New approaches to construction of transgenic animals with high level tissue-specific expression of foreign genes: construction and reconstruction of genomic domains

The major problems in constructing transgenic animals and approaches to their solution are discussed. Modern views of the structural-functional organization of the eukaryotic genome are considered. The domain hypothesis of the genome organization is analyzed in detail, as many problems associated with a low level and a lack of tissue specificity of transgene expression can be solved at the step of construction (or reconstruction of existing domains).     

Structural-functional peculiarities of the wing apparatus of insects that do not have and do have the maneuvering flight

The work considers character of behavior in flight and discusses peculiarities of structural-functional organization of the wing apparatus of two representatives of insects—the migratory Asian locust Locusta migratoria (a low-maneuvering insect) and the dragonfly-darner Aeshna sp. (an insect able to perform complex maneuvers in air). The main principles underlying the insect wing apparatus activity are considered and the mechanisms allowing the dragonflies to perform complex maneuvers in the flight are analyzed in detail.     

System-theoretical (Holistic) approach to the modelling of structural-functional relationships of biomolecules and their evolution: an example of triterpene glycosides from sea cucumbers (Echinodermata, holothurioidea)

Triterpene glycosides from sea cucumbers (Holothurioidea, Echinodermata) are used as a model for studying the biochemical evolution for correlation between the glycoside membranolytic activity and biological functions. Concepts of evolutionary morphology are applied at the molecular level. The concept of Van-der-Klaauve's- Dullemeijer's system-theoretical (holistic) approach is used for the model of structural-functional relationships of the glycosides. Network diagrams of structural-functional relationships have been prepared for many glycosides. The diagrams correlate well with experimental data and show a very complex and flexible action of the natural selection on the structural fragments of the glycosides. The diagrams also show overlapping in the functional components that provide stability to the general structural plan of glycosides during evolution. The method may be applied to other biomolecules.     

The role of the hemopoiesis-inducing microenvironment in the mechanisms of the regeneration of hemopoiesis after cytostatic exposure]

On the model of adriamycine-induced hemopoiesis hypoplasia it has been shown that the accelerated differentiation of hemopoietic precursors regeneration is of great importance in regeneration of hemopoiesis. This differentiation is provided by preceded recovery of bone marrow structural-functional organization. The important role in regeneration of hemopoiesis belongs to hemopoietic microenvironmental elements which express its induced influence by the increase of colony-stimulating and erythropoietic activities, interleukin-1 and interleukin-3 production.     

Structural-functional model of the mitotic chromosome

In the present review the structural role of noncoding DNA, mechanisms of differential staining of mitotic chromosomes, and structural organization of different levels of DNA compactization are discussed. A structural-functional model of the mitotic chromosome is proposed based on the principle of discreteness of structural levels of DNA compactization.     

Effect of NMDA receptor activity on histone H3 methylation and its asymmetry in the hippocampal pyramidal neurons of rats with different excitability thresholds under normal and stress conditions

Process of methylation of histone H3 for lysine 4 (H3K4) was studied in hippocampal pyramidal neurons of rats—intact and submitted to emotional-pain stress with active and inactivated channels of NMDA-receptors with taking into account the interhemisphere lateralization and in connection with the genetically determined level of excitability of the animals’ nervous system. There were revealed interstrain differences in the basal level of the H3K4 methylation whose direction depends on structural-functional peculiarities of hippocampal fields and lateralization. Under action of stress the direction of the observed changes in the degree of the H3K4 methylation depended on the functional states of channels of NMDA-receptors. On the background of active receptors the proportion of immunopositive cells predominantly increased. In the CA1 field this change was not connected with excitability and lateralization, whereas in the CA3 field it had a complex character and depended on these two factors. At inactivation of channels of NMDA-receptors the portion of immunopositive nuclei as a result of the stress action, on the contrary, predominantly decreased; interstrain specificity of these changes was connected with lateralization, while its direction in different hippocampal fields was different. Action of the short-time emotional-pain stress did not lead to a change of shape of interhemisphere at active state of receptors, whereas at inactivation of receptors it changes depending on the structural-functional organization of hippocampus and on excitability of the nervous system.     

Levels of organization of living systems: Cooperons

All creatures living on Earth are traditionally discussed in the context of structuralmorphological approach, in frame of which there are considered various systems (for instance, organisms and ecosystems) that have different sizes and organization and use different resources for their existence. These characteristics are sometimes added by some particular functional and ecological characteristics, but usually with respect to the structural ones. We believe that such traditional approach, although illustrating, but distracts from the circumstance that any living systems is to be considered an integrated structural-functional complex, the maintenance of existence of this system being impossible without the processes occurring constantly in it and aimed at preserving this complex. This leads us to the concept of cooperons—the self-preserved dynamic structures existing only as a result of various specifically organized cooperative processes (their intensities can vary depending on circumstances). From our point of view, all living systems are cooperons of different hierarchy levels. Some other systems, specifically the symbiotic ones, also are cooperons. In frame of this concept, it is possible to discuss functioning of living systems of different types of organization in a new context closer to physiologists, both for the case of “norm” and for the situation when the cooperative interrelations of parts of the system are impaired (for instance, in systemic diseases).     

Conservatism of the Insulin Signaling System in Evolution of Invertebrate and Vertebrate Animals

The insulin system including hormone insulin and signaling mechanisms realizing a wide spectrum of its regulatory effect is one of the major systems in the animals and human organism. At present the history of origin of this regulatory system in the course of evolution starts to be formed. There are grounds to believe that it appeared in unicellular eukaryotes, developed in multicellular ones, and achieved significant perfection in higher vertebrates. This paper analyzes the structural-functional organization of insulin-like peptides, their receptors, and the corresponding signaling mechanisms in four types of invertebrates (sponges, nematodes, molluscs, arthropods) in comparison with those in higher vertebrates. There is revealed evolutionary conservatism in the common structural-functional organization of insulin-like peptides of invertebrates and insulin of vertebrate animals; receptors of insulin-like peptides of invertebrates and receptors of insulin and insulin-like growth factor 1 of vertebrates that have tyrosine kinase activity; the insulin-like signaling systems including signaling blocks, similar by their primary structure in invertebrate and vertebrate animals (IRS-proteins, G-proteins, adenylyl cyclase, protein kinases A and C, etc.). The point of view is put forward that the conservatism of the functional blocks of the insulin system does not mean the absence of evolutionary changes of this system as a whole. Examples of such evolutionary changes leading to complication of the insulin system organization at supramolecular and cellular levels and to an increase of efficiency of its functioning are presented.     

The formation of the microcirculatory bed of the neuromuscular systems of the tongue in human prenatal ontogeny]

A complex of adequate neurohistological and injection methods with use of mathematical analysis of the data obtained has been performed to study prenatal and early postnatal periods of ontogenesis of the microcirculatory bed of the human tongue neuromuscular systems. Certain changes of the degree in organization and structural-functional integration have been revealed; they demonstrate periodicity of the morphological changes of the vasculo-neural complex of the extra- and intrafusal part of the muscular tissue. In the neuromuscular spindles the microvascular network of capillaries is formed, their volumetric part changes in the process of development in greater degree than the microvascular bed of the extrafusal muscular fibers. In formation of the microcirculatory vascular bed of the neuromuscular spindles not only capillaries, getting into them together with nervous fibers, but also microvessels of the surrounding muscle tissue participate. This determines a higher level of the vascularization degree of the intrafusal muscle fibers.     

Structuro-functional organization of the blood-brain barrier

The analysis of the authors and published data allowed to conclude that the blood-brain barrier was a complex structural-functional system. Its basic components are endothelial cells, basal membrane, pericytes, tissue basophils, and astrocytes. The role of these structural elements in the permeability of blood-brain barrier has been studied. Organ-specific peculiarities of the brain tissue basophils have been established in rats, cats, and dogs. The astrocyte-capillary complexes were found to be very reactive, and at the same time, very plastic CNS structures.     

Ultrastructural organization of the basic substance of human dermis]

The data on ultrastructural organization of the ground substance in the human dermis obtained electron histochemically are represented. Five types of ruthenium positive structures of polysaccharide origin are detected: retinal structure (I), amorfous substance (II), membranes of collagen fibrils (III) and elastic fibres (V), fine ruthenium positive streakness of collagen fibrils (IV). These structures, except fine streakness, form a united polysaccharide system of the dermis participating in maintenance of structural-functional integrity of the connective tissue (collagen-elastic) carcass of the dermis. Two mechanisms, interconnected and oppositely directed, perform this function: the buffer mechanism preventing the connective tissue fibers and collagen fibrils to approach each other, and the binding mechanism preventing the fibrils and fibers to dissociate. The reticular structure performs mainly this function at the level of fibers, and the amorphous substance does it at the level of fibrils.     

On the mechanism of the nonspecific cell response to the action of damaging agents and the nature of hormesis

A conception of the molecular mechanism of the universal nonspecific cell response (NCR) to the action of all damaging factors of physical and chemical nature is described. The mechanism is shown to be closely related to the general principles of the structural-functional organization of cells and to the properties of biological macromolecules. Among them are the phenomenon of nonspecific regulation of the enzyme activity by low-molecular substances and the compartmentation of the latter within the cell, which is provided by the system of intracellular membranes. Special attention is paid to the role of disturbance of the barrier function, of membranes in the development of the nonspecific cell response, and the activation of repair of cell injuries. Based on the theory of nonspecific cell response, the stimulating effect of weak action of agents that damage the cells at high doses (the phenomenon named as hormesis) is explained.     

Morphogenetic characteristics of the mammary glands of autoimmune F1 mice (NZB x NZW)

The morphogenesis of mammary glands was studied in the normal and autoimmune F1(NZW X NZB) mice. In the lactation cycle of the autoimmune mice the normal course of structural-functional rearrangements of parenchyma and stroma in the developing and involuting mammary glands was disturbed. A conclusion has been reached that the modification of stromal elements, first of all involved in the autoimmune disease, is the leading link in the abnormal development of mammary glands.     

Predicting rules on organization of cis-regulatory elements, taking the order of elements into account

MOTIVATION: In eukaryotes, rules regarding organization of cis-regulatory elements are complex. They sometimes govern multiple kinds of elements and positional restrictions on elements. RESULTS: We propose a method for detecting rules, by which the order of elements is restricted. The order restriction is expressed as element patterns. We extract all the element patterns that occur in promoter regions of at least the specified number of genes. Then, we find significant patterns based on the expression similarity of genes with promoter regions containing each of the extracted patterns. When we applied our method to Saccharomyces cerevisiae, we detected significant patterns overlooked by previous methods, thus demonstrating the utility of our method for analyses of eukaryotic gene regulation. We also suggest that several types of element organization exist: (i) those in which only the order of elements is important, (ii) order and distance both are important and (iii) only the combination of elements is important. AVAILABILITY: The program for extracting element patterns is available upon request.     

The organization of time in biological systems

A notion of organization of time similar to the notion of organization of space in architecture has been introduced. The level and pattern of organization of time in biological systems differs from that in physical and chemical systems, which presents an independent problem. Analysis of the problem leads to a new definition of life as a process of renormalization of possibilities described by a Bayes formula. This definition leads to the notion of self-monitoring as a property of every biological system, and of complicated structure of the biological present, including the physical past and physical future. This is naturally followed by determination by far past, and, hence, memory, and determination by future, i.e. preadaptation, surpassing reflection, aim-setting etc. A direct dependence of a number of elements of a complex system on its stability has been demonstrated. The self-monitoring and organization of time can be traced at various levels of biological hierarchy from intracellular to biosphere level.     

The behavioral effects of the destruction of the nucleus basalis magnocellularis in the cat forebrain]

Behavioural experiments were carried out on cats by the method modelling complicatedly organized non-automatized behaviour with elements of generalization and abstraction. By the results of fulfillment of test tasks by animals with partial destruction of the macrocellular basal nucleus the conclusion is made on the participation of this formation in the structural-functional ensuring of complex integrative forms of activity-thinking and learning. The suggested mechanism of drawing of the basal nucleus in gnostic and cognitive processes in the non-specific ensuring of the system of structures directly participated in thinking and learning.     

The organization of biological membranes

A nomenclature for the organization of biological membranes is proposed. The terms primary (composition), secondary (transverse and lateral distribution), tertiary (membrane stacking/unstacking), and quaternary (membrane-membrane, cell-cell interactions) levels of organization are used by analogy with protein structure, but at each level the membrane organization is more complex and dynamic than protein structure.     

Ultrastructural organization of capillary endotheliocytes of the popliteal and iliac lymph nodes in the rat

The popliteal and iliac lymph nodes have different regional specialization. The former belong to somatic lymph nodes, while the latter get lymph also from internal organs; this explains certain differences in their structural-functional organization. Some objective quantitative data have been obtained that characterize ultrastructure of blood capillaries in the rat popliteal and iliac lymph nodes under normal conditions of the organism's functioning. They demonstrate essential differences in the level of transendothelial transport and, hence, functional activity of these organs.