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Abstract Purines and their derivatives control intracellular energy homeostasis and nucleotide synthesis, and act as signaling molecules. Here, we combine structural and sequence information to define a purine-binding motif that is present in sensor domains of thousands of bacterial receptors that modulate motility, gene expression, metabolism, and second-messenger turnover. Microcalorimetric titrations of selected sensor domains validate their ability to specifically bind purine derivatives, and evolutionary analyses indicate that purine sensors share a common ancestor with amino-acid receptors. Furthermore, we provide experimental evidence of physiological relevance of purine sensing in a second-messenger signaling system that modulates c-di-GMP levels.

ABSTRACT Bacteria sense changes in their environment and transduce signals to adjust their cellular functions accordingly. For this purpose, bacteria employ various sensors feeding into multiple signal transduction pathways. Signal recognition by bacterial sensors is studied mainly in a few model organisms, but advances in genome sequencing and analysis offer new ways of exploring the sensory repertoire of many understudied organisms. The human gut is a natural target of this line of study: it is a nutrient-rich and dynamic environment and is home to thousands of bacterial species whose activities impact human health. Many gut commensals are also poorly studied compared to model organisms and are mainly known through their genome sequences. To begin exploring the signals human gut commensals sense and respond to, we have designed a framework that enables the identification of sensory domains, prediction of signals that they recognize, and experimental verification of these predictions. We validate this framework’s functionality by systematically identifying amino acid sensors in selected bacterial genomes and metagenomes, characterizing their amino acid binding properties, and demonstrating their signal transduction potential.IMPORTANCESignal transduction is a central process governing how bacteria sense and respond to their environment. The human gut is a complex environment with many living organisms and fluctuating streams of nutrients. One gut inhabitant, Escherichia coli, is a model organism for studying signal transduction. However, E. coli is not representative of most gut microbes, and signaling pathways in the thousands of other organisms comprising the human gut microbiota remain poorly understood. This work provides a foundation for how to explore signals recognized by these organisms.

THE PURPOSE. The purpose of this work was to use the associated paradigm for a correct quantum-chemical description of non-catalytic and catalytic supercritical fluid processes of transesterification of triglycerides with alcohols and hydrolysis of triglycerides and to model a one-stage process for obtaining biodiesel fuel, carried out under supercritical fluid conditions with its subsequent scaling to the commercial level.METHODS. The Gaussian09 software product was used to describe quantum chemical studies. The process modeling was carried out using the ASPEN Plus® v2006 software product. The behavior of thermodynamic systems at high temperatures and pressures is modeled using "RK ASPEN EOS". For modeling processes carried out at low pressures, mathematical models UNIQUAC and UNIFAC-LL were used. The scaling of the process was carried out in the VMGSim program.RESULTS. The third part of the review focuses on the quantum-chemical modeling of the transesterification reaction carried out under supercritical fluid conditions. It is shown that taking into account the associative paradigm makes it possible to obtain calculated reaction rate constants that agree in order with the experimental values. And also an analysis was carried out and the results of modeling the process of obtaining biodiesel fuel and scaling it to a commercial level, with a capacity of up to 9000 tons / year, were presented.CONCLUSION. The conducted analysis showed that biodiesel fuel can be a competitive fuel in our and the world market.

ABSTRACTIn this hybrid review, we have first collected and reviewed available information on the structure and function of the enigmatic cache domains in α2δ proteins. These are organized into two double cache (dCache_1) domains, and they are present in all α2δ proteins. We have also included new data on the key function of these domains with respect to amino acid and gabapentinoid binding to the universal amino acid–binding pocket, which is present in α2δ-1 and α2δ-2. We have now identified the reason why α2δ-3 and α2δ-4 do not bind gabapentinoid drugs or amino acids with bulky side chains. In relation to this, we have determined that the bulky amino acids Tryptophan and Phenylalanine prevent gabapentin from inhibiting cell surface trafficking of α2δ-1. Together, these novel data shed further light on the importance of the cache domains in α2δ proteins.

THE PURPOSE. The purpose of the work was to systematize the results of the work of domestic and foreign authors on the thermophysical properties of media and substances involved in the process of obtaining biodiesel fuel. METHODS. To measure the isobaric heat capacity, the predominant use is given to the methods of heat-conducting and scanning calorimeters, the measurement of the thermal conductivity by the heated filament method. Kinematic and dynamic viscosities are measured, respectively, on standard glass viscometers at atmospheric pressure and by the drop weight method. RESULTS. The results of a study of a wide range of thermophysical properties of thermodynamic systems involved in the process of obtaining biodiesel fuel under supercritical fluid conditions are presented. Attention is paid to the density, isobaric heat capacity, thermal conductivity, dynamic and kinematic viscosity of both the feedstock and the resulting biodiesel fuel, presented in a wide range of temperature and pressure changes, including nearcritical, as well as taking into account the thermal effects caused by the dissolution and change in the structures of substances under the influence of fluid reagent. CONCLUSION. The presented data will be necessary at the stages of designing and scaling a particular technology for the production of biodiesel fuel, both on a laboratory scale and at an industrial level.

The COVID-19 epidemic is being revealed from a new angle every month. In particular, with the appearance of the delta strain, mucormycosis began to manifest in some patients, which had previously been extremely rare. Mucormycosis is a rare, aggressive infection caused by filamentous fungi of the Mucorales family and associated with high morbidity and mortality rates. The main risk factors for the mucormycosis in patients with COVID-19 are diabetes mellitus and diabetic ketoacidosis, uncontrolled hyperglycemia and massive use of glucocorticoids, vascular damage, thrombosis, lymphopenia, which often occur against the background of COVID-19 and make a person vulnerable to secondary or opportunistic fungal infection. We present a clinical case of mucormycosis in a 21-year-old female patient with COVID-19-associated severe pneumonia and concomitant type I diabetes mellitus. The patient was hospitalized and received standard therapy during inpatient treatment, including glucocorticosteroids in accordance with the severity of the course of COVID-19. On the 12th day from the hospitalization, the patient's condition deteriorated significantly, and the visible changes in the skin and soft tissues of the face, characteristic of mucormycosis appeared. Despite the drug therapy correction, the patient died because of the acute respiratory failure in combination with septic fungal damage of the brain stem.

THE PURPOSE. The presented work aims to analyze the realities and prospects for the use of working media in the production of biodiesel fuel, including the supercritical fluid state. METHODS. Methods for obtaining biodiesel fuel are considered, including the method of transesterification, as the most common, as well as methods of pyrolysis and the combined process of hydrolysis and esterification. RESULTS. Traditional (industrially used methods for producing biodiesel fuel), as well as methods involving supercritical fluid media at their core, are considered. Along with a description of the state of affairs on the issues under discussion in the world, the results of our own research carried out by the team of authors of this article are also presented. Attention is drawn to the prospects of ultrasonic emulsification of the reaction mixture and the use of heterogeneous catalysts in order to mitigate supercritical fluid conditions for the process of obtaining biodiesel fuel and save energy. The conditions for obtaining biodiesel fuel without free glycerol and converting it into a fuel component are also discussed. CONCLUSION. Transesterification carried out under supercritical fluid conditions provides significant advantages over the traditional process and, especially in terms of the possibility of using a variety of raw materials, including low-quality ones, facilitates the procedure for isolating the final product and, finally, makes it possible to switch from relatively small-scale implementations with batch reactors to high-performance plants with flow reactors.

Islamic education in the Samara region at the turn of the 19th–20th centuries began to change gradually: from the existence of the Kadimist (old-fashioned) system to the appearance of the Jadid (new-fashioned). This article highlights the most significant Jadid educational institutions of the Volga-Ural region, thanks to which it became possible to develop religious schools of a new format in the Samara province. The work is written on the basis of unpublished archival data contained in the archives of the Samara Provincial Government, the Samara Governor of the Central State Archive of the Samara region. The dynamics of the emergence and development of Jadid schools since the late 19th – early 20th centuries is analyzed in connection with the sources of their financing in the territory of the Samara Region. At the beginning of the 20th century, the growth in the number of new-fangled institutions in the province became especially noticeable, their appearance was dictated, among other things, by the changed financial situation in the Muslim communities of the Volga-Ural region – the appearance of a layer of bourgeois ready to invest in the activities of educational institutions of a new format. This study confirms that the main source of funding for both Kadimist and Jadid educational institutions in Samara province were donations from parishioners and individual major benefactors, which proves the existence of divergent ideological approaches to the question of the place and role of religious education in the development of the Ummah among Volga-Ural Muslims in the period under study.

ABSTRACT To adapt and proliferate, bacteria must sense and respond to the ever-changing environment. Transmembrane transcription regulators (TTRs) are a family of one-component transcription regulators that respond to extracellular information and influence gene expression from the cytoplasmic membrane. How TTRs function to modulate expression of their target genes while localized to the cytoplasmic membrane remains poorly understood. In part, this is due to a lack of knowledge regarding the prevalence of TTRs among prokaryotes. Here, we show that TTRs are highly diverse and prevalent throughout bacteria and archaea. Our work demonstrates that TTRs are more common than previously appreciated and are enriched within specific bacterial and archaeal phyla and that many TTRs have unique transmembrane region properties that can facilitate association with detergent-resistant membranes. IMPORTANCE One-component signal transduction systems are the major class of signal transduction systems among bacteria and are commonly cytoplasmic. TTRs are a group of unique one-component signal transduction systems that influence transcription from the cytoplasmic membrane. TTRs have been implicated in a wide array of biological pathways critical for both pathogens and human commensal organisms but were considered to be rare. Here, we demonstrate that TTRs are in fact highly diverse and broadly distributed in bacteria and archaea. Our findings suggest that transcription factors can access the chromosome and influence transcription from the membrane in both archaea and bacteria. This study challenges thus the commonly held notion that signal transduction systems require a cytoplasmic transcription factor and highlights the importance of the cytoplasmic membrane in directly influencing signal transduction.

IntroductionCardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting.MethodsTo investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole (n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period.ResultsWhile no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = −3.33 (0.60), P < 0.001 and dipyridamole: B = −3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = −2.69 (0.74), P < 0.001 and dipyridamole: B = −17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [B−3.12 (1.42), P = 0.012] and stroke [B = −3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [B = −17.05 (1.01), P < 0.001].ConclusionLate cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.

ABSTRACT Maintaining cell envelope integrity is of vital importance for all microorganisms. Not surprisingly, evolution has shaped conserved protein protection networks that connect stress perception, transmembrane signal transduction, and mediation of cellular responses upon cell envelope stress. The phage shock protein (Psp) stress response is one such conserved protection network. Most knowledge about the Psp response derives from studies in the Gram-negative model bacterium Escherichia coli, where the Psp system consists of several well-defined protein components. Homologous systems were identified in representatives of the Proteobacteria, Actinobacteria, and Firmicutes. However, the Psp system distribution in the microbial world remains largely unknown. By carrying out a large-scale, unbiased comparative genomics analysis, we found components of the Psp system in many bacterial and archaeal phyla and describe that the predicted Psp systems deviate dramatically from the known prototypes. The core proteins PspA and PspC have been integrated into various (often phylum-specifically) conserved protein networks during evolution. Based on protein domain-based and gene neighborhood analyses of pspA and pspC homologs, we built a natural classification system for Psp networks in bacteria and archaea. We validate our approach by performing a comprehensive in vivo protein interaction study of Psp domains identified in the Gram-positive model organism Bacillus subtilis and found a strong interconnected protein network. Our study highlights the diversity of Psp domain organizations and potentially diverse functions across the plethora of the microbial landscape, thus laying the ground for studies beyond known Psp functions in underrepresented organisms. IMPORTANCE The PspA protein domain is found in all domains of life, highlighting its central role in Psp networks. To date, all insights into the core functions of Psp responses derive mainly from protein network blueprints representing only three bacterial phyla. Despite large overlaps in function and regulation, the evolutionary diversity of Psp networks remains largely elusive. Here, we present an unbiased protein domain- and genomic context-centered approach that describes and classifies Psp systems. Our results suggest so-far-unknown Psp-associated roles with other protein networks giving rise to new functions. We demonstrate the applicability of our approach by dissecting the Psp protein network present in Bacillus subtilis and demonstrate Psp domains working in concert with other cell envelope stress response systems. We find that the Psp-like protein universe reflects a surprising diversity within the bacterial and archaeal microbial world.

The coronavirus disease 2019 (COVID-19) pandemic is associated with high virulence, mortality and healthcare burden around the world. One of its features is procoagulant activity, which leads to a high incidence of thromboembolic events in the lungs and other organs. Therefore, from the very onset of the moderate COVID-19, low molecular weight heparins began to be used as anticoagulants, which proved to have a beneficial effect on mortality and the disease course and were included in all guidelines. However, the question on anticoagulant therapy need after discharge from the hospital is controversial. The opinions of various medical professional communities on this issue are divided. In particular, some of them, including the Russian Ministry of Health guidelines recommend 30-45day anticoagulation using novel oral anticoagulants (dabigatran, rivaroxaban, apixaban), but other sources do not provide such recommendations. This review discusses the effectiveness of anticoagulant therapy after COVID-19, as well as the need to use stratification scales to assess this therapy.

The coronavirus disease 2019 (COVID-19) affects not only the respiratory system, but also the cardiovascular system in 20-28% of cases, causing endothelial dysfunction, vasculitis, hyper- and hypocoagulation, myocarditis, endothelial dysfunction and other adverse effects. The presence of cardiovascular risk factors and diseases has been shown to worsen the disease severity and increase mortality from COVID-19. Recent studies have also found that elevations in some serum cardiovascular biomarkers can stratify the disease severity, in particular rates of hospitalizations to an internal medicine or intensive care unit, intubation, and mortality. They can be divided into markers of damage (TnT/I, creatine phosphokinase (CPK) and CPK-MB, myoglobin, NT-proBNP), coagulation (prothrombin time, fibrinogen and D-dimer), as well as prospective biomarkers for which the available evidence base is limited but there is a pathophysiological rationale (homocysteine and sST2). This review presents studies on the use of above serum biomarkers to stratify the risk of death in patients with COVID-19.

In this paper, we present the results of dispersion of thermodynamically immiscible polypropylene (PP) and ethylene-propylene triple synthetic rubber (EPTSR) polymer blends using the Solution-Enhanced Dispersion by Supercritical Fluid (SEDS) technique at operation conditions in the pressure range of (8 to 25) MPa and at temperatures t = 40 °C and 60 °C. The kinetics of crystallization and phase transformation in polymer blends obtained by conventional method (melt blending) and by mixing in the SEDS process have been studied using the DSC technique. The effects of the SEDS operation process on the physical—chemical (melting temperature, heat of fusion) and mechanical (microparticle size) characteristics of the SEDS-produced polymer blends were studied.

The classic Osborn wave in the form of characteristic changes at the depolarization end or ventricular repolarization beginning is more often associated with hypothermia (body temperature below 35,6° C). Some researchers have noticed Osborn wave at normal body temperature, various pathological conditions and diseases: hypercalcemia, myocardial ischemia, postoperative pericarditis, with central nervous system, etc. We presented a case report of a 72-year-old female inpatient with moderate COVID-19, confirmed by polymerase chain reaction, and 48% lung damage. Before admission to the hospital, electrocardiogram had no Osborn wave, which first appeared at admission. There was a significant increase in serum C-reactive protein and a moderate increase in serum biomarkers and no changes in intervals and segments on the electrocardiogram. The appearance of Osborn wave may be associated with intramyocardial electrolyte imbalance, a consequence of antiviral and antibacterial therapy that violate intraventricular conduction.

ABSTRACT The only universally conserved family of transcription factors comprises housekeeping regulators and their specialized paralogs, represented by well-studied NusG and RfaH. Despite their ubiquity, little information is available on the evolutionary origins, functions, and gene targets of the NusG family members. We built a hidden Markov model profile of RfaH and identified its homologs in sequenced genomes. While NusG is widespread among bacterial phyla and coresides with genes encoding RNA polymerase and ribosome in all except extremely reduced genomes, RfaH is mostly limited to Proteobacteria and lacks common gene neighbors. RfaH activates only a few xenogeneic operons that are otherwise silenced by NusG and Rho. Phylogenetic reconstructions reveal extensive duplications and horizontal transfer of rfaH genes, including those borne by plasmids, and the molecular evolution pathway of RfaH, from “early” exclusion of the Rho terminator and tightened RNA polymerase binding to “late” interactions with the ops DNA element and autoinhibition, which together define the RfaH regulon. Remarkably, NusG is not only ubiquitous in Bacteria but also common in plants, where it likely modulates the transcription of plastid genes. IMPORTANCE In all domains of life, NusG-like proteins make contacts similar to those of RNA polymerase and promote pause-free transcription yet may play different roles, defined by their divergent interactions with nucleic acids and accessory proteins, in the same cell. This duality is illustrated by Escherichia coli NusG and RfaH, which silence and activate xenogenes, respectively. We combined sequence analysis and recent functional and structural insights to envision the evolutionary transformation of NusG, a core regulator that we show is present in all cells using bacterial RNA polymerase, into a virulence factor, RfaH. Our results suggest a stepwise conversion of a NusG duplicate copy into a sequence-specific regulator which excludes NusG from its targets but does not compromise the regulation of housekeeping genes. We find that gene duplication and lateral transfer give rise to a surprising diversity within the only ubiquitous family of transcription factors.

ABSTRACT Chemoreceptor-based signaling pathways are among the major modes of bacterial signal transduction, and Pseudomonas aeruginosa PAO1 is an important model to study their function. Of the 26 chemoreceptors of this strain, PctA has a broad ligand range and responds to most of the proteinogenic amino acids, whereas PctB and PctC have a much narrower range and show strong ligand preference for l-glutamine and γ-aminobutyrate, respectively. Using several comparative genomics approaches, we show that these receptors are paralogs: pctA gene duplication in the common ancestor of the genus Pseudomonas led to pctC, whereas pctB originated through another, independent pctA duplication in the common ancestor of P. aeruginosa. Thus, the broad-range amino acid chemoreceptor was evolutionarily older, and chemoreceptors that complemented “missing” amino acid sensing abilities arose later in specific Pseudomonas lineages. Using comparative sequence analysis, newly solved crystal structures of PctA, PctB, and PctC ligand-binding domains, and their molecular dynamics simulations, we identified a conserved amino acid recognition motif and changes in the ligand-binding pocket that led to novel ligand specificities. In addition, we determined major forces driving the evolution of this group of chemoreceptors. IMPORTANCE Many bacteria possess a large number of chemoreceptors that recognize a variety of different compounds. More than 60% of the genomes analyzed in this study contain paralogous chemoreceptors, suggesting that they emerge with high frequency. We provide first insight on how paralogous receptors have evolved and show that two chemoreceptors with a narrow ligand range have evolved from an ancestral protein with a broad chemoeffector spectrum. Protein structures show that multiple changes in the ligand-binding site account for the differences in the ligand spectrum. This work lays the ground for further studies aimed at establishing whether the principles of ligand-binding evolution reported here can be generalized for a wider spectrum of sensory proteins in bacteria.

The article considers a model of supercritical СО2 ‒ extraction technology of ethylene oxide emission from its aqueous solution, which is proposed to replace energy consuming desorption process. The possibility of using normal alkanes as modifiers of the main extractant is considered. A comparative analysis of the energy consumption ofsupercritical and traditional technologies is carried out.Methods. The Hysys program was used to model the processes.Results.Was simmulated the extraction process of ethylene oxide separation from its aqueous solution using as an extractant pure and modified with propane, n-butane, n-pentane supercritical carbon dioxide supplemented with further purification and concentration of the desired product.The results indicate the inappropriateness of using n-butane and n-pentane as an additive to carbon dioxide. Comparison of three technological schemes (traditional and two extraction schemes with pure and modified carbon dioxide) shows that the energy consumption for heating the rectification columns is significantly lower in the case of SC-CO2 extraction technologies (115 MW ‒ traditional technology, 36 and 79 MW for SC ‒ CO2 extraction technology without additives and with the addition of propane, respectively), while the combined capacities of pumps and compressors were the least for traditional technology. But, since the degree of extraction of ethylene oxide in the extraction scheme with the addition of propane turned out to be practically equal to unity (0.996), the considered energy indices, referred to the kilogram of the product obtained, turned out to be the best for this scheme.

Supercritical fluid extraction regeneration of the ion-exchange KU-2FPP catalyst is investigated. Results of change of mass of the catalyst are presented during regeneration at T = 383-393 K and P = 15-25 MPa and IR spectrums of chloroformic extracts of the studied catalyst samples. Results of the conducted researches allow to draw a conclusion on effective removal of polar and unpolar organic compounds. However the collateral reaction connected with emergence of dialkylphthalate is a probable cause of inefficiency of regeneration process with participation of SC-CO2 as the extractant. And use supercritical propane - butane mix (T = 393 K, P = 10-15 MPa) as the supercritical extractant allows to restore activity of the catalyst to the level meeting the requirements of industrial use.

An experimental study of the process of obtaining biodiesel fuel by reaction of transesterification of rapeseed oil in an ethanol medium in supercritical fluid conditions in the temperature range 623 - 653 K, pressure 30 MPa, molar ratios "ethyl alcohol-rapeseed oil" 12: 1, 18: 1. The influence of heterogeneous catalysts on the amount of product obtained is established.

The paper represents the results of implementation of liquid and supercritical fluid extraction processes in order to extract oil-products from oil sludge. A mixture consisting of propane (75 wt%) and butane (25 wt%) has been applied as the extractant. Initial oil sludge is characterized by the absence of water and content of solids in an amount of 12.05% by weight. The extraction processes have been conducted in a temperature range of85-160°C and pressure range of 5-50 MPa.

The results of experimental studies of solubility of TNT in pure and modified supercritical carbon dioxide (SC-CO2) are presented. Studies were carried out in a temperature range of 308.15-333.15 K and pressure interval 10.0-35.0 MPa on circulating type supercritical fluid extraction plant, R-401 produced by "Reaction Engineering Ink. " (South Korea). Experimental solubility data was described using the Peng-Robinson equation of state. The results of SC-CO2 - extraction of TNT from samples of hard burning materials and the efficiency of this process are shown.

Amphiphilic poly(dimethylsiloxane-ethylene-propylene oxide)-polyisocyanurate cross-linked block copolymers based on triblock copolymers of propylene and ethylene oxides with terminal potassium-alcoholate groups (PPEG), octamethylcyclotetrasiloxane (D4) and 2,4-toluene diisocyanate (TDI) were synthesized and investigated. In the first stage of the polymerization process, a multiblock copolymer (MBC) was previously synthesized by polyaddition of D4 to PPEG. The usage of the amphiphilic branched silica derivatives associated with oligomeric medium (ASiP) leads to the structuring of block copolymers via the transetherification reaction of the terminal silanol groups of MBC with ASiP. The molar ratio of PPEG, D4, and TDI, where the polymer chains are packed in the “core-shell” supramolecular structure with microphase separation of the polyoxyethylene, polyoxypropylene and polydimethylsiloxane segments as the shell, was established. Polyisocyanurates build the “core” of the described macromolecular structure. The obtained polymers were studied as membrane materials for the separation of gas mixtures CO2/CH4 and CO2/N2. It was found that obtained polymers are promising as highly selective and productive membrane materials for the separation of gas mixtures containing CO2, CH4 and N2.