[Developing the Mathematical Method in order to Search for Latent Periodicity in Protein Amino Acid Sequences with Deletions and Insertions].

A mathematical method was developed in order to search for latent periodicity in protein amino acid and other symbolical sequences using the dynamic programming and random matrixes. The method permits detection of the latent periodicity with insertions and deletions in the previously unknown positions. The developed method was applied to search for the periodicity in the amino acid sequences of some proteins and the periodicity in EUR/USD exchange rate since 2001. The presence of the long period length with insertions and deletions in amino acid sequences was shown. The period length of 7 amino acids was found in proteins containing supercoiled areas (coiled coil), the period length of 6 and 5 and more amino acids was also demonstrated. The existence of the period length of 6 and 7 days as well as 24 and 25 hours in the analyzed financial time series, which can be detected with insertions and deletions only, is revealed. The reasons of the occurence of the latent periodicity with insertions and deletions in the amino acid sequences and financial time series are discussed.

IL-1ß/HMGB1 complexes promote The PGE2 biosynthesis pathway in synovial fibroblasts.

PGE2 is a potent lipid mediator of pain and oedema found elevated in RA. Microsomal prostaglandin E synthase-1 (mPGES-1) is a terminal enzyme of the PGE2 pathway inducible by proinflammatory cytokines. mPGES-1 is markedly upregulated in RA synovial tissue despite antirheumatic treatments, suggesting that multiple inflammatory stimuli contribute to its induction. High-mobility group box chromosomal protein 1 (HMGB1) is known to induce inflammation both by direct interaction with TLR4 and by enhancement of other proinflammatory molecules signalling, through complex formation. The high expression of extracellular HMGB1 within the inflamed synovium, implies its pro-arthritogenic role in RA. We aimed to investigate the effects of IL-1ß/HMGB1 complexes on mPGES-1 and other enzymes of the PGE2 pathway in synovial fibroblasts (SFs) from patients with arthritis. Furthermore, we studied the effect of COX-2 inhibition and IL-1RI antagonism on prostanoid and cytokine production by SFs. Stimulation of SFs with HMGB1 in complex with suboptimal amounts of IL-1ß significantly increased mPGES-1 and COX-2 expressions as well as PGE2 production, as compared to treatment with HMGB1 or IL-1ß alone. Furthermore, NS-398 reduced the production of IL-6 and IL-8, thus indicating that IL-1ß/HMGB1 complexes modulate cytokine production in part through prostanoid synthesis. Treatment with IL-1RA completely abolished the induced PGE2 and cytokine production, suggesting an effect mediated through IL-1RI. IL-1ß/HMGB1 complexes promote the induction of mPGES-1, COX-2 and PGE2 in SF. The amplification of the PGE2 biosynthesis pathway by HMGB1 might constitute an important pathogenic mechanism perpetuating inflammatory and destructive activities in rheumatoid arthritis.

[Immunobiologically active compounds from skin].

This paper describes physiochemical and biological properties of 3 immunologically active compounds extracted by acetone from porcine skin. High pressure gel chromatography confirmed their heterogeneity. RP-HPLC of compound 2 (C2 or K-activin) also characterizes it as a heterogeneous entity. It was shown to inhibit proliferation of cultured fibroblasts from human fetuses and exhibit weak activity in general anaphylactic reaction (anaphylactic shock) and skin anaphylactic reaction. A summary of data on immunologically active compounds are presented with special emphasis laid on acetone-extractable K-activin.

Search for potential reading frameshifts in cds from Arabidopsis thaliana and other genomes.

A new mathematical method for potential reading frameshift detection in protein-coding sequences (cds) was developed. The algorithm is adjusted to the triplet periodicity of each analysed sequence using dynamic programming and a genetic algorithm. This does not require any preliminary training. Using the developed method, cds from the Arabidopsis thaliana genome were analysed. In total, the algorithm found 9,930 sequences containing one or more potential reading frameshift(s). This is ∼21% of all analysed sequences of the genome. The Type I and Type II error rates were estimated as 11% and 30%, respectively. Similar results were obtained for the genomes of Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Rattus norvegicus and Xenopus tropicalis. Also, the developed algorithm was tested on 17 bacterial genomes. We compared our results with the previously obtained data on the search for potential reading frameshifts in these genomes. This study discussed the possibility that the reading frameshift seems like a relatively frequently encountered mutation; and this mutation could participate in the creation of new genes and proteins.

Effects of immunosuppressive treatment on microsomal prostaglandin E synthase 1 and cyclooxygenases expression in muscle tissue of patients with polymyositis or dermatomyositis.

OBJECTIVES: To investigate the expression of microsomal prostaglandin E (PGE) synthase 1 (mPGES-1) and cyclooxygenase (COX) in muscle biopsies from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive treatment. METHODS: mPGES-1 and COX expression was evaluated by immunohistochemistry in muscle tissue from healthy individuals and from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive treatment. The number of inflammatory cell infiltrates, T lymphocytes and macrophages was estimated before and after treatment. To localise the mPGES-1 expression double immunofluorescence was performed with antibodies against mPGES-1, CD3, CD68, CD163 and a fibroblast marker. A functional index was used to assess muscle function. RESULTS: In patients with myositis, mPGES-1, COX-2 and COX-1 expression was significantly higher compared to healthy individuals and associated with inflammatory cells. Double immunofluorescence demonstrated a predominant expression of mPGES-1 in macrophages. Conventional immunosuppressive treatment resulted in improved but still lower muscle function than normal. A decreased number of CD68-positive macrophages and reduced COX-2 expression in muscle tissue was also seen. By contrast, following the same treatment no significant changes were observed in muscle tissue regarding number of infiltrates, T lymphocytes, CD163-positive macrophages or mPGES-1 protein levels. CONCLUSIONS: Increased expression of mPGES-1, COX-1 and COX-2 at protein level was observed in muscle tissue from patients with myositis compared to healthy individuals. Conventional immunosuppressive treatment led to a significant downregulation of COX-2 in myositis muscle tissue. However, the expression of mPGES-1 and COX-1 remained unchanged indicating a role of these enzymes in the chronicity of these diseases.

[The problems and perspectives of schoolchildren's health promotion at the municipal level].

The paper gives the results of studies aimed at evaluating the efficiency of the interdepartmental interaction system in schoolchildren's health promotion at the municipal level and at substantiating the recommendations for its optimization in case of the Leninsky District (Yekaterinburg). A package of measures, such as to develop the network of health-promotion schools, to assist in introducing effective health-saving technologies, to upgrade the personnel's competence in health culture, and to develop monitoring systems is proposed.

Perinatal essential fatty acid deficiency influences body weight and bone parameters in adult male rats.

Fetal and postnatal nutrition have long-term effects on the risk for development of diseases late in life in humans and animals. The aim of the present study was to investigate the effect of dietary deficiency of essential fatty acids (EFA) in the perinatal period on later body weight and bone mass. During late gestation and throughout lactation, rats were fed a control or an EFA-deficient (EFAD) diet. At 3 weeks of age the offspring were weaned onto an ordinary chow and followed until adult age. The mean body weight of adult rats receiving the EFAD diet during the perinatal period was significantly increased from 12 weeks of age compared to the controls (P<0.05). Analysis by peripheral quantitative computerized tomography (pQCT) at 44 weeks of age showed that the trabecular volumetric bone mineral density (BMD) of the femur was significantly decreased (P<0.05) but the cortical bone mineral content, cortical area, and cortical thickness were increased (P<0.05) in the EFAD group of rats. The length of the femur was not affected. In conclusion, neonatal EFA deficiency was in adult rats associated with increased body weight and significant changes in both cortical and trabecular bone. The results indicate that regulatory mechanisms related to bone mass seemed to be programmed by EFA in the perinatal period. The nature of this modulation needs to be identified.

Essential fatty acid deficiency affects the fatty acid composition of the rat small intestinal and colonic mucosa differently.

The intestinal mucosal fatty acid (FA) composition was investigated in Sprague-Dawley rats after 7 and 23 weeks on an isocaloric diet with qualitatively different essential fatty acid (EFA) composition. For comparison, serum and red blood cell (RBC) membranes were investigated in parallel. The molar percentage of most FAs differed significantly between serum and RBC membranes both in controls and rats fed an EFA deficient (EFAD) diet. The influence of the EFA diet was similar on serum and RBC membrane phospholipids except for arachidonic acid (AA) which was more markedly decreased in serum than in RBC membranes. The FA composition was similar in ileal and colonic mucosa, markedly differing from the jejunal mucosa, in which the AA concentration was lower (13.0+/-0.8 versus 16.8+/-0.5 and 15. 7+/-2.8 mol%) and the linoleic acid (LA) concentration higher (34. 0+/-1.6 versus 17.8+/-1.3 and 15.5+/-2.8 mol%, respectively). The EFAD diet induced a more than five-fold decrease in the jejunal and ileal concentration of LA from 33.9+/-1.6 to 6.0+/-1.5 mol% and 17. 8+/-1.3 to 2.1+/-0.7 mol%, respectively. AA decreased more in the ileal and colonic mucosa than in the jejunum. The changes in the FA composition of the intestinal compartments after EFAD diet were different from that in serum and RBC membranes, and did not further change after 23 weeks compared to 7 weeks after introduction of the diet. The study shows that dietary influences are tissue specific and serum or RBC membranes do not mirror local changes in any of the different intestinal segments.

Composition and permeability of syncytiotrophoblast plasma membranes in pregnancies complicated by intrauterine growth restriction.

The objective of this study was to determine placental membrane permeabilities to water, urea and mannitol in intrauterine growth restriction (IUGR) and compare them to normal gestational age matched controls. Further, we wished to investigate whether potential changes in permeability were related to changes in membrane fluidity, cholesterol or phospholipid fatty acid content of the membranes. Syncytiotrophoblast microvillous (MVM) and basal membranes (BM) were isolated from normal and IUGR placentas at term. Passive permeability to water, urea, and mannitol showed no significant alterations in IUGR compared to controls. Cholesterol content in BM, but not in MVM, was lower in placentas from pregnancies complicated by IUGR. However, membrane fluidity did not change in these pregnancies. The phospholipid fatty acid composition of the plasma membranes isolated from all placentas showed a predominance of unsaturated fatty acid species in the BM and saturated species in the MVM. In the MVM from IUGR, mead acid (20:3), behenic acid (22:0) and nervonic acid (24:1) constituted higher percentages of the total when compared to normally grown controls. In the BM from IUGR, mead acid (20:3) was increased relative to the total phospholipid fatty acid content. In conclusion, the syncytiotrophoblast membranes exhibit only minor changes in passive permeability and composition when the pregnancy is complicated by IUGR.

Enlarged similarity of nucleic acid sequences.

The concept of nucleic acid sequence base alternations is presented. The number of base alterations for the sequences of different length is established. The definition of "enlarged similarity" of nucleic acids sequences on the basis of sequence base alterations is introduced. Mutual information between sequences is used as a quantitative measure of enlarged similarity for two compared sequences. The method of mutual information calculation is developed considering the correlation of bases in compared sequences. The definitions of correlated similarity and evolution similarity between compared sequences are given. Results of the use of enlarged similarity approach for DNA sequences analysis are discussed.

Latent periodicity of DNA sequences from some human gene regions.

The mutual information is used to reveal of DNA sequences latent periodicity. Latent periodicity of DNA sequence is periodic. ity with low level of homology between any two periods inside DNA sequence. The mutual information between artificial numerical sequence and DNA sequence is calculated. The length of artificial sequence period is changed from 2 to 250. High level of mutual information between artificial and DNA sequences allows to find any type of latent periodicity of DNA sequence. The latent periodicity of some DNA coding regions is considered. For example, 24 exon of Apo B-100 gene from HSAP821 clone contains latent period 84 bases long. The IGF-I receptor gene from HSIGFIRR clone contains the region with latent period 57 bases long. Possible significance of latent periodicity is discussed.

[Presence of MIR-elements in the complete nucleotide sequence of human chromosome 22]. / Prisutstvie MIR-lementov v polnoi nukleotidnoi posledovatel'nosti khromosmy 22 cheloveka.

The location of mammalian interspersed repeats (MIRs) and their density have been determined in the complete nucleotide sequence of human chromosome 22. The approach developed by us has allowed detection of 9675 MIRs at a statistically significant level, which by 15% exceeds the MIR number revealed by all previous approaches. It has been demonstrated that a considerable amount of MIRs missed by the algorithms applied earlier occurs in known DNA sequences of the human genome. The study of the MIR density revealed substantial irregularity of their distribution along the chromosome. The data on the MIRs thus found and the computer program searching for diverged sequences are available by E-mail: katrin2@mail.ru or katrin22@mtu-net.ru.

[The informational concept of searching for periodicity in symbol sequences]. / Informatsionnaia kontseptsiia poiska periodichnosti v simvol'nykh posledovatel'nostiakh.

Method of informational decomposition has been developed, allowing one to reveal hidden periodicity in any symbol sequences. The informational decomposition is calculated without conversion of a symbol sequence into the numerical one, which facilitates finding periodicities in a symbol sequence. The method permits introducing an analog of the autocorrelation function of a symbol sequence. The method developed by us has been applied to reveal hidden periodicities in nucleotide and amino acid sequences, as well as in different poetical texts. Hidden periodicity has been detected in various genes, testifying to their quantum structure. The functional and structural role of hidden periodicity is discussed.

[Discovery of "masked" ribonucleases in highly purified preparations of RNA]. / Obnaruzhenie "skrytykh" ribonukleaz v vysokoochishchennykh preparatakh RNK.

It was found that RNA preparations isolated with the help of various inhibitors of RNAses from different eukariotic tissues, followed by thorough deproteinization contain particular ribonucleases ("masked" RNAses). These RNAses were supposed to be connected with RNA molecules and are not active. They may be activated by changes of RNA molecule conformation. Apparently the "marked" RNAses can take part in (a) processing of large precursor RNA molecules; (b) regulation of gene expression by means of specially cut RNA fragments.

[Interaction of T-activin with peritoneal macrophages]. / Vzaimodeistvie T-aktivina s peritoneal'nym makrofagami.

The action of T-activin on peritoneal macrophages of CBA mice after its introduction into the animals has been studied. In intact mice the phagocytic activity of macrophages and their resistance to the cytopathogenic action of Salmonella typhimurium live cells remains unchanged. The injection of corpuscular pertussis vaccine into mice leads to a decrease in the resistance of macrophages to the action of salmonellae. The simultaneous injection of T-activin into mice in doses of 0.1 and 1.0 microgram per animal abolishes the damaging action of the vaccine. The analysis of the in vitro action of T-activin on macrophages of intact mice revealed that the preliminary incubation of cells with the preparation sharply increases their resistance to the action of salmonellae, while its introduction simultaneously with bacteria or after them rapidly leads to the death of macrophages. The action of T-activin is supposed to be linked with triggering the biosynthetic processes mediating the resistance of macrophages to the cytopathogenic action of salmonellae.

[Course of the rheumatic process in mitral heart defects after primary and repeated courses of treatment with titrated gamma-globulin]. / Techenie revmaticheskogo protsessa u bol'nykh mitral'nymi porokami serdtsa posle pervichnykh i povtornykh kursov lecheniia titrovannym gamma-globulinom.

Titrated gamma-globulin, which the authors used in the preoperative management of patients with acquired valvular disease and minimum rheumatism activity, contained high titers of antibodies against the antigens of streptococcus (streptokinase, streptohyaluronidase, streptolysin 0) and Coxsackie A13, A18, and B3 viruses. Its use in combination with antirheumatic agents did not cause any complications and made it possible to reduce the activity of the process in most cases with grade I and after repeated courses also in grade II activity of rheumatism. Treatment with titrated gamma-globulin stimulates the organism's defence forces (factors of nonspecific immunity: complement, lysozyme, interferon) and leads to diminution of the isolation of cardiotropic viruses from blood and bioptic material of the atria of patients.

[Clinico-physiological assessment of the mechanisms of compensation and paracompensation in patients with mitral stenosis]. / Kliniko-fiziologicheskaia otsenka mekhanizmov kompensatsii i parakompensatsii u bol'nykh mitral'nymi stenozami.

The paper presents the results of an examination of 292 patients with Stages II-V mitral stenosis. Clinical, roentgenological, and electrocardiographic characteristics of the defect were analysed. Physical fitness and gas exchange during exercise were studied in 183 patients with Stages III and IV mitral stenosis. The findings were compared with the intensity of tissue oxygen exchange and the levels of myocardial myoglobin. The patients with mitral stenosis exhibited lower exercise tolerance that was more pronounced in Stage IV. The patients also displayed characteristic profound disturbances in work energy regimen, lower reserve potentialities and functional mobility of the cardiorespiratory system. The pronounced changes in the acid-base balance and gas composition of their capillary blood in Stage IV mitral stenosis during exercise may be explained by a sharply marked arteriolar barrier in the pulmonary circulation (a paracompensatory reaction). The comparison of physiological and clinical findings has enabled the relationship of mechanisms responsible for compensation and paracompensation to be evaluated at various stages of mitral stenosis.

[Analysis of immunoregulatory peptides of the thymus using high performance liquid chromatography]. / Analiz immunoreguliatornykh peptidov timusa metodom vysokoéffektivnozhidkostnoi khromatografii.

High performance liquid chromatography (gel filtration and chromatography in the reverse phase) was applied to analyse a composition of the heterogenous immunoregulating peptide preparation T-activine isolated from calf thymus. Gel chromatography at high pressure on the column TSK G2000 SW enabled to separate T-activine into 3 subfractions at a preparative scale. Physico-chemical properties and biological activity of these fractions were studied in vitro. Subfraction B with molecular mass of 1.0-3.5 kD and pI below 5.9 proved to be the most active.