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.     

Slip and Twinning in Polycrystalline Alumina (α-Al2O3) Deformed under Hydrostatic Pressure between 600° and 1000°C

The microstructure of polycrystalline alumina deformed under hydrostatic pressure and at low temperature is investigated by transmission electron microscopy. Deformation occurs mainly by prism plane slip and rhombohedral twinning. Introduction of hydrogen leads to a significant decrease in the yield stress. In large grain size alumina deformed with hydrogen, accommodation of twinning involves dislocation reactions in the twin boundary and in the grains rather than by cracking. Prism plane dislocations decompose into basal dislocations by cross slip probably due to a decrease of Peierls stress for basal slip in the presence of hydrogen.     

Phonons and spin excitations in the extended t-J model

We consider the effects of spin-phonon coupling within the slave-boson mean-field treatment of the extended t-J model. With no additional assumptions the theory is found to give a semi-quantitative account of the frequency and linewidth anomalies observed for certain phonon modes in Y Ba₂Cu₃O₇ at the superconducting transition. We report also investigations of the role of this coupling in affecting thermodynamic properties and spin dynamics.     

L'IPAH, version canadienne-fran?aise de l'échelle de Levenson mesurant le lieu de contr?le tridimensionnel.

Assessed the reliability and validity of the French-Canadian version of H. Levenson's (1973) internality, powerful others, and chance locus of control scales. Data from 2 studies of 294 middle-class adults show that the French-Canadian version of the scales was comparable to that of the original version. The importance of utilizing the appropriate statistical models of analysis to benefit from the multidimensional model of locus of control is emphasized. (English abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

évaluation du livre intitulé manuel de gérontologie sociale 2.

Reviews the book, Manuel de gérontologie sociiale 2 by Jean Carette (1992). The Handbook of Social Gerontology 2 constitutes a practical complement of volume 1 which related to the social aspects of ageing and the retirement. Volume 2 relates mainly to the social intervention whose objective is to support the action and the collective mobilization individuals and associations of retirements. Using a 30-year experiment with groups of retirees, either in preparation of retirement, or in the collective action, the author approaches a new ground in gerontology. He proposes a new approach--social gerontology, (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Telechelic polydimethylsiloxanes with terminal acetylenic groups prepared by phase-transfer catalysis

Telechelic, hydroxyalkyl terminated polydimethylsiloxanes were obtained under mild conditions via hydrosilylation of allyl alcohol or ethylene glycol monoallyl ether by oligomeric αω-hydride terminated polydimethylsiloxanes, with the use of a platinum catalyst. They were subsequently modified in a phase transfer catalyzed reaction by propargyl bromide, to give telechelic polysiloxanes terminated by acetylenic groups. The synthetic pathway is described and the characterization of the obtained products is presented.     

An efficient purification method for detonation nanodiamonds

This article reports the purification process of detonation soot to obtain pure nanodiamond powder. Nanodiamonds are synthesized by detonation using a high explosive mixture composed of trinitrotoluene and hexogen. The detonation of the charge leads to a powder containing nanodiamonds as well as metallic impurities and sp² carbon species. Further, to remove metallic particles, an unusual acidic treatment (hydrofluoric/nitric acids; i.e. fluorinated aqua regia) was set up. To eliminate sp² carbon species such as graphite and amorphous carbon, a thermal oxidation treatment was performed at 420 °C under air in a furnace during several hours. Transmission Electronic Microscopy, Raman spectroscopy, X-ray diffraction and Thermo-Gravimetric Analysis showed that this purification process is very efficient. From TGA measurements, a model of the carbon grain combustion was developed by considering graphitic shells surrounding the nanodiamond particles, and was used to demonstrate that the selective oxidation of graphite was experimentally realistic. Moreover, another model was set up from specific area measurements to evaluate the thickness of the functional groups surrounding the nanodiamonds after the oxidation of sp² carbonaceous species. The treatment described herein was achieved on several tens of grams of product and could be easily adapted to the industrial scale.     

Expressing the equivalence of non‐isothermal and isothermal heat sterilization processes

Currently, the sterility of heat‐processed food and pharmaceuticals is assessed in terms of an F₀ value, based on the equivalence of the heat treatment to an isothermal process at a reference temperature. This F₀ value, however, has a meaning if, and only if, the inactivation kinetics of the targeted spores (or cells) follow a first‐order relationship and the temperature dependence of the D value, the reciprocal of the rate constant, is log‐linear. There is growing evidence that these conditions are not satisfied by many spores, including those of Clostridium botulinum and vegetative cells. Consequently, a replacement for the F₀ value is proposed in the form of a momentary equivalent time at the reference temperature based on the actual survival pattern of the spores, which need not be log‐linear. This equivalent time can be calculated together with the theoretical survival ratio in real time, thus enabling an operator to monitor the lethality of ongoing industrial heat processes. The concept is demonstrated with published survival data of C. botulinum, for which the Weibullian and log‐logistic models served as primary and secondary models, respectively. The safety factor according to the proposed method is in the number of added minutes of processing, beyond the theoretical time needed to reduce the survival ratio of the targeted spores or cells to a level that would produce practical (or commercial) sterility. Copyright © 2006 Society of Chemical Industry     

Motion synthesis and editing for the generation of new sign language content

Machine Translation - Existing work on the animation of signing avatars often relies on pure procedural techniques or on the playback of Motion Capture (MoCap) data. While the first solution...     

Differential Effects of STCH and Stress-Inducible Hsp70 on the Stability and Maturation of NKCC2

Mutations in the Na-K-2Cl co-transporter NKCC2 lead to type I Bartter syndrome, a life-threatening kidney disease. We previously showed that export from the ER constitutes the limiting step in NKCC2 maturation and cell surface expression. Yet, the molecular mechanisms involved in this process remain obscure. Here, we report the identification of chaperone stress 70 protein (STCH) and the stress-inducible heat shock protein 70 (Hsp70), as two novel binding partners of the ER-resident form of NKCC2. STCH knock-down increased total NKCC2 expression whereas Hsp70 knock-down or its inhibition by YM-01 had the opposite effect. Accordingly, overexpressing of STCH and Hsp70 exerted opposite actions on total protein abundance of NKCC2 and its folding mutants. Cycloheximide chase assay showed that in cells over-expressing STCH, NKCC2 stability and maturation are heavily impaired. In contrast to STCH, Hsp70 co-expression increased NKCC2 maturation. Interestingly, treatment by protein degradation inhibitors revealed that in addition to the proteasome, the ER associated degradation (ERAD) of NKCC2 mediated by STCH, involves also the ER-to-lysosome-associated degradation pathway. In summary, our data are consistent with STCH and Hsp70 having differential and antagonistic effects with regard to NKCC2 biogenesis. These findings may have an impact on our understanding and potential treatment of diseases related to aberrant NKCC2 trafficking and expression.