Polymeric mannosides prevent DC-SIGN-mediated cell-infection by cytomegalovirus

International audienceHuman cytomegalovirus (HCMV) is a beta-herpesvirus with a high prevalence in the population. HCMV is asymptomatic for immunocompetent adults but is a leading cause of morbidity for new born and immunocompromised patients. It was recently shown that the envelope glycoprotein B (gB) of HCMV interacts with the Dendritic Cell-Specific ICAM-3 Grabbing Non integrin (DC-SIGN) to infect the host. In this work we developed a set of DC-SIGN blockers based on mono-, di-, tetra and polyvalent mannosides. The multivalent mannosides were designed to interact with the carbohydrate recognition domains of DC-SIGN in a chelate or bind and recapture process, and represent the first chemical antiadhesives of HCMV reported so far. Polymeric dextrans coated with triazolylheptylmannoside (THM) ligands were highly potent, blocking the gB and DC-SIGN interaction at nanomolar concentrations. The compounds were further assessed for their ability to prevent the DC-SIGN mediated HCMV infection of dendritic cells. A dextran polymer coated with an average of 902 THM ligands showed an outstanding effect in blocking the HCMV trans-infection with IC50 values down to the picomolar range (nanomolar when expressed in THM concentration). Each THM moiety on the polymer surpassed the antiadhesive effect of the methylmannoside reference by more than four orders of magnitude. The compound proved non-cytotoxic at the high concentration of 2 mM and therefore represents an interesting antiadhesive candidate against HCMV and potentially against other virus hijacking dendritic cells to infect the host

Multi-view Normal Estimation – Application to Slanted Plane-Sweeping

In this paper, we show how to estimate the normals of a 3D surface from a minimum of two views, assuming that the poses of a calibrated camera are perfectly known. For each pair of image points, the normal at the corresponding 3D point is expressed in function of the local gradients of the grey level, whatever the type of image formation (orthogonal or perspective projection). As an application, this allows us to fully estimate the inter-image homography, which not only depends on the relative pose between views, but also on the local orientation of the surface. Hence, the photo-consistency between patches from two images, which is the basis of the so-called “plane-sweeping” method, is improved. Experiments on synthetic and real data validate our approach

Pediatr Obes

BACKGROUND: The nine French regional health networks for the prevention and care of paediatric obesity offer a 2-year program of multidisciplinary primary care (medical, dietetical, psychological, adapted physical activity) based on multicomponent lifestyle interventions. OBJECTIVES: To assess the short-term and long-term impact of care management. METHODS: The impact of the multidisciplinary care was assessed by changes in the body mass index (BMI) Z score during the period of the care, and at least 2 years after the end. Anthropometric data were collected at baseline and at the end of the care either through a digital medical file or through direct phone contacts with the referring. Long-term outcomes were assessed through studies relative to post follow-up evaluation. RESULTS: At the end of the period of the care in a network, 72.9% of 6947 children had decreased their BMI Z score from 3.6 +/- 1.0 DS at baseline to 3.3 +/- 1.1 DS at the end. The four studies relative to long-term evaluation showed a pursuit of the decrease of BMI Z score during the 5.1 years after the beginning of the care. CONCLUSIONS: The care provided by regional French networks for prevention and care of paediatric obesity induce a reduction of BMI that continues afterwards

Glycopolymers as Antiadhesives of E. coil Strains Inducing Inflammatory Bowel Diseases

International audiencen-Heptyl alpha-D-mannose (HM) is a nanomolar antagonist of FimH, a virulence factor of E. coli. Herein we report on the construction of multivalent HM-based glycopolymers as potent antiadhesives of type 1 piliated E. coli. We investigate glycopolymer/FimH and glycopolymer/bacteria interactions and show that HM-based glycopolymers efficiently inhibit bacterial adhesion and disrupt established cell-bacteria interactions in vitro at very low concentration (0.1 mu M on a mannose unit basis). On a valency-corrected basis, HM-based glycopolymers are, respectively, 10(2) and 10(6) times more potent than HM and D-mannose for their capacity to disrupt the binding of adherent-invasive E. coli to T84 intestinal epithelial cells. Finally, we demonstrate that the antiadhesive capacities of HM-based glycopolymers are preserved ex vivo in the colonic loop of a transgenic mouse model of Crohns disease. All together, these results underline the promising scope of HM-based macromolecular ligands for the antiadhesive treatment of E. coli induced inflammatory bowel diseases