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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.

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.

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.

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.

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.

Wood as a material is a natural composite with a complex hierarchically arranged structure. All scale levels of wood structure contribute to its macroscopic mechanical properties. The nature of such characteristics and deformation modes differs radically at different scale levels. Wood macroscopic properties are well studied, and the relevant information can be easily found in the literature. However, the knowledge of the deformation mechanisms at the mesoscopic level corresponding to the cellular structure of early and late wood layers of annual growth rings is insufficient. It hinders building the comprehensive multiscale model of how wood mechanical properties are formed. This paper described the results of scanning of mechanical properties of softwood and hardwood samples, such as common pine, small-leaf lime, and pedunculate oak, by means of nanoindentation (NI). The NI technique allows varying the size of deformed region within a wide range by altering maximal load (Pmax) applied to the indenter so that one can repeatedly and non-destructively test wood structural components at different scale levels on the same sample without changing the technique or equipment. It was discovered that the effective microhardness (Heff) and Young's modulus (Eeff) decreased manifold with Pmax growing from 0.2 to 2 000 mN. This drop in Heff was observed when the locally deformed region grew, and resulting from Pmax increase generally follows the rule similar to the Hall-Petch relation for yield stress, strength, and hardness initially established for metals and alloys, though obviously in those cases the underlying internal mechanisms are quite different. The nature and micromechanisms of such size effect (SE) in wood revealed using NI were discussed in this study. At Pmax < 0.2 mN, the deformed area under the pyramidal Berckovich indenter was much smaller than the cell wall width. Hence, in this case, NI measured the internal mechanical properties of the cell wall material as long as free boundaries impact could be neglected. At Pmax > 200 mN, the indentation encompassed several cells. The measured mechanical properties were significantly affected by bending deformation and buckling collapse of cell walls, reducing Heff and Eeff substantially. At Pmax ≈ 1–100 mN, an indenter interacted with different elements of the cell structure and capillary network, resulting in intermediate values of Heff and Eeff. Abrupt changes in Heff and Eeff at annual growth ring boundaries allow accurate measuring of rings width, while smoother and less pronounced changes within the rings allow identification of earlywood and latewood layers as well as any finer changes during vegetation season. The values of ring width measured using NI and standard optical method coincide with 2%−3% accuracy. The approaches and results presented in this study could improve the understanding of nature and mechanisms lying behind the micromechanical properties of wood, help to optimize the technologies of wood farming, subsequent reinforcement, and utilization, as well as to develop new highly informative techniques in dendrochronology and dendroclimatology.

The present study considers the samples of an Ti-6Al-4V alloy obtained by selective laser melting with the addition of a 10% Cu-Al powder mixture. The microstructure, elemental composition and phase composition, as well as the physico-chemical properties, have been investigated by the methods of electron microscopy, X-ray phase analysis, and bending testing. The obtained samples have a relative density of 98.5 ± 0.1%. The addition of the Cu-Al powder mixture facilitates supercooling during crystallization and solidification, which allows decreasing the size and changing the shape of the initial β-Ti grains. The constant cooling rate of the alloy typical for the SLM technology has been shown to be able to prevent martensitic transformation. The formation of a structure that consists of β-Ti grains, a dispersed eutectoid mixture of α-Ti and Ti2Cu grains, and a solid solution of Al in Cu has been revealed. In the case of doping by the 10% Cu-Al mixture, the physico-mechanical properties are improved. The hardness of the samples amounts to 390 HRC, with the bending strength being 1550 ± 20 MPa and deformation of 3.5 ± 0.2%. The developed alloy can be recommended for applications in the production of parts of jet and car engines, implants for medicine, and corrosion-resistant parts for the chemical industry.

ABSTRACT The identification of microbial genes essential for survival as those with lethal knockout phenotype (LKP) is a common strategy for functional interrogation of genomes. However, interpretation of the LKP is complicated because a substantial fraction of the genes with this phenotype remains poorly functionally characterized. Furthermore, many genes can exhibit LKP not because their products perform essential cellular functions but because their knockout activates the toxicity of other genes (conditionally essential genes). We analyzed the sets of LKP genes for two archaea, Methanococcus maripaludis and Sulfolobus islandicus, using a variety of computational approaches aiming to differentiate between essential and conditionally essential genes and to predict at least a general function for as many of the proteins encoded by these genes as possible. This analysis allowed us to predict the functions of several LKP genes including previously uncharacterized subunit of the GINS protein complex with an essential function in genome replication and of the KEOPS complex that is responsible for an essential tRNA modification as well as GRP protease implicated in protein quality control. Additionally, several novel antitoxins (conditionally essential genes) were predicted, and this prediction was experimentally validated by showing that the deletion of these genes together with the adjacent genes apparently encoding the cognate toxins caused no growth defect. We applied principal component analysis based on sequence and comparative genomic features showing that this approach can separate essential genes from conditionally essential ones and used it to predict essential genes in other archaeal genomes.IMPORTANCEOnly a relatively small fraction of the genes in any bacterium or archaeon is essential for survival as demonstrated by the lethal effect of their disruption. The identification of essential genes and their functions is crucial for understanding fundamental cell biology. However, many of the genes with a lethal knockout phenotype remain poorly functionally characterized, and furthermore, many genes can exhibit this phenotype not because their products perform essential cellular functions but because their knockout activates the toxicity of other genes. We applied state-of-the-art computational methods to predict the functions of a number of uncharacterized genes with the lethal knockout phenotype in two archaeal species and developed a computational approach to predict genes involved in essential functions. These findings advance the current understanding of key functionalities of archaeal cells.

Objective: Advances in cancer treatment over the past decades have improved long-term patient survival but increased the incidence of chemotherapy-associated cardiotoxicity (CAC). The study of quality of life (QoL) indicators is becoming a relevant and integral subject for the management of patients receiving high doses of antitumor therapy. In particular, CAC carries a high burden on the healthcare system and the patient's daily lifestyle due to a decrease in the body's functional capacity. Due to the increasing life expectancy of patients with cancer, the issues of maintaining a high QoL are becoming increasingly important. The purpose of the study is to conduct a comprehensive assessment of QoL in patients with breast cancer during neoadjuvant chemotherapy (NAC). Methods: The study included 72 patients with breast cancer who underwent a comprehensive assessment of the cardiovascular system at the National Medical Research Center for Cardiovascular Surgery. A.N. Bakulev" as continuous cardiac monitoring during NAC. To assess the quality of life, all patients filled out the standardized questionnaire SF-36, EQ-5D-5L, as well as indicators on the international Karnofsky and ECOG (Eastern Cooperative Oncology Group) scales. The possible relationship between various indicators of the questionnaire with internationally validated scales, as well as data from the clinical status of patients, was studied. Results: A significant deterioration in the QoL of patients receiving NAC was observed in all analyzed indicators: mental and physical health indicators, Karnofsky scores, ECOG and EQ 5D-5L sharply decreased, the prevalence of general weakness, shortness of breath and decreased exercise tolerance increased. According to scale SF-36, initially low indicators were observed in a large number of patients (80 and 82%, respectively); at the intermediate and final stages, almost all patients showed a deterioration in their condition compared to the outcome (p = 0.0002–0.0001). Predictors of a pronounced negative deviation in QoL indicators are the presence of initial reduced ECOG and Karnofsky scores, as well as the presence of an initial decrease in exercise tolerance, the presence of weakness and shortness of breath. Conclusion: During continuous cardiac monitoring, we demonstrated a deterioration in all indicators of QoL, according to questionnaires and validated international scales during NAC in patient with breast cancer. Predictors of a pronounced decrease in QoL indicators are the presence of initial reduced ECOG and Karnofsky scores, as well as the presence of an initial decrease in exercise tolerance, the presence of weakness and shortness of breath. The Karnofsky scale and ECOG can be adapted for objective assessment of QoL indicators during NAC.

Subject. Innovative development of Russian regions. Dynamics of the basic parameters of innovative activity which characterise three blocks of innovation functions: process block, result block, and resource block. Objectives. To research basic parameters of innovative activity, to establish whether there is balance/disbalance between the process, result, and resource blocks of the innovative development of regions. Experimental. Theoretically, the study is based on the dialectical method, which was used to formulate the hypothesis of the study: the low level of innovative development of regions is due to the spatial and functional disbalance of their innovation subsystems, which include process, resource, and result blocks. To identify the state and dynamics of the innovative development of Russian regions, an empirical analysis of the basic parameters of this process was carried out. These parameters reflect various aspects of the innovative development of regions: the state of innovation processes, results, and used resources. Model regions (representative regions) were selected as a result of cluster analysis. The dynamics of the basic parameters for the period of 2010-2021 was estimated by the correlation-regression method. The forecast for the period of 2022-2024 was created by extrapolating the data for each function describing the actual dynamics with a sufficient degree of reliability. Results and discussion. We propose to assess innovation processes by five innovation functions combined into three blocks: process block (functional diversification, technological diversification, and technological concentration); result block (production concentration); and resource block (resource concentration). The results of the analysis showed that the development of functional diversification is unstable in most model regions, which makes it impossible to reliably predict its further dynamics. There is a steady growth, though of varied degree, in technological diversification and technological concentration in all model regions. Production concentration (result block) and resource concentration (resource block) are characterised by unstable trends and an overall tendency towards deterioration over the period of 2010-2021.

Despite the high medical and socioeconomic burden of non-alcoholic fatty liver disease (NAFLD), treatments that could effectively reduce histological liver damage in this condition are lacking. As providing only qualitative data is a major limitation of most histological scoring systems, we aimed to develop a simple and straightforward algorithm for semiquantitative analysis of scored histology data using the extended Fisher’s exact test in the R environment. As an illustrative example, we used the effects of L-ornithine L-aspartate (LOLA) and empagliflozin (EMPA) in a 3-month chemical/dietary murine model of NAFLD. 100 C57Bl/6 mice were randomized into 4 groups: Intact (n = 10), Control (NAFLD; n = 30), LOLA (NAFLD + 1.5 g·kg−1 b.w./d LOLA orally; n = 30), and EMPA (NAFLD + 10 mg·kg−1 b.w./d EMPA orally; n = 30). LOLA reduced hepatitis activity (p < 0.05), cholestasis, necrosis, and fibrosis severity (p < 0.01), and EMPA prevented necrosis (p < 0.05) and reduced fibrosis severity (p < 0.01). The statistical approach we suggest can be used as a simple complementary tool for exploratory analysis of scored histology data.

Genomes of bacteria and archaea contain a much larger fraction of unidirectional (serial) gene pairs than convergent or divergent gene pairs. Many of the unidirectional gene pairs have short overlaps of −4 nt and −1 nt. As shown previously, translation of the genes in overlapping unidirectional gene pairs is tightly coupled. Two alternative models for the fate of the post-termination ribosome predict either that overlaps or very short intergenic distances are essential for translational coupling or that the undissociated post-termination ribosome can scan through long intergenic regions, up to hundreds of nucleotides. We aimed to experimentally resolve the contradiction between the two models by analyzing three native gene pairs from the model archaeon Haloferax volcanii and three native pairs from Escherichia coli. A two reporter gene system was used to quantify the reinitiation frequency, and several stop codons in the upstream gene were introduced to increase the intergenic distances. For all six gene pairs from two species, an extremely strong dependence of the reinitiation efficiency on the intergenic distance was unequivocally demonstrated, such that even short intergenic distances of about 20 nt almost completely abolished translational coupling. Bioinformatic analysis of the intergenic distances in all unidirectional gene pairs in the genomes of H. volcanii and E. coli and in 1,695 prokaryotic species representative of 49 phyla showed that intergenic distances of −4 nt or −1 nt (= short gene overlaps of 4 nt or 1 nt) were by far most common in all these groups of archaea and bacteria. A small set of genes in E. coli, but not in H. volcanii, had intergenic distances of around +10 nt. Our experimental and bioinformatic analyses clearly show that translational coupling requires short gene overlaps, whereas scanning of intergenic regions by the post-termination ribosome occurs rarely, if at all. Short overlaps are enriched among genes that encode subunits of heteromeric complexes, and co-translational complex formation requiring precise subunit stoichiometry likely confers an evolutionary advantage that drove the formation and conservation of overlapping gene pairs during evolution.

This paper is devoted to the analysis of fluctuations in the solar wind plasma and interplanetary magnetic field parameters observed by Solar Orbiter and WIND spacecraft at different scales ranging from ~103 to 107 km. We consider two long data intervals where the distances between the spacecraft are 0.1 and 0.5 AU, respectively, and they are located close to the Sun–Earth line. Transformation of the fluctuation’s properties on the way from the Sun to Earth is analyzed for different types of solar wind associated with quasi-stationary and transient solar phenomena. The time series of bulk speed are shown to undergo a slight modification, even for large spacecraft separation, while the time series of the interplanetary magnetic field magnitude and components as well as proton density may be transformed even at a relatively short distance. Though the large-scale solar wind structures propagate the distance up to 0.5 AU without significant change, local structures at smaller scales may be modified. The statistical properties of the fluctuations such as relative standard deviation or probability distribution function and its moments remain nearly unchanged at different distances between the two spacecraft and are likely to depend mostly on the type of the solar wind.

Abstract Background Symbiotic relationships are ubiquitous in the biosphere. Inter-species symbiosis is impacted by intra-specific distinctions, in particular, those defined by the age structure of a population. Older individuals compete with younger individuals for resources despite being less likely to reproduce, diminishing the fitness of the population. Conversely, however, older individuals can support the reproduction of younger individuals, increasing the population fitness. Parasitic relationships are commonly age structured, typically, more adversely affecting older hosts. Results We employ mathematical modeling to explore the differential effects of collaborative or competitive host age structures on host-parasite relationships. A classical epidemiological compartment model is constructed with three disease states: susceptible, infected, and recovered. Each of these three states is partitioned into two compartments representing young, potentially reproductive, and old, post-reproductive, hosts, yielding 6 compartments in total. In order to describe competition and collaboration between old and young compartments, we model the reproductive success to depend on the fraction of young individuals in the population. Collaborative populations with relatively greater numbers of post-reproductive hosts enjoy greater reproductive success whereas in purely competitive populations, increasing the post-reproductive subpopulation reduces reproductive success. Conclusions We demonstrate that, in collaborative host populations, pathogens strictly impacting older, post-reproductive individuals can reduce population fitness even more than pathogens that directly impact younger, potentially reproductive individuals. In purely competitive populations, the reverse is observed, and we demonstrate that endemic, virulent pathogens can oxymoronically form a mutualistic relationship with the host, increasing the fitness of the host population. Applications to endangered species conservation and invasive species containment are discussed.

Abstract Background Evolutionary rate is a key characteristic of gene families that is linked to the functional importance of the respective genes as well as specific biological functions of the proteins they encode. Accurate estimation of evolutionary rates is a challenging task that requires precise phylogenetic analysis. Here we present an easy to estimate protein family level measure of sequence variability based on alignment column homogeneity in multiple alignments of protein sequences from Clade-Specific Clusters of Orthologous Genes (csCOGs). Results We report genome-wide estimates of variability for 8 diverse groups of bacteria and archaea and investigate the connection between variability and various genomic and biological features. The variability estimates are based on homogeneity distributions across amino acid sequence alignments and can be obtained for multiple groups of genomes at minimal computational expense. About half of the variance in variability values can be explained by the analyzed features, with the greatest contribution coming from the extent of gene paralogy in the given csCOG. The correlation between variability and paralogy appears to originate, primarily, not from gene duplication, but from acquisition of distant paralogs and xenologs, introducing sequence variants that are more divergent than those that could have evolved in situ during the lifetime of the given group of organisms. Both high-variability and low-variability csCOGs were identified in all functional categories, but as expected, proteins encoded by integrated mobile elements as well as proteins involved in defense functions and cell motility are, on average, more variable than proteins with housekeeping functions. Additionally, using linear discriminant analysis, we found that variability and fraction of genomes carrying a given gene are the two variables that provide the best prediction of gene essentiality as compared to the results of transposon mutagenesis in Sulfolobus islandicus. Conclusions Variability, a measure of sequence diversity within an alignment relative to the overall diversity within a group of organisms, offers a convenient proxy for evolutionary rate estimates and is informative with respect to prediction of functional properties of proteins. In particular, variability is a strong predictor of gene essentiality for the respective organisms and indicative of sub- or neofunctionalization of paralogs.

The ongoing problem of inconsistency in the stages of system development encourages the development and elaboration of approaches and methods aimed at eliminating the causes of their occurrence. According to the research community, one of the most promising approaches is to involve users in the development process. Six directions in the implementation of the approach to user involvement in the system development process were formed and analyzed in the article. The analysis of the applicability of such approaches and methods to the task of involving the user in the process of developing an information data model is carried out. The problems of this direction were highlighted. To solve these problems, the sensemaking approach principles which is a development of the methodology for sensemaking proposed by Brenda Dervin, are proposed to use. On the basis of the proposed sensemaking approach, the implementation of the proposed approach is shown with the help of the development of the method, a method for constructing the specification of the information model was developed. The steps of the method are represented by methods that implement the idea of involving the user in the development process by analyzing his work with elements of documentation support.

Textiles and nonwovens (including those used in ventilation systems as filters) are currently one of the main sources of patient cross-infection. Healthcare-associated infections (HAIs) affect 5–10% of patients and stand as the tenth leading cause of death. Therefore, the development of new methods for creating functional nanostructured coatings with antibacterial and antiviral properties on the surfaces of textiles and nonwoven materials is crucial for modern medicine. Antimicrobial filter technology must be high-speed, low-energy and safe if its commercialization and mass adoption are to be successful. Cerium oxide nanoparticles can act as active components in these coatings due to their high antibacterial activity and low toxicity. This paper focuses on the elaboration of a high-throughput and resource-saving method for the deposition of cerium oxide nanoparticles onto nonwoven fibrous material for use in air-conditioning filters. The proposed spraying technique is based on the use of an aerodynamic emitter and simultaneous suction. Cerium oxide nanoparticles have successfully been deposited onto the filter materials used in air conditioning systems; the antibacterial activity of the ceria-modified filters exceeded 4.0.

Reactions of picolinamides with 1,3-propanesultone in methanol followed by the treatment with ketones led to a series of previously unknown chemical transformations, yielding first pyridinium salts (2a–f), with a protonated endocyclic nitrogen atom, and then heterocyclic salts (3a–j) containing an imidazolidin-4-one ring. The structures of intermediate and final products were determined by IR and 1H, 13C NMR spectroscopy, and X-ray study. The effects of the ketone and alcohol structures on the product yield were studied by quantum-chemical calculations. The stability of salts 3a–j towards hydrolysis and alcoholysis makes them excellent candidates for the search for new types of biologically active compounds.

Abstract Background Bacteria and archaea produce an enormous diversity of modified peptides that are involved in various forms of inter-microbial conflicts or communication. A vast class of such peptides are Ribosomally synthesized, Postranslationally modified Peptides (RiPPs), and a major group of RiPPs are graspetides, so named after ATP-grasp ligases that catalyze the formation of lactam and lactone linkages in these peptides. The diversity of graspetides, the multiple proteins encoded in the respective Biosynthetic Gene Clusters (BGCs) and their evolution have not been studied in full detail. In this work, we attempt a comprehensive analysis of the graspetide-encoding BGCs and report a variety of novel graspetide groups as well as ancillary proteins implicated in graspetide biosynthesis and expression. Results We compiled a comprehensive, manually curated set of graspetides that includes 174 families including 115 new families with distinct patterns of amino acids implicated in macrocyclization and further modification, roughly tripling the known graspetide diversity. We derived signature motifs for the leader regions of graspetide precursors that could be used to facilitate graspetide prediction. Graspetide biosynthetic gene clusters and specific precursors were identified in bacterial divisions not previously known to encode RiPPs, in particular, the parasitic and symbiotic bacteria of the Candidate phyla radiation. We identified Bacteroides-specific biosynthetic gene clusters (BGC) that include remarkable diversity of graspetides encoded in the same loci which predicted to be modified by the same ATP-grasp ligase. We studied in details evolution of recently characterized chryseoviridin BGCs and showed that duplication and horizonal gene exchange both contribute to the diversification of the graspetides during evolution. Conclusions We demonstrate previously unsuspected diversity of graspetide sequences, even those associated with closely related ATP-grasp enzymes. Several previously unnoticed families of proteins associated with graspetide biosynthetic gene clusters are identified. The results of this work substantially expand the known diversity of RiPPs and can be harnessed to further advance approaches for their identification.