Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

Mlcrolasers based on silica microspheres

Light can be confined efficiently in the high-Q, small-volume whispering-gallery-modes observed in silica microspheres. By coupling these microspheres to eroded optical fibers and fiber tips, direct mapping of the whispering-gallery modes has been achieved and the mode numbers have been assessed. The properties of these modes have allowed us to obtain laser action with very low thresholds in Nd-doped silica microspheres. Further projects in the field of non-linear optics and cavity quantum electrodynamics are described.     

Oxidized Fullerene Derivatives Containing Hydroxyl, Nitro and Fluorine Groups

Oxidation of fullerene was performed with fuming nitric acid and a soluble orange compound was synthesized and identified as polyhydroxy-polynitro fullerene. The formation of fullerene derivatives containing oxygen and fluorine were attempted by different methods using F₂, HF aqueous solution and fuming nitric acid. Resulting compounds were generally characterized by X-ray diffraction and IR and NMR spectroscopy.     

Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn’s disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 10⁹/L, respectively, to ≈13 days (both HR and RR) at 350 × 10⁹/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2.     

Differently sized native milk fat globules separated by microfiltration: fatty acid composition of the milk fat globule membrane and triglyceride core

The aim of this study was to characterize the fatty acid composition of the core and membrane of differently sized milk fat globules separated by microfiltration, which can now be used to manufacture dairy products. Native milk fat globules of various mean diameters, ranging from d₄₃ = 2.3 µm to 8.0 µm, were obtained using microfiltration of raw whole milk. After milk fat globule washing, the milk fat globule membrane (MFGM) and the triglyceride core (TC) were separated by manual churning. After total lipid extraction from each fraction, their fatty acid composition was characterized using methyl ester analysis by gas chromatography. Regardless of season, no significant differences were observed in the fatty acid composition of the MFGM phospholipids. Conversely, significant differences were found in the fatty acid composition of TC; particularly, small fat globule TC contained more medium‐chain fatty acids and less stearic acid than large fat globule TC. These results show that the previously observed differences in total fatty acid composition among differently sized milk fat globules are due to their triglyceride composition and MFGM amount rather than to the composition of the MFGM.     

Copolymerization of norbornene with norbornene terminated polystyrene macromonomer in the presence of Ni-based/MAO catalytic systems

Copolymerization of -norbornenyl polystyrene macromonomer (NBE-PS) with norbornene (NBE) using Ni-based catalysts in combination with methylaluminoxane (MAO) was investigated. The nature of the catalyst, the of the polystyrene macromonomer as well as the [NBE-PS]/[NBE] ratio have been shown to be important parameters to obtain graft copolymers with high NBE-PS incorporation (up to 43 wt%). The compatibilization ability of these graft copolymers has been checked for PS/PNBE blends. The length of the grafts was proved not to be an important parameter to consider compatibilization of the PS/PNBE blend.     

Protecting biodegradable coatings releasing antimicrobial agents

This article describes the synthesis and in vitro analysis of poly(ester anhydride) antimicrobial protection coatings. Poly(ester anhydride)s composed of ricinoleic acid, sebacic acid, terephthalic acid, and isophthalic acid were used in this study. The polymers were compatible with various fillers commonly used in paint preparation. The in vitro experiments showed that the polymers are able to release diuron, an antimicrobial agent, for months. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Rheological,thermal, and morphological properties of blends based on poly(propylene), ethylene propylene rubber,and ethylene-1-octene copolymer that could result from end of life vehicles: Effect of maleic anhydride grafted poly(propylene)

The objective of this work is to study the properties of blends that could result from the recycling of end-of-life vehicles (ELV). While ethylene propylene rubber (EPR) and ethylene propylene diene monomer (EPDM) have been used extensively as elastomeric additives in poly(propylene) (PP), they can be substituted by ethylene-1-octene copolymer (EOC). As a consequence, the matter resulting from the sorting of ELV might be more complex and made of PP, EPR, and EOC. The effect of incorporating EOC [that is a polyethylene elastomer (PEE)] and maleic anhydride grafted polypropylene (PP-g-MAH) on the rheological, thermal, and morphological properties of PP/EPR blends has been investigated. Blends of various compositions (with and without compatibilizer) were prepared using a corotating twin-screw extruder. The results were compared to the ones presented by a commercial (PP/EPR) blend. The EPR phase is dispersed in the form of spherical particles in (PP/EPR). The EOC phase is dispersed in the form of aggregated particles. Dynamic viscoelastic and differential scanning calorimetry properties of (PP/EPR)/EOC blends shows the incompatibility of the components even in presence of PP-g-MAH copolymer. POLYM. ENG. SCI., 47:1009–1015, 2007. © 2007 Society of Plastics Engineers     

Exploring factors related to users’ experience of public transport route choice: influence of context and users profiles

This exploratory study aims to achieve a better understanding of the users-related factors that affect the choice of routes in public transport (PT). We also look at what can motivate route and modes changes towards alternatives in a real situation. We investigated the experience of 19 users of PTs, using the critical incident technique (Flanagan in Psychol Bull 51(4):327, 1954). We asked participants to report incidents (i.e. situations) in cases they were very satisfied or dissatisfied with their choice. For both situations, the case of their usual route and case of an alternative were considered. A total of 91 incidents were collected and analysed using a multiple correspondences analysis. Additionally, users’ profiles were characterized and superposed to the analysis of incidents content. The main results are as follows. First, the user’s choice of PT route depends on the context (i.e. aim of the travel, time of day). Second, taking an alternative to the usual PT route or using a route combining different transport modes is determined by the context and by factors related to the pleasantness of the travel (e.g. to accompany a friend along the travel). Finally, depending on the user’s profile (i.e. combination of attitude towards PT and demographic variables), the factors taken into account to make the choice of a PT route are related to the efficiency or the pleasantness of the trip. These results show the importance of the contextual factors and the users’ profiles in route choice. They suggest that these factors should be further taken into account in new tools and services for mobility.