L’haptoglobine chez les enfants atteints de paludisme grave a Plasmodium falciparum de 0 à 15 ans : Relations avec l’âge, la parasitémie et le taux d’hémoglobine

Objectifs : Cette étude avait pour objectifs d’évaluer l’haptoglobine chez les enfants âgés de 0 à 15 ans atteints de paludisme grave à Plasmodium falciparum, et de rechercher les relations entre cette protéine de l’inflammation avec l’âge, la densité parasitaire et le taux d’hémoglobine.Méthodologie et résultats : Il s’agissait d’une étude prospective  transversale chez 70 enfants atteints de paludisme grave à Plasmodium falciparum dont l’âge variait entre 0 et 15 ans recrutés aux services de Pédiatrie des Centres Hospitaliers et Universitaires (CHU) de Cocody et de Yopougon (Abidjan). Les résultats ont montré qu’au cours du paludisme grave à Plasmodium falciparum chez les enfants, on notait une hypohaptoglobinémie chez la majorité des malades (69,44 à 88,2%). Le taux moyen d’haptoglobine est plus bas chez les enfants de 0 à 5 ans, traduisant une hémolyse plus importante. Le taux moyen de cette protéine était proportionnel à l’âge et au taux moyen d’hémoglobine, mais inversement proportionnel à la densité parasitaire moyenne.Conclusion et application des résultats : Cette étude a montré qu’au cours du paludisme grave à .Plasmodium falciparum chez les enfants, le taux d’haptoglobine était associé à l’âge, à la parasitémie et au taux d’hémoglobine. Dans les pays en développement où l’anémie palustre est cause du décès de milliers d’enfants de moins de 5 ans par an, l’haptoglobine pourrait être un excellent marqueur pour le suivi des états inflammatoires et de la réémission des hémolyses intra vasculaires en pratique pédiatrique.Mots clés : Paludisme grave à Plasmodium falciparum, haptoglobine, enfants

Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists

CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human Class A G protein-coupled receptors (GPCRs). CCR2 is expressed on monocytes, immature dendritic cells and T cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2(1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases(2) including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer(3). These disease associations have motivated numerous preclinical studies and clinical trials(4) (see ClinicalTrials.gov) in search of therapies that target the CCR2:chemokine axis. To aid drug discovery efforts(5), we solved a structure of CCR2 in a ternary complex with an orthosteric (BMS-681(6)) and allosteric (CCR2-RA-[R](7)) antagonist. BMS-681 inhibits chemokine binding by occupying the orthosteric pocket of the receptor in a previously unseen binding mode. CCR2-RA-[R] binds in a novel, highly druggable pocket that is the most intracellular allosteric site observed in Class A GPCRs to date; this site spatially overlaps the G protein-binding site in homologous receptors. CCR2-RA-[R] inhibits CCR2 non-competitively by blocking activation-associated conformational changes and formation of the G protein-binding interface. The conformational signature of the conserved microswitch residues observed in double-antagonist-bound CCR2 resembles the most inactive GPCR structures solved to date. Like other protein:protein interactions, receptor:chemokine complexes are considered challenging therapeutic targets for small molecules, and the present structure suggests diverse pocket epitopes that can be exploited to overcome drug design obstacles

FRIPON: A worldwide network to track incoming meteoroids

Context. Until recently, camera networks designed for monitoring fireballs worldwide were not fully automated, implying that in case of a meteorite fall, the recovery campaign was rarely immediate. This was an important limiting factor as the most fragile - hence precious - meteorites must be recovered rapidly to avoid their alteration. Aims. The Fireball Recovery and InterPlanetary Observation Network (FRIPON) scientific project was designed to overcome this limitation. This network comprises a fully automated camera and radio network deployed over a significant fraction of western Europe and a small fraction of Canada. As of today, it consists of 150 cameras and 25 European radio receivers and covers an area of about 1.5 × 106km2. Methods. The FRIPON network, fully operational since 2018, has been monitoring meteoroid entries since 2016, thereby allowing the characterization of their dynamical and physical properties. In addition, the level of automation of the network makes it possible to trigger a meteorite recovery campaign only a few hours after it reaches the surface of the Earth. Recovery campaigns are only organized for meteorites with final masses estimated of at least 500 g, which is about one event per year in France. No recovery campaign is organized in the case of smaller final masses on the order of 50 to 100 g, which happens about three times a year; instead, the information is delivered to the local media so that it can reach the inhabitants living in the vicinity of the fall. Results. Nearly 4000 meteoroids have been detected so far and characterized by FRIPON. The distribution of their orbits appears to be bimodal, with a cometary population and a main belt population. Sporadic meteors amount to about 55% of all meteors. A first estimate of the absolute meteoroid flux (mag < -5; meteoroid size ≥∼1 cm) amounts to 1250/yr/106km2. This value is compatible with previous estimates. Finally, the first meteorite was recovered in Italy (Cavezzo, January 2020) thanks to the PRISMA network, a component of the FRIPON science project