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Supplementary Figure 1 from Functional Epigenomics Identifies Genes Frequently Silenced in Prostate Cancer

Supplementary Table 1 from Functional Epigenomics Identifies Genes Frequently Silenced in Prostate Cancer

Supplementary Tables 2-3 from Functional Epigenomics Identifies Genes Frequently Silenced in Prostate Cancer

Supplementary Figure and Table Legends from Functional Epigenomics Identifies Genes Frequently Silenced in Prostate Cancer

In many cases, silencing of gene expression by CpG methylation is causally involved in carcinogenesis. Furthermore, cancer-specific CpG methylation may serve as a tumor marker. In order to identify candidate genes for inactivation by CpG methylation in prostate cancer, the prostate cancer cell lines LNCaP, PC3, and Du-145 were treated with 5-aza-2′ deoxycytidine and trichostatin A, which leads to reversion of epigenetic silencing. By microarray analysis of 18,400 individual transcripts, several hundred genes were found to be induced when compared with cells treated with trichostatin A. Fifty re-expressed genes were selected for further analysis based on their known function, which implied a possible involvement in tumor suppression. Twelve of these genes showed a significant degree of CpG methylation in their promoters. Six genes were silenced by CpG methylation in the majority of five analyzed prostate cancer cell lines, although they displayed robust mRNA expression in normal prostate epithelial cells obtained from four different donors. In primary prostate cancer samples derived from 41 patients, the frequencies of CpG methylation detected in the promoter regions of these genes were: GPX3, 93%; SFRP1, 83%; COX2, 78%; DKK3, 68%; GSTM1, 58%; and KIP2/p57, 56%. Ectopic expression of SFRP1 or DKK3 resulted in decreased proliferation. The expression of DKK3 was accompanied by attenuation of the mitogen-activated protein kinase pathway. The high frequency of CpG methylation detected in the promoters of the identified genes suggests a potential causal involvement in prostate cancer and may prove useful for diagnostic purposes.

Агроконсалтинг крестьянских фермерских хозяйств по вопросам инвестиционной деятельности оказывает непосредственное влияние на повышение доступности государственной поддержки для малых форм хозяйствования. Инвестиции в агробизнес являются не только мощным стимулом для развития приоритетных подотраслей агропромышленного комплекса и фермерского движения, но и косвенным фактором устойчивого развития сельского поселения, с территорией которого связано производство сельскохозяйственной продукции. Деятельность информационно-консультативных систем в агропродовольственном комплексе направлена на эффективную передачу достижений научно-технологического развития товаропроизводителям, что определяет одну из важнейших функций сельскохозяйственного консультирования в части анализа возникающих или существующих проблем, а также принятия оптимальных решений по их преодолению. В статье проанализирован механизм консалтингового сопровождения фермеров от момента появления предпринимательской идеи по созданию или расширению собственного малого бизнеса до реализации инвестиционного проекта. Проведенное исследование раскрывает взаимосвязь уровня трудоемкости консалтинга и уровня ответственности исполнителя данных услуг за выполненные работы с содержанием видов агроконсалтинга по существу. В результате исследования предложены рекомендации по повышению качества консалтингового сопровождения инвестиционных проектов крестьянских фермерских хозяйств с учетом фактора неопределенности.

It is noted that in the context of rapid digitalization of all aspects of the social order, when complex processes can be launched by pressing a button by a person’s decision, the degree of responsibility of each member of society for their decisions and actions increases many times over. A measure of this responsibility is functional literacy, an important component of which is subject - matter functional mathematical literacy, as the ability to think mathematically, formulate, apply and interpret mathematics to solve problems in a variety of practical contexts. Math literacy helps people understand the role of mathematics in the world, make well - founded judgments and make decisions that should be made by constructive, active and reflective citizens in the XXI century. According to the authors, an effective tool for the formation of mathematical literacy of students in the context of a future profession, prior to the systematic study of methods of applied professionally - oriented mathematical modeling, is the solution of specially selected model professionally - oriented problems (MPOP). In particular, this is important when training future medical workers, where the possibilities and effectiveness of using mathematical methods are clearly underestimated. As part of the implementation of the educational program of secondary professional education of a medical profile (SPE MP), the article touches on a number of issues related to the use of specially selected model professionally - oriented problems (MPOP) of physical, mathematical, informational, economic, and other contents. Such problems are assessed as a tool of achieving an educational result, expressed in the formation and development of professional intelligence and competencies among students of SPE MP in the specialty 31.02.04 “Medical Optics”.

Abnormal excitation of the heart can cause cardiac arrhythmias, which may result in cardiac arrest and sudden cardiac death. Currently, the most efficient way to stop lethal cardiac arrhythmias is high-voltage defibrillation. This method is extremely effective. However, it has serious disadvantages, as it is painful and can damage the heart. In this paper, we studied in-silico process of overdrive pacing of arrhythmia sources, which in some cases can also stop cardiac arrhythmias and does not require the application of high voltages. We investigated this process in the Luo–Rudy ionic model for cardiac cells and in case of circular anisotropy of cardiac tissue. We showed that we could efficiently remove the arrhythmia sources in the form of rotating spiral waves in such a system in a certain parameter range. However, anisotropy by itself can cause additional dynamics of the spiral waves: drift and break up. We studied manifestations of these effects and discussed their possible effects on the overdrive pacing. This paper is an extended version of the paper [1] which was submitted to the ICCS 2018 conference proceedings.

The article analyzes the images of animals in lyrical works of the famous Austrian expressionist poet Georg Trakl. Animals are the representatives of the biological kingdom of the same name. The images of mammals, as well as the images of insects, birds, and a worm are sequentially considered. There are twelve representatives. The images of animals are analyzed as elements of the artistic world of the works of the poet, which determines the novelty of the conclusions of this article. Each of the animals, according to the hypothesis, has a symbolic meaning, and the meaning is very stable, it moves from one poetic work to another. The symbolic meanings of the images of the animal kingdom in the poems of Georg Trakl are generally consistent with those established in common European culture, as evidenced by reference to the dictionaries of symbols (four authoritative sources are used). The authors reveal the semantic content of the image of each animal in specific texts, and compare it with the interpretation of its symbolic meaning in culture. As a result, conclusions are drawn about the coincidence of the full or partial semantic meaning of images in European culture (literature) and in Trakl's poems.

Nonlinear waves of electrical excitation initiate cardiac contraction. Abnormal wave propagation in the heart, e.g., spiral waves, can lead to sudden cardiac arrest. This study analyzed the dynamics of spiral waves under the influence of an instability called negative filament tension, and examined how the spiral waves can be eliminated through high-frequency pacing. A generic anatomical model of the left ventricle of the human heart and the Aliev-Panfilov model for cardiac tissue were used. The study showed that the source of such arrhythmia is elongated filaments with lengths that can be 10-20 times greater than the characteristic thickness of the heart wall. In anisotropic tissue, the filament elongated before it was annihilated at the base of the heart. The spiral waves were eliminated through overdrive pacing with stimulation periods from 0.8 to 0.95 relative to the spiral wave period. The minimum time for the expulsion was about 10 s. © 2021 American Physical Society. Russian Science Foundation, RSF: 17-71-20024 Our work involved simulations at the “Uran” cluster of IMM UB RAS (Ekaterinburg). Our research is supported by a Russian Science Foundation grant (Project 17-71-20024).