- Neutrino Physics Research
- Receptor Mechanisms and Signaling
- Astrophysics and Cosmic Phenomena
- Dark Matter and Cosmic Phenomena
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Adenosine and Purinergic Signaling
- Neuropeptides and Animal Physiology
- Photoreceptor and optogenetics research
- Particle physics theoretical and experimental studies
- Musicology and Musical Analysis
- Chemical Synthesis and Analysis
- Renaissance and Early Modern Studies
- Gamma-ray bursts and supernovae
- Pharmacological Receptor Mechanisms and Effects
- Body Composition Measurement Techniques
- Birth, Development, and Health
- Glioma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Neuroscience and Neuropharmacology Research
- Gestational Diabetes Research and Management
- Neurotransmitter Receptor Influence on Behavior
- Radiation Detection and Scintillator Technologies
- Lipid Membrane Structure and Behavior
- Electrical and Bioimpedance Tomography
Aix-Marseille Université
2024-2025
Centre de physique des particules de Marseille
2024-2025
Centre National de la Recherche Scientifique
2024-2025
University of Pavia
2016-2023
Università Cattolica del Sacro Cuore
2022-2023
Agostino Gemelli University Polyclinic
2022
Istituti di Ricovero e Cura a Carattere Scientifico
2022
Università Campus Bio-Medico
2018
MRC Laboratory of Molecular Biology
2008-2016
Medical Research Council
2008
There are approximately 350 non-odorant G protein-coupled receptors (GPCRs) encoded by the human genome, many of which predicted to be potential therapeutic targets, but there only two structures available represent whole family. We hypothesized that improving detergent stability these and simultaneously locking them into one preferred conformation will greatly improve chances crystallization. developed a generic strategy for isolation detergent-solubilized thermostable mutants GPCR,...
Structural studies on mammalian integral membrane proteins have long been hampered by their instability in detergent. This is particularly true for the agonist conformation of G protein-coupled receptors (GPCRs), where it thought that movement helices occurs upon binding results a looser and less stable packing protein. Here, we show mutagenesis coupled to specific selection strategy can be used stabilize antagonist conformations adenosine A 2a receptor. Of 27 mutations identified improve...
Structural studies on G-protein-coupled receptors have been hampered for many years by their instability in detergent solution and the number of potential conformations that can adopt. Recently, structures β1 β2 adrenergic adenosine A2a receptor were determined antagonist-bound state, a conformation is thought to be more stable than agonist-bound state. In contrast these receptors, neurotensin (NT) NTS1 much less solution. We therefore used systematic mutational approach coupled with...
Significance Reactive oxygen species (ROS) are far from being only an inevitable byproduct of respiration. They instead actively generated by NADPH oxidases (NOXs), a family highly regulated enzymes that underpin complex functions in the control cell proliferation and antibacterial defense. By investigating individual catalytic domains, we elucidate core NOX 3D structure. An array cofactors is spatially organized to transfer reducing electrons intracellular milieu ROS-generating site,...
NADPH-oxidases (NOXs) purposefully produce reactive-oxygen-species (ROS) and are found in most kingdoms of life. The seven human NOXs each characterized by a specific expression profile fine regulation to spatio-temporally tune ROS concentration cells tissues. One the best known roles for is host protection against pathogens but themselves important second messengers involved tissue regeneration modulation pathways that induce sustain cell proliferation. As such, attractive pharmacological...
The serotonin transporter (SERT) is an integral membrane protein responsible for the clearance of from synaptic cleft following release neurotransmitter. SERT plays a prominent role in regulation serotoninergic neurotransmission and molecular target multiple antidepressants as well substances abuse. Here we show that associates with lipid rafts both heterologous expression systems rat brain inclusion into microdomains critical uptake activity. present subpopulation rafts, which soluble...
The serotonin transporter (SERT) plays a critical role in the maintenance of normal neurotransmission by [5-hydroxytryptamine (5-HT)]. Recent evidence suggests that SERT and other neurotransmitter transporters are tightly regulated. Activation protein kinase C results decrease SERT-mediated 5-HT uptake, which is due to an internalization transporter. However, date little known about mechanism proteins involved down-regulation One candidate SERT-regulatory SNARE (soluble...
It is now accepted that reactive oxygen species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS‐controlled production played by NADPH oxidases (NOXs), a group seven membrane‐bound enzymes (NOX1‐5 DUOX1‐2) whose unique function to produce ROS. Here, we describe regulation NOX5, widespread family member present cyanobacteria, protists, plants, fungi, animal kingdom. We show calmodulin‐like...
KM3NeT is a Cherenkov-light based neutrino telescope located in the Mediterranean Sea, comprising two detectors ARCA (Sicily, It) and ORCA (Var, Fr). Currently at ∼15% of its total deployment, with completion expected by 2029, it has an energy sensitivity ranging from MeV to PeV. The infrastructure well suited detect astrophysical neutrinos thanks wide field view high duty cycle. In context multi-messenger astronomy, aims quickly reconstructing data identify candidates, both search for...
GPCR subtypes possess distinct functional and pharmacological profiles, thus development of subtype-selective ligands has immense therapeutic potential. This is especially the case for angiotensin receptor AT1R AT2R, where a negative control been described AT2R activation highlighted as an important cancer drug target. We describe strategy to fine-tune ligand selectivity AT2R/AT1R through electronic aromatic-prolyl interactions. Through this high affinity (Ki = 3 nM) agonist analogue that...
This study compares the incidence of new-onset symptoms within 24 hours after enhanced magnetic resonance imaging (eMRI) with intravenous administration gadodiamide or gadoterate meglumine compared a control group undergoing unenhanced MRI (uMRI).A prospective cohort (n = 1088 patients) was designed to assess meglumine. The participants underwent structured questionnaire by phone call before and scan check for that were not present scan. included list active questions aimed test prevalence...
Abstract Background Thyroid autoantibodies (ThyAb) and subclinical hypothyroidism occur more frequently in pregnant women with insulin-dependent diabetes mellitus than healthy women. Few studies have investigated the presence of ThyAb gestational (GDM), no significant association between pregnancy thyroid function has been reported. Objective To assess biochemical profile estimate prevalence a group at increased risk GDM due to family personal factors, investigate relationship positive...
The multi-disciplinary tumor board (MTB) is essential to quality cancer care and currently recommended offer the best personalized clinical approach, but little has been published regarding MTBs in neuro-oncology (nMTBs). aim of present paper describe our nMTB, evaluate its impact on management decisions, assess role neuroradiologists.The retrospective evaluation cases discussed at nMTB from March 2017 2020. From electronic records, we extracted epidemiological, other specific data nMTB....
EROS (essential for reactive oxygen species) protein is indispensable expression of gp91 phox , the catalytic core phagocyte NADPH oxidase. deficiency in humans a novel cause severe immunodeficiency, chronic granulomatous disease, but its mechanism action was unknown until now. We elucidate role EROS, showing it acts at earliest stages maturation. It binds immature 58 kDa directly, preventing degradation and allowing glycosylation via oligosaccharyltransferase machinery incorporation heme...
Precise synapse formation is essential for normal functioning of the nervous system. Retinal photoreceptors establish selective contacts with bipolar cells, aligning neurotransmitter release apparatus postsynaptic signaling cascades. This involves transsynaptic assembly between dystroglycan-dystrophin complex on photoreceptor and orphan receptor GPR179 cell, which mediated by extracellular matrix protein pikachurin (also known as EGFLAM). plays a critical role in synaptic organization signal...
NADPH oxidases (NOXs) are membrane enzymes whose sole function is the generation of reactive oxygen species. Humans have seven NOX isoenzymes that feature distinct functions in immune response and cell signaling but share same catalytic core comprising a FAD-binding dehydrogenase domain heme-binding transmembrane domain. We previously described mutation stabilizes prokaryotic homolog human NOX5. The thermostable mutant exhibited large 19 °C increase apparent melting temperature (app Tm) much...