Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation

BACKGROUND: X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes. RESULTS: Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing. CONCLUSIONS: This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis

High energy hadrons in EAS at mountain altitude

An extensive simulation has been carried out to estimate the physical interpretation of dynamical factors such as , in terms of high energy interaction features, concentrated in the present analysis on the average transverse momentum. It appears that the large enhancement observed for versus primary energy, suggesting in earliest analysis a significant rise of with energy, is only the result of the limited resolution of the detectors and remains in agreement with a wide range of models used in simulations.Comment: 13 pages, 6 PostScript figures, LaTeX Subm. to JPhys

Development of the procedure of testing with the application of the expert evaluation method in psychophysiology

This article provides a detailed description of the stages of development of an information system of personalized psychophysiological testing using expert evaluation. The process of the information system design is presented, the developed functional models, database and algorithm of testing by students-experts are demonstrate

Androgen deprivation therapy and hormonal status in men with COVID-19

Severe course of COVID-19 among men compared to the female led to a detailed study of the hormonal status of men with COVID-19. The earliest works about this focused on the incidence and severity of COVID-19 depending on the intake of androgen deprivation therapy. At the same time, different classes of androgen deprivation therapy have different effects on androgen concentration that was not always considered in the analysis. In this regard, we conducted a review of the available literature data with a targeted study of works that included androgen deprivation therapy with a unidirectional effect on the concentration of male sex hormones. In addition, we conducted a review of studies focused on the relationship between COVID-19 and androgens (testosterone and dihydrotestosterone)

Органическое вещество в экосистеме залива Владимира (Японское море): ресурс питания и возможный фактор экологического риска

Исследование содержания органического вещества в водной среде и донных отложениях крайне важно для понимания аккумуляционного процесса в отношении поступающих в среду акватории токсических веществ и элементов, а также выявления негативных изменений в экосистеме и потенциальных экологических рисков при осуществлении природопользования. Цель работы — проанализировать значение органического вещества как фактора контаминации среды залива Владимира (Японское море) и оценить токсичность гидробионтов и экологический риск для экосистемы и здоровья человека. Комплексная работа выполнена с применением химико-аналитических, микробиологических и гидробиологических методов; она включает математическую и картографическую обработку данных и расчёт коэффициентов загрязнения и экологического риска. Проведён анализ проб морской воды, донных отложений и макробентоса, отобранных в заливе Владимира в июле 2014 г. Определены химико-экологические и микробиологические параметры вод залива, позволяющие оценить процессы накопления органического вещества в водной среде и донных отложениях и установить трофический статус экосистемы в летний период. Выявлены массовые виды и группы макробентоса, определены показатели обилия донного населения, свидетельствующие о высоких уровнях биомассы. Установлена численность металлрезистентных групп бактерий в поверхностных водах. Оценено содержание и пространственное распределение тяжёлых металлов (ТМ) в донных отложениях. Установлены концентрации ТМ в гонадах морских ежей. Результаты микробиологической оценки соотнесены с ПДК; они выявляют значительное загрязнение вод залива (более 3 ПДК) в отношении Cd. Для Ni, Cu, Zn и Cd в донных отложениях обнаружено превышение фоновых концентраций, для Cd и Zn — превышение кларковых значений. Проверена корреляционная связь концентраций органического вещества в донных отложениях с содержанием в них ТМ, а также связь концентраций ТМ в грунтах и гонадах морских ежей (значимая корреляция выявлена в отношении Zn). Для донных отложений определены фактор загрязнения Cf, характеризующий их загрязнение в заливе цинком как высокое, а кадмием и медью — как очень высокое, а также степень загрязнения Cd, свидетельствующая о среднем уровне загрязнения донных осадков в целом. Проведён расчёт индексов экологического риска. По величине SQG-Q грунты залива отнесены к категории умеренно токсичных. Установлено: согласно нормативам Технического регламента Таможенного союза «О безопасности пищевой продукции» 021/2011, содержание Cd и Pb в гонадах морских ежей из залива Владимира не превышает допустимых уровней, однако по значению ILCR (индекс нарастающего пожизненного риска) можно сделать прогноз об опасности возникновения онкологических заболеваний при употреблении гонад в пищу

Intellectual assessment of staff sufficiency for innovative development of the sustainable regional agro-industrial complex

The paper is devoted to the problems of assessment of staff sufficiency for regional economy agroindustrial sector’s innovative development. The proposed approach is based on the application of models and methods of expert assessment and digital intelligent technologie

Observation of TeV Gamma Rays from the Crab Nebula with Milagro Using a New Background Rejection Technique

The recent advances in TeV gamma-ray astronomy are largely the result of the ability to differentiate between extensive air showers generated by gamma rays and hadronic cosmic rays. Air Cherenkov telescopes have developed and perfected the "imaging" technique over the past several decades. However until now no background rejection method has been successfully used in an air shower array to detect a source of TeV gamma rays. We report on a method to differentiate hadronic air showers from electromagnetic air showers in the Milagro gamma ray observatory, based on the ability to detect the energetic particles in an extensive air shower. The technique is used to detect TeV emission from the Crab nebula. The flux from the Crab is estimated to be 2.68(+-0.42stat +- 1.4sys) x10^{-7} (E/1TeV)^{-2.59} m^{-2} s^{-1} TeV^{-1}, where the spectral index is assumed to be as given by the HEGRA collaboration.Comment: 22 pages, 11 figures, submitted to Astrophysical Journa

Staghorn stone and squamous cell carcinoma of the renal pelvis: a clinical case and literature review

Squamous cell carcinoma of the renal pelvis is a rare neoplasm. The incidence does not exceed 1% of all neoplasms of this localization. In the general population, up to 90% of all neoplasms of the renal pelvis are represented by urothelial carcinoma, while from 0.7% to 7.0% of cases are squamous cell carcinoma. Stones of the renal collecting system are found in 14 – 50% of patients with squamous cell carcinoma of the pelvis. As a possible etiopathogenetic mechanism, chronic inflammation on the background of a stone is considered, leading to squamous urothelial metaplasia with subsequent keratinization and malignization. Clinical manifestation of squamous cell carcinoma of the renal pelvis is nonspecific and is primarily associated with manifestations of urolithiasis. Squamous cell carcinoma of the renal pelvis is characterised by high aggressiveness, insensitivity to chemotherapy and radiation therapy, and consequently an unfavourable prognosis. The survival rate of most patients is less than one year from the diagnosis, while the 5-year survival rate does not exceed 10%. We present our own clinical case of a patient with a staghorn stone and squamous cell carcinoma of the renal pelvis