Zwitterionic polymer ligands: An ideal surface coating to totally suppress protein-nanoparticle corona formation?

International audienceIn the last few years, zwitterionic polymers have been developed as antifouling surface coatings. However, their ability to completely suppress protein adsorption at the surface of nanoparticles in complex biological media remains undemonstrated. Here we investigate the formation of hard (irreversible) and soft (reversible) protein corona around model nanoparticles (NPs) coated with sulfobetaine (SB), phosphorylcholine (PC) and carboxybetaine (CB) polymer ligands in model albumin solutions and in whole serum. We show for the first time a complete absence of protein corona around SB-coated NPs, while PC-and CB-coated NPs undergo reversible adsorption or partial aggregation. These dramatic differences cannot be described by naïve hard/soft acid/base electrostatic interactions. Single NP tracking in the cytoplasm of live cells corroborate these in vitro observations. Finally, while modification of SB polymers with additional charged groups lead to consequent protein adsorption, addition of small neutral targeting moieties preserves antifouling and enable efficient intracellular targeting

Beta-Carotene Reduces Body Adiposity of Mice via BCMO1

Evidence from cell culture studies indicates that β-carotene-(BC)-derived apocarotenoid signaling molecules can modulate the activities of nuclear receptors that regulate many aspects of adipocyte physiology. Two BC metabolizing enzymes, the BC-15,15′-oxygenase (Bcmo1) and the BC-9′,10′-oxygenase (Bcdo2) are expressed in adipocytes. Bcmo1 catalyzes the conversion of BC into retinaldehyde and Bcdo2 into β-10′-apocarotenal and β-ionone. Here we analyzed the impact of BC on body adiposity of mice. To genetically dissect the roles of Bcmo1 and Bcdo2 in this process, we used wild-type and Bcmo1-/- mice for this study. In wild-type mice, BC was converted into retinoids. In contrast, Bcmo1-/- mice showed increased expression of Bcdo2 in adipocytes and β-10′-apocarotenol accumulated as the major BC derivative. In wild-type mice, BC significantly reduced body adiposity (by 28%), leptinemia and adipocyte size. Genome wide microarray analysis of inguinal white adipose tissue revealed a generalized decrease of mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) target genes. Consistently, the expression of this key transcription factor for lipogenesis was significantly reduced both on the mRNA and protein levels. Despite β-10′-apocarotenoid production, this effect of BC was absent in Bcmo1-/- mice, demonstrating that it was dependent on the Bcmo1-mediated production of retinoids. Our study evidences an important role of BC for the control of body adiposity in mice and identifies Bcmo1 as critical molecular player for the regulation of PPARγ activity in adipocyte

Aujourd'hui le Moyen Age, archéologie et vie quotidienne en France Méridionale

[catalogue d'exposition], 1981-1983, Sénanque, Marseille, Arles, Toulon, Perpignan, Montpellier, Nice, GapInternational audienceCe catalogue d’exposition itinérante, fait la synthèse des principaux travaux du Laboratoire d’Archéologie Médiévale Méditerranéenne d’Aix-en-Provence (URA 6 du CRA CNRS) en 1981 réunis par l’équipe de Gabrielle Démians d’Archimbaud. L’habitat, les gestes de la vie quotidienne, le commerce et l’artisanat sont illustrés par les fouilles effectuées dans le Midi de la France, par de nombreux objets, en céramique, verre, pierre, os et métal ainsi que par les sources écrites, et les analyses de laboratoire, innovantes à cette époque

Small-scale commodity frontiers:The bioeconomy value chain of castor oil in Madagascar

The European Commission defines the bioeconomy as a “transition economy which seeks to increase efficiency, optimize use and decrease environmental impact through the reduction of waste and greenhouse gas emissions.” However, attempts to substitute or control nature through efficient bio-based technology have not lived up to expectations and much of the industry still relies on globally sourced biomass to drive the bioeconomy. This article examines the social and political economic relations surrounding small-scale production of the feedstock castor oil plant (castor, Ricinus communis) in the deep south of Madagascar. Theorizing the bioeconomy through the lens of a “small-scale commodity frontier,” it builds from recent injunctions by Jason Moore to show how the appropriation of cheap nature (including paid and unpaid labour) is both historically and geographically co-produced. The castor value chain is held up as a way to transform regional economies and a “silver bullet” to alleviate poverty and address food security in some of the most economically marginal areas of Madagascar. We adopt a regional and feminist political ecology approach to illustrate what is behind this discursive cloak of “development imaginaries,” making visible the social relations surrounding castor production and demonstrating the historical marginalization involved in producing the frontier

PLoS Pathog

Cytomegalovirus (CMV) is a leading infectious cause of morbidity in immune-compromised patients. γδ T cells have been involved in the response to CMV but their role in protection has not been firmly established and their dependency on other lymphocytes has not been addressed. Using C57BL/6 αβ and/or γδ T cell-deficient mice, we here show that γδ T cells are as competent as αβ T cells to protect mice from CMV-induced death. γδ T cell-mediated protection involved control of viral load and prevented organ damage. γδ T cell recovery by bone marrow transplant or adoptive transfer experiments rescued CD3ε-/- mice from CMV-induced death confirming the protective antiviral role of γδ T cells. As observed in humans, different γδ T cell subsets were induced upon CMV challenge, which differentiated into effector memory cells. This response was observed in the liver and lungs and implicated both CD27+ and CD27- γδ T cells. NK cells were the largely preponderant producers of IFNγ and cytotoxic granules throughout the infection, suggesting that the protective role of γδ T cells did not principally rely on either of these two functions. Finally, γδ T cells were strikingly sufficient to fully protect Rag-/-γc-/- mice from death, demonstrating that they can act in the absence of B and NK cells. Altogether our results uncover an autonomous protective antiviral function of γδ T cells, and open new perspectives for the characterization of a non classical mode of action which should foster the design of new γδ T cell based therapies, especially useful in αβ T cell compromised patients

Mono-organotin oxo-clusters

International audienc

Etude par RMN DOSY de l échange de ligands à la surface de nanoparticules d or en suspension

Les nanoparticules d'oxydes, de semi conducteurs ou de métaux représentent une part importante de la recherche dans le domaine des nanotechnologies. Leurs propriétés particulières en font des objets intéressants pour différents domaines tels que la catalyse, les biotechnologies, l optique ou l électronique. Cependant, si leurs propriétés résultent majoritairement de la taille nanométrique de leur cœur inorganique, ces nanoparticules comprennent généralement une couronne de ligands organiques qui vont contrôler la taille et la morphologie lors de la synthèse et gérer la stabilité des suspensions. Ces ligands de surface jouent également un rôle primordial au niveau de la fonctionnalisation qui est un prérequis pour un grand nombre d'applications. Les nanoparticules d'or, connues depuis de nombreuses années, sont un exemple représentatif de nanoparticules stabilisées par une couronne de molécules organiques telles que des thiols, des amines ou des phosphines. En conséquence, une bonne connaissance de la chimie de surface des nanoparticules ainsi qu un bon contrôle du greffage ou de l échange des ligands de surface est cruciale pour leur utilisation. Cependant, mesurer l affinité d une molécule organique pour une nanoparticule en suspension est loin d'être une tâche simple, surtout quand les ligands sont impliqués dans un équilibre entre une forme libre et une forme liée. Dans ce contexte, la RMN DOSY1 se présente comme un outil de caractérisation structurale et dynamique en parfaite complémentarité avec la diffusion de la lumière, la microscopie électronique en transmission et la chromatographie. La DOSY offre l'avantage d'être une méthode d'analyse bien adaptée pour distinguer, en suspension et sans séparation physique, les ligands liés à la surface des nanoparticules des ligands libres en solution, sur la base d'une différence de coefficient de diffusion due à la différence de taille entre les nanoparticules et les ligands. Cette technique a été mise en œuvre pour l étude de suspensions de nanoparticules d or stabilisées par différents types de ligands (thiols, phosphines, citrates, amines),2-5 permettant de quantifier les fractions libres et liées. Elle a également permis de suivre, in situ, les réactions d échange des ligands avec d'autres de nature identique ou différente et d évaluer, ainsi, leur affinité pour la surface des nanoparticules d or.Gold nanoparticles (NPs) have gained great interest over the past two decades due to their unique physical and chemical properties and their promising applications in many fields such as catalysis, optoelectronics, biology and medicine. These NPs are often capped by a shell of organic ligands in order to control the nucleation and growth steps during synthesis. Moreover, these ligands can afterwards be substituted by other ones to change the properties, such as hydrophobicity, biocompatibility, solubility and chemical reactivity, of the NPs. Therefore, controlling the composition of the organic layer on the NP surface as well as a fine characterisation of the interfacial affinity is very important. Unfortunately, measuring this affinity is far from a simple task, especially when the ligands are involved in dynamic exchange processes between a free and a grafted form. NMR spectroscopy has already been used to characterize molecules grafted on NPs and especially DOSY (Diffusion Ordered Spectroscopy) NMR, provides a powerful and versatile tool, enabling one to measure diffusion coefficients and to differentiate free and bound molecules according to their mobility without need for a physical separation step5. A variety of preparation methods and four types of capping agents1,2,3,4a-b (thiols, amines, phosphines, and citrate) have been explored to prepare functionalized gold NPs. DOSY NMR has been used to quantify free and grafted molecules, to characterize the interface of NPs and particularly to investigate the exchange mechanisms of bound ligands with several other types of molecules and, as a result, to evaluate the affinity, estimated through thermodynamic parameters.PARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Design of hybrid organic-inorganic materials synthesized via sol-gel chemistry

International audienc

Structure du bis(2-propanol)-bis-μ-(2-propanolato)-hexakis(2-propanolato)dicérium(IV)

International audienc