Transitions of B-DNA to alternative DNA structures (ADS) can be triggered by negative torsional strain, which occurs during replication and transcription, and may lead to genomic instability. However, how ADS are recognized in cells is unclear. We found that the binding of candidate anticancer drug, curaxin, to cellular DNA results in uncoiling of nucleosomal DNA, accumulation of negative supercoiling and conversion of multiple regions of genomic DNA into left-handed Z-form. Histone chaperone FACT binds rapidly to the same regions via the SSRP1 subunit in curaxin-treated cells. In vitro binding of purified SSRP1 or its isolated CID domain to a methylated DNA fragment containing alternating purine/pyrimidines, which is prone to Z-DNA transition, is much stronger than to other types of DNA. We propose that FACT can recognize and bind Z-DNA or DNA in transition from a B to Z form. Binding of FACT to these genomic regions triggers a p53 response. Furthermore, FACT has been shown to bind to other types of ADS through a different structural domain, which also leads to p53 activation. Thus, we propose that FACT acts as a sensor of ADS formation in cells. Recognition of ADS by FACT followed by a p53 response may explain the role of FACT in DNA damage prevention.
This paper is concerned with the theory of nucleation and growth of crystals in a metastable polymer melt with allowance for the polymerization of a monomer. A mathematical model consisting of the heat balance equation, equations governing the particle-radius distribution function and the polymerization degree is formulated. The exact steady-state analytical solutions are found. In the case of unsteady-state crystallization with polymerization, the particle-size distribution function is determined analytically for different space–time regions by means of the Laplace transform. Two functional integro-differential equations governing the dimensionless temperature and polymerization degree are deduced. These equations are solved by means of the saddle-point technique for the evaluation of a Laplace-type integral. The time-dependent distribution function, temperature and polymerization degree at different polymerization rates and nucleation kinetics are derived with allowance for the main contribution to the Laplace-type integral. In addition, the general analytical solution by means of the saddle-point technique and an example showing how to construct the analytical solutions in particular cases are given in the appendices. The analytical method developed in the present paper can be used to describe the similar phase transition phenomena in the presence of chemical reactions. This article is part of the theme issue ‘Heterogeneous materials: metastable and non-ergodic internal structures’.
This paper presents the results of a replication study performed to investigate earlier Soviet studies conducted between 1974 and 1991 that showed immunological and reproductive effects of long-term low-level exposure of rats to radiofrequency (RF) electromagnetic fields. The early studies were used, in part, for developing exposure standards for the USSR population and thus it was necessary to confirm the Russian findings. In the present study, the conditions of RF exposure were made as similar as possible to those in the earlier experiments: Wistar rats were exposed in the far field to 2450 MHz continuous wave RF fields with an incident power density in the cages of 5 W/m² for 7 h/day, 5 days/week for a total of 30 days, resulting in a whole-body SAR of 0.16 W/kg. Effects of the exposure on immunological parameters in the brain and liver of rats were evaluated using the complement fixation test (CFT), as in the original studies, and an additional test, the more modern ELISA test. Our results, using CFT and ELISA, partly confirmed the findings of the early studies and indicated possible effects from non-thermal RF exposure on autoimmune processes. The RF exposure resulted in minor increases in formation of antibodies in brain tissue extract and the exposure did not appear to be pathological. In addition, a study was conducted to replicate a previous Soviet study on effects from the injection of blood serum from RF-exposed rats on pregnancy and foetal and offspring development of rats, using a similar animal model and protocol. Our results showed the same general trends as the earlier study, suggesting possible adverse effects of the blood serum from exposed rats on pregnancy and foetal development of intact rats, however, application of these results in developing exposure standards is limited.
Эффективный расчёт условий равновесия осесимметричной плазмы произвольной формы и с произвольным распределением давления и плотности тока по радиусу является одной из первоочередных задач теоретических исследований в проблеме УТС. Данная статья посвящена описанию многомодульного вычислительного кода SPIDER, предназначенного для численного моделирования равновесия и эволюции плазмы токамака в различных вариантах постановки соответствующих задач. Разработанные методы решения прямой и обратной задачи равновесия плазмы со свободной границей позволяют точно определять положение плазмы и токи в катушках полоидального поля в токамаках. Численный расчёт квазиравновесной эволюции плазмы с учётом диффузии магнитного поля и вихревых токов в проводящих структурах может быть использован для моделирования управления положением плазмы и расчёта её динамики во время срыва тока и развития периферийных локализованных неустойчивостей (ELM). Код может быть также применён для моделирования влияния анизотропии давления и вращения на равновесие плазмы.
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