Transpressional tectonics and Carboniferous magmatism in the Limousin, Massif Central, France: Structural and ⁴⁰Ar/³⁹Ar investigations

New structural, microstructural, and 40Ar/39 Ar data from the NW Massif Central (France) provide additional constraints on the timing and tectonic setting of late Variscan granite magmatism. Previous studies had emphasized the role of late orogenic extension in the emplacement of granite plutons in the Limousin region. In contrast, the new data set is consistent with syntectonic emplacement of magma in a dextral simple shear active from 350 to 300 Ma in a transpressional regime. As an alternative hypothesis to late orogenic extension, we propose that magmas migrated into tensional bridges between active P shears associated with a lithospheric shear zone comparable to a pop-up structure. The Galician region, in the western end of the Ibero-Armorican tectonic arc, exhibits major left-lateral ductile shear zones which can be interpreted as conjugate structures to the Limousin and Armorican shear zones. Copyright 2007 by the American Geophysical Union

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis

The integrin α(v)β(3) plays an important role in angiogenesis. It is expressed on tumoral endothelial cells as well as on some tumor cells. RGD peptides are well-known to bind preferentially to the α(v)β(3) integrin. In this context, targeting tumor cells or tumor vasculature by RGD-based strategies is a promising approach for delivering anticancer drugs or contrast agents for cancer therapy and diagnosis. RGD-based strategies include antagonist drugs (peptidic or peptidomimetic) of the RGD sequence, RGD-conjugates, and the grafting of the RGD peptide or peptidomimetic, as targeting ligand, at the surface of nanocarriers. Although all strategies are overviewed, this review aims to particularly highlight the position of RGD-based nanoparticles in cancer therapy and imaging. This review is divided into three parts: the first one describes the context of angiogenesis, the role of the integrin α(v)β(3), and the binding of the RGD peptide to this integrin; the second one focuses on RGD-based strategies in cancer therapy; while the third one focuses on RGD-based strategies in cancer diagnosis

Design and development of polymeric nanoparticles for targeted delivery of nucleic acid-based therapeutics to tumor sites

Nucleic acids are widely used as potent therapeutics in cancer research. They can either promote gene expression by bringing a gene either not expressed or under-expressed into tumor cells (cDNA), or alternatively silence expression of genes such as oncogenes (RNAi mediators). However, before they can be efficiently translated to the clinic, this technology requires some optimization: nucleic acids and their vehicles need for instance to be protected from rapid elimination from the bloodstream (opsonization, clearance, and nuclease-mediated degradation) and the specificity of tumor addressing has to be validated. Hence a polymeric nanoparticular carrier encapsulating nucleic acids, either plasmid DNA or siRNA, was developed. Nanoparticles are composed of (1) PLGA, a well tolerated and biodegradable polymer, (2) PEG groups to avoid opsonization, (3) PEI moieties to complex nucleic acids and to enhance cytosolic delivery and (4) RGD sequence for active tumor targeting. Nanoparticles were formulated by double emulsion or water-in-oil-in-water method. Physical properties of such nanoparticles were assessed by dynamic light scattering (size and polydispersity index) and laser doppler electrophoresis (zeta potential). The efficiency of nucleic acid encapsulation into the carrier was determined by the Picogreen assay. Cytotoxicity and transfection capacity were assessed in an in vitro model of B16F10 melanoma cells. To date, various designs of nanoparticles were successfully formulated with appropriate size, surface charge and encapsulation efficiency. The PLGA nanoparticles did not show cytotoxic effects on cells and, although less efficient than PEI alone, allowed DNA delivery into tumor cells

PLGA-based nanoparticles: an overview of biomedical applications

Poly(lactic-co-glycolic acid) (PLGA) is one of the most successfully developed biodegradable polymers. Among the different polymers developed to formulate polymeric nanoparticles, PLGA has attracted considerable attention due to its attractive properties: (i) biodegradability and biocompatibility, (ii) FDA and European Medicine Agency approval in drug delivery systems for parenteral administration, (iii) well described formulations and methods of production adapted to various types of drugs e.g. hydrophilic or hydrophobic small molecules or macromolecules, (iv) protection of drug from degradation, (v) possibility of sustained release, (vi) possibility to modify surface properties to provide stealthness and/or better interaction with biological materials and (vii) possibility to target nanoparticles to specific organs or cells. This review presents why PLGA has been chosen to design nanoparticles as drug delivery systems in various biomedical applications such as vaccination, cancer, inflammation and other diseases. This review focuses on the understanding of specific characteristics exploited by PLGA-based nanoparticles to target a specific organ or tissue or specific cells

Propriétés physico-chimiques et propriétés électroniques de pérovskite 2D Ca2Nb3O10 à haute permittivité diélectrique déposée sur silicium

National audienceLes pérovskites suscitent un intérêt fondamental et appliqué considérable du fait de leur large spectre de fonctionnalités physiques, allant de propriétés diélectriques, ferroélectriques, ferromagnétiques et piézoélectriques remarquables jusqu’à la supraconductivité et la magnétorésistance colossale. L’intégration de ces matériaux en couches minces nécessite des méthodes de croissance complexes (ablation laser pulsée, épitaxie par jets moléculaires) incluant souvent un recuit post-dépôt à haute température (>600°C) favorisant la réactivité aux interfaces et la génération de défauts cristallins induits notamment par la contrainte thermique. Dans ce contexte, l’exfoliation chimique de pérovskites lamellaires de type Dion-Jacobson permet la mise en œuvre de dépôts couche par couche, homogènes sur de grandes surfaces, via une méthode de type Langmuir-Blodgett (LB) à budget thermique nul [1].Dans cette communication nous présentons une étude du transfert de monofeuillets Ca2Nb3O10 sur une surface de silicium en vue de leur intégration comme isolant à forte permittivité diélectrique (ɛr=200) [2] dans des structures MOS (metal-oxide-semiconductor). Des monocristaux de la phase Dion-Jacobson KCa2Nb3O10 ont été préparés par réaction à l’état solide à partir de précurseurs de K2CO3, Nb2O5 et CaCO3. Dans les cristaux obtenus, les ions potassium sont d’abord échangés par des protons en milieu acide. L’exfoliation chimique des nanofeuillets de Ca2Nb3O10 est ensuite obtenue en substituant aux protons des ions tétrabutylammonium massifs permettant la délamination de la structure [3]. La solution colloïdale de nanofeuillets obtenue est finalement utilisée pour des dépôts LB sur substrat de silicium présentant un oxyde natif en surface. Dans un premier temps, nous démontrons par spectroscopie de photoélectrons X (XPS) que les traitements chimiques conventionnels permettant de nettoyer la surface du silicium en microélectronique n’affectent pas les nanofeuillets de pérovskite déposés, ouvrant ainsi la voie à leur intégration sur ce substrat. Dans un second temps, nous avons étudié conjointement par XPS et microscopie à effet tunnel (STM) la stabilité thermique des nanofeuillets. Si les feuillets n’évoluent pas lors d’un recuit sous ultravide à 160°C, nous démontrons la formation de lacunes d’oxygène en surface des nanofeuillets à 400°C associée à une réduction partielle des atomes de Nb. Cet effet est parfaitement réversible par recuit à 100°C à l’air. Enfin nous avons réalisé des structures MOS Au/Ca2Nb3O10/Si et étudié leurs propriétés électroniques locales par microscopie à émission d’électrons balistiques [4]. Les mesures ponctuelles locales à la verticale d’un nanofeuillet démontrent une hauteur de barrière tunnel de 1.5 eV à l’interface Au/Ca2Nb3O10. L’étude des propriétés électriques des MOS intégrant un monofeuillet constitue la perspective naturelle de ce travail. Nous envisageons également l’intégration de ces barrières tunnel modèles (rugosité nulle) dans des jonctions tunnel magnétiques épitaxiées. [1] Yuan et al. ACS Appl. Mater. Interfaces, 7, 27473−27478, (2015).[2] M. Osada et al. ACS Nano, 4, 5225-5232, (2015).[3] F. Baudouin et al. Thin Solid Films, 693,137682 (2020).[4] S. Guézo et al. Appl. Phys. Lett. 93, 172116, (2008)

Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors

The monocarboxylate transporter MCT family member MCT1 can transport lactate into and out of tumor cells. While most oxidative cancer cells import lactate through MCT1 to fuel mitochondrial respiration, the role of MCT1 in glycolysis-derived lactate efflux remains less clear. In this study we identified a direct link between p53 function and MCT1 expression. Under hypoxic conditions, p53 loss promoted MCT1 expression and lactate export produced by elevated glycolytic flux, both in vitro and in vivo. p53 interacted directly with the MCT1 gene promoter and altered MCT1 mRNA stabilization. In hypoxic p53-/- tumor cells, NF-κB further supported expression of MCT1 to elevate its levels. Following glucose deprivation, upregulated MCT1 in p53-/- cells promoted lactate import and favored cell proliferation by fuelling mitochondrial respiration. We also found that MCT1 expression was increased in human breast tumors harboring p53 mutations and coincident features of hypoxia, with higher MCT1 levels associated with poorer clinical outcomes. Together, our findings identify MCT1 as a target for p53 repression and they suggest that MCT1 elevation in p53-deficient tumors allows them to adapt to metabolic needs by facilitating lactate export or import depending on the glucose availability

Radiation exposure of microorganisms living in radioactive mineral springs

International audienceThe TIRAMISU collaboration gathers expertise from biologists, physicists, radiochemists and geologists within the Zone-Atelier Territoires Uranifères (ZATU) in France to analyze the radiation exposure of microorganisms living in naturally radioactive mineral springs. These springs are small waterbodies that are extremely stable over geological time scales and display different physicochemical and radiological parameters compared to their surroundings. Water and sediment samples collected in 27 mineral springs of the volcanic Auvergne region (Massif Central, France) have been studied for their microbial biodiversity and their radionuclide content. Among the microorganisms present, microalgae (diatoms), widely used as environmental indicators of water quality, have shown to display an exceptional abundance of teratogenic forms in the most radioactive springs studied (radon activity up to 3700 Bq/L). The current work presents a first assessment of the dose received by the diatoms inhabiting these ecosystems. According to ERICA tool, microorganisms living in most of the sampled mineral springs were exposed to dose rates above 10 μGy/h due to the large concentration of radium in the sediments (up to 50 Bq/g). Radiological analyses of water and sediments were used as inputs to Monte Carlo simulations at micro-(GATE) and nano- (Geant4-DNA) scale in order to assess the direct and indirect damages on the diatom DNA.</jats:p

Radiation exposure of microorganisms living in radioactive mineral springs

International audienceThe TIRAMISU collaboration gathers expertise from biologists, physicists, radiochemists and geologists within the Zone-Atelier Territoires Uranifères (ZATU) in France to analyze the radiation exposure of microorganisms living in naturally radioactive mineral springs. These springs are small waterbodies that are extremely stable over geological time scales and display different physicochemical and radiological parameters compared to their surroundings. Water and sediment samples collected in 27 mineral springs of the volcanic Auvergne region (Massif Central, France) have been studied for their microbial biodiversity and their radionuclide content. Among the microorganisms present, microalgae (diatoms), widely used as environmental indicators of water quality, have shown to display an exceptional abundance of teratogenic forms in the most radioactive springs studied (radon activity up to 3700 Bq/L). The current work presents a first assessment of the dose received by the diatoms inhabiting these ecosystems. According to ERICA tool, microorganisms living in most of the sampled mineral springs were exposed to dose rates above 10 μGy/h due to the large concentration of radium in the sediments (up to 50 Bq/g). Radiological analyses of water and sediments were used as inputs to Monte Carlo simulations at micro-(GATE) and nano- (Geant4-DNA) scale in order to assess the direct and indirect damages on the diatom DNA