How many antiviral small interfering RNAs may be encoded by the mammalian genomes?

<p>Abstract</p> <p>Background</p> <p>The discovery of RNA interference phenomenon (RNAi) and understanding of its mechanisms has revolutionized our views on many molecular processes in the living cell. Among the other, RNAi is involved in silencing of transposable elements and in inhibition of virus infection in various eukaryotic organisms. Recent experimental studies demonstrate few cases of viral replication suppression via complementary interactions between the mammalian small RNAs and viral transcripts.</p> <p>Presentation of the hypothesis</p> <p>It was found that >50% of the human genome is transcribed in different cell types and that these transcripts are mainly not associated with known protein coding genes, but represent non-coding RNAs of unknown functions. We propose a hypothesis that mammalian DNAs encode thousands RNA motifs that may serve for antiviral protection. We also presume that the evolutional success of some groups of genomic repeats and, in particular, of transposable elements (TEs) may be due to their ability to provide antiviral RNA motifs to the host organism. Intense genomic repeat propagation into the genome would inevitably cause bidirectional transcription of these sequences, and the resulting double-stranded RNAs may be recognized and processed by the RNA interference enzymatic machinery. Provided that these processed target motifs may be complementary to viral transcripts, fixation of the repeats into the host genome may be of a considerable benefit to the host. It fits with our bioinformatical data revealing thousands of 21-28 bp long motifs identical between human DNA and human-pathogenic adenoviral and herpesviral genomes. Many of these motifs are transcribed in human cells, and the transcribed part grows proportionally to their lengths. Many such motifs are included in human TEs. For example, one 23 nt-long motif that is a part of human abundant Alu retrotransposon, shares sequence identity with eight human adenoviral genomes.</p> <p>Testing the hypothesis</p> <p>This hypothesis could be tested on various mammalian species and viruses infecting mammalian cells.</p> <p>Implications of the hypothesis</p> <p>This hypothesis proposes that mammalian organisms may use their own genomes as sources of thousands of putative interfering RNA motifs that can be recruited to repress intracellular pathogens like proliferating viruses.</p> <p>Reviewers</p> <p>This article was reviewed by Eugene V. Koonin, Valerian V. Dolja and Yuri V. Shpakovski.</p

EVALUATION OF THE EFFICIENCY OF APPLICATION OF METHOD 5C AT THE ENTERPRISE

This article discusses the use of Kaizen using Lean methods and employee involvement in continuous improvement activities.В настоящей статье рассмотрен вариант применения Кайдзен с помощью методов бережливого производства и вовлеченности работников в деятельность по постоянному улучшению

The Yongbyon Reactor as an Object af The Six-Party Talks an the DPRK’s Nuclear Program (Based on the Materials of the American Press)

The article was submitted on 28.03.2020.В статье проводится анализ событий шестисторонних переговоров по ядерной программе Северной Кореи, касающихся проблемы функционирования реактора в Йонбёне, через призму американских СМИ. Актуальность темы обусловлена тем, что именно Йонбёнский научно-исследовательский центр стал первым ядерным комплексом в КНДР, который позволил Северной Корее производить оружейный плутоний, что широко обсуждалось в средствах массовой информации США. Реализация ядерной программы оказала большое влияние на американо-северокорейские отношения, в которых Соединенные Штаты стремились контролировать действия КНДР в этой сфере. Для решения проблемы использования ядерного центра в Йонбёне в 2003–2009 гг. была организована серия Шестисторонних переговоров при участии США, КНР, России, Японии, Республики Корея и КНДР. Так как этот вопрос был непосредственно связан с Соединенными Штатами и их внешней политикой, он широко освещался в американских СМИ, главным образом в «Нью-Йорк таймс» и «Лос-Анджелес таймс», материалы которых послужили основным источником в написании данной статьи. Если в «Нью-Йорк таймс» чаще всего публиковались резолюции, итоги официальных встреч, цитировались тексты официальных документов, то в «Лос-Анджелес таймс» шестисторонние переговоры освещались лишь фрагментарно. В данной статье также использовались материалы местных газет, таких как «Остин америкэн стейтмент» и «Ньюс Джорнал», которые, в силу своей локальной специфики, освещали лишь наиболее важные события. Отметим, что практически во всех исследуемых изданиях освещалась не только точка зрения США, но и других стран-участниц шестисторонних переговоров. Большая часть публикаций отражала официальное мнение правительства Соединенных Штатов, подвергая критике позицию КНДР, однако редакция ряда газет выражала свое несогласие с жесткой позицией США по отношению к ядерной программе Северной Кореи. В статье рассматривается и анализируется позиция американской прессы в отношении данной проблемы, делаются обоснованные выводы.The article analyses events of the Six-Party Talks on North Korea’s nuclear program concerning the problem of the Yongbyon reactor functioning through the prism of the US press. The relevance of the topic is due to the fact that the Yongbyon research center became the first nuclear complex in the DPRK which allowed North Korea to produce weapons-grade plutonium that was widely discussed in the US media. The implementation of the nuclear program had a great impact on US-North Korean relations, with the United States seeking to control the actions of the DPRK in this area. To solve the problem of using the Yongbyon nuclear center, a series of the Six–Party Talks were conducted in the period of 2003–2009 with the participation of the United States, China, Russia, Japan, the Republic of Korea and the North Korean. Since this issue was directly related to the United States and its foreign policy, it was widely covered in the American media, mainly in «The New York Times» and the «Los Angeles Times», whose materials served as a main source for this article. «The New York Times» mostly published resolutions, the results of official meetings, quoted the texts of official documents. In the meantime, the «Los Angeles Times» covered the six-party talks only incompletely and partially. This article also used material of local newspapers, such as the «Austin American-Statesman », the «News Journal» which due to their local specificity covered only the most important events. It should be noted that almost all the publications under study covered not only the point of view of the United States, but also the one of the other countries participating in the Six-Party Talks. Most of the publications reflected an official opinion of the United States government criticizing the position of the DPRK`s administration. In the meanwhile, the editors of a number of newspapers expressed their disagreement with the tough position of the United States concerning North Korea’s nuclear program. The article examines and analyzes the position of the US press in relation to this problem, and reasonable conclusions are made

Moonlight functions of glycolytic enzymes in cancer

Since an extensive genome research has started, basic principle “one gene—one protein—one function” was significantly revised. Many proteins with more than one function were identified and characterized as “moonlighting” proteins, which activity depend not only on structural peculiarities but also on compartmentation and metabolic environment. It turned out that “housekeeping” glycolytic enzymes show important moonlight functions such as control of development, proliferation, apoptosis, migration, regulation of transcription and cell signaling. Glycolytic enzymes emerged very early in evolution and because of the limited content of genomes, they could be used as ancient regulators for intercellular and intracellular communication. The multifunctionality of the constitutively expressed enzymes began to serve cancer cell survival and growth. In the present review we discuss some moonlight functions of glycolytic enzymes that important for malignant transformation and tumor growth

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Novel robust biomarkers for human bladder cancer based on activation of intracellular signaling pathways

Sherpa Romeo blue journal. Open access article. Creative Commons Attribution 3.0 License (CC BY 3.0) applies.We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression in 17 cancer and seven non-cancerous bladder tissue samples. These experiments were done in two independent laboratories located in Russia and Canada. We calculated pathway activation strength values for the investigated transcriptomes and identified signaling pathways that were regulated differently in bladder cancer (BC) tissues compared with normal controls. We found, for both experimental datasets, 44 signaling pathways that serve as excellent new biomarkers of BC, supported by high area under the curve (AUC) values. We conclude that the OncoFinder approach is highly efficient in finding new biomarkers for cancer. These markers are mathematical functions involving multiple gene products, which distinguishes them from “traditional” expression biomarkers that only assess concentrations of single genes.Ye

МОЛЕКУЛЯРНЫЕ МАРКЕРЫ РАКА МОЧЕВОГО ПУЗЫРЯ: ОТ ЧАСТНОГО К ЦЕЛОМУ

Bladder cancer (BC) is the second most common urinary tract malignancy. Early diagnosis of BC generally increases the probability of successful treatment in a patient. The paper considers noninvasive diagnosis methods for BC and gives a database of the known molecular markers of this disease.Рак мочевого пузыря (РМП) занимает 2-е место по распространенности среди злокачественных опухолей мочеполовой системы. Ранняя диагностика РМП, как правило, существенно повышает вероятность успешного лечения пациента. В статье рассмотрены методы неинвазивной диагностики РМП и приводится база данных известных молекулярных маркеров этого заболевания

SYMBOL AS ONE OF THE PECULIARITIES OF FICTION DISCOURSE (BY WAY OF EXAMPLE OF THE WORKS BY THE ENGLISH SPEAKING AND RUSSIAN SPEAKING WRITERS)

The paper analyses symbol as one of the peculiarities of fiction discourse. Conventional symbols appear in fiction just as often as they appear in daily speech. They can be easily understood and interpreted. Writers employ authorial symbols for revealing artistic images and describing events. The researchers of this sphere affirm that symbols can both enrich a work of literature giving it additional meanings and, at the same time, especially for a non-expert, they can burden it and make the work of literature beyond one’s full comprehension. Conventional symbols often allude to other works from our cultural heritage, such as the Bible, ancient history and literature, and works written by the English speaking and Russian speaking authors. Sometimes understanding a story may require knowledge of history, politics and current events in the modern world. Private symbols do not have pre-established associations: the meanings that are attached to them emerge from the context of the work in which they occur. A writer gives his own personal symbolic significance to an object, event or color. The aim of the research consists in revealing and analysing the authorial symbols and examining them in fiction discourse. Practical value of the research consists in the possibility of applying its results in preparing for lecture courses and seminars on modern British and American literature and stylistics

Analysis of Experience in the Transition of Enterprises to the Standard ISO 45001:2018

In March 2018, the International Standard for the development of personnel health and safety management systems for optimizing labor relations at enterprises was published. The publication of the new ISO 45001: 2018 affected the interests of organizations certified for compliance with OHSAS 18001. The article analyzes and systematizes the problems faced by enterprises when switching to ISO 45001: 2018 “Occupational Health and Safety Management Systems - Requirements and Recommendations for Application ".В марте 2018 года опубликован Международный стандарт по разработке систем управления охраной здоровья и безопасностью персонала для оптимизации трудовых отношений на предприятиях. Публикация нового ISO 45001:2018 затронула интересы организаций, сертифицированных на соответствие ОHSAS 18001. В статье проведен анализ и систематизация проблем, с которыми столкнулись предприятия при переходе на стандарт ISO 45001:2018 «Системы менеджмента охраны здоровья и безопасности труда – Требования и рекомендации по применению»

Морфологическое изучение активности матриксных металлопро-теиназ и соотношения коллагена I/III в тканях пародонта в процессе комплексного лечения пациентов с хроническим и агрессивным течением пародонтита

The article presents the results of a follow up morphological study of matrix metalloproteinase activity and collagen type I/III ratio in periodontal tissue of patients with chronic and aggressive periodontitis after conservative and surgical treatment. The results of clinical and morphological studies have shown that the condition of periodontal tissues depends not only on the severity of periodontitis, but also on the nature of the inflammatory process course - chronic or aggressive.В статье представлены результаты морфологического изучения активности матриксных металлопротеиназ и соотношения коллагена I/III в тканях пародонта у пациентов с хроническим и агрессивным течением пародонтита в динамике после проведения консервативного и хирургического лечения. Результаты клинических и морфологических исследований показали, что состояние тканей пародонта зависит не только от степени тяжести пародонтита, но и от характера течения воспалительного процесса - хронического или агрессивного