Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Introduction: Most studies on nematode-malaria interactions were conducted outside of the Americas. The objective of the present study was thus to study the relation between malaria and nematodes in a cohort of children in an Amazonian village. Methods: Odds ratios for intestinal nematode infections as an explanatory variable to malaria resistant vs. malaria sensitive were computed. Results: Ascaris lumbricoides was significantly more frequent in the ‘resistant’ malaria group than in the ‘sensitive’ one. Conclusions: Despite its low statistical power, the present results find that Ascaris was associated with less malaria, as observed by a number of studies.
ISSN: 0142-6338

inserm-01410100
http://www.hal.inserm.fr/inserm-01410100
http://www.hal.inserm.fr/inserm-01410100/document
http://www.hal.inserm.fr/inserm-01410100/file/worms%20malaria%20camopi%20j%20trop%20pediatrics.pdf
http://www.hal.inserm.fr/inserm-01410100/file/GI%20nematodes%20tab%20aurelia%29.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We isolated and characterized 26 microsatellite loci for Macrorhynchia phoenicea (Busk, 1852), a rather common tropical hydrozoan from the Indo-Pacific. The number of alleles per locus ranged from 4 to 24. The observed heterozygosity ranged from 0.000 to 0.970 and the expected heterozygosity from 0.029 to 0.833. Ten loci were at HardyeWeinberg equilibrium. No pair of loci presented linkage disequilibrium. Transferability of up to 18 loci was positive across four other Aglaopheniidae species from different genera. These loci will be used in studying reef population connectivity for these particular species at the scale of the Indo-Pacific, a promising but little explored research field.
ISSN: 0305-1978

hal-01253779
https://hal.archives-ouvertes.fr/hal-01253779
https://hal.archives-ouvertes.fr/hal-01253779/document
https://hal.archives-ouvertes.fr/hal-01253779/file/Biochemical%20Systematics%20and%20Ecology%202015%20Postaire_hal.pdf
DOI : 10.1016/j.bse.2015.08.011

Éditeur(s) : HAL CCSD IRD
Résumé : International audience
Malaria remains a major health problem in French Guiana despite the decrease in the number of cases since 2010. A previous study in Camopi, an Amerindian village on the Oyapock River, revealed that Plasmodium falciparum malaria incidence was significantly related to landscape features and that its spatial distribution exhibited some obvious patterns. In the present study, we first identified the spatial patterns that exhibit a significant Moran's index of spatial auto-correlation and that significantly explain P. falciparum malaria incidence within the multiple linear regression framework. Secondly, we linked these patterns with remotely sensed environmental features. The selected model is composed of five spatial components: three patterns, representing 50.7% of the total variance, are associated with large scale variations of the incidence, and the remaining patterns are associated with local scale variations and represent 28.7% of the total variance. Different hamlet clusters that have specificities in terms of P. falciparum malaria incidence rate, environmental characteristics and mosquito control strategies have been identified. The methodology proposed in the present study can provide useful knowledge on the spatial distribution of the P. falciparum malaria incidence in Camopi at different scales and on possible explanation of such distribution, as a function of the scale.
Symposium of the Latin American Society for Remote Sensing and Spatial Information Systems (SELPER)
Cayenne, French Guiana

ird-00797353
http://hal.ird.fr/ird-00797353
http://hal.ird.fr/ird-00797353/document
http://hal.ird.fr/ird-00797353/file/Roux_et_al_SELPER_2012.pdf
IRD : fdi:010058342

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28°C as compared to 37°C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.
Toxicology and Applied Pharmacology

hal-01063914
https://hal.archives-ouvertes.fr/hal-01063914
DOI : 10.1016/j.taap.2014.07.020

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
UNLABELLED: ABSTRACT: BACKGROUND: Malaria is a major health issue in French Guiana. Amerindian communities remain the most affected. A previous study in Camopi highlighted the predominant role of environmental factors in the occurrence of malaria. However, all parameters involved in the transmission were not clearly identified. A new survey was conducted in order to clarify the risk factors for the presence of malaria cases in Camopi. METHODS: An open cohort of children under seven years of age was set up on the basis of biologically confirmed malaria cases for the period 2001-2009. Epidemiological and observational environmental data were collected using two structured questionnaires. Data were analysed with a multiple failures multivariate Cox model. The influence of climate and the river level on malaria incidence was evaluated by time-series analysis. Relationships between Anopheles darlingi human biting rates and malaria incidence rates were estimated using Spearman's rank correlation. RESULTS: The global annual incidence over the nine-year period was 238 per 1,000 for Plasmodium falciparum, 514 per 1,000 for Plasmodium visa and 21 per 1,000 for mixed infections. The multivariate survival analysis associated higher malaria incidence with living on the Camopi riverside vs. the Oyapock riverside, far from the centre of the Camopi hamlet, in a home with numerous occupants and going to sleep late. On the contrary, living in a house cleared of all vegetation within 50 m and at high distance of the forest were associated with a lower risk. Meteorological and hydrological characteristics appeared to be correlated with malaria incidence with different lags. Anopheles darlingi human biting rate was also positively correlated to incident malaria in children one month later. CONCLUSIONS: Malaria incidence in children remains high in young children despite the appearance of immunity in children around three years of age. The closeness environment but also the meteorological parameters play an important role in malaria transmission among children under seven years of age in Camopi.
ISSN: 1475-2875

inserm-00633771
http://www.hal.inserm.fr/inserm-00633771
http://www.hal.inserm.fr/inserm-00633771/document
http://www.hal.inserm.fr/inserm-00633771/file/1475-2875-10-246.pdf
DOI : 10.1186/1475-2875-10-246

Éditeur(s) : HAL CCSD
Résumé : Benzophenone derivatives (BPs) are used as UV filters in many different products. These lipophilic compounds were recently described as ubiquitous contaminant of different compartiments of aquatic systems, including fish. In this study, we evaluated estrogenic activity of ten BPs in a model fish species, the zebrafish (Danio rerio), by combining newly developed in vitro and in vivo models. In vitro, three specific zebrafish reporter gene models expressing zebrafish estrogen receptors (ZfERs) in zebrafish hepatic cell line (ZFL) were used.Estrogenic activity of BPs was quantify in vivo by using a newly developed transgenic zebrafish line that expresses green fluorescent protein (GFP) under the control of the cyp19a1b promoter. The cyp19a1b gene codes for the brain aromatase B that is under the control of estrogens. Vitellogenin (Vtg), a marker of estrogenic compound, was used to assess the potential estrogenic effect of certain BPs in male fish. Five of 10 BPs induced an estrogenic activity on the three models: BP2, THB, BP1, 4BP, while BP and 234 BP were non active. We noted diffrence in BPs ranking depending on the zfER subtypes suggesting ?/? receptor selectivity by certain BPs. By quantifying GFP expression in live zebrafish, we confirm the estrogenic activity of some BP, i.e., BP1, THB, 4BP and 44'BP, as shown by their ability to induce GFP in a concentration-dependent manner. However, the ranking of BPs as a function of their estrogenic activity assay is different between models. For instance, 4BP was the most estrogenic compound in vivo but not in vitro. Differences were also noticed regarding the estrogenic activity of BP2. In vitro, BP2 has strong activity but had no effect on GFP in cyp19a1b-GFP embryo. However, BP2 induced strongly Vtg in male. The lack of estrogenic activity of BP2 in embryo may be related to difference of biodisponibility and/or metabolisation of this compound between embryo and adult fish. Our approach allows to characterize the estrogenic potency of emerging pollutants, using innovative in vitro and in vivo assays within a unique model fish species. The differences observed between assays deserve further studies to characterize the behavior of compounds in the different biological models in term of biodisponibility and metabolism.
1. European Conference on the Replacement, Reduction and Refinement of Animal Experiments in Ecotoxicology
Dübendorf, Switzerland

ineris-00971019
https://hal-ineris.archives-ouvertes.fr/ineris-00971019
INERIS : EN-2012-243

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Plasmodium vivax malaria is an important public health issue in the Amazon region, and it accounts for approximately 84 % of cases of the disease. Migration across the border between Brazil and French Guiana contributes to the maintenance of the disease. The aim of this study was to evaluate the therapeutic and parasitological responses of patients with P. vivax malaria treated with chloroquine and primaquine in the socio-environmental context of cross-border interactions between Brazil and French Guiana. The factors controlled were diagnostic agreement, adherence, adjustment of primaquine doses for patient weight, and quality of the drugs used. A prospective study was conducted in 2011 with 103 individuals aged 10-60 years with a positive diagnosis of P. vivax treated with chloroquine (10 mg base/kg on the first day, followed by 7.5 mg/kg on the second and third days) and primaquine for 7 days, who were followed for 28 days. The primaquine doses were adjusted for the patients' weight. A number of factors were determined: epidemiological characteristics, origin of patients, signs and symptoms, initial parasitaemia and parasitaemia clearance time, blood concentrations of chloroquine and primaquine, quality of anti-malarial drugs and diagnostic agreement. Ninety-five patients were followed for 28 days. There was a 100 % agreement in microscopic diagnosis between field laboratory and reference centre. The adhesion to the treatment was 100 %. Of these patients, 32.6 % received a weight-adjusted dose of primaquine. The chloroquine and primaquine tablets were consistent with the optimal quality limits for human consumption. The investigated patients achieved optimal blood exposure to anti-malarial drugs. The parasitological and therapeutic response was adequate in 99.0 % of cases. In the municipality of Oiapoque, the therapeutic regime used for the treatment of P. vivax malaria using chloroquine combined with primaquine remains effective, when external factors are controlled, such as the quality of anti-malarial drugs, the adhesion to the treatment prescribed, the correct diagnostic and the adjustment of primaquine dose for patient body weight.
ISSN: 1475-2875

Droits : http://creativecommons.org/licenses/by/
pasteur-01229355
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355/file/s12936-015-0925-7.pdf
PUBMEDCENTRAL : PMC4600333

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
The nine countries sharing the Amazon forest accounted for 89% of all malaria cases reported in the Americas in 2008. Remote sensing can help identify the environmental determinants of malaria transmission and their temporo-spatial evolution. Seventeen studies characterizing land cover or land use features, and relating them to malaria in the Amazon subregion, were identified. These were reviewed in order to improve the understanding of the land cover/use class roles in malaria transmission. The indicators affecting the transmission risk were summarized in terms of temporal components, landscape fragmentation and anthropic pressure. This review helps to define a framework for future studies aiming to characterize and monitor malaria.
ISSN: 1475-2875

inserm-00834790
http://www.hal.inserm.fr/inserm-00834790
http://www.hal.inserm.fr/inserm-00834790/document
http://www.hal.inserm.fr/inserm-00834790/file/1475-2875-12-192.pdf
DOI : 10.1186/1475-2875-12-192

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Genetic diversity is crucial for species' maintenance and persistence, yet is often overlooked in conservation studies. Species diversity is more often reported due to practical constraints, but it is unknown if these measures of diversity are correlated. In marine invertebrates, adults are often sessile or sedentary and populations exchange genes via dispersal of gametes and larvae. Species with a larval period are expected to have more connected populations than those without larval dispersal. We assessed the relationship between measures of species and genetic diversity, and between dispersal ability and connectivity. We compiled data on genetic patterns and life history traits in nine species across five phyla. Sampling sites spanned 600km in the northwest Mediterranean Sea and focused on a 50-km area near Marseilles, France. Comparative population genetic approaches yielded three main results. (i) Species without larvae showed higher levels of genetic structure than species with free-living larvae, but the role of larval type (lecithotrophic or planktotrophic) was negligible. (ii) A narrow area around Marseilles, subject to offshore advection, limited genetic connectivity in most species. (iii) We identified sites with significant positive contributions to overall genetic diversity across all species, corresponding with areas near low human population densities. In contrast, high levels of human activity corresponded with a negative contribution to overall genetic diversity. Genetic diversity within species was positively and significantly linearly related to local species diversity. Our study suggests that local contribution to overall genetic diversity should be taken into account for future conservation strategies.
ISSN: 0962-1083

hal-01681650
https://hal.archives-ouvertes.fr/hal-01681650
DOI : 10.1111/mec.14389

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We isolated and characterized 26 microsatellite loci for Macrorhynchia phoenicea (Busk, 1852), a rather common tropical hydrozoan from the Indo-Pacific. The number of alleles per locus ranged from 4 to 24. The observed heterozygosity ranged from 0.000 to 0.970 and the expected heterozygosity from 0.029 to 0.833. Ten loci were at HardyeWeinberg equilibrium. No pair of loci presented linkage disequilibrium. Transferability of up to 18 loci was positive across four other Aglaopheniidae species from different genera. These loci will be used in studying reef population connectivity for these particular species at the scale of the Indo-Pacific, a promising but little explored research field.
ISSN: 0305-1978

hal-01359419
https://hal.archives-ouvertes.fr/hal-01359419
DOI : 10.1016/j.bse.2015.08.011

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aryl hydrocarbon receptor-dependent genomic effects of environmental polycyclic aromatic hydrocarbons (PAHs) have been shown to be modulated by non-genomic protein kinase C (PKC)-related pathways. The present study was designed to determine whether PKC activation may also impair estrogenic genomic response triggered by PAHs. Treatment by the PKC activator phorbol 12-myristate 13-acetate (PMA) was found to markedly and differentially impair the up-regulation of estrogenic markers triggered by the estrogenic PAH benzanthracene (BZA) in cultured human mammary cells; BZA-mediated mRNA up-regulation of pS2 and amphiregulin was thus increased, whereas that of progesterone receptor and CXCL12 was repressed. BZA/PMA cotreatment however failed to alter BZA-mediated increase of activity of a luciferase gene reporter construct driven by an estrogen response element, thus discarding any global effect of PMA toward BZA-triggered estrogen receptor activation. Various chemicals inhibiting PKCs or extracellular signal-regulated kinase (ERK) as well as the knock-down of PKCδ expression counteracted the PMA-mediated increase of pS2 mRNA up-regulation triggered by BZA, demonstrating that it was dependent on PKCs, including PKCδ isoform, and ERKs. This non-genomic modulation of estrogenic effects of PAHs by PKC activation may have to be considered when considering the deleterious effects of these environmental contaminants towards the endocrine system.
ISSN: 0887-2333

inserm-00872862
http://www.hal.inserm.fr/inserm-00872862
DOI : 10.1016/j.tiv.2012.05.006
PUBMED : 22643241

Éditeur(s) : HAL CCSD WILEY-BLACKWELL Wiley
Résumé : International audience
Connectivity among populations determines the dynamics and evolution of populations, and its assessment is essential in ecology in general and in conservation biology in particular. The robust basis of any ecological study is the accurate delimitation of evolutionary units, such as populations, metapopulations and species. Yet a disconnect still persists between the work of taxonomists describing species as working hypotheses and the use of species delimitation by molecular ecologists interested in describing patterns of gene flow. This problem is particularly acute in the marine environment where the inventory of biodiversity is relatively delayed, while for the past two decades, molecular studies have shown a high prevalence of cryptic species. In this study, we illustrate, based on marine case studies, how the failure to recognize boundaries of evolutionary-relevant unit leads to heavily biased estimates of connectivity. We review the conceptual framework within which species delimitation can be formalized as falsifiable hypotheses and show how connectivity studies can feed integrative taxonomic work and vice versa. Finally, we suggest strategies for spatial, temporal and phylogenetic sampling to reduce the probability of inadequately delimiting evolutionary units when engaging in connectivity studies.
ISSN: 0962-1083

hal-01218810
https://hal.archives-ouvertes.fr/hal-01218810
DOI : 10.1111/mec.13048

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Malaria remains one of the most common vector-borne diseases in the world and the definition of novel control strategies can benefit from the modeling of transmission processes. However, data-driven models are often difficult to build, as data are very often incomplete, heterogeneous in nature and in quality, and/or biased. In this context, a knowledge-based approach is proposed to build a robust and general landscape-based hazard index for malaria transmission that is tailored to the Amazonian region. A partial knowledge-based model of the risk of malaria transmission in the Amazonian region, based on landscape features and extracted from a systematic literature review, was used. Spatialization of the model was obtained by generating land use and land cover maps of the cross-border area between French Guiana and Brazil, followed by computing and combining landscape metrics to build a set of normalized landscape-based hazard indices. An empirical selection of the best index was performed by comparing the indices in terms of adequacy with the knowledge-based model, intelligibility and correlation with P. falciparum incidence rates. The selected index is easy to interpret and successfully represents the current knowledge about the role played by landscape patterns in malaria transmission within the study area. It was significantly associated with P. falciparum incidence rates, using the Pearson and Spearman correlation coefficients (up to 0.79 and 0.75, respectively; p-value < 0.001), and the linear regression coefficient of determination (reaching 0.63; p-values < 0.001). This study establishes a spatial knowledge-driven, landscape-based hazard malaria index using remote sensing that can be easily produced on a regular basis and might be useful for malaria prediction, surveillance, and control. Keywords: remote sensing; land use and land cover; landscape metric; knowledge-based hazard modeling; malaria; cross-border area between French Guiana and Brazil
ISSN: 2072-4292

hal-01355255
https://hal.archives-ouvertes.fr/hal-01355255
https://hal.archives-ouvertes.fr/hal-01355255/document
https://hal.archives-ouvertes.fr/hal-01355255/file/010066865.pdf
IRD : fdi:010066865

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28°C as compared to 37°C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.
ISSN: 0041-008X

inserm-01067804
http://www.hal.inserm.fr/inserm-01067804
http://www.hal.inserm.fr/inserm-01067804/document
http://www.hal.inserm.fr/inserm-01067804/file/pintot_et_al._manuscript.pdf
DOI : 10.1016/j.taap.2014.07.020

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
: Context:Masculinization depends on the fetal testis. Exposure of the human fetus during pregnancy to paracetamol or/and to other mild-analgesics is associated with an increased risk of cryptorchidism.Objective:We aimed at determining whether mild analgesics disrupted the morphology and endocrine function of the human testis.Design:We used an in vitro system based on the culture of human fetal testes exposed or not to paracetamol, its metabolite AM404, aspirin, indomethacin, ketoconazole at 10(-4) M to 10(-7) M.Setting:The study was conducted at the University of Rennes I.Patients/Participants:Human fetal testes were from pregnant women following induced abortion, between 7 and 12 weeks of gestation (GW).Main Outcome Measures:Testosterone (radioimmunoassay: RIA), Anti-Müllerian Hormone (AMH; ELISA), insulin-like factor 3 (INSL3; RIA), prostaglandin D2 and E2 (PGD2 and PGE2, respectively; ELISA), were assayed in the media. Testicular cells were counted using histology and image analysis. The possible nuclear receptor-mediated activities of the analgesics were investigated using reporter cell lines expressing estrogen (ERs), androgen (AR) and peroxysome proliferator-activated γ ( PPARγ) receptors.Results:Indomethacin and aspirin stimulated testosterone production, particularly by the younger testes (8-9 GW vs 10-12 GW). Paracetamol, AM404 and ketoconazole decreased INSL3 levels. Aspirin stimulated, whereas ketoconazole inhibited AMH production. PGE2 levels were inhibited by paracetamol, and aspirin in the 7-12 GW testes, and by indomethacin but only in 7-9.86 GW old testes. The inhibitory trends seen for PGD2 were not statistically significant.Conclusions:Analgesics at concentrations relevant to human exposure cause endocrine disturbances in the fetal testis. We suggest that the fetal human testis displays slight critical age windows for sensitivity to direct exposure to aspirin, indomethacin and paracetamol. The analgesic-induced inhibition of INSL3 may be the mechanism by which analgesics increase the risk of cryptorchidism. Greater caution is required concerning consumption of analgesics during pregnancy.
ISSN: 0021-972X

inserm-00876125
http://www.hal.inserm.fr/inserm-00876125
DOI : 10.1210/jc.2013-2531
PUBMED : 24030937

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Malaria is a major public health problem in French Guiana, where Plasmodium vivax has become the dominant malaria species since 2000. As in others endemic areas, it is important to specify the pattern of vivax malaria relapses and to try to discriminate efficiently re-infections from relapses. METHODS: This study was conducted in children born between January 1, 2001 and December 31, 2008 in Camopi, an Amerindian village located in the Amazon forest (n = 325), using an open cohort design. Primary and secondary attack rates of P. vivax were calculated using survival analysis. With the difference between the primary and secondary rates, this study aimed to estimate indirectly P. vivax relapse rate and evaluate its time evolution. RESULTS: Of the 1042 malaria attacks recorded, 689 (66%) were due to P. vivax (without mixed infection). One hundred and fifty one children had their primary attack with P. vivax and 106 had their two first attacks with P. vivax. In the absence of primaquine treatment, it was shown that P. vivax relapses mainly occurred during the first three months after the first attack. Thirty percent of children never had a relapse, 42% had a relapse before the first month after primary attack, 59% before the second month and 63% before the third month. CONCLUSION: This study confirmed that the relapse pattern in Camopi was compatible with the pattern described for the P. vivax Chesson (tropical) strain. In addition, due to the relapse rate time evolution, a simple arbitrary classification rule could be constructed: before 90 days after the primary attack, the secondary attack is a relapse; after 90 days, it is a re-infection. Adapted management of malaria cases based on these results could be devised.
ISSN: 1475-2875

inserm-00663913
http://www.hal.inserm.fr/inserm-00663913
http://www.hal.inserm.fr/inserm-00663913/document
http://www.hal.inserm.fr/inserm-00663913/file/1475-2875-8-278.pdf
DOI : 10.1186/1475-2875-8-278

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Co-exposure to environmental polycyclic aromatic hydrocarbons (PAHs) and interleukin (IL)-1β induces expression of the tumor-promoting cytokine IL-6 in cancer cells. The present study was designed to determine whether such an IL-6 up-regulation also occurs in response to co-treatment by PAHs and tumor necrosis factor (TNF)-α, an inflammatory cytokine commonly found in tumor microenvironment. Co-exposure to the prototypical PAH benzanthracene (BZA) and TNF-α was found to markedly induce mRNA expression and secretion of IL-6 in human breast cancer cells MCF-7, whereas exposure to either BZA or TNF-α alone was without significant effect. Co-treatment by BZA and TNF-α-containing conditioned media from human inflammatory macrophages similarly up-regulated IL-6 expression in MCF-7 cells. BZA/TNF-α-mediated IL-6 induction in MCF-7 cells was counteracted by silencing aryl hydrocarbon receptor (AhR), known to mediates most of PAH effects. IL-6 up-regulation was moreover associated with NF-κB activation and was abolished by using chemical NF-κB inhibitors or knocking-down expression of the p65/RelA NF-κB subunit. Taken together, these data indicate that co-exposure to BZA/TNF-α induces IL-6 expression by AhR- and NF-κB-dependent pathways in MCF-7 cancer cells. This regulation of IL-6 by environmental PAHs, that is dependent of inflammatory cytokine microenvironment, may contribute to the well-known carcinogenic properties of these organic pollutants.
ISSN: 0009-2797

inserm-00818896
http://www.hal.inserm.fr/inserm-00818896
DOI : 10.1016/j.cbi.2013.01.005
PUBMED : 23396138

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 BioMed Central
Résumé : International audience
UNLABELLED: ABSTRACT: BACKGROUND: Malaria remains a major health problem in French Guiana, with a mean of 3800 cases each year. A previous study in Camopi, an Amerindian village on the Oyapock River, highlighted the major contribution of environmental features to the incidence of malaria attacks. We propose a method for the objective selection of the best multivariate peridomestic landscape characterisation that maximises the chances of identifying relationships between environmental features and malaria incidence, statistically significant and meaningful from an epidemiological point of view. METHODS: A land-cover map, the hydrological network and the geolocalised inhabited houses were used to characterise the peridomestic landscape in eleven discoid buffers with radii of 50, 100, 200, 300, 400, 500, 600, 700, 800, 900 and 1000 metres. Buffer-based landscape characterisations were first compared in terms of their capacity to discriminate between sites within the geographic space and of their effective multidimensionality in variable space. The Akaike information criterion (AIC) was then used to select the landscape model best explaining the incidences of P. vivax and P. falciparum malaria. Finally, we calculated Pearson correlation coefficients for the relationships between environmental variables and malaria incidence, by species, for the more relevant buffers. RESULTS: The optimal buffers for environmental characterisation had radii of 100 m around houses for P. vivax and 400 m around houses for P. falciparum. The incidence of P. falciparum malaria seemed to be more strongly linked to environmental features than that of P. vivax malaria, within these buffers. The incidence of P. falciparum malaria in children was strongly correlated with proportions of bare soil (r = -0.69), land under high vegetation (r = 0.68) and primary forest (r = 0.54), landscape division (r = 0.48) and the number of inhabited houses (r = -0.60). The incidence of P. vivax malaria was associated only with landscape division (r = 0.49). CONCLUSIONS: The proposed methodology provides a simple and general framework for objective characterisation of the landscape to account for field observations. The use of this method enabled us to identify different optimal observation horizons around houses, depending on the Plasmodium species considered, and to demonstrate significant correlations between environmental features and the incidence of malaria.
ISSN: 1476-072X

inserm-00674075
http://www.hal.inserm.fr/inserm-00674075
http://www.hal.inserm.fr/inserm-00674075/document
http://www.hal.inserm.fr/inserm-00674075/file/1476-072X-10-65.pdf
DOI : 10.1186/1476-072X-10-65

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
: Malaria is a public health problem in French Guiana. Plasmodium vivax is the most frequent parasite. The objective of this analysis was to estimate the proportion of relapses in the burden of vivax malaria using the statistical rule stating that any case of vivax malaria occurring less than 90 days following a first episode is a relapse.A total of 622 subjects were followed for 2,9 years with 336 first single episodes of P. vivax malaria, and a total of 1,226 episodes of vivax malaria among which 559 were relapses (45.5%). For 194 patients having had falciparum malaria followed by vivax malaria it was estimated that 19% of the vivax episodes occurred less than 90 days following the falciparum episode and thus were possibly relapses due to the activation of latent hypnozoites. Despite the number of vivax cases and the number of relapses, there were only 28 recorded primaquine prescriptions (3.4% of vivax episodes, 4.5% of subjects).The present study points out that despite the fact that nearly half of the P. vivax cases, many of which in children, are caused by latent hypnozoites, only a minority of them benefit from primaquine radical cure. The obstacles to this are discussed and suggestions are made to reduce the burden of vivax malaria in Camopi and other remote health centres in French Guiana.
ISSN: 1475-2875

inserm-00903890
http://www.hal.inserm.fr/inserm-00903890
http://www.hal.inserm.fr/inserm-00903890/document
http://www.hal.inserm.fr/inserm-00903890/file/1475-2875-12-367.pdf
DOI : 10.1186/1475-2875-12-367