1-C-phosphonomethyl- and 1-C-difluorophosphonomethyl-1,4-imino-L-arabinitols as Galf transferase inhibitors: A comparison

International audienceThe convenient preparation of iminopentitol derivatives, based on a 1,4-dideoxy-1,4-imino-l-arabinitol scaffold carrying β-phosphono(difluoromethyl) or β-phosphonomethyl appendages, as Galf-1P mimics, is reported. The compounds were tested for their ability to inhibit GlfT2, a vital galactofuranosyltransferase involved in the cell wall biosynthesis of mycobacteria. Interestingly, the Galf-1P mimics lacking a fluorine atom (7 and 8) were very poor inhibitors, showing less than 20% inhibition of GlfT2, whereas compounds 2 and 3, which contains a difluoromethylenephosphonate moiety were more potent inhibitors. Compound 3 that is fully deprotected was the most potent showing a significant IC50 value (0.9 mm), despite the absence of the diphosphate linkage present in the parent sugar nucleotide. This study paves the way to the synthesis of more complex β-phosphonomethyl-imino-l-arabinitol derivatives as simplified mimics of UDP-α-d-Galf

Chair/bedside diagnosis of oral and respiratory tract infections, and identification of antibiotic resistances for personalised monitoring and treatment

Global healthcare systems are struggling with the enormous burden associated with infectious diseases, as well as the incessant rise of antimicrobial resistance. In order to adequately address these issues, there is an urgent need for rapid and accurate infectious disease diagnostics. The H2020 project DIAGORAS aims at diagnosing oral and respiratory tract infections using a fully integrated, automated and user-friendly platform for physicians' offices, schools, elderly care units, community settings, etc. Oral diseases (periodontitis, dental caries) will be detected via multiplexed, quantitative analysis of salivary markers (bacterial DNA and host response proteins) for early prevention and personalised monitoring. Respiratory Tract Infections will be diagnosed by means of DNA/RNA differentiation so as to identify their bacterial or viral nature. Together with antibiotic resistance screening on the same platform, a more efficient treatment management is expected at the point-of-care. At the heart of DIAGORAS lies a centrifugal microfluidic platform (LabDisk and associated processing device) integrating all components and assays for a fully automated analysis. The project involves an interface with a clinical algorithm for the comprehensive presentation of results to end-users, thereby increasing the platform's clinical utility. DIAGORAS' performance will be validated at clinical settings and compared with gold standards

Chair/bedside diagnosis of oral and respiratory tract infections, and identification of antibiotic resistances for personalised monitoring and treatment

textabstractGlobal healthcare systems are struggling with the enormous burden associated with infectious diseases, as well as the incessant rise of antimicrobial resistance. In order to adequately address these issues, there is an urgent need for rapid and accurate infectious disease diagnostics. The H2020 project DIAGORAS aims at diagnosing oral and respiratory tract infections using a fully integrated, automated and user-friendly platform for physicians' offices, schools, elderly care units, community settings, etc. Oral diseases (periodontitis, dental caries) will be detected via multiplexed, quantitative analysis of salivary markers (bacterial DNA and host response proteins) for early prevention and personalised monitoring. Respiratory Tract Infections will be diagnosed by means of DNA/RNA differentiation so as to identify their bacterial or viral nature. Together with antibiotic resistance screening on the same platform, a more efficient treatment management is expected at the point-of-care. At the heart of DIAGORAS lies a centrifugal microfluidic platform (LabDisk and associated processing device) integrating all components and assays for a fully automated analysis. The project involves an interface with a clinical algorithm for the comprehensive presentation of results to end-users, thereby increasing the platform's clinical utility. DIAGORAS' performance will be validated at clinical settings and compared with gold standards

Sociabilité et politique en milieu rural

Du soulèvement des nudz-piedz bretons aux militants de la Confédération paysanne, en passant par les sans-culottes ruraux, cet ouvrage évoque toute une variété de mobilisations sociales et politiques en milieu rural, essentiellement en France, mais également dans des territoires étrangers (Espagne, Portugal, Allemagne, Italie), de la fin du Moyen Âge à la période contemporaine. Une quarantaine de chercheurs travaillant sur différentes périodes historiques ont été rassemblés pour réaliser ce projet ambitieux. Historiens, sociologues ou politistes, tous partagent un intérêt commun pour les mondes ruraux qu’ils interrogent ici à travers le concept de sociabilité. Cette approche leur permet de faire éclater l’unicité supposée d’une « communauté rurale », mais aussi de souligner la diversité des mondes ruraux en fonction des groupes envisagés et des territoires investis. Les diverses contributions oscillent entre une attention portée aux rapports sociaux et politiques qui se construisent dans la durée, et l’analyse d’événements déstabilisateurs comme les émeutes. Les sociabilités rurales ainsi décrites apparaissent à la fois perturbées et révélées par des événements singuliers, des révoltes, des soulèvements, des crises sociales, des guerres, etc. Forgés notamment dans les pratiques de travail et les fréquentations sociales, les réseaux de sociabilité évoqués dans cet ouvrage sont multiples. Ils peuvent être d’ordre familial ou générationnel, mais aussi, pour les formes les plus institutionnalisées, d’ordre syndical ou partisan. Le rapprochement des deux notions - sociabilité et politique - est au cœur de la réflexion de chacun des auteurs. Il permet à la fois d’explorer très finement les liens sociaux sur lesquels se construit le pouvoir politique, et aussi d’investir la sociabilité militante de différentes organisations. En abordant dans le temps long la question de la singularité des comportements sociaux et politiques en milieu rural à travers le concept de sociabilité, cet ouvrage entend favoriser l’échange interdisciplinaire et, en particulier, le rapprochement en cours entre les sciences historiques et la sociologie politique