Relative Importance of Soluble and Microsomal Epoxide Hydrolases for the Hydrolysis of Epoxy-Fatty Acids in Human Tissues

Epoxy-fatty acids (EpFAs) are endogenous lipid mediators that have a large breadth of biological activities, including the regulation of blood pressure, inflammation, angiogenesis, and pain perception. For the past 20 years, soluble epoxide hydrolase (sEH) has been recognized as the primary enzyme for degrading EpFAs in vivo. The sEH converts EpFAs to the generally less biologically active 1,2-diols, which are quickly eliminated from the body. Thus, inhibitors of sEH are being developed as potential drug therapeutics for various diseases including neuropathic pain. Recent findings suggest that other epoxide hydrolases (EHs) such as microsomal epoxide hydrolase (mEH) and epoxide hydrolase-3 (EH3) can contribute significantly to the in vivo metabolism of EpFAs. In this study, we used two complementary approaches to probe the relative importance of sEH, mEH, and EH3 in 15 human tissue extracts: hydrolysis of 14,15-EET and 13,14-EDP using selective inhibitors and protein quantification. The sEH hydrolyzed the majority of EpFAs in all of the tissues investigated, mEH hydrolyzed a significant portion of EpFAs in several tissues, whereas no significant role in EpFAs metabolism was observed for EH3. Our findings indicate that residual mEH activity could limit the therapeutic efficacy of sEH inhibition in certain organs.     

Water-Soluble Gold(III)–Metformin Complex Alters Mitochondrial Bioenergetics in Breast Cancer Cells

Chemical control of mitochondrial dynamics and bioenergetics can unravel fundamental biological mechanisms and therapeutics for several diseases including, diabetes and cancer. We synthesized stable, water-soluble gold(III) complexes (Auraformin) supported by biguanide metformin or phenylmetformin for efficacious inhibition of mitochondrial respiration. The new compounds were characterized following the reaction of [C N]-cyclometalated gold(III) compounds with respective biguanides. Auraformin is solution stable in a physiologically relevant environment. We show that auraformin decreases mitochondrial respiration efficiently in comparison to the clinically used metformin by 100-fold. The compound displays significant mitochondrial uptake and induces antiproliferative activity in the micromolar range. Our results shed light on the development of new scaffolds as improved inhibitors of mitochondrial respiration.     

Morphology and ionic conductivity relationship in silk/cellulose biocomposites

The relationship between morphology and the ionic conductivity of polysaccharide–protein bio‐electrolyte membranes is explored in this study. Structural proteins and polysaccharides form hydrophobic and electrostatic interactions, and the resulting matrices can exhibit novel and useful properties. However, transforming these natural biomacromolecules from their native state to a more usable form is challenging. The structural, morphological, thermal, mechanical and electrical properties of biomaterials composed of microcrystalline cellulose and Bombyx mori silk when regenerated together using ionic liquids and various coagulation agents were investigated using a diverse set of techniques including Fourier transform infrared spectroscopy, SEM, TGA, DSC, X‐ray scattering, AFM‐based nanoindentation and dielectric relaxation spectroscopy. The surface topography of the films reveals morphological changes with varying coagulation agents and ionic liquids. It was found that the thermal and mechanical properties were dependent on intermolecular interactions dictated by the type of ionic liquid used during the coagulation process. X‐ray scattering provided information on how the cellulose crystallinity varied with coagulation agent. Specifically, samples coagulated with hydrogen peroxide showed an increase in cellulose crystallinity impacting properties such as elasticity, hardness and ionic conductivity of the biocomposites. In addition, the results revealed a strong correlation between β‐sheet content and ionic conductivity and cellulose crystallinity. The results provided evidence that the ionic conductivity is dependent on protein β‐sheet content and cellulose crystallinity. © 2019 Society of Chemical Industry     

Effect of Bi2O3 on phase formation and microstructure evolution of mullite ceramics from mechanochemically activated oxide mixtures

Mullite ceramics with hollow whisker structure have been synthesized firstly through ordinary sintering process. The effects of Bi₂O₃ and processing, on mullitization behavior and morphology development of mullite ceramics, derived from the mechanochemically activated mixture of Al₂O₃ and SiO₂, were investigated in this paper. When the content of Bi₂O₃ was less than 10?mol%, the mullite grains show a short rod-like morphology, without the formation of whisker. As the content of Bi₂O₃ was increased to more than 10?mol%, the formation temperature of mullite was decreased from 1400?°C to 1100?°C. After sintering at 1400?°C, well-developed mullite whiskers with hollow structure were formed. The formation process and growth mechanism of hollow structural whiskers in mullite ceramic doped with high content of Bi₂O₃ were discussed in detail.     

Passivating ligand and solvent contributions to the electronic properties of semiconductor nanocrystals

We examine in detail the impact of passivating ligands (i.e., amines, phosphines, phosphine oxides and pyridines) on the electronic and optical spectra of Cd(33)Se(33) quantum dots (QDs) using density functional theory (DFT) and time-dependent DFT (TDDFT) quantum-chemical methodologies. Most ligand orbitals are found deep inside in the valence and conduction bands of the QD, with pyridine being an exception by introducing new states close to the conduction band edge. Importantly, all ligands contribute states which are highly delocalized over both the QD surface and ligands, forming hybridized orbitals rather than ligand-localized trap states. In contrast, the states close to the band gap are delocalized over the QD atoms only and define the lower energy absorption spectra. The random detachment of one of ligands from the QD surface results in the appearance of a highly localized unoccupied state inside the energy gap of the QD. Such changes in the electronic structure are correlated with the respective QD-ligand binding energy and steric ligand-ligand interactions. Polar solvent significantly reduces both effects leading to delocalization and stabilization of the surface states. Thus, trap and surface states are substantially eliminated by the solvent. Polar solvent also blue-shifts (e.g., 0.3-0.4 eV in acetonitrile) the calculated absorption spectra. This shift increases with an increase of the dielectric constant of the solvent. We also found that the approximate single-particle Kohn-Sham (KS) approach is adequate for calculating the absorption spectra of the ligated QDs. Besides a systematic blue-shift, the KS spectra are in very good agreement with their respective counterparts calculated with the more accurate TDDFT method.     

Using information theory to assess the diversity, complexity, and development of communicative repertoires.

The application of quantitative and comparative measures from information theory on animal communication can provide novel insights into the ecological, environmental, social, and contextual properties that shape the structure, organization, and function of signal repertoires. Using 2 phylogenetically different mammalian species that share similar ecological and social constraints as examples, the authors quantitatively examined the internal structure and development of a subsystem of these species' vocal repertoires in comparison with that of human language and illustrated that these species exhibit convergent developmental processes. The authors also discussed how predictions on the structure and organization of animal communication systems can be made from this new application of information theoretic measures with respect to behavioral ecology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive aspects of chronic depression.

Previous research on chronic depression has focused on its link with other mood disorders and Axis II personality disorders. However, there are few data examining whether the cognitive perspective applies to this condition. In this cross-sectional study, 42 outpatients with chronic depression were compared with 27 outpatients with nonchronic major depressive disorder and 24 never psychiatrically ill controls on cognitive variables thought to be related to vulnerability to depression (e.g., dysfunctional attitudes, attributional style, a ruminative response style, and maladaptive core beliefs). Both depressed groups were more elevated than a never-ill comparison group. However, chronically depressed individuals were generally more elevated on measures of cognitive variables than those with major depressive disorders even after controlling for mood state and personality disorder symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scalar expectancy theory and peak-interval timing in humans.

The properties of the internal clock, temporal memory, and decision processes used to time short durations were investigated. The peak-interval procedure was used to evaluate the timing of 8-, 12-, and 21-s intervals, and analyses were conducted on the mean response functions and on individual trials. A distractor task prevented counting, and visual feedback on accuracy and precision was provided after each trial. Mean response distributions were (a) centered at the appropriate real-time criteria, (b) highly symmetrical, and (c) scalar in their variability. Analysis of individual trials indicated more memory variability relative to response threshold variability. Taken together, these results demonstrate that humans show the same qualitative timing properties that other animals do, but with some quantitative differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)