Exploration of plant genomes in the FLAGdb++ environment

Background : In the contexts of genomics, post-genomics and systems biology approaches, data integration presents a major concern. Databases provide crucial solutions: they store, organize and allow information to be queried, they enhance the visibility of newly produced data by comparing them with previously published results, and facilitate the exploration and development of both existing hypotheses and new ideas. Results : The FLAGdb++ information system was developed with the aim of using whole plant genomes as physical references in order to gather and merge available genomic data from in silico or experimental approaches. Available through a JAVA application, original interfaces and tools assist the functional study of plant genes by considering them in their specific context: chromosome, gene family, orthology group, co-expression cluster and functional network. FLAGdb++ is mainly dedicated to the exploration of large gene groups in order to decipher functional connections, to highlight shared or specific structural or functional features, and to facilitate translational tasks between plant species (Arabidopsis thaliana, Oryza sativa, Populus trichocarpa and Vitis vinifera). Conclusion : Combining original data with the output of experts and graphical displays that differ from classical plant genome browsers, FLAGdb++ presents a powerful complementary tool for exploring plant genomes and exploiting structural and functional resources, without the need for computer programming knowledge. First launched in 2002, a 15th version of FLAGdb++ is now available and comprises four model plant genomes and over eight million genomic features

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Avant-propos.

Marchand Philippe, Grevet René. Avant-propos.. In: Revue du Nord, tome 78, n°317, Octobre-décembre 1996. Les débuts de l'Ecole républicaine (1792-1802) pp. 663-664

De l'Ecole d'Ancien Régime aux débuts de l'Ecole contemporaine. La genèse d'un double enjeu (Artois et Boulonnais, fin XVIIe - 1815)

Grevet René, Marchand Philippe. De l'Ecole d'Ancien Régime aux débuts de l'Ecole contemporaine. La genèse d'un double enjeu (Artois et Boulonnais, fin XVIIe - 1815). In: Revue du Nord, tome 71, n°282-283, Juillet-décembre 1989. La Révolution française au pays de Carnot, Le Bon, Merlin de Douai, Robespierre... pp. 1085-1092

Mode d'action et toxicité des trichothécènes

Les trichothécènes possèdent une toxicité variable mais qui se manifeste par des troubles similaires : baisses de performances, vomissements, lésions cutanées, digestives et hématopoïétiques ainsi qu'une modulation des défenses immunitaires (le plus souvent une immunodépression). Le porc et les volailles sont les espèces les plus sensibles. Ces toxines ne sont ni cancérigènes ni tératogènes. Elles agissent sur la membrane plasmique, inhibent la traduction et induisent un stress oxydatif. Si leurs mécanismes d'action sont communs, leur potentiel toxique est influencé par leur cinétique et leur capacité à atteindre et à se lier à leurs cibles intracellulaires. Bien que les profils cinétiques varient selon les espèces et les toxines, les trichothécènes sont rapidement absorbés après un métabolisme digestif intense, se distribuent très largement dans l'organisme et sont intensément métabolisés dans le foie et rapidement éliminés.TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE-EN Vétérinaire (315552301) / SudocSudocFranceF

De l'Ecole d'Ancien Régime aux débuts de l'Ecole contemporaine. La genèse d'un double enjeu (Artois et Boulonnais, fin XVIIe - 1815)

Grevet René, Marchand Philippe. De l'Ecole d'Ancien Régime aux débuts de l'Ecole contemporaine. La genèse d'un double enjeu (Artois et Boulonnais, fin XVIIe - 1815). In: Revue du Nord, tome 71, n°282-283, Juillet-décembre 1989. La Révolution française au pays de Carnot, Le Bon, Merlin de Douai, Robespierre... pp. 1085-1092

René Grevet, « L'enseignement élémentaire dans le contexte éducatif français, 1685-1835 » ; « La Province et l'Etat : paradoxes culturels et engagements politiques (Artois, Boulonnais/Pas-de-Calais), fin XVIIe siècle-début XIXe siècle »

Marchand Philippe, Legay Marie-Laure, Grevet René. René Grevet, « L'enseignement élémentaire dans le contexte éducatif français, 1685-1835 » ; « La Province et l'Etat : paradoxes culturels et engagements politiques (Artois, Boulonnais/Pas-de-Calais), fin XVIIe siècle-début XIXe siècle ». In: Revue du Nord, tome 91, n°330, Avril-juin 1999. pp. 367-376

René Grevet, « L'enseignement élémentaire dans le contexte éducatif français, 1685-1835 » ; « La Province et l'Etat : paradoxes culturels et engagements politiques (Artois, Boulonnais/Pas-de-Calais), fin XVIIe siècle-début XIXe siècle »

Marchand Philippe, Legay Marie-Laure, Grevet René. René Grevet, « L'enseignement élémentaire dans le contexte éducatif français, 1685-1835 » ; « La Province et l'Etat : paradoxes culturels et engagements politiques (Artois, Boulonnais/Pas-de-Calais), fin XVIIe siècle-début XIXe siècle ». In: Revue du Nord, tome 91, n°330, Avril-juin 1999. pp. 367-376

Exploration of plant genomes in the FLAGdb⁺⁺environment

Abstract Background In the contexts of genomics, post-genomics and systems biology approaches, data integration presents a major concern. Databases provide crucial solutions: they store, organize and allow information to be queried, they enhance the visibility of newly produced data by comparing them with previously published results, and facilitate the exploration and development of both existing hypotheses and new ideas. Results The FLAGdb++ information system was developed with the aim of using whole plant genomes as physical references in order to gather and merge available genomic data from in silico or experimental approaches. Available through a JAVA application, original interfaces and tools assist the functional study of plant genes by considering them in their specific context: chromosome, gene family, orthology group, co-expression cluster and functional network. FLAGdb++ is mainly dedicated to the exploration of large gene groups in order to decipher functional connections, to highlight shared or specific structural or functional features, and to facilitate translational tasks between plant species (Arabidopsis thaliana, Oryza sativa, Populus trichocarpa and Vitis vinifera). Conclusion Combining original data with the output of experts and graphical displays that differ from classical plant genome browsers, FLAGdb++ presents a powerful complementary tool for exploring plant genomes and exploiting structural and functional resources, without the need for computer programming knowledge. First launched in 2002, a 15th version of FLAGdb++ is now available and comprises four model plant genomes and over eight million genomic features.</p