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Received August 28, 2018; revised October 10, 2018; accepted November 6, 2018 The loss of apical-basal cell polarity is a necessary stage of the epithelial-mesenchymal transition (EMT). Polarized epithelial cells interact with the basement membrane (BM) and, in particular, with laminins, the major components of BM. Here, we examined the effect of the transition of colon cancer cells from 2D polarized state to non-polarized 3D state on the expression of EMT associated genes, as well as the role of laminins 332 and 411 (LM-332 and LM-411) in this process. The three studied cell lines, HT-29, HCT-116 and RKO, were found to have different sensitivity to cultivation conditions (2D to 3D changes) and to addition of laminins. One of the possible reasons for this maybe a difference in the initial 2D state of the cells. In particular, it was shown that the cell lines were at different EMT stages. HT-29 exhibited more epithelial expression profile, RKO was more mesenchymal, and HCT-116 was in an intermediate state. The most laminin-sensitive cell line was HCT-116. The magnitude and the specificity of cell response to LM-332 and LM-411 depended on the expression pattern of laminins' receptors. EMT gene expression profile was not substantially changed neither during the transition from 2D to 3D state, nor the presence of laminins' isoforms. However, we detected changes in expression of SNAI1 and ZEB1 genes encoding transcription factors that control the EMT process. Notably, in all three studied cell lines, the expression of SNAI1 was enhanced in response to laminin treatment.

Laminins are a family of extracellular heterotrimeric glycoproteins that are the main structural component of basement membranes (BMs), perform a barrier function, and are important for adhesion, differentiation, migration, and resistance to apoptosis of various cells, including cancer cells. The review summarizes the current knowledge of how laminins produced by cancer and normal cells influence the key stages of carcinogenesis. Laminin 332 (LN-332) and LN-111 enhance proliferation of certain cancer cells and increase the tumour growth. LN-111 increases resistance to apoptosis, induces differentiation, and inhibits the epithelial-mesenchymal transition (EMT) of cancer cells. LN-332 is associated with higher adhesion and higher migration potential of cancer cells. LN-411 and LN-421 significantly increase motility of cancer cells. LN-332 and LN-511 facilitate cell-cell adhesion and affect the efficacy of cell-cell interactions. The laminin chains α4 and α5 are important for the development and function of blood and lymphatic vessels. The expression ratio of the α4 and α5 laminin chains defines the BM permeability to leukocytes and, presumably, cancer cells in blood and lymphatic vessels. Interactions between LN-511 and α2-containing laminins enhance self-renewal and survival of circulating cancer stem cells. Moreover, laminins are involved in the formation of premetastatic niches and new colonies. Endogenous expression of the α4 laminin chain stimulates proliferation of individualised circulating cancer cells in vitro and in vivo and facilitates micrometastasis.

Thermodynamic parameters of the cloverleaf secondary structure of tRNAs of several major taxons (archaebacteria, eubacteria, eukaryotes, chloroplasts, and mitochondria) were subjected to computer analysis. The distribution of free-energy values was close to normal in all groups (except for the mitochondrial tRNA). In the organisms existing under extreme environmental conditions, the stability of the tRNA secondary structure was higher. Comparative analysis of teh frequency of ¿quasi-complementary¿ GU pairs in stems of randomly generated and real sequences demonstrated preferential fixation of such pairs in the contexts with the most favorable thermodynamics parameters. Noncanonic pairs in tRNA stems set limits on the presence of highly mutable CG dinucleotides. Moreover, the effect of noncanonic pairs other than GU on the frequency of such dinucleotides is far more pronounced than that of GU pairs.

Under investigation is congruent variation of movable elements, the "genome parasites" (GP), and genome proper, as the "host". Several differential equations are studied that describe the following situations. 1. GP is able to insert in free sites only, existing in autonomous stage (outside of the genome) limited time only. 2. GP inserts in free sites only, being able to exist autonomously relatively long time. 3. GP inserts in both free and occupied sites ("molecular memory"), existing autonomously relatively short time, its prototype being Alu-like repetitions in mammals. 4. GP inserts in both free and occupied sites, and is able to live autonomously, its prototype being retrovirus. In is presumed that the genome is tolerant to "selfish" breeding of GP as long as proportion of invaded sites does not exceed some critical value. It is shown that co-evolutionary complication of GP--from the simplest one that is able to insert in free sites only, through acquiring terminal repetitions ("molecular memory"), up to complicated entities existing outside of genome--accompanied by alteration of selective co-evolutionary limitations on genome size: limitations from above--no limitations--limitations from below. Thus, genetical movable elements can be considered as intrinsic factor of progressive, co-evolutionary stipulated complication of the genome.

Some families of isoacceptor tRNAs were studies using VOSTORG software package for phylogenetic analysis. While analysing the evolutionary trees in was shown that the fixation of double substitutions AU<-->GC in spiral double-stranded regions passes two stages with intermediate station, such as non-canonical base pairs. In all the families studied double substitutions can be explained not only by passages through slightly deleterious GU pairs. Comparative analysis of B2-like repeats shown the absence of compensatory substitutions in the parts which are homologous to RNA stem regions. The data obtained let us assume that compensatory substitutions in the RNA helical regions represent an expressive example of non-directed adaptive molecular coevolution.

A series of new scute mutants noted for reduction in one pair of bristles (humerals), but different penetrance with respect to this character, were induced in the system of P--M hybrid dysgenesis. In situ hybridization technique was used to determine the sites of the MEs pertaining to six families in 6 scute mutants and 18 isogenic lined derived from those. Through calculating the similarity indices, similarity with respect to the pattern of total distribution of all MEs examined was estimated for the lines. Results obtained favour the correlation between penetrance and ME localization. The "ME pattern-penetrance" dependence was verified using the isogenic lines. The matrix of similarity indices and the similarity tree were constructed for the mutant lines following comparative analysis of distribution of 132 hybridization sites. The structure of the tree gives in a number (3-4) of blocks made up by isogenic lines of different origin. The rank of stocks following merely ordering them as regards penetrance and the structure of both the tree and the matrix run together pretty well; what's more, compact blocks of labelled sites answer to the groups of stocks of close penetrance. Our results suggest that penetrance with respect to the number of numerals should directly depend on the peculiarities of ME localization in the genomes of mutant lines.

Evolutionary development of immunity multigene systems seems to involve host-parasite molecular coevolution, as evidenced by comparison of metasoans and unicellular organisms in fixation rates of neutral and adaptive point mutations per one pair of corresponding genes. The estimations we attempted revealed that organisms with maximal restriction of Ig-like gene repertoire expression by an individual immune cell are more adaptive in formation of competent antigen-induced immune response, provided that the magnitude of potential repertoire of functional Ig-like receptors exceeds lymphoid cell population size. In contrast, when phage and bacteria populations are in coevolution, there is no need to limit the repertoire of expressive genes encoding bacteria surface receptor proteins which are recognized by a phage adsorption system. Other hypotheses of evolutionary premises and stimulus of immune genes expression limitation (allelic, isotypic etc.) are critically discussed.

By means of phylogenetic comparison of main immunoglobulin-like multigene families (MF) and of different C-domain sequences representing them, the order of divergences of these MF in the process of evolution of the system was analysed. The order proved to be in good agreement with the ordered fashion of MF's involvement into recombinational rearrangements during the immune cell development. Indeed, according to topology of the tree for 34 C-domains, all MHC antigens are separated from the rest of Ig-like sequences, at first. Secondly, beta-chain of T-receptor is branched off the main stem of divergences, then there is a serium of divergences of CH-domains for different Ig-classes, and at last, kappa- and lambda-chains are separated. It is mu-chain of IgM which first of all branched off within an each group of isofunctional CH-sequences in the tree (CH1, CH2, CH3, CH4). The same order of events could be seen in ontogeny of the immune system. The results suggest that the appearance of a new MF of Ig-like type (or a new cluster of genetic segments within the MF) in the course of evolution could mean the addition of a new step in the regulatory system of immunologic gene expression already involved. In other words, this is unique example of recapitulation at the molecular-genetical level.