76 research outputs found

    Unrecognized sequence homologies may confound genome-wide association studies

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    Genome-wide association studies (GWAS) have become a preferred method to identify new genetic susceptibility loci. This technique aims to understanding the molecular etiology of common diseases, but in many cases, it has led to the identification of loci with no obvious biological relevance. Herein, we show that previously unrecognized sequence homologies have caused single-nucleotide polymorphism (SNP) microarrays to incorrectly associate a phenotype to a given locus when in fact the linkage is to another distant locus. Using genetic differences between male and female subjects as a model to study the effect of one specific genomic region on the whole SNP microarray, we provide strong evidence that the use of standard methods for GWAS can be misleading. We suggest a new systematic quality control step in the biological interpretation of previous and future GWAS

    Multicultural Interdisciplinary Handbook: tools for learning history and geography in a multicultural perspective (MIH)

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    [ES] MIH project (Multicultural Interdisciplinary Handbook: tools for learning History and Geography in a multicultural perspective) is a Comenius Multilateral Project funded with support from the European Commission that has been developed from 2009 to 2011.Conceived from the idea of educating lower and upper Secondary School pupils in a process of construction of a European identity by involving them in the culture of other countries, MIH project meets this need by providing new methodological and ICT tools that could help teachers and pupils to plunge deeper into both cultures and languages of another nations via their History and Geography, and opens the way to introduce a European perspective in History and Geography school curricula and classroom activities

    Intercultural Education through Religious Studies (IERS): COMENIUS Multilateral project

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    [EN] Religious and cultural diversity are today more than ever a critical and political challenge as the recent emergencies related to geo-political and economical global transformations clearly show. European countries are concerned by a big immigration flow that demands an educational effort in order to foster the mutual understanding and integration. According to Toledo guiding principles, IERS project meets the needs of an innovative approach in teaching about religions and beliefs at school by providing teachers of humanistic disciplines with new tools that help teachers and pupils to plunge deeper into religions and cultures of non-european countries, as well as raising the knowledge of the religious traditions that contributed to the common European cultural Identity, promoting it in the best way suited for encourage intra -and extra- European cultural dialogue attitudes. The Project aims to support the development of social, civic and intercultural transversal key competences by educating towards a positive understanding of cultural and religious differences, a readiness to engage in dialogue and to avoid or manage conflicts. By encouraging teachers and pupils to expose themselves to the differences and commonalities of religious topics, it promotes also the values of democracy, equality and human rights as it deals with social and civic dimensions of both intercultural and interreligious dialogue. The project will involve high school in-service teachers by developing a complete set of didactical tools and training experiences. The results will be: 1. A baseline study which analyzes the actual situation of teaching about religions throughout Europe; 2. New innovative didactic tools such as Multimedia Digital Modules to be used in classroom activities, accompanied by a Handbook with didactical guidelines for teachers. 3. Teacher support activities (virtual community, training activities, developing of didactical projects to apply in classroom)

    Quelques pistes didactiques pour enseigner l\u27histoire des marrons et leurs représentations

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    Colloque « Les marronnages et leurs productions sociales, culturelles dans les Guyanes et le bassin caribéen du XVIIème au XXème siècles : bilans et perspectives de rechercheDire, montrer, penser le marronnage (traditions orales, littérature, arts, musées.

    Molecular characterization of cell death induced by a compatible interaction between Fusarium oxysporum f. sp. linii and flax (Linum usitatissimum) cells

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    The cellular and molecular events associated with cell death during compatible interaction between Fusarium oxysporum sp. linii and a susceptible flax (Linum usitatissimum) cell suspension are reported here. In order to determine the physiological and molecular sequence of cell death of inoculated cells, reactive oxygen species (ROS) production, mitochondrial potential, lipoxygenase, DNase, protease and caspase-3-like activities, lipid peroxidation and secondary metabolite production were monitored. We also used microscopy, in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) and DNA fragmentation assay. Cell death was associated with specific morphological and biochemical changes that are generally noticed in hypersensitive (incompatible) reaction. An oxidative burst as well as a loss of mitochondrial potential of inoculated cells, an activation of lipoxygenase and lipid peroxidation were noted. Enzyme-mediated nuclear DNA degradation was detectable but oligonucleosomal fragmentation was not observed. Caspase-3-like activity was dramatically increased in inoculated cells. Phenylpropanoid metabolism was also affected as demonstrated by activation of PAL and PCBER gene expressions and reduced soluble lignan and neolignan contents. These results obtained in flax suggest that compatible interaction triggers a cell death sequence sharing a number of common features with the hypersensitive response observed in incompatible interaction and in animal apoptosis

    An untargeted liquid chromatography-mass spectrometry-based workflow for the structural characterization of plant polyesters

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    International audienceCell wall localized heterogeneous polyesters are widespread in land plants. The composition of these polyesters, such as cutin, suberin, or more plant-specific forms such as the flax seed coat lignan macromolecule, can be determined after total hydrolysis of the ester linkages. The main bottleneck in the structural characterization of these macromolecules, however, resides in the determination of the higher order monomer sequences. Partial hydrolysates of the polyesters release a complex mixture of fragments of different lengths, each present in low abundance and therefore are challenging to structurally characterize. Here, a method is presented by which liquid chromatography-mass spectrometry (LC-MS) profiles of such partial hydrolysates are searched for pairs of related fragments. LC-MS peaks that show a mass difference corresponding to the addition of one or more macromolecule monomers were connected in a network. Starting from the lowest molecular weight peaks in the network, the annotation of the connections as the addition of one or more polyester monomers allows the prediction of consecutive and increasingly complex adjacent peaks. Multi-stage MS (MSn) experiments further helped to reject, corroborate, and sometimes refine the structures predicted by the network. As a proof of concept, this procedure was applied to partial hydrolysates of the flax seed coat lignan macromolecule, and allowed to characterize 120 distinct oligo-esters, consisting of up to six monomers, and containing monomers and linkages for which incorporation in the lignan macromolecule had not been described before. These results showed the capacity of the approach to advance the structural elucidation of complex plant polyesters

    Etching of the seed cuticle by cold plasma shortens imbibitional leakage in Linum usitatissimum L.

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    International audiencePre-sowing treatment of seeds with cold plasma, a reactive mixture of charged particles, is an emerging, environmentally friendly method, shown to improve water absorption, germination and seedling growth in many crop species. We studied how plasma affects different structural layers in flax seed coats, and focused on the effects on some of the earliest germination events, directly related to imbibition: solute leakage and mucilage extrusion. We characterized the ultrastructure of flax seed coats using scanning electron microscopy (SEM) and observed mucilage extrusion in situ, using environmental SEM. Time-courses of water uptake and solute leakage during germination were recorded, respectively, by weighing the seeds and semi-quantitative metabolite profiling of the exudates using GC-MS, LC-MS and LC-UV. Plasma treatment perforated the cuticle of flax seeds but did not visibly etch the underlying mucilage secretory cell (MSC) walls. Plasma treated seeds took up more water than untreated seeds during imbibition. Mucilage expansion of untreated seeds detached the distal MSC walls from the radial walls and extrusion occurred, relatively slowly, via sparse cracks in the distal cell wall layer. In plasma treated seeds, mucilage extrusion occurred fast, via rupture of distal cell walls of almost every single MSC, and the junctions between distal and radial MSC walls remained intact. Initially, imbibitional solute leakage was higher in plasma treated seeds but the leakage had quasi stopped after one hour of imbibition. In untreated seeds, the leakage continued amply more than two hours after the start of imbibition. Fragments of the lignan macromolecule, stored in parenchymatous cells under the MCS, were released more abundantly in the spermosphere of plasma treated than untreated flax seeds. It is concluded that plasma treatment etches the cuticle of flax seeds and weakens the underlying MSC cell walls, and that such treatment leads to significantly faster recovery of membranes during imbibition, reducing leakage time in germinating seeds

    Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy.

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    International audienceRecent findings in idiopathic membranous nephropathy (MN) suggest that in most patients, the disease is because of anti-phospholipase A(2) receptor (PLA(2) R1) autoantibodies. Our aim was to analyze the prevalence and significance of anti-PLA(2) R1 antibodies in recurrent and de novo MN after transplantation. We assessed circulating PLA(2) R1 autoantibodies by a direct immunofluorescence assay based on human embryonic kidney cells transfected with a PLA(2) R1 cDNA, and the presence of PLA(2) R1 antigen in immune deposits. We showed that PLA(2) R1 was involved in 5 of 10 patients with recurrent MN, but in none of the 9 patients with de novo MN. We also showed a marked heterogeneity in the kinetics and titers of anti-PLA(2) R1, which may relate to different pathogenic potential. We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence. Because PLA(2) R1 autoantibody was not always associated with recurrence, its predictive value should be carefully analyzed in prospective studies
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