Avis d'expert sur la détermination des caractéristiques d'inflammabilité du chanvre

International audienceDes dépôts de chanvre de faible épaisseur (de l'ordre de quelques mm) sont sensibles au phénomène d'auto-échauffement avec amorçage d'une combustion retardée dans l'ensemble du dépôt. Le contact de points chauds peut amorcer localement un phénomène identique de combustion lente qui, à terme, va s'étendre à la totalité du dépôt. Sur la base du retour d'expérience mettant en oeuvre des travaux de meulage et de tronçonnage en présence de solide combustible pulvérulent, ainsi que des valeurs expérimentales des caractéristiques d'inflammabilité du chanvre, l'INERIS a démontré que le chanvre est un matériau susceptible de s'auto-échauffer en présence de points chauds tels que des travaux de meulage et de tronçonnage. On ne peut que rappeler les risques particuliers engendrés par les travaux par point chaud et la nécessité de les prévenir par la mise en oeuvre rigoureuse de mesures techniques et organisationnelles adaptées. Une "analyse des risques" préalable, une transposition écrite des règles à respecter, la sensibilisation des opérateurs salariés ou sous-traitants, un nettoyage soigné dans un rayon de 11 m autour de la zone de travail et le contrôle des travaux après la fin des travaux sont des actions indispensables pour garantir la sécurité

Biodereplication of antiplasmodial extracts: application of the amazonian medicinal plant piper coruscans kunth

Improved methodological tools to hasten antimalarial drug discovery remain of interest, especially when considering natural products as a source of drug candidates. We propose a biodereplication method combining the classical dereplication approach with the early detection of potential antiplasmodial compounds in crude extracts. Heme binding is used as a surrogate of the antiplasmodial activity and is monitored by mass spectrometry in a biomimetic assay. Molecular networking and automated annotation of targeted mass through data mining were followed by mass-guided compound isolation by taking advantage of the versatility and finely tunable selectivity offered by centrifugal partition chromatography. This biodereplication workflow was applied to an ethanolic extract of the Amazonian medicinal plant Piper coruscans Kunth (Piperaceae) showing an IC50 of 1.36 ug/mL on the 3D7 Plasmodium falciparum strain. It resulted in the isolation of twelve compounds designated as potential antiplasmodial compounds by the biodereplication workflow. Two chalcones, aurentiacin (1) and cardamonin (3), with IC50 values of 2.25 and 5.5 uM, respectively, can be considered to bear the antiplasmodial activity of the extract, with the latter not relying on a heme-binding mechanism. This biodereplication method constitutes a rapid, efficient, and robust technique to identify potential antimalarial compounds in complex extracts such as plant extracts

Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen

Effect of population structure corrections on the results of association mapping tests in complex maize diversity panels

Association mapping of sequence polymorphisms underlying the phenotypic variability of quantitative agronomical traits is now a widely used method in plant genetics. However, due to the common presence of a complex genetic structure within the plant diversity panels, spurious associations are expected to be highly frequent. Several methods have thus been suggested to control for panel structure. They mainly rely on ad hoc criteria for selecting the number of ancestral groups; which is often not evident for the complex panels that are commonly used in maize. It was thus necessary to evaluate the effect of the selected structure models on the association mapping results. A real maize data set (342 maize inbred lines and 12,000 SNPs) was used for this study. The panel structure was estimated using both Bayesian and dimensional reduction methods, considering an increasing number of ancestral groups. Effect on association tests depends in particular on the number of ancestral groups and on the trait analyzed. The results also show that using a high number of ancestral groups leads to an over-corrected model in which all causal loci vanish. Finally the results of all models tested were combined in a meta-analysis approach. In this way, robust associations were highlighted for each analyzed trait

Contrasting Population Structures of the Genes Encoding Ten Leading Vaccine-Candidate Antigens of the Human Malaria Parasite, Plasmodium falciparum

The extensive diversity of Plasmodium falciparum antigens is a major obstacle to a broadly effective malaria vaccine but population genetics has rarely been used to guide vaccine design. We have completed a meta-population genetic analysis of the genes encoding ten leading P. falciparum vaccine antigens, including the pre-erythrocytic antigens csp, trap, lsa1 and glurp; the merozoite antigens eba175, ama1, msp's 1, 3 and 4, and the gametocyte antigen pfs48/45. A total of 4553 antigen sequences were assembled from published data and we estimated the range and distribution of diversity worldwide using traditional population genetics, Bayesian clustering and network analysis. Although a large number of distinct haplotypes were identified for each antigen, they were organized into a limited number of discrete subgroups. While the non-merozoite antigens showed geographically variable levels of diversity and geographic restriction of specific subgroups, the merozoite antigens had high levels of diversity globally, and a worldwide distribution of each subgroup. This shows that the diversity of the non-merozoite antigens is organized by physical or other location-specific barriers to gene flow and that of merozoite antigens by features intrinsic to all populations, one important possibility being the immune response of the human host. We also show that current malaria vaccine formulations are based upon low prevalence haplotypes from a single subgroup and thus may represent only a small proportion of the global parasite population. This study demonstrates significant contrasts in the population structure of P. falciparum vaccine candidates that are consistent with the merozoite antigens being under stronger balancing selection than non-merozoite antigens and suggesting that unique approaches to vaccine design will be required. The results of this study also provide a realistic framework for the diversity of these antigens to be incorporated into the design of next-generation malaria vaccines

Where the Lake Meets the Sea: Strong Reproductive Isolation Is Associated with Adaptive Divergence between Lake Resident and Anadromous Three-Spined Sticklebacks

Contact zones between divergent forms of the same species are often characterised by high levels of phenotypic diversity over small geographic distances. What processes are involved in generating such high phenotypic diversity? One possibility is that introgression and recombination between divergent forms in contact zones results in greater phenotypic and genetic polymorphism. Alternatively, strong reproductive isolation between forms may maintain distinct phenotypes, preventing homogenisation by gene flow. Contact zones between divergent freshwater-resident and anadromous stickleback (Gasterosteus aculeatus L.) forms are numerous and common throughout the species distribution, offering an opportunity to examine these contrasting hypotheses in greater detail. This study reports on an interesting new contact zone located in a tidally influenced lake catchment in western Ireland, characterised by high polymorphism for lateral plate phenotypes. Using neutral and QTL-linked microsatellite markers, we tested whether the high diversity observed in this contact zone arose as a result of introgression or reproductive isolation between divergent forms: we found strong support for the latter hypothesis. Three phenotypic and genetic clusters were identified, consistent with two divergent resident forms and a distinct anadromous completely plated population that migrates in and out of the system. Given the strong neutral differentiation detected between all three morphotypes (mean F-ST = 0.12), we hypothesised that divergent selection between forms maintains reproductive isolation. We found a correlation between neutral genetic and adaptive genetic differentiation that support this. While strong associations between QTL linked markers and phenotypes were also observed in this wild population, our results support the suggestion that such associations may be more complex in some Atlantic populations compared to those in the Pacific. These findings provide an important foundation for future work investigating the dynamics of gene flow and adaptive divergence in this newly discovered stickleback contact zone

Vers la synthèse totale asymétrique du norditerpène (+)-hainanolide (méthodologies et stratégies)

L'hainanolide ou harringtonolide est un norditerpène cytotoxique isolé d un Cephalotaxus. Il présente une structure polycyclique en forme de cage, dont la stéréochimie absolue a été déterminée par une analyse de diffraction des rayons X sur un d érivé bromé. Cette structure originale comporte quatre carbocycles, dont un tropone, ainsi que deux ponts éther et lactone transannulaires. Notre stratégie de synthèse comporte quatre étapes clefs. Le cycle tropone sera formé en fin de synthèse à partir d un diényne dont le motif diène sera formé par par métathèse d enyne. Une cascade d inspiration biomimétique, formera le système des ponts oxygénés à partir d un intermédiaire époxyde. Une réaction de Diels-Alder intramoléculaire stéréocontrolée formera un cycle cyclohexènique pivot de cette synthèse. Le précurseur de la réaction de Diels-Alder sera préparé à partir d un acétal du Dérythrose issu de la valorisation du pool chiral et plus particulièrement du D-glucose. Pour construire le cycle tropone, une cyclisation originale de type [4+2+1] était initialement prévue. Cette étape étant tardive, la synthèse et l utilisation d un modèle d étude de la réaction ont été effectuées. Le modèle comporte une partie diénique installée par une réorganisation d ényme catalysée par le chlorure de platine, et un alcyne terminal introduit par la méthodologie de Corey-Fuchs. Le composé modèle construit peut-être considéré comme une simplification d un intermédiaire de synthèse tardif prévu lors de la synthèse de l hainanolide. Il conserve un cycle un cinq chaînons, un système diénique et une chaine aliphatique comportant un alcyne terminal nécessaires à la cyclisation. Les quatre méthodologies de cyclisation explorées sont basées sur les conditions de Wender, Montgomery, Fischer et Heck.Hainanolide or harringtonolide is a cytotoxic norditerpene from Cephalotaxus. It presents a polycyclic cage-shaped structure whose absolute stereochemistry had been determined by an X-ray crystallographic analysis of a brominated derivative. This original structure contains four fused carbocycles, especially a tropone, and two lactone and ether transannular bridges. Our synthetic strategy contains four key steps. The tropone cycle will be obtained lately from a dienyne, whose dienic part will be formed by an enyne metathesis. A biomimetically inspired cascade would allow forming the lactone and ether bridges from an epoxyde intermediate. A pivotal asymmetric cyclohexene ring will be generated by a stereoselective intramolecular Diels-Alder precursor (IMDA) reaction. The Diels-Alder precursor will be constructed from D-erythose acetal which is derived from the chiral pool (D-glucose).In order to study the formation of tropone ring by an original [4+2+1] cyclization, the synthesis and use of a model compound was done. The model compound contains a diene part installed by PtCl2-catalyzed enyne reorganization, and a terminal alkyne introduced by the Corey-Fuchs methodology. Our first strategy to form the tropone cycle consisted in a [4+2+1] cyclization reaction. This key step being planned at the end of the synthesis, a methodological study was essential. The model compound can be considered as a simplification of a late synthetic intermediate of the total synthesis. It conserves a five-membered cycle, a dienic system and an aliphatic chain with a terminal alkyne necessary for the cyclization. Four methodologies have been explored based on Wender, Montgomery, Fischer or Heck conditions.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-Museum Hist.Naturelle (751052304) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Stereodivergent Total Syntheses of (+)-Mycaperoxides C, D, G Methyl Ester and (-)-Mycaperoxide B

Mycaperoxides are natural endoperoxides isolated from different Mycale genus sponges, showing significant antiviral or antibacterial activities. We report herein the first total syntheses of representative congeners of this family from sclareol using a stereodivergent approach. Thus, an innovative oxidative ring expansion of cyclobutanol was used to bring the 1,2-dioxane subunit, and a Mukaiyama aldol reaction on peroxycarbenium species was utilized to install the propionic acid subunit. During the study toward (+)-mycaperoxide D methyl ester (2), the isolation of the eight possible diastereomers under their ethyl thioester form allowed to build a pertinent database for further NMR assignment studies. Thus, we completed the total syntheses of (+)-mycaperoxides D, C, G methyl ester, and (-)-mycaperoxide B in 11 to 15 steps, confirming their origi-nal assignment