RatDEGdb: a knowledge base of differentially expressed genes in the rat as a model object in biomedical research.

The animal models used in biomedical research cover virtually every human disease. RatDEGdb, a knowledge base of the differentially expressed genes (DEGs) of the rat as a model object in biomedical research is a collection of published data on gene expression in rat strains simulating arterial hypertension, age-related diseases, psychopathological conditions and other human afflictions. The current release contains information on 25,101 DEGs representing 14,320 unique rat genes that change transcription levels in 21 tissues of 10 genetic rat strains used as models of 11 human diseases based on 45 original scientific papers. RatDEGdb is novel in that, unlike any other biomedical database, it offers the manually curated annotations of DEGs in model rats with the use of independent clinical data on equal changes in the expression of homologous genes revealed in people with pathologies. The rat DEGs put in RatDEGdb were annotated with equal changes in the expression of their human homologs in affected people. In its current release, RatDEGdb contains 94,873 such annotations for 321 human genes in 836 diseases based on 959 original scientific papers found in the current PubMed. RatDEGdb may be interesting first of all to human geneticists, molecular biologists, clinical physicians, genetic advisors as well as experts in biopharmaceutics, bioinformatics and personalized genomics. RatDEGdb is publicly available at https://www.sysbio.ru/RatDEGdb.

Differential expression of 10 genes in the hypothalamus of two generations of rats selected for a reaction to humans.

Individual behavioral differences are due to an interaction of the genotype and the environment. Phenotypic manifestation of aggressive behavior depends on the coordinated expression of gene ensembles. Nonetheless, the identification of these genes and of combinations of their mutual influence on expression remains a difficult task. Using animal models of aggressive behavior (gray rats that were selected for a reaction to humans; tame and aggressive rat strains), we evaluated the expression of 10 genes potentially associated with aggressiveness according to the literature: Cacna1b, Cacna2d3, Drd2, Egr1, Gad2, Gria2, Mapk1, Nos1, Pomc, and Syn1. To identify the genes most important for the manifestation of aggressiveness, we analyzed the expression of these genes in two generations of rats: 88th and 90th. Assessment of gene expression levels was carried out by real-time PCR in the hypothalamus of tame and aggressive rats. This analysis confirmed that 4 out of the 10 genes differ in expression levels between aggressive rats and tame rats in both generations. Specifically, it was shown that the expression of the Cacna1b, Drd2, Egr1, and Gad2 genes does not differ between the two generations (88th vs 90th) within each strain, but significantly differs between the strains: in the tame rats of both generations, the expression levels of these genes are significantly lower as compared to those in the aggressive rats. Therefore, these genes hold promise for further studies on behavioral characteristics. Thus, we confirmed polygenic causes of phenotypic manifestation of aggressive reactions.

[The features of opisthorchiasis papillitis diagnosis]. / Osobennosti klinicheskoi diagnostiki opistorkhoznogo papillita.

AIM: To develop an optimal diagnostic algorithm in order to the most reliable decrease of inflammatory changes severity in large duodenal papilla in patients with chronic opisthorchiasis. MATERIAL AND METHODS: Medical reports of 384 patients with opisthorchiasis-induced cholangitis have been analyzed. Diagnostic methods were abdominal ultrasound, endoscopic ultrasound of terminal common bile duct, CT scans, MRI of abdominal organs including magnetic resonance cholangiopancreatography and esophagogastroduodenoscopy with biopsy of the papilla, ERCP and PTHC. Comprehensive general and individual analysis of each of them has determined their advantages and disadvantages. CONCLUSION: Examination should by comprehensive to evaluate visual appearance of large duodenal papilla, lumen dimensions, state of its walls with histological research. Imaging tests are favorable to determine the diagnosis of papillitis due to possible assessment of lumen dimensions and state of the walls. While making a choice the priority should be given to endoscopic ultrasound examination. It allows visual inspection, assessment of the lumen, the walls of papilla and provides biopsy of deep structures.

Hidden heterogeneity of transcription factor binding sites: A case study of SF-1.

Steroidogenic factor 1 (SF-1) belongs to a small group of the transcription factors that bind DNA only as a monomer. Three different approaches-Sitecon, SiteGA, and oPWM-constructed using the same training sample of experimentally confirmed SF-1 binding sites have been used to recognize these sites. The appropriate prediction thresholds for recognition models have been selected. Namely, the thresholds concordant by false positive or negative rates for various methods were used to optimize the discrimination of steroidogenic gene promoters from the datasets of non-specific promoters. After experimental verification, the models were used to analyze the ChIP-seq data for SF-1. It has been shown that the sets of sites recognized by different models overlap only partially and that an integration of these models allows for identification of SF-1 sites in up to 80% of the ChIP-seq loci. The structures of the sites detected using the three recognition models in the ChIP-seq peaks falling within the [-5000, +5000] region relative to the transcription start sites (TSS) extracted from the FANTOM5 project have been analyzed. The MATLIGN classified the frequency matrices for the sites predicted by oPWM, Sitecon, and SiteGA into two groups. The first group is described by oPWM/Sitecon and the second, by SiteGA. Gene ontology (GO) analysis has been used to clarify the differences between the sets of genes carrying different variants of SF-1 binding sites. Although this analysis in general revealed a considerable overlap in GO terms for the genes carrying the binding sites predicted by oPWM, Sitecon, or SiteGA, only the last method elicited notable trend to terms related to negative regulation and apoptosis. The results suggest that the SF-1 binding sites are different in both their structure and the functional annotation of the set of target genes correspond to the predictions by oPWM+Sitecon and SiteGA. Further application of Homer software for de novo identification of enriched motifs in ChIP-Seq data for SF-1ChIP-seq dataset gave the data similar to oPWM+Sitecon.

DIAGNOSTICS AND TREATMENT OF OBSTRUCTIVE JAUNDICE AT CHRONIC OPISTHORCHIASIS.

A comparative analysis of possibilities of visual methods of diagnostics was made in order to reveal the causes of obstructive jaundice in chronic opisthorchiasis. There was estimated the possibility of topical diagnostics of rate and character of the bile passages block while conducting MR-imaging cholangiography. Types of architectonics of the bile passages were specified in chronic opisthorchiasis. A differentiated algorithm of treatment was developed and applied in relation to the obtained data.

[Capabilities of a Multivox hardware-software system in the radiodiagnosis of facial skeleton injury].

The authors evaluated the efficiency of a Multivox RIS hardware-software system in optimizing the radiodiagnosis of facial skeleton injury. An attempt was undertaken to systematize an approach to the comprehensive radiographic examination of patients with craniofacial polytrauma. It is shown that an image can be postprocessed using the Multivox RIS hardware-software system, which contributes to the comprehensive analysis of obtained images, by applying different radiographic studies; moreover, digital X-ray study has the most diagnostic value and rationality for isolated maxillofacial trauma and multislice spiral computed tomography has them for mixed, concurrent, and multiple injuries. The developed algorithm for examining the patients with facial skeleton trauma unifies and optimizes the diagnosis of craniofascial injuries at different sites.

[Capacities of digital mammography in screening].

The purpose of the study was to estimate the capacities of digital mammography in screening in women followed up by a mammologist in the Surgut Clinical Perinatal Center. The results of analog and digital mammography were compared using a Senographe DS in 1772 subjects who had been followed up by a mammologist in the Surgut Clinical Perinatal Center for 3-7 years. Females in whom mammography was first made as a basic study on a digital mammography were identified in an individual group of 887 subjects. Analysis of the capacities of analog and digital mammography indicated many advantages of the latter.

[Treatment of the patients with complications of colon malignant tumors].

Results of surgical treatment of 106 patients with complications of colon malignant tumors are analyzed. Diagnostic and treatment algorithm for these patients has been developed and used in clinical practice. Standardization and use of this algorithm permitted to increase the rate of radical operations from 48.9 to 62.6%, to reduce the rate of purulent complications more in 2 times and postoperative lethality - in 1.6 times.

Bioinformatical and experimental approaches to investigation of transcription factor binding sites in vertebrate genes.

The development of computer-assisted methods for transcription factor binding sites (TFBS) recognition is necessary for study the DNA regulatory transcription code. There are a great number of experimental methods that enable TFBS identification in genome sequences. The experimental data can be used to elaborate multiple computer approaches to recognition of TFBS, each of which has its own advantages and limitations. A short review of the characteristics of computer methods of TFBS prediction based on various principles is presented. Methods used for experimental monitoring of predicted sites are analyzed. Data concerning DNA regulatory potential and its realization at the chromatin level, obtained using these methods, are discussed along with approaches to recognition of target genes of certain transcription factors in the genome sequences.

[Testing the procedure for virtual colonoscopy and its possible place in the algorithm of study of colonic diseases].

The paper presents the experience in testing virtual colonoscopy on examining patients with colonic diseases. The potentialities of virtual colonoscopy in imaging tumors, polyps, diverticula, and strictures of the colon are assessed. The place of the procedure in the algorithms of examination of patients is defined. Its advantages and disadvantages are preliminarily estimated.

[Recognition of the potential SF-1 binding sites by SiteGA method, their experimental verification and search for new SF-1 target genes].

The SF-1 (Steroidogenic Factor-1) is a transcription factor known as a key regulator of the steroidogenic gene expression. SF-1 is required for the development and functioning at all levels of the hypothalamic-pituitary-gonadal and adrenal axis. Also it plays an essential role in sex determination. SF-1 is a member of the nuclear receptor superfamily and it activates gene expression by binding to DNA in a monomeric form. Here, we report the results of potential SF-1 binding sites identification by using the SiteGA recognition method. The SiteGA method was implemented using a genetic algorithm (GA) involving a iterative discriminant analyses of local dinucleotide context characteristics. These characteristics were compiled not only over the core binding sites region but over its flanks as well. Developed SiteGA method is characterized by considerably better recognition accuracy when compared to that for the weight matrix method. The experimental tests demonstrated that 83% of the sites recognized by the SiteGA method in the regulatory regions of steroidogenic genes, indeed, interact with the SF-1 factor. We also estimated the density of predicted sites in regulatory region of genes, the members of different functional groups and developed the criterion to search for new SF-1 target genes in genome sequences.

[Cytomorphometric diagnosis of dysplasias during dyshormonal and hyperplastic processes in the mammary gland].

A hundred and twenty-nine cytograms of benign tumors of the breast with different degrees of its dysplasia were morphometrically analyzed, by using a "MECOS-Ts" set for digital microscopy. The informative differentially diagnostic morphometric signs of nuclei were identified in mild, moderate, and severe epithelial dysplasias of the breast. The derived quantitative decision rules may reduce the error of a differential diagnosis of severe dysplasia by 2-3.5 times, as compared with a visual microscopy-based diagnosis.

[Prophylactics of complications of operations on the colon (experimental-clinical investigation)].

One of important aspects influencing the results of surgical treatment of patients with diseases of the colon is thought to be stepwise diagnostic and treatment measures. A retrospective analysis of treatment of 171 patients with pathology of the colon has been made. A medical-diagnostic algorithm has been developed and introduced which allowed improvement of effectiveness of medical aid in the group under study. Of importance was also modernization of certain technical aspects of operation. Efficiency of the developed method of the formation of colonic anastomosis with strengthening the line connection with a plate "Tahokomb" was proved in experiment and confirmed in clinical practice. The application of the medical-diagnostic algorithm allowed unification and standardization of approaches to treatment of patients with a pathology of the colon and better results were obtained with 3 times less number of complications.

Binding sites for transcription factor SF-1 in promoter regions of genes encoding mouse steroidogenesis enzymes 3betaHSDI and P450c17.

Using gel retardation of DNA samples and specific antibodies, binding sites for the transcription factor SF-1 were found in positions -53/-44 and -285/-270 in the promoter region of the mouse Cyp17 gene and in position -117/-108 of the promoter region of the mouse 3betaHSDI gene.

Predisposition to alcoholism, tryptophan oxygenase activity, and structure of intron 6 in the corresponding gene of C57BL/6J, CC57BR/Mv, and BALB/cJ mice.

Crossbred CC57BR/Mv mice inherited tryptophan oxygenase gene and predisposition to alcohol consumption from parent BALB/c and C57BL mice, respectively. In CC57BR/Mv mice no relationships were found between alcohol consumption, tryptophan oxygenase activity, and single nucleotide substitutions in intron 6 of the TDO2 gene associated with predisposition to alcoholism in humans.

[A comparative morphometric analysis of cytograms of invasive ductal and invasive lobular breast cancer]. / Sravnitel'nyi morfometricheskii analiz tsitogramm invazivnogo protokovogo i invazivnogo dol'kovogo raka molochnoi zhelezy.

The most informative for differential diagnosis parameters (surface and nucleus polarization) were determined on the basis of morphometric analysis of 42 cytograms of invasive duct cancer (IDC) and 39 cytograms of invasive lobular breast cancer (ILC) using the computer analyzer MEKOC-C. Combination of these two parameters allowed the authors to elaborate a decisive rule for differential diagnosis of these two cancers (the mistake is reduced to 8.6%). The analysis of 8 informative morphometric nuclear parameters has shown that in ILC the nuclei are more monomorphic, less in square and perimeter, nucleoli are less numerous than in IDC. The study gives objective criteria for preoperative differential cytological diagnosis between IDC and ILC.

[The characteristics of the neuropsychotropic activity of bromantane in laboratory animals]. / Kharakteristika neiropsikhotropnoi aktivnosti bromantana u laboratornykh zhivotnykh.

Bromantan [N-2-(para-(bromphenyl)-N-2-(aminoadamantan)] possesses psychostimulating activity in experiments on animals. With LD50 8100 mg/kg (mice, intraperitoneal injection) activates simple and complicated forms of behavior, induces EEG effects typical of psychostimulators, is an antagonist of substances with a deprivationg neuropsychotropic effect. Bromantan is characterized by a positive effect on mnemonic processes and on obtaining the results of complex operant activity in rats.

[Adamantane derivatives enhancing body's resistance to emergencies]. / Proizvodnye adamantana, povyshaiushchie ustoichivost' organizma k ékstremal'nym vozdeistviiam.

A total of 329 novel adamantane derivatives have been synthesized and pharmacologically studied. Among them, the compounds containing halogen-containing aromatic radicals in the second position show the most pronounced effect on animal resistance to the emergencies induced by its habitat and performance. N-(2-adamantyl)-N-(para-bromphenyl)amine (bromantane) possesses a low toxicity, a high ability to enhance the physical and operant working maintenance of animals, to accelerate its recovery in developed fatigue, in hyperthermia and hypoxia in particular. 2-(para-chlorobenzoylamine)adamantane (chlodantane) has the processes of a rapid-action adaptogenic agent by enhancing the resistance of animals to various physical and toxically chemical noxious agents. The two compounds have immunostimulating effects in secondary stress-induced immunodeficiencies whose mechanism of action is a membranous protective activity.

[The diagnosis and treatment of chronic osteomyelitis in patients with spinal cord trauma]. / Diagnostika i lechenie khronicheskogo osteomielita u bol'nykh so spinnomozgovoi travmoi.

Results of examination and treatment of 75 patients with a trauma disease of the spinal cord with bedsores are presented. Osteomyelitis which developed in places of localization of longstanding bedsores took place in 39% of patients. The general complex of treatment included associated intraosseous and direct endolymphatic antibiotic therapy as the main treatment as well as the efficient preoperative preparation. Good clinical effect was obtained.