New Insights Into the Role of Cav2 Protein Family in Calcium Flux Deregulation in Fmr1-KO Neurons

Fragile X syndrome (FXS), the most common form of inherited intellectual disability (ID) and a leading cause of autism, results from the loss of expression of the Fmr1 gene which encodes the RNA-binding protein Fragile X Mental Retardation Protein (FMRP). Among the thousands mRNA targets of FMRP, numerous encode regulators of ion homeostasis. It has also been described that FMRP directly interacts with Ca2+ channels modulating their activity. Collectively these findings suggest that FMRP plays critical roles in Ca2+ homeostasis during nervous system development. We carried out a functional analysis of Ca2+ regulation using a calcium imaging approach in Fmr1-KO cultured neurons and we show that these cells display impaired steady state Ca2+ concentration and an altered entry of Ca2+ after KCl-triggered depolarization. Consistent with these data, we show that the protein product of the Cacna1a gene, the pore-forming subunit of the Cav2.1 channel, is less expressed at the plasma membrane of Fmr1-KO neurons compared to wild-type (WT). Thus, our findings point out the critical role that Cav2.1 plays in the altered Ca2+ flux in Fmr1-KO neurons, impacting Ca2+ homeostasis of these cells. Remarkably, we highlight a new phenotype of cultured Fmr1-KO neurons that can be considered a novel cellular biomarker and is amenable to small molecule screening and identification of new drugs to treat FXS

Muscarinic cholinergic receptors in pancreatic acinar carcinoma of rat

SCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

Heart rate variability in HIV patients

info:eu-repo/semantics/nonPublishe

Early alteration of sympatho-vagal balance in HIV infected patients

info:eu-repo/semantics/nonPublishe

Early alteration of QT-dynamicity in HIV-infected patients

info:eu-repo/semantics/publishe

Diet-Induced Obesity Alters the Circadian Expression of Clock Genes in Mouse Gustatory Papillae

International audienc

Helicopter engine particulate matter emissions characterization

International audienceWe will present the results of ANTARES campaign

Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.

BackgroundMalaria, an Anopheles-borne parasitic disease, remains a major global health problem causing illness and death that disproportionately affects developing countries. Despite the incidence of malaria, which remains one of the most severe infections of human populations, there is no licensed vaccine against this life-threatening disease. In this context, we decided to explore the expression of Plasmodium vaccine antigens fused to the granule bound starch synthase (GBSS), the major protein associated to the starch matrix in all starch-accumulating plants and algae such as Chlamydomonas reinhardtii.Methods and findingsWe describe the development of genetically engineered starch granules containing plasmodial vaccine candidate antigens produced in the unicellular green algae Chlamydomonas reinhardtii. We show that the C-terminal domains of proteins from the rodent Plasmodium species, Plasmodium berghei Apical Major Antigen AMA1, or Major Surface Protein MSP1 fused to the algal granule bound starch synthase (GBSS) are efficiently expressed and bound to the polysaccharide matrix. Mice were either immunized intraperitoneally with the engineered starch particles and Freund adjuvant, or fed with the engineered particles co-delivered with the mucosal adjuvant, and challenged intraperitoneally with a lethal inoculum of P. Berghei. Both experimental strategies led to a significantly reduced parasitemia with an extension of life span including complete cure for intraperitoneal delivery as assessed by negative blood thin smears. In the case of the starch bound P. falciparum GBSS-MSP1 fusion protein, the immune sera or purified immunoglobulin G of mice immunized with the corresponding starch strongly inhibited in vitro the intra-erythrocytic asexual development of the most human deadly plasmodial species.ConclusionThis novel system paves the way for the production of clinically relevant plasmodial antigens as algal starch-based particles designated herein as amylosomes, demonstrating that efficient production of edible vaccines can be genetically produced in Chlamydomonas

Electrophilic and nucleophilic gas phase reactivity of the Janus cluster-based anions [{Mo 6 Cl 8 }Cl 5 □] − (□ = lacuna)

International audienceThe lacunary monocharged anion [{Mo6Cli8}Cla5□a]− presents concomitantly a strongly electrophilic site and a nucleophilic one. This Janus character in terms of reactivity is confirmed by its gas phase reaction with [Br6Cs4K]− to form [{Mo6Cli8}Cla5Bra]2− and by its unusual self-reactivity leading to [{Mo6Cli8}Cla6]2− dianions