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Biomedical subjects

Patrick Durand

Publications and source records attributed to Patrick Durand.

At least 19 recordsLinked to original sources

Direct and indirect inferences on parasite mating and gene transmission patterns. Pangamy in the cattle tick Rhipicephalus (Boophilus) microplus.

Mating system plays a determinant role in the maintenance and distribution of genetic variation. Difficulties in applying standard methods of indirect inferences onto parasitic life-cycles partly explain the current lack of knowledge on parasite mating systems. The present study develops a combination of direct and indirect inference methods circumventing such difficulties, and illustrates in particular how such a combination modifies our understanding of the biology of the southern cattle tick, Rhipicephalus microplus. To directly assess how females and males pair in natural populations, we sampled 225 mating pairs, genotyped them at six microsatellite loci, and analysed the correlation between mating status and genetic relatedness. This analysis revealed pangamy, i.e. a random association of male and female genotypes. In addition, indirect methods inferred that sib-groups of ticks exploit distinct individual-cows, and hence that ticks probably move among cows during their parasitic lifetime. Altogether, these results negate the expectation of a high frequency of sib-mating, and show the coexistence of genetically diverging stocks within tick cohorts and populations. These results have several consequences for our understanding of R. microplus. For instance, while existing models of pesticide resistance management look perfectly applicable to this species, the epidemiological models of the micropathogens it vectors needs revision. More largely, the methods developed here would help clarify the evolutionary patterns of any dioceous parasite.

Animals↗

Browsing repeats in genomes: Pygram and an application to non-coding region analysis.

BACKGROUND: A large number of studies on genome sequences have revealed the major role played by repeated sequences in the structure, function, dynamics and evolution of genomes. In-depth repeat analysis requires specialized methods, including visualization techniques, to achieve optimum exploratory power. RESULTS: This article presents Pygram, a new visualization application for investigating the organization of repeated sequences in complete genome sequences. The application projects data from a repeat index file on the analysed sequences, and by combining this principle with a query system, is capable of locating repeated sequences with specific properties. In short, Pygram provides an efficient, graphical browser for studying repeats. Implementation of the complete configuration is illustrated in an analysis of CRISPR structures in Archaea genomes and the detection of horizontal transfer between Archaea and Viruses. CONCLUSION: By proposing a new visualization environment to analyse repeated sequences, this application aims to increase the efficiency of laboratories involved in investigating repeat organization in single genomes or across several genomes.

Codon↗

Population genetics and molecular epidemiology or how to "débusquer la bête".

Parasites represent a great proportion of the world's living organisms and are of overwhelming significance because of their impact on hosts (evolutionarily, medically, agronomical and economically). The knowledge of the population biology of such organisms is thus of fundamental importance to population biologists. Most parasites cannot be studied by direct methods and their biology has to be assessed via indirect means, most notably using molecular markers. In this review, we present the molecular tools, the null models employed, the statistical tools available and the kinds of inferences one can make when using molecular markers to study the ecology/epidemiology of host-parasite systems (molecular ecology/molecular epidemiology). We conclude with relevant examples, most issued from our laboratory, to illustrate the pros and cons of such methods for the study of parasites, vectors, micropathogens and their hosts and briefly discuss future needs.

Animals↗

Host sex and parasite genetic diversity.

Is the genetic diversity of parasites infecting male and female hosts equal or different? This is the question we address in this paper by studying the neutral genetic variability of the plathyhelminth trematode Schistosoma mansoni within males and females of its natural murine host Rattus rattus in the marshy forest focus of Guadeloupe (French West Indies). Using seven microsatellite markers, we demonstrate that parasites from male hosts are genetically more diversified than parasites from female hosts. Three hypotheses are discussed that could explain this pattern: 1) a host sex-specific duration of cercariae recruitment; 2) a difference in the behaviour of male and female hosts that would lead to the exposure of males to a greater diversity of parasites; and 3) a host sex-biased immunocompetence that would lead to the selection of more genetically diversified individuals in male than in female rats. This finding is the first empirical evidence that each host sex may play different roles in the maintenance of parasite genetic diversity and so in their evolutionary dynamics and epidemiology.

Animals↗

Incidence of tick-borne relapsing fever in west Africa: longitudinal study.

BACKGROUND: The ongoing drought in sub-Saharan countries has led to the colonisation of west African Savanna by Ornithodoros sonrai; this tick acts as a vector for Borrelia crocidurae, which causes tick-borne relapsing fever (TBRF). Our aim was to ascertain the incidence of TBRF in west Africa. METHODS: From 1990 to 2003, we monitored the incidence of TBRF in Dielmo, Senegal, by daily clinical surveillance and by blood testing of individuals with a fever. From 2002 to 2005, we investigated the presence of O sonrai in 30 villages in Senegal, Mauritania, and Mali, and measured by PCR the prevalence of B crocidurae. FINDINGS: The average incidence of TBRF over 14 years was 11 per 100 person-years (range from 4 in 1990 to 25 in 1997). All age-groups presented a high incidence of the disease. In addition to relapses, repeated infections in the same individuals were common, with some affected by up to six distinct infections during the study period. Epidemiological studies indicated that 26 of the 30 studied villages (87%) were colonised by the vector tick O sonrai and that the average B crocidurae infection rate of the vector was 31%. INTERPRETATION: The incidence of TBRF at the community level is the highest described in Africa for any bacterial disease. The presence of the vector tick in most villages investigated and its high infection rate suggest that TBRF is a common cause of fever in most rural areas of Senegal, Mauritania, and Mali.

Adolescent↗

Spatialised fate factors for nitrate in catchments: modelling approach and implication for LCA results.

The challenge for environmental assessment tools, such as Life Cycle Assessment (LCA) is to provide a holistic picture of the environmental impacts of a given system, while being relevant both at a global scale, i.e., for global impact categories such as climate change, and at a smaller scale, i.e., for regional impact categories such as aquatic eutrophication. To this end, the environmental mechanisms between emission and impact should be taken into account. For eutrophication in particular, which is one of the main impacts of farming systems, the fate factor of eutrophying pollutants in catchments, and particularly of nitrate, reflects one of these important and complex environmental mechanisms. We define this fate factor as: the ratio of the amount of nitrate at the outlet of the catchment over the nitrate emitted from the catchment's soils. In LCA, this fate factor is most often assumed equal to 1, while the observed fate factor is generally less than 1. A generic approach for estimating the range of variation of nitrate fate factors in a region of intensive agriculture was proposed. This approach was based on the analysis of different catchment scenarios combining different catchment types and different effective rainfalls. The evolution over time of the nitrate fate factor as well as the steady state fate factor for each catchment scenario was obtained using the INCA simulation model. In line with the general LCA model, the implications of the steady state fate factors for nitrate were investigated for the eutrophication impact result in the framework of an LCA of pig production. A sensitivity analysis to the fraction of nitrate lost as N(2)O was presented for the climate change impact category. This study highlighted the difference between the observed fate factor at a given time, which aggregates both storage and transformation processes and a "steady state fate factor", specific to the system considered. The range of steady state fate factors obtained for the study region was wide, from 0.44 to 0.86, depending primarily on the catchment type and secondarily on the effective rainfall. The sensitivity of the LCA of pig production to the fate factors was significant concerning eutrophication, but potentially much larger concerning climate change. The potential for producing improved eutrophication results by using spatially differentiated fate factors was demonstrated. Additionally, the urgent need for quantitative studies on the N(2)O/N(2) ratio in riparian zones denitrification was highlighted.

Animal Husbandry↗

GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins.

BACKGROUND: A large variety of biological data can be represented by graphs. These graphs can be constructed from heterogeneous data coming from genomic and post-genomic technologies, but there is still need for tools aiming at exploring and analysing such graphs. This paper describes GenoLink, a software platform for the graphical querying and exploration of graphs. RESULTS: GenoLink provides a generic framework for representing and querying data graphs. This framework provides a graph data structure, a graph query engine, allowing to retrieve sub-graphs from the entire data graph, and several graphical interfaces to express such queries and to further explore their results. A query consists in a graph pattern with constraints attached to the vertices and edges. A query result is the set of all sub-graphs of the entire data graph that are isomorphic to the pattern and satisfy the constraints. The graph data structure does not rely upon any particular data model but can dynamically accommodate for any user-supplied data model. However, for genomic and post-genomic applications, we provide a default data model and several parsers for the most popular data sources. GenoLink does not require any programming skill since all operations on graphs and the analysis of the results can be carried out graphically through several dedicated graphical interfaces. CONCLUSION: GenoLink is a generic and interactive tool allowing biologists to graphically explore various sources of information. GenoLink is distributed either as a standalone application or as a component of the Genostar/Iogma platform. Both distributions are free for academic research and teaching purposes and can be requested at academy@genostar.com. A commercial licence form can be obtained for profit company at info@genostar.com. See also http://www.genostar.org.

Computer Graphics↗

A method for improving the management of controversial wetland.

Valley bottom wetlands in agricultural landscapes often are neglected in national and regional wetland inventories. Although these areas are small, located in the bottomlands of the headwater catchments, and scattered in the rural landscape, they strongly influence hydrology, water quality, and biodiversity over the whole catchment area. Valley bottom wetlands often are considered as controversial wetlands. Awareness of the functional role of wetlands is increasing, in parallel with their progressive disappearance in intensive farming landscapes. The need to improve tools for controlling wetland management is a primary consideration for decision makers and land users. This article proposes a method for the inventory of valley bottom wetlands. The method is based on the functional analysis of potential, existing, and efficient valley bottom wetlands (the PEEW approach). Several indicators are proposed for checking the validity of such an approach. Potential wetlands are delineated by means of a topographic index using topographic and pedoclimatic criteria computed from a Digital Elevation Model and easily accessible databases. Existing wetlands are identified from observed surface moisture, the presence of specific wetland vegetation, or soil feature criteria. Efficient wetlands are defined through a given function, such as flow or pollutant regulation or biodiversity control. An analysis of areas at the limits between potential, existing, and efficient wetlands highlights land cultivated or drained in the past, which currently represents negotiating areas in which rehabilitation and other intended management actions can be implemented.

Agriculture↗

Founder effects, inbreeding and effective sizes in the Southern cattle tick: the effect of transmission dynamics and implications for pest management.

Since its immigration in the Pacific island of New Caledonia in 1942 (i.e. about 240 tick-generations ago), the cattle tick Boophilus microplus has experienced a remarkable adaptive diversification there. In order to better understand the population factors involved, we have investigated the B. microplus population structure on that main host-species, Bos taurus. This study was based microsatellite loci and confirmed that the island colonization came along with a significant bottleneck. Knowledge on B. microplus biology led us to expect B. microplus populations to be composed of highly inbred lineages irregularly dispatched among the individual hosts belonging to the same herds. Instead, this study evidenced a weak inbreeding level and an absence of genetic differentiation within herds. Complementarily, a significant signal of isolation by distance exhibited that human-traffic of cattle does not promote high tick dispersal within the island. Finally, the tick density was found to be about a few hundreds of reproducing adults per squared kilometre, for a gene dispersal range of about a few hundred metres per tick generation. Results are discussed with regard to the evolution of new adaptive changes.

Animals↗

Genetic diversity and structure of African Plasmodium falciparum populations in urban and rural areas.

The genetic variability and population structure of Plasmodium falciparum are key factors in malaria control strategies. Studies have suggested no P. falciparum population structure although linkage disequilibrium was observed in some African areas. We have assessed length polymorphism at 6-22 microsatellites in four urban and rural sites (Djibouti, Dakar, Niamey, and Zouan-Hounien, n = 240 blood samples). Results have shown a P. falciparum population structure in Africa (Fst = 0.17-0.24), lower genetic diversity in Djibouti (He = 0.53) than in the other sites (He = 0.73-0.76), and 3) significant linkage disequilibrium in Djibouti. These results could be related to geographic isolation and low flow of parasites between sites. They also suggest a potential effect of rural suburbs to generate genetic diversity in towns. This could affect the dispersal of selected drug resistance and should be considered when adapting urban malaria control strategies.

Africa↗

Fucoidan a sulfated polysaccharide from brown algae is a potent modulator of connective tissue proteolysis.

Fucoidans are sulfated fucosylated polymers from brown algae cell wall that exhibit some heparin/heparan sulfate properties. We previously demonstrated that these polysaccharides were able in vitro to stimulate dermal fibroblast proliferation and extracellular matrix deposition. Here, we investigated the action of a 16kDa fucoidan fraction on parameters involved in connective tissue breakdown. This fucoidan is able to inhibit gelatinase A secretion and stromelysin 1 induction by interleukin-1beta on dermal fibroblasts in culture. Furthermore, we observed that fucoidan increases the rate of association of MMPs with their specific inhibitors namely TIMPs. Using tissue sections of human skin in ex vivo experiments, we evidenced that this polysaccharide was able to minimize human leukocyte elastase activity resulting in the protection of human skin elastic fiber network against the enzymatic proteolysis due to this serine proteinase. These results suggested that fucoidan could be used for treating some inflammatory pathologies in which uncontrolled extracellular matrix degradation takes place.

Cells, Cultured↗

Suffix-tree analyser (STAN): looking for nucleotidic and peptidic patterns in chromosomes.

SUMMARY: We have developed STAN (suffix-tree analyser), a tool to search for nucleotidic and peptidic patterns within whole chromosomes. Pattern syntax uses a string variable grammar-like formalism which allows the description of complex patterns including ambiguities, insertions/deletions, gaps, repeats and palindromes. STAN is based on a reduction to multipart matching on a suffix-tree data structure and can handle large DNA sequences, whether assembled or not.

Amino Acid Sequence↗

Host genotype by parasite genotype interactions underlying the resistance of anopheline mosquitoes to Plasmodium falciparum.

BACKGROUND: Most studies on the resistance of mosquitoes to their malaria parasites focus on the response of a mosquito line or colony against a single parasite genotype. In natural situations, however, it may be expected that mosquito-malaria relationships are based, as are many other host-parasite systems, on host genotype by parasite genotype interactions. In such systems, certain hosts are resistant to one subset of the parasite's genotypes, while other hosts are resistant to a different subset. METHODS: To test for genotype by genotype interactions between malaria parasites and their anopheline vectors, different genetic backgrounds (families consisting of the F1 offspring of individual females) of the major African vector Anopheles gambiae were challenged with several isolates of the human malaria parasite Plasmodium falciparum (obtained from naturally infected children in Kenya). RESULTS: Averaged across all parasites, the proportion of infected mosquitoes and the number of oocysts found in their midguts were similar in all mosquito families. Both indices of resistance, however, differed considerably among isolates of the parasite. In particular, no mosquito family was most resistant to all parasites, and no parasite isolate was most infectious to all mosquitoes. CONCLUSIONS: These results suggest that the level of mosquito resistance depends on the interaction between its own and the parasite's genotype. This finding thus emphasizes the need to take into account the range of genetic diversity exhibited by mosquito and malaria field populations in ideas and studies concerning the control of malaria.

Analysis of Variance↗

PIMWalker: visualising protein interaction networks using the HUPO PSI molecular interaction format.

UNLABELLED: This article reports on PIMWalker, a free and interactive tool for visualising protein interaction networks. PIMWalker handles the unified molecular interaction (MI) format defined by members of the Proteomics Standards Initiative (the PSI MI format), and it is thus directly and easily usable by bench biologists. PIMWalker also comes with a documented, open-source Javatrade mark application programming interface allowing the bioinformatic programmer to easily extend the functions. AVAILABILITY: PIMWalker is available under a free license from http://pim.hybrigenics.com/pimwalker.

Computer Graphics↗

Dispersal in a parasitic worm and its two hosts: consequence for local adaptation.

Characterizing host and parasite population genetic structure and estimating gene flow among populations is essential for understanding coevolutionary interactions between hosts and parasites. We examined the population genetic structure of the trematode Schistosoma mansoni and its two host species (the definitive host Rattus rattus and the intermediate host Biomphalaria glabrata) using microsatellite markers. Parasites were sampled from rats. The study was conducted in five sites of the Guadeloupe Island, Lesser Antilles. Mollusks display a pattern of isolation by distance whereas such a pattern is not found neither in schistosomes nor in rats. The comparison of the distribution of genetic variability in S. mansoni and its two host species strongly suggests that migration of parasites is principally determined by that of the vertebrate host in the marshy focus of Guadeloupe. However, the comparison between genetic differentiation values in schistosomes and rats suggests that the efficacy of the schistosome rat-mediated dispersal between transmission sites is lower than expected given the prevalence, parasitic load and migration rate of rats among sites. This could notably suggest that rat migration rate could be negatively correlated to the age or the infection status of individuals. Models made about the evolution of local adaptation in function of the dispersal rates of hosts and parasites suggest that rats and mollusks should be locally adapted to their parasites.

Animals↗

Sex-specific correlation between heterozygosity and clone size in the trematode Schistosoma mansoni.

The mode of reproduction (sexual and/or asexual) and the mating system determine the patterns of gene transmission and genotype formation across generations. Schistosoma mansoni is a dioecious trematode that necessarily alternates sexual and asexual reproduction during its life cycle. In a previous study of the distribution of S. mansoni genetic variability within and between definitive host individuals, we noticed that deleting multilocus genotypes from each infrapopulation so as to keep only one copy of each multilocus genotype, seemed to have a substantial effect on FIS values. More precisely, female FIS increased when repeated genotypes were removed whereas no effect was observed on male FIS. This suggested that multilocus genotypes at high frequency tended to be more heterozygous. The aim of the present study is specifically to test and analyse this phenomenon. We demonstrate that the number of repetitions per clone correlates with individual heterozygosity. This effect is however, sex-specific: only female clone size correlates with heterozygosity. We discuss this phenomenon in relation to the heterozygosity-fitness relationship and the sex-specific response to inbreeding depression.

Animals↗

Test of pangamy by genetic analysis of Schistosoma mansoni pairs within its natural murine host in Guadeloupe.

Mating system plays a determinant role in the maintenance and distribution of genetic variations. It can be assessed indirectly by analyzing the distribution of the genetic variability within populations or directly by considering how mating pairs are formed. In the present study, 71 pairs of adult Schistosoma mansoni worms sampled from naturally infected rats were genotyped to investigate how male and female schistosomes paired according to their genetic relatedness. Among all samples, pangamy, the random association between males and females, could not be rejected. Whereas the schistosome mating system has been intensively studied under experimental conditions, to the best of our knowledge, our study is the first to attempt to understand the way in which males and females pair in natural conditions.

Animals↗

Sex-specific genetic structure: new trends for dioecious parasites.

In dioecious parasite species, genetic structure can differ between sexes, as recently demonstrated for the digenetic trematode Schistosoma mansoni and the ectoparasitic tick Ixodes ricinus. This article presents some of the methods that allow detecting such a pattern in natural populations. The proximate and ultimate factors that potentially generate a sex-specific genetic structure are discussed, as are evolutionary and epidemiological consequences for dioecious parasites and vectors.

Animals↗