STRESS AND STRAIN STATE OF THE KAZAKH SHIELD FROM THE EARTHQUAKE FOCAL MECHANISMS DATA

The paper presents the results obtained during the study of seismicity of the Kazakh shield based on the data from seismic stations of the Institute of Geophysical Researches of Kazakhstan which are a part of the international monitoring systems. Emphasis has been placed on seismic activation in 2016–2018 in the middle part of the Central Kazakhstan arch, previously considered aseismic. The earthquake focal mechanisms determined for 40 seismic events recorded in the investigated area are based on the displacement directions of the first arriving P waves.On the basis of the analysis of the earthquake focal mechanism data set, an assessment has been made of the present-day stress-strain state of the Earth’s crust of the low-seismicity Kazakh shield. It is shown that a system of stresses in the investigated area is characterized by conditions for near-horizontal compression whose direction is consistent with the direction of movement of the Alpine geomorphostructures. It has been found that the earthquake sources in the investigated area are dominated by reverse faults and reverse-slip faults which correspond structurally to the northeast-striking and submeridional tectonic faults, thus testifying to present-day seismic activation of the northeastern thrusts.This study allowed for concluding that the seismic events considered are human-induced, i.e. technogenic-tectonic, earthquakes. A long-term technogenic impact reducing the strength of rocks in fault zones can be a cause of critical stress drop in earthquake sources located in the Kazakh shield. The data on the character of motions and stresses in the earthquake sources influencing on shaking intensity will be used in combination with other methods for the assessment of natural and technogenic hazards related to geodynamic processes

НАПРЯЖЕННО-ДЕФОРМИРОВАННОЕ СОСТОЯНИЕ КАЗАХСКОГО ЩИТА ПО ДАННЫМ МЕХАНИЗМОВ ОЧАГОВ ЗЕМЛЕТРЯСЕНИЙ

The paper presents the results obtained during the study of seismicity of the Kazakh shield based on the data from seismic stations of the Institute of Geophysical Researches of Kazakhstan which are a part of the international monitoring systems. Emphasis has been placed on seismic activation in 2016–2018 in the middle part of the Central Kazakhstan arch, previously considered aseismic. The earthquake focal mechanisms determined for 40 seismic events recorded in the investigated area are based on the displacement directions of the first arriving P waves.On the basis of the analysis of the earthquake focal mechanism data set, an assessment has been made of the present-day stress-strain state of the Earth’s crust of the low-seismicity Kazakh shield. It is shown that a system of stresses in the investigated area is characterized by conditions for near-horizontal compression whose direction is consistent with the direction of movement of the Alpine geomorphostructures. It has been found that the earthquake sources in the investigated area are dominated by reverse faults and reverse-slip faults which correspond structurally to the northeast-striking and submeridional tectonic faults, thus testifying to present-day seismic activation of the northeastern thrusts.This study allowed for concluding that the seismic events considered are human-induced, i.e. technogenic-tectonic, earthquakes. A long-term technogenic impact reducing the strength of rocks in fault zones can be a cause of critical stress drop in earthquake sources located in the Kazakh shield. The data on the character of motions and stresses in the earthquake sources influencing on shaking intensity will be used in combination with other methods for the assessment of natural and technogenic hazards related to geodynamic processes.Приводятся результаты изучения сейсмичности Казахского щита по данным сейсмических станций Института геофизических исследований Республики Казахстан, входящих в международные системы мониторинга. Отмечена активизация сейсмичности в 2016–2018 гг. в центральной части Центрально-Казахстанского свода, считавшейся ранее асейсмичной. Для 40 сейсмических событий, зарегистрированных в рассматриваемом районе, построены механизмы очагов по направлениям смещений в первых вступлениях Р-волн.На основе анализа совокупности всех полученных данных о механизмах очагов землетрясений выполнена оценка современного напряженно-деформированного состояния земной коры слабосейсмичного Казахского щита. Показано, что система напряжений на рассматриваемой территории характеризуется условиями близгоризонтального сжатия в направлении, согласующемся с направлением движения альпийских геоморфоструктур. Установлено превалирование в очагах землетрясений исследуемого региона взбросо- и взбросо-сдвиговых подвижек по плоскостям разрывов, которые находят структурное соответствие с тектоническими разломами северо-восточного и субмеридионального простирания, свидетельствующее о сейсмической активизации северо-восточных надвигов в настоящее время.На основе проведенного исследования сделан вывод, что рассматриваемые сейсмические события являются землетрясениями, спровоцированными техногенной деятельностью человека, т.е. техногенно-тектоническими. В результате длительного техногенного воздействия, вызывающего снижение прочности пород разломных зон, в структурах Казахского щита происходит формирование очагов землетрясений с более низким уровнем критических напряжений. Сведения о характере подвижек и напряжений в очагах землетрясений, влияющих на интенсивность сотрясений, в комплексе с другими методами будут использоваться для оценки природных и техногенных опасностей, связанных с геодинамическими процессами

Experience in managing patients with Churg-Strauss syndrome.

Our goal was to analyze the possibilities of impro­ving the diagnostics of CSS and to improve the effectiveness of treatment according to the existing literature and our own experience of long-term care for patients with eosinophilic granulomatosis with polyangiitis or Churg-Strauss syndrome (CSS). The medical histories of three female patients aged 26 to 46-years and a 20-year-old male patient were considered. The duration of the disease before the established diagnosis was 5-17 years. Anamnesis and medical documents analysis showed a typical CSS debut in the form of allergic rhinitis, nasal polyps, which were recurrent after polypectomy, and respiratory disorders, which were regarded as bronchitis or bronchial asthma – corresponding to the first phase, also called the prodromal or allergic stage of CSS. The prodromal period lasts up to 10 years or more and is characterized by various allergic manifestations, more often –  pollinosis or bronchial asthma, that is difficult to control. But CSS can be suspected because of low effectiveness of the therapy with inhaled steroids, lack of effect of antibiotics and eosinophilia more than 10% that occurs periodically. Even in the third stage of CSS in systemic manifestations of vasculitis and severe secondary lesions of organs and tissues with functional impairment, constant intake of maintenance doses of corticosteroids and cytostatics allows to achieve stabilization of the process in patients with CSS

KDM2A represses transcription of centromeric satellite repeats and maintains the heterochromatic state

Heterochromatin plays an essential role in the preservation of epigenetic information, the transcriptional repression of repeti- tive DNA elements and inactive genes, and the proper segregation of chromosomes during mitosis. Here we identify KDM2A, a JmjC-domain containing histone demethylase, as a heterochro- matin-associated and HP1-interacting protein that promotes HP1 localization to chromatin. We show that KDM2A is required to maintain the heterochromatic state, as determined using a candidate-based approach coupled to an in vivo epigenetic reporter system. Remarkably, a parallel and independent siRNA screen also detected a role for KDM2A in epigenetic silencing. Moreover, we demonstrate that KDM2A associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Dissecting the relationship between heterochromatin and centromeric RNA transcription is the basis of ongoing studies. We demonstrate that forced expression of these satellite RNA transcripts compromise the heterochromatic state and HP1 localization to chromatin. Finally, we show that KDM2A is required to sustain centromeric integ- rity and genomic stability, particularly during mitosis. Since the disruption of epigenetic control mechanisms contributes to cellular transformation, these results, together with the low levels of KDM2A found in prostate carcinomas, suggest a role for KDM2A in cancer development

Удаление минеральных и органических веществ из поверхностных вод с использованием нанофильтрационных мембран

Screening investigations of organic and mineral substances’ removal from the different surface water sources by nanofiltration membranes have been carried out. It has been found that degree of water purification from organic substances was high, regardless to their concentration and filtrate conversion. On the contrary, removal degree for dissolved mineral substances depended highly on nanofiltration operating conditions and the water source origin.Проведены скрининговые исследования по удалению минеральных и органических веществ из поверхностных источников при помощи нанофильтрационных (НФ) мембран. В качестве объектов исследования были выбраны образцы поверхностных вод: р. Западная Двина (г. Витебск), р. Полота (г. Полоцк) и р. Свислочь (г. п. Свислочь, ТЭЦ-5). Исследования показали, что использование НФ мембран позволяет достигнуть высокой степени очистки воды от органических загрязнений независимо от степени отбора фильтрата и концентрации органических веществ в исходной воде. Степень удаления растворенных минеральных веществ зависит от рабочих параметров процесса нанофильтрации и источника происхождения воды

Global histone modification fingerprinting in human cells using epigenetic reverse phase protein array

The balance between acetylation and deacetylation of histone proteins plays a critical role in the regulation of genomic functions. Aberrations in global levels of histone modifications are linked to carcinogenesis and are currently the focus of intense scrutiny and translational research investments to develop new therapies, which can modify complex disease pathophysiology through epigenetic control. However, despite significant progress in our understanding of the molecular mechanisms of epigenetic machinery in various genomic contexts and cell types, the links between epigenetic modifications and cellular phenotypes are far from being clear. For example, enzymes controlling histone modifications utilize key cellular metabolites associated with intra- and extracellular feedback loops, adding a further layer of complexity to this process. Meanwhile, it has become increasingly evident that new assay technologies which provide robust and precise measurement of global histone modifications are required, for at least two pressing reasons: firstly, many approved drugs are known to influence histone modifications and new cancer therapies are increasingly being developed towards targeting histone deacetylases (HDACs) and other epigenetic readers and writers. Therefore, robust assays for fingerprinting the global effects of such drugs on preclinical cell, organoid and in vivo models is required; and secondly, robust histone-fingerprinting assays applicable to patient samples may afford the development of next-generation diagnostic and prognostic tools. In our study, we have used a panel of monoclonal antibodies to determine the relative changes in the global abundance of post-translational modifications on histones purified from cancer cell lines treated with HDAC inhibitors using a novel technique, called epigenetic reverse phase protein array. We observed a robust increase in acetylation levels within 2–24 h after inhibition of HDACs in different cancer cell lines. Moreover, when these cells were treated with N-acetylated amino acids in addition to HDACs, we detected a further increase in histone acetylation, demonstrating that these molecules could be utilized as donors of the acetyl moiety for protein acetylation. Consequently, this study not only offers a novel assay for diagnostics and drug screening but also warrants further research of the novel class of inexpensive, non-toxic natural compounds that could potentiate the effects of HDAC inhibitors and is therefore of interest for cancer therapeutics

Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI

Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents viral gene expression through the assembly of repressive chromatin remodeling complexes targeting incoming viral genomes. However, it has remained unclear how initial transcriptional activation of the adenoviral genome is achieved. Here we show that Daxx mediated repression of the immediate early Ad E1A promoter is efficiently counteracted by the capsid protein VI. This requires a conserved PPxY motif in protein VI. Capsid proteins from other DNA viruses were also shown to activate the Ad E1A promoter independent of Ad gene expression and support virus replication. Our results show how Ad entry is connected to transcriptional activation of their genome in the nucleus. Our data further suggest a common principle for genome activation of DNA viruses by counteracting Daxx related repressive mechanisms through virion proteins

Microarray analysis of LTR retrotransposon silencing identifies Hdac1 as a regulator of retrotransposon expression in mouse embryonic stem cells

Retrotransposons are highly prevalent in mammalian genomes due to their ability to amplify in pluripotent cells or developing germ cells. Host mechanisms that silence retrotransposons in germ cells and pluripotent cells are important for limiting the accumulation of the repetitive elements in the genome during evolution. However, although silencing of selected individual retrotransposons can be relatively well-studied, many mammalian retrotransposons are seldom analysed and their silencing in germ cells, pluripotent cells or somatic cells remains poorly understood. Here we show, and experimentally verify, that cryptic repetitive element probes present in Illumina and Affymetrix gene expression microarray platforms can accurately and sensitively monitor repetitive element expression data. This computational approach to genome-wide retrotransposon expression has allowed us to identify the histone deacetylase Hdac1 as a component of the retrotransposon silencing machinery in mouse embryonic stem cells, and to determine the retrotransposon targets of Hdac1 in these cells. We also identify retrotransposons that are targets of other retrotransposon silencing mechanisms such as DNA methylation, Eset-mediated histone modification, and Ring1B/Eed-containing polycomb repressive complexes in mouse embryonic stem cells. Furthermore, our computational analysis of retrotransposon silencing suggests that multiple silencing mechanisms are independently targeted to retrotransposons in embryonic stem cells, that different genomic copies of the same retrotransposon can be differentially sensitive to these silencing mechanisms, and helps define retrotransposon sequence elements that are targeted by silencing machineries. Thus repeat annotation of gene expression microarray data suggests that a complex interplay between silencing mechanisms represses retrotransposon loci in germ cells and embryonic stem cells

Beating the odds: programming proliferation in the mammalian heart

Editorial summary The heart is one of the least regenerative organs in the human body; adult cardiac myocytes divide at extremely low frequency. Therefore, meaningful induction of cardiac regeneration requires in-depth understanding of myocyte cell-cycle control. Recent insights into how myocytes can be coaxed into duplicating in vivo might inform emerging therapeutics