ß-Like DNA polymerases and prospects for their use as targets in chemotherapy of tumors.

DNA polymerases ß are enzymes that perform repair of damaged DNA. In the cells of malignant tumors, there is a change in the production and properties of these enzymes, which is accompanied by altered viability of tumor cells. Analysis of the publications available in Russian and international databases (Pubmed, Elsevier) on the structure and properties of DNA polymerases ß and their role in cell growth and proliferation, published over the past 20 years, has shown overexpression of genes encoding ß-like DNA polymerases in many types of malignant tumors cells. This explains the maintenance of their viability and proliferative activity. Targeted inhibition of ß-like DNA polymerases is accompanied by antiproliferative and antitumor effects. Stable paramagnetic isotopes of magnesium (25Mg2+) or other divalent metals (43Ca2+ and 67Zn2+) with uncompensated nuclear spin isotopes, as well as short single-stranded polydeoxyribonucleotides, can be used as promising antitumor pharmacophores.

Photonuclear production of medical radioisotopes 161Tb and 155Tb.

The production possibility of 161Tb and 155Tb by irradiating of natural dysprosium with gamma rays obtained by decelerating an electron beam with an energy of 55 MeV has been demonstrated experimentally. The yield of 161Tb was 14.4 × 103 Bq × µA-1 × h-1 × cm2 × gDy2O3-1. Simultaneously, upon irradiation, 155Dy is formed with the yield of 25 × 103 Bq × µA-1 × h-1 × cm2 × gDy2O3-1, which leads to the formation of 1.6 × 103 Bq × µA-1 × h-1 × cm2 × gDy2O3-1 of 155Tb. It has been shown that the isolation of terbium radioisotopes from tens of mg of dysprosium target can be achieved by extraction chromatography, and final separation yield was 39%. The impurity of 160Tb is 7.3% of the 161Tb activity at EOB.

Magnetocaloric Effect, Structure, Spinodal Decomposition and Phase Transformations Heusler Alloy Ni-Mn-In.

Ni46Mn41In13 (close to 2-1-1 system) Heusler alloy was studied by magnetization measurement dependence on the temperature in magnetic fields of up to 13.5 T. The magnetocaloric effect measured by the direct method in quasi-adiabatic conditions showed a maximum value of ∆Tad = -4.2 K at a temperature T = 212 K in a magnetic field of 10 T in the region of martensitic transformation. The structure of the alloy was studied by transmission electron microscopy (TEM) as a function of the temperature and the thickness of the sample foil. In the temperature range from 353 to 215 K, at least two processes were established. The results of the study indicate that the concentration stratification occurs according to the mechanism of spinodal decomposition (conditionally spinodal decomposition) into nanoscale regions. At a temperature of 215 K and lower, martensitic phase with 14 M modulation is observed in the alloy at thicknesses greater than 50 nm. Some austenite is also observed. In foils with thickness of less than 50 nm in a temperature range from 353 to 100 Km only the initial austenite, which has not transformed, was found.

Oligomerization of ß-Like DNA Polymerases in the Presence of Fe2+ Ions.

This work presents data on the relationship between the oligomeric state and catalytic activity of ß-like DNA polymerases isolated from three cancer cell lines upon replacement of magnesium ions with iron. It was shown that the suppression of the catalytic activity of ß-like DNA polymerases in the presence of divalent iron ions is related to enzyme oligomerization that can be responsible for the suppression of the magnetic isotope effect.

Restoration of the Indicator Properties of Whole-cell Luminescent Biosensors.

Whole-cell biosensors are widely used to produce medical diagnostic tests, but in the long term, they tend to lose their indicator properties. Consequently, it is crucial to find ways to restore these properties and prolong the shelf life of the tests. Here, we propose to use electromagnetic radiation with optimally selected parameters of frequency, power, and exposure time. The impact of radiation parameters on biosensor luminescence was studied as well as the effects of different types of radiation coming from laser sources (λ = 875 nm), a LED source (λ = 850 ÷ 890 nm), and microwave units (at frequencies 42.22, 53.53, 61.18 и 34 ÷ 38 GHz). IR treatment resulted in dose-dependent suppression of biosensor luminescence. The luminescence level when exposed to microwave radiation depends on the radiation time and frequency. Also, it has been found that optimal selection of the main radiation parameters enables to restore indicator properties partially lost by biosensors during storage. We explain the mechanism responsible for the sensitizing effect of radiation, which implies the polarization of solvent dipoles and changes in mobility of acceptor molecules. This, in turn, leads to a shift in the chemical equilibrium states and triggers a cascade of biochemical reactions that lead to restoration of the lost indicator properties of biosensors. The study of antagonistic activity has revealed that restored biosensors provide reliable test results after the expiration of their warranty period.

Radiation-Chemical Biotechnology for Producing Ultrashort (50-100n) Single-Chain Polydeoxyribonucleotides with Anticancer Activity.

The fundamental possibility of obtaining ultrashort (50n-100n) single-stranded polydeoxyribonucleotides by the method of radiation-chemical destruction of total yeast DNA was established and their anticancer activity was shown.

L, D-Polydeoxyribonucleotides to provide an essential inhibitory effect on DNA polymerase ß of human myeloid leukemia HL60 cells.

The inhibitory effect of D and L-polynucleotides of a given length (40-50n) on the catalytic activity of DNA polymerase ß isolated from chromatin cells of acute myeloid leukemia HL-60 was evaluated. The synthesized L enantiomer was found to have a higher inhibitory activity than the synthesized and isolated D enantiomers of polynucleotides. The work also proposes a biophysical model that describes this effect.

Self-propagating high-temperature synthesis of (Ho1-xLax)2O3 nanopowders for magneto-optical ceramics.

Weakly agglomerated nanoparticles of (Ho1-xLax)2O3 solid solutions were synthesized with the help of a self-propagating high-temperature synthesis (SHS). The nanopowders were studied by a simultaneous thermal analysis (TG-DSC), X-ray diffraction (XRD), BET and FT-IR spectroscopy methods. Changes of the particles morphology after annealing at different temperatures and ball milling were investigated by a scanning electron microscopy (SEM) and a dynamic light scattering (DLS) method. It was found that annealing at a temperature of 900 °C in air and ball milling of the SHS nanopowders allow obtaining rounded shape particles with a mean diameter of about 20 nm and C-type cubic crystal structure. Up to 10 mol.% of the lanthana was shown to dissolve in the holmium oxide nanoparticles.

Grazing-Incidence La/B-Based Multilayer Mirrors for 6.x nm Wavelength.

We studied a possibility of fabricating LaN/B grazing incidence multilayer mirrors for 6.x nm radiation at a relatively large angle of incidence (AOI = 77° off-normal). LaN/B multilayers with a periodicity of 15 nm were successfully fabricated. But when stored in air for one week they showed strong deterioration of the surface due to oxidation of the topmost LaN layers, even though the multilayer was capped with a thin B film. In a series of experiments with variable LaN thickness it was found that the B protective properties depend on the thickness of the underlying LaN layer. Based on these experiments a 15 nm LaN/La/B multilayer with a passivation layer of only 0.4 nm of LaN was fabricated, which did not show any deterioration of the surface within a testing period of half a year. An initial reflectivity of 74.5% at ≈6.66 nm, AOI = 77° off-normal was achieved, which was reduced by 0.5% absolute in half a year, due to contamination of the top B layer.

Effect of Calcium on Slow Force Responses in Isolated Right Ventricle Preparations of Healthy and Hypertrophied Myocardium in Male and Female Rats.

Effect of different Ca2+ concentrations in the bathing solution [Ca2+]o on the parameters of single isometric contraction and slow force response to stretching was studied in isolated preparations of healthy and hypertrophied myocardium of male and female Wistar rats. In all groups of experimental animals, the increase in calcium concentration was followed by a decrease in the myocardium slow response intensity. We revealed a complementary relationship between the current and medium-term systems of myocardial contractility regulation by the length of the myocardium aimed at the maintenance of the constant level during adaptation to the load. Slow responses of the hypertrophied rat heart myocardium were suppressed in comparison with those in the healthy myocardium and their intensity did not depend on animal sex.

Detection of human neuronal α7 nicotinic acetylcholine receptors by conjugates of snake α-neurotoxin with quantum dots.

Fluorescent derivatives are widely used to study the structure and functions of proteins. Quantum dots (QDs), fluorescent semiconductor nanocrystals, have a high quantum yield and are much more resistant to bleaching compared to organic dyes. Conjugates of α-neurotoxins with QDs were used for visualization of human α7 acetylcholine receptors heterologously expressed in GH4C1 pituitary adenoma cells. Specific staining of cells by the conjugated toxins was observed.

Exploiting Le Chatelier's principle for a one-pot synthesis of nontoxic HHogGNPs with the sharpest nanoscopic features suitable for tunable plasmon spectroscopy and high throughput SERS sensing.

Applying Le Chatelier's principle, a one-pot synthesis method is reported that generates highly anisotropic hedgehog gold nanoparticles (HHogGNPs), undemanding of a preformed seed or surfactant. These non-toxic HHogGNPs are potent candidates for nanomedicinal applications owing to their broad-band plasmon tunability, gigantic Raman enhancement and remarkable retention in a highly salted physiological environment.

Contractility of Right Ventricular Myocardium in Male and Female Rats during Physiological and Pathological Hypertrophy.

Sex differences in the morphogenesis and adaptation of the mechanisms controlling myocardium contractility during physiological and pathological hypertrophy of the right ventricle were demonstrated in mature rats. The study revealed sex-dependent effects of physiological and pathological cardiac hypertrophy on the coefficient of variation of the cardiomyocyte diameter, length-dependent control of the contractile force, and the maximum velocity of isotonic shortening.

Reuse of ultrafine mineral wool production waste in the manufacture of refractory concrete.

The paper deals with the mineral wool production waste (cupola dust - CD), presents CD characterization and aims to reuse CD in production of refractory concrete with calcium aluminate cement. The study of CD covers its chemical, phase and thermal analyses along with the morphological study and determination of particles size distribution. Zeta-potential, electrical conductivity and pH values of CD suspension are presented in the paper as well. Commercial microsilica additive in refractory concrete has been replaced with cupola dust. Compositions of refractory concrete have been prepared by incorporating 1%, 2% and 3% of CD. The bulk density, ultrasonic wave velocity, cold crushing strength and thermal shock resistance of the created refractory concrete have been determined. Based on experimental results, it has been found that cupola dust may be used for the production of refractory concrete. The environmental impact related to the CD reuse in refractory concrete production has been evaluated as well.

[Factors Associated With Development of Atrial Fibrillation After Coronary Artery Bypass Grafting].

PURPOSE: to identify factors associated with development of atrial fibrillation (AF) in the early postoperative period of coronary artery bypass grafting (CABG). METHODS: A total of 376 patients with ischemic heart disease who underwent CABG were enrolled in the study. RESULTS: During the observation period AF occurred in 74 patients (19.7%, 93% men, mean age 64.0+/-6.4 years), an average of 3.6+/-2 days after surgery. Multivariate regression analysis showed that odds ratio (OR) for AF in patients with age >59 years was 1.5 (95% confidence interval [CI], 1.1-3.5; p=0.04), aortic cross-clamping time >43 min - 2.4 (95% CI, 1.05-6.2; p=0.03), left atrial dimension (LAD) >39 mm - 5.0 (95% CI, 2.0-12.6; p=0.0006), left ventricular ejection fraction (LVEF) <51% - 3.6 (95% CI, 1.6-8.3, p=0.002). During ROC - analysis the high sensitivity was observed for LAD >39 mm (82%, =0.001), high specificity - for LVEF <51% (80%, =0.0009), highest positive likelihood ratio for LVEF <51% - 2.56 (=0.0009), greatest negative likelihood ratio for LAD >39 mm - 0.31 (=0.001). CONCLUSION: In our study, the risk of AF development in the early postoperative period of CABG depended on the patients age, left atrial size, left ventricular ejection fraction, and aortic cross-clamping time during CABG.

Nonconventional three-finger toxin BMLCL from krait Bungarus multicinctus venom with high affinity interacts with nicotinic acetylcholine receptors.

Nonconventional three-finger toxin BMLCL was isolated from B. multicinctus venom, and its interaction with different subtypes of nicotinic acetylcholine receptor (nAChR) was studied. It was found that BMLCL is able to interact with high efficiency with both α7 and muscle type nAChRs.

High-reflectance La/B-based multilayer mirror for 6.x nm wavelength.

We report a hybrid thin-film deposition procedure to significantly enhance the reflectivity of La/B-based multilayer structures. This is of relevance for applications of multilayer optics at 6.7-nm wavelength and beyond. Such multilayers showed a reflectance of 64.1% at 6.65 nm measured at 1.5-degrees off-normal incidence at PTB (BESSY-II). This was achieved by a special scheme of La passivation. The La layer was nitridated to avoid formation of the optically unfavorable LaBx compound at the B-on-La interface. To avoid the also undesired BN formation at the La-on-B interface, a time-dosed nitridation at the initial stage was applied. This research revealed a good potential for further increase in the reflectivity of multilayer structures at 6.7 nm.

[MORPHOLOGICAL AND VISCOELASTIC PROPERTIES OF ISIAH RATS MYOCARDIUM DURING THE DEVELOPMENT OF ARTERIAL HYPERTENSION].

The comprehensive study of morphometrical parameters and viscoelastic properties of right ventricle and left ventricle papillary muscles of ISIAH rats during the development of arterial hypertension has been carried out. It is established the significant increase of the index of heart mass to body mass and to tibia length of ISIAH rats in comparison with WAG rats of the same age. There are no any significant differences of "stress-strain" dependences of all experimental groups.

[Characteristics of load dependent relaxation of normal and hypertrophied myocardium in male and female rats].

Under monocrotaline treatment of rat right ventricle myocardium preparations significant changes in morphometric indices for male, but not for female preparations are adduced as compared to the control group. Peculiarities of adaptation of mechanocalcium uncoupling mechanism, one of important regulation mechanisms of rat myocardial contractility, were first revealed. Myocardial pressure overload results in the increase of time to peak force without alteration of characteristic time of isometric tension, relaxation for male rats under myocardial hypertrophy compared with control group rats. In addition, the decrease of the load dependent relaxation index in the male rats was obtained. Characteristics of myocardial contractility of female rats have not significant changes as compared to the control group.