The Pathophysiological Role of CoA

The importance of coenzyme A (CoA) as a carrier of acyl residues in cell metabolism is well understood. Coenzyme A participates in more than 100 different catabolic and anabolic reactions, including those involved in the metabolism of lipids, carbohydrates, proteins, ethanol, bile acids, and xenobiotics. However, much less is known about the importance of the concentration of this cofactor in various cell compartments and the role of altered CoA concentration in various pathologies. Despite continuous research on these issues, the molecular mechanisms in the regulation of the intracellular level of CoA under pathological conditions are still not well understood. This review summarizes the current knowledge of (a) CoA subcellular concentrations; (b) the roles of CoA synthesis and degradation processes; and (c) protein modification by reversible CoA binding to proteins (CoAlation). Particular attention is paid to (a) the roles of changes in the level of CoA under pathological conditions, such as in neurodegenerative diseases, cancer, myopathies, and infectious diseases; and (b) the beneficial effect of CoA and pantethine (which like CoA is finally converted to Pan and cysteamine), used at pharmacological doses for the treatment of hyperlipidemia.     

Antitumor Effects of Vitamin D Analogs on Hamster and Mouse Melanoma Cell Lines in Relation to Melanin Pigmentation

Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH)₂D₃) limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity. We therefore examined the effect of secosteroidal analogs, both classic (1,25(OH)₂D₃ and 25(OH)D₃), and novel relatively non-calcemic ones (20(OH)D₃, calcipotriol, 21(OH)pD, pD and 20(OH)pL), on proliferation, colony formation in monolayer and soft-agar, and mRNA and protein expression by melanoma cells. Murine B16-F10 and hamster Bomirski Ab cell lines were shown to be effective models to study how melanogenesis affects anti-melanoma treatment. Novel Vitamin D analogs with a short side-chain and lumisterol-like 20(OH)pL efficiently inhibited rodent melanoma growth. Moderate pigmentation sensitized rodent melanoma cells towards Vitamin D analogs, and altered expression of key genes involved in Vitamin D signaling, which was opposite to the effect on heavily pigmented cells. Interestingly, melanogenesis inhibited ligand-induced Vitamin D receptor translocation and ligand-induced expression of VDR and CYP24A1 genes. These findings indicate that melanogenesis can affect the anti-melanoma activity of Vitamin D analogs in a complex manner.     

Deposition of calcium hydroxyapatite on negatively charged polyphosphazene surfaces

A number of polyphosphazenes with negatively charged β‐alanine (β‐Ala) and γ‐amino butyric acid (GABA) side groups were synthesized and studied for their ability to initiate the growth of hydroxyapatite (HAp) during exposure to simulated body fluid (SBF). All the polymers were hydrolytically sensitive, with the final hydrolysis rate dependent on the specific active side groups (GABA > β‐Ala). These systems also underwent extensive mineralization, with calcium phosphate deposited across their entire surface during exposure to SBF (up to 115 wt % gain after 4 weeks). This degree of deposition is a major advance over previously reported polyphosphazene systems, which underwent a maximum of 27 wt % gain after immersion in SBF for 4 weeks. The extent of mineralization over the surface was monitored using environmental scanning electron microscopy (ESEM) coupled with energy dispersive X‐ray spectroscopy (EDS). In addition, X‐ray diffraction (XRD) was used to determine the identity of the mineralized material. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41741.     

The Impact of Linseed Oil Lipids on the Physical Properties of Corn Crisps and the Possibility of Obtaining Crisps Enriched with n‐3 Fatty Acids

Linseed oil, also known as flaxseed oil, is obtained from the dried, ripened seeds of the flax plant (Linum usitatissimum). The oil is obtained by pressing, sometimes followed by solvent extraction supported by a refining process. Linseed oil is an edible oil that is in demand as a nutritional supplement, as a source of α‐linolenic acid an n‐3 fatty acid. The aim of this work was to investigate: (1) the influence of the corn crisp extrusion process on the degradation of fatty acids in linseed oil (LO) and some preparations obtained from the linseed oil such as ethyl ester (EE) and free fatty acids (FFA) added to the corn in order to increase the nutritional value of the crisps, (2) influence of the oil and two fatty preparations obtained from it on the quality of corn crisps, (3) interaction of the lipid fraction with starch. The extrusion process did not degrade the fatty acids significantly. Expansion ratio obtained in the corn crisp extrusion process decreased from 620 % down to 153 %, the size of pores/thickness of the starch–protein walls forming the structure of the extruded product decreased from 10 μm down to 4 μm, the hardness of the crisps increased from 20 to 75 N, and number of lipid–starch complexes increased with rising polarity of the lipid fraction. FFA were complexed mostly by starch (about 90 %), to a lesser degree by EE (about 60 %) and to the least extent by triacylglycerols (about 10 %). The studies performed under industrial conditions using the single screw extruder for the production of corn crisps with the application of standard parameters of the extrusion process indicated that the addition of a mass of 5 % of the various lipids (triacylglycerols of linseed oil, ethyl esters and fatty acids obtained from linseed oil) to corn grits prior to the extrusion process significantly affect the quality of corn crisps.     

The improvement of ecological characteristics of coatings from cured epoxy resins by hot water extraction

Amine curing agents pose serious health hazards and controlling their release is crucially important. Extraction of unbounded amine from cured epoxy polymers can improve the ecological characteristics of such products. Even 1 min exposure of cured epoxy resins to hot water reduces three- to ten-fold the residual amount of amine present in the epoxy polymer. Different temperatures and extraction times were tested, enabling the selection of the most optimal extraction conditions, which correspond to 5 min of heating in 100°C. This additional cost-effective extraction step is very easy to perform and leads to a significant reduction of unbounded curing agent, making cured epoxy resins much more eco-friendly products. The documented positive and linear trends of logarithms of viscosity and the amount of released amine suggest the selection from such curing agents and such epoxy resins that are characterized by lowest possible viscosities, which guarantees that there is only a low amount of unbounded amine that needs to be released from the polymer.     

DNA interaction of the CcrM DNA methyltransferase: a mutational and modeling study

Caulobacter crescentus CcrM is a DNA-(adenine N6)-methyltransferase that methylates adenine in the sequence GANTC with high specificity. To investigate its mechanism of DNA recognition, we used the crystal structure of a related methyltransferase (M1.MboII, which modifies GAAGA) as a starting point, and docked into it a DNA substrate to identify the protein regions that approach the DNA. After alignment of CcrM and M1.MboII, we identified four candidate regions in CcrM to contain residues involved in DNA recognition. We mutated 20 amino acid residues within these regions, purified the CcrM variants, and determined their DNA-binding and catalytic activity on a cognate GANTC substrate and on nine near-cognate substrates, each of which contained a single base-pair substitution in the recognition sequence. Altogether, we identified four residues in two of the regions, mutations of which resulted in a strong (>100-fold) reduction of methylation activity. Our data show that DNA recognition by CcrM is a cooperative process, because disruption of critical contacts led to loss of catalytic activity but not to a relaxation in specificity. In addition, we identified a change in the readout of the fifth base pair in the GANTC sequence with two other CcrM variants that showed smaller reductions in overall activity. Based on this and the sequence alignment of CcrM with other DNA methyltransferases of same or related recognition sequence, we propose roles for these two regions in DNA recognition by CcrM.     

Interfacial reactions of Sn–Zn–Ag–Cu alloy on soldered Al/Cu and Al/Al joints

This work shows the effect on the soldering process of the addition of Ag and Cu to Sn–Zn alloys. Soldering of Al/Cu and Al/Al joints was performed for a time of 3?min, at a temperature of 250°C, with the use of flux. Aging was carried out at 170°C for Al/Cu and Al/Al joints for 1 and 10 days. During the aging process, intermetallic layers grew at the interface of the Al/Cu joint at the Cu substrate. Intermetallic layers were not observed during wetting of Al/Al joints. On the contrary, dissolution of the Al substrate and migration of Al-rich particles into the bulk of the solder were observed. The experiment was designed to demonstrate the effect of Ag and Cu addition on the dissolution of Al substrate during the soldering and aging processes. In the solder alloys, small precipitates of AgZn₃ and Cu₅Zn₈ were observed.     

Bimetallic Au–Cu, Ag–Cu/CrAl3O6 Catalysts for Methanol Synthesis

The influence of silver and gold addition on the activity and physicochemical properties of supported Cu/CrAl₃O₆ catalysts was the aim of this work. The reduction of CrAl₃O₆ support shows only one reduction stage attributed to Cr (VI) species reduction originating from previously oxidized binary oxide. Supported copper catalysts reduce in one or two stages depending on copper concentration representing the reduction of copper oxide—CuO, copper oxide chemically combined with Cr(III) oxide as copper chromite—CuCr₂O₄ and Cr(VI) species originating from surface chromate ions CrO₄ ^2?. Additionally, the introduction of silver into supported copper catalysts Cu/CrAl₃O₆ can led to the appearance of silver chromate phase. XRD investigations of support CrAl₃O₆ alone, supported copper and gold and silver promoted copper supported catalysts calcined at 400, 700 and 900 °C indicated the presence of highly amorphous alumina γ-Al₂O₃ like structure network in which some of cationic locations of aluminum were occupied by chromium atoms and small quantities of α-Cr₂O₃ phase. Additionally, for copper, silver–copper, and gold–copper supported catalysts the following oxide phases were distinguished: monometallic oxides CuO, Ag₂O, binary oxides CuAl₂O₄, Ag₂CrO₄, CuCr₂O₄ and even ternary oxide CuAlCrO₄. In the case of gold promoted copper supported catalysts metallic gold phase was detected. Activity tests carried out for these catalysts show that the most active was 20 wt.% Cu/CrAl₃O₆ catalyst. Promotion of copper catalysts by silver improves the activity in methanol synthesis, what can be assigned to silver chromate formation. The analogical gold chromate like formation was not confirmed.     

Thermal Expansion,Electrical Resistivity,and Spreading Area of Sn-Zn-In Alloys

Thermal expansion and electrical resistivity of alloys based on Sn-Zn eutectic with 0.5, 1.0, 1.5, and 4.0 wt.% additions of In were studied. Thermal expansion measurements were performed using thermomechanical analysis tester over 223-373 K temperature range. Electrical resistivity measurements were performed with four-probe method over 298-423 K temperature range. The electrical resistivity of alloys increases linearly with temperature and concentration of In; also coefficient of thermal expansion of the studied alloys increases with In concentration. Scanning electron microscopy revealed simple eutectic microstructure with In dissolved in Sn-rich matrix. The results obtained were compared with the available literature data. Spreading tests on Cu of Sn-8.8Zn alloys with 0.5, 1.0, and 1.5 at.% of In were performed. Wetting tests were performed at 250 °C, by sessile drop method, by means of flux, and wetting times were 3, 8, 15, 30, and 60 min. In general, no clear effect of wetting time on spreading was observed.     

Interfacial Phenomena in Al/Al,Al/Cu,and Cu/Cu Joints Soldered Using an Al-Zn Alloy with Ag or Cu Additions

The studies of soldered joints were carried out in systems: Al/solder/Al, Al/solder/Cu, Cu/solder/Cu, where the solder was (Al-Zn)_EUT, (Al-Zn)_EUT with 0.5, 1.0, and 1.5 at.% of Ag and (Al-Zn)_EUT with 0.5, 1.0, and 1.5 at.% of Cu addition. Brazing was performed at 500 °C for 3 min. The EDS analysis indicated that the composition of the layers starting from the Cu pad was CuZn, Cu5Zn8, and CuZn4, respectively. Wetting tests were performed at 500 °C for 3, 8, 15, and 30 min, respectively. Thickness of the layers and their kinetics of growth were measured based on the SEM micrographs. The formation of interlayers was not observed from the side of Al pads. On the contrary, dissolution of the Al substrate and migration of Al-rich particles into the bulk of the solder were observed.