Molecular dynamics of human alpha-fetoprotein fragment LDSYQCT and its analogs at different dielectric constants

A comparative study of the conformation dynamics of the human alpha-fetoprotein fragment LDSYQCT and heptapeptides derived from it by point substitutions has revealed a significant influence of electrostatic interactions on the set of preferred conformations and dynamics of amino acid residues when the peptides with blocked termini are examined at ? = 1. Peptide flexibility rises when the termini are left free (charged). At ? = 10 or 80, the set of probable conformations for all residues expands to much the same extent, i.e., at higher permittivity of the medium the dynamic effects of amino acid changes are leveled off.     

Prebiotic Syntheses Under Shock in the Water – Formamide – Potassium Bicarbonate – Sodium Hydroxide System

Origins of Life and Evolution of Biospheres - Syntheses under shock in nitrogen bubbled samples of the water – formamide – bicarbonate – sodium hydroxide system at...     

Systemic Neurochemical Alterations in Schizophrenic Brain: Glutamate Metabolism in Focus

We have used a systemic approach to establish a relationship between enzyme measures of glial glutamate and energy metabolism (glutamine synthetase and glutamine synthetase-like protein, glutamate dehydrogenase isoenzymes, brain isoform creatine phosphokinase) and two major glial proteins (glial fibrillary acidic protein and myelin basic protein) in autopsied brain samples taken from patients with schizophrenia (SCH) and mentally healthy subjects (23 and 22 cases, respectively). These biochemical parameters were measured in tissue extracts in three brain areas (prefrontal cortex, caudate nucleus, and cerebellum). Significant differences in the level of at least one of the glutamate metabolizing enzymes were observed between two studied groups in all studied brain areas. Different patterns of correlative links between the biochemical parameters were found in healthy and schizophrenic brains. These findings give a new perspective to our understanding of the impaired regulation of enzyme levels in the brain in SCH.     

A molecular dynamics simulation study of human alpha-fetoprotein-derived peptide and its analogues. Influence of dielectric constant

A comparative study of the conformation dynamics of a series of heptapeptides: the human alpha-fetoprotein fragment LDSYQCT and its seven analogues has been conducted. The effect of the dielectric constant of medium on the dynamics of heptapeptide conformation is considered. It is shown that electrostatic interactions have a marked effect on several accessible conformations and the dynamics of the behavior of amino acid residues.     

Glutamate Metabolizing Enzymes in Prefrontal Cortex of Alzheimer’s Disease Patients

Amounts of glutamate metabolizing enzymes such as glutamate dehydrogenase (GDH), glutamine synthetase (GS), GS-like protein (GSLP), and phosphate-activated glutaminase (PAG) were compared in prefrontal cortex of control subjects and patients with Alzheimer disease (AD). The target proteins were quantified by ECL-Western immunoblotting in extracts from brain tissue prepared by two different techniques separating enzymes preferentially associated with cytoplasm (GDH I and II isoenzymes, GS, and partially GSLP) and membrane (GDH III, PAG, and partially GSLP) fractions. Amounts of all listed enzymes were found significantly increased in the patient group compared with controls. Some links between the measured values were observed in the control, but not in the AD patient group. The results may suggest for the pathological interruption of regulatory relations between distinct enzymes of glutamate metabolism in brain of AD patients.     

Exploring of Primate Models of Tick-Borne Flaviviruses Infection for Evaluation of Vaccines and Drugs Efficacy

Tick-borne encephalitis virus (TBEV) is one of the most prevalent and medically important tick-borne arboviruses in Eurasia. There are overlapping foci of two flaviviruses: TBEV and Omsk hemorrhagic fever virus (OHFV) in Russia. Inactivated vaccines exist only against TBE. There are no antiviral drugs for treatment of both diseases. Optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against TBE and relative flaviviruses. The models for TBE and OHF using subcutaneous inoculation were tested in Cercopithecus aethiops and Macaca fascicularis monkeys with or without prior immunization with inactivated TBE vaccine. No visible clinical signs or severe pathomorphological lesions were observed in any monkey infected with TBEV or OHFV. C. aethiops challenged with OHFV showed massive hemolytic syndrome and thrombocytopenia. Infectious virus or viral RNA was revealed in visceral organs and CNS of C. aethiops infected with both viruses; however, viremia was low. Inactivated TBE vaccines induced high antibody titers against both viruses and expressed booster after challenge. The protective efficacy against TBE was shown by the absence of virus in spleen, lymph nodes and CNS of immunized animals after challenge. Despite the absence of expressed hemolytic syndrome in immunized C. aethiops TBE vaccine did not prevent the reproduction of OHFV in CNS and visceral organs. Subcutaneous inoculation of M. fascicularis with two TBEV strains led to a febrile disease with well expressed viremia, fever, and virus reproduction in spleen, lymph nodes and CNS. The optimal terms for estimation of the viral titers in CNS were defined as 8–16 days post infection. We characterized two animal models similar to humans in their susceptibility to tick-borne flaviviruses and found the most optimal scheme for evaluation of efficacy of preventive and therapeutic preparations. We also identified M. fascicularis to be more susceptible to TBEV than C. aethiops.     

Molecular dynamics of oligopeptides 6. A comparative study of poincare cross-section of monopeptide frames in media with different hydrophobicity

A comparative study of the molecular dynamics of natural amino acid residues and their closest homologues and isomers was carried out. Molecular dynamics protocols not interfering with the principle of equidistribution of energy with respect to degrees of freedom were used. Poincare cross-sections, auto- and cross-correlation of complex exponential curves as a function of dihedrons were considered. The classification of dynamic properties of conformational degrees of freedom in the series of amino acid residues was carried out.     

Molecular dynamics of oligopeptides. A comparative study of residue interactions in dipeptides

The molecular dynamics of dipeptides of natural amino acids were examined using protocols that do not violate the principle of equal distribution of energy over the degrees of freedom. Comparative analysis involved autocorrelation functions of complex exponentials from dihedrals. The mutual influence of residues was classified by the effects on the dynamic properties of the neighbors.     

Biocrystalline structures in the nucleoids of the stationary and dormant prokaryotic cells

Compaction and biocrystallization of the nucleoid are presently considered as a necessary and important stage in the transformation of the cell ultrastructure during change of microbial cultures strategies from growth to survival. Nucleoid biocrystallization in the stationary phase cells is achieved due to structural regularity of the DNA complexes with the histone-like Dps protein. Our experiments with Escherichia coli mutants, overproducers of the Dps protein, confirmed nucleoid biocrystallization in the late stationary phase cells. Since nucleoid biocrystallization was revealed in E. сoli cells without Dps overproduction at late stages of starvation, it is constitutive in the cycle of development of microbial populations. The present work concentrated on detection of the nucleoid biocrystalline structure in (1) long-starved (21 day in the chemostat mode) bacterial cells (genera Arthrobacter and Pseudomonas), (2) dormant ametabolic (anabiotic) cells of such prokaryotes as archaea and non-spore-forming bacteria, (3) endospores of bacilli, (4) streptomycete exospores, and (5) in the cells surviving in permafrost for (2?3 Ma). The topics discussed include nucleoid biocrystallization as a necessary stage of maturation of the dormant microbial cells providing for survival and preservation of the species, dynamics of nucleoid biocrystallization during maturation of the dormant cells, and its possible role for the preservation of genetic information in the case of autolysis of most of the cells in a developing culture.     

Comparative study of molecular dynamics,diffusion, and permeability for ligands in biomembranes of different lipid composition

A comparative study of several model lipid bilayers of different composition, which included analysis of kinetic parameters of model lipid bilayers and permeability of bilayer membranes for small molecules, has been carried out. The conformity of results of numeric experiments to experimental data (structure of membrane lipid bilayers, lateral diffusion coefficients, and relative permeability of biomembranes for ligands) is discussed in the framework of a standard molecular dynamics protocol.