Low-frequency (ELF–VLF) radio atmospherics study at the Ukrainian Antarctic Akademik Vernadsky station

This paper describes the results of the atmospherics measurements in the extremely low-frequency (ELF) and very low-frequency (VLF) frequency ranges performed at the Akademik Vernadsky station (64.26W; 65.25S) during February–April 2019. The main objective of the study was the implementation of a single-site technique for monitoring the lower ionosphere parameters and locating globally distributed powerful lightning discharges.У даній статті описано результати вимірювань атмосфериків в діапазонах наднизькочастотних (ННЧ) і дуже низькочастотних (ДНЧ), виконаних на Українській антарктичній станції (УАС) «Академік Вернадський» (64.26 W; 65.25 S) протягом лютого—квітня 2019 року. Основною метою дослідження була реалізація однопозиційного методу для моніторингу параметрів нижньої іоносфери та локації потужних грозових розрядів, розподілених по всій планеті

Transcriptional regulation of the AP-1 and Nrf2 target gene sulfiredoxin

“Two-cysteine” peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus, reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin’s role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here. the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress

Labour subject’s professional culture as an integrative phenomenon

Essence, structure and mission of modern specialist’s professional culture are analyzed in the article. The author reveals the basic theoretical and methodological background of investigating labour subject’s professional culture as an integrative phenomenon. In this context actual determinants, which characterize direction, character, development psychological specificity and display of labour subject’s professional culture, are specified and revealed. Herewith, the multi-faceted mission of conditions and factors is pointed and characterized. On the one hand, they contribute to development of labour subject’s professional culture, but, on the other hand, some of the pointed determinants block this process. The particular place in the article is occupied by the realized integrative approach which allows characterizing labour subject’s professional culture, its development and functioning as an integrative phenomenon in a systematic way. For increasing efficiency of this process the psychological model of achieving this goal in the concrete labour system is made and tested

Retroviral reporter systems for the assessment of activity of stress-induced signal transduction pathways controlled by p53, HIF-1 and HSF-1 transcription factors

The tumor suppressor p53, hypoxia-inducible factor 1 (HIF-1), and heat-shock factor 1 (HSF-1) are the key transcription factors involved in the stress response to damage of the genetic material, hypoxia, or heat shock, respectively. Since these factors play a considerable role in tumor development and progression, modulation of their activities may be used in cancer therapy. To quantitate the transcriptional activities of p53, HIF-1, and HSF-1, reporter constructs were obtained on the basis of retroviral and lentiviral vectors, allowing generation of reporter cultures from almost all cell types. Induction of the reporter ?-galactosidase gene, which reflected the activity of p53 or HIF-1, proved to depend on the concentration of an activating agent and to correlate with induction of the endogenous target genes of the transcription factors. Inhibition of p53 or HIF-1? expression with specific small interfering RNAs (siRNAs) completely abolished the activating effect of stress conditions. The reporter constructs were proposed for screening chemical compounds or genetic elements (siRNA or cDNA libraries) that modulate the activity of p53, HIF-1, or HSF-1 and for studying the components of the relevant signaling pathways

Sestrin-2 is significantly increased in malignant pleural effusions due to lung cancer and is potentially secreted by pleural mesothelial cells

Objectives: Sestrin-2 (Sesn2) belongs to a family of highly conserved antioxidant proteins that were discovered as p53-inducible proteins and inhibits cell growth and proliferation. Our aim was to assess the levels of Sesn2 in malignant pleural effusions of lung cancer patients compared to benign pleural effusions. Design and methods: We enrolled 73 patients (55/males and 18/females) diagnosed with pleural effusion (PE). PEs were grouped as 44 malignant pleural effusions (MPEs; lung cancer) and 29 benign (BPE; 7 congestive heart failure, 9 tuberculosis, 13 parapneumonic). Pleural fluid (PF) Sesn2 levels were determined by enzyme-linked immunosorbent assay (ELISA) kit. Standard biochemical PF analysis was also performed and Sesn2 levels were correlated with PF lactate dehydrogenase (LDH), protein, cell counts and age. Results: Sesn2 was detected in 24/44 patients with MPEs and in 3/29 patients with BPEs (p = 0.0001). The mean value (mean ± SEM) of Sesn2 in patients with MPEs was 0.54 ± 0.22 ng/mL while in BPEs it was 0.12 ± 0.04 ng/mL (p = 0.0004). In MPEs Sesn2 pleural fluid levels did not correlate with PF LDH and cell counts (p = 0.89 and p = 0.64 respectively). Conclusions: Our study shows that Sesn2 is significantly increased in MPEs compared to BPEs. Moreover, the lack of correlation of Sesn2 levels with PF cell counts and PF LDH suggests that it is potentially secreted by pleural mesothelial cells. © 2016 The Canadian Society of Clinical Chemists

Transcriptional Inhibition of the Human Papilloma Virus Reactivates Tumor Suppressor p53 in Cervical Carcinoma Cells

Inactivation of tumor suppressor p53 accompanies the majority of human malignancies. Restoration of p53 function causes death of tumor cells and is potentially suitable for gene therapy of cancer. In cervical carcinoma, human papilloma virus (HPV) E6 facilitates proteasomal degradation of p53. Hence, a possible approach to p53 reactivation is the use of small molecules suppressing the function of viral proteins. HeLa cervical carcinoma cells (HPV-18) with a reporter construct containing the ?-galactosidase gene under the control of a p53-responsive promoter were used as a test system to screen a library of small molecules for restoration of the transcriptional activity of p53. The effect of the two most active compounds was studied with cell lines differing in the state of p53-dependent signaling pathways. The compounds each specifically activated p53 in cells expressing HPV-18 and, to a lesser extent, HPV-16 and exerted no effect on control p53-negative cells or cells with the intact p53-dependent pathways. Activation of p53 in cervical carcinoma cells was accompanied by induction of p53-dependent CDKN1 (p21), inhibition of cell proliferation, and induction of apoptosis. In addition, the two compounds dramatically decreased transcription of the HPV genome, which was assumed to cause p53 reactivation. The compounds were low-toxic for normal cells and can be considered as prototypes of new anticancer drugs

Analysis and ways of improvement of method of preparation of operative personnel for providing of electric stations safety

Проведен анализ существующих технических и программных средств обучения оперативно-диспетчерского персонала электрических станций, рассмотрены требования к и их характеристикам, на основе системного подхода к вопросам технической реализации автоматизации реальных энергообъектов и учёта временного критерия был предложен вариант построения информационно-алгоритмической структуры модели – тренажёра, который позволяет проследить и имитировать прохождение информационных потоков от нижних к верхним уровням, таким образом, увеличивается количество штатных и нештатных ситуаций, при которых необходимо принимать оперативное решение в режиме реального времени.Проведений аналіз існуючих технічних і програмних засобів навчання оперативно-диспетчерського персоналу електричних станцій, розглянуті вимоги до і їх характеристикам, на основі системного підходу до питань технічної реалізації автоматизації реальних енергооб'єктів і обліку тимчасового критерію був запропонований варіант побудови інформаційно-алгоритмічної структури моделі – тренажера, який дозволяє прослідкувати і імітувати проходження інформаційних потоків від нижніх до верхніх рівнів, таким чином, збільшується кількість штатних і нештатних ситуацій, при яких необхідно ухвалювати оперативне рішення в режимі реального часу.The analysis of existent technical and programmatic facilities of teaching of operatively-controller's personnel of the electric stations is conducted, requirements are considered to to and to their descriptions, on the basis of approach of the systems to the questions of technical realization of automation of the real energy object and account of temporal criterion the variant of construction of informatively-algorithmic structure of model was offered – trainer which allows to trace and imitate passing informative streams from lower to the top levels, thus, the amount of regular and nonpermanent situations at which it is necessary to make operative decision in the real-time mode is multiplied

Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma.

Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as javax.xml.bind.JAXBElement@4375628f Using a focused genetic screen, we identified javax.xml.bind.JAXBElement@76a4bdfb as a relevant target of the 6q deletion and demonstrate tumor suppression by javax.xml.bind.JAXBElement@26a2409a in vivo. Moreover, javax.xml.bind.JAXBElement@3203074e is a direct target of the lymphoma-specific javax.xml.bind.JAXBElement@5a0a6a9b gain-of-function mutation ( javax.xml.bind.JAXBElement@9925f44 javax.xml.bind.JAXBElement@3d00687c ). javax.xml.bind.JAXBElement@179321e5 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. javax.xml.bind.JAXBElement@1e44df3e loss represents an alternative to javax.xml.bind.JAXBElement@5b7cbcd mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, javax.xml.bind.JAXBElement@3bca108f javax.xml.bind.JAXBElement@3558921a mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies