Modeling of substrate and inhibitory complexes of histidine-aspartic protease

A three-dimensional structure of histo-aspartic protease (HAP), a pepsin-like enzyme from the causative agent of malaria Plasmodium falciparum, is suggested on the basis of homologous modeling followed by equilibration by the method of molecular dynamics. The presence of a His residue in the catalytic site instead of an Asp residue, which is characteristic of pepsin-like enzymes, and replacement of some other conserved residues in the active site make it possible for the enzyme to function by the covalent mechanism inherent in serine proteases. The detailed structures of HAP complexes with pepstatin, a noncovalent inhibitor of aspartic proteases, and phenylmethylsulfonyl fluoride, a covalent inhibitor of serine proteases, as well as with a pentapeptide substrate are discussed.     

Effect of a pulsed high-current discharge on hydrogen-air mixtures

A self-consistent model describing the influence of a pulsed discharge on H₂-air mixtures is developed. The model includes the processes of ionization, dissociation, and excitation of the gas molecules by electron impacts; a set of ion-molecular reactions determining the time evolution of the charged particle densities; the processes involving electronically excited atoms and molecules; and a set of reactions describing the ignition of hydrogen-oxygen mixtures. Results are presented from simulations of the oxidation dynamics of hydrogen molecules in a stoichiometric H₂-air mixture and the ignition of such a mixture under the action of a pulsed high-current discharge. The simulation results are compared with available experimental data and calculations performed by other authors.     

Study of the linear conversion of lower hybrid waves in the FT-1 tokamak by the enhanced time-of-flight scattering technique

The propagation of lower hybrid (LH) waves in a tokamak plasma in the presence of an LH resonance surface is studied experimentally with the use of a specially elaborated technique based on the backscattering of the probing microwave radiation in the upper hybrid resonance region. The technique provides resolution in the wave vectors of the scattering density fluctuations. The conditions are determined under which the LH wave propagates in accordance with the predictions of linear theory and is converted into the short-wave-length ion Bernstein mode. The parameter range is found in which the predictions of linear theory fail to hold and the nonlinear effects come into play during LH wave conversion. The radial wavelengths of the LH and ion Bernstein waves are determined.     

Distribution of unselectively bound ligands along DNA

Unselective and reversible adsorption of ligands on DNA for a model of binding proposed by Zasedatelev, Gursky, and Volkenshtein is considered. In this model, the interaction between neighboring ligands located at the distance of i binding centers is characterized by the statistical weight a(i). Each ligand covers L binding centers. For this model, expressions for binding averages are represented in a new simple form. This representation is convenient for the calculation of the fraction of inter-ligand distances of i binding centers f(d)(i) and the fraction of binding centers included in the distances of i binding centers f(bc)(i) for various types of interaction between bound ligands. It is shown that, for non-cooperative binding, contact cooperativity and long-range cooperativity, the fraction of the zero inter-ligand distance f(d)(0) is maximal at any relative concentration of bound ligands (r). Calculations demonstrate that, at low r, f(d)(0) approximately r . a(o), and f(d)(i) approximately r at 1 1/r-L, then f(d)(i) rapidly decreases with i at any r for all types of inter-ligand interaction. At high ligand concentration (r is close to r(max) = L(-1)), f(d)(0) is close to unity and f(d)(i) rapidly decreases with i for any type of inter-ligand interaction. For strong contact cooperativity, f(d)(0) is close to unity in a much lager r interval ((0.5-1) . r(max)), and f(d)(1) approximately a(o)(-1) at r approximately 0.5 . r(max). In the case of long-range interaction between bound ligands, the dependence f(d)(i) is more complex and has a maximum at i approximately (1/r-L)(1/2) for anti-cooperative binding. f(bc)(i) is maximal at i approximately 1/r-L for all types of binding except the contact cooperativity. A strong asymmetry in the influence of contact cooperativity and anticooperativity on the ligand distribution along DNA is demonstrated.     

Positioning of the NOR-bearing chromosomes in relation to nucleoli in daughter cells after mitosis

It is known that chromosomes occupy non-random positions in the cell nucleus. However, it is not clear to what extent their nuclear positions, together with their neighborhood, are conserved in daughter cells. To address specific aspects of this problem, we used the model of the chromosomes carrying ribosomal genes that are organized in clusters termed Nucleolus Organizer Regions (NORs). We compared the association of chosen NOR-bearing chromosomes (NOR-chromosomes) with nucleoli, as well as the numbers of nucleoli, in the pairs of daughter cells, and established how frequently the daughter cells had equal numbers of the homologs of certain NOR-chromosomes associated with individual nucleoli. The daughter cells typically had different numbers of nucleoli. At the same time, using immuno-FISH with probes for chromosomes 14 and 15 in HeLa cells, we found that the cell pairs with identical combinations appeared significantly more frequently than predicted by the random model. Thus, although the total number of chromosomes associated with nucleoli is variable, our data indicate that the position of the NOR-bearing chromosomes in relation to nucleoli is partly conserved through mitosis.     

The use of molecular genetic methods for prognosis of aerobic and anaerobic performance in athletes

The distribution of genotypes and alleles of ACE (I/D polymorphism), ACTN3 (R577X), NOS3 (5/4), UCP2 (Ala55Val), and UCP3 (-55C/T) genes, as well as the correlation between the genotype and physiological parameters, was studied in rowers (n = 230) and in a control group (n = 855). The genotypes were determined by analyzing restriction fragment length polymorphism. Physiological parameters were determined with a PM 3 rowing ergometer and a MetaMax 3B gas analyzer. The frequency of the ACE II genotype was significantly higher in elite rowers (n = 107) than in the control subjects. The frequency of the ACTN3 XX genotype, unfavorable for development of speed and strength qualities, was twofold lower in all rowers than in the control subjects. The frequencies of the ACE I, ACTN3 R, UCP2 Val, and UCP3 T alleles increased in the athletes along with an increase in skill, which suggested natural sports selection. In addition, ACE I, NOS3 5, UCP2 Val, and UCP3 T alleles correlated with a high aerobic performance. Thus, the ACE I, NOS3 5, UCP2 Val, and UCP3 T alleles may be regarded as genetic markers associated with enhanced aerobic performance and may be included in a diagnostic system for prognosis of human physical performance.     

Preliminary study on biomarkers for the fungal resistance in Vitis vinifera leaves

We examined the leaf chemical composition of six seedlings obtained by self-pollination of the Bulgarian wine-making variety Storgozia as well as the cultivar Bouquet, which is the susceptible parent of Storgozia. The chemical composition was investigated in the framework of a program for identification of metabolites associated with disease resistance in grape-vine. Acetone, dichloromethane and butanol extracts, as well as volatiles obtained from fresh material were analyzed by GC/MS. Based on the correlations of the GC/MS data and estimated resistance of the leaves towards the etiological agents of powdery mildew, downy mildew and botrytis as biomarkers for the fungal resistance, we proposed 16 individual metabolites – - and γ-tocopherol, squalene, -amyrine, stigmasta-3,5-diene-7-one, hexahydrofarnesyl acetone, glycolic acid, 3-hydroxybutanoic acid, 3-hydroxycaproic acid, malic acid, tartaric acid, erythronic acid, arabinoic acid, monoethyl phosphate, undecyl laurate and isopropyl myristate. The obtained correlations were confirmed by cluster analysis.