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

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

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

Characteristic patterns of microRNA expression in human bladder cancer

MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate gene expression. Their altered expression and functional activity have been observed in many human cancers. MiRNAs represent promising diagnostic and prognostic molecular biomarkers, and also serve as novel therapeutic targets. We performed a systematic analysis of scientific reports that link differences in miRNA expression with the pathogenesis of bladder cancer. This literature review is the first comprehensive database of miRNA molecules with biased expression profiles in bladder cancer. Among the 95 differentially expressed miRNAs that we identified from the literature, we classify 48 as upregulated in bladder cancer, 35 as downregulated, and 12 as contradictory (contradictory data were reported in one or more studies on the gene). In addition, we discuss the possible roles of differentially expressed miRNAs in the regulation of intracellular signaling pathways in bladder cancer

Molecular Ensembles of Microbiotic Metabolites in Carcinogenesis

The mechanisms of carcinogenesis are extremely complex and involve multiple components that contribute to the malignant cell transformation, tumor growth, and metastasis. In recent decades, there has been a growing interest in the role of symbiotic human microbiota in the regulation of metabolism and functioning of host immune system. The symbiosis between a macroorganism and its microbiota has given rise to the concept of a holoorganism. Interactions between the components of a holoorganism have formed in the process of coevolution, resulting in the acquisition by microbiotic metabolites of a special role of signaling molecules and main regulators of molecular interactions in the holoorganism. As elements of signaling pathways in the host organism, bacterial metabolites have become essential participants in various physiological and pathological processes, including tumor growth. At the same time, signaling metabolites often exhibit multiple effects and impact both the functions of the host cells and metabolic activity and composition of the microbiome. This review discusses the role of microbiotic metabolites in the induction and prevention of malignant transformation of cells in the host organism and their impact on the efficacy of anticancer therapy, with special emphasis on the involvement of some components of the microbial metabolite molecular ensemble in the initiation and progression of tumor growth

Evolutionary View on Lactate-Dependent Mechanisms of Maintaining Cancer Cell Stemness and Reprimitivization

The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate’s role in the malignant transformation becomes more relevant in the light of the “atavistic theory of carcinogenesis,” which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect

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

MOLECULAR MARKERS OF BLADDER CANCER: FROM THE PARTICULAR TO THE GENERAL

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