Molecular mechanisms of aging and immune system regulation in Drosophila

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.     

Silica nanoparticles inhibit the cation channel TRPV4 in airway epithelial cells

Background

Silica nanoparticles (SiNPs) have numerous beneficial properties and are extensively used in cosmetics and food industries as anti-caking, densifying and hydrophobic agents. However, the increasing exposure levels experienced by the general population and the ability of SiNPs to penetrate cells and tissues have raised concerns about possible toxic effects of this material. Although SiNPs are known to affect the function of the airway epithelium, the molecular targets of these particles remain largely unknown. Given that SiNPs interact with the plasma membrane of epithelial cells we hypothesized that they may affect the function of Transient Receptor Potential Vanilloid 4 (TRPV4), a cation-permeable channel that regulates epithelial barrier function. The main aims of this study were to evaluate the effects of SiNPs on the activation of TRPV4 and to determine whether these alter the positive modulatory action of this channel on the ciliary beat frequency in airway epithelial cells.

Results

Using fluorometric measurements of intracellular Ca²⁺ concentration ([Ca²⁺]_i) we found that SiNPs inhibit activation of TRPV4 by the synthetic agonist GSK1016790A in cultured human airway epithelial cells 16HBE and in primary cultured mouse tracheobronchial epithelial cells. Inhibition of TRPV4 by SiNPs was confirmed in intracellular Ca²⁺ imaging and whole-cell patch-clamp experiments performed in HEK293T cells over-expressing this channel. In addition to these effects, SiNPs were found to induce a significant increase in basal [Ca²⁺]_i, but in a TRPV4-independent manner. SiNPs enhanced the activation of the capsaicin receptor TRPV1, demonstrating that these particles have a specific inhibitory action on TRPV4 activation. Finally, we found that SiNPs abrogate the increase in ciliary beat frequency induced by TRPV4 activation in mouse airway epithelial cells.

Conclusions

Our results show that SiNPs inhibit TRPV4 activation, and that this effect may impair the positive modulatory action of the stimulation of this channel on the ciliary function in airway epithelial cells. These findings unveil the cation channel TRPV4 as a primary molecular target of SiNPs.

     

Temperature stimuli-responsive nanoparticles from chitosan-graft-poly(N-vinylcaprolactam) as a drug delivery system

This work describes the preparation of thermosensitive chitosan-graft-poly(N-vinylcaprolactam) nanoparticles by ionic gelation and their potential use as a controlled drug delivery system, using doxorubicin as a model drug. A systematic study of the effect of the main processing parameters on both the size and thermoresponsive behavior of nanoparticles was investigated. The size of the particles is strongly dependent on the length of the poly(N-vinylcaprolactam) grafted chains and the concentration of the copolymer and crosslinking agent solutions. The molecular structure of the copolymer plays an essential role in the phase transition temperature of the particles, which decreases with the length of PVCL grafted chain. The system displayed proper drug-association parameters, and the drug-loaded nanoparticles exhibited dose-dependent cytotoxicity. A significant increase in the doxorubicin delivery rate was observed above the phase transition temperature (40 °C). These features indicate that these nanoparticles are suitable for the development of a new thermally controlled anti-cancer drug delivery system. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47831.     

Eutectic modification in a low-chromium white cast iron by a mixture of titanium,rare earths,and bismuth: Part II. effect on the wear behavior

In this work, we studied the wear behavior of a low-Cr white cast iron (WCI) modified with ferrotitanium-rare earths-bismuth (Fe-Ti-RE-Bi) up to 2%. These additions modified the eutectic carbide structure of the alloy from continuous ledeburite into a blocky, less interconnected carbide network. The modified structure was wear tested under pure sliding conditions against a hardened M2 steel counter-face using a load of 250 N. It was observed that wear resistance increased as the modifier admixture increased. The modified structure had smaller more isolated carbides than the WCI with no Fe-Ti-RE-Bi additions. It was observed that large carbides fracture during sliding, which destabilizes the structure and causes degradation in the wear behavior. A transition from abrasive to oxidative wear after 20 km sliding occurred for all alloys. In addition, the modified alloys exhibited higher values of hardness and fracture toughness. These results are discussed in terms of the modified eutectic carbide microstructure.     

Defects in axisymmetrically drawn bars caused by longitudinal superficial imperfections in the initial material

Metallic wires and bars are produced by axisymmetric drawing of hot rolled material and must not display surface defects that impair their service use or whose opening during subsequent cold forming is unacceptable. Experimental and numerical (Finite Element Analysis - FEA) analyses of the evolution of longitudinal superficial defects in copper bars during seven successive axisymmetric drawing passes are presented. The initial experimental defects displayed a rectangular cross-section, 1 mm wide and 0.3, 0.6 or 0.9 mm deep; the two latter evolved after drawing into the “inverted Y” defect already reported in the literature, but the former led to a newly reported “double V” defect. There was a good agreement between the results from experiments and FEA and further analyses were then carried only through FEA, covering two other materials (a carbon steel and aluminum), a decrease in the defect width (from 1.0 to 0.5 mm) and an inclination of 15° or 30° of the walls of the 1.0 mm wide rectangular defect. The defect evolution was similar for the three materials; the decrease in the defect width enhanced the incidence of “inverted Y” defects, and indicated the formation of newly reported “Radial” and “Inverted V” defects. The inclination of the defect walls led to the possibility of a change from the “inverted Y” defect to a “double V” one. Defects 0.3 mm deep and with walls at 30° were eliminated by the present drawing sequence. A novel approach for the prediction of the effect of the initial superficial imperfections on the final drawn stock, through the so called “defect evolution maps” is presented.     

Evaluation of the aromatic structure of coal tar pitch by solid and solution state n.m.r.

Rapid magic angle spinning has been used to obtain sideband-free high field ¹³C n.m.r. spectra of coal tar pitches in the solid state. However, the unfavourable cross-polarization and ¹H relaxation characteristics make it difficult to accurately estimate concentrations of quaternary aromatic carbon using the dipolar dephasing method. The concentrations of bridgehead aromatic carbon in the whole pitch and toluene-insoluble fraction investigated were deduced using a combination of solid and solution state n.m.r. and elemental analyses.     

Fractal Extra-Framework Species in De-aluminated LaY Zeolites and Their Catalytic Activity

Lanthanum-containing Y (LaY) zeolites were prepared by ionic exchange from NaY parent zeolite. The LaY zeolites were de-aluminated by steaming. De-aluminated zeolites presented different Si/Al ratio. The physicochemical properties of these catalysts were characterized by X-ray diffraction, pyridine and xenon adsorption, infrared spectroscopy and ²⁹Si, ²⁷Al, ¹²⁹Xe, ¹³⁹La solid-state nuclear magnetic resonance spectroscopy. Furthermore, a fractal geometry approach was adopted to describe the evolution in the texture as a consequence of de-alumination. The catalytic properties of materials were evaluated in the n-hexane cracking reaction. The catalyst with the highest catalytic activity was the zeolite highest de-aluminated (Si/Al ratio of 3.7). Such performance was attributed on the one hand, to active extra-framework aluminum species hosted in the large cavities of zeolites and, on the other hand to redistribution of lanthanum species into the zeolite as a consequence of de-alumination.     

Modélisation de la cinétique de biodégradation de phénol par granules aérobies

This work describes a model of the biodegradation of phenol carried out by aerobic granules. These granules were obtained by culturing an activated sludge supernatant in a sequencing batch reactor fed with a synthetic waste water and subsequently, by acclimation to phenol (100 mg/L). The kinetics of phenol biodegradation by the aerobic granules was investigated over a wide range of initial phenol concentrations (40–1112 mg/L) in shake‐flask cultures. A Haldane‐type model was adjusted to the experimental results, which depicts successfully the phenol biodegradation profiles in the entire range of initial concentrations studied by using only one set of parameters. It is our view that the proposed model could contribute to the knowledge about the ability of aerobic granular systems to biodegrade toxic, inhibitory compounds such as phenol.     

Gasification and co-gasification of biomass wastes: Effect of the biomass origin and the gasifier operating conditions

Air gasification of different biomass fuels, including forestry (pinus pinaster pruning) and agricultural (grapevine and olive tree pruning) wastes as well as industry wastes (sawdust and marc of grape), has been carried out in a circulating flow gasifier in order to evaluate the potential of using these types of biomass in the same equipment, thus providing higher operation flexibility and minimizing the effect of seasonal fuel supply variations. The potential of using biomass as an additional supporting fuel in coal fuelled power plants has also been evaluated through tests involving mixtures of biomass and coal–coke, the coke being a typical waste of oil companies. The effect of the main gasifier operating conditions, such as the relative biomass/air ratio and the reaction temperature, has been analysed to establish the conditions allowing higher gasification efficiency, carbon conversion and/or fuel constituents (CO, H₂ and CH₄) concentration and production. Results of the work encourage the combined use of the different biomass fuels without significant modifications in the installation, although agricultural wastes (grapevine and olive pruning) could to lead to more efficient gasification processes. These latter wastes appear as interesting fuels to generate a producer gas to be used in internal combustion engines or gas turbines (high gasification efficiency and gas yield), while sawdust could be a very adequate fuel to produce a H₂-rich gas (with interest for fuel cells) due to its highest reactivity. The influence of the reaction temperature on the gasification characteristics was not as significant as that of the biomass/air ratio, although the H₂ concentration increased with increasing temperature.