Xenobiotic-induced activation of human aryl hydrocarbon receptor target genes in Drosophila is mediated by the epigenetic chromatin modifiers

Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR\u27s target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway. Invertebrate AHR homologs are activated by endogenous ligands whereas vertebrate AHR can be activated by both endogenous and exogenous ligands (xenobiotics). Several studies using mammalian cultured cells have demonstrated that transcription of the AHR target genes can be activated by exogenous AHR ligands, but little is known about the effects of AHR in a living organism. Here, we examined the effects of human AHR and its ligands using transgenic Drosophila lines with an inducible human AhR gene. We found that exogenous AHR ligands can increase as well as decrease the transcription levels of the AHR target genes, including genes that control proliferation, motility, polarization, and programmed cell death. This suggests that AHR activation may affect the expression of gene networks that could be critical for cancer progression and metastasis. Importantly, we found that AHR target genes are also controlled by the enzymes that modify chromatin structure, in particular components of the epigenetic Polycomb Repressive complexes 1 and 2. Since exogenous AHR ligands (alternatively - xenobiotics) and small molecule inhibitors of epigenetic modifiers are often used as pharmaceutical anticancer drugs, our findings may have significant implications in designing new combinations of therapeutic treatments for oncological diseases. © Akishina et al

Sparkling extreme-ultraviolet bright dots observed with Hi-C

Observing the Sun at high time and spatial scales is a step toward understanding the finest and fundamental scales of heating events in the solar corona. The high-resolution coronal (Hi-C) instrument has provided the highest spatial and temporal resolution images of the solar corona in the EUV wavelength range to date. Hi-C observed an active region on 2012 July 11 that exhibits several interesting features in the EUV line at 193 Å. One of them is the existence of short, small brightenings "sparkling" at the edge of the active region; we call these EUV bright dots (EBDs). Individual EBDs have a characteristic duration of 25 s with a characteristic length of 680 km. These brightenings are not fully resolved by the SDO/AIA instrument at the same wavelength; however, they can be identified with respect to the Hi-C location of the EBDs. In addition, EBDs are seen in other chromospheric/coronal channels of SDO/AIA, which suggests a temperature between 0.5 and 1.5 MK. Based on their frequency in the Hi-C time series, we define four different categories of EBDs: single peak, double peak, long duration, and bursty. Based on a potential field extrapolation from an SDO/HMI magnetogram, the EBDs appear at the footpoints of large-scale, trans-equatorial coronal loops. The Hi-C observations provide the first evidence of small-scale EUV heating events at the base of these coronal loops, which have a free magnetic energy of the order of 1026 erg. © 2014. The American Astronomical Society. All rights reserved

Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification

Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans

ИСТОЧНИКИ ОБРАЗОВАНИЯ РАДИОАКТИВНЫХ ОТХОДОВ НА ГИДРОМЕТАЛЛУРГИЧЕСКИХ ЗАВОДАХ ПО ПЕРЕРАБОТКЕ УРАНОВЫХ РУД

A distinctive feature of enterprises for extracting and processing uranium ore is the inevitable pollution by solid, liquid and gaseous waste. The amount of radioactive waste (RW) is most significant in the nuclear fuel cycle. In spite of its relatively low activity it is the major contributor to the formation of radiation hazards to the people and environment. The radioactivity of uranium ores and of their processing waste is due to natural radionuclides of uranium (238U and 235U) and thorium (232Th) radioactive decay chains.Отличительной особенностью предприятий по добыче и переработке урановых руд является неизбежное загрязнение окружающей среды твердыми, жидкими и газообразными отходами. По своим объемам данные радиоактивные отходы (РАО) являются наиболее значительными в ядерно-топливном цикле и, несмотря на их сравнительно низкую активность, вносят основной вклад в формирование радиационно-опасных факторов для населения и объектов окружающей среды. Радиоактивность урановых руд и отходов их переработки обусловлена природными радионуклидами урановой (238U и 235U) и ториевой (232Th) цепочек радиоактивного распада. В статье рассмотрена основная схема образования РАО на технологическом переделе сорбции урана из пульп выщелачивания гидрометаллургического завода по переработке урановых руд и приведена оценка образования радионуклидного состава пульпы, направляемой на хвостохранилище. При ликвидации хвостохранилищ должны быть обеспечены стабильность, гидрологический контроль, минимальное поступление загрязненных вод на установки очистки вод, прекращение поступления радона в атмосферу

Analysis of the frequency of radiological signs of destructive changes in the hard tissues of the disto-aproximal surfaces of the second permanent molars in the presence of the third molars

Ризик розвитку карієсу залежить від наявності карієсогенних чинників. Дистальноапроксимальні поверхні коронок зубів характеризуються як ділянки з низькою карієсрезистентністю. Незважаючи на різноманіття засобів та предметів гігієнічного догляду за порожниною рота, проблема карієсу в цій зоні залишається актуальною. При цьому положення зубу у зубному ряду може спричиняти суттєвий вплив на можливість реалізації навіть досконалих мануальних навичок очищення даної ділянки та сприяти формуванню патологічних змін твердих тканин

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis

Digital receivers for low-frequency radio telescopes UTR-2, URAN, GURT

This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. Since 1998, digital receivers performing on-the-fly dynamic spectrum calculations or waveform data recording without data loss have been used at the UTR-2 radio telescope, the URAN VLBI system, and the GURT new generation radio telescope. Here we detail these receivers developed for operation in the strong interference environment that prevails in the decameter wavelength range. Data collected with these receivers allowed us to discover numerous radio astronomical objects and phenomena at low frequencies, a summary of which is also presented.Comment: 24 pages, 15 figure

ИНФОРМАЦИОННАЯ СИСТЕМА ТИПОВОЙ ИСПЫТАТЕЛЬНОЙ ЛАБОРАТОРИИ РАДИАЦИОННОГО КОНТРОЛЯ

Development of information-analytical system of radiation control is based on existing methods and hardware-software measuring instruments for the purpose of systematizing, storing and processing the results of analysis of samples of various composition and origin. Studying a large flow of environmental and technological samples includes the most difficult task to ensure the required accuracy of calculation of activities and errors, especially at low activities levels at the threshold of detectable area. The information system hardware includes a set of devices designed to measure the activity of the samples, and a local computer network. The server part of the software package includes a client-server database management system and a web application for database administration. In addition to the standard programs included in the delivery of radiometric equipment the client part of the software package includes the program "ODRA", developed using object-oriented language C# in Microsoft Visual Studio. The program "ODRA" includes modules for calculating the specific (volumetric) activity of radionuclides in low-active samples of materials and environmental objects, as well as for calculating the relative and absolute error of activity determination. The program has a convenient graphical user interface for database communication. The information system of the radiation testing laboratory of the enterprise that conducts work with radioactive materials has undergone a four-year approbation in the experimental production mode at VNIIHT in 2014-2017 and can significantly reduce the processing time of the results of determining the radioactivity of technological and environmental samples and reduce the operator error factor.Информационно-аналитическая система радиационного контроля разработана на основе существующих методик и аппаратно-программных средств измерений с целью систематизации, хранения и обработки результатов анализа проб образцов исследуемых сред, разнообразных по составу и происхождению. При исследовании большого потока проб экологического мониторинга различных территорий и технологических проб производственных и научных подразделений, наиболее сложной остается задача обеспечения требуемой точности расчета активностей и погрешностей в минимально детектируемой области. Аппаратное обеспечение информационной системы включает совокупность приборов, предназначенных для измерения активности образцов, и локальную вычислительную сеть. Серверная часть программного комплекса включает клиент-серверную систему управления базами данных и веб-приложение по администрированию базы данных. Клиентская часть программного комплекса, помимо стандартных программ, входящих в комплект поставки радиометрического оборудования, включает программу «ОДРА» (Обработка Данных Радиационного Анализа), разработанную на объектно-ориентированном языке C# в среде разработки Microsoft Visual Studio. В программу «ОДРА» включены модули для расчета удельной (объемной) активностей радионуклидов в материалах и объектах окружающей среды для низкоактивных образцов, а также для расчета относительной и абсолютной погрешности определения активности. Программа обладает удобным графическим интерфейсом для работы с базой данных. Информационная система испытательной лаборатории радиационного контроля предприятия, проводящего работы с радиоактивными материалами, прошла четырехлетнюю апробацию в режиме опытно-промышленной эксплуатации в АО «ВНИИХТ» в 2014-2017 гг. и позволяет значительно сократить время обработки результатов определения радиоактивности технологических и экологических проб и снизить фактор ошибки оператора

Antrax in Primorsky Territory (1919–2020). Communication 2. Episootiological- Epidemiological Situation and Zoning of Administrative Territories

The aim of the study was to analyze the epizootiological and epidemiological situation in the Primorsky Territory (1919–2020) and to zone the administrative districts in regard to anthrax. Materials and methods. Accounting and reporting documents, information and archival materials were collected and analyzed, statistical reference books and literature sources were used. A comprehensive epizootiological and epidemiological survey of 12 supposed places of anthrax burials and cattle burial grounds was carried out, and their biological hazard assessed. Results and discussion. Within the framework of updating the Cadastre of stationary potentially hazardous as regards anthrax areas in the Russian Federation (2005), the number of infected farm animals and human cases was specified: according to official data, over the period of 1930–1979, the disease in 173 animals and 34 people with five deaths was registered in 82 stationary unfavorable for anthrax areas of 22 municipalities of the region. Together with the veterinary service of the region, an audit of 12 supposed places of anthrax burials in seven districts of the region was conducted. Based on the results of a comprehensive epizootiological and epidemiological survey, high biological hazard was established for 2 and potential one – for 1 anthrax burials. The culture of Bacillus anthracis isolated on the territory of Primorsky Territory belongs to one of the canonical SNP clusters – A.Br.008/009 of the global genetic line A (subgroup A1). Five criteria for assessing the epizootiological and epidemiological disadvantage for anthrax and the ranking of indicators of the administrative territories in the region have been determined. Zoning of the administrative territories of the region according to risk of anthrax has been carried out. Prophylactic anti-epizootic and anti-epidemic measures have been put forward

The first and only combination of basal and prandial insulin analogs degludec and aspart: the position of Russian endocrinologists

Insulin therapy for diabetes mellitus is the most effective way to control glycemia with the progression of the disease and the ineffectiveness of other sugar-lowering drugs. At the same time, the existing limitations of traditional insulin preparations, along with increasing attention to the individualized treatment of this disease, are pushing developers to create drugs that most closely reproduce the effect of natural human insulin. In this regard, the appearance of a combination of insulin analogs, the action profile of which practically imitates insulin secretion by a healthy pancreas, presents new possibilities in the treatment of diabetes mellitus. Insulin degludec / insulin aspart (IDegAsp, Ryzodeg®, Novo Nordisk, Denmark) is the first and only soluble combination preparation containing 70% of the ultra-long-acting insulin analogue degludec and 30% of the ultra-short-acting insulin analogue aspart in one injection, which meets the need for both basal and prandial insulin. The combined drug has nothing in common with traditional mixed insulin preparations (both human and analog) and provides doctors and patients with significant advantages over the latter. The article presents the position of Russian experts-diabetologists with extensive experience in the use of IDegAsp regarding the role and place of the drug in real clinical practice. Data from real clinical practice confirm that IDegAsp is a reasonable choice for starting and intensifying insulin therapy for type 2 diabetes mellitus when basal and prandial glycemic control is required. The use of the drug is most appropriate in patients who are on basal, biphasic, basal-plus/basal-bolus regimens and who do not achieve the goals of glycemic control during prior therapy. One of the leading reasons for choosing IDegAsp may also be a lower risk of developing hypoglycemia compared to insulin analogues of previous generations — biphasic insulin aspart and basal insulin glargine 100 U/ml. In addition, IDegAsp is a simple, flexible and safe insulin therapy for patients on premix therapy and basal-plus/basis-bolus regimens who require basal and prandial glycemic control. IDegAsp is a simple, flexible and safe insulin therapy. The greatest benefit of this drug use can be obtained by patients for whom adherence to a complex therapy regimen is difficult (the elderly, with cognitive impairment, after a stroke, with dementia), as well as patients who have an active lifestyle, accompanied by irregular food intake. It is important to note that since January 1, 2021, there is no need for a decision by a special medical commission to prescribe (IDegAsp) Ryzodeg®. This fact, as well as a significant price reduction at the end of 2020, opens up broader prospects for using the drug in the routine practice of a Russian endocrinologist