests that prenatal DDE exposure may be associated with respiratory health symptoms in young children (below 18 months), whereas prenatal PCB 153 levels were not associated with such symptoms.
Epidemiology (Cambridge, Mass.)

hal-01063930
https://hal.archives-ouvertes.fr/hal-01063930
DOI : 10.1097/EDE.0000000000000097
PUBMED : 24776790

Éditeur(s) : HAL CCSD
Résumé : International audience
Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants. We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies. The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a random- and fixed-effects meta-analysis. Women who ate fish >1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (≤ 1 time/wk); the adjusted RR of fish intake >1 but <3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake ≥ 3 times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher intake of fish during pregnancy gave birth to neonates with a higher birth weight by 8.9 g (95% CI: 3.3, 14.6 g) for >1 but <3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for ≥ 3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts. This large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weight.
The American Journal of Clinical Nutrition

hal-01118513
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118513
PUBMED : 24335057
DOI : 10.3945/ajcn.113.067421

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways
ISSN: 1553-7366

Droits : http://creativecommons.org/licenses/by/
hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/file/journal.ppat.1005153.pdf
DOI : 10.1371/journal.ppat.1005153

Éditeur(s) : HAL CCSD American Geophysical Union
Résumé : International audience
The Iberian Massif is the best exposed segment of the European Variscan Belt. It includes relatively well preserved terranes that were accreted by transpression along time and resulted in a number of geotectonic units that formed part of the Late Paleozoic assembly of the Pangaea Supercontinent. In SW Iberia, these units are the Central Iberian Zone (CIZ), Ossa Morena Zone (OMZ), and the South Portuguese Zone (SPZ). A 210 km long NE-SW magnetotelluric profile was carried out through the CIZ, from the OMZ-CIZ boundary toward the north, reaching the Tagus (Cenozoic) basin. Data dimensionality analysis resulted in a suitable 2-D electrical resistivity structure, allowing a 2-D inversion of the data set. Complementary available geophysical data (deep seismic, gravity and aeromagnetic) and a comparison with a detailed geological cross section led us to constrain the interpretation of the 2-D electrical resistivity structure of the CIZ crust. The results show, for the upper crust, the existence of diverse conductive/resistive bodies that correlate well with known geological features (sedimentary basins, faults, granitic plutons, mineralized systems). A mild but steady conductive band is located along the middle and lower crust that is interpreted as a mafic granulite basement. The upper section of this band connects with several elongated shallow conductors, providing further evidence for the existence, in the Central Iberian Zone, of a complex decollement system where the major faults are rooted. Such a crustal architecture is viewed as the northward continuation of the Variscan large-scale structures previously recognized in the southern sectors (OMZ and SPZ).
ISSN: 0148-0227

hal-00671036
https://hal.archives-ouvertes.fr/hal-00671036
DOI : 10.1029/2010JB007538

Éditeur(s) : HAL CCSD
Résumé : International audience
We assessed whether maternal employment during pregnancy - overall and in selected occupational sectors - is associated with birth weight, small for gestational age (SGA), term low birth weight (LBW), length of gestation, and preterm delivery in a population-based birth cohort design. We used data from >200 000 mother-child pairs enrolled in 13 European birth cohorts and compared employed versus non-employed women. Among employees, we defined groups of occupations representing the main sectors of employment for women where potential reproductive hazards are considered to be present. The comparison group comprised all other employed women not included in the occupational sector being assessed. We performed meta-analyses of cohort-specific estimates and explored heterogeneity. Employees had a lower risk of preterm delivery than non-employees [adjusted odds ratio (OR adj) 0.86, 95% confidence interval (95% CI) 0.81-0.91]. Working in most of the occupational sectors studied was not associated with adverse birth outcomes. Being employed as a nurse was associated with lower risk SGA infants (OR adj0.91, 95% CI 0.84-0.99) whereas food industry workers had an increased risk of preterm delivery (OR adj1.50, 95% CI 1.12-2.02). There was little evidence for heterogeneity between cohorts. This study suggests that, overall, employment during pregnancy is associated with a reduction in the risk of preterm birth and that work in certain occupations may affect pregnancy outcomes. This exploratory study provides an important platform on which to base further prospective studies focused on the potential consequences of maternal occupational exposures during pregnancy on child development.
Scandinavian journal of work, environment & health

Droits : info:eu-repo/semantics/OpenAccess
hal-01151621
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151621
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151621/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151621/file/Maternal%20occupation%20during%20pregnancy_supplementary%20material.pdf
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151621/file/Maternal%20occupation%20during%20pregnancy_accepted.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p'-DDE) can impair fetal growth; however, the exposure-response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure-response relationship between PCB-153 and p-p'-DDE and birth outcomes; to evaluate whether any no exposure-effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother-child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive models were used to evaluate the shape of the relationships between organochlorine compounds and birth outcomes. We observed an inverse linear exposure-response relationship between prenatal exposure to PCB-153 and birth weight [decline of 194g (95% CI -314, -74) per 1μg/L increase in PCB-153]. We showed effects on birth weight over the entire exposure range, including at low levels. This reduction seems to be stronger among children of mothers who were non-Caucasian or had smoked during pregnancy. The most susceptible subgroup was girls whose mothers smoked during pregnancy. After adjusting for absolute GWG or estimated fat mass, a reduction in birth weight was still observed. This study suggests that the association between low-level exposure to PCB-153 and birth weight exists and follows an inverse linear exposure-response relationship with effects even at low levels, and that maternal smoking and ethnicity modify this association.
ISSN: 0160-4120

hal-01118572
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118572
PUBMED : 25314142
DOI : 10.1016/j.envint.2014.09.013

Éditeur(s) : HAL CCSD BioMed Central
Résumé : [b]Background[/b]: [i]Amblyomma variegatum[/i] and [i]A. hebraeum[/i] are two ticks of veterinary and human health importance in south-east Africa. In Zimbabwe they occupy parapatric (marginally overlapping and juxtaposed) distributions. Understanding the mechanisms behind this parapatry is essential for predicting the spatio-temporal dynamics of Amblyomma spp. and the impacts of associated diseases. It has been hypothesized that exclusive competition between these species results from competition at the levels of male signal reception (attraction-aggregation-attachment pheromones) or sexual competition for mates. This hypothesis predicts that the parapatry described in Zimbabwe could also be present in other countries in the region. [br/][b]Methods[/b]: To explore this competitive exclusion hypothesis we conducted field surveys at the two species' range limits in Mozambique to identify areas of sympatry (overlapping areas) and to study potential interactions (communicative and reproductive interference effects) in those areas. At sympatric sites, hetero-specific mating pairs were collected and inter-specific attractiveness/repellent effects acting at long and short distances were assessed by analyzing species co-occurrences on co-infested herds and co-infested hosts.[br/] [b]Results[/b]: Co-occurrences of both species at sampling sites were infrequent and localized in areas where both tick and host densities were low. At sympatric sites, high percentages of individuals of both species shared attachment sites on hosts and inter-specific mating rates were high. Although cross-mating rates were not significantly different for[i] A. variegatum[/i] and [i]A. hebraeum[/i] females, attraction towards hetero-specific males was greater for [i]A. hebraeum[/i] females than for A. variegatum females and we observed small asymmetrical repellent effects between males at attachment sites.[br/][b]Conclusions[/b]: Our observations suggest near-symmetrical reproductive interference between [i]A. variegatum[/i] and [i]A. hebraeum[/i], despite between-species differences in the strength of reproductive isolation barriers acting at the aggregation, fixation and partner contact levels. Theoretical models predict that sexual competition coupled with hybrid inviability, greatly reduces the probability of one species becoming established in an otherwise suitable location when the other species is already established. This mechanism can explain why the parapatric boundary in Mozambique has formed within an area of low tick densities and relatively infrequent host-mediated dispersal events.
ISSN: 1756-3305

hal-01220744
https://hal.archives-ouvertes.fr/hal-01220744
https://hal.archives-ouvertes.fr/hal-01220744/document
https://hal.archives-ouvertes.fr/hal-01220744/file/2015%20Bournez%20Parasites%20%26%20Vectors_%7B365AAFF5-7041-480B-9B77-9CD0485A9B72%7D.pdf
DOI : 10.1186/s13071-015-1116-7

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
ISSN: 2047-217X

hal-01429002
https://hal.archives-ouvertes.fr/hal-01429002
DOI : 10.1186/s13742-016-0118-5