Synthesis of new 1-alkyl-, 1-benzyl-, and 1-aryloxyethyl-substituted 4,5-dichloroimidazoles and their antimicrobial,protistocidal, and fungistatic properties

Previously unknown 1-alkyl-, 1-benzyl-, and 1-aryloxyethylderivatives of dichloroimidazoles and products of their structural transformation were synthesized from 4,5-dichloroimidazole or 2-methyl-4,5- dichloroimidazole using alkyl, benzyl or aryloxyethyl halides. These N-substituted compounds were shown to have a weak antibacterial activity against some pathogenic gram-positive and gram-negative bacteria (Staphylococcus aureus and Escherichia coli). At the same time, some of the obtained compounds demonstrated a significant protistocidal activity against Colpoda steinii, which can exceed in strength the activity of clinically used veterinary drug Baycox. Moreover, these compounds showed a pronounced fungistatic effect.     

Multiparticle computer simulation of photosynthetic electron transport in a thylakoid membrane

A method for multiparticle computer simulation of photosynthetic electron transport in a thylakoid membrane has been developed. The basic principles of this method were described previously. The method is used to describe the cyclic electron flow around photosystem I. The effects of size and shape of the reaction volume on the kinetics of interaction of a mobile carrier with a protein complex and the limited diffusion of reactants were studied. It was shown that the kinetic parameters of photosynthetic electron transport processes depend on the distribution of protein complexes in the membrane. It was shown that the limited nature of diffusion of plastoquinone molecules in the membrane leads to a tenfold decrease in the efficient diffusion coefficient. It was shown that the occurrence of two phases of dark reduction of photooxidized P700+ is due to a heterogeneous spatial organization of the thylakoid membrane of a chloroplast.     

Detection of the 5382insC mutation in the human <Emphasis Type="Italic">BRCA1</Emphasis> gene with fluorescent labeled oligonucleotides

Analysis of genetic predisposition to cancer provides valuable information for early cancer detection or even prevention. The 5382insC insertion in the BRCA1 gene is the most frequent mutation among those associated with high breast cancer risk in women of East European origin. A method for 5382insC detection with fluorescent labeled allele-specific oligonucleotides in the Duplex Scorpion format has been developed. The method can be used under real-time PCR conditions as well as under the conditions of end-point fluorescence measurement following regular PCR. The adequacy of the method was demonstrated in the study of the 5382insC mutation frequency in breast cancer patients. A total of 564 genomic DNA samples from breast cancer patients were screened. Eleven patients (1.95%) were found to carry the mutation under consideration in the heterozygous state. The 5382insC allele frequency in the breast cancer patient group was 0.0098. The method is appropriate in clinical practice to detect individuals at high breast cancer risk, as well as in large-scale population studies.     

Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones,novel analogues of antitumor anthracene-9,10-diones

We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53^?/? cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b]thiophene-5,10-dione derivatives.     

Molecular Implications of Repeated Aggression: Th,Dat1, Snca and Bdnf Gene Expression in the VTA of Victorious Male Mice

Background

It is generally recognized that recurrent aggression can be the result of various psychiatric disorders. The aim of our study was to analyze the mRNA levels, in the ventral tegmental area (VTA) of the midbrain, of the genes that may possibly be associated with aggression consistently shown by male mice in special experimental settings.

Methodology/Principal Findings

The genes were Th, Dat1, Snca and Bdnf; the male mice were a group of animals that had each won 20 daily encounters in succession and a group of animals that had the same winning track record followed by a no-fight period for 14 days. Increased Th, Dat1 and Snca mRNA levels were in the fresh-from-the-fight group as compared to the controls. Increased Th and Dat1 mRNA levels were in the no-fight winners as compared to the controls. Significant positive correlations were found between the level of aggression and Th and Snca mRNA levels.

Conclusions

Repeated positive fighting experience enhances the expression of the Th, Dat1 and Snca genes, which are associated with brain dopaminergic systems. The expression of the Th and Dat1 genes stays enhanced for a long time.     

Multiparticle computer simulation of protein interactions in the photosynthetic membrane

The basic principles of the design of direct multiparticle models and the results of multiparticle computer simulation of electron transfer by mobile protein carriers in the photosynthetic membrane of a chloroplast thylakoid are presented. The reactions of complex formation of the plastocyanin with cytochrome f and the pigment-protein complex of photosystem I, as well as of ferredoxin with FNR and photosystem I are considered. The regulatory role of diffusion and electrostatic interactions as well as the effect of the shape of the reaction volume and ionic strength on the rate of electron transport are discussed.     

Comparative study of hepatoprotective action of remaxol, reamberin and ademethionine in liver injury induced by antituberculosis drugs (experimental study)

The hepatoprotective activity of remaxol, reamberin and ademethionine was studied on a model of the liver injury induced by antituberculosis drugs. The study included 30 male uninbred albino rats. The following antituberculosis drugs were used: isoniazid (50 mg/kg) subcutaneously + rifampicin (250 mg/kg) intragastrically + pyrazinamide (45 mg/kg) intragastically (by the procedure of Yu. I. Slivka, 1989). Remaxol, reamberin and ademethionine were administered 1.5 hour prior to the antituberculosis drugs. The treatment course was 14 days. It was shown that remaxol, reamberin and ademethionin were able to correct the structural and functional disorders in the liver due to the use of the antituberculosis drugs. By the impact on the biochemical indices, evident of the liver function condition, remaxol showed the maximum effect. The effect of ream-berin was somewhat lower and the results of the ademethionine use were less significant. Remaxol had also a distinct effect as for lowering the level of the structural injuries in the liver, evident from recovery of the organ histoarchitectonics, less extended carbohydrate, albuminous and fatty degeneration, more active intracellular regeneration. It was noted that ademethionine had an insignificant effect on necrobiosis. Moreover, there was once detected a large necrosis focus, evident of possible stimulation of the liver tissue alteration by the drug.     

Flying over water: how “On bird species diversity” influenced aquatic ecology

Habitat complexity has long been known to influence animal community structure by increasing the number of available habitats. Fifty years have passed since MacArthur brothers published the seminal paper “On bird species diversity”, which revolutionized studies of habitat structure. This paper first evidenced and quantified the relationship between species diversity (birds) and habitat structural complexity (the number of stratified layers of landscape vegetation). In this article, we aim to pay homage to R. H. MacArthur’s contribution and to briefly analyze the citation history and influence of “On bird species diversity”, focusing primarily on aquatic studies. We searched for all papers that cited “On bird species diversity” on Thomson Reuters (ISI—Web of Knowledge) and analyzed them for temporal citation trends. In addition, considering only aquatic papers, we explored whether and how habitat complexity was measured, as well as the ecological organization level, attributes of organisms, taxonomic groups and study design (observational or experimental). “On bird species diversity” citations increased over time, but this paper was less cited by limnologists compared to terrestrial and marine scientists. The majority of investigations in aquatic ecosystems quantified habitat complexity, but few used mathematical modeling. The high number of citations, which continues to increase, shows the great influence of “On bird species diversity” on ecological studies and typifies it as a classic in the ecological literature. However, the low citation frequency found in papers devoted to freshwater ecosystems indicates that limnologists in general neglect this original contribution in studies of habitat complexity.     

Biological properties of the alpha-mannanase of Rhodococcus erythropolis

When Rhodococcus erythropolis is cultivated under the submerged conditions in a medium containing yeast mannan as a sole carbon source, it synthesizes exocellular alpha-mannanase which hydrolyzes alpha-1,2 and alpha-1,3 bonds in a mannan molecule. The alpha-mannanase of R. erythropolis exerts distinct lectin properties under the conditions which entirely exclude its enzyme activity.