Programmable multimetallic linear nanoassemblies of ruthenium–DNA conjugates

A new ruthenium–DNA conjugates family was synthesized, made up of a ruthenium complex bound to one or two identical DNA strands of 14–58 nucleotides. The formation of controlled linear nanoassemblies containing one to seven ruthenium complexes is described

Gum Arabic in solution: Composition and multi-scale structures

Gum Arabic is a natural acacia tree exudate containing hyperbranched polysaccharides and proteins. Here, we perform a dual chromatographic separation together with small-angle X-ray and neutron scattering structural characterizations. We show that the different species present in Gum Arabic can not be easily classified in distinct families. They are rather build from various combinations of two building blocks that are evidenced by a mismatch between small-angle X-ray and neutron scattering. One block corresponds to hyperbranched polysaccharides, which we describe as three-dimensional multi-scale porous colloids possessing three length scales of 7, 2 and 0.7 nm. The other block corresponds to protein chains that organize as Gaussian chains in solution and are prone to aggregation. A large array of polysaccharide/protein conjugates was identified, which differs in size, hydrophobicity and amino-acid content. Still, their structure is always the juxtaposition of the two building blocks structures. Additionally, small-angle neutron scattering reveals that large-scale structures are ubiquitous in Gum Arabic solutions and originate from the self-association of both free and conjugated polypeptide chains. Despite its compositional complexity, Gum Arabic solutions thus possess a robust multi-scale structure that is mainly impacted by concentration and ionic repulsions

Formulation of Aqueous Dispersions of PEKK by a Quantitative Structure Property Relationship Approach and Application to Thermoplastic Sizing on Carbon Fiberss

The development of formulations for thermoplastic sizing on carbon fibers requires water dispersions of small polymer particles (< 20 µm). PolyEtherKetoneKetone (PEKK) is a high-performance polymer used as a matrix in Carbon Fiber Reinforced Polymers (CFRP) or as a sizing agent. To limit the formulation steps and the use of organic solvents, the sonofragmentation process can be used to deagglomerate polymers, directly in the final aqueous formulation. The sonofragmentation process is controlled by multiple parameters and, in order to identify the key parameters, a quantitative structure property relationship (QSPR) study was performed using artificial neural networks (ANN). The 40 formulations of this study were characterized with the aim of quantifying the sonofragmentation effect. Various physicochemical techniques were used: Photon Correlation Spectroscopy (PCS), destabilization velocity of the dispersions by analytical centrifugation, and scanning electron microscopy. The results obtained showed that only two parameters (mass concentration of surfactant and duration of sonication) had a notable effect on the sonofragmentation process. By controlling these two parameters, it was possible to define a design space in the stability domain of the formulations and to calculate a sonofragmentation efficiency (ϕ) for four singular zones. Image analysis showed that the sonofragmentation process was accompanied by an increase in the number of particles with Particle size (Ps) < 20 µm. In optimized aqueous formulations, the majority of particles should have Ps < 20 µm

Sustainable process for adipic acid production from cyclohexene in microemulsion

Adipic acid appears as an intermediate compound for the synthesis of polyamides and preferentially for the production of nylon-6,6 polyamide. It can be synthesized by the oxidation of cyclohexene by hydrogen peroxide in microemulsion media which has the main advantage to lead a better contact between the two phases thus increasing the yield of the reaction. The microemulsion is generated by stearyl dimethyl benzyl ammonium chloride (C18) as a surfactant avoiding the use of harmful organic solvents and phase-transfer catalysts. The reaction is performed under mild conditions (85 °C, 8 h) with sodium tungstate, - a no heavy metal catalyst - leading to the production of adipic acid in high yield (>80%). By recycling the catalyst and the surfactant, the process becomes truly green

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Nouvelle approche métabolomique appliquée à la mesure de l'exposition aux faibles doses de contaminants chimiques: incidence des pesticides et POP sur l'obésité et le diabète de type 2

International audienceLe nombre de cas d'obésité mondiale a doublé depuis 1980 et triplé chez les enfants. Le plus souvent l'évolution de la prévalence du diabète se superpose à celle de l'obésité. Les causes de cette épidémie de diabète de type 2, touchant plus de 5% de la popula-tion Française, restent complexes et la suralimentation et le mode de vie sédentaire ne peuvent pas, à eux seuls, l'expliquer. Les perturbateurs endocriniens* (PE), ubiquitaires dans notre environnement, sont capables de modifier certaines voies de signalisa-tion cellulaire du métabolisme du glucose et des lipides. Chez l’Homme, des études épidémiologiques ont montré un lien direct entre l’exposition à certains polluants organiques persistants* (POP), dont les insecticides organochlorés* (OC) et les polychlorobi-phényles* (PCB) et la survenue d’un syndrome métabolique* ou d’un diabète de type 2, dans les années qui suivent une exposition aigüe (1). Les restrictions dans l'utilisation des OC et des PCB, liées à la convention de Stockholm de 2001 ont entrainé une diminu-tion de ces polluants, mais certains métabolites du DDT tel le dichlorodiphényldichloroéthylène (p,p’-DDE) et l'hexachlorobenzène (HCB) ou les PCB, persistants et bioaccumulables, sont encore retrouvés dans de nombreux organismes vivants. Pour les pesticides organophosphorés (OP), il n'existe pas aujourd'hui de consensus sur les conséquences pour l’Homme, liées à une exposition préna-tale à ces substances, alors que des études sur l'animal ont montré un effet (2). Il est apparu nécessaire de développer de nou-veaux outils d'investigations, permettant de relier de faibles doses de polluants chimiques à des effets mesurables sur la santé humaine. C'est dans ce contexte que la première publication de cette note, une étude métabolomique* chez l'adulte menée par Salihovic et al. (mars 2016), cherche à identifier les signaux enzymatiques, métaboliques et hormonaux perturbés par des faibles doses d'OC. Dans la seconde publication, Debost-Legrand et al (avril 2016), cherchent à relier l'exposition prénatale à des cocktails complexes de faibles doses de POP, OC et OP et la modification dans la sécrétion de deux hormones du métabolisme du glucose: l'insuline et l'adiponectine. Ces deux études permettent de passer de l'analyse des effets épidémiologiques, souvent liés à des expositions aiguës, à l'identification des mécanismes de signalisation cellulaire grâce au métabolome, modifié par une exposition à un ou plusieurs agents chimiques. Ce changement d'échelle représente une avancée majeure dans l'approche des effets molécu-laires exercés par de faibles doses de mélanges complexes. Dans les deux publications présentées, c'est le métabolisme du glucose et des lipides qui semble être le plus impacté par ces cocktails de polluants, renforçant l'hypothèse d'une incidence continue de certains perturbateurs endocriniens, OC et OP sur le diabète de type 2 et l'obésité

A new method for labelling enkephalins and LC/LIF/MS studies

communication oral

Nouvelle méthode de marquage des enképhalines. Etude LC/LIF/MS et analyse conformationnelle par échange H/D.

affich

Analysis of the retention of tetracyclines on reversed-phase columns: Chemometrics, design of experiments and quantitative structure-property relationship (QSPR) study for interpretation and optimization

International audienc