Myosin Binding Protein-C Forms Amyloid-Like Aggregates In Vitro

This work investigated in vitro aggregation and amyloid properties of skeletal myosin binding protein-C (sMyBP-C) interacting in vivo with proteins of thick and thin filaments in the sarcomeric A-disc. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) found a rapid (5–10 min) formation of large (>2 μm) aggregates. sMyBP-C oligomers formed both at the initial 5–10 min and after 16 h of aggregation. Small angle X-ray scattering (SAXS) and DLS revealed sMyBP-C oligomers to consist of 7–10 monomers. TEM and atomic force microscopy (AFM) showed sMyBP-C to form amorphous aggregates (and, to a lesser degree, fibrillar structures) exhibiting no toxicity on cell culture. X-ray diffraction of sMyBP-C aggregates registered reflections attributed to a cross-β quaternary structure. Circular dichroism (CD) showed the formation of the amyloid-like structure to occur without changes in the sMyBP-C secondary structure. The obtained results indicating a high in vitro aggregability of sMyBP-C are, apparently, a consequence of structural features of the domain organization of proteins of this family. Formation of pathological amyloid or amyloid-like sMyBP-C aggregates in vivo is little probable due to amino-acid sequence low identity (<26%), alternating ordered/disordered regions in the protein molecule, and S–S bonds providing for general stability.     

Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease

Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging nature of characterizing the secondary structure of amyloids in cells. To overcome this and investigate the molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging, to detect structural changes in proteins and lipids. Specifically, we evaluated the formation of β-sheet structures in different monogenic and bigenic cellular models of Alzheimer’s disease that we generated for this study. We report on the possibility to discern different amyloid signatures directly in cells using infrared microspectroscopy and demonstrate that bigenic (amyloid-β, α-synuclein) and (amyloid-β, Tau) neuron-like cells display changes in β-sheet load. Altogether, our findings support the notion that different molecular mechanisms of amyloid aggregation, as opposed to a common mechanism, are triggered by the specific cellular environment and, therefore, that various mechanisms lead to the development of Alzheimer’s disease.     

Phenolic Compounds Cannabidiol,Curcumin and Quercetin Cause Mitochondrial Dysfunction and Suppress Acute Lymphoblastic Leukemia Cells

Anticancer activity of different phenols is documented, but underlying mechanisms remain elusive. Recently, we have shown that cannabidiol kills the cells of acute lymphoblastic leukemia (ALL) by a direct interaction with mitochondria, with their consequent dysfunction. In the present study, cytotoxic effects of several phenolic compounds against human the T-ALL cell line Jurkat were tested by means of resazurin-based metabolic assay. To unravel underlying mechanisms, mitochondrial membrane potential (∆Ψ_m) and [Ca²⁺]_m measurements were undertaken, and reactive oxygen species generation and cell death were evaluated by flow cytometry. Three out of eight tested phenolics, cannabidiol, curcumin and quercetin, which displayed a significant cytotoxic effect, also dissipated the ∆Ψ_m and induced a significant [Ca²⁺]_m increase, whereas inefficient phenols did not. Dissipation of the ∆Ψ_m by cannabidiol was prevented by cyclosporine A and reverted by Ru360, inhibitors of the permeation transition pore and mitochondrial Ca²⁺ uniporter, respectively. Ru360 prevented the phenol-induced [Ca²⁺]_m rise, but neither cyclosporine A nor Ru360 affected the curcumin- and quercetin-induced ∆Ψ_m depolarization. Ru360 impeded the curcumin- and cannabidiol-induced cell death. Thus, all three phenols exert their antileukemic activity via mitochondrial Ca²⁺ overload, whereas curcumin and quercetin suppress the metabolism of leukemic cells by direct mitochondrial uncoupling.     

Microstructure and thermoelectric properties of Bi_(1.9)Lu_(0.1)Te_3 compound

Effect of fabrication conditions on micros tructure and thermoelectric properties of the Bi_(1.9)Lu_(0.1)Te_3 compound was studied.Starting nanopowder with mean nanoparticle size of ～37 nm was synthesized by a microwave-solvothermal method.In order to prepare samples with various micro-grained structures,the synthesized nanopowder was compacted by two methods.The first method is cold isostatic pressing with further hightemperature annealing,while the second method is spark plasma sintering at various temperatures of process(653 and 683 K).It is found that mean grain size is equal to～290,～730 and ～1160 nm for cold isostatically pressed and spark plasma sintered at 653 and 683 K samples,respectively.The micro-grained sample with maximum mean grain size shows the best thermoelectric properties.This sample is structurally inhomogeneous and has the lowest thermal conductivity and the specific electrical resistivity.Maximum dimensionless figure of merit for this sample is equal to ～0.9 for temperature range of450-500 K.     

OLEDs based on some mixed-ligand terbium carboxylates and zinc complexes with tetradentate Schiff bases: Mechanisms of electroluminescence degradation

Mixed-ligand terbium carboxylates—Tb(Carb)₃(TPPO)₂ (HCarb = HSal (salicylic acid), Hpobz (2-phenoxybenzoic acid); TPPO = triphenylphosphine oxide) and zinc complexes with tetradentate Schiff bases—ZnSB (H₂SB = H₂SAL1, H₂SAL2 (derivatives of salicylic aldehyde); H₂MO1, H₂MO2 (derivatives of o-vanillin)) were used as electroluminescent (EL) layers in organic light emitting diodes (OLEDs). These devices have undergone reversible and irreversible mechanisms of EL degradation. The reversible one is mainly associated with charge carrier trap filling. At the same time several mechanisms of irreversible degradation were observed under UV light irradiation, heating and ageing in ambient conditions. The degradation mechanisms of OLEDs under heating from 293 K to 320 K were related to the changes in the interface regions. The initial degradation was eliminated by (1) an application of alternating bias voltage; (2) a decrease of the substrate temperature and the velocity of the thermal evaporation of materials. The degradation of OLEDs was not observed under low UV irradiation that is promising for OLEDs operation under day light.     

A comparison of bismuth nanoforms obtained in vacuum and air by microwave heating of bismuth powder

The synthesis of bismuth nanotubes in the conditions of microwave (MW) heating is reported as a lower-cost and simple technique in comparison with the traditional methods. The nanotubes were prepared by heating the Bi powder (a) in air for 15, 30, 60, and 90 min and (b) in vacuum for 5, 10, and 15 min in a domestic MW-oven (2.45 GHz, 1300 W). The products were characterized by TEM and AFM. A mechanism of formation for bismuth nanotubes in different conditions (air and vacuum) is presented.     

Potato Expressing Beetle-Specific Bacillus thuringiensis Cry3Aa Toxin Reduces Performance of a Moth

Expression of the Bacillus thuringiensis beetle-specific toxin Cry3Aa, which renders a genetically modified potato cultivar resistant to the Colorado potato beetle Leptinotarsa decemlineata, exerts a deleterious effect on the polyphagous moth Spodoptera littoralis. The caterpillars of S. littoralis feed less and produce smaller pupae on the genetically modified cultivar (NewLeaf Superior) than on the parental nontransgenic cultivar (Superior). The conversion efficiencies of total dry matter, combustion heat, carbon, and nitrogen from leaves to insect biomass are similar on both cultivars. In spite of similar food utilization and a relatively small difference in the body mass at pupation, female adults that developed from caterpillars fed on NewLeaf Superior lay a mean of 309 eggs compared to a mean of 713 eggs deposited by females that developed from caterpillars fed on Superior. Because of this difference and a simultaneous reduction in fertility (egg hatchability) from 78 to 48%, a pair of adults that fed as larvae on NewLeaf Superior produces only 148 larvae, whereas a pair of adults that fed as larvae on Superior produces 556 larvae. We suggest that small amounts of Cry3Aa that accumulate in insect tissue and persist until the adult stage are responsible for the decline in reproduction.     

Features of low-temperature oxidation of hydrogen in the medium of nitrogen,carbon dioxide,and water vapor at elevated pressures

The article discusses novel research results on combustion features of high-density Н₂/О₂ mixtures (ρ_H2 = 0.70–1.89 mol/dm³, ρ_O2 = 0.32–0.81 mol/dm³) diluted with nitrogen, carbon dioxide, or water vapor (from 46 to 76% mol.) at the uniform heating (1 K/min) of tubular reactor. Based on time dependencies of temperature increment in the reaction mixtures caused by the heat release during oxidation of H₂, it is found that the self-ignition temperature of Н₂/О₂/N₂ and Н₂/О₂/H₂O mixtures is by ≈ 30 K lower than that of the Н₂/О₂/СО₂ mixture. Unlike combustion of H₂ in the N₂ medium, in the CO₂ and H₂O media a chain-thermal explosion is observed at a certain concentration of reagents. The influencing mechanisms of diluents on the H₂ oxidation dynamics, as well as the contribution of homogeneous and heterogeneous reactions in the heat release are revealed. It is established that high heat capacity of H₂/O₂/CO₂ mixture, chemical interaction between its components, and presence of CO₂ molecules adsorbed on the reactor inner surface, are the factors determining the H₂ oxidation dynamics in CO₂ medium. At oxidation of H₂ in the H₂O medium, the process takes place against the background of water evaporation and, as a consequence, is characterized by increased heat capacity and thermal conductivity of the H₂/O₂/H₂O reaction mixture.     

Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors

The identification and characterization of ligand-receptor binding sites are important for drug development. Trace amine-associated receptors (TAARs, members of the class A GPCR family) can interact with different biogenic amines and their metabolites, but the structural basis for their recognition by the TAARs is not well understood. In this work, we have revealed for the first time a group of conserved motifs (fingerprints) characterizing TAARs and studied the docking of aromatic (β-phenylethylamine, tyramine) and aliphatic (putrescine and cadaverine) ligands, including gamma-aminobutyric acid, with human TAAR1 and TAAR6 receptors. We have identified orthosteric binding sites for TAAR1 (Asp68, Asp102, Asp284) and TAAR6 (Asp78, Asp112, Asp202). By analyzing the binding results of 7500 structures, we determined that putrescine and cadaverine bind to TAAR1 at one site, Asp68 + Asp102, and to TAAR6 at two sites, Asp78 + Asp112 and Asp112 + Asp202. Tyramine binds to TAAR6 at the same two sites as putrescine and cadaverine and does not bind to TAAR1 at the selected Asp residues. β-Phenylethylamine and gamma-aminobutyric acid do not bind to the TAAR1 and TAAR6 receptors at the selected Asp residues. The search for ligands targeting allosteric and orthosteric sites of TAARs has excellent pharmaceutical potential.