Sialylated N-glycans mediate monocyte uptake of extracellular vesicles secreted from Plasmodium falciparum-infected red blood cells

Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum (Pf) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf-derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf-infected RBCs carry significantly higher sialylated complex N-glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N-glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N-glycans to mediate EV uptake by the human immune system cells

Antibiotiques chez le patient insuffisant rénal : actualisation des adaptations posologiques à la pratique clinique en infectiologie

Antibiotic prescription in chronic kidney disease patients poses a twofold problem. The appropriate use of antibacterial agents is essential to ensure efficacy and to prevent the emergence of resistance, and dosages should be adapted to the renal function to prevent adverse effects. SiteGPR is a French website for health professionals to help with prescriptions to chronic kidney disease patients. A working group of infectious disease specialists and nephrology pharmacists reviewed the indications, dosing regimens, administration modalities, and dose adjustments of antibiotics marketed in France for patients with renal failure. Data available on the SiteGPR website and detailed in the present article aims to provide an evidence-based update of infectious disease recommendations to health professionals managing patients with chronic kidney disease

Eye movements reveal learning and information-seeking in attentional template acquisition

Visual attention serves to select relevant visual information. However, observers often first need to find out what is relevant. Little is known about this information-seeking process and how it affects attention. We employed a cued visual search task in combination with eye tracking to investigate which oculomotor measures reflect the acquisition of information for a subsequent task. A cue indicated as to which target to look for in a following search display. Cue-target combinations were repeated several times, enabling learning of the target. We found that reductions in cue fixation times and saccade size provided stable indices of learning. Despite the learning, participants continued to attend to repeated cues. Several factors contribute to people attending to information they already know: First, the information value provided by the cue continues to drive attention. Second, even in the absence of information value, attention continues to be directed to cue features that previously signalled relevant information. Third, the decision to attend to a known cue depends on cognitive effort. We propose that this combination of information value, previous relevance, and effort is best captured within an information-seeking framework, and that oculomotor parameters provide a useful proxy for uncovering these factors and their interactions

Tighter MIP models for Barge Container Ship Routing

This paper addresses the problem of optimal planning of a liner service for a barge container shipping company. Given estimated weekly demands between pairs of ports, our goal is to determine the subset of ports to be called and the amount of containers to be shipped between each pair of ports, so as to maximize the profit of the shipping company. In order to save possible leasing or storage costs of empty containers at the respective ports, our approach takes into account the repositioning of empty containers. The line has to follow the outbound–inbound principle, starting from the port at the river mouth. We propose a novel integrated approach in which the shipping company can simultaneously optimize the route (along with repositioning of empty containers), the choice of the final port, length of the turnaround time and the size of its fleet. To solve this problem, a new mixed integer programming model is proposed. On the publicly available set of benchmark instances for barge container routing, we demonstrate that this model provides very tight dual bounds and significantly outperforms the existing approaches from the literature for splittable demands. We also show how to further improve this model by projecting out arc variables for modeling the shipping of empty containers. Our numerical study indicates that the latter model improves the computing times for the challenging case of unsplittable demands. We also study the impact of the turnaround time optimization on the total profit of the company

Le site atelier du Grand Morin

Orateur invité.info:eu-repo/semantics/nonPublishe

Extracellular Cleavage of Cadherin-11 by ADAM Metalloproteases Is Essential for Xenopus Cranial Neural Crest Cell Migration

Cell adhesion molecules such as cadherins alternate their expression throughout cranial neural crest (CNC) development, yet our understanding of the role of these molecules during CNC migration remains incomplete. The “mesenchymal” cadherin-11 is expressed in the CNC during migration yet prevents migration when overexpressed in the embryo, suggesting that a defined level of cadherin-11–mediated cell adhesion is required for migration. Here we show that members of the meltrin subfamily of ADAM metalloproteases cleave the extracellular domain of cadherin-11 during CNC migration. We show that a fragment corresponding to the putative shed form of cadherin-11 retains biological activity by promoting CNC migration in vivo, in a non-cell–autonomous manner. Additionally, cleavage of cadherin-11 does not affect binding to β-catenin and downstream signaling events. We propose that ADAM cleavage of cadherin-11 promotes migration by modifying its ability to support cell–cell adhesion while maintaining the membrane-bound pool of β-catenin associated with the cadherin-11 cytoplasmic domain