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.     

Experimental determination of pesticide processing factors during extraction of seed oils

ABSTRACT

Processing Factors (PFs) reflect the concentration or dilution of pesticide residues resulting from food processing. PFs are key elements to demonstrate the compliance of processed foods with Maximum residue levels (MRLs) as set by Regulation 396/2005. While efforts have been made by the European Food Safety Authority (EFSA) and by national authorities to compile PFs from processing studies, such PFs are not available for all pesticides/processed product combinations. The EU vegetable oil and proteinmeal industry association (FEDIOL) has therefore developed a theoretical approach to approximate MRLs in crude vegetable oils and fats, based on the partition coefficient (log P_ow) of the pesticides and on the oil content of the raw materials. To substantiate this approach, a pilot-scale processing study was initiated with rapeseeds spiked with selected pesticides and the experimental PFs for these pesticides determined. The aims of this study were (i) to study the reliability of pilot-scale conditions for PF determination and (ii) to assess the experimental PFs obtained in comparison to the theoretical PFs proposed by FEDIOL. This study demonstrated that production yields obtained for crude oil and meal in this processing study are similar to those in industrial processes even if differences were observed in the individual production steps (mechanical or solvent extraction steps). The experimental PFs obtained confirmed that the chosen fat-soluble pesticides did concentrate in the oil fraction. For metalaxyl-M having a log P_ow lower than 3, a partitioning between the oil and the meal was observed, as expected. By comparing the experimental PFs and theoretical PFs, it can be concluded that the FEDIOL approach can be recommended as a suitable tool when PFs derived from specific processing studies are missing. Similar studies on pesticides with wider ranges of log P_ow are required in order to complete our conclusions on default PFs for vegetable oils.     

Self‐similarity analysis of vehicle driver's electrodermal activity

This paper characterizes stress levels via a self‐similarity analysis of the electrodermal activity (EDA) collected in a real‐world driving context. To characterize the EDA richness over scales, the fractional Brownian motion (FBM) process and its corresponding exponent H, estimated via a wavelet‐based approach, are used. Specifically, an automatic scale range selection is proposed in order to detect the linearity in a log scale diagram. The procedure is applied to the EDA signals, from the open database drivedb, originally captured on the foot and the hand of the drivers during a real‐world driving experiment, designed to evoke different levels of arousal and stress. The estimated Hurst exponent H offers a distinction in stress levels when driving in highway versus city, with a reference to restful state of minimal stress level. Specifically, the estimated H values tend to decrease when the driving environmental complexity increases. In addition, the estimated H values on the foot EDA signals allow a better characterization of the driving task than that of hand EDA. The self‐similarity analysis was applied to various physiological signals in literature but not to the EDA so far, a signal which was found to correlate most with human affect. The proposed analysis could be useful in real‐time monitoring of stress levels in urban driving spaces, among other applications.     

Presentation of a mixed reality software with a HoloLens headset for a nutrition workshop

Multimedia Tools and Applications - Microsoft has recently released a mixed reality headset called HoloLens. This semi-transparent visor headset allows the user who wears it to view the projection...     

An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases

The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low-to-sub-micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex-bases) has been successfully coupled to both ribose and 2′-deoxyribose sugars by using the N-deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno-expanded tricyclic heterocyclic base, as well as several distal and proximal flex-bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.     

Temperature stability of a pure metakaolin based K-geopolymer: Part 2. Variations in the mesoporous network and its rehydration stability

The thermal behavior of a model MK-based K-geopolymer was investigated between room temperature and 1400°C in order to evaluate its potentiality for high-temperature applications. The purpose of our study was to monitor the behavior of a geopolymer during a temperature rise in order to better understand its variations with respect to temperature. The works from the present paper focus only changes in the porous network; it follows a first part devoted to variations in the mineral matrix. The results obtained here show that the geopolymer material preserves its porous integrity up to 800°C, while maintaining the reversibility of water exchanges corresponding to about 25 weight percent. Together with the results of part 1, the findings of this study allow us to affirm that geopolymer materials are only very little affected by temperatures up to 800°C, or even 900°C (keeping its mesoporous amorphous structure).     

Improving the performances of earth air heat exchangers through Constructal design

Earth to air heat exchanger (EAHE) is a well‐known technique used to preheat or precool outdoor air before blowing it into a building. However, its geometry is often very simple as it consists in one or multiple straight pipes, while more complex arrangements can be found in heat exchangers design. In this paper, we explore the advantage of designing an EAHE as a network through the Constructal law point of view. A methodology is first proposed to design a single pipe EAHE when the need is defined in terms of cooling power, overall efficiency and enthalpy difference between the inlet air and the ground. Next, the single pipe EAHE is used as a reference for designing a tree‐shaped network under the constraint of identical fluid volume and cooling power. The geometrical features are allowed to change for the different branches of the network. The network coefficient of performance is found to increase significantly with the bifurcation level, illustrating the superior performances of the network. This approach was found to be robust as the improvements were not depending on the cooling demand or the environmental conditions. However, further work is needed to move from this theoretical result to practical considerations.     

Slip Length Measurements Using µPIV and TIRF-Based Velocimetry

The goal of this paper is to review progress (mostly recent) made in micro and nanovelocimetry, focusing on two techniques: µPIV (microparticle image velocimetry) and nanoPTV (nanoparticle tracking velocimetry). The paper focuses on the measurement of slippage (taken as a benchmark for these techniques), concentrating on work done in our group. We review the developments of µPIV that led, in the last ten years, to the achievement of 100 nm accuracy in the measurement of slip lengths. Later, this approach was complemented by nanoPTV, which recently obtained ±5 nm precision. Here, we also mention recent application of these techniques toward better characterization of microgel and polymer flows. As a whole, the two techniques have conveyed valuable information on flow behavior within and close to the boundaries of microchannels, on the importance of wetting, and on the role of surface heterogeneities. µPIV is commercially available but nanoPTV is not mature. Interesting instrumental developments are expected in the future for the latter technique.     

Screening of plant species for the phytotreatment of wastewater containing sulphonated anthraquinones

Sulphonated anthraquinones are known to be recalcitrant to biodegradation and are not eliminated by traditional wastewater treatment plants, leading to their accumulation in fresh water. Due to the high cost and limited efficiency of existing physical-chemical treatments, alternative cheaper processes are required to remove these compounds from industrial effluents. Four plant species were tested under hydroponic conditions for their ability to treat model effluents contaminated with mono- and disulphonated anthraquinones. Among them, Rheum rabarbarum (rhubarb) showed the most promising results and was chosen for further investigation. The apparent transpiration stream concentration factor obtained with this plant species reached up to 2.5, indicating a strong phytotreatment potential that should be further explored then exploited.     

Kinetic and mechanistic investigations of progesterone reaction with ozone

The removal of progesterone by ozone in aqueous solution was studied in this work. The absolute rate constant was evaluated and first by-products were identified. The reaction was studied in the 2.0-8.0 pH range and was found to be a second-order reaction, first-order relative to each compound concentration. The rate constant, determined by kinetic experiments in presence of an OH radical scavenger (tert-butanol), was independent of pH. The value was evaluated to be equal to 480+/-30 M(-1)s(-1) by two kinetic methods. Mass spectrometry analyses were performed to investigate primary degradation products generated by the reaction of ozone with progesterone. Two by-products were evidenced. According to these results, a degradation pathway of progesterone reacting with ozone was proposed.