Hypermethylation of TUSC5 genes in breast cancer tissue

Aim: Breast cancer (BC) is one of the most common forms of cancer amongst females. Early diagnosis, prognosis and therapy plays crucial role in the survival of patients with breast cancer. The study was aimed on identification of potential markers for early BC diagnostics by means of genome-wide comparative analysis of gene expression in cancer and normal tissue of breast. Methods: The analysis of gene expression in 15 invasive adenocarcinoma specimens and 15 normal breast tissue was conducted using the full-genome microarrays Sentrix HumanWD-6V3 BeadChip (Illumina). Methylation of TP53INK1 and TUSС5 promoters was interrogated by the combined bisulfite restriction analysis (COBRA). Results: Analysis of gene expression in the samples of breast adenocarcinoma revealed abnormal expression of more than 2,300 genes. While genes TFF1, S100P, ERBB2, TOP2A, CDF15, HOOK1, DNAJC12, CORO2A were up-regulated in cancer, decreased expression was found for genes TUSC5, SFRP1, PPPQR1B, NTRK4, TIMP4, BARD1, AKR1C2, TP53INK1 and others. Analysis of DNA methylation of TUSC5 by COBRA revealed higher levels of exon 1 methylation (11/12) in samples of breast cancer, whereas the gene was essentially unmethylated in matched normal appearing tissue of breast (2/12). TP53INK1 gene was methylated neither in cancer nor in normalcy. Conclusion: A total of 149 genes exhibited the highest difference in expression in cancer versus normal appearing tissue of breast. Most prominent down-regulated candidates, TUSC5 and TP53INK1, were reported for the first time in breast cancer and may be considered as potential markers of the disease. Aberrant DNA hypermethylation of TUSC5 suggests epigenetic mechanism of cancer associated down-regulation

Hypermethylation of TUSC5 genes in breast cancer tissue.

Breast cancer (BC) is one of the most common forms of cancer amongst females. Early diagnosis, prognosis and therapy plays crucial role in the survival of patients with breast cancer. The study was aimed on identification of potential markers for early BC diagnostics by means of genome-wide comparative analysis of gene expression in cancer and normal tissue of breast. The analysis of gene expression in 15 invasive adenocarcinoma specimens and 15 normal breast tissue was conducted using the full-genome microarrays Sentrix HumanWD-6V3 BeadChip (Illumina). Methylation of TP53INK1 and TUSС5 promoters was interrogated by the combined bisulfite restriction analysis (COBRA). Results: Analysis of gene expression in the samples of breast adenocarcinoma revealed abnormal expression of more than 2,300 genes. While genes TFF1, S100P, ERBB2, TOP2A, CDF15, HOOK1, DNAJC12, CORO2A were up-regulated in cancer, decreased expression was found for genes TUSC5, SFRP1, PPPQR1B, NTRK4, TIMP4, BARD1, AKR1C2, TP53INK1 and others. Analysis of DNA methylation of TUSC5 by COBRA revealed higher levels of exon 1 methylation (11/12) in samples of breast cancer, whereas the gene was essentially unmethylated in matched normal appearing tissue of breast (2/12). TP53INK1 gene was methylated neither in cancer nor in normalcy. Conclusion: A total of 149 genes exhibited the highest difference in expression in cancer versus normal appearing tissue of breast. Most prominent down-regulated candidates, TUSC5 and TP53INK1, were reported for the first time in breast cancer and may be considered as potential markers of the disease. Aberrant DNA hypermethylation of TUSC5 suggests epigenetic mechanism of cancer associated down-regulation. Key Words: differentially expressed genes, DNA methylation, breast cancer

Complex model of asynchronous electric drives with ansys software

В работе рассматриваются особенности построения комплексной модели асинхронного электропривода с тиристорным преобразователем напряжения с использованием программных средств ANSYS и представлены результаты моделирования.The paper discusses the features of the construction of a complex model of the asynchronous electric drive with thyristor voltage converter using ANSYS software and modeling results are represented

A study on L-threonine and L-serine uptake in Escherichia coli K-12

In the current study, we report the identification and characterization of the yifK gene product as a novel amino acid carrier in E. coli K-12 cells. Both phenotypic and biochemical analyses showed that YifK acts as a permease specific to L-threonine and, to a lesser extent, L-serine. An assay of the effect of uncouplers and composition of the reaction medium on the transport activity indicates that YifK utilizes a proton motive force to energize substrate uptake. To identify the remaining threonine carriers, we screened a genomic library prepared from the yifK-mutant strain and found that brnQ acts as a multicopy suppressor of the threonine transport defect caused by yifK disruption. Our results indicate that BrnQ is directly involved in threonine uptake as a low-affinity but high-flux transporter, which forms the main entry point when the threonine concentration in the external environment reaches a toxic level. By abolishing YifK and BrnQ activity, we unmasked and quantified the threonine transport activity of the LIV-I branched chain amino acid transport system and demonstrated that LIV-I contributes significantly to total threonine uptake. However, this contribution is likely smaller than that of YifK. We also observed the serine transport activity of LIV-I, which was much lower compared with that of the dedicated SdaC carrier, indicating that LIV-I plays a minor role in the serine uptake. Overall, these findings allow us to propose a comprehensive model of the threonine/serine uptakesubsystem in E. coli cells

Digital receivers for low-frequency radio telescopes UTR-2, URAN, GURT

This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. Since 1998, digital receivers performing on-the-fly dynamic spectrum calculations or waveform data recording without data loss have been used at the UTR-2 radio telescope, the URAN VLBI system, and the GURT new generation radio telescope. Here we detail these receivers developed for operation in the strong interference environment that prevails in the decameter wavelength range. Data collected with these receivers allowed us to discover numerous radio astronomical objects and phenomena at low frequencies, a summary of which is also presented.Comment: 24 pages, 15 figure

The ART-XC telescope on board the SRG observatory

ART-XC (Astronomical Roentgen Telescope - X-ray Concentrator) is the hard X-ray instrument with grazing incidence imaging optics on board the Spektr-Roentgen-Gamma (SRG) observatory. The SRG observatory is the flagship astrophysical mission of the Russian Federal Space Program, which was successively launched into orbit around the second Lagrangian point (L2) of the Earth-Sun system with a Proton rocket from the Baikonur cosmodrome on 13 July 2019. The ART-XC telescope will provide the first ever true imaging all-sky survey performed with grazing incidence optics in the 4-30 keV energy band and will obtain the deepest and sharpest map of the sky in the energy range of 4-12 keV. Observations performed during the early calibration and performance verification phase as well as during the on-going all-sky survey that started on 12 Dec. 2019 have demonstrated that the in-flight characteristics of the ART-XC telescope are very close to expectations based on the results of ground calibrations. Upon completion of its 4-year all-sky survey, ART-XC is expected to detect ~5000 sources (~3000 active galactic nuclei, including heavily obscured ones, several hundred clusters of galaxies, ~1000 cataclysmic variables and other Galactic sources), and to provide a high-quality map of the Galactic background emission in the 4-12 keV energy band. ART-XC is also well suited for discovering transient X-ray sources. In this paper, we describe the telescope, results of its ground calibrations, major aspects of the mission, the in-flight performance of ART-XC and first scientific results.Comment: 19 pages, 30 figures, accepted for publication in Astronomy and Astrophysic

ДИНАМИЧЕСКИЙ СКРИНИНГ ПРЕДРАКОВЫХ СОСТОЯНИЙ ПИЩЕВОДА С ПОМОЩЬЮ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКОГО АНАЛИЗА

Introduction. Esophageal adenocarcinoma develops from areas of intestinal metaplasia in Barrett’s esophagus, similar to how intestinal metaplasia transforms into gastric adenocarcinomas in the stomach. Atypia with intraepithelial neoplasia is difficult to distinguish from reactive and regenerative changes, especially in erosive mucosa of the esophagus. Observation of patients with Barrett’s esophagus allows the identification of adenocarcinoma in the earlier, more curable stages in many patients.The aim of our study was to study the prospects of using a classifier based on miRNA profiling in histological samples of Barrett’s esophagus to determine the risk of malignancy and treatment tactics.Material and Methods. In this study, 119 samples of archival histological material in the form of paraffin blocks were used: 89 samples of gastric mucosa with dysplasia and 30 samples of Barrett’s esophagus. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p,-31-5p,-34a-5p,-375 was determined using real-time RT-PC R. Samples were stratified into different groups using the C-RT decision tree algorithm.Results. 26.7 % of Barrett’s esophagus samples were classified by expression of the proposed miRNAs as cancer, which may indicate a potential development of a malignant tumor in the mucosa of the esophagus when morphological changes have not yet been found.Введение. Специализированный кишечный эпителий с признаками атипической гиперплазии при пищеводе Барретта наиболее часто подвергается малигнизации и является предшественником аденокарциномы пищевода, аналогично тому, как в  желудке кишечная метаплазия трансформируется в аденокарциному. Атипия при внутриэпителиальной неоплазии в пищеводе Барретта трудно отличима от реактивных и регенераторных изменений, особенно при эрозированной слизистой пищевода. Анализ молекулярных маркеров является перспективным подходом в качестве дополнения к морфологическому исследованию при эндоскопическом скрининге пищевода Барретта. Цель исследования – изучение перспективности применения классификатора, основанного на профилировании миРНК в гистологических образцах пищевода Барретта, для определения риска злокачественности и тактики лечения.Материал и методы. В работе было использовано 119 образцов архивного гистологического материала в виде парафиновых блоков: 89 образцов язв желудка с дисплазией и 30 образцов пищевода Барретта. Уровень экспрессии микроРНК-145-5p, -150-5p, -20a-5p, -21-5p, -31-5p, -34a-5p, -375 определялся с помощью ОТ-ПЦР в реальном времени. Стратификацию образцов на разные группы проводили с помощью алгоритма построения дерева принятия решений c-Rt. Результаты. С помощью экспрессии предложенного набора миРНК 26,7 % образцов пищевода Барретта были классифицированы как рак, что может свидетельствовать о потенциальном развитии злокачественной опухоли в слизистой пищевода, когда морфологические изменения еще не найдены.