Statistical fluctuations in processes of gene expression regulation: consideration of the problem from point of view of statistical mechanics

The regulation of gene expression is a basic problem of biology. In some cases, the gene activity is regulated by specific binding of regulatory proteins to DNA. In terms of statistical mechanics, this binding is described as the process of adsorption of ligands on the one-dimensional lattice and has a probability nature. As a random physical process, the adsorption of regulatory proteins on DNA introduces a noise to the regulation of gene activity. We derived equations, which make it possible to estimate this noise in the case of the binding of the lac repressor to the operator and showed that these estimates correspond to experimental data. Many ligands are able to bind nonspecifically to DNA. Nonspecific binding is characterized by a lesser equilibrium constant but a greater number of binding sites on the DNA, as compared with specific binding. Relations are presented, which enable one to estimate the probability of the binding of a ligand on a specific site and on nonspecific sites on DNA. The competition between specific and nonspecific binding of regulatory proteins plays a great role in the regulation of gene activity. Similar to the one-dimensional "lattice gas" of particles, ligands adsorbed on DNA produce "one-dimensional" pressure on proteins located at the termini of free regions of DNA. This pressure, an analog of osmotic pressure, may be of importance in processes leading to changes in chromatin structure and activation of gene expression.     

Model of three dimensional structure of the immunodominant epitope of gp120 HIV(Thailand)

The geometry of five preferred structures of the immunodominant epitope of the HIV(Thailand) protein gp120, derived earlier from the NMR spectroscopy data, was refined using the quantum chemical methods. As a result, (i) the energy characteristics of the initial structures were improved significantly, (ii) their relative locations on the scale of formation heats were determined, and (iii) the energy barriers dividing the conformers under study were computed. On this basis, only two out of five starting structures were proposed as biologically relevant conformations for the virus immunogenic crown. The results obtained are discussed in connection with the literature data on the structure of the HIV-1 principal neutralizing determinant.     

Effect of infrared laser radiation on sorption of dry cartilage and connective tissue preparations

Cartilaginous and connective tissues were exposed to a moderate-intensity IR laser treatment with IR radiometric temperature control. The isotherms of water sorption by dry preparations of intact and laser-treated tissues were obtained and calculated in terms of well known models. It was shown that the sorption capacity of a monolayer of tissues decreases with increasing temperature during laser treatment. Changes in the supramolecular structure of the extracellular matrix of tissues (loss of regularity) upon IR laser exposure are discussed.     

Two-level heterogenous energy migration. Modeling and application to purple bacteria

The dynamics of migration of electronic excitations and the efficiency of their trapping in two-dimensional ensembles of molecules were analyzed. Molecules were characterized using the following parameters: the width of long-wavelength bands, the values of extinction and rate constant of deactivation of electronic excitations, critical distances of migration close to those of dye molecules, in particular, bacteriochlorophyll a and purple bacteria. A comparative analysis of two-dimensional models of energy migration made it possible to chose a model with an optimum light-harvesting on traps from the largest numbers of light-absorbing molecules. It was shown that in ensembles of molecules having different spectral characteristics (spectral shifts between the short- and long-wavelength fractions of the molecules are hear 800 cm-1) the efficiency of excitation trapping is approximately 90 and 80% for the number of light-harvesting molecules per one trap 210 and 580, respectively.     

Reaction of rats organ cells to inhibition of protein biosynthesis by sublethal doses of cycloheximide

Time-dependent responses of cellular systems in rat organs and Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in blood to the blocking of translation by sublethal doses of cycloheximide (CHI) was studied by EPR spectroscopy and radioisotope techniques. It was shown that, within the early post-CHI-treatment time, the suppression of deoxyribonucleotide and DNA biosynthesis, the activation of catabolic enzymes, the inhibition of electron transfer in the mitochondrial electron transport chain, the activation and the following inactivation of cytochrome P-450, and an intensive production of nitrosyl complexes in rat blood and organs occur. In addition, the activation of the synthesis of steroid hormones in adrenal gland was revealed within 1-24 h after cycloheximide injection. In response to these metabolic disturbances, nonspecific compensatory recovery reactions developed, first of all, the "reprograming" of the translation process to produce new protein-synthesizing elements instead of cycloheximide-blocked ones. The activation of protein synthesis promotes the recovery of deoxyribonucleotide and DNA synthesis, the restoration of the redox state of mitochondrial and microsomal electron transport chains in organs as well as an increase of Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in rat blood. These metabolic processes result in the full recovery of the functional ability of organs.     

Age-specific morphological-functional characteristics of the rabbit's hippocampal neurons during conditioning

Formation of trace rhythm recruitment (an analogue of conditioned time reflex) was studies in CA3 hippocampal neurons of alert young (less than one year), old (54-65 months), and very old rabbits after a prolonged (10-20 min) electro-cutaneous stimulation of a forelimb with the frequency of 0.5-1 Hz. Comparative analysis of neuronal spike activity in young and old rabbits showed that in the late ontogeny the number of spontaneously active neurons was significantly decreased, the proportion of slowly firing neurons increased, the interspike intervals and intervals between spike groups became longer, the number of spikes in a group reduced. The ability of hippocampal neurons to acquire and reproduce the rhythm of the previous stimulation declined with age. No appropriate rhythms were found in neurons of very old animals. A nonspecific increase in neuronal baseline activity was observed in old rabbits after the stimulation. Deterioration of morphological structures of hippocampal neurons and glial cells may explain the impairment of mnestic processes in late ontogeny.     

The origin of neointimal cells in the rat carotid artery after balloon angioplasty

At present the issue of a possible role of circulating stem cells and precursors in pathological vascular wall remodeling after angioplasty remains unsolved. Therefore the origin of neointimal cells was examined in the rat carotid artery after balloon angioplasty using morphological and immunocytochemical approaches. It is shown that at the early stages (1-7 days) after vessel injury acute inflammatory response arises in the arterial wall recruiting neutrophils, monocytes, macrophages as well as large amounts of low-differentiated blood-derived cells. At the late stages (10-28 days), at the area of injured intima, a new hyperplastic intima (neointima) is formed, which consists of cells carrying specific smooth muscle markers--alpha-actin and smoothelin. The study on cell proliferative behaviour in the injured vessel wall by bromodeoxyuridine showed that in the process of neointima formation blood-born rather than resident cells are involved. Probably, early smooth muscle and endothelial precursor cells penetrate into injured area with blood stream, where they proliferative and differentiate into mature cells.     

Structural and functional analysis of glucose adsorption at high maltose concentrations in the rat small intestine in vivo

To elucidate the mechanism of glucose absorption at high substrate concentrations, we studied structural and ultrastructural peculiarities of enterocytes arranged at different levels along the intestinal villus. The preparations were obtained from an isolated segment of the rat small intestine after its perfusion with maltose solutions with both low (25 mM) and high (100 mM) concentrations, respectively. Under conditions of chronic experiment at high substrate concentration, an enlargement of intercellular clefts, indicating glucose absorption, occurred in deeper areas of the villus. Besides, also in chronic experiment, we studied kinetics of maltose hydrolysis and derived glucose absorption in the isolated segment of the rat small intestine after its perfusion with maltose at superhigh (up to 200 mM) initial concentrations. Based on these data, a conclusion is made that active transport is the main mechanism of absorption of glucose derived from maltose hydrolysis, operating both at low disaccharide concentrations, and in the range of its superhigh (up to 200 mM) concentrations.     

Plants in urbanized natural environment: florogenesis,coenogenesis and population structure

Published data on both flora and phytocoenosis genesis and plant population dynamics are reviewed. Urbanized environment is rated as a stress factor for single plants and their communities. The change of plant population structure in cities and towns is analysed as the important indicator of the environment quality. The problems of phytoindication of environment quality in cities and towns for its optimization are considered.