Hengzongshu/ArticleAgent huggingface dataset:
RIL (product of PDLIM4 gene) is an actin-associated protein that has previously been shown to stimulate actin bundling by interacting with actin-cross-linking protein α-actinin-1 and increasing its affinity to filamentous actin. Here, we report that the alternatively spliced isoform of RIL, denoted here as RILaltCterm, functions as a dominant-negative modulator of RIL-mediated actin reorganization. RILaltCterm is regulated at the level of protein stability, and this protein isoform accumulates particularly in response to oxidative stress. We show that the alternative C-terminal segment of RILaltCterm has a disordered structure that directs the protein to rapid degradation in the core 20 S proteasomes. Such degradation is ubiquitin-independent and can be blocked by binding to NAD(P)H quinone oxidoreductase NQO1, a detoxifying enzyme induced by prolonged exposure to oxidative stress. We show that either overexpression of RILaltCterm or its stabilization by stresses counteracts the effects produced by full-length RIL on organization of actin cytoskeleton and cell motility. Taken together, the data suggest a mechanism for fine-tuning actin cytoskeleton rearrangement in response to stresses. RIL (product of PDLIM4 gene) is an actin-associated protein that has previously been shown to stimulate actin bundling by interacting with actin-cross-linking protein α-actinin-1 and increasing its affinity to filamentous actin. Here, we report that the alternatively spliced isoform of RIL, denoted here as RILaltCterm, functions as a dominant-negative modulator of RIL-mediated actin reorganization. RILaltCterm is regulated at the level of protein stability, and this protein isoform accumulates particularly in response to oxidative stress. We show that the alternative C-terminal segment of RILaltCterm has a disordered structure that directs the protein to rapid degradation in the core 20 S proteasomes. Such degradation is ubiquitin-independent and can be blocked by binding to NAD(P)H quinone oxidoreductase NQO1, a detoxifying enzyme induced by prolonged exposure to oxidative stress. We show that either overexpression of RILaltCterm or its stabilization by stresses counteracts the effects produced by full-length RIL on organization of actin cytoskeleton and cell motility. Taken together, the data suggest a mechanism for fine-tuning actin cytoskeleton rearrangement in response to stresses.
Eukaryotic chromosomes are spatially segregated into topologically associating domains (TADs). Some TADs are attached to the nuclear lamina (NL) through lamina-associated domains (LADs).

Here, we identified LADs and TADs at two stages of Drosophila spermatogenesis – in bamΔ86 mutant testes which is the commonly used model of spermatogonia (SpG) and in larval testes mainly filled with spermatocytes (SpCs).

We found that initiation of SpC-specific transcription correlates with promoters’ detachment from the NL and with local spatial insulation of adjacent regions. However, this insulation does not result in the partitioning of inactive TADs into sub-TADs. We also revealed an increased contact frequency between SpC-specific genes in SpCs implying their de novo gathering into transcription factories. In addition, we uncovered the specific X chromosome organization in the male germline. In SpG and SpCs, a single X chromosome is stronger associated with the NL than autosomes. Nevertheless, active chromatin regions in the X chromosome interact with each other more frequently than in autosomes. Moreover, despite the absence of dosage compensation complex in the male germline, randomly inserted SpG-specific reporter is expressed higher in the X chromosome than in autosomes, thus evidencing that non-canonical dosage compensation operates in SpG.
Intellectual disability (ID) is an important medical and social problem that can be caused by different genetic and environmental factors. One such factor could be rDNA amplification and changes in rRNA expression and maturation. The aim of the present study was to investigate rRNA levels in patients with heteromorphism of the p-arms of acrocentric chromosomes bearing nucleolus organizer regions compared to a healthy control group. Frequencies of p-arms enlargements in patients with ID and in healthy people were analyzed by G-banding screening. rRNA gene copy numbers on affected acrocentric chromosomes in peripheral blood lymphocytes were evaluated in ID patients and healthy bearers using FISH, and in immortalized lymphocytes of one patient – using FISH and real time PCR. Simultaneously, levels of 18S, 28S and 5,8S rRNA in both groups by means of qRT-PCR were investigated. No difference in acrocentric chromosome heteromorphism frequency in patients versus the healthy group were found. However, we found an amplification of rDNA, a significant elevation in 28S and 5.8S rRNA expression and changes in the 28S/18S rRNA ratio in ID patients compared to healthy controls. At the same time, FISH appeared to be not reliable enough for copy number evaluation, but RT-PCR showed rDNA copy changes in heteromorphic cells compared to normal. Our findings indicate a loss of the correct regulation of rDNA activity and processing after amplification. This could disturb the ribosomal apparatus and thus lead to intellectual disability via at least two mechanisms.
Traditionally weak financial and legal basis for royal absolutism in England forced monarchs to rely thoroughly on ideology. The concept of passive obedience promoted by the loyal Anglican clergy was one of the key elements of the absolutist ideology of the 17th century. This doctrine was employed as a counterbalance to revolutionary resistance and monarchomach theories embraced by protestant dissenters and papist recusants alike.

During the course of the century the doctrine was embraced by numerous representatives of the Church of England’s establishment, including, but not limited to, John Donn, Roger Maynwaring, George Hickes, Edmund Bohun and many others and disseminated via an array of sermons and pamphlets. One component of the doctrine: non-resistance, was particularly stressed. Several political, social and economic factors conditioned the employment of this doctrine. The first instance of its pronouncement followed the failure of the Gunpowder plot and the necessity to refute catholic contractual theories. Charles I saw the doctrine of passive obedience as both the means to maintain social peace and promote fiscal interests.

The new impetus the doctrine gained in the later years of the Restoration: an attempt to integrate it into the ‘ancient constitution’ failed, yet the doctrine of passive obedience was taken up as the chief ideological tool by the Anglican church and employed as a mighty instrument of suppressing resistance and dissent. The Glorious Revolution weakened the grasp of the doctrine in the minds of the English, though by no means killed it. Yet, the regime erected by the Convention of 1689 and strengthened by William of Orange claimed as much of its legitimacy in revolutionary resistance. Thus, henceforth the ideas of passive obedience and non-resistance could not be used as the sole basis of legitimate power in England.
The long-term evolution of a circumstellar disk starting from its formation and ending in the T Tauri phase was simulated numerically with the purpose of studying the evolution of dust in the disk with distinct values of viscous α-parameter and dust fragmentation velocity v_frag.

We solved numerical hydrodynamics equations in the thin-disk limit, which are modified to include a dust component consisting of two parts: sub-micron-sized dust and grown dust with a maximum radius a_r. The former is strictly coupled to the gas, while the latter interacts with the gas via friction. The conversion of small to grown dust, dust growth, and dust self-gravity are also considered.

We found that the process of dust growth known for the older protoplanetary phase also holds for the embedded phase of disk evolution. The dust growth efficiency depends on the radial distance from the star - a_r is largest in the inner disk and gradually declines with radial distance. In the inner disk, a_r is limited by the dust fragmentation barrier. The process of small-to-grown dust conversion is very fast once the disk is formed. The total mass of grown dust in the disk (beyond 1 AU) reaches tens or even hundreds of Earth masses already in the embedded phase of star formation and even a greater amount of grown dust drifts in the inner, unresolved 1 AU of the disk. Dust does not usually grow to radii greater than a few cm. A notable exception are models with α<= 10^{-3}, in which case a zone with reduced mass transport develops in the inner disk and dust can grow to meter-sized boulders in the inner 10 AU. Grown dust drifts inward and accumulates in the inner disk regions. This effect is most pronounced in the α<= 10^{-3} models where several hundreds of Earth masses can be accumulated in a narrow region of several AU from the star by the end of embedded phase.
Purpose. To assess changes in nucleic acid (NA) metabolism in severe burn injury and to develop recommendations for correction of the alimentary status taking into account changes in the NA metabolism. Materials and methods. All patients (37 patients with II–III degree thermal burns and a burn area of more than 40%) were divided into 2 groups: Group I included survivors (23 patients), group II consisted of the deceased. The intensity of the NA metabolism was assessed based on the dynamics of the of uric acid (UA) and oligonucleotides serum concentrations. Results. In the acute period of burn injury, marked decrease in UA levels (less than 100 μmol/l), with gradual stabilization in survivors is typical. In addition, a 2–3-fold increase in the concentration of serum oligonucleotides compared to the normal limit is typical for survivors in the acute period, and these changes were significantly different from the group of deceased patients starting from day 5. Taking into account the data obtained, the level of serum UA can be recommended in clinical practice for the assessment of alimentary status in burn disease, as well as a criterion for f the prescription of glutamine administration in critically ill patients. In patients with burn disease a decrease in the UA level to less than 100 μmol/l was regarded as an absolute indication for the use of L-glutamine products. The use of glutamine in patients with significant decrease in UA levels was accompanied by a significant increase in the intensity of NA metabolism, which was demonstrated by both an increase in uric acid levels (by 85% by day 10 after the start of glutamine administration, P<0.01) and restoration of repair processes. Conclusion. Therefore, there was a marked alteration of NA metabolism in both groups of patients with severe burn injury. At the same time, surviving patients are characterized by rapid recovery of NA metabolism. Glutamine was employed as a pharmacological agent that effectively abrogates the depression of NA metabolism.
ApoE expression status was proved to be a highly specific marker of energy metabolism rate in the brain. Along with its neighbor, Translocase of Outer Mitochondrial Membrane 40 kDa (TOMM40) which is involved in mitochondrial metabolism, the corresponding genomic region constitutes the neuroenergetic hotspot. Using RNA-Seq data from a murine model of chronic stress a significant positive expression coordination of seven neighboring genes in ApoE locus in five brain regions was observed. ApoE maintains one of the highest absolute expression values genome-wide, implying that ApoE can be the driver of the neighboring gene expression alteration observed under stressful loads. Notably, we revealed the highly statistically significant increase of ApoE expression in the hypothalamus of chronically aggressive (FDR < 0.007) and defeated (FDR < 0.001) mice compared to the control. Correlation analysis revealed a close association of ApoE and proopiomelanocortin (Pomc) gene expression profiles implying the putative neuroendocrine stress response background of ApoE expression elevation therein.
The mechanical properties of the CsH2PO4 and hybrid compounds with different polymers (SKF-26, UPTFE, Butvar B-98) was determined by the Vickers microhardness test for the first time. It was shown that increase in the volume fraction of the polymer results in the low HV values corresponding to the high robustness of the membranes to plastic deformation. Mechanical properties of hybrid compounds depend on polymer type and the best results were obtained for SKF-26. The improvement of mechanical properties makes the investigated composite polymer electrolytes promising for use as proton-conducting membranes in the medium-temperature range.
Rota–Baxter operators of nonzero weight on matrix algebras that arise from decompositions of the entire algebra into a direct vector space sum of two subalgebras

Classify all Rota–Baxter operators of nonzero weight on the matrix algebra of order three over an algebraically closed field of characteristic zero

Complete classification of such operators that do not arise from the decompositions of the entire algebra into a direct vector space sum of two subalgebras
The paper deals with mathematical modelling of the process of an explosion of a cloud of reactive gases and its impact on the environment. The research may be relevant to ensure fire safety and to prevent explosion hazards at industrial production facilities that use reactive gas mixtures as a working medium and at high-pressure industrial pipelines used for their transportation. The goal of the study is to develop and test a computational technology for numerical modelling of clouds of reactive gas mixture expansions and loads evaluation. To describe the chemical processes in the explosion, a simplified mathematical model is proposed which based on the assumption of frozen chemical reactions. Using the model, a set of User Defined Functions is implemented in ANSYS Fluent and applied for solving a problem of a “propylene-air” cloud explosion inside the T-shape tube with two closed and one open ends.
This experimental work identifies spatial vortex parameters at the exit of the tangential swirler based directly on velocity distributions obtained by Stereo-PIV method with using pressure pulsations in the acoustic field of swirling jets.

The velocity measurements are carried out for high swirl jet close to exit of swirler nozzle (Re = 23000 and Sh = 1.54).

The spatial distribution of the PVC is captured with statistical analysis of instantaneous velocity fields and phase-averaged vorticity distribution.
Experimental data on the nonlinear wave train development in 3D supersonic boundary layer over a 45° swept-wing at Mach number 2 are presented. Travelling artificial disturbances were introduced in the boundary layer by periodical glow discharge at frequencies 10 and 20 kHz. The appearance of additional peaks in β′-spectra for subharmonic frequency is shown. The experiments indicate the presence of asymmetric subharmonic resonance mechanism in 3D supersonic boundary layer. The method of finding resonant triads demonstrate the presence of several three-wave triads in a wide range of transverse wave numbers for the fundamental frequency.
Opisthorchiasis caused by food-borne trematode Opisthorchis felineus is a substantial public health problem, with 17 million persons infected worldwide. This chronic disease is associated with hepatobiliary inflammation, cholangiocyte dysplasia, cholangiofibrosis, intraepithelial neoplasia, and even cholangiocarcinoma among chronically infected individuals. To provide first insights into the mechanism by which O. felineus infection causes precancerous liver lesions, we investigated the level of oxidative stress (lipid peroxidation byproducts and 8-hydroxy-2′-deoxyguanosine) as well as the time course profiles of chronic inflammation and fibrogenesis markers in the dynamics of opisthorchiasis from 1 month to 1.5 years postinfection in an experimental model based on golden hamsters Mesocricetus auratus. For the first time, we showed that O. felineus infection provokes time-dependent accumulation of oxidative hepatobiliary lesions in the injured liver of hamsters. In particular, over the course of infection, lipid peroxidation byproducts 4-hydroxynonenal and malondialdehyde were upregulated; these changes in general correlate with the dynamics of hepatic histopathological changes. We detected macrophages with various immunophenotypes and elevated levels of CD68, COX2, and CD163 in the O. felineus–infected animals. Meanwhile, there was direct time-dependent elevation of TNF-α (R = 0.79; p < 0.001) and CD163 protein levels (R = 0.58; p = 0.022). We also provide quantitative data about epithelial hyperplasia marker CK7 and a marker of myofibroblast activation (α smooth muscle actin). Our present data provide first insights into the histopathological mechanism by which O. felineus infection causes liver injuries. These findings support the inclusion of O. felineus in Group 1 of biological carcinogens.
The paper deals with experimental investigations of the surface perturbation effects on the flame propagation velocity along the surface of the liquid. It is revealed that at low velocities the effect is quite significant. Under certain conditions the flame even stabilizes for some time. The experiments were conducted to elucidate the mechanism of flame propagation. However, it was impossible to determine expressly the flame propagation mechanism along the surface, because this requires visualization of gas flows.
Nowadays interest in the problem of the "resource curse" has increased.

This article examines the patterns of functioning of the "resource curse" in 41 countries, classified by different groups of income and oil production for the period of 1990-2016, based on the analysis of panel data.

The results of cross-country econometric studies of the effects of resource dependence are presented, the consequences in terms of economic growth were analyzed, and the situation taking place in Russia was estimated.
The Bertaut approach associated with charge spreading so as to enhance the rate of convergence of Coulomb series in crystals is extended to the case of an arbitrary multiple spreading with a given initial spreading function. It is shown that the effect of spreading may in general be treated as a uniform transformation of space, providing that zero mean potential as a universal spatial property is sustained. As a result, electrostatic potentials driven by different orders of multiple spreading can be obtained from the same energy functional in a consistent manner. It is found that the effect of multiple spreading gives rise to more advanced forms described, for example, by simple exponential decrease, but the functional description based on a Gaussian spreading turns out to be invariant. In addition, the effects of a multiple charge spreading based on simple exponential and Gaussian spreading functions are compared as typical of molecular calculations.
Background: Previously, the results of phase II AURORA clinical study of levilimab in subjects with active rheumatoid arthritis (RA) have been reported 1 .

Methods: The study is ongoing at 21 clinical sites in Russia and Belarus. All randomized subjects have completed 24 weeks of study between November 2019 and January 2021. 154 adults, aged ≥18 years with the diagnosis of RA (ACR 2010) for at least 24 weeks, and confirmed disease activity at screening despite treatment with MTX for the last 12 weeks (in a stable dose 15-25 mg/week, for at least 4 weeks) were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52). The randomization and treatment allocation were carried out by a central computer-based system. Subjects, caregivers, and those assessing the outcomes were blinded to group assignment. The hypothesis of superiority of levilimab over placebo was tested for two co-primary efficacy outcomes: proportion of subjects who achieved ACR20 at week 12 and proportion of subjects who achieved LDA of RA (DAS28-CRP <3.2) at Week 24 of the study. For ethical reasons, subjects who haven’t achieved minimal clinical response at week 12 (≥20% reduction in the number of tender/swollen joints; 66/68) received rescue therapy at the discretion of the Investigator, and all subsequent efficacy assessments for those were considered missing. For the primary efficacy analysis, subjects with missing data due to study discontinuation or rescue therapy prescription were considered non-responders (non-responder imputation, NRI). Otherwise, the analysis was performed on observed cases. Safety was assessed through monitoring of adverse events (AEs).

Conclusion: The study confirmed superior efficacy of levilimab + MTX over placebo + MTX in subjects with MTX resistant active RA. No new safety signals were detected.
Strains of red fox ( Vulpes vulpes ) with markedly different behavioural phenotypes have been developed in the famous long-term selective breeding programme known as the Russian farm-fox experiment.

Here we sequenced and assembled the red fox genome and re-sequenced a subset of foxes from the tame, aggressive and conventional farm-bred populations to identify genomic regions associated with the response to selection for behaviour. Analysis of the re-sequenced genomes identified 103 regions with either significantly decreased heterozygosity in one of the three populations or increased divergence between the populations.

A strong positional candidate gene for tame behaviour was highlighted: SorCS1 , which encodes the main trafficking protein for AMPA glutamate receptors and neurexins and suggests a role for synaptic plasticity in fox domestication. Other regions identified as likely to have been under selection in foxes include genes implicated in human neurological disorders, mouse behaviour and dog domestication. The fox represents a powerful model for the genetic analysis of affiliative and aggressive behaviours that can benefit genetic studies of behaviour in dogs and other mammals, including humans.
In this note, we introduce a class of algebras that are in some sense related to conformal algebras. This class (called TC-algebras) includes Weyl algebras and some of their (associative and Lie) subalgebras. By a conformal algebra we generally mean what is known as $H$-pseudo-algebra over the polynomial Hopf algebra $H=\Bbbk[T_1,..., T_n]$. Some recent results in structure theory of conformal algebras are applied to get a description of TC-algebras.