Prospects for Regenerative Resort Treatment of Digestive System Diseases of Patient with Harmful Working Conditions

Purpose: examine the nature of violations of the functional condition of the digestive system among people working in harmful and dangerous working conditions and evaluate the effectiveness of the use of sanatorium-and-Spa treatment. Materials and Methods: We investigated the efficiency of natural physical factors in the rehabilitation of 50 employees of companies with harmful working conditions. Results: A significant distribution of digestive system functional pathological disorders is registered in this group.onclusions: After the carried out treatment the improvement in physical status of patients and normalization of the majority of laboratory parameters is noted, thereby increasing the reserve health and working efficiency of people with harmful conditions of their professional environment

Analysis of whole-genome binding patterns of GAGA and CNC transcription factors during Drosophila melanogaster development

On the basis of available data of ChIP-seq and ChIPchip experiments performed using antibodies against GAGA and CNC transcription factors, genome-wide binding mapping of these factors at hours 0–12 and 16–24 of Drosophila embryogenesis, as well as on white pre-pupae stage, was conducted. It was shown that the bulk of GAGA and CNC binding falls into promoter regions and introns, with the maximal density of peaks in the vicinity of the transcription start site. Moreover, in both 0–12 and 16–24 hour old embryos GAGA and CNC are frequently co-localized, while on white pre-pupae stage there is no co-localization of these factors on a genome–wide scale. In order to select a set of genes potentially co-regulated by GAGA and CNC, the study of their co-binding in annotated regulatory regions (promoter areas and segments corresponding to the 5’-UTR and 3’-UTR of mRNA) was performed. The results obtained clearly demonstrated that the sets of genes characterized by co-binding of both factors vary greatly at different stages. Thus from 353 genes with overlapped GAGA and CNC binding loci on the 0–12 hour old embryos and 611 genes on the 0–12 hour old embryos only 61 genes “belong” to both stages. For an explanation it is proposed that different sets of target genes are regulated by combinations of various GAGA and CNC isoforms, which are characterized by distinct expression patterns during drosophila embryogenesis. Functional annotation analysis of genes, in whose regulatory regions both GAGA and CNC were found at all investigated stages, demonstrates enrichment by genes controlling embryogenesis, neurogenesis and wing development. The data obtained suggest the interaction of GAGA and CNC during D. melanogaster embryogenesis

Recognition of interferon-inducible sites, promoters, and enhancers

BACKGROUND: Computational analysis of gene regulatory regions is important for prediction of functions of many uncharacterized genes. With this in mind, search of the target genes for interferon (IFN) induction appears of interest. IFNs are multi-functional cytokines. Their effects are immunomodulatory, antiviral, antibacterial, and antitumor. The interaction of the IFNs with their cell surface receptors produces an activation of several transcription factors. Four regulatory factors, ISGF3, STAT1, IRF1, and NF-κB, are essential for the function of the IFN system. The aim of this work is the development of computational approaches for the recognition of DNA binding sites for these factors and computer programs for the prediction of the IFN-inducible regions. RESULTS: We developed computational approaches to the recognition of the binding sites for ISGF3, STAT1, IRF1, and NF-κB. Analysis of the distribution of these binding sites demonstrated that the regions -500 upstream of the transcription start site in IFN-inducible genes are enriched in putative binding sites for these transcription factors. Based on selected combinations of the sites whose frequencies were significantly higher than in the other functional gene groups, we developed methods for the prediction of the IFN-inducible promoters and enhancers. We analyzed 1004 sequences of the IFN-inducible genes compiled using microarray data analyses and also about 10,000 human gene sequences from the EPD and RefSeq databases; 74 of 1,664 human genes annotated in EPD were significantly IFN-inducible. CONCLUSION: Analyses of several control datasets demonstrated that the developed methods have a high accuracy of prediction of the IFN-inducible genes. Application of these methods to several datasets suggested that the number of the IFN-inducible genes is approximately 1500–2000 in the human genome

Detection of new regulatory SNPs associated with colorectal cancer predisposition

A new approach to the search for regulatory SNPs (rSNPs) based on the use of ENCODE project data on ChIP-seq and RNA-seq experiments was developed. The approach was successfully used for the detection of rSNPs associated with colorectal cancer susceptibility. To start out with, we used raw sequence data of 15 independent ChIP-seq experiments run on colorectal cancer cell line HCT-116, which allowed us to generate the initial pool of 7985 SNPs located in regulatory regions. For further selection of functional SNPs, we used the ChIP-seq binding bias analysis and revealed 775 SNPs that are more likely to influence transcription regulation in HCT-116 cells. Then the RNA-seq bias analysis in HCT-116 cells was performed. As a result, we confirmed the functionality of 231 SNPs, which were classified as rSNPs. In order to select rSNPs potentially associated with colorectal cancer we chose those in strong linkage disequilibrium with SNPs asso-ciated with this pathology according to GWAS and ClinVar data. Functional annotation analysis of genes containing the rSNPs selected confirmed the involvement of BAIAP2L1 and BUB3 genes in colorectal cancer predisposition. We also found two genes (RRAGD and FZD6) playing a role in the RAS/MAРK and WNT signaling pathways. Although the involvement of the RAS/MAРK and WNT pathways in colon cancer is a well-known fact, these two genes are still unknown candidates. Moreover, we found 14 new candidate genes with promise for further study of colorectal cancer predisposition

DISCOVERY OF POLARIZATION REVERBERATION IN NGC 4151

Observations of the optical polarization of NGC 4151 in 1997–2003 show variations of an order of magnitude in the polarized flux while the polarization position angle remains constant. The amplitude of variability of the polarized flux is comparable to the amplitude of variability of the total U-band flux, except that the polarized flux follows the total flux with a lag of 8±3 days. The time lag and the constancy of the position angle strongly favor a scattering origin for the variable polarization rather than a non-thermal synchrotron origin. The orientation of the position angle of the polarized flux (parallel to the radio axis) and the size of the lag imply that the polarization arises from electron scattering in a flattened region within the low-ionization component of the broad-line-region. Polarization from dust scattering in the equatorial torus is ruled out as the source of the lag in polarized flux because it would produce a larger lag and polarization perpendicular to the radio axis. We note a long-term change in the percentage polarization at similar total flux levels and we attribute this to a change in the number of scatterers on a timescale of years

The functional insight into the genetics of cardiovascular disease: results from the post-GWAS study

Cardiovascular diseases (CVDs), the leading cause of death worldwide, generally refer to a range of pathological conditions with the involvement of the heart and the blood vessels. A sizable fraction of the susceptibility loci is known, but the underlying mechanisms have been established only for a small proportion. Therefore, there is an increasing need to explore the functional relevance of trait-associated variants and, moreover, to search for novel risk genetic variation. We have reported the bioinformatic approach allowing effective identification of functional non-coding variants by integrated analysis of genome-wide data. Here, the analysis of 1361 previously identified regulatory SNPs (rSNPs) was performed to provide new insights into cardiovascular risk. We found 773,471 coding co-segregating markers for input rSNPs using the 1000 Genomes Project. The intersection of GWAS-derived SNPs with a relevance to cardiovascular traits with these markers was analyzed within a window of 10 Kbp. The effects on the transcription factor (TF) binding sites were explored by DeFine models. Functional pathway enrichment and protein– protein interaction (PPI) network analyses were performed on the targets and the extended genes by STRING and DAVID. Eighteen rSNPs were functionally linked to cardiovascular risk. A significant impact on binding sites of thirteen TFs including those involved in blood cells formation, hematopoiesis, macrophage function, inflammation, and vasoconstriction was found in K562 cells. 21 rSNP gene targets and 5 partners predicted by PPI were enriched for spliceosome and endocytosis KEGG pathways, endosome sorting complex and mRNA splicing REACTOME pathways. Related Gene Ontology terms included mRNA splicing and processing, endosome transport and protein catabolic processes. Together, the findings provide further insight into the biological basis of CVDs and highlight the importance of the precise regulation of splicing and alternative splicing

Infectious lesions of placenta as cause of miscarriage

Analysis of the literature demonstratesimportant role played of infections in causes of miscarriage. The paper is based upon retrospective analysis of 12371 screening results of histological and selective immunohistochemical studies of placentas in 2009-12. Preterm births were in 706 cases (5.71%). Infection of the placenta was noted in early preterm labor in all cases (100%), and in premature labor at 28-36 weeks of gestation – in 97.35% of natural delivery cases and in 92.09% when cesarean delivery. Are described the typical structural changes that allow to suspect infections caused by Treponema pallidum, herpes viruses, human immunodeficiency virus, parvovirus with following verification by immunohistochemical study

The ultradian rhythm of glucocorticoid secretion and the time course of target gene regulation

Glucocorticoid hormones (cortisol in humans and corticosterone in rodents) are secreted in discrete pulses during a day with a periodicityof approximately 1 h (ultradian rhythm), and this pattern is also maintained in plasma and extracellular fluid. However, the vast majority of studies on gene regulation by glucocorticoids typically assess gene responses regardless the ultradian rhythm. These experiments are usually performed using long-term stimulation with synthetic hormones (dexamethasone and triamcinolone), which form much more stable complexes with glucocorticoid receptor (GR) then natural hormones. This review summarizes the current scarce information, obtained in experiments mimicking the ultradian mode of natural hormone secretion in cultured cells and in animal models. The results of these experiments clearly demonstrate that ultradian stimulation by natural hormones induces rapid GR exchange with glucocorticoid response elements and leads to cyclic GR mediated transcriptional regulation (gene pulsing) at the level of nascent RNA. In contrast, synthetic glucocorticoids, having much higher receptor affinity, fail to disengage from nuclear receptors with sufficient speed to support the ultradian cycles, thereby uncoupling extracellular hormone fluctuations from appropriate receptor function at response elements. This alters RNA accumulation profiles dramatically. These findings suggest potentially important consequences of ultradian secretion. The transcriptional program induced by hormone pulses differs significantly from that generated by constant hormone treatment. Thus, treatment with synthetic glucocorticoids may not provide an accurate assessment of physiological hormone action