Structural plasticity of the nuclear envelope and the endoplasmic reticulum

The nuclear envelope is a double membrane structure, continuous with endoplasmic reticulum, and the morphological organization of both these structures is quite conservative. However, nuclear envelope and endoplasmic reticulum demonstrate distinct structural plasticity, i. e., based on common organization, cells may form various non-canonical membrane structures that are observed only in specialized types of cells or appear in different pathologies. In this review, we will discuss the mechanisms of the biogenesis of such non-canonical structures, and the possible role of this plasticity in the development of pathological processes.Ядерна оболонка – двомембранна структура, неперервна з ендоплазматичним ретикулумом, причому морфологічна організація цих структур досить консервативна. Однак для ядерної оболонки і ендоплазматичного ретикулуму характерна виражена структурна пластичність, тобто на основі спільної організації в клітинах можуть формуватися різні неканонічні структури, які виявляються або в спеціалізованих клітинах, або за розвитку деяких патологій. У представленому огляді розглянуто механізми біогенезу подібних неканонічних структур, а також можливу роль структурної пластичності у розвитку патологічних процесів.Ядерная оболочка – двухмембранная структура, непрерывная с эндоплазматическим ретикулумом, причем морфологическая организация этих структур достаточно консервативна. Однако для ядерной оболочки и эндоплазматического ретикулума характерна выраженная структурная пластичность, т. е. на основе общей организации в клетках могут формироваться различные неканонические структуры, выявляющиеся либо в специализированных клетках, либо при развитии некоторых патологий. В настоящем обзоре рассмотрены механизмы биогенеза подобных неканонических структур, а также возможная роль структурной пластичности в развитии патологических процессов

The accumulation of the basic domain of HIV-1 Tat protein in the nuclei and the nucleoli is different from the accumulation of full-length Tat proteins

Aim. Protein fragments coding for nuclear (NLS) and/or nucleolar (NoLS) localization signals are often used for the investigation of the mechanisms of protein accumulation inside the nuclei and the nucleoli, but it is possible that accumulation mechanisms in full-length proteins will be different. Methods. Here, we compared the nuclear and nucleolar accumulation of HIV-1 Tat protein and its basic domain containing both NLS and NoLS. Results. The pattern of accumulation of the basic domain of HIV-1 Tat protein in the nuclei and the nucleoli is different from that of full-length Tat proteins: the basic domain is accumulated weaker inside the nuclei, but stronger in the nucleoli as compared to the full-length protein. Conclusion. The molecular mechanism of nuclear and nucleolar accumulation of full-length Tat protein might be different from that of the Tat protein fragments.Мета. При вивченні механізмів накопичення білків в ядрі і полісом часто використовують фрагменти білка, що кодують сигнали ядерної (NLS) і ядерцевої (NoLS) локалізації, які зливають з маркерними білками. Проте механізми накопичення повнорозмірних білків можуть бути іншими. Методи. У цій роботі ми порівняли накопичення в ядрі і полісом ВІЛ-1 Tat білка і основного домену цього білка, що містить NLS і NoLS. Результати. Показано, що накопичення основного домену Tat білка в ядрі і полісом відрізняється від накопичення цілих білків (фрагмент білка гірше, ніж цілий білок накопичується в ядрі, але краще в полісом). Висновки. Видається ймовірним, що молекулярний механізм накопичення в ядрі і полісом повнорозмірного Тат білка можуть відрізнятися від механізму, описаного з використанням фрагментів білка.Цель. При изучении механизмов накопления белков в ядре и ядрышке часто используют участки белка, кодирующие сигналы ядерной (NLS) и ядрышковой (NoLS) локализации, которые сливают с маркерными белками. Однако механизмы накопления полноразмерных белков могут быть другими. Методы. В настоящей работе мы сравнили накопление в ядре и ядрышке HIV-1 Tat белка и основного домена этого белка, содержащего NLS и NoLS. Результаты. Показано, что накопление основного домена Tat белка в ядре и ядрышке отличается от накопления целых белков (фрагмент белка хуже, чем целый белок накапливается в ядре, но лучше в ядрышке). Выводы. Представляется вероятным, что молекулярный механизм накопления в ядре и ядрышке полноразмерного Tat белка могут отличаться от механизма, описанного с использованием фрагментов белка

FORMATION OF THE COMMERCIAL INFRASTRUCTURE OF THE EURASIAN ECONOMIC UNION’S COMMON POWER MARKET

The commercial infrastructure formation is a key challenge of creating a common electric power market for the Eurasian Economic Union member states (Russia, Belarus, Kazakhstan, Kyrgyzstan and Armenia) provided for in the Treaty on the Eurasian Economic Union. The comparative analysis of electricity trading arrangements in the Eurasian Economic Union states have been presented in the article. It has been shown, that there are notable differences between combined power markets of these group of states in terms of the organization of trade relations (participants, infrastructure services, rules on trade and pricing policies). It has been established, that only the characteristics of the Russian electric power market fully comply with the requirements of program documents for the Eurasian Economic Union common electric power market. The appropriate recommendations on measures to adapt the power markets of other Eurasian Economic Union States to these requirements have been give

THE ESTABLISHMENT OF SALES MARKUPS OF GUARANTEEING ELECTRICITY SUPPLIERS BY METHOD OF COMPARISON OF ANALOGUES: DECREASE OR INCREASE

The first results of the comparative method application for fixing regulated retail markups of guaranteeing electricity suppliers in Russia have been analyzed. The goal of the comparative method adoption is the improvement of guaranteeing electricity supplier’s effectiveness. Analysis of the legislation displayed, that the comparative method normalizes the guaranteeing electricity supplier’s yardstick revenue rates and limits the retail markups increase factors, mainly by the consumer price index. However, new methodologyapplication during the transition period led to outstripping inflation growth rate of guaranteeing electricity supplier’s retail markups. It has been identified, that in most Russian regions it was caused by the base period costs diminishing and (or) ‘yardstick cost’ limits inflating. It has been assumed, that after transition period expiry default electricity supplier’s retail markups growth ratio will be comparable to the consumer price index rate

Comparative analysis of nuclear localization signal (NLS) prediction methods

Aim. Comparative analysis of six state-of-the-art nuclear localization signal (NLS) prediction methods (PSORT II, NucPred, cNLSMapper, NLStradamus, NucImport and seqNLS). Methods. Each program was tested for correct predictions using a dataset of 155 experimentally determined NLSs and for false-positives using a dataset of 155 transmembrane proteins, which putatively lack NLS. Results. The most suitable NLS predictors wer fond to be NucPred, NLStradamus and seqNLS; these programs provide the maximum rate of correct to wrong predictions among the tested programs. However, the best results obtained by these programs were only ~ 45 % of the correct predictions. Conclusion. The identification of novel NLSs by predictors still requires experimental verification.Мета. Ідентифікація сигналів ядерної локалізації (NLS) в амінокислотній послідовності білків за допомогою експериментальних методів залишається коштовним і тривалис процесом. Тому в останній час велику популярність отримали комп'ютерні методи прогнозування NLS. Методи. В даній статті ми провели порівняльний аналіз достовірності прогнозування NLS шести різних програм (PSORT II, ​​NucPred, cNLSMapper, NLStradamus, NucImport та SeqNLS). Для кожного алгоритма було оцінена доля істинно позитивних прогнозів на вибірки з 155 експериментально визначених NLS з 128 білків людини, а також частку помилкових подій у вибірці з 155 трансмембранних білків людини, які, як видно, позбавлені NLS. Результати. Найбільшу кількість вірно прогнозованих NLS при найменшій частці хибнопозитивних результатів було отримано для трьох програм: NucPred, NLStradamus та seqNLS. Однак навіть при набільшій ступені достовірності дані алгоритми прогнозують вірно не більше 45 % експериментально визначених NLS. Висновки. Використання будь-яких алгоритмів прогнозування NLS вимагає експериментальної перевірки отриманих результатів.Цель. Идентификация сигналов ядерной локализации (NLS) в аминокислотной последовательности белка экспериментальными методами остается дорогостоящим и долгим процессом. Поэтому в последнее время большую популярность получили компьютерные методы предсказания NLS. Методы. В данной статье мы провели сравнительный анализ достоверности предсказания NLS шести различных программ (PSORT II, NucPred, cNLSMapper, NLStradamus, NucImport и SeqNLS). Для каждого алгоритма была оценена доля истинно положительных предсказаний на выборке из 155 экспериментально определенных NLS из 128 человеческих белков, а также доля ложноположительных предсказаний на выборке из 155 трансмембранных белков человека, которые, предположительно, лишены NLS. Наибольшее количество правильно предсказанных NLS при наименьшей доле ложноположительных результатов было получено для трех программ: NucPred, NLStradamus и seqNLS. Однако даже при наибольшей степени достоверности данные алгоритмы предсказывают правильно не более 45% экспериментально определенных NLS, т.е. использование любых алгоритмов предсказания NLS требует экспериментальной проверки получаемых результатов

Non-linear Dose Response of Lymphocyte Cell Lines to Microtubule Inhibitors

Microtubule (MT) inhibitors show anti-cancer activity in a wide range of tumors in vitro and demonstrate high clinical efficacy. To date they are routinely included into many chemotherapeutic regimens. While the mechanisms of MT inhibitors' interactions with tubulin have been well-established, the relationship between their concentration and effect on neoplastic cells is not completely understood. The common notion is that tumor cells are most vulnerable during division and all MT inhibitors block them in mitosis and induce mitotic checkpoint-associated cell death. At the same time multiple evidence of more subtle effects of lower doses of MT inhibitors on cell physiology exist. The extent of efficacy of the low-dose MT inhibitor treatment and the mechanisms of resulting cell death currently present a critical issue in oncology. The prospect of MT inhibitor dose reduction is promising as protocols at higher concentration have multiple side effects. We assessed cell cycle changes and cell death induced by MT inhibitors (paclitaxel, nocodazole, and vinorelbine) on human lymphoid B-cell lines in a broad concentration range. All inhibitors had similar accumulation effects and demonstrated "trigger" concentrations that induce cell accumulation in G2/M phase. Concentrations slightly below the "trigger" promoted cell accumulation in sub-G1 phase. Multi-label analysis of live cells showed that the sub-G1 population is heterogeneous and may include cells that are still viable after 24 h of treatment. Effects observed were similar for cells expressing Tat-protein. Thus cell cycle progression and cell death are differentially affected by high and low MT inhibitor concentrations

Non-linear Dose Response of Lymphocyte Cell Lines to Microtubule Inhibitors

Microtubule (MT) inhibitors show anti-cancer activity in a wide range of tumors in vitro and demonstrate high clinical efficacy. To date they are routinely included into many chemotherapeutic regimens. While the mechanisms of MT inhibitors’ interactions with tubulin have been well-established, the relationship between their concentration and effect on neoplastic cells is not completely understood. The common notion is that tumor cells are most vulnerable during division and all MT inhibitors block them in mitosis and induce mitotic checkpoint-associated cell death. At the same time multiple evidence of more subtle effects of lower doses of MT inhibitors on cell physiology exist. The extent of efficacy of the low-dose MT inhibitor treatment and the mechanisms of resulting cell death currently present a critical issue in oncology. The prospect of MT inhibitor dose reduction is promising as protocols at higher concentration have multiple side effects. We assessed cell cycle changes and cell death induced by MT inhibitors (paclitaxel, nocodazole, and vinorelbine) on human lymphoid B-cell lines in a broad concentration range. All inhibitors had similar accumulation effects and demonstrated “trigger” concentrations that induce cell accumulation in G2/M phase. Concentrations slightly below the “trigger” promoted cell accumulation in sub-G1 phase. Multi-label analysis of live cells showed that the sub-G1 population is heterogeneous and may include cells that are still viable after 24 h of treatment. Effects observed were similar for cells expressing Tat-protein. Thus cell cycle progression and cell death are differentially affected by high and low MT inhibitor concentrations

Prognostic Markers in Peripheral T-Cell Lymphoma

Based on their own experience and knowledge of the literature, the authors review the pathobiological characteristics of peripheral T-cell lymphomas (PTCLs), focusing on the available prognostic indicators. The International Prognostic Index (IPI), which is based on age, performance status, lactate dehydrogenase [LDH], stage, and extranodal involvement, appears to be efficient as a prognostic index for PTCLs, at least in part and especially for certain PTCL subtypes. However, it is not so satisfactory for the two commonest PTCLs, PTCL not otherwise specified (PTCL/NOS) and angioimmunoblastic T-cell lymphoma (AITL), for which novel scores, possibly based on the biologic features of the tumors, have been explored. An Italian cooperative group proposed a revision of the IPI for PTCL unspecified (PTCL-U), the Prognostic Index for PTCL-U (PIT), which includes age, performance status, LDH, and bone marrow involvement. The PIT apparently offered some advantages, but they were not confirmed in subsequent studies. A clinical-biological score (the Bologna score) was then proposed, including tumor proliferation and clinical features (age, LDH, and performance status). This score appears promising and offers the intriguing advantage of integrating biological and clinical elements, but independent validation on a large series is still warranted. More recently, gene expression profiling has been used to identify novel molecular prognostic factors. In particular, inactivation of the NFκB pathway, high expression of proliferation-associated genes, and cytotoxic molecular phenotype seem to be associated with a worse outcome. So far, however, none of these indicators has been validated in an independent series. Finally, various reports have dealt specifically with the prognostication of NK-derived tumors, including nasal and nasal-type lymphomas. Both the IPI and dedicated models have turned out to be of prognostic relevance for these tumors. In conclusion, although the IPI is somewhat effective for PTCL prognostication, novel scores that are more refined and possibly disease-specific are warranted. The validation process for several models, including clinical-pathological and molecular models, is now ongoing

Comment on Piña et al. Ten Approaches That Improve Immunostaining: A Review of the Latest Advances for the Optimization of Immunofluorescence. Int. J. Mol. Sci. 2022, 23, 1426

With great interest, I have read the article “Ten Approaches That Improve Immunostaining: A Review of the Latest Advances for the Optimization of Immunofluorescence” written by Piña et al. [...