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Alpha-Mannosidosis (AM) is an ultra-rare storage disorder caused by a deficiency of lysosomal alpha-mannosidase encoded by the MAN2B1 gene. Clinical presentation of AM includes mental retardation, recurrent infections, hearing loss, dysmorphic features, and motor dysfunctions. AM has never been reported in Tunisia. We report here the clinical and genetic study of six patients from two Tunisian families with AM. The AM diagnosis was confirmed by an enzymatic activity assay. Genetic investigation was conducted by Sanger sequencing of the mutational hotspots for the first family and by ES analysis for the second one. In the first family, a frameshift duplication p.(Ser802GlnfsTer129) was identified in the MAN2B1 gene. For the second family, ES analysis led to the identification of a missense mutation p.(Arg229Trp) in the MAN2B1 gene in four affected family members. The p.(Ser802GlnfsTer129) mutation induces a premature termination codon which may trigger RNA degradation by the NMD system. The decrease in the levels of MAN2B1 synthesis could explain the severe phenotype observed in the index case. According to the literature, the p.(Arg229Trp) missense variant does not have an impact on MAN2B1 maturation and transportation, which correlates with a moderate clinical sub-type. To explain the intra-familial variability of cognitive impairment, exome analysis allowed the identification of two likely pathogenic variants in GHR and SLC19A3 genes potentially associated to cognitive decline. The present study raises awareness about underdiagnosis of AM in the region that deprives patients from accessing adequate care. Indeed, early diagnosis is critical in order to prevent disease progression and to propose enzyme replacement therapy.

Background and Purpose: Stroke is reported as a consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in several reports. However, data are sparse regarding the details of these patients in a multinational and large scale. Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke, intracranial hemorrhage, and cerebral venous or sinus thrombosis among SARS-CoV-2–infected patients. We further investigated the risk of large vessel occlusion, stroke severity as measured by the National Institutes of Health Stroke Scale, and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with acute ischemic stroke. In addition, we explored the neuroimaging findings, features of patients who were asymptomatic for SARS-CoV-2 infection at stroke onset, and the impact of geographic regions and countries’ health expenditure on outcomes. Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least 1 eligible stroke patient. Of 432 patients included, 323 (74.8%) had acute ischemic stroke, 91 (21.1%) intracranial hemorrhage, and 18 (4.2%) cerebral venous or sinus thrombosis. A total of 183 (42.4%) patients were women, 104 (24.1%) patients were P =0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; P Conclusions: We observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.

Background Estimates of leptospirosis morbidity identified Oceania as the region with highest burden. Besides Australia and New Zealand, Oceania is home of Pacific Island Countries and Territories, most of which are developing countries facing a number of challenges. Their archipelago geography notably affects health infrastructure and access to healthcare. Although human leptospirosis was formerly identified in Vanuatu, there is a lack of knowledge of this disease in the country. We aimed to identify leptospirosis in outpatients visiting the hospital. Methodology/Principal findings We conducted a clinical study to investigate leptospirosis as a cause of non-malarial acute febrile illness in Vanuatu. A total 161 outpatients visiting the outpatient clinics at Port Vila Central Hospital for internal medicine were recruited over 20 month. We showed that leptospirosis significantly affects humans in Vanuatu: 12 cases were confirmed by real-time PCR on acute blood samples (n = 5) or by high serology titers evidencing a recent infection (MAT titer ≥800 or ELISA≥18 Units, n = 7). A high rate of positive serology was also evidenced, by MAT (100, Author summary Leptospirosis is thought to impose its highest burden to tropical island populations, especially in the Pacific region of Oceania. Yet, very few information has ever been reported from some of the Pacific Island Countries and Territories, including Vanuatu. In this study, we aimed at evidencing leptospirosis in a convenience sample of outpatients visiting Port Vila Central Hospital, the major hospital of this archipelago country in the South Pacific. Using reference laboratory techniques, our study confirms a significant number of acute leptospirosis cases, as well as a high level of previous exposure in outpatients visiting this hospital. Risk factor analysis point to livestock and lifestyle as important factors exposing to leptospirosis in this developing country. Furthermore, there is evidence that the disease probably has a higher incidence in remote islands outside of the capital of Efate in this very wide archipelago. Taken together, our results point to a need of increased awareness, notably in peripheral health centers and of better access to laboratory confirmation for surveillance.

International audience; Population structure is a potential problem when testing for adaptive phenotypic differences among populations. The observed phenotypic differences among populations can simply be due to genetic drift, and if the genetic distance between them is not considered, the differentiation may be falsely interpreted as adaptive. Conversely, adaptive and demographic processes might have been tightly associated and correcting for the population structure may lead to false negatives. Here, we evaluated this problem in the cosmopolitan weed Capsella bursa-pastoris. We used RNA-Seq to analyse gene expression differences among 24 accessions, which belonged to a much larger group that had been previously characterized for flowering time and circadian rhythm and were genotyped using genotyping-by-sequencing (GBS) technique. We found that clustering of accessions for gene expression retrieved the same three clusters that were obtained with GBS data previously, namely Europe, the Middle East and Asia. Moreover, the three groups were also differentiated for both flowering time and circadian rhythm variation. Correction for population genetic structure when analysing differential gene expression analysis removed all differences among the three groups. This may suggest that most differences are neutral and simply reflect population history. However, geographical variation in flowering time and circadian rhythm indicated that the distribution of adaptive traits might be confounded by population structure. To bypass this confounding effect, we compared gene expression differentiation between flowering ecotypes within the genetic groups. Among the differentially expressed genes, FLOWERING LOCUS C was the strongest candidate for local adaptation in regulation of flowering time.

International audience; Structured populations, and replicated zones of contact between species, are an ideal opportunity to study regions of the genome with unusual levels of differentiation; and these can illuminate the genomic architecture of species isolation, and the spread of adaptive alleles across species ranges. Here, we investigated the effects of gene flow on divergence and adaptation in the Mytilus complex of species, including replicated parental populations in quite distant geographical locations. We used target enrichment sequencing of 1269 contigs of a few kb each, including some genes of known function, to infer gene genealogies at a small chromosomal scale. We show that geography is an important determinant of the genomewide patterns of introgression in Mytilus and that gene flow between different species, with contiguous ranges, explained up to half of the intraspecific outliers. This suggests that local introgression is both widespread and tends to affect larger chromosomal regions than purely intraspecific processes. We argue that this situation might be common, and this implies that genome scans should always consider the possibility of introgression from sister species, unsampled differentiated backgrounds, or even extinct relatives, for example Neanderthals in humans. The hypothesis that reticulate evolution over long periods of time contributes widely to adaptation, and to the spatial and genomic reorganization of genetic backgrounds, needs to be more widely considered to make better sense of genome scans.

International audience; AIMS:This study sought to investigate regional variation in clinical characteristics, therapy utilization, and post-discharge outcomes among patients hospitalized for heart failure (HHF) enrolled in the multinational ASTRONAUT (Aliskiren Trial on Acute Heart Failure Outcomes) trial.METHODS AND RESULTS:The ASTRONAUT trial randomized 1615 HHF patients with ejection fraction ≤40% to aliskiren or placebo. Enrolled patients were from Eastern Europe (n = 495, 30.7%), Asia/Pacific (n = 439, 27.2%), Western Europe (n = 395, 24.5%), Latin America (n = 163, 10.1%), and North America (n = 123, 7.6%). Marked differences were seen across geographic regions in terms of baseline demographics, vital signs, laboratory tests, co-morbidity burden, and use of guideline-recommended therapies. All-cause death at 12 months ranged from 7.3% in North America to 26.7% in Asia/Pacific, with differences largely driven by sudden cardiac death. Rates of repeat HHF at 12 months ranged from 22.7% in Latin America to 43.9% in North America. After adjustment for patient characteristics, region was an independent predictor of death at 12 months, with highest risk in Asia/Pacific (hazard ratio 3.04, 95% confidence interval 1.47-6.29, compared with North America) and lowest risk in North America and Western Europe. There was no association between region and the composite of cardiovascular mortality or HHF.CONCLUSION:For patients enrolled in this HHF trial, baseline characteristics and risk of death differed markedly by geographic region. Rates of death and repeat HHF demonstrated a general inverse relationship. Global differences in patient characteristics and outcomes should be accounted for when designing future HHF clinical trials.

International audience; We designed a single nucleotide primer extension (SNaPshot) assay for Pneumocystis jirovecii genotyping, targeting mt85 SNP of the mitochondrial large subunit ribosomal RNA locus, to improve minority allele detection. We then analyzed 133 consecutive bronchoalveolar lavage (BAL) fluids tested positive for P. jirovecii DNA by quantitative real-time PCR, obtained from two hospitals in different locations (Hospital 1 [n = 95] and Hospital 2 [n = 38]). We detected three different alleles, either singly (mt85C: 39.1%; mt85T: 24.1%; mt85A: 9.8%) or together (27%), and an association between P. jirovecii mt85 genotype and the patient's place of hospitalization (p = 0.011). The lowest fungal loads (median = 0.82 × 10(3) copies/μl; range: 15-11 × 10(3) ) were associated with mt85A and the highest (median = 1.4 × 10(6) copies/μl; range: 17 × 10(3) -1.3 × 10(7) ) with mt85CTA (p = 0.010). The ratios of the various alleles differed between the 36 mixed-genotype samples. In tests of serial BALs (median: 20 d; range 4-525) from six patients with mixed genotypes, allele ratio changes were observed five times and genotype replacement once. Therefore, allele ratio changes seem more frequent than genotype replacement when using a SNaPshot assay more sensitive for detecting minority alleles than Sanger sequencing. Moreover, because microscopy detects only high fungal loads, the selection of microscopy-positive samples may miss genotypes associated with low loads.

International audience; Background. Study of meningococcal carriage is essential to understanding the epidemiology of Neisseria meningitidis infection.Methods. Twenty cross-sectional carriage surveys were conducted in 7 countries in the African meningitis belt; 5 surveys were conducted after introduction of a new serogroup A meningococcal conjugate vaccine (MenAfriVac). Pharyngeal swab specimens were collected, and Neisseria species were identified by microbiological and molecular techniques.Results. A total of 1687 of 48 490 participants (3.4%; 95% confidence interval [CI], 3.2%–3.6%) carried meningococci. Carriage was more frequent in individuals aged 5–14 years, relative to those aged 15–29 years (adjusted odds ratio [OR], 1.41; 95% CI, 1.25–1.60); in males, relative to females (adjusted OR, 1.17; 95% CI, 1.10–1.24); in individuals in rural areas, relative to those in urban areas (adjusted OR, 1.44; 95% CI, 1.28–1.63); and in the dry season, relative to the rainy season (adjusted OR, 1.54; 95% CI, 1.37–1.75). Forty-eight percent of isolates had genes encoding disease-associated polysaccharide capsules; genogroup W predominated, and genogroup A was rare. Strain diversity was lower in countries in the center of the meningitis belt than in Senegal or Ethiopia. The prevalence of genogroup A fell from 0.7% to 0.02% in Chad following mass vaccination with MenAfriVac.Conclusions. The prevalence of meningococcal carriage in the African meningitis belt is lower than in industrialized countries and is very diverse and dynamic, even in the absence of vaccination.

International audience; We identified 3 lineages among multidrug-resistant (MDR) Salmonella enterica serotype Typhi isolates in the Gulf of Guinea region in Africa during the 2000s. However, the MDR H58 haplotype, which predominates in southern Asia and Kenya, was not identified. MDR quinolone-susceptible isolates contained a 190-kb incHI1 pST2 plasmid or a 50-kb incN pST3 plasmid.

To the Editor: Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic virus in the family Bunyaviridae, genus Phlebovirus, which affects mainly domestic ruminants and humans on continental Africa, Madagascar, and the Arabian Peninsula (1). RVFV is transmitted between ruminants mainly by bites of mosquitoes of several genera (1). Infection can lead to mild symptoms or can cause abortion in pregnant animals and high mortality rates among newborns. Humans are mostly infected by aerosol transmission when handling infected tissues (aborted fetuses or meat), which results in dengue-like illness. Some cases in humans can be in a severe form (hemorrhagic fever and meningoencephalitis), which can be fatal. Outbreaks in southern and eastern Africa are associated with periods of heavy rainfall (1). In eastern Africa, RVFV is believed to be maintained during interepizootic periods through vertical transmission in Aedes spp. mosquitoes (1). It has been suspected that wild mammals, especially rodents, play a role in the maintenance of RVFV during interepizootic periods (2). However, evidence of a wild mammal reservoir in the epidemiologic cycle of RVFV has yet to be demonstrated (2). In Madagascar, the first RVFV isolate was obtained from mosquitoes captured in the Perinet Forest (Andasibe, Moramanga District) in 1979, outside an epizootic period (3). Two epizootic episodes occurred, during 1990–91 and 2008–09 (4). After the most recent episode, domestic ruminants were shown to be involved in RVFV circulation during interepizootic periods (5,6); together with the potential vertical transmission in Aedes spp. mosquitoes in Madagascar, they might play a role in the maintenance of RVFV. However, genetic evidence indicates that RVFV outbreaks in Madagascar are not associated with emergence from enzootic cycles but that they are associated with recurrent virus introductions from mainland east Africa (7). Although these mechanisms for RVFV epidemiology on Madagascar are documented, the possibility of a wild mammal reservoir cannot be excluded. We therefore explored the role of wild terrestrial small mammals in the maintenance of RVFV in Madagascar, especially the nonnative, abundant, and ubiquitous black rats (Rattus rattus) (8), as has been suggested in rural Egypt (9,10). For this study, 1,610 blood samples were obtained from different species of wild terrestrial small mammals in Madagascar (Figure). Permits to capture and collect animals were obtained from national authorities. Animals were sampled from October 2008 through March 2010 at a site in the Anjozorobe-Angavo (Anjozorobe District) forest corridor (18°18′′41.9′ S, 48°00′′57.6′ E), where RVFV was first detected in humans and cattle in February 2008 (4) and within 100 km from where the first RVFV was isolated in 1979 (3). We collected 378 serum samples from 11 native Tenrecidae (Afrosoricida) tenrecs, 114 samples from 6 native Nesomyidae (Rodentia) rodents, and 471 samples from introduced R. rattus (Muridae, Rodentia) rats (Technical Appendix). In addition, during 2008, we obtained serum samples from 647 R. rattus or R. norvegicus rats living near humans in areas where RVFV was reportedly circulating during 2008 and 2009: the districts of Ankazobe, Antsiranana, Betafo, Ihosy, Marovoay, and Moramanga (4,5) (Figure). Figure Collection sites of wild terrestrial small mammals on Madagascar and the number of mammals tested for Rift Valley fever virus (RVFV). At certain localities, the genus and species of sampled rats were Rattus rattus or R. norvegicus. Serum samples were tested for IgG against RVFV by ELISA, as described (4), by using peroxidase-labeled recombinant protein A/G (Pierce, Rockford, IL, USA) or anti-mouse or rat IgG (H+L) according to the ability to recognize the immunoglobulin of species endemic to Madagascar (data not shown). The results were negative for all samples tested. Liver and spleen samples from 947 animals caught in the Anjozorobe-Angavo forest corridor were also tested. Approximately 50–100 mg of liver and spleen from each individual was mixed and homogenized at a dilution of 1:10 in culture medium containing 40% fetal bovine serum. After centrifugation, supernatants were collected and pooled by species (maximum 5 individuals/pool). RNA was extracted from pooled supernatants by using TRIzol LS reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturers’ instructions. Detection of RVFV RNA was attempted by using real-time reverse transcription PCR (4). The results were negative for the 220 monospecific pools tested. Serologic and virologic results from rodent and tenrec samples collected during and after the epizootic 2008–2009 periods were negative for RVFV; 72.8% had been collected in municipalities where RVFV cases were reported. This finding does not indicate a role of native Rodentia and Afrosoricida mammals in the epidemiology of RVFV in Madagascar, nor does it indicate evidence of infection of Rattus spp. rats, as suggested in Egypt (9,10). The absence of infection in Rattus spp. rats during a period of intense RVFV circulation does not support its potential role during the outbreak and, a fortiori, in the maintenance of RVFV during interepizootic periods. Among wild terrestrial mammals in Madagascar, animals of the orders Carnivora and Primata are not considered as candidates for the maintenance of RVFV; however, bats (order Chiroptera) and introduced bushpigs (order Artiodactyla , family Suidae, genus Potamochoerus) could be candidates, and their role in RVFV maintenance should be investigated (2). At present, no evidence is available for the maintenance of RVFV in wild terrestrial small mammals (native and introduced) in Madagascar. Technical Appendix: Taxonomy of small terrestrial animals sampled in Anjozorobe, Madagascar, October 2008 and 2009, March 2009 and 2010 Click here to view.(15K, pdf)

International audience; Given the gradual improvement of living conditions and aging, dementia and related syndromes are becoming serious problems in the developing countries. A cross-sectional door to door type study in neighbourhood, was conducted from October 2008 to January 2009, in the general population in Bangui, order to help get a better understanding of the prevalence and risk factors of dementia among people over 65 living in the Central African capital. Of the 496 elderly respondents, 188 had cognitive disorders. After a neuropsychological examination, 40 of these subjects were diagnosed with dementia. The prevalence of dementia was 8.1% (IC 95% = [5.7-10.5]). The average age of subjects with dementia, ranging from 65 to 90 years, was 76.0 ± 7.1 years. There was a significant risk of developing dementia for an increase of ten years old (OR = 2.6, 95% CI [1.5 to 4.5]). The sex-ratio was 6/34. 82.5% of the demented had never attended school. 70.0% showed a state of malnutrition (BMI ≤ 18,5 kg/m(2)), significantly associated with dementia (OR = 3.3; IC 95% = [1.5-7.3]). The blood pressure was high in 67.5% of demented which is significantly associated with dementia (OR = 2.4; IC 95% = [1.1-5.4]). A recent change in financial status was a factor significantly associated with dementia (OR = 6.4; IC 95% = [1.8-22.5]). These results support the existence of dementia in urban Africa. The observed prevalence is close to those found in high-income countries. Further studies should be conducted which includes both the rural and urban Africa, to better understand the problem and solutions consider to comprehensive care and prevention axes adapted to our context.

Marked phenotypic variation characterizes isolates of Toxoplasma gondii, a ubiquitous zoonotic parasite that serves as an important experimental model for studying apicomplexan parasites. Progress in identifying the heritable basis for clinically and epidemiologically significant differences requires a robust system for describing and interpreting evolutionary subdivisions in this prevalent pathogen. To develop such a system, we have examined more than 950 isolates collected from around the world and genotyped them using three independent sets of polymorphic DNA markers, sampling 30 loci distributed across all nuclear chromosomes as well as the plastid genome. Our studies reveal a biphasic pattern consisting of regions in the Northern Hemisphere where a few, highly clonal and abundant lineages predominate; elsewhere, and especially in portions of South America are characterized by a diverse assemblage of less common genotypes that show greater evidence of recombination. Clustering methods were used to organize the marked genetic diversity of 138 unique genotypes into 15 haplogroups that collectively define six major clades. Analysis of gene flow indicates that a small number of ancestral lineages gave rise to the existing diversity through a process of limited admixture. Identification of reference strains for these major groups should facilitate future studies on comparative genomics and identification of genes that control important biological phenotypes including pathogenesis and transmission.

International audience; Inadequate waste management leads to many environmental issues and the adoption of an efficient and sustainable waste management has become a priority objective of the EU. However, besides the demographic factors, the various socio-economic and geographical conditions of this complex space lead to major disparities in municipal waste management between North and South, East and West. This paper aims to do a spatial-temporal analysis of the Eurostat indicators using ascending hierarchical cluster analysis that divides the member states into five typological classes. The resulted maps highlight territorial disparities among Member States on municipal waste management and also reveal the evolution of environmental policies between 2003-2009 related to the EU acquis.

International audience; Sleeping sickness is more prevalent in three historical regions of Central African Republic. Control measures were organized by the colonial authorities through health services to fight against this disease and other major diseases. Multivariate analysis and the government helped in controlling the disease in the focus of Nola-Bilolo, which was formerly hyperendemic. The authors report the results of the control measures that resulted in the extinction of the disease in this outbreak. This is a retrospective study from 1991 to 2008, and the data were collected from the National Program to fight against human African trypanosomiasis in Bangui and in the diagnostic and treatment center of Nola. It was highly endemic, with more than 300 cases recorded in the year 1991. The average number of cases was 200.8 per year between 1992 and 1998. Less than 50 cases per year were recorded from 2000 to 2006, and no cases have been detected since 2007. 69.35% of the patients were actively screened. 5,000 conical deltamethrin-impregnated traps (Gouteux and Lancien) had been used in 15 districts in the city of Nola and 46 surrounding villages by 20 trappers fully supported by the program. This is an example of regular active mass screening. Systematic treatment of detected cases and well-conducted vector control measures give hope to the affected populations to live peacefully in order to contribute to the development of their country.

International audience; This review gives an update of current knowledge on the clinical pleiomorphism of Leishmania, with a special emphasis on the case of asymptomatic carriage. The first part describes the numerous unusual expressions of the disease that occur besides the classic (visceral, cutaneous, and mucocutaneous) forms of leishmaniases. The second part deals with progress in the understanding of disease outcome in humans, and the possible future approaches to improve our knowledge in the field. The third part highlights the role of the too often neglected asymptomatic carrier compartment. This group could be key to understanding infraspecific differences in virulence and pathogenicity of the parasite, as well as identifying the genetic determinants involved in the expression of the disease.

International audience; The Neolithic is a key period in the history of the European settlement. Although archaeological and present-day genetic data suggest several hypotheses regarding the human migration patterns at this period, validation of these hypotheses with the use of ancient genetic data has been limited. In this context, we studied DNA extracted from 53 individuals buried in a necropolis used by a French local community 5,000 y ago. The relatively good DNA preservation of the samples allowed us to obtain autosomal, Y-chromosomal, and/or mtDNA data for 29 of the 53 samples studied. From these datasets, we established close parental relationships within the necropolis and determined maternal and paternal lineages as well as the absence of an allele associated with lactase persistence, probably carried by Neolithic cultures of central Europe. Our study provides an integrative view of the genetic past in southern France at the end of the Neolithic period. Furthermore, the Y-haplotype lineages characterized and the study of their current repartition in European populations confirm a greater influence of the Mediterranean than the Central European route in the peopling of southern Europe during the Neolithic transition.

Correspondance: Carine Brouat, Fax: +33 (0) 4 9962 3345; E-mail: brouat@mpl.ird.fr; International audience; The black rat (Rattus rattus) is the main reservoir of plague (Yersinia pestis infection) in Madagascar's rural zones. Black rats are highly resistant to plague within the plague focus (central highland), whereas they are susceptible where the disease is absent (low altitude zone). To better understand plague wildlife circulation and host evolution in response to a highly virulent pathogen, we attempted to determine genetic markers associated with plague resistance in this species. To this purpose, we combined a population genomics approach and an association study, both performed on 249 AFLP markers, in Malagasy R. rattus. Simulated distributions of genetic differentiation were compared to observed data in four independent pairs, each consisting of one population from the plague focus and one from the plague-free zone. We found 22 loci (9% of 249) with higher differentiation in at least two independent population pairs or with combining P-values over the four pairs significant. Among the 22 outlier loci, 16 presented significant association with plague zone (plague focus vs. plague-free zone). Population genetic structure inferred from outlier loci was structured by plague zone, whereas the neutral loci dataset revealed structure by geography (eastern vs. western populations). A phenotype association study revealed that two of the 22 loci were significantly associated with differentiation between dying and surviving rats following experimental plague challenge. The 22 outlier loci identified in this study may undergo plague selective pressure either directly or more probably indirectly due to hitchhiking with selected loci.

The three-gene APL1 locus encodes essential components of the mosquito immune defense against malaria parasites. APL1 was originally identified because it lies within a mapped QTL conferring the vector mosquito Anopheles gambiae natural resistance to the human malaria parasite, Plasmodium falciparum, and APL1 genes have subsequently been shown to be involved in defense against several species of Plasmodium. Here, we examine molecular population genetic variation at the APL1 gene cluster in spatially and temporally diverse West African collections of A. gambiae. The locus is extremely polymorphic, showing evidence of adaptive evolutionary maintenance of genetic variation. We hypothesize that this variability aids in defense against genetically diverse pathogens, including Plasmodium. Variation at APL1 is highly structured across geographic and temporal subpopulations. In particular, diversity is exceptionally high during the rainy season, when malaria transmission rates are at their peak. Much less allelic diversity is observed during the dry season when mosquito population sizes and malaria transmission rates are low. APL1 diversity is weakly stratified by the polymorphic 2La chromosomal inversion but is very strongly subdivided between the M and S “molecular forms.” We find evidence that a recent selective sweep has occurred at the APL1 locus in M form mosquitoes only. The independently reported observation of a similar M-form restricted sweep at the Tep1 locus, whose product physically interacts with APL1C, suggests that epistatic selection may act on these two loci causing them to sweep coordinately., Author Summary Immune defense genes are sometimes highly variable in host populations, reflecting selective pressure to combat diverse pathogens. In other instances, where there are only a few dominant pathogens, natural selection may favor only one or a few defense alleles. Here, we show that both adaptive strategies can occur in the same genes under different circumstances. We examined diversity in the APL1 genes of the human malaria vector mosquito Anophleles gambiae, which play a role in defense against malaria parasites. We found that the APL1 genes are exceptionally polymorphic, being 10-fold more diverse than typical A. gambiae genes. The distribution of APL1 allelic diversity, however, is strongly structured depending on whether the genes are carried by the M or S “molecular forms” of the vector, which are thought to constitute newly forming species. We show that despite the evolutionary maintenance of APL1 diversity in the S form of A. gambiae, there is evidence of strong recent directional selection on APL1 genes in the M form. Independent research has shown that Tep1, a gene which encodes a protein that physically interacts with the APL1C protein, also harbors high allelic diversity in the S form and shows evidence of recent directional selection in the M form, suggesting that the evolutionary trajectories of the Tep1 and APL1 defense loci may be correlated.

International audience; BACKGROUND: The mainland of the Americas is home to a remarkable diversity of languages, and the relationships between genes and languages have attracted considerable attention in the past. Here we investigate to which extent geography and languages can predict the genetic structure of Native American populations. METHODOLOGY/PRINCIPAL FINDINGS: Our approach is based on a Bayesian latent cluster regression model in which cluster membership is explained by geographic and linguistic covariates. After correcting for geographic effects, we find that the inclusion of linguistic information improves the prediction of individual membership to genetic clusters. We further compare the predictive power of Greenberg's and The Ethnologue classifications of Amerindian languages. We report that The Ethnologue classification provides a better genetic proxy than Greenberg's classification at the stock and at the group levels. Although high predictive values can be achieved from The Ethnologue classification, we nevertheless emphasize that Choco, Chibchan and Tupi linguistic families do not exhibit a univocal correspondence with genetic clusters. CONCLUSIONS/SIGNIFICANCE: The Bayesian latent class regression model described here is efficient at predicting population genetic structure using geographic and linguistic information in Native American populations.

International audience; Ptaeroxylaceae is an Afro-Malagasy family containing three genera, Bottegoa, Cedrelopsis, and Ptaeroxylon. Although the family is morphologically well delimited, it is currently considered part of the subfamily Spathelioideae in a broadly circumscribed orange family (Rutaceae). The Malagasy Cedrelopsis has traditionally been associated with different families of the order Sapindales and its phylogenetic placement in Rutaceae sensu lato has yet to be tested with molecular data. The present molecular phylogenetic study reaffirms the monophyly of Ptaeroxylaceae and its placement in Spathelioideae. Therefore, molecules and morphology support close affinities between Bottegoa, Cedrelopsis, and Ptaeroxylon and also their current generic circumscriptions. We report a case of an evolutionary change from one-seeded to two-seeded carpels within the Harrisonia-Cneorum-Ptaeroxylaceae clade of Spathelioideae. Finally, the sister-group relationship between the African Bottegoa and the Afro-Malagasy Ptaeroxylon-Cedrelopsis clade suggests an African origin of Cedrelopsis.

International audience; OBJECTIVE: To determine how severe were the conditions leading to termination of pregnancy for foetal anomaly (TOPFA) in France. METHODS: Detailed indications for TOPFA were extracted from medical charts. RESULTS: Of 2465 completed records, indications were: chromosomal anomalies n = 963 (39.1%), malformations of a single organ without chromosomal or genetic aetiologies n = 898 (36.4%), multiple malformations without chromosomal or genetic aetiologies n = 238 (9.7%), obstetrical complications n = 161 (6.5%), non-chromosomal genetic diseases n = 158 (6.4%), foetal infections n = 21 (0.9%), unexplained severe oligohydramnios n = 20 (0.8%), foetal exposure to teratogenic agents n = 6. Overall, 33.3% of anomalies were lethal (e.g. anencephaly), 25.2% were expected to result in isolated mental retardation (e.g. Down) and 35.1% in substantial handicap (e.g. myelomeningocele). In 6.4% of cases, the anomaly was either of late onset (e.g. Huntington's disease) or with uncertain prognosis (e.g. agenesis of corpus callosum) or severity was debatable (e.g. single limb agenesis, sickle cell disease). CONCLUSIONS: Although there is no indisputable definition of which anomalies are 'severe', 93.6% of the decisions to terminate the pregnancy were made by women and professionals in reaction to anomalies which clearly were lethal or would lead to substantial physical and/or mental disabilities.

International audience; Squirrel monkeys (genus Saimiri) are distributed over a wide area encompassing the Amazon Basin: French Guiana, Suriname, and Guyana, together with Western Panama and Western Costa Rica. The genus Saimiri includes a complex of species and subspecies displaying considerable morphological variation. Taxonomic and systematic studies have identified, in this genus, one to seven species comprising up to 16 subspecies. The phylogenetic relationships between these taxa are poorly understood. Molecular markers have yielded a consistent framework for the systematics of Central and South American Saimiri, identifying four distinct clades: S. oerstedii, S. sciureus, S. boliviensis, and S. ustus. Here, we reconsider the phylogenetic and biogeographic history of Saimiri on the basis of mitochondrial (mtDNA) sequence data, focusing mostly on individuals originating from the Amazon Basin. We studied 32 monkeys with well-defined geographic origins and inferred the phylogenetic relationships between them on the basis of full-length cytochrome b gene nucleotide sequences. The high level of gene diversity observed (0.966) is consistent with the high level of behavioral and morphological variation observed across the geographic range of the genus: 20 mtDNA haplotypes were identified with a maximum divergence of 4.81% between S. b. boliviensis and S. ustus. In addition to confirming the existence of the four clades previously identified on the basis of molecular characters, we suggest several new lineages, including S. s. macrodon, S. s. albigena, S. s. cassiquiarensis, and S. s. collinsi. We also propose new patterns of dispersion and diversification for the genus Saimiri, and discuss the contribution of certain rivers and forest refuges to its structuring.

Background Buruli ulcer, the third mycobacterial disease after tuberculosis and leprosy, is caused by the environmental mycobacterium M. ulcerans. Various modes of transmission have been suspected for this disease, with no general consensus acceptance for any of them up to now. Since laboratory models demonstrated the ability of water bugs to transmit M. ulcerans, a particular attention is focused on the transmission of the bacilli by water bugs as hosts and vectors. However, it is only through detailed knowledge of the biodiversity and ecology of water bugs that the importance of this mode of transmission can be fully assessed. It is the objective of the work here to decipher the role of water bugs in M. ulcerans ecology and transmission, based on large-scale field studies. Methodology/Principal Findings The distribution of M. ulcerans-hosting water bugs was monitored on previously unprecedented time and space scales: a total of 7,407 water bugs, belonging to large number of different families, were collected over one year, in Buruli ulcer endemic and non endemic areas in central Cameroon. This study demonstrated the presence of M. ulcerans in insect saliva. In addition, the field results provided a full picture of the ecology of transmission in terms of biodiversity and detailed specification of seasonal and regional dynamics, with large temporal heterogeneity in the insect tissue colonization rate and detection of M. ulcerans only in water bug tissues collected in Buruli ulcer endemic areas. Conclusion/Significance The large-scale detection of bacilli in saliva of biting water bugs gives enhanced weight to their role in M. ulcerans transmission. On practical grounds, beyond the ecological interest, the results concerning seasonal and regional dynamics can provide an efficient tool in the hands of sanitary authorities to monitor environmental risks associated with Buruli ulcer., Author Summary Buruli ulcer, caused by Mycobacterium ulcerans, is a devastating skin disease. Most cases of Buruli ulcer occur in poor rural communities. As a result, treatment is frequently sought too late and about 25% of those infected—particularly children—become permanently disabled. Outbreaks of Buruli ulcer have always been associated with swampy areas. However, the route(s) of bacillus transmission is (are) still unclear. This Mycobacterium species resides in water where it colonizes many ecological niches such as aquatic plants, herbivorous animals and predatory/carnivorous insects. For several years the role of water bugs as hosts and vectors of M. ulcerans was suspected and was demonstrated under laboratory conditions. The aim of this work was to further assess the role of water bugs as hosts and vectors of M. ulcerans in environmental context. This work identifies several water bug families as hosts of M. ulcerans in Buruli ulcer endemic area. The detection of bacilli in saliva of human biting insects provides further evidence for their role in M. ulcerans transmission. Interestingly, three of these insects are good flyers, and as such could participate in M. ulcerans dissemination.

International audience; Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by a distinctive pattern of bone and joint destruction. RA patients have an increased risk of death. The incidence and prevalence of RA vary across populations, statistical methods, and disease definitions. In North America and Northern Europe, the incidence of RA is estimated at 20 to 50 cases per 100,000 population and the prevalence at 0.5% to 1.1%. Lower incidences and prevalences have been reported in Southern Europe, and few data are available for developing countries. Some studies showed declining incidences and prevalences after the 1960s. RA is a multifactorial disease that results from interactions between genetic and environmental factors. The main genetic factors are HLA-DRB1 and the tyrosine-phosphatase gene PTPN22. Among environmental factors implicated in the development of RA, smoking shows the strongest association with RA susceptibility and is also linked to worse outcomes. The aim of this review is to discuss the available data on the incidence and prevalence of RA, as well as the genetic and environmental risk factors associated with RA.

International audience; Reductive evolution and massive pseudogene formation have shaped the 3.31-Mb genome of Mycobacterium leprae, an unculturable obligate pathogen that causes leprosy in humans. The complete genome sequence of M. leprae strain Br4923 from Brazil was obtained by conventional methods (6x coverage), and Illumina resequencing technology was used to obtain the sequences of strains Thai53 (38x coverage) and NHDP63 (46x coverage) from Thailand and the United States, respectively. Whole-genome comparisons with the previously sequenced TN strain from India revealed that the four strains share 99.995% sequence identity and differ only in 215 polymorphic sites, mainly SNPs, and by 5 pseudogenes. Sixteen interrelated SNP subtypes were defined by genotyping both extant and extinct strains of M. leprae from around the world. The 16 SNP subtypes showed a strong geographical association that reflects the migration patterns of early humans and trade routes, with the Silk Road linking Europe to China having contributed to the spread of leprosy.

E-mail: jjrobledo@gmail.com; International audience; The estimation of recent gene immigration is fundamental to a wide range of evolutionary and conservation studies. In a risk assessment context, gene flow estimation procedures are needed that are both accurate and readily amenable to formal evaluation of statistical uncertainty. However, genetic methods for estimating recent migration rates that are specific and have been thoroughly evaluated are scarce. Here we use an original and straightforward maximum-likelihood method to estimate recent uniparental gametic immigration from non-local plantations into an endangered population of the Iberian relict pine variety Pinus sylvestris var. nevadensis D. H. Christ. Our approach is not intended to ascertain population membership of individuals, but rather to obtain accurate immigration rate estimates with reliable confidence limits. We found very high (approximately 40%) pollen introgression at the seed-crop level into the Scots pine relict, and substantial (10-15%) male gametic introgression among naturally regenerated recruits. Using numerical simulation, we show that our method yields uniparental gametic immigration estimates that are expected to be virtually unbiased and usually accurate under our sampling conditions. Among four tested methods to estimate the confidence intervals for immigration estimates, the profile-likelihood method was the best, as it outperformed bootstrapping procedures and yielded coverage close to nominal limits under different sample sizes and migration rates. This study presents a method by which researchers can facilitate decision making within a gene flow risk assessment context.

International audience; Most genetic studies on the origins of Native Americans have examined data from mtDNA and Y-chromosome DNA. To complement these studies and to broaden our understanding of the origin of Native American populations, we present an analysis of 1,873 X-chromosomes representing Native American (n = 438) and other continental populations (n = 1,435). We genotyped 36 polymorphic sites, forming an informative haplotype within an 8-kb DNA segment spanning exon 44 of the dystrophin gene. The data reveal continuity from a common Eurasian ancestry between Europeans, Siberians, and Native Americans. However, the loss of two haplotypes frequent in Eurasia (18.8 and 7%) and the rise in frequency of a third haplotype rare elsewhere, indicate a major population bottleneck in the peopling of the Americas. Although genetic drift appears to have played a greater role in the genetic differentiation of Native Americans than in the latitudinally distributed Eurasians, we also observe a signal of a differentiated ancestry of southern and northern populations that cannot be simply explained by the serial southward dilution of genetic diversity. It is possible that the distribution of X-chromosome lineages reflects the genetic structure of the population of Beringia, itself issued from founder effects and a source of subsequent southern colonization(s).

International audience; OBJECTIVE: Visceral leishmaniasis is an important health problem in Tunisia. The aim of this study was to update the epidemiological and clinical features of the disease. DESIGN: We performed a retrospective systematic sampling of epidemiological and clinical data collected from the medical records of 1,096 cases of visceral leishmaniasis diagnosed between 1996 and 2006 all over the country. RESULTS: The mean annual incidence of cases was 99.6 cases/year. The mean annual incidence rate was 1.04 cases/100,000 inhabitants, showing an important increase compared to former studies. As expected, children under 5 years (866 cases) were the most affected with a mean annual incidence rate of 9.6 cases/100,000 (p

The definitive version is available at ww3.interscience.wiley.com. En libre-accès sur Archimer : http://archimer.ifremer.fr/doc/2009/publication-6801.pdf; International audience; The distribution of the archaeal communities in deep subseafloor sediments [0-36 m below the seafloor (mbsf)] from the New Caledonia and Fairway Basins was investigated using DNA- and RNA-derived 16S rRNA clone libraries, functional genes and denaturing gradient gel electrophoresis (DGGE). A new method, Co-Migration DGGE (CM-DGGE), was developed to access selectively the active archaeal diversity. Prokaryotic cell abundances at the open-ocean sites were on average approximately 3.5 times lower than at a site under terrestrial influence. The sediment surface archaeal community (0-1.5 mbsf) was characterized by active Marine Group 1 (MG-1) Archaea that co-occurred with ammonia monooxygenase gene (amoA) sequences affiliated to a group of uncultured sedimentary Crenarchaeota. However, the anoxic subsurface methane-poor sediments (below 1.5 mbsf) were dominated by less active archaeal communities, such as the Thermoplasmatales, Marine Benthic Group D and other lineages probably involved in the methane cycle (Methanosarcinales, ANME-2 and DSAG/MBG-B). Moreover, the archaeal diversity of some sediment layers was restricted to only one lineage (Uncultured Euryarchaeota, DHVE6, MBG-B, MG-1 and SAGMEG). Sequences forming two clusters within the Thermococcales order were also present in these cold subseafloor sediments, suggesting that these uncultured putative thermophilic archaeal communities might have originated from a different environment. This study shows a transition between surface and subsurface sediment archaeal communities.

International audience; A growing literature investigates associations between neighborhood social environments and coronary heart disease (CHD). After reviewing the literature, we present a theoretical model of the mechanisms through which geographic life environments may influence CHD, focusing particularly on the social-interactional environment. We suggest that, in addition to the common notions of social cohesion or fragmentation and social disorder, eco-epidemiologists should consider neighborhood identities and stigmatization processes. We posit that neighborhood social interactions affect the wide set of affective, cognitive, and relational experiences individuals have in their neighborhoods, which in turn influence the psycho-cognitive antecedents of behavior and in the end shape health behavior. Finally, we discuss key methodological challenges relevant to the advent of a new generation of neighborhood studies, including the operational definition of neighborhoods, non-residential environments, ecometric measurement, model specification strategies, mediational models, selection processes and notions of empirical/structural confounding, and the relevance of observational versus interventional studies.

International audience; From the mandibular lymph nodes of wild red foxes (Vulpes vulpes) hunted in the region of Gmünd, Lower Austria, two gram-negative, oxidase- and urease-positive, coccoid rod-shaped bacteria (strains 257 and 284) were isolated. Cells were fast growing, nonmotile, and agglutinated with monospecific anti-Brucella (M) serum. Both strains were biochemically identified as Ochrobactrum anthropi by using the API 20NE test. However, sequencing of the 16S rRNA and recA genes clearly identified strains 257 and 284 as Brucella spp. Further molecular analysis by omp2a/b gene sequencing, multilocus sequence typing and multilocus variable number tandem repeats analysis revealed Brucella microti, a recently described Brucella species that has originally been isolated from diseased common voles (Microtus arvalis) in South Moravia, Czech Republic in 2000. Our findings demonstrate that B. microti is prevalent in a larger geographic area covering the region of South Moravia and parts of Lower Austria. Foxes could have become infected by ingestion of infected common voles.

International audience; In this work we investigated about the presence of a correlation between a (CA)n repeat located in exon 29 of NOS1 gene and the beta-thalassemia trait in Corsica Island (France). We genotyped a sample of individuals with beta-thalassemia minor (N=110) and an ethnically matched control (N=113) from Balagna, a region of Corsica Island (France). Results highlighted the high frequencies of allele with 16 and 17 repeats in the thalassemic sample. From these results we suggest, that high frequencies of alleles with 16 and 17 repeats, could be a consequence of past malarial endemicity.

10 pages; International audience; Genes of the major histocompatibility complex (MHC) are the most polymorphic loci known in vertebrates. Two main hypotheses have been put forward to explain the maintenance of MHC diversity: pathogen-mediated selection and MHC-based mate choice. Host-parasite interactions can maintain MHC diversity via frequency-dependent selection, heterozygote advantage, and diversifying selection (spatially and/or temporally heterogeneous selection). In this study, we wished to investigate the nature of selection acting on the MHC class I across spatially structured populations of house sparrows (Passer domesticus) in France. To infer the nature of the selection, we compared patterns of population differentiation based on two types of molecular markers: MHC class I and microsatellites. This allowed us to test whether the observed differentiation at MHC genes merely reflects demographic and/or stochastic processes. At the global scale, diversifying selection seems to be the main factor maintaining MHC diversity in the house sparrow. We found that (i) overall population differentiation at MHC was stronger than for microsatellites, (ii) MHC marker showed significant isolation by distance. In addition, the slope of the regression of F(ST) on geographical distance was significantly steeper for MHC than for microsatellites due to a stronger pairwise differentiation between populations located at large geographical distances. These results are in agreement with the hypothesis that spatially heterogeneous selective pressures maintain different MHC alleles at local scales, possibly resulting in local adaptation.

Background Alveolar echinococcosis (AE) is a severe helminth disease affecting humans, which is caused by the fox tapeworm Echinococcus multilocularis. AE represents a serious public health issue in larger regions of China, Siberia, and other regions in Asia. In Europe, a significant increase in prevalence since the 1990s is not only affecting the historically documented endemic area north of the Alps but more recently also neighbouring regions previously not known to be endemic. The genetic diversity of the parasite population and respective distribution in Europe have now been investigated in view of generating a fine-tuned map of parasite variants occurring in Europe. This approach may serve as a model to study the parasite at a worldwide level. Methodology/Principal Findings The genetic diversity of E. multilocularis was assessed based upon the tandemly repeated microsatellite marker EmsB in association with matching fox host geographical positions. Our study demonstrated a higher genetic diversity in the endemic areas north of the Alps when compared to other areas. Conclusions/Significance The study of the spatial distribution of E. multilocularis in Europe, based on 32 genetic clusters, suggests that Europe can be considered as a unique global focus of E. multilocularis, which can be schematically drawn as a central core located in Switzerland and Jura Swabe flanked by neighbouring regions where the parasite exhibits a lower genetic diversity. The transmission of the parasite into peripheral regions is governed by a “mainland–island” system. Moreover, the presence of similar genetic profiles in both zones indicated a founder event., Author Summary Echinococcus multilocularis is a tapeworm of the red fox, which represents a considerable health threat to respectively infected humans. Main endemic areas are located in China, Siberia, and central Europe. Alarmed by an emerging or reemerging situation in Europe, the question of how the parasite gets spatially and temporally spread and transmitted becomes essential to prepare appropriate control programs. The question was tackled by using genetic data on a large sample size of E. multilocularis adult stage tapeworms, combined with geographical site location data input. The historically documented endemic area, represented by the northern Alpine arch, was shown to harbour the highest genetic richness and diversity, as compared to surrounding areas in northern and eastern Europe. The spatial and temporal spread of different E. multilocularis genotypes in Europe seems to be ruled by a founder event, linked to exportation of parasites from the central core to newly identified (western and eastern) areas or subregions, where these parasites could subsequently disseminate under geographical separation from the original foci.

Background Helicobacter pylori colonizes the human stomach and is associated with gastritis, peptic ulcer, and gastric cancer. This ubiquitous association between H. pylori and humans is thought to be present since the origin of modern humans. The H. pylori genome encodes for an exceptional number of restriction and modifications (R-M) systems. To evaluate if R-M systems are an adequate tool to determine the geographic distribution of H. pylori strains, we typed 221 strains from Africa, America, Asia, and Europe, and evaluated the expression of different 29 methyltransferases. Results Independence tests and logistic regression models revealed that ten R-M systems correlate with geographical localization. The distribution pattern of these methyltransferases may have been originated by co-divergence of regional H. pylori after its human host migrated out of Africa. The expression of specific methyltransferases in the H. pylori population may also reflect the genetic and cultural background of its human host. Methyltransferases common to all strains, M. HhaI and M. NaeI, are likely conserved in H. pylori, and may have been present in the bacteria genome since the human diaspora out of Africa. Conclusion This study indicates that some methyltransferases are useful geomarkers, which allow discrimination of bacterial populations, and that can be added to our tools to investigate human migrations., This work was partially supported by New England Biolabs, Inc. (USA)

The emergence of farming during the Neolithic transition, including the domestication of livestock, was a critical point in the evolution of human kind. The goat ( Capra hircus ) was one of the first domesticated ungulates. In this study, we compared the genetic diversity of domestic goats to that of the modern representatives of their wild ancestor, the bezoar, by analyzing 473 samples collected over the whole distribution range of the latter species. This partly confirms and significantly clarifies the goat domestication scenario already proposed by archaeological evidence. All of the mitochondrial DNA haplogroups found in current domestic goats have also been found in the bezoar. The geographic distribution of these haplogroups in the wild ancestor allowed the localization of the main domestication centers. We found no haplotype that could have been domesticated in the eastern half of the Iranian Plateau, nor further to the east. A signature of population expansion in bezoars of the C haplogroup suggests an early domestication center on the Central Iranian Plateau (Yazd and Kerman Provinces) and in the Southern Zagros (Fars Province), possibly corresponding to the management of wild flocks. However, the contribution of this center to the current domestic goat population is rather low (1.4%). We also found a second domestication center covering a large area in Eastern Anatolia, and possibly in Northern and Central Zagros. This last domestication center is the likely origin of almost all domestic goats today. This finding is consistent with archaeological data identifying Eastern Anatolia as an important domestication center.

International audience; Previous research suggests that hepatitis C detection is lower in rural than in urban areas and depends on geographic accessibility to care. To what extent differences in socioeconomic context could explain these disparities remains unknown. This study assessed the respective influence of the socioeconomic context and of the distance to primary care on the hepatitis C detection rates in a well-defined population of 1,005,817 inhabitants covered by a universal health insurance system in the Côte d'Or and the Doubs areas of France. The 1938 cases of hepatitis C newly diagnosed in the survey area between 1994 and 2001 were included. The patients' 'cantons' of residence were classified into six socioeconomic clusters according to 19 quantitative indicators. Age and sex-standardized hepatitis C detection rate ratios (DRR) for the six clusters were estimated and a multilevel Poisson model investigated whether detection rates varied across clusters after adjusting for distance to the nearest general practitioner. Standardized DRR (95% CI) were higher in both "lower-income urban" and "upper-income urban" clusters and lower in the following clusters: "outer suburb", "industrial rural" and economically "dynamic rural". Adjusting for distance to general practitioner reduced the rate difference between socioeconomic clusters: for a distance to general practitioner equalling 0km (practice in the municipality) and compared to the "upper-income urban" cluster, only the "lower-income urban" cluster had higher DRR. In the six clusters, detection rates decreased as the distance to general practitioner increased (DRR 0.89 95% CI 0.84-0.96 for a 1-km change) but the decrease was more marked in both urban clusters. In this population with good primary care affordability, geographic proximity to general practitioner, rather than socioeconomic context of neighborhood, appeared to be the main factor limiting hepatitis C detection.

A general feature of the demography of large ungulates is that many demographic traits are dependent on female body mass at early ages. Thus, identifying the factors affecting body mass variation can give important mechanistic understanding of demographic processes. Here we relate individual variation in autumn and winter body mass of moose calves living at low density on an island in northern Norway to characteristics of their mother, and examine how these relationships are affected by annual variation in population density and climate. Body mass increased with increasing age of their mother, was lower for calves born late in the spring, decreased with litter size and was larger for males than for female calves. No residual effects of variation in density and climate were present after controlling for annual variation in mother age and calving date. The annual variation in adult female age structure and calving date explained a large part (71–75%) of the temporal variation in calf body mass. These results support the hypotheses that (a) body mass of moose calves are affected by qualities associated with mother age (e.g. body condition, calving date); and (b) populations living at low densities are partly buffered against temporal fluctuations in the environment.

Alveolar echinococcosis (AE)—caused by the cestode Echinococcus multilocularis —is a severe zoonotic disease found in temperate and arctic regions of the northern hemisphere. Even though the transmission patterns observed in different geographical areas are heterogeneous, the nuclear and mitochondrial targets usually used for the genotyping of E. multilocularis have shown only a marked genetic homogeneity in this species. We used microsatellite sequences, because of their high typing resolution, to explore the genetic diversity of E. multilocularis . Four microsatellite targets (EmsJ, EmsK, and EmsB, which were designed in our laboratory, and NAK1, selected from the literature) were tested on a panel of 76 E. multilocularis samples (larval and adult stages) obtained from Alaska, Canada, Europe, and Asia. Genetic diversity for each target was assessed by size polymorphism analysis. With the EmsJ and EmsK targets, two alleles were found for each locus, yielding two and three genotypes, respectively, discriminating European isolates from the other groups. With NAK1, five alleles were found, yielding seven genotypes, including those specific to Tibetan and Alaskan isolates. The EmsB target, a tandem repeated multilocus microsatellite, found 17 alleles showing a complex pattern. Hierarchical clustering analyses were performed with the EmsB findings, and 29 genotypes were identified. Due to its higher genetic polymorphism, EmsB exhibited a higher discriminatory power than the other targets. The complex EmsB pattern was able to discriminate isolates on a regional and sectoral level, while avoiding overdistinction. EmsB will be used to assess the putative emergence of E. multilocularis in Europe.

The scale of larval dispersal of marine organisms is important for the design of networks of marine protected areas. We examined the fate of coral reef fish larvae produced at a small island reserve, using a mass-marking method based on maternal transmission of stable isotopes to offspring. Approximately 60% of settled juveniles were spawned at the island, for species with both short (1 month) pelagic larval durations. If natal homing of larvae is a common life-history strategy, the appropriate spatial scales for the management and conservation of coral reefs are likely to be much smaller than previously assumed.

influence de la localisation et de la profondeur. Les evenements de blanchissement corallien sont parmi les perturbations les plus frequentes et les plus devastatrices que subissent les recifs coralliens. A Moorea (Polynesie francaise), entre mars et juillet 2002, une moyenne de 55 ± 14% des colonies a blanchi. L'intensite du blanchissement variait fortement en fonction des genres consideres, de la localisation et de la profondeur, atteignant 72% en certaines stations. Les coraux ont davantage blanchi au niveau des stations profondes qu'aux faibles profondeurs, et plus sur la cote nord que sur la cote ouest. Cette forte variabilite a petite echelle spatiale est probablement le resultat d'interactions entre des facteurs extrinseques, comme l'hydrodynamisme, et intrinseques, comme des adaptations differentielles des associations algues/corail a l'augmentation de la temperature.

The influence of changes in population structures of modern humans and human pathogens is likely reciprocal. In my opinion, a quantitative approach to study this co-influence in a historical perspective requires, in particular, adequate estimators of genetic distances that are well developed for human but not yet for microbial populations. Here, I propose a simple measure of genetic distance between geographic populations within a microbial species based on the observed difference in the frequencies of its genotypes. Further, I apply the proposed method to principal components analysis of Mycobacterium tuberculosis, and interpret the geographic distribution of its VNTR haplotypes in the light of human historical and recent migrations. The proposed approach may be helpful for a quantitative understanding of human-microbial interactions that constitute an integral part of the global history.

International audience

a Centre de Genetique Moleculaire et Cellulaire (CGMC), CNRS UMR 5534, Universite Claude Bernard Lyon 1, Villeurbanne, France b Laboratoire d’Anthropologie des Populations du Passe, CNRS UMR 5199 PACEA, Universite Bordeaux 1, Talence, France c UCD School of Biology and Environmental Science, UCD, BelWeld, Dublin 4, Ireland d Laboratoire d’Ecologie des Hydrosystemes Fluviaux, CNRS UMR 5023, Universite Claude Bernard Lyon 1, Villeurbanne, France e Biogeosciences-Dijon, CNRS UMR 5561, Universite de Bourgogne, Centre des Sciences de la Terre, Dijon, France f Department of Palaeontology, Royal Belgian Institute of Natural Sciences, Brussels, Belgium g Department of Biology, University College London, WC1E 6BT, UK h Institute of Archaeology and Ethnography SB RAS, Novosibirsk, Russia i Laboratoire de Biometrie et Biologie Evolutive, CNRS UMR 5558, Universite Claude Bernard Lyon 1, Villeurbanne, France

International audience; Since the 1970s, the nassariid gastropod Cyclope neritea has been extending its range north along the French Atlantic coasts from the Iberian Peninsula. This may be due to natural spread because of the recent warming of the northeastern Atlantic. However, human-mediated introductions related to shellfish culture may also be a probable explanation for this sudden range expansion. To examine these two hypotheses, we carried out a comprehensive study based on mitochondrial gene sequences (cytochrome oxidase I) of the five recently colonized French bays as well as 14 populations located in the recognized native range of the species. From a total of 594 individuals, we observed 29 haplotypes to split into three divergent clades. In the native range, we observed a low molecular diversity, strong genetic structure and agreement between geography and gene genealogies. Along the French coasts, we observed the opposite: high genetic diversity and low genetic structure. Our results show that recurrent human-mediated introductions from several geographical areas in the native range may be a source for the French Atlantic populations. However, despite the low dispersal ability of C. neritea, the isolation-by-distance pattern in France suggested that this gastropod may have been present (although unnoticed) on the French Atlantic coasts before the 1970s. As C. neritea shows characteristics of a cryptogenic species, the classification of Atlantic populations as either native or introduced is not straightforward. Cryptogenic species should be studied further to determine the status of new populations close to their recognized native range.

International audience; Latent membrane protein 1 (LMP-1) is an Epstein-Barr virus-encoded oncoprotein expressed in approximately 50-70% of nasopharyngeal carcinoma (NPC). Previous studies have shown that NPC-derived LMP-1 variants carrying 30 bp deletion and specific mutations in the 3'C-terminal region confer high oncogenic potential and a weak immunogenicity. Although numerous polymorphism studies of LMP-1 have been carried out so far in the Asian population with NPC, very little is known in this regard on NPC patients from Northern Africa where there is a significantly high occurrence of this tumor. In our study, we examined the frequency of different LMP-1 sequence variants derived from Moroccan NPC patients. As compared to healthy donors, NPC patients showed a high prevalence of the 30bp deletion variant of LMP-1 (i.e. 84% vs. 36%; p

This study aimed to investigate the spatial and space-time distributions of cases of childhood acute leukaemia (CL) during 1990-2000 over the whole French territory. A global spatial heterogeneity and a spatial autocorrelation were first considered using the methods proposed by Potthoff and Whittinghill, Moran and Rogerson methods. The presence of space-time interaction between the places of residence and the dates of diagnosis was investigated with the Knox's test. Finally, the Kulldorff's statistic permitted to scan the whole territory in search for localised clusters. Two time periods were considered (1990-1994, 1995-2000). Overall, a statistically significant spatial heterogeneity of a very small magnitude was observed in the incidence of CL over 1990-1994, but neither over 1995-2000 nor over the whole time period. Moreover, a significant overdispersion of 5.5% was evidenced for 0-4 year children living in isolated areas with more than 50 inhabitants per km(2). Cases older than 10 years living in the same area at diagnosis also tended to cluster within 6 months.

International audience; BACKGROUND AND AIM: A north-south gradient in inflammatory bowel disease (IBD) incidence has been found in Europe and the United States. Its existence is inferred from comparisons of registries that cover only small portions of territories. Several studies suggest that IBD incidence in the north has reached a plateau, whereas in the south it has risen sharply. This evolution tends to reduce the north-south gradient, and it is uncertain whether it still exists. In France, patients with IBD are fully reimbursed for their health expenses by the national health insurance system, which is a potential source of data concerning the incidence of IBD at the national level. The aim of this study was to assess the geographical distribution of Crohn's disease (CD) and ulcerative colitis (UC) in France and to test the north-south gradient hypothesis. METHODS: This study was conducted in metropolitan France and included patients to whom IBD reimbursement was newly attributed between January 1, 2000 and December 31, 2002. Data provided relate to age, sex, postcode area of residence, and IBD type. The mapping of geographical distribution of smoothed relative risks (RR) of CD and UC was carried out using a Bayesian approach, taking into account autocorrelation and population size in each département. RESULTS: In the overall population, incidence rates were 8.2 for CD and 7.2 for UC per 100,000 inhabitants. A clear north-south gradient was shown for CD. Départements with the highest smoothed RR were located in the northern third of France. By contrast, the geographical distribution of smoothed RR of UC was homogeneous. CONCLUSIONS: This study shows a north-south gradient in France for CD but not for UC.

The human N-acetyltransferase genes NAT1 and NAT2 encode two phase-II enzymes that metabolize various drugs and carcinogens. Functional variability at these genes has been associated with adverse drug reactions and cancer susceptibility. Mutations in NAT2 leading to the so-called slow-acetylation phenotype reach high frequencies worldwide, which questions the significance of altered acetylation in human adaptation. To investigate the role of population history and natural selection in shaping NATs variation, we characterized genetic diversity through the resequencing and genotyping of NAT1, NAT2, and the pseudogene NATP in a collection of 13 different populations with distinct ethnic backgrounds and demographic pasts. This combined study design allowed us to define a detailed map of linkage disequilibrium of the NATs region as well as to perform a number of sequence-based neutrality tests and the long-range haplotype (LRH) test. Our data revealed distinctive patterns of variability for the two genes: the reduced diversity observed at NAT1 is consistent with the action of purifying selection, whereas NAT2 functional variation contributes to high levels of diversity. In addition, the LRH test identified a particular NAT2 haplotype (NAT2*5B) under recent positive selection in western/central Eurasians. This haplotype harbors the mutation 341T-->C and encodes the "slowest-acetylator" NAT2 enzyme, suggesting a general selective advantage for the slow-acetylator phenotype. Interestingly, the NAT2*5B haplotype, which seems to have conferred a selective advantage during the past approximately 6,500 years, exhibits today the strongest association with susceptibility to bladder cancer and adverse drug reactions. On the whole, the patterns observed for NAT2 well illustrate how geographically and temporally fluctuating xenobiotic environments may have influenced not only our genome variability but also our present-day susceptibility to disease.

0168-6496 (Print) Journal Article; Samples were taken from several hop fields presenting various symptoms. Fifty-nine pure filamentous fungal strains were isolated and identified through genomic DNA preparations, PCR amplification of the ribosomal DNA internal transcribed spacer region and database interrogations. The most frequent genera were Alternaria (16 isolates) and Epicoccum (14 isolates). The ecosystem was shown to be very diverse, since as many as 27 species belonging to 17 genera were recovered. Furthermore, many of the isolated fungi are known to be involved in phytopathogenesis.