Therapeutical effect of modified adamantane copolymer compounds: study of molecular mechanisms.

Copolymers of N-polyvinylpyrrolidone-acrylic acid (AB-1) and adamantane derivatives are known to possess marked antiviral activity in in vitro and in ovo models. Among the constructed preparations of AB-1 modified by adamantane derivatives some, especially AB-4 (modified by deitiforin), were found to show more extended antiviral activity and to inhibit markedly virus reproduction in susceptible permissive cell cultures and chicken embryos. In AB-4 treated cells and allantoic sacs, virus titers (influenza virus, herpes virus, and HIV) and virus antigen concentration were decreased. On the other hand, herpes virus-specific thymidine kinase and of DNA-polymerases isolated from Escherichia coli, Plectonema boryanum, and herpes virus type 1 infected murine brain tissue retained their activity after incubation with AB-4 or AB-2. The compounds investigated, in view of their effect on virus reproduction, are thought to be prospective as antiviral agents.     

Birth and death of protein domains: A simple model of evolution explains power law behavior

Background  

Power distributions appear in numerous biological, physical and other contexts, which appear to be fundamentally different. In biology, power laws have been claimed to describe the distributions of the connections of enzymes and metabolites in metabolic networks, the number of interactions partners of a given protein, the number of members in paralogous families, and other quantities. In network analysis, power laws imply evolution of the network with preferential attachment, i.e. a greater likelihood of nodes being added to pre-existing hubs. Exploration of different types of evolutionary models in an attempt to determine which of them lead to power law distributions has the potential of revealing non-trivial aspects of genome evolution.     

Requirements of Pseudomonas aeruginosaDissociants in Glucose, Nitrate, and Phosphate. Limiting Concentrations of the Nutrients during Batch Cultivation

Requirements of R-, S-, and M-dissociants of Pseudomonas aeruginosaK-2 strain in glucose, nitrate, and phosphate, as well as the error of determination, have been calculated from the data of 250 experiments on their batch cultivation on the media with the various initial content of these resources. The resource requirements of R- and S-dissociants appear indistinguishable within the error limits. The requirements of M-dissociant significantly differ from those of R- and S-forms; however, due to specific growth of the M-form, the confidence intervals of the measured values can overlap with those of R-space and S-forms. The obtained requirement values allow an evaluation of the studied resources concentration limiting the culture growth.     

A Method to Simultaneously Detect Changes in Intracellular Ca<Superscript>2+</Superscript> Concentration and Cell Volume

A method to simultaneously assess the changes in intracellular calcium concentration and cell volume in single cells was developed using the Ca²⁺-sensitive fluorescent probe Fura-2 and a three-dimensional image-surface reconstruction technique, respectively. Studies with this method showed that Fura-2 loading had no significant effect on the kinetics of A549 human epithelial cell swelling in a hypotonic solution, as well as the volume restoration kinetics. Significant changes in intracellular Ca²⁺ concentration were not observed in the examined volume modulation range. The results suggest that Ca²⁺-mediated signaling pathways are not involved in the autoregulation of the cell volume in A549 cells exposed to hypotonic conditions.     

ATP-Mediated Compositional Change in Peripheral Myelin Membranes: A Comparative Raman Spectroscopy and Time-Of-Flight Secondary Ion Mass Spectrometry Study

In the present paper we addressed a mechanism of the myelin reorganization initiated by extracellular ATP and adenosine in sciatic nerves of the frog Rana temporaria. In combination with Raman microspectroscopy, allowing noninvasive live-cell measurements, we employed time-of-flight secondary ion mass spectrometry (TOF-SIMS) to follow the underlying changes in chemical composition of myelin membranes triggered by the purinergic agents. The simultaneous increase in lipid ordering degree, decrease in membrane fluidity and the degree of fatty acid unsaturation were induced by both ATP and adenosine. Mass spectrometry measurements revealed that ATP administration also led to the marked elevation of membrane cholesterol and decrease of phosphotidylcholine amounts. Vesicular lipid transport pathways are considered as possible mechanisms of compositional and structural changes of myelin.     

Mechanisms of the inhibition of Fe2+-induced oxidation of phosphatidylcholine by polyhydroxynaphthoquinones

The kinetics of egg phosphatidylcholine oxidation induced by an artificial prooxidant Fe2+--ascorbate system or hematine was followed by oxygen uptake. The protective effect of natural free radical scavangers--polyhydroxynaphthoquinones, ionol (BHT), alpha-tocopherol and EDTA was estimated by the decrease of the phosphatidylcholine oxidation rate. EDTA was shown to inhibit the Fe2+--ascorbate-induced oxidation but had no effect on the hematine-induced oxidation. The inhibiting effect of polyhydroxynaphthoquinones on Fe2+--ascorbate-induced oxidation was 10-100 times as high as that on hematine-induced oxidation. The effects of BHT and alpha-tocopherol were the same in both models. Natural polyhydroxynaphthoquinones interacted with the free radical diphenylpicrylhydrazyl in stoichiometric ratios coinciding with the number of beta-hydroxyls in naphthoquinone molecules; the methylation of these hydroxyls fully suppressed such an interaction. Two possible mechanisms of action of polyhydroxynaphthoquinones as antioxidative agents are discussed. The first of these is coupled with the formation of Fe2+--PHNQ complexes, while the second one--with their effect as free radical scavengers. In both cases, beta-hydroxyls of naphthoquinone molecules were shown to play a key role.