Internalization pathways into cancer cells of gadolinium-based radiosensitizing nanoparticles

International audienceOver the last few decades, nanoparticles have been studied in theranostic field with the objective of exhibiting a long circulation time through the body coupled to major accumulation in tumor tissues, rapid elimination, therapeutic potential and contrast properties. In this context, we developed sub-5 nm gadolinium-based nanoparticles that possess in vitro efficient radiosensitizing effects at moderate concentration when incubated with head and neck squamous cell carcinoma cells (SQ20B). Two main cellular internalization mechanisms were evidenced and quantified: passive diffusion and macropinocytosis. Whereas the amount of particles internalized by passive diffusion is not sufficient to inducein vitro a significant radiosensitizing effect, the cellular uptake by macropinocytosis leads to a successful radiotherapy in a limited range of particles incubation concentration. Macropinocytosis processes in two steps: formation of agglomerates at vicinity of the cell followed by their collect via the lamellipodia (i.e. the "arms") of the cell. The first step is strongly dependent on the physicochemical characteristics of the particles, especially their zeta potential that determines the size of the agglomerates and their distance from the cell. These results should permit to control the quantity of particles internalized in the cell cytoplasm, promising ambitious opportunities towards a particle-assisted radiotherapy using lower radiation doses

Le retour d'expérience sur la gestion d'un événement d'ampleur, un retour d'expérience singulier : l'exemple de la gestion des inondations de mai-juin 2016 par le SDIS 77

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Le retour d'expérience sur la gestion d'un événement d'ampleur, un retour d'expérience singulier : l'exemple de la gestion des inondations de mai-juin 2016 par le SDIS 77

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Measles Virus-Imposed Remodeling of the Autophagy Machinery Determines the Outcome of Bacterial Coinfection

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Direct antiviral properties of TLR ligands against HBV replication in immune-competent hepatocytes

Abstract Current therapies for chronic hepatitis B virus (HBV) infections are effective at decreasing the viral load in serum, but do not lead to viral eradication. Recent studies highlighted the therapeutic or “adjuvant” potential of immune-modulators. Our aim was to explore the direct anti-HBV effect of Toll-Like-Receptors (TLR) agonists in hepatocytes. HBV-infected primary human hepatocytes (PHH) or differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists. Amongst all TLR ligands tested, Pam3CSK4 (TLR1/2-ligand) and poly(I:C)-(HMW) (TLR3/MDA5-ligand) were the best at reducing all HBV parameters. No or little viral rebound was observed after treatment arrest, implying a long-lasting effect on cccDNA. We also tested Riboxxol that features improved TLR3 specificity compared to poly(I:C)-(HMW). This agonist demonstrated a potent antiviral effect in HBV-infected PHH. Whereas, poly(I:C)-(HMW) and Pam3CSK4 mainly induced the expression of classical genes from the interferon or NF-κB pathway respectively, Riboxxol had a mixed phenotype. Moreover, TLR2 and TLR3 ligands can activate hepatocytes and immune cells, as demonstrated by antiviral cytokines produced by stimulated hepatocytes and peripheral blood mononuclear cells. In conclusion, our data highlight the potential of innate immunity activation in the direct control of HBV replication in hepatocytes, and support the development of TLR-based antiviral strategies

Large-scale phenotyping of 1,000 fungal strains for the degradation of non-natural, industrial compounds

International audienceFungal biotechnology is set to play a keystone role in the emerging bioeconomy, notably to address pollution issues arising from human activities. Because they preserve biological diversity, Biological Resource Centres are considered as critical infrastructures to support the development of biotechnological solutions. Here, we report the first large-scale phenotyping of more than 1,000 fungal strains with evaluation of their growth and degradation potential towards five industrial, human-designed and recalcitrant compounds, including two synthetic dyes, two lignocellulose-derived compounds and a synthetic plastic polymer. We draw a functional map over the phylogenetic diversity of Basidiomycota and Ascomycota , to guide the selection of fungal taxa to be tested for dedicated biotechnological applications. We evidence a functional diversity at all taxonomic ranks, including between strains of a same species. Beyond demonstrating the tremendous potential of filamentous fungi, our results pave the avenue for further functional exploration to solve the ever-growing issue of ecosystems pollution

Design and characterization of a single photoelectron calibration system for the NectarCAM camera of the medium-sized telescopes of the Cherenkov Telescope Array

International audienceIn this work, we describe the optical properties of the single photoelectron (SPE) calibration system designed for NectarCAM, a camera proposed for the Medium Sized Telescopes (MST) of the Cherenkov Telescope Array (CTA). One of the goals of the SPE system, as integral part of the NectarCAM camera, consists in measuring with high accuracy the gain of its photo-detection chain. The SPE system is based on a white painted screen where light pulses are injected through a fishtail light guide from a dedicated flasher. The screen – placed 15 mm away from the focal plane – is mounted on an XY motorization that allows movements over all the camera plane. This allows in-situ measurements of the SPE spectra via a complete scan of the 1855 photo-multiplier tubes (PMTs) of NectarCAM. This calibration process will enable the reduction of the systematic uncertainties on the energy reconstruction of γ -rays coming from distant astronomical sources and detected by CTA.We discuss the design of the screen used in the calibration system and we present its optical performances in terms of light homogeneity and timing of the signal

Annuaire du Collège de France 2017-2018

La 118e édition de l’Annuaire du Collège de France reflète l’activité scientifique de l’institution pour l’année académique 2017-2018. Elle contient notamment les résumés détaillés des enseignements ainsi qu’une présentation des recherches menées par les professeurs du Collège de France, leurs laboratoires et équipes de recherche. Avec les contributions de : Philippe Aghion, Édouard Bard, Gérard Berry, Patrick Boucheron, Jean-Pierre Brun, Dominique Charpin, Anne Cheng, Jean-Louis Cohen, Françoise Combes, Antoine Compagnon, Jean Dalibard, Stanislas Dehaene, François Déroche, Bernard Derrida, Philippe Descola, Denis Duboule, Thomas Ebbesen, Edhem Eldem, Alain Fischer, Marc Fontecave, Jean-Luc Fournet, Antoine Georges, Frantz Grenet, Nicolas Grimal, Edith Heard, François Héran, Jean-Jacques Hublin, Henry Laurens, Thomas Lecuit, Alain De Libera, Pierre-Louis Lions, Stéphane Mallat, Claire Mathieu, Pierre-Michel Menger, Carlo Ossola, Christine Petit, Vinciane Pirenne-Delforge, Alain Prochiantz, Jean-Noël Robert, Barbara Romanowicz, Thomas Römer, Pierre Rosanvallon, Clément Sanchez, Philippe Sansonetti, Bénédicte Savoy, Victor Stoichita, Sanjay Subrahmanyam, Alain Supiot, Jean-Marie Tarascon, Hugues de Thé, Claudine Tiercelin, Claire Voisin

Annuaire du Collège de France 2015-2016

La 116e édition de l’Annuaire du Collège de France reflète l’activité scientifique de l’institution pour l’année académique 2015-2016. Elle contient notamment les résumés détaillés des enseignements ainsi qu’une présentation des recherches menées par les professeurs du Collège de France, leurs laboratoires et équipes de recherche