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International audience; Dietary synthetic emulsifiers have recently been shown to promote metabolic syndrome and alter the gut microbiota. The effects of natural emulsifiers, such as vegetable lecithin, remain poorly described. Our objective was to evaluate, in mice, the impact of soy and rapeseed lecithin (SL and RL), both rich in essential α-linolenic acid (ALA), on HFD-induced adiposity, inflammation and the gut microbiota. For 13 weeks, male Swiss mice (n=72) were fed a Chow diet, a HFD devoid of ALA, or different ALA-enriched HFD (identical ALA content: 4.7%) containing 0% lecithin (HF-0L), a nutritional dose (10%) of SL or RL (HF-10SL, HF-10RL) or a supplemental dose of RL (20%; HF-20RL). Biometric parameters and the epididymal adipose tissue (EAT) were analysed; hepatic lipid composition was determined by GC-FID, gene expression by RT-qPCR, and faecal microbiota composition by 16S sequencing. In all groups fed ALA-rich diets, the proportion of ALA in both liver triacylglycerols and phospholipids was increased, but the vectorisation of ALA as lecithin did not further increase its hepatic bioavailability, compared to an oil (HF-0L). The incorporation of 10% SL, but not RL, in ALA-enriched HFD significantly increased weight gain (p

International audience

International audience; BACKGROUND: CKD is associated with increased oxidative stress that correlates with occurrence of cardiovascular events. Modifications induced by increased oxidative stress particularly affect circulating lipoproteins such as HDL that exhibit antiatheromatous and antithrombotic properties in vitro. METHODS: To explore the specific role of oxidative modifications of HDL in CKD and their effect on the platelet-targeting antiaggregant properties of HDL, we used a CKD (5/6 nephrectomy) rabbit model. For ex vivo assessment of the antiaggregant properties of HDL, we collected blood samples from 15 healthy volunteers, 25 patients on hemodialysis, and 20 on peritoneal dialysis. We analyzed malondialdehyde, 4-hydroxynonenal (HNE), and 4-hydroxy-2-hexenal protein adduct levels. Platelet aggregation and activation were assessed by aggregometry, thromboxane B2 assay, or FACS. We modified HDL from controls by incubating it overnight at 37°C with 100 µM of HNE. RESULTS: HDL from CKD rabbits and patients on hemodialysis had HNE adducts. The percentage of platelet aggregation or activation induced by collagen was significantly higher when platelets were incubated with HDL from CKD rabbit and hemodialysis groups than with HDL from the control group. In both rabbits and humans, platelet aggregation and activation were significantly higher in the presence of HNE-modified HDL than with HDL from their respective controls. Incubation of platelets with a blocking antibody directed against CD36 or with a pharmacologic inhibitor of SRC kinases restored the antiaggregative phenotype in the presence of HDL from CKD rabbits, patients on hemodialysis and peritoneal dialysis, and HNE-modified HDL. CONCLUSIONS: HDL from CKD rabbits and patients on hemodialysis exhibited an impaired ability to inhibit platelet aggregation, suggesting that altered HDL properties may contribute to the increased cardiovascular risk in this population.

International audience; Optimum amplification in surface enhanced Raman scattering (SERS) from individual nanoantennas is expected when the excitation is slightly blue-shifted with respect to the localized surface plasmon resonance (LSPR), so that the LSPR peak falls in the middle between the laser and the Stokes Raman emission. Recent experiments have shown when moving the excitation from the visible to the near-infrared that this rule of thumb is no more valid. The excitation has to be red-shifted with respect to the LSPR peak, up to 80 nm, to obtain highest SERS. Such discrepancy is usually attributed to a near-field (NF) to far-field (FF) spectral shift. Here we critically discuss this hypothesis for the case of gold nanocylinders. By combining multiwavelength-excitation SERS experiments with numerical calculations, we show that the red-shift of the excitation energy does not originate from a spectral shift between the extinction (FF) and the near-field distribution (NF), which is found to be not larger than 10 nm. Rather, it can be accounted for by looking at the peculiar spectral dependence of the near-field intensity on the cylinders diameter, characterized by an initial increase, up to 180 nm diameter, followed by a decrease and a pronounced skewness.

This thesis deals with radiation measurement. More particularly it concerns gamma ray spectroscopy for low level wastes. It consists in modeling the full efficiency calibration coefficient of the measured scene. It is essential to quantify the activity/mass of the measured object. This thesis is split in two parts. The first part consists in HPGE detector characterization. The HPGe characterization is available in space and energy range. The second part consists in determining the full efficiency calibration coefficient of the measured scene without operator hypothesis. First work is the development of an automated methodology to obtain detector characterization. HPGe detector characterization has similar performance to the real detector with a control of the discrepancy between them. HPGe detector characterization is achieved without expert, on field condition with a convergence criterion lower than 5%. Second work is a feasibility study for activity quantification of complex waste package without operator hypothesis. It will be possible by using metamodeling. Metamodeling generate quickly a set of configurations of the calibration coefficient with regard to input data. Configurations are sorted out according some criterions.; Cette thèse s’inscrit dans le domaine de la métrologie des rayonnements ionisants. Plus particulièrement dans la mesure par spectrométrie gamma des actinides contenus dans les colis et fûts de déchets. Le travail mené consiste à modéliser le coefficient d’étalonnage de la scène de mesure, élément indispensable à la quantification de l’activité (ou à la masse de radionucléides recherchée) de l’objet mesuré. La thèse comporte deux parties. La première partie traite de la modélisation de la réponse numérique spatiale et énergétique équivalente à la réponse réelle du détecteur, étape indispensable pour remonter à l’activité de l’objet. La seconde partie traite de la quantification du coefficient d’étalonnage de la scène de mesure sans hypothèse de l’opérateur. Le premier travail de thèse est la mise au point d’une méthodologie quasi automatisée d’obtention d’une réponse numérique équivalente à la réponse réelle du détecteur à un critère de convergence fixé. La réponse numérique est obtenue, sans expert, en conditions de terrain avec un critère de convergence inférieur à 5%. Le second travail est une étude de faisabilité sur la quantification de l’activité pour des colis complexes sans hypothèse de l’opérateur grâce à l’utilisation de métamodèles. Les métamodèles permettent de générer rapidement un ensemble de configurations du coefficient d’étalonnage par rapport aux données d’entrée. Les configurations sont ensuite triées pour sélectionner le coefficient d'étalonnage correspondant à la scène de mesure.

International audience; There is evidence that high-density lipoproteins (HDLs) may regulate platelet function, but disparate results exist regarding the effects of oxidized HDLs on platelets. The objective of our study was to determine the role of in vivo oxidized HDLs on platelet aggregation. Platelet aggregation and redox status were investigated in 5 patients with abetalipoproteinemia (ABLP) or homozygous hypobetalipoproteinemia, two rare metabolic diseases characterized by the absence of apolipoprotein B-containing lipoproteins, compared to 5 control subjects. Platelets isolated from plasma of patients with ABLP aggregated 4 to 10 times more than control platelets, depending on the agonist. By contrast, no differences in the extent of platelet aggregation were observed between ABLP platelet-rich plasma (PRP) and control PRP, suggesting the presence of a protective factor in ABLP plasma. ABLP HDLs inhibited agonist-induced platelet aggregation by binding to SR-BI, while control HDLs had no effect. On the other hand, lipoprotein-deficient plasma from patients with ABLP did not inhibit platelet aggregation. Severe oxidative stress was evidenced in patients with ABLP. Compared to control HDLs, ABLP HDLs showed a 40% decrease of α-tocopherol and an 11-fold increased malondialdehyde concentration. These results demonstrate that in vivo oxidized HDLs do not lose their antiaggregatory properties despite oxidation.-Calzada, C., Véricel, E., Colas, R., Guillot, N., El Khoury, G., Drai, J., Sassolas, A., Peretti, N., Ponsin, G., Lagarde, M., Moulin, P. Inhibitory effects of in vivo oxidized high-density lipoproteins on platelet aggregation: evidence from patients with abetalipoproteinemia.

The work presented in this manuscript focuses on the different possibilities leading to the optimization of the signal of localized surface plasmon resonance (LSPR) based nanosensors and fabricated by some techniques enabling a precise control of the geometry of metallic nanostructures. Nanosensors based on LSPR and surface enhanced Raman scattering (SERS) have been especially studied. The first part of this manuscript reminds the key parameters leading to the optimization of the signal of such nanosensors, i.e., the nanostructures material, the size and the shape of the nanostructures, the surrounding medium, the incident electric field polarization, the gap between the nanoparticles and the higher order LSPR. The second part is focused on SERS nanosensors by exposing the optimization principle and possibilities of the signal in the case of arrays of gold nanoparticles. Finally, the last part is devoted to the observation of the shape of the local electromagnetic field around the nanoparticles (amplitude and decay length) by the study of the near-field coupling between gold nanoparticles of different shapes.; Le travail présenté dans ce manuscrit a permis de mettre en lumière les différentes possibilités menant à l'optimisation de l'efficacité de capteurs basés sur la résonance de plasmons de surface localisé (RPSL) et fabriqués par des techniques contrôlant précisément la géométrie des nanostructures métalliques. L'accent a été mis plus particulièrement sur les capteurs par RPSL et sur les capteurs par diffusion Raman exaltée de surface (DRES). Le premier chapitre a rappelé les paramètres clés menant à l'optimisation recherchée, i.e., la nature du métal, la taille de la nanoantenne, sa forme, son milieu environnant, la polarisation du champ électrique incident, la séparation entre les nanoparticules et la présence d'ordres supérieurs. Le second chapitre s'est davantage centré sur les capteurs DRES en exposant le principe et les possibilités d'optimisation de leur signal dans le cas de rangées de nanostructures d'or. Le chapitre 3 s'est consacré à l'observation de l'allure du champ électromagnétique local (amplitude et longueur de décroissance) par l'étude du couplage champ proche entre les nanoparticules d'or.

The work presented in this manuscript focuses on the different possibilities leading to the optimization of the signal of localized surface plasmon resonance (LSPR) based nanosensors and fabricated by some techniques enabling a precise control of the geometry of metallic nanostructures. Nanosensors based on LSPR and surface enhanced Raman scattering (SERS) have been especially studied. The first part of this manuscript reminds the key parameters leading to the optimization of the signal of such nanosensors, i.e., the nanostructures material, the size and the shape of the nanostructures, the surrounding medium, the incident electric field polarization, the gap between the nanoparticles and the higher order LSPR. The second part is focused on SERS nanosensors by exposing the optimization principle and possibilities of the signal in the case of arrays of gold nanoparticles. Finally, the last part is devoted to the observation of the shape of the local electromagnetic field around the nanoparticles (amplitude and decay length) by the study of the near-field coupling between gold nanoparticles of different shapes.; Le travail présenté dans ce manuscrit a permis de mettre en lumière les différentes possibilités menant à l'optimisation de l'efficacité de capteurs basés sur la résonance de plasmons de surface localisé (RPSL) et fabriqués par des techniques contrôlant précisément la géométrie des nanostructures métalliques. L'accent a été mis plus particulièrement sur les capteurs par RPSL et sur les capteurs par diffusion Raman exaltée de surface (DRES). Le premier chapitre a rappelé les paramètres clés menant à l'optimisation recherchée, i.e., la nature du métal, la taille de la nanoantenne, sa forme, son milieu environnant, la polarisation du champ électrique incident, la séparation entre les nanoparticules et la présence d'ordres supérieurs. Le second chapitre s'est davantage centré sur les capteurs DRES en exposant le principe et les possibilités d'optimisation de leur signal dans le cas de rangées de nanostructures d'or. Le chapitre 3 s'est consacré à l'observation de l'allure du champ électromagnétique local (amplitude et longueur de décroissance) par l'étude du couplage champ proche entre les nanoparticules d'or.

Docosahexaenoic acid (DHA) is a n-3 polyunsaturated fatty acid known for its protective effects against cardiovascular disease. However high doses of DHA may nevertheless counteract its beneficial effects owing to the presence of six double bounds in the fatty acyl chain. Our first objective was to determine the effects of increasing DHA consumption by healthy men on both platelet function and oxidative stress. The second objective was to analyse the effects of DHA on gene expression of enzymes controlling redox status and prostanoid formation, using human megakaryocytes MEG-01 as a model of platelet precursors. Our results show that ingestion of low doses of DHA (400 to 1600 mg) decreases the platelet aggregation response. A lower dose shows an anti-oxidant action. This result is reinforced by the transcriptional effects obtained on MEG-01 cells. Our results could explain the beneficial influence of n-3 polyunsaturated fatty acids at low doses on cardiovascular diseases., L'acide docosahexaénoïque (DHA) est un acide gras polyinsaturé n-3 connu pour son rôle protecteur contre les maladies cardiovasculaires. Cependant une utilisation importante de DHA peut néanmoins contrebalancer les effets bénéfiques par la formation de produits d'oxydation dommageables. Notre travail a été de déterminer les effets de l'ingestion de doses croissantes de DHA chez l'Homme sain sur les fonctions, le métabolisme et l'état redox des plaquettes sanguines et d'analyser son action sur un modèle de précurseurs des plaquettes, la lignée humaine de mégacaryocytes MEG-01. Nos résultats montrent que l'ingestion de faibles doses de DHA (400 à 1600 mg) diminue la réponse plaquettaire. Une dose plus faible montre un effet anti-oxydant. Ceci est conforté par les effets transcriptionnels obtenus sur les cellules MEG-01. Ceci pourrait contribuer à l'explication de l'influence bénéfique des acides gras polyinsaturés n-3 à faible dose sur les maladies cardio-vasculaires.