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Aim to analyze the indicators of distortion-product otoacoustic emissions (DPOAE) in persons exposed to the noise of small arms and, on the basis of the most significant of them, to determine the probability of developing hearing loss. Material and methods. We examined 30 male volunteer shooters (60 ears) aged from 19 to 30 years. The shooters fired 30 shots from the AK74M in short bursts (2-3 shots in a burst) at targets when performing shooting exercises from three positions: from the knee, standing and lying down, in a free acoustic field without the use of personal protective equipment of the hearing organ. All participants were examined for distortion-product otoacoustic emissions (DPOAE) before and after firing from small arms. The method of binary logistic regression was used to develop a predictive model. Results. A mathematical model has been developed to assess the probability of developing hearing loss according to the indicators of DPOAE before exposure to the noise of small arms. This model, with a standard classification threshold of p = 0.5, has an accuracy of 83.3%, sensitivity of 79.0%, specificity of 88.0%. According to the results of the ROC analysis for the resulting model, the area under the characteristic curve was equal to 0.924 (0.834;1.0), which indicates the excellent quality of the mathematical model. Conclusion. The most significant were the signal/noise indicator (dB) at a frequency of 4.2 kHz on the left and the level of otoacoustic emission (dB) at a frequency of 4.2 kHz on the left before noise exposure. These indicators, as well as the age of the shooter, allow us to assess the probability of developing hearing loss.

The phase velocity of a laser-driven wakefield can be efficiently controlled in a plasma channel. A beatwave of two long laser pulses is used. The frequency difference between these two laser pulses equals the local plasma frequency, so that the slow resonant excitation of the plasma wave is possible. Because the driver energy is spread over many plasma periods, the interference pattern can run with an arbitrary velocity along the channel and generate the wakefield with the same phase velocity. This velocity is defined by the channel radius and the structure of laser transverse modes excited in the channel. The wake velocity can be matched exactly to the witness velocity. This can be the vacuum speed of light for ultra-relativistic witnesses, or subluminal velocities for low-energy, weakly relativistic witnesses such as muons.

A synthetic route to 1,4,6,10-tetraazaadamantanes (TAADs) bearing free and protected amino groups at the bridge N-atoms has been developed via intramolecular cyclotrimerization of C=N units in the corresponding tris(hydrazonoalkyl)amines. In a similar fashion, unsymmetrically substituted TAADs having both amino and hydroxy groups at the bridge N-atoms were prepared via a hitherto unknown co-trimerization of oxime and hydrazone groups. The use of N-TAAD derivatives as potential ligands and receptors was showcased through forming boron chelates and host–guest complexes with water and simple alcohols.

To date, in domestic and foreign literature, there are more and more reports of the successful use of glucocorticosteroids for the treatment of pathology of the inner ear by local intratympanic administration. Many methods are being developed to deliver drugs to the structures of the inner ear. As you know, the systemic administration of glucocorticosteroids has a number of contraindications and a large number of side effects, due to a wide spectrum of action. Exogenous glucocorticoids disrupt the natural balance of the hypothalamic-pituitary-adrenal system, interfering with the negative feedback regulation system, which requires a long time to fully restore. The intratympanic method of administering glucocorticosteroids makes it possible to bypass the above undesirable effects and at the same time provide the desired therapeutic effect on the vestibular and cochlear structures of the inner ear. With regard to the effect on the structures of the inner ear, intratympanic use of glucocorticosteroids turned out to be more effective than the systemic one, which is associated with the presence of a hematoperilymphatic barrier, comparable in its permeability to the blood-brain barrier. Moreover, when administered systemically, large doses of steroids are required to achieve a sufficient concentration of the drug in the fluids of the inner ear. To date, many questions remain regarding the routes by which the drug penetrates to the structures of the inner ear, the principles of distribution of the drug within the cochlear fluids, as well as the anatomical obstacles that may be encountered on the way to achieving the desired therapeutic effect. The purpose of this article is to highlight the current achievements in the field of research on the routes of penetration of drugs, in particular glucocorticosteroids, to the structures of the inner ear from the tympanic cavity.

The article considers the terminology used while regulating employment relations in the bodies of the Investigative Committee of the Russian Federation. Attention is drawn to the fact that these relations have a significant specificity, which should be taken into account, but is not always taken into account when issuing departmental normative legal acts of the Investigative Committee of the Russian Federation. The article offers options of elimination of existing shortcomings in the use of terms «worker», «employee» in relation to the Investigative Committee of the Russian Federation. Purpose: to identify gaps in the legal regulation of employment relations in the Investigative Committee of the Russian Federation. Methods: the authors apply empirical methods of comparison, description, interpretation; theoretical methods of formal and dialectical logic; specific scientific methods: legal-dogmatic and interpretation of legal norms. Results: the study reveals the dual nature of employment relations in the Investigative Committee of the Russian Federation. The features of regulating the legal status of a staff member of the Investigative Committee of the Russian Federation and the content of his professional activities make it possible to identify gaps in the legal technique and legal language of the normative legal acts of the Investigative Committee of the Russian Federation.

The article describes various installation schemes for roofing structures and suspended ceilings using combined method for industrial buildings. The article inspects three installation options for assembling building elements: transversal motion of the crane across spans, working motion of the crane across the spans with idle returns, and installation spanwise. The advantages and disadvantages of each mounting option are also discussed. The article describes in detail methods of installing structural elements of a building, which allows the work to be completed with minimal labor costs. Schemes for installing coating structures and suspended ceilings using combined method are also considered.

Intelligent systems represent a new direction in the electrical power industry, and training students in this area requires appropriate updating of curricula and laboratory equipment. In this regard, it is necessary to create educational and research complexes in special disciplines to train specialists in intelligent electric power systems. This article presents an educational and research laboratory complex with elements of artificial intelligence for diagnosing the technical condition of equipment in electric power complexes. A free version of the IDE was used as an integrated development environment, which provides the basic functions and tools necessary for developing and debugging Python projects. The software part of the complex has been developed, including a digital twin of the laboratory installation, an executive part and a neural network model.

Serine-arginine (SR) protein kinase 1 (SRPK1) catalyzes the phosphorylation of SR proteins, which are a conserved family of splicing factors that contain a domain rich in arginine and serine repeats. SR proteins play important roles in constitutive pre-mRNA splicing and are also important regulators of alternative splicing. During herpes simplex virus infection, SRPK1 is inactivated and its cellular distribution is markedly altered by interaction with the viral protein ICP27, resulting in hypophosphorylation of SR proteins. Mutational analysis previously showed that the RGG box motif of ICP27 is required for interaction with SRPK1; however, the mechanism for the inhibition and the exact role of the RGG box was unknown. Here, we used solution nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC) to demonstrate that the isolated peptide comprising the RGG box of ICP27 binds to SRPK1 with high affinity, competing with a native substrate, the SR repeat region of SR protein SRSF1. We determined the crystal structure of the complex between SRPK1 and an RGG box peptide, which revealed that the viral peptide binds to the substrate docking groove, mimicking the interactions of SR repeats. Site-directed mutagenesis within the RGG box further confirmed the importance of selected arginine residues for interaction, relocalization, and inhibition of SRPK1 in vivo Together these data reveal the molecular mechanism of the competitive inhibition of cellular SRPK1 by viral ICP27, which modulates SRPK1 activity.IMPORTANCE Serine arginine (SR) proteins are a family of mRNA regulatory proteins that can modulate spliceosome association with different splice sites and therefore regulate alternative splicing. Phosphorylation within SR proteins is necessary for splice-site recognition, and this is catalyzed by SR protein kinase 1 (SRPK1). The herpes simplex virus (HSV-1) protein ICP27 has been shown previously to interact with and downregulate SRPK1 activity in vivo; however, the molecular mechanism for this interaction and inhibition was unknown. Here, we demonstrate that the isolated peptide fragment of ICP27 containing RGG box binds to SRPK1 with high affinity, and competes with a native cellular substrate. Elucidation of the SRPK1-RGG box crystal structure further showed that a short palindromic RGRRRGR sequence binds in the substrate docking groove of SRPK1, mimicking the binding of SR repeats of substrates. These data reveal how the viral protein ICP27 inactivates SRPK1, promoting hypophosphorylation of proteins regulating splicing.

Kaposi's sarcoma-associated herpesvirus (KSHV) transcribes a long noncoding polyadenylated nuclear (PAN) RNA, which promotes the latent to lytic transition by repressing host genes involved in antiviral responses as well as viral proteins that support the latent state. KSHV also expresses several early proteins including ORF57 (Mta), a member of the conserved multifunctional ICP27 protein family, which is essential for productive replication. ORF57/Mta interacts with PAN RNA via a region termed the Mta responsive element (MRE), stabilizing the transcript and supporting nuclear accumulation. Here, using a close homolog of KSHV ORF57 from herpesvirus saimiri (HVS), we determined the crystal structure of the globular domain in complex with a PAN RNA MRE, revealing a uracil specific binding site that is also conserved in KSHV. Using solution NMR, RNA binding was also mapped within the disordered N-terminal domain of KSHV ORF57, and showed specificity for an RNA fragment containing a GAAGRG motif previously known to bind a homologous region in HVS ORF57. Together these data located novel differential RNA recognition sites within neighboring domains of herpesvirus ORF57 homologs, and revealed high-resolution details of their interactions with PAN RNA, thus providing insight into interactions crucial to viral function.

In situ illumination of liquid-state NMR samples allows to characterise light-dependent chemical and biological phenomena, but, in practice, the position of an NMR sample deep within the bore of a spectrometer magnet renders such illumination challenging. Here, the authors demonstrate the working principles of a sample illumination device, with an LED array positioned directly at the top of special sample tube, which is inserted into the NMR spectrometer.

In the pandemic new coronavirus infection (COVID-19), different clinical symptoms are observed depending on its dominant strain. The Omicron strain affects the nasal mucosa, causing the possibility of complications such as tubootitis and acute otitis media. Untimely or incomplete treatment of otitis media can contribute to the development of chronic forms of the course. Inflammatory process in the middle ear always proceeds with impaired hearing function due to the development of adhesions in the tympanic cavity. In patients with a reduced immune status, weakened course of the coronavirus infection itself, recovery comes later with a long recovery of hearing acuity, so it is very important to start treatment at the first manifestations of pain in the ear. In addition, the danger of otitis media against the background of SARS-CoV-2, if not treated in time, is the development of serious complications – mastoiditis, meningeal syndrome. Local analgesic therapy in the form of analgesic ear drops is recommended to reduce inflammation of the eardrum tissues. The combination of phenazone and lidocaine allows you to quickly stop the pain, block the development of phases of inflammation in the middle ear. Using a combination of phenazone and lidocaine reduces the time of onset of the analgesic effect, while increasing the intensity and duration of action, which is very important, especially in children. These components are not resorbed and have no systemic effect on the patient’s body. The combination of phenazone and lidocaine can be used in the treatment of children of all age groups, adults, pregnant women and nursing mothers.

Protein liquid-liquid phase separation is an important phenomenon in biology. Here, the authors demonstrate an approach to characterize the evolution of protein phases in both time and space using a fluorinated probe molecule in NMR spectroscopy.

The paper presents datasets of plant species of two industrial cities Sterlitamak and Salavat (Republic of Bashkortostan) is presented. These cities are part of the Southern Bashkortostan urban agglomeration and are amongst the three largest in the Republic. The population of Sterlitamak is about 276,000. There are large oil refineries and other large industrial transport infrastructure facilities. Datasets are prepared on the basis of long-time field research by Ya. Golovanov (2008 - 2016). Technical preparation of the datasets was carried out by M. Lebedeva and M. Drap. The herbarium samples are stored in the herbarium collections of the South Ural Botanical Garden Institute and the Ufa Institute of Biology (UFA). The data paper describes three datasets on species occurrences. It presents occurrences of species in different types of habitats (anthropogenically transformed and semi-natural). The datasets consists of 5,462 occurrence records totally. Most of the records (5,359) are georeferenced.The total number of records in three datasets is 5,462. They contain of vascular plant species occurrences in the two industrial cities of the Southern Urals (Sterlitamak and Salavat). There are both alien and natural species occurrences in different types of habitats (antropogenically transformed and semi-natural).

The results of long-terms vegetation studies of the Kulan plateau, which is lo- cated in the Badhyz reserve in the southeastern Turkmenistan, are presented. The geographical position of the region and the diversity of landscapes pro- moted to the formation of the specific flora, represented by various groups of Mediterranean, Iranian, Turanian, as well as Middle and Central Asian species. Very specific ephemeroid plant communities with Poa bulbosa и Carex pachysty­ lis dominated in lower layer were syntaxonomically studied for the first time. The upper layer includes the tall herbs, especially Ferula badrakema, an endemic species of Badhyz. Communities were classified as the suballiance Poo bulbosae– Ferulenion badrakemii suball. nov. of the alliance Vulpio persicae–Caricion pachystylidis Świerszcz et al. 2020 of the order Cymbopogono–Brachypodietalia ramosi Horvatič 1963 of the class Lygeo sparti–Stipetea tenacissimae Rivas-Mart. 1978 nom. conserv. propos. Сommunities of grasses on slight turf sands are classified as part of the provisional alliance Stipagrostion pennati prov. The position of the alliance in the system of high-rank syntaxa has not yet been determined. The 5 new associa- tions and 6 subassociations were allocated.

The TREX complex mediates the passage of bulk cellular mRNA export to the nuclear export factor TAP/NXF1 via the export adaptors ALYREF or UIF, which appear to act in a redundant manner. TREX complex recruitment to nascent RNA is coupled with 5' capping, splicing and polyadenylation. Therefore to facilitate expression from their intronless genes, herpes viruses have evolved a mechanism to circumvent these cellular controls. Central to this process is a protein from the conserved ICP27 family, which binds viral transcripts and cellular TREX complex components including ALYREF. Here we have identified a novel interaction between HSV-1 ICP27 and an N-terminal domain of UIF in vivo, and used NMR spectroscopy to locate the UIF binding site within an intrinsically disordered region of ICP27. We also characterized the interaction sites of the ICP27 homolog ORF57 from KSHV with UIF and ALYREF using NMR, revealing previously unidentified binding motifs. In both ORF57 and ICP27 the interaction sites for ALYREF and UIF partially overlap, suggestive of mutually exclusive binding. The data provide a map of the binding sites responsible for promoting herpes virus mRNA export, enabling future studies to accurately probe these interactions and reveal the functional consequences for UIF and ALYREF redundancy.

The UL69 protein from human cytomegalovirus (HCMV) is a multifunctional regulatory protein and a member of the ICP27 protein family conserved throughout herpesviruses. UL69 plays many roles during productive infection, including the regulation of viral gene expression, nuclear export of intronless viral RNAs, and control of host cell cycle progression. Throughout the ICP27 protein family, an ability to self-associate is correlated with the functions of these proteins in transactivating certain viral genes. Here, we determined the domain boundaries of a globular ICP27 homology domain of UL69, which mediates self-association, and characterized the oligomeric state of the isolated domain. Size exclusion chromatography coupled with multiangle light scattering (SEC-MALS) revealed that residues 200 to 540 form a stable homo-tetramer, whereas a shorter region comprising residues 248 to 536 forms a homo-dimer. Structural analysis of the UL69 tetramer by transmission electron microscopy (TEM) revealed a dimer-of-dimers three-dimensional envelope with bridge features likely from a region of the protein unique to betaherpesviruses. The data provide a structural template for tetramerization and improve our understanding of the structural diversity and features necessary for self-association within UL69 and the ICP27 family.IMPORTANCE Human cytomegalovirus (HCMV) infection is widespread in the human population but typically remains dormant in an asymptomatic latent state. HCMV causes disease in neonates and adults with suppressed or impaired immune function, as the virus is activated into a lytic state. All species of herpesvirus express a protein from the ICP27 family which functions as a posttranscriptional activator in the lytic state. In HCMV, this protein is called UL69. The region of sequence conservation in the ICP27 family is a folded domain that mediates protein interactions, including self-association and functions in transactivation. All members thus far analyzed homo-dimerize, with the exception of UL69, which forms higher-order oligomers. Here, we use biochemical and structural data to reveal that UL69 forms stable tetramers composed of a dimer of dimers and determine a region essential for cross-dimer stabilization.

AbstractCretaceous massifs of the Eurasian continent are unique not only for their geological features but also for the peculiar flora. Therefore, the identification and study of the biodiversity of these unique objects is currently an actual task. Comprehensive studies of the flora and vegetation of the Aktolagay cretaceous massif (Republic of Kazakhstan) were carried out in 2019. One of the study aspects was the consideration of the ecological and biological features of several plant species typical for this territory. The research is devoted to the study of five plant species: Astragalus lasiophyllus Lеdеb., Astragalus vulpinus Willd., Matthiola tatarica (Pall.) DC., Eremurus inderiensis (M. Bieb.) Regel, Tragopogon ruber S.G. Gmel. The coenopopulations (CP) of the species are located in the lower parts of the slopes, as well as in aligned areas at the foot on cretaceous substrates, and on sandstone soils. The total density of the studied CPs varies from 2.2 to 6.6 ind./m2, the effective density varies from 1.6 to 4.9 ind./m2. The studied coenopopulations belong to normal incomplete ones. The most typical feature is the absence of seedlings, juvenile and senile individuals in the spectrum, while the peak falls on mature generative individuals, in the Mattiolla tatarica coenopopulations – on virginile individuals. Coenopopulations differ in their type ("delta-omega" criterion): the Matthiola tatarica one is young, the CP of Astragalus lasiophyllus is transitional, the CPs of Astragalus vulpinus and Eremurus inderiensis are maturing, and the CP of Tragogon ruber is mature. The recruitment index is high in the CP of Matthiola tatarica (3.05), in the rest of the CPs it is not higher than one (0.36-0.82), the ageing index is equal or close to zero (0.00–0.10). Most morphometric features show the low levels of variability and plasticity.

Mammalian 15-lipoxygenases (ALOX15) are lipid peroxidizing enzymes that exhibit variable functionality in different cancer and inflammation models. The pathophysiological role of linoleic acid- and arachidonic acid-derived ALOX15 metabolites rendered this enzyme a target for pharmacological research. Several indole and imidazole derivatives inhibit the catalytic activity of rabbit ALOX15 in a substrate-specific manner, but the molecular basis for this allosteric inhibition remains unclear. Here, we attempt to define a common pharmacophore, which is critical for this allosteric inhibition. We found that substituted imidazoles induce weaker inhibitory effects when compared with the indole derivatives. In silico docking studies and molecular dynamics simulations using a dimeric allosteric enzyme model, in which the inhibitor occupies the substrate-binding pocket of one monomer, whereas the substrate fatty acid is bound at the catalytic center of another monomer within the ALOX15 dimer, indicated that chemical modification of the core pharmacophore alters the enzyme–inhibitor interactions, inducing a reduced inhibitory potency. In our dimeric ALOX15 model, the structural differences induced by inhibitor binding are translated to the hydrophobic dimerization cluster and affect the structures of enzyme–substrate complexes. These data are of particular importance since substrate-specific inhibition may contribute to elucidation of the putative roles of ALOX15 metabolites derived from different polyunsaturated fatty acids in mammalian pathophysiology.