Experimental conditions for the molecular hybridization in vitro between iodine and native subunits of isoenzymes 1 and 5 of lactate dehydrogenase (LDH) are described. It is also shown that the covalently fixed on the polyacrylamide beads rat J125 labelled LDH-5 and J125 labelled aldolase A, under conditions of complete dissociation of the quaternary structure of these enzymes, only one of the four subunits remain bound with the beads. Subunit of LDH-5, which is covalently bound with the polyacrylamide beads, is capable to hybridize (reassociated) with 3 native subunits. In addition, the immobilized LDH-5 subunits and aldolase A are capable to hybridize with J125 labelled subunits of these enzymes. Thus, when thyrosine, lysine and N-terminal amino acids are modified, subunits of LDH-5 and aldolase A retain their capacity to restore their quaternary structures.
Hepatocellular carcinoma (HCC) is a common severe type of liver cancer characterized by an extremely aggressive course and low survival rates. It is known that disruptions in the regulation of apoptosis activation are some of the key features inherent in most cancer cells, which determines the pharmacological induction of apoptosis as an important strategy for cancer therapy. The computer design of chemical compounds capable of specifically regulating the external signaling pathway of apoptosis induction represents a promising approach for creating new effective ways of therapy for liver cancer and other oncological diseases. However, at present, most of the studies are devoted to pharmacological effects on the internal (mitochondrial) apoptosis pathway. In contrast, the external pathway induced via cell death receptors remains out of focus. Aberrant gene methylation, along with hepatitis C virus (HCV) infection, are important risk factors for the development of hepatocellular carcinoma. The reconstruction of gene networks describing the molecular mechanisms of interaction of aberrantly methylated genes with key participants of the extrinsic apoptosis pathway and their regulation by HCV proteins can provide important information when searching for pharmacological targets. In the present study, 13 criteria were proposed for prioritizing potential pharmacological targets for developing anti-hepatocarcinoma drugs modulating the extrinsic apoptosis pathway. The criteria are based on indicators of the structural and functional organization of reconstructed gene networks of hepatocarcinoma, the extrinsic apoptosis pathway, and regulatory pathways of virus-extrinsic apoptosis pathway interaction and aberrant gene methylation-extrinsic apoptosis pathway interaction using ANDSystem. The list of the top 100 gene targets ranked according to the prioritization rating was statistically significantly ( p -value = 0.0002) enriched for known pharmacological targets approved by the FDA, indicating the correctness of the prioritization method. Among the promising potential pharmacological targets, six highly ranked genes ( JUN , IL10 , STAT3 , MYC , TLR4 , and KHDRBS1 ) are likely to deserve close attention.
Two novel databases, GenSensor and ConSensor, have been developed. GenSensor accumulates information on the sensitivities of the prokaryotic genes to external stimuli and may facilitate designing of novel genosensors; ConSensor contains data about the structure and efficiency of the available genosensor plasmid constructs. Using these databases, candidate genes for the design of novel multiple functional genosensors were searched, and the Escherichia coli dps gene was chosen as the candidate. The genetic construct derived from its promoter was developed and tested for its sensitivity to various stress agents: hydrogen peroxide (oxidative stress), phenol (protein and membrane damaging), and mitomycin C (DNA damaging). This genosensor was found to be sensitive to all stress conditions applied confirming its ability to serve as multi-functional genosensor. The GenSensor and ConSensor databases are available at .
In this paper, we perform an analysis of bacterial cell-cycle models implementing different strategies to coordinately regulate genome replication and cell growth dynamics. It has been shown that the problem of coupling these processes does not depend directly on the dynamics of cell volume expansion, but does depend on the type of cell growth law. Our analysis has distinguished two types of cell growth laws, "exponential" and "linear", each of which may include both exponential and linear patterns of cell growth. If a cell grows following a law of the "exponential" type, including the exponential V(t) = V(0) exp (kt) and linear V(t) = V(0)(1 + kt) dynamic patterns, then the cell encounters the problem of coupling growth rates and replication. It has been demonstrated that to solve the problem, it is sufficient for a cell to have a repressor mechanism to regulate DNA replication initiation. For a cell expanding its volume by a law of the "linear" type, including exponential V(t) = V(0) + V(1) exp (kt) and linear V(t) = V(0) + kt dynamic patterns, the problem of coupling growth rates and replication does not exist. In other words, in the context of the coupling problem, a repressor mechanism to regulate DNA replication, and cell growth laws of the "linear" type displays the attributes of universality. The repressor-type mechanism allows a cell to follow any growth dynamic pattern, while the "linear" type growth law allows a cell to use any mechanism to regulate DNA replication.
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