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.     

The effect of solidification time and heat treatment on the fatigue properties of a cast 319 aluminum alloy

Solidification time and heat treatment are known to have a large effect on the microstructure of cast aluminum alloys. This study was conducted to quantify how the fatigue properties of a 319-type aluminum alloy are affected by solidification time and heat treatment. Both porosity-containing (non-hot isostatically pressed (HIP)) and porosity-free (HIP) samples in the T6 (“peak aged”) or T7 (“overaged”) heattreated conditions were tested. As the solidification time increased, the average initiating pore diameter increased and stress-controlled fatigue life decreased. Heat treatment was observed to have a large effect on fatigue properties of the HIP samples. However, in the non-HIP fatigue samples, heat treatment did not significantly change the fatigue life or fatigue strength of the cast 319-type alloy. The absence of an influence of heat treatment on fatigue response is attributed to the predominance of the microporosity in fatigue crack initiation in cast aluminum.     

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.     

Preexercise meal composition alters plasma large neutral amino acid responses during exercise and recovery

This study was designed to determine metabolic and physical performance responses to ingestion of pre-exercise meals with different macronutrient and fiber profiles. Twelve physically active subjects (6 males and 6 females) were used to investigate the metabolic and physical performance consequences of consuming pre-exercise meals consisting of oat, corn, or wheat cereals. A fasting trial served as the control, and all subjects received each treatment in a Latin-square design. Blood samples were drawn before and 85 min after meal ingestion, during 90 min of cycling exercise (60% VO2peak), after a 6.4 km performance ride, and during 60 min of recovery. Expired air samples were collected to determine nutrient utilization. Resting carbohydrate oxidation rates and plasma insulin concentrations after oat ingestion were less than after wheat, and corn and wheat ingestion, respectively (P < 0.05). During exercise, the change in plasma glucose from pre-exercise was greater after consuming wheat and corn compared with oat (P < 0.05), and it was inversely related to pre-exercise plasma insulin concentration (r = -0.55, P = 0.0001). Plasma free fatty acid concentrations were inversely related to plasma lactate concentrations (r = -0.58, P = 0.0001). Free fatty acid concentrations and fat oxidation were greater in fasting trials than all others, but performance ride times did not differ among treatments. Plasma branched-chain amino acid concentrations resembled their respective meal profiles throughout exercise, the performance ride, and recovery. These results indicate that pre-exercise meal composition can influence glucose homeostasis during early exercise and plasma branched-chain amino acid concentrations over a substantial range of metabolic demands.     

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 adaptive tracking algorithm for direction finding and array shape estimation in a nonstationary environment

This paper presents an adaptive tracking algorithm for the subspace-based direction of arrival estimation of multiple sources in a nonstationary, environment. The nonstationarities are due to moving sources or to timevarying distortions of the sensor array shape. The proposed algorithm relies on the properties of a linear operator, referred to as the Propagator, which only exploits the linear independency of the source steering vectors. The Propagator allows not only the calibration of the array shape, but also the determination of the source and the noise subspaces without any eigendecomposition of the cross-spectral matrix of the received signals. A gradientbased adaptive algorithm is here proposed for the on-line estimation of the Propagator. A theoretical analysis of the behaviour of this algorithm in a nonstationary environment is given. Simulations are carried out in the case of moving sources and in the case of a time-varying array shape. They exhibit the good performances of the proposed algorithm.     

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.