Cardiotonic steroids differentially affect intracellular Na+ and [Na+]i/[K+]i-independent signaling in C7-MDCK cells

Recently, we reported that ouabain kills renal epithelial and vascular endothelial cells independently of elevation of the [Na(+)](i)/[K(+)](i) ratio. These observations raised the possibility of finding cardiotonic steroids (CTS) that inhibit the Na(+),K(+) pump without attenuating cell survival and vice versa. To test this hypothesis, we compared CTS action on Na(+),K(+) pump, [Na(+)](i) content, and survival of Madin-Darby canine kidney cells. At a concentration of 1 microM, ouabain and other tested cardenolides, as well as bufadienolides such as bufalin, cinobufagin, cinobufotalin, and telobufotoxin, led to approximately 10-fold inhibition of the Na(+),K(+) pump, a 2-3-fold decrease in staining with dimethylthiazol-diphenyltetrazolium (MTT), and massive death indicated by detachment of approximately 80% of cells and caspase-3 activation. In contrast, Na(+),K(+) pump inhibition and elevation of [Na(+)](i) seen in the presence of 3 microM marinobufagenin (MBG) and marinobufotoxin did not affect MTT staining and cell survival. Inhibition of the Na(+),Rb(+) pump in K(+)-free medium was not accompanied by a decline of MTT staining and cell detachment but increased sensitivity to CTS. In K(+)-free medium, half-maximal inhibition of (86)Rb influx was observed in the presence of 0.04 microM ouabain and 0.1 microM MBG, whereas half-maximal detachment and decline of MTT staining were detected at 0.03 and 0.004 microM of ouabain versus 10 and 3 microM of MBG, respectively. Both ouabain binding and ouabain-induced [Na(+)](i),[K(+)](i)-independent signaling were suppressed in the presence of MBG. Thus, our results show that CTS exhibit distinctly different potency in Na(+),K(+) pump inhibition and triggering of [Na(+)](i)/[K(+)](i)-independent signaling, including cell death.     

Specific features of distribution and ecology of two species of armorhead sculpins of the genus Gymnocanthus (Cottidae) in Pacific waters of the northern Kuril Islands and Southeastern Kamchatka

Based on materials of 1992?C2012, data on the occurrence, spatial-bathymetric distribution, and size-weight composition of armorhead sculpin Gymnocanthus galeatus and purplegray sculpin G. detrisus and species accompanying them in catches in Pacific waters of the northern Kuril Islands and southeastern Kamchatka are provided. These comparatively numerous, medium-sized representatives of the family Cottidae (maximal length of the former species 49 cm, weight 1400 g and that of the latter, 48 cm and 1140 g) in the period of study occurred uniformly at depths of 76 to 596 m at a near-bottom temperatures of ?1.2 to + 4.5°C. Their maximum by density concentrations were constantly recorded at the beam of the Fourth Kuril Strait, from the oceanic side of the Paramushir and Shumshu Islands, and off the southeastern extremity of Kamchatka mainly in the lower part of the shelf (depths of 80?C200 m) at temperatures of ?1.0 to +2.5°C. Regularities of spatial-bathymetric distribution of different size groups of these species were analyzed. It was shown that the occurrence and the size of catches of both armorhead sculpins in Pacific waters of the northern Kuril Islands and southeastern Kamchatka are subjected to some inrterannual, seasonal, and diurnal dynamics.     

The effects of inhibitors and magnesium ions on the activity of the thermostable extracellular cAMP-Specific phosphodiesterase of <Emphasis Type="Italic">Physarum polycephalum</Emphasis> plasmodium

Plasmodium of myxomycete Physarum polycephalum produces cyclic nucleotide phosphodiesterase (PDE). The extracellular PDE is cAMP-specific and highly thermostable. This study demonstrates that the extracellular PDE of Ph. polycephalum is weakly inhibited by caffeine, isobutylmethylxantine and theophiline (type I mammalian PDE nonspecific inhibitors), dipyridamole (mammalian PDE5, PDE6, PDE8 and PDE10 inhibitors), and erythro-9-[3-(2-hydroxynonyl)]-adenine (mammalian PDE2 inhibitor). The enzyme does not require Mg²⁺ for the activity. The results show that the Ph. polycephalum extracellular PDE differs from class I PDEs, represented by mammalian PDE1-PDE11, and, most likely, belongs to a poorly investigated class II PDEs.     

Distribution of cryptic shrew species of the genus Sorex (Mammalia) on the plain between the Don and Kuban rivers as inferred by molecular markers

Microsatellite and mtDNA markers have been used to identify two pairs of cryptic species Sorex araneus L. (Sorex satunini Ogn.) and Sorex minutus L. (S. volnuchini Ogn.). The new data were obtained on the distribution of these species on the plain between the Don and Kuban rivers. The shrew S. volnuchini and Caucasian mole are distributed on the plain areas up to the Eya River. The endemic species of the Caucasus, the shrews S. satunini and S. volnuchini, are widely distributed across the valleys alongside small streams on the steppe plain. Both species are most abundant on thick grasslands, bushy scrub, and deciduous woodlands. They don??t show any clear differences in habitat preferences.     

Synthesis of GnRH analogues and their application in targeted gene delivery systems

A set of GnRH analogues containing the nuclear localization signal (NLS) of the SV-40 virus was synthesized using solid phase peptide synthesis and chemical ligation techniques. Selective chemical ligation was achieved through hydrazone formation upon the interaction of NLS hydrazide and GnRH analogue modified with pyruvic acid. The efficiency of the synthesized compounds was demonstrated in experiments on transfection of various human cancer cell lines with reporter luciferase and β-galactosidase genes, as well as suicide thymidine kinase gene of HSV-1. Selectivity of the peptide-DNA complex effect on cancer cells is achieved as a result of its penetration through the cell membrane via GnRH receptor-mediated endocytosis pathway.     

Modeling of the composition of materials for soft X-ray sources used in research on inertial confinement fusion

A method for calculating and optimizing the composition of materials for soft X-ray sources used in research on inertial confinement fusion is described. For a target-converter, a material composition is determined with which the conversion of laser light into X radiation is highly efficient. A comparative analysis is carried out of the efficiencies of generation of soft X-ray emission in the plasmas of some composite materials of thin conductors (wires) used as loads in X-and Z-pinches. Numerical calculations of the optical plasma properties are reported whose results make it possible to judge the emissivity of plasmas of different materials. The results obtained are compared to the data from other studies.