Influence of the reducing-end anomeric configuration of the Man9 epitope on DC-SIGN recognition

High-mannose (Man9GlcNAc2) is the main carbohydrate unit present in viral envelope glycoproteins such as gp120 of HIV and the GP1 of Ebola virus. This oligosaccharide comprises the Man9 epitope conjugated to two terminal N-acetylglucosamines by otherwise rarely-encountered β-mannose glycosidic bond. Formation of this challenging linkage is the bottleneck of the few synthetic approaches described to prepare high mannose. Herein, we report the synthesis of the Man9 epitope with both alpha and beta configurations at the reducing end, and subsequent evaluation of the impact of this configuration on binding to natural receptor of high-mannose, DC-SIGN. Using fluorescence polarization assays, we demonstrate that both anomers bind to DC-SIGN with comparable affinity. These relevant results therefore indicate that the more synthetically-accesible Man9 alpha epitope may be deployed as ligand for DC-SIGN in both in vitro and in vivo biological assays.Ministerio de Economía y Competitividad CTQ2017- 86265-P, PGC2018-099497-B-100, IJCI-2015-2327

Advancing global & regional reanalyses

This report outlines the structure of and summarizes the recommendations made at the 5th International Conference on Reanalysis (ICR5), attended by 259 participants from 37 countries, in Rome (Italy), on 13-17 November 2017. It first summarizes the conference structure. Then, the key recommendations of ICR5 are given for the five main conference topics: production; observations (data rescue and preparation); data assimilation methods; quality assurance of reanalysis; and applications in science, services, and policymaking. Lastly, five high-level recommendations are proposed to managing agencies on how best to advance the field of reanalyses, which serves tens of thousands of users, via enhanced research, development, and operations

Rapid On‐chip Synthesis of Complex Glycomimetics from N‐glycan Scaffolds for Improved Lectin Targeting

International audienceC-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines. The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site. Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes. All surface-based reactions were monitored by MALDI-TOF MS to assess conversion and purity of spot compositions. Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes

Smartphones benefits for psychics diseases

International audience1. Home Care Services: Needs and Limits Carpe Diem at Finistère and Agef, are two home care services specialized in providing support for people suffering from psychological or cognitive lnesses. Their services are targeted to people presenting neurodegenerative pathologies and those requiring support for intellectual, sensorial, and motor activities due to an illness (strokes, Parkinson’s disease, multiple sclerosis). Usually, patients of both home care services have expressed their interest on technologies [1] that could reduce their dependence on relatives or caregivers when going outside. Patients’ demand is usually for systems enabling localization and quick emergency intervention from an unnoticeable and non-stigmatic device. Their main objective is to feel autonomous when their body is letting them own and to alleviate the caregiver's burden. 2. A Collaborative Project. As an open platform, the Android Smartphone combined with sensors and Saas (Software as a Service) applications will now bring innovative services [2] to fragile people (elderly, disabled, people with chronic diseases or mental illness...). AlyaCom, in partnership with Carpe Diem and Agef, has developed a Machine to Machine Mediation Platform (M2M²P) which is able to provide a wide range of services to these people and to caregivers (emergency calls, information services, tracking and tracing services..). In this way, they are now able to create, around each fragile person, a customized ecosystem of inter-operable solutions, covering the needs of security, solidarity, and tele-monitoring. 3. Results People are no longer confined at home, they are free to move around with an attractive and modern mobile phone. Moreover, AlyaCom can provide a user interface (remotely tailored by caregivers) for people with visual or cognitive disabilities by taking advantage of the touch screen, sounds, and vibration of the Android Smartphone. [1] S. Pennec, " The technologies in the city, markers of strangeness of the old age or possible mediators of citizenship? ", The age and the power in question: age and decide in the city, Acts Roma CD and www.reiactis.org site, University of Rouen, October 8-9th, 2008. [2] A. Delattre, A. Thépaut, M.T. Segarra, M. L’Hostis, P.M. Chapon, "Android and geolocation at service of the elderly", International Society for Gerontechnology, 7th World Conference 27-30 may 2010, Vancouver, Canada

Glycomimetic ligands block the interaction of SARS-CoV-2 spike protein with C-type lectin co-receptors

International audienceThe C-type lectin receptors DC-SIGN and L-SIGN bind to glycans on the SARS-CoV-2 spike glycoprotein and promote trans-infection of ACE2-expressing cells. We tested C2 triazole-modified mono- and pseudo-di-mannosides as inhibitors of DC/L-SIGN binding to a model mannosylated protein (Man-BSA) and to SARS-CoV2 spike, finding that they inhibit the interaction of both lectins with the spike glycoprotein in a Surface Plasmon Resonance (SPR) assay and are more potent than mannose by up to 36-fold (DC-SIGN) and 10-fold (L-SIGN). The molecules described here are the first known glycomimetic ligands of L-SIGN

Aimants et champs magnétiques en orthopédie dento-faciale

Après avoir rappelé quelques généralités concernant les aimants, les auteurs analysent les notions de forces d'interaction et de proximité, de repérage des directions des forces, puis étudient le comportement des aimants en répulsion et plus particulièrement leur utilisation en tant que moyens d'ingression. Des applications expérimentales sur Typodont sont ensuite exposées et discutées

Android and geolocation for the elderly

International audienceAs an open mobile platform, Android has the potential to bring innovative services to the elderly. In particular, the use of geolocation technology for the elderly makes it possible to identify the area within which the elderly live and move, and therefore, study the nature, length, and frequency of their trips. In this we propose to use this information to better identify the needs of the elderly and propose arrangements of the urban planning

Local critical power is an index of local endurance

International audienceThe hypothesis thal critical power (CP) is significantly lower than the maximal aerobic power of the knec cxtensors has hccn tested in nine endurance-traincd subjccts, sevcn gymnasts and sevcn weight lirters. CP was calculated as heing equal to the slopc of the linear relationship bct\veen exhaustion lime and work pcrformcd at exhaustion on a knee-extcnsion ergometer. CP was comparcd with the power output at the end of a progressive knee-cxtension exercise (Prcnk) and the power outputs eorresponding to exhaustion times equal to 4 (P4 min), 6 (/\min), K (Px min) and 10 min (P 10 min), calculated according to the lincar relationship betwecn work and exhaustion time. The hypolhesis thal CP corresponds to a steady state in metabolic and physiological pararneters \vas testcd in the gymnasts and the \veight lillers hy comparing CP with the fatigue thresholds of the integratcd electromyog:ram (iEMGFT). lac-tate leve] (Lap 1). oxygen uptake (V0 2 IT) and heart rate (HR 1 Tl· The resulls of the present study demonstrate that the value of CP or a local cxercise cannot be con-sidcred as the equivalent of' the maximal aerobic power for general excrcises. The values or P4 1111 n, P6 min· Py, mirn P1o min and Pr~; 1 k wcre significantly higher than CP, and eorresponded to 13~, 126. 119, 115 and 151 "A, CP. re-spectivcly. The results of the present study indicatc that CP can be considcred as an index of muscular endurance. lndeed, LtF 1 , iEMG f-T· V0 2 FT and HRF· 1 vvere nol significantly different from CP. Ail of these fatigue thresholds wcre significantly correlatcd with CP (r > 0.92). Moreovcr. the highest coefficient of corre-Paris. /-rance lation (r = 0.71; P < 0.01) bctween the percentage of maximal aerobic power in cycling that corresponds to a blood lactate concentration of 4 mmol · 1-1 (OBLA 0 1Ô) and the difTerent local aerobic indices was observed with CP

Synthesis, self-assembly and Langerin recognition studies of a resorcinarene-based glycocluster exposing a hyaluronic acid thiodisaccharide mimetic

International audienceHerein, we report the synthesis of an octavalent glycocluster exposing a thiodisaccharide mimetic of the repetitive unit of hyaluronic acid, βSGlcA(1 → 3)βSGlcNAc, constructed on a calix[4]resorcinarene scaffold by CuAAC reaction of suitable precursors. This glycocluster showed a strong tendency toward self-aggregation. DOSY-NMR and DLS experiments demonstrated the formation of spherical micelles of d ≅ 6.2 nm, in good agreement. TEM micrographs showed the presence of particles of different sizes, depending on the pH of the starting solution, thus evidencing that the negative charge on the micelle surface due to ionization of the GlcA residues plays an important role in the aggregation process. STD-NMR and DLS experiments provided evidence of the interaction between the synthetic glycocluster and Langerin, a relevant C-type lectin. This interaction was not observed in the STD-NMR experiments performed with the basic disaccharide, providing evidence of a multivalent effect