On prediction of folding nuclei in globular proteins

The approach described in this paper on the prediction of folding nuclei in globular proteins with known three dimensional structures is based on a search of the lowest saddle points through the barrier separating the unfolded state from the native structure on the free-energy landscape of protein chain. This search is performed by a dynamic programming method. Comparison of theoretical results with experimental data on the folding nuclei of two dozen of proteins shows that our model provides good phi value predictions for proteins whose structures have been determined by X-ray analysis, with a less limited success for proteins whose structures have been determined by NMR techniques only. Consideration of a full ensemble of transition states results in more successful prediction than consideration of only the transition states with the minimal free energy. In conclusion we have predicted the localization of folding nuclei for three dimensional protein structures for which kinetics of folding is studied now but the localization of folding nuclei is still unknown.     

The influence of mesenchymal stem cells on bone tissue regeneration upon implantation of demineralized bone matrix

Mesenchymal stem cells (MSC) are resident pluripotent cells of bone marrow stroma. MSC are able to differentiate into chondroblasts, adipocytes, neurons, glia, cardiomyocytes, or osteoblasts. The problem of MSC usage in cell therapy of bone defects is widely discussed at present. The experiments were carried out using rats of inbred line Wistar-Kyoto. MSC were isolated from bone marrow and cultivated in vitro. Demineralized bone matrices (DBM) were obtained from parietal bones of rats and hens. Part of DBM was loaded with MSC. Bone defects were made in cranium parietal regions. DBM with or without MSC or metal plates were transplanted in these regions. It was shown that the application of MSC increased angiogenesis and osteogenesis in the damaged bone. The implantation of rat's DBM with MSC led to the formation of a full value bone. MSC suppressed inflammation, when transplantation of hen's DBM was carried out. The application of MSC always improved bone tissue regeneration.     

Influence of intracellular pH on character of mice peritoneal macrophage response to red light irradiation

It was detected that exposure of macrophages to red light (600-740 nm) led to the changes in their intracellular pH and hydrolytic activity. The character of these changes depends on the initial level of pH in the cells. The maximum effect of irradiation is detected if the initial pH level is low. It is possible that Na/H-exchanger takes part in normalizing effect of red light on intracellular pH level.     

Mathematical modeling of electron and protein transport, coupled with ATP synthesis in chloroplasts

A mathematical model of electron and proton transport in chloroplasts of higher plants was developed, which takes into account the lateral heterogeneity of the lamellar system. Based on the results of numerical experiments, lateral profiles of pH in the thylakoid lumen and in the narrow gap between grana thylakoids under different metabolic conditions (in the state of photosynthetic control and under photophosphorylation conditions) were simulated. Lateral profiles of pH in the thylakoid lumen and in the intrathylakoid gap were simulated for different values of the proton diffusion coefficient and stroma pH. The model demonstrated that there might be two mechanisms of regulation of electron and proton transport in chloroplasts: (1) the slowing down of noncyclic electron transport due to a decrease in the intrathylakoid pH, and (2) the retardation of plastoquinone reduction due to slow diffusion of protons inside the narrow gap between the thylakoids of grana.     

Neuronal interaction at the cell body level in the snail CNS. Neuroactive environment heterogeneity

In experiments on Lymnaea stagnalis, a single neuron isolated from the PeA cluster was used as moveable sensor for monitoring extracellular environment of the CNS surface. At the serotoninergic PeA area, two novel neuroactive factors were detected: inhibitory and excitatory ones. The former is transiently released whenever extracellular 5-HT increases. A distinctive feature of the latter is that it narrows the action potential of the sensor cell. The findings demonstrate that natural neuro-active factors occur in the soma vicinity in effective concentrations, thus suggesting that, in the snail brain, activity of central neurons is controlled by neurotransmitters operating at the cell body level.     

Types of the peptide modulation of the vagus nerve effect on the heart rhythm

In anaesthetised cats, effects of 24 regulatory peptides upon inhibitory tonic and synchronizing components of vagal chronotropic action, were studied. The findings allowed to divide the peptidergic vagotropic activity into three types: (1) a selective action upon inhibitory tonic vagal effect; (2) a selective modulation of synchronizing vagal effect; (3) opposite changes in the vagal chronotropic effect components. The peptides seem to be able to modulate both the vagal bradycardia and the functional structure of parasympathetic chronotropic effect.     

Tumor-associated changes in the buccal epithelium in human breast and thyroid pathology

The estimation of the malignancy-associated changes in oral mucosa of patients with benign and malignant processes in mammary and thyroid gland is carried out on the basis of textural and densitometric indices of the interphase nuclei of the epitheliocytes with the help of the methods of mathematical statistics.     

Single amino acid substitutions in the Ca2+-binding site of recoverin.II.The unusual behavior of the protein upon the binding of calcium ions

The structural properties of myristoylated forms of recombinant recoverin of the wild type and of its mutants with damaged second and/or third Ca(2+)-binding sites were studied by fluorimetry and circular dichroism. The interaction of wild-type recoverin with calcium ions was shown to induce unusual structural rearrangements in its molecule. In particular, protein binding with Ca2+ ions results in an increase in the mobility of the environment of Trp residues, in higher hydrophobicity, and in elevated thermal stability (its thermal transition shifts by 15 degrees C to higher temperatures) but has almost no effect on its secondary structure. Similar structural changes induced by Ca2+ are also characteristic of the -EF2 mutant of recoverin whose second Ca(2+)-binding site is modified and cannot bind calcium ions. The structural properties of the -EF3 and -EF2,3 mutants (whose third or simultaneously second and third Ca(2+)-binding sites, respectively, are modified and damaged) are practically indifferent to calcium ions.