Search

Improved RNA virus understanding is critical to studying animal and plant health, and environmental processes. However, the continuous and rapid RNA virus evolution makes their identification and characterization challenging. While recent sequence-based advances have led to extensive RNA virus discovery, there is growing variation in how RNA viruses are identified, analyzed, characterized, and reported. To this end, an RdRp Summit was organized and a hybrid meeting took place in Valencia, Spain in May 2023 to convene leading experts with emphasis on early career researchers (ECRs) across diverse scientific communities. Here we synthesize key insights and recommendations and offer these as a first effort to establish a consensus framework for advancing RNA virus discovery. First, we need interoperability through standardized methodologies, data-sharing protocols, metadata provision and interdisciplinary collaborations and offer specific examples as starting points. Second, as an emergent field, we recognize the need to incorporate cutting-edge technologies and knowledge early and often to improve omic-based viral detection and annotation as novel capabilities reveal new biology. Third, we underscore the significance of ECRs in fostering international partnerships to promote inclusivity and equity in virus discovery efforts. The proposed consensus framework serves as a roadmap for the scientific community to collectively contribute to the tremendous challenge of unveiling the RNA virosphere.

Aim. To evaluate the clinical effectiveness, safety and compare the incidence of hospitalization during treatment with antiviral drugs with a direct mechanism of action (riamilovir and umifenovir) in people with acute respiratory viral infections (ARVI) in an outpatient setting. Materials and methods. The study included 150 outpatients with ARVI aged 18–27 years: 50 patients received riamilovir 250 mg 3 times a day for 5 days, the second group included 50 patients who received umifenovir 200 mg 4 times a day for 5 days, 50 individuals received only pathogenetic treatment. Results. The use of direct-acting antiviral drugs was characterized by the least severity of pain and aches in the body, general weakness, and in the group of patients receiving riamilovir, the lowest severity of rhinitis, cough, and the lowest morning body temperature were recorded compared to other groups. In riamilovir group reduction in the duration of the disease was observed. The lowest frequency of ARVI pathogens detection was observed on the 6th day in riamilovir group. Outpatient treatment with riamilovir was accompanied by a minimal number of cases of the disease requiring hospitalization. Conclusion. The use of direct antiviral drugs contributes to the rapid relief of ARVI symptoms in patients receiving medical care on an outpatient basis. The antiviral drug riamilovir showed the most pronounced effectiveness (clinical and laboratory).

ABSTRACT Metatranscriptomics is uncovering more and more diverse families of viruses with RNA genomes comprising the viral kingdom Orthornavirae in the realm Riboviria. Thorough protein annotation and comparison are essential to get insights into the functions of viral proteins and virus evolution. In addition to sequence- and hmm profile‑based methods, protein structure comparison adds a powerful tool to uncover protein functions and relationships. We constructed an Orthornavirae “structurome” consisting of already annotated as well as unannotated (“dark matter”) proteins and domains encoded in viral genomes. We used protein structure modeling and similarity searches to illuminate the remaining dark matter in hundreds of thousands of orthornavirus genomes. The vast majority of the dark matter domains showed either “generic” folds, such as single α-helices, or no high confidence structure predictions. Nevertheless, a variety of lineage-specific globular domains that were new either to orthornaviruses in general or to particular virus families were identified within the proteomic dark matter of orthornaviruses, including several predicted nucleic acid-binding domains and nucleases. In addition, we identified a case of exaptation of a cellular nucleoside monophosphate kinase as an RNA-binding protein in several virus families. Notwithstanding the continuing discovery of numerous orthornaviruses, it appears that all the protein domains conserved in large groups of viruses have already been identified. The rest of the viral proteome seems to be dominated by poorly structured domains including intrinsically disordered ones that likely mediate specific virus-host interactions.IMPORTANCEAdvanced methods for protein structure prediction, such as AlphaFold2, greatly expand our capability to identify protein domains and infer their likely functions and evolutionary relationships. This is particularly pertinent for proteins encoded by viruses that are known to evolve rapidly and as a result often cannot be adequately characterized by analysis of the protein sequences. We performed an exhaustive structure prediction and comparative analysis for uncharacterized proteins and domains (“dark matter”) encoded by viruses with RNA genomes. The results show the dark matter of RNA virus proteome consists mostly of disordered and all-α-helical domains that cannot be readily assigned a specific function and that likely mediate various interactions between viral proteins and between viral and host proteins. The great majority of globular proteins and domains of RNA viruses are already known although we identified several unexpected domains represented in individual viral families.

Various approaches to solving the problem of speech command recognition in real time using artificial neural networks (ANN) of several types are considered. A brief overview of deep fully-connected, convolutional and recurrent neural networks is given. It is shown that ANNs of convolutional and recurrent types are capable of providing the required level of performance and accuracy when performing inference in real time. A comparison is given of the performance of convolutional and recurrent algorithms when ported to the K1879VM6Ya hardware platform from the NeuroMatrix family of high-performance digital signal processors. When porting, the features of the microprocessor architecture were considered. All basic operations are performed on a vector matrix coprocessor. The advantage of convolutional ANN has been demonstrated. Considering the results of research into a neural network of this type on the K1879VM6Ya platform, it was transferred to a more productive hardware accelerator - the K1879VM8Ya system-on-chip. The prospects for creating a speech recognition system on the K1879VM8Ya platform are considered.

Viroids and viroid-like covalently closed circular (ccc) RNAs are minimal replicators that typically encode no proteins and hijack cellular enzymes for replication. The extent and diversity of viroid-like agents are poorly understood. We developed a computational pipeline to identify viroid-like cccRNAs and applied it to 5,131 metatranscriptomes and 1,344 plant transcriptomes. The search yielded 11,378 viroid-like cccRNAs spanning 4,409 species-level clusters, a 5-fold increase compared to the previously identified viroid-like elements. Within this diverse collection, we discovered numerous putative viroids, satellite RNAs, retrozymes, and ribozy-like viruses. Diverse ribozyme combinations and unusual ribozymes within the cccRNAs were identified. Self-cleaving ribozymes were identified in ambiviruses, some mito-like viruses and capsid-encoding satellite virus-like cccRNAs. The broad presence of viroid-like cccRNAs in diverse transcriptomes and ecosystems implies that their host range is far broader than currently known, and matches to CRISPR spacers suggest that some cccRNAs replicate in prokaryotes.

The one of the main problems of congestion processes at bus stopping points (SP) is that an increase in the number of buses and routes leads to a disruption in the organization of their passage through the SP. The poor organization of bus passage through the SP can lead to the fact that during peak hours, the buses queue can stretch for hundreds of meters. The forming buses into a group can reduce the congestions at the SP and increase their throughput, as a result of the simultaneous arrival and departure of buses from the SPs. In order to check the stated hypothesis, experimental and theoretical studies were carried out on the process of passing buses through the SP “Revolution Sq." on Lenin Ave., Chelyabinsk city, Russia. In this article was found that, when using three buses in one group, the passenger service time at the SP will be reduced in the range of (52-56) %. This result can lead to assert that the buses movement in a group through the SP will increase its capacity by approximately 50% and reducing the possibility of congestion at bus stopping points. Purpose. Reducing the congestion at the bus stopping points by forming groups of buses. Methodology. In the article the observation and comparison methods are used as the analysis methods. Results. The most informative parameters showing some aspects of carrying out the analysis of export operations are received. Practical implications. The diagrams of the main data of experimental studies and theoretical dependences of the dwell time that spent by three buses in one group and three buses arriving one by one at SP “Revolution Sq." are got from the route numbers in the morning and evening.

High-throughput RNA sequencing offers broad opportunities to explore the Earth RNA virome. Mining 5,150 diverse metatranscriptomes uncovered >2.5 million RNA virus contigs. Analysis of >330,000 RNA-dependent RNA polymerases (RdRPs) shows that this expansion corresponds to a 5-fold increase of the known RNA virus diversity. Gene content analysis revealed multiple protein domains previously not found in RNA viruses and implicated in virus-host interactions. Extended RdRP phylogeny supports the monophyly of the five established phyla and reveals two putative additional bacteriophage phyla and numerous putative additional classes and orders. The dramatically expanded phylum Lenarviricota, consisting of bacterial and related eukaryotic viruses, now accounts for a third of the RNA virome. Identification of CRISPR spacer matches and bacteriolytic proteins suggests that subsets of picobirnaviruses and partitiviruses, previously associated with eukaryotes, infect prokaryotic hosts.

Subject. Institutional support for the development of the Donbas during the process of its adaptation to the social and economic system of the Russian Federation. The state and development prospects of institutional subsystems: business, public authority, financial, and non-commercial sectors. Purpose. To study the main parameters of the institutional subsystems in the Donbas and determine the problems and the vectors of institutional, social, and economic development of the region in the situation of an armed conflict running parallel to its integration with Russian institutes. Research methods. The theoretical basis of the study was the dialectical method, which allowed us to consider social, economic, and institutional systems of the Donbas in the context of integration of the region in Russian social environment. To determine the problems of social, economic, and institutional development of the region, the monographic method was used. It allowed us to review the existing approaches to the state and prospects of the economy and the supporting institutes during the period of integration into the Russian Federation. A retrospective analysis was a key practical research method. It helped to determine the dynamics of the main institutional subsystems of the region from the point of view of modernisation of the functions implemented by such institutes as business, public authority, financial, and non-commercial sector during the armed conflict of 2014-2021 and the special military operation. Results and discussion. After its inclusion into the Russian Federation, the institutional support of the development of the Donbas requires a fundamental transformation in order to adapt to new conditions. The transformation should involve a comprehensive transformation of the social and economic model of the region and its infrastructure, diversification, and modernisation of the development institutes. At the same time, it is necessary to take into account the weaknesses of the institutional system of the region. They include external threats caused by the armed conflict which started in 2014 and caused damage to the business institute; a dramatic reduction in the number of stimuli for the functioning of financial institutes, especially for the innovative and investment activities; underdevelopment of non-commercial organisations; and a high level of bureaucracy in public institutions. The new institutional model should be aimed at decreasing the vulnerability of the region to geopolitical and economic crises and its dependence on heavy industry and coal mining, while developing high-tech industries and innovations, and investing in education, healthcare, and the retraining of the labour force. It is therefore necessary to develop reasonable adaptation strategies and programmes, including appointing responsible executives to the governmental and municipal bodies and developing mechanisms for the financing of projects aimed at the economic growth and well-being of the population.

The study aims to understand the role of solar wind current sheets (CSs) in shaping the spectrum of turbulent fluctuations and driving dissipation processes in space plasma. Local non-adiabatic heating and acceleration of charged particles in the solar wind is one of the most intriguing challenges in space physics. Leading theories attribute these effects to turbulent heating, often associated with magnetic reconnection at small-scale coherent structures in the solar wind, such as CSs and flux ropes. We identify CSs observed at 1 AU in different types of the solar wind around and within an interplanetary coronal mass ejection (ICME) and analyze the corresponding characteristics of the turbulent cascade. It is found that the spectra of fluctuations of the interplanetary magnetic field may be reshaped due to the CS impact potentially leading to local disruptions in energy transfer along the cascade of turbulent fluctuations. Case studies of the spectra behavior at the peak of the CS number show their steepening at MHD scales, flattening at kinetic scales, and merging of the spectra into a single form, with the break almost disappearing. In the broader vicinity of the CS number peak, the behavior of spectral parameters changes sharply, but not always following the same pattern. The statistical analysis shows a clear correlation between the break frequency and the CS number. These results are consistent with the picture of turbulent reconnection at CSs. The CS occurrence is found to be statistically linked with the increased temperature. In the ICME sheath, there are two CS populations observed in the hottest and coldest plasma.

Cardiovascular diseases continue to be the main cause of hospital mortality and lead to great disability of the working population. Numerous clinical and experimental studies have shown that inflammation is the main factor causing the growth and progression of atherosclerosis. Despite significant progress in basic therapy aimed at both preventing the development of heart failure (HF) and treating it, the prognosis in patients after their first hospitalization remains extremely unfavorable. HF is the leading cause of morbidity and mortality worldwide. Various stimuli at different stages of HF pathophysiology trigger a cascade of proinflammatory reactions with the release of interleukins, the formation of reactive oxygen species, mitochondrial DNA damage and the induction of autophagy. Based on the presented results from experimental and clinical studies, it can be expected that a better understanding of the molecular aspects in the pathophysiology of HF will open opportunities for the development of new therapeutic monoclonal antibodies.

A comprehensive census of McrBC systems, among the most common forms of prokaryotic Type IV restriction systems, followed by phylogenetic analysis, reveals their enormous abundance in diverse prokaryotes and a plethora of genomic associations. We focus on a previously uncharacterized branch, which we denote coiled-coil nuclease tandems (CoCoNuTs) for their salient features: the presence of extensive coiled-coil structures and tandem nucleases. The CoCoNuTs alone show extraordinary variety, with three distinct types and multiple subtypes. All CoCoNuTs contain domains predicted to interact with translation system components, such as OB-folds resembling the SmpB protein that binds bacterial transfer-messenger RNA (tmRNA), YTH-like domains that might recognize methylated tmRNA, tRNA, or rRNA, and RNA-binding Hsp70 chaperone homologs, along with RNases, such as HEPN domains, all suggesting that the CoCoNuTs target RNA. Many CoCoNuTs might additionally target DNA, via McrC nuclease homologs. Additional restriction systems, such as Type I RM, BREX, and Druantia Type III, are frequently encoded in the same predicted superoperons. In many of these superoperons, CoCoNuTs are likely regulated by cyclic nucleotides, possibly, RNA fragments with cyclic termini, that bind associated CARF (CRISPR-Associated Rossmann Fold) domains. We hypothesize that the CoCoNuTs, together with the ancillary restriction factors, employ an echeloned defense strategy analogous to that of Type III CRISPR-Cas systems, in which an immune response eliminating virus DNA and/or RNA is launched first, but then, if it fails, an abortive infection response leading to PCD/dormancy via host RNA cleavage takes over.

Improved RNA virus understanding is critical to studying animal and plant health, and environmental processes. However, the continuous and rapid RNA virus evolution makes their identification and characterization challenging. While recent sequence-based advances have led to extensive RNA virus discovery, there is growing variation in how RNA viruses are identified, analyzed, characterized, and reported. To this end, an RdRp Summit was organized and a hybrid meeting took place in Valencia, Spain in May 2023 to convene leading experts with emphasis on early career researchers (ECRs) across diverse scientific communities. Here we synthesize key insights and recommendations and offer these as a first effort to establish a consensus framework for advancing RNA virus discovery. First, we need interoperability through standardized methodologies, data-sharing protocols, metadata provision and interdisciplinary collaborations and offer specific examples as starting points. Second, as an emergent field, we recognize the need to incorporate cutting-edge technologies and knowledge early and often to improve omic-based viral detection and annotation as novel capabilities reveal new biology. Third, we underscore the significance of ECRs in fostering international partnerships to promote inclusivity and equity in virus discovery efforts. The proposed consensus framework serves as a roadmap for the scientific community to collectively contribute to the tremendous challenge of unveiling the RNA virosphere.

Objective: The use of checkpoint inhibitors in cancer will continue to expand in the coming years, which is a promising area for future clinical research. However, diagnosis of immune-related side effects is challenging due to its heterogeneous clinical manifestations, which range from subclinical to fulminant manifestations with high in-hospital mortality. A potential mechanism may be proliferation and clonal expansion of antigens by T lymphocytes in tumor cells and affected self-tissues. The exact pathophysiological mechanism remains unclear and the risk profile of patients experiencing cardiotoxicity is unknown. The aim of our work is to focus on the immune side effects of immunotherapy and their mechanisms. Methods: We used PubMed (Medline) database, Google Scholar for evidence search. The search depth was up to 10 years. The search phrases used were: “immune side effects”, “cardiotoxicity of immunotherapy”, “checkpoint inhibitors”. Search result by keywords in the PubMed (Medline) database, Google Scholar found a total of 205 publications. Number publications after removing duplicates amounted to 165. After analyzing the titles and their abstracts, 40 publications met the goal, 17 publications passed the full-text screening. Thus, our review finally included 13 studies. Results: Immune checkpoint inhibitors are the most notable breakthrough in the treatment of cancer, but the wide range of adverse events associated with the immune system should not be ignored. According to the analysis of the studies cardiac adverse are reported in 13.3% of patients receiving such therapy, myocarditis – 2.1% and cardiac arrhythmias – 9%, other cardiovascular pathology is rare. The exact pathophysiological mechanism remains unclear and the risk profile of patients experiencing cardiotoxicity is unknown. Conclusion: Continued intensive efforts by the research communities and interdisciplinary collaborations in oncology and cardiology will help address these challenges and thereby allow immunotherapy to achieve its maximum potential benefit in the treatment of cancer.

Relevance. The fact that hydrogenic deposits are developed using combined technologies, and the criteria for combining technologies have not been sufficiently developed. Aim. To select the optimal method of deposit development, taking into account the characteristics of the uranium ores composing it. Objects. The Semizbai sandstone deposit, which lies in loose sedimentary rocks, is localized within a 36 km long section with a width of 10 km. Methods. Analysis of the theory and practice of field development, finding dependencies between operational indicators, modeling, methods of mathematical statistics, technical and economic calculations and approbation of some provisions. Results. The authors have given characteristic of systems for developing hydrogenic deposits and substantiated the necessity of combining metal extraction technologies by leaching with traditional technologies in the conditions of the deposit. Alternative technologies for metal leaching using interacting wells and with metal leaching in a pile are detailed. The mechanism and differences in the conditions of uranium leaching in a quicksand array and in a heap was clarified. The authors have carried out comparative characteristic of alternative options for field development, indicating, among other things, their advantages and disadvantages. It was determined that leaching parameters depend on speed and efficiency of opening new reaction areas with a different mechanism for removing uranium from mineral particles. It is proved that the efficiency of the development of hydrogenic deposits is increased by combining the processes of borehole hydro extraction of ores and heap leaching of metals. The authors proposed the model of decision-making sequence with an arbitrary source of information based on the criterion of discounted profit from mining. Conclusions. The results of the study may be in demand when revaluing reserves, modernizing systems for the development and optimization of methods for managing the quality of mining products. The recommended methods of monitoring the combined development of hydrogenic deposits contribute to increasing the completeness of subsurface use.

ABSTRACT Endosomal sorting complexes required for transport (ESCRT) play key roles in protein sorting between membrane-bounded compartments of eukaryotic cells. Homologs of many ESCRT components are identifiable in various groups of archaea, especially in Asgardarchaeota, the archaeal phylum that is currently considered to include the closest relatives of eukaryotes, but not in bacteria. We performed a comprehensive search for ESCRT protein homologs in archaea and reconstructed ESCRT evolution using the phylogenetic tree of Vps4 ATPase (ESCRT IV) as a scaffold and using sensitive protein sequence analysis and comparison of structural models to identify previously unknown ESCRT proteins. Several distinct groups of ESCRT systems in archaea outside of Asgard were identified, including proteins structurally similar to ESCRT-I and ESCRT-II, and several other domains involved in protein sorting in eukaryotes, suggesting an early origin of these components. Additionally, distant homologs of CdvA proteins were identified in Thermoproteales which are likely components of the uncharacterized cell division system in these archaea. We propose an evolutionary scenario for the origin of eukaryotic and Asgard ESCRT complexes from ancestral building blocks, namely, the Vps4 ATPase, ESCRT-III components, wH (winged helix-turn-helix fold) and possibly also coiled-coil, and Vps28-like domains. The last archaeal common ancestor likely encompassed a complex ESCRT system that was involved in protein sorting. Subsequent evolution involved either simplification, as in the TACK superphylum, where ESCRT was co-opted for cell division, or complexification as in Asgardarchaeota. In Asgardarchaeota, the connection between ESCRT and the ubiquitin system that was previously considered a eukaryotic signature was already established.IMPORTANCEAll eukaryotic cells possess complex intracellular membrane organization. Endosomal sorting complexes required for transport (ESCRT) play a central role in membrane remodeling which is essential for cellular functionality in eukaryotes. Recently, it has been shown that Asgard archaea, the archaeal phylum that includes the closest known relatives of eukaryotes, encode homologs of many components of the ESCRT systems. We employed protein sequence and structure comparisons to reconstruct the evolution of ESCRT systems in archaea and identified several previously unknown homologs of ESCRT subunits, some of which can be predicted to participate in cell division. The results of this reconstruction indicate that the last archaeal common ancestor already encoded a complex ESCRT system that was involved in protein sorting. In Asgard archaea, ESCRT systems evolved toward greater complexity, and in particular, the connection between ESCRT and the ubiquitin system that was previously considered a eukaryotic signature was established.