Transcriptome and Proteome Analyses Reveal Stage-Specific DNA Damage Response in Embryos of Endangered Sturgeon

DNA damage during early life stages may have a negative effect on embryo development, inducing malformations that have long-lasting effects during adult life. Therefore, in the current study, we analyzed the effect of DNA damage induced by genotoxicants (camptothecin (CPT) and olaparib) at different stages of embryo development. We analyzed the survival, DNA fragmentation, transcriptome, and proteome of the endangered sturgeon Acipenser ruthenus. Sturgeons are non-model fish species that can provide new insights into the DNA damage response and embryo development. The transcriptomic and proteomic patterns changed significantly after exposure to genotoxicants in a stage-dependent manner. The results of this study indicate a correlation between phenotype formation and changes in transcriptomic and proteomic profiles. CPT and olaparib downregulated oxidative phosphorylation and metabolic pathways, and upregulated pathways involved in nucleotide excision repair, base excision repair, and homologous recombination. We observed the upregulated expression of zona pellucida sperm-binding proteins in all treatment groups, as well as the upregulation of several glycolytic enzymes. The analysis of gene expression revealed several markers of DNA damage response and adaptive stress-response, which could be applied in toxicological studies on fish embryo. This study is the first complex analysis of the DNA damage response in endangered sturgeons.

The Effect of Electric Energy Accumulation by Hydrated ZrO2 – Nanoparticles

The dimensional effect of the accumulation of an electric charge with a density of up to 270 μF/g by the system of compacted zirconium dioxide nanoparticles during exposure in an electric field (5000 V/m) under normal physical conditions is determined. Based on a qualitative complex analysis of the forms of appearance of the effect, it is shown that the place of localization of different charge carriers is the surface of nanoparticles. The supposed mechanism of this effect is considered using the theory of dispersed systems, the band theory, and the theory of contact phenomena in semiconductors. It was concluded that this mechanism is due to the phenomenon of localization of electron-type charge nanoparticles in the near-surface zone of the material in contact with the adsorption ion atmosphere. This effect is relevant for modern nanoelectronics, microsystem technology, and printed electronics.

Role of the Plenum of Russian Supreme Court in the judicial practice formation

The subject. The article considers the role of the Plenum of Russian Supreme in forming judicial practice on the example of giving qualification to the crimes committed against sexual freedom and inviolability, as well as against property and public health.The objective of the article is to conduct a complex analysis of the function of the decisions, taken by the Plenum of Russian Supreme Court, in the formation of a unified vector of judicial practice. The authors dare to refute the hypothesis hat judicial practice can be recognized as a source of law.The methodological basis of the research is the dialectical theory of development and interrelation of phenomena. Historical, formal-logical, systematic methods of knowledge have been identified as relevant to the topic of the study.The main results, scope of application. The authors draw attention to the problem of evaluative features used in the process of law enforcement when interpreting the norms of the Special Part of the Criminal Code of the Russian Federation. A norm with such signs acquires an unformalized essence from the point of view of the boundaries of criminalization of a particular phenomenon. On the other hand, the nature of crimes is so diverse that without the flexibility of criminal law regulation (allowing the use of evaluative features), the application of the norm taking into account specific circumstances in a particular case may not be possible. The authors also consider issues related to the characteristics of the objective side, the end time of these crimes, the application of the formula of a single ongoing crime and its separation from related compounds. The process of law enforcement is based on such guidelines as the norms of law, judicial discretion, established judicial practice, the position of the Plenum of Russian Supreme Court. Attributing an explanatory role to the decisions of the Plenum of Russian Supreme Court does not completely eliminate the shortcomings inherent in legal technology. Correcting the current situation with the help of judicial discretion is not always justified, since this is possible only if there is a legitimate alternative. Assigning the status of a precedent to a judicial decision may lead to the substitution of the law by decisions taken in a particular case.Conclusions. The judicial practice concerning these issues is completely different. Despite the existence of similar situations, courts, as a rule, qualify an offense using various norms of the law, which negatively affects compliance with the principle of legality. The issue related to the function of the decisions of the Plenum of Russian Supreme Court in the formation of a single vector of judicial practice has been and remains debatable. The continued addition of new articles to criminal legislation, on the one hand, indicates the desire of the legislator to bring it to perfection, but, on the other hand, forms a mechanism for clarifying the rules of its application, which sometimes leads to their contradictory interpretation. At the same time, crime and punishment should be determined only by legislation.

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

Computational Inference of DNA Folding Principles: From Data Management to Machine Learning

DNA is the molecular basis of life and would total about three meters if linearly untangled. To fit in the cell nucleus at the micrometer scale, DNA has, therefore, to fold itself into several layers of hierarchical structures, which are thought to be associated with functional compartmentalization of genomic features like genes and their regulatory elements. For this reason, understanding the mechanisms of genome folding is a major biological research problem. Studying chromatin conformation requires high computational resources and complex data analyses pipelines. In this chapter, we first present the PyGMQL software for interactive and scalable data exploration for genomic data. PyGMQL allows the user to inspect genomic datasets and design complex analysis pipelines. The software presents itself as a easy-to-use Python library and interacts seamlessly with other data analysis packages. We then use the software for the study of chromatin conformation data. We focus on the epigenetic determinants of Topologically Associating Domains (TADs), which are region of high self chromatin interaction. The results of this study highlight the existence of a “grammar of genome folding” which dictates the formation of TADs and boundaries, which is based on the CTCF insulator protein. Finally we focus on the relationship between chromatin conformation and gene expression, designing a graph representation learning model for the prediction of gene co-expression from gene topological features obtained from chromatin conformation data. We demonstrate a correlation between chromatin topology and co-expression, shedding a new light on this debated topic and providing a novel computational framework for the study of co-expression networks.

Domain-Specific Multi-Level IR Rewriting for GPU

Most compilers have a single core intermediate representation (IR) (e.g., LLVM) sometimes complemented with vaguely defined IR-like data structures. This IR is commonly low-level and close to machine instructions. As a result, optimizations relying on domain-specific information are either not possible or require complex analysis to recover the missing information. In contrast, multi-level rewriting instantiates a hierarchy of dialects (IRs), lowers programs level-by-level, and performs code transformations at the most suitable level. We demonstrate the effectiveness of this approach for the weather and climate domain. In particular, we develop a prototype compiler and design stencil- and GPU-specific dialects based on a set of newly introduced design principles. We find that two domain-specific optimizations (500 lines of code) realized on top of LLVM’s extensible MLIR compiler infrastructure suffice to outperform state-of-the-art solutions. In essence, multi-level rewriting promises to herald the age of specialized compilers composed from domain- and target-specific dialects implemented on top of a shared infrastructure.

Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification

Some compounds reported as active against SARS CoV were selected, and docking studies were performed using the main protease of SARS CoV-2 as the receptor. The docked complex analysis shows that the ligands selectively bind with the target residues and binding affinity of amentoflavone (–10.1 kcal mol–1), isotheaflavin-3’-gallate (–9.8 kcal mol–1), tomentin A and D (–8.0 and –8.8 kcal mol–1), theaflavin-3,3’-digallate (–8.6 kcal mol–1), papyriflavonol A (–8.4 kcal mol–1), iguesterin (–8.0 kcal mol–1) and savinin (–8.3 kcal mol–1) were ranked above the binding affinity of the reference, co-crystal ligand, ML188, a furan-2-carboxamide-based compound. To pinpoint the drug-like compound among the top-ranked compounds, the Lipinski’s rule of five and pharmacokinetic properties of all the selected compounds were evaluated. The results detailed that savinin exhibits high gastrointestinal absorption and can penetrate through the blood-brain barrier. Also, modifying these natural scaffolds with excellent binding affinity may lead to discovering of anti-SARS CoV agents with promising safety profiles.

The phenomenon of media culture in the modern world

The purpose of the Article. The urgency of the work is due to the fact that atypical digital phenomena are increasingly integrated into people's lives digital phenomena (in particular, from the Internet), which require compliance with certain standards of behavior. First of all, they are determined by the rules of the information environment and media culture. Given the fact that most of the news, information, data we receive from Internet sources, the issue of research of media culture from various aspects, is undoubtedly relevant. The aim of this paper research functions, tasks, and complex analysis of components of media culture, specifics of their functioning. The methodology involves the use of general and special techniques, in particular, analysis, synthesis, abstraction, specification, descriptive method, partial forecasting. The result of this work is to reveal the development of scientific thought about the place and role of media culture is considered. Approaches to the definition of this concept in the scientific literature are analyzed. The main issues to be solved by a media culture in the future are revealed. The ratio of general, communicative, information and media culture is demonstrated and substantiated. It is established that its architecture includes multifunctional channels, and systematicity and integrity are considered as their basic properties. Particular attention is paid to the functional purpose of media culture and the characteristics of the respective positions. Cautions have been formulated regarding the probable consequences of the digitalization of a certain part of cultural heritage. The topicality is due to the introduction of the author's proposals for the disclosure of the basic concept and components of media culture, as well as outlines a number of global issues that are designed to solve media culture. Scientific Novelty. The practical significance of the study is justified by the possibility of applying its results in lectures and seminars on journalism, philosophy, sociology, cybersecurity, and other educational areas. Conclusions. Based on the results of our work, let us summarize that contemporary media culture represents a new form of intellectual response. Each next stage of cultural development will be less bookish, tactile than the previous one. This is justified, on the one hand, by the rapid digitalization of all cultural institutions, and, on the other hand, by the desire of the very recipients to simplify data processing in such an array of information. It is established that a unified approach to the interpretation of “media culture” has the maximum to reflect the main characteristics of culture as a generalized concept. Thus, under the media culture is proposed to understand the part of the general culture, the main type of culture of the information society, on the one hand - reflects its general level of development, and on the other - forms the overall effect and intellectual influence, usually from the new media (television, online press, social networks, radio, film) on public opinion, preferences, and values. Prospects for further research we see in analyzing ways of introducing media literacy into the modern educational system. Keywords: digitalization, media culture, bricolage media sphere, latest media, convergent media, infographics.