Neuroprotective Properties of Quinone Reductase 2 Inhibitor M-11, a 2-Mercaptobenzimidazole Derivative

The ability of NQO2 to increase the production of free radicals under enhanced generation of quinone derivatives of catecholamines is considered to be a component of neurodegenerative disease pathogenesis. The present study aimed to investigate the neuroprotective mechanisms of original NQO2 inhibitor M-11 (2-[2-(3-oxomorpholin-4-il)-ethylthio]-5-ethoxybenzimidazole hydrochloride) in a cellular damage model using NQO2 endogenous substrate adrenochrome (125 µM) and co-substrate BNAH (100 µM). The effects of M-11 (10–100 µM) on the reactive oxygen species (ROS) generation, apoptosis and lesion of nuclear DNA were evaluated using flow cytometry and single-cell gel electrophoresis assay (comet assay). Results were compared with S29434, the reference inhibitor of NQO2. It was found that treatment of HT-22 cells with M-11 results in a decline of ROS production triggered by incubation of cells with NQO2 substrate and co-substrate. Pre-incubation of HT-22 cells with compounds M-11 or S29434 results in a decrease of DNA damage and late apoptotic cell percentage reduction. The obtained results provide a rationale for further development of the M-11 compound as a potential neuroprotective agent.     

Structure-activity relationship in water-gas shift reaction over gold catalysts supported on Y-doped ceria

The utilization of pure hydrogen as an energy source in fuel cells gave rise to renewed interest in developing active and stable water-gas shift catalysts. Gold catalysts have proven to be very efficient for water-gas shift reaction at low temperature. The aim of the present study was to investigate the effect of:(i) different preparation methods(impregnation and coprecipitation) to obtain a modified ceria support,and(ii) the amount of Y_2 O_3(1.0 wt%, 2.5 wt%, 5.0 wt% and 7.5 wt%) as dopant on the water-gas shift activity of Au/CeO_2 catalysts. An extended characterization by means of S_(BET), XRD, HRTEM/HAADF, FTIR,H_2-TPR and CO-TPR measurements in combination with careful evaluation of the catalyst behavior allowed to shed light on the parameters governing the water-gas shift activity. The catalysts show very high activity(90% CO conversion) in the temperature range 180-220 ℃,with a slightly better performance of the gold catalysts on supports prepared by impregnation. The decreased activity with increasing Y_2 O_3 concentration is related to the hindering of oxygen mobility due to ordering of surface oxygen vacancies in vicinity of segregated Y~(3+). The effect of catalyst pre-treatments and the stability of the best performing samples were examined as well.     

Integrated synthetic, pharmacological, and computational investigation of cis-2-(3,5-dichlorophenylcarbamoyl)cyclohexanecarboxylic acid enantiomers as positive allosteric modulators of metabotropic glutamate receptor subtype 4

2‐(3,5‐Dichlorophenylcarbamoyl)cyclohexanecarboxylic acid ( 1 ) is a potent and selective positive allosteric modulator of metabotropic glutamate receptor subtype 4 (mGluR4). The activity of 1 was reported to reside in the cis diastereomer with equal potency between its enantiomeric forms (Niswender et al., Mol. Pharmacol. 2008 , 74, 1345–1358). In the present study, the asymmetric synthesis of each of the cis enantiomers was performed, and their activities were compared with that of the racemic trans. In our assays, the cis enantiomers differ in potency, with one of them (1R,2S) higher and the other (1S,2R) lower than the racemic trans. High‐level quantum chemical calculations were carried out to characterize the structures of minimum energy in all‐isomer conformational space as well as particular intermediates between conformational transitions. Computational analysis identified structural features of 1 that can play a role in mGluR4 functionality and establish the basis for subsequent work, in which molecular chirality constructed on conformations derived from those found for the active (1R,2S) enantiomer can provide new ideas for drug discovery. Comparison between experimental and theoretical circular dichroism spectra confirmed both the absolute configuration of the (1R,2S) compound and its calculated most stable conformation, thereby supporting experimental and theoretical work.     

Powder Metallurgy Use of Waste from Bearing Production

A technology has been developed for improving the properties of ShKhl7 steel powder, obtained from bearing production waste sludge by familiar technological processes. On the basis of theoretical and experimental studies, we have ascertained the optimal conditions for ball milling, grinding, and heat treatment of the powders so as to improve their fluidity and bulk density. The technological and strength characteristics of the powders studied make them suitable for the production of serviceable parts by powder metallurgy methods.__________Translated from Poroshkovaya Metallurgiya, Nos. 1–2(441), pp. 106–112, January–February, 2005.     

Studying the active layer of oligotrophic bogs in the Taiga zone of Western Siberia

In this paper, we identify and describe the active and inert horizons of oligotrophic bogs. These often appear to be a fire risk to oil and gas extraction industries, but these bogs are a complex biological system also. We describe three structural layers for the active horizon. These are the turf layer, the porous layer, the intermediate layer. We have investigated the morphological characteristics of these layers. For each layer, we gave the measurement of physical parameters – pH, general mineralisation, conductivity, coefficient of ash and moisture. In each selected layer we study microbiological parameters – microbial biomass, the carbon of microbial biomass, basal respiration and microbial metabolic quotient. Microbiological studies have established the boundary between the aerobic and anaerobic conditions in active layer of oligotrophic bogs. In each layer, we have established the biochemical characteristics of layers studying enzymes catalase and invertase. The obtained data make it possible to assess the functional processes in the active horizon of the wetland’s ecosystem.     

New hard ternary Hf–Ir–B borides formed by reaction hafnium diboride with iridium

A variety of the ternary Hf–Ir–B phases formed via the reaction between iridium and hafnium diboride at elevated temperatures was found. The data on the phase and elemental composition, as well as crystal structure, obtained by powder and single-crystal X-ray diffraction, scanning electron microscopy/energy-dispersive X-ray spectrometer, and time-of-flight neutron diffraction analysis unambiguously confirm that HfIr₃B_x solid solution, two known ternary borides (HfIr₃B₄, Hf₂Ir₅B₂), as well as two novel ternary HfIr_2.1B_1.3 and HfIr_5.7B_2.7 phases, are formed at elevated temperatures. This result is fundamentally different from that previously obtained by us for the Hf–Ir–C system in which only one binary intermetallic compound, HfIr₃, was produced. The measured Vickers microhardness for all the aforementioned ternary borides (13–19 GPa) allows us to consider them hard. The coefficients of thermal expansion of ternary borides were measured by in situ high-temperature X-ray analysis.     

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.     

Comparison of the Effect of Horizontal Vibrations on Interfacial Waves in a Two-Layer System of Inviscid Liquids to Effective Gravity Inversion

We study the waves at the interface between two thin horizontal layers of immiscible liquids subject to high-frequency tangential vibrations. Nonlinear governing equations are derived for the cases of two- and three-dimensional flows and arbitrary ratio of layer thicknesses. The derivation is performed within the framework of the long-wavelength approximation, which is relevant as the linear instability of a thin-layers system is long-wavelength. The dynamics of equations is integrable and the equations themselves can be compared to the Boussinesq equation for the gravity waves in shallow water, which allows one to compare the action of the vibrational field to the action of the gravity and its possible effective inversion.     

The Interaction of Rigid Cylinders in a Low Reynolds Number Pulsational Flow

The interaction of two rigid cylinders with parallel axes in a viscous liquid subjected to translational vibrations perpendicular to the plane containing the cylinder axes is considered in the framework of the low Reynolds number approximation. It is shown that the interaction type substantially depends on the distance between the cylinders. If this distance exceeds the viscous Stokes length, then the vibrations lead to the cylinder attraction. For the distances shorter than the Stokes length, the behaviour is opposite.