A model of human cardiovascular system containing a loop for the autonomic control of mean blood pressure

We propose a model for the human cardiovascular system that describes the cardiac cycle, the autonomic regulation of heart and vessels, the baroreflex, and the formation of blood pressure. The model also allows for the influence of respiration on these processes. It has been found that an allowance for nonlinearity and insertion of a loop for the autonomic control of mean blood pressure (having the form of selfoscillating time-delay system) enables obtaining model signals with statistical and spectral characteristics that are qualitatively and quantitatively similar to those for experimental signals. The model reproduces the phenomenon of synchronization of the loop for mean blood pressure regulation with a basic frequency of approximately 10 s by the signal of respiration.     

Expression of human serum albumin in methylotrophic yeast Pichia pastoris and its structural and functional analysis

The stable strain of methylotrophic yeast Pichia pastoris secreting human serum albumin into cultural medium was obtained. Optimal conditions for expression of the protein were determined. We characterized the recombinant protein by mass spectrometry and circular dichroism and analyzed its catalytic activity.     

The Formation Of Parallel RNA-RNA Duplexes In Vitro

Abstract

Over the years the structural properties of nucleic acids have been of interest, providing data that may be of importance for DNA and RNA organization and function in the cell. We have attempted to look for the formation of parallel RNA-RNA duplexes in vitro. RNA molecules comprising complementary in the same polarity alternating stretches of A and U of increasing length were enzymatically synthesized and annealed in physiological conditions. The fractionation in the denaturing Polyacrylamide gels revealed the formation of two types of full-length parallel RNase A - stable duplexes established either by A-U or by A-A and U-U self pairs. These results suggest novel structural properties of versatile RNA molecules that potentially may be realized in vivo.     

Antibody proteases: induction of catalytic response

Most of the data accumulated throughout the years on investigation of catalytic antibodies indicate that their production increases on the background of autoimmune abnormalities. The different approaches to induction of catalytic response toward recombinant gp120 HIV-1 surface protein in mice with various autoimmune pathologies are described. The peptidylphosphonate conjugate containing structural part of gp120 molecule is used for reactive immunization of NZB/NZW F₁, MRL, and SJL mice. The specific modification of heavy and light chains of mouse autoantibodies with Val-Ala-Glu-Glu-Glu-Val-PO(OPh)₂ reactive peptide was demonstrated. Increased proteolytic activity of polyclonal antibodies in SJL mice encouraged us to investigate the production of antigen-specific catalytic antibodies on the background of induced experimental autoimmune encephalomyelitis (EAE). The immunization of autoimmune-prone mice with the engineered fusions containing the fragments of gp120 and encephalitogenic epitope of myelin basic protein (MBP_89-104) was made. The proteolytic activity of polyclonal antibodies isolated from the sera of autoimmune mice immunized by the described antigen was shown. Specific immune response of SJL mice to these antigens was characterized. Polyclonal antibodies purified from sera of the immunized animals revealed proteolytic activity. The antiidiotypic approach to raise the specific proteolytic antibody as an internal image of protease is described. The second order monoclonal antibodies toward subtilisin Carlsberg revealed pronounced proteolytic activity.     

Evolutonary modifications of molecular structure of ATP-synthase gamma-subunit

The ATP-synthase gamma-subunit (FoF1) belongs to the rotor part of this oligomeric complex. Catalytic hydrolysis of adenosine triphosphate (ATP) is accompanied by rotation of gamma-polypeptide inside the sphere formed by six subunits (alphabeta)3 of the enzyme. The gamma-subunit regulates ATPase and ATP-synthase activities of the FoF1. In the present work, evolutionary and reverse changes of this regulatory polypeptide and their effect on properties of the enzyme are studied. It is suggested that elongation of the gamma-subunit globular part had resulted from the atpC intragene duplication in the process of adaptive evolution. The evolved fragment participates in light regulation of the chloroplast ATP-synthase.     

Electrochemical reduction of sterol-14α-demethylase from <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> (CYP51b1)

The electrochemical reduction of the heme protein sterol-14α-demethylase from Mycobacterium tuberculosis (CYP51b1, or further CYP51) was investigated. Direct electron transfer was demonstrated between CYP51 and graphite screen-printed electrodes modified with gold nanoparticles and with the membrane-like synthetic surfactant didodecyl dimethylammonium bromide. The formal potential of the Fe³⁺/Fe²⁺ pair, E _1/2, is equal to −273 mV (vs. Ag/AgCl). The cathodic current corresponding to the reduction of oxygen by immobilized heme protein was registered in the presence of oxygen. Addition of lanosterol, one of the substrates of the CYP51 family, to the oxygenated solution caused a concentration-dependent increase in the reduction current in voltammetric and amperometric experiments. Ketoconazole, an inhibitor of CYP51, inhibited the catalytic cathodic current in the presence of lanosterol. Electrochemical reduction of CYP51 may serve as an adequate alternative to the reconstituted system, which requires additional redox partners for the exhibition of catalytic activity of heme proteins of the cytochrome P450 superfamily. Published in Russian in Biokhimiya, 2007, Vol. 72, No. 6, pp. 805–811.     

Contribution to the Microlepidoptera Fauna of the South of Krasnoyarsk Territory and the Republic of Khakassia

This paper provides a list of 125 species from 22 families of Microlepidoptera collected in the south of Krasnoyarsk Territory and in the Republic ofKhakassia, with 63 species (50%) and 2 families (Bucculatricidae and Elachistidae) recorded in the region for the first time, and 11 species from 6 families being new to Siberia: Cauchas fibulella, Nemophora fasciella, N. minimella (Adelidae), Phyllonorycter sorbicola, Phyllocnistis extrematrix (Gracillariidae), Cosmiotes freyerella, Elachista subocellea (Elachistidae), Caryocolum alsinella, Scrobipalpula diffluella (Gelechiidae), Agonopterix intersecta (Depressariidae), and Ypsolopha horridella (Ypsolophidae). Three species are new to science: Phyllonorycter sp. and Phyllocnistis verae (Gracillariidae) from the suburbs of Krasnoyarsk and Chrysoesthia sp. (Gelechiidae) from the Republic of Khakassia. Almost half of the faunistic findings belong to two families, Gelechiidae (34 species) and Gracillariidae (24 species). In the former family, the number of species distributed in Krasnoyarsk Territory and/or Khakassia was increased by 1.5 times based on our collection. Trophic specialization remains unknown only for 7 of the 125 species. Most (90%) of the remaining 118 species are phytophagous, the others are saprophagous; 53 species are known as leaf miners. Phytophagous species feed on plants of 36 families and 21 orders. The largest number of microlepidopteran species inhabit plants of the orders Rosales and Fagales (25 and 24 species, respectively). Twelve species are known as pests: Tineidae (4 species), Gracillariidae, Gelechiidae (2 species in each), Argyresthiidae, Choreutidae, Lyonetiidae, and Plutellidae (one species in each). Four pest species have expanded beyond the Palaearctic in the last century: Choreutis pariana (Choreutidae), Scrobipalpa atriplicella (Gelechiidae), Plutella xylostella (Plutellidae), and Niditinea fuscella (Tineidae).     

Thermodynamic and kinetic basis for recognition and repair of 8-oxoguanine in DNA by human 8-oxoguanine-DNA glycosylase

We have used a stepwise increase in ligand complexity approach to estimate the relative contributions of the nucleotide units of DNA containing 7,8-dihydro-8-oxoguanine (oxoG) to its total affinity for human 8-oxoguanine DNA glycosylase (OGG1) and construct thermodynamic models of the enzyme interaction with cognate and non-cognate DNA. Non-specific OGG1 interactions with 10–13 nt pairs within its DNA-binding cleft provides approximately 5 orders of magnitude of its affinity for DNA (ΔG° approximately −6.7 kcal/mol). The relative contribution of the oxoG unit of DNA (ΔG° approximately −3.3 kcal/mol) together with other specific interactions (ΔG° approximately −0.7 kcal/mol) provide approximately 3 orders of magnitude of the affinity. Formation of the Michaelis complex of OGG1 with the cognate DNA cannot account for the major part of the enzyme specificity, which lies in the k_cat term instead; the rate increases by 6–7 orders of magnitude for cognate DNA as compared with non-cognate one. The k_cat values for substrates of different sequences correlate with the DNA twist, while the K_M values correlate with ΔG° of the DNA fragments surrounding the lesion (position from −6 to +6). The functions for predicting the K_M and k_cat values for different sequences containing oxoG were found.     

Hippocampal ripple oscillations (200 Hz) in mechanisms of memory consolidation

A current status of knowledge about high-frequency (140-200 Hz) ripple oscillations in the CA1 hippocampal subfield is summarized and considered in the context of two-stage model of the hippocampal memory processing. A large body of evidence suggests highly-selective recruitment of pyramidal cells and interneurons in the generation of the oscillatory pattern after co-operative sharp-wave-related discharge of CA3 pyramidal neurons. We also discuss a role of transmission via gap junctions in the mechanisms of ripple oscillations as well as their adaptive aminergic (histaminergic) modulation. Patterns of neuronal firing in the hippocampus observed during ripple oscillations reproduce space-dependant neuronal activity from the previous waking period. Together with a data about efficacy of high-frequency stimulation for induction of synaptic modification it points out a role for ripples in the formation of long-term memory. Focal ultra fast ripples (up to 500 Hz) have been shown to participate in the development of temporal lobe epilepsy.