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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.

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.

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 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 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 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 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).

Error-related potentials (ErrPs) have attracted attention in part because of their practical potential for building brain-computer interface (BCI) paradigms. BCIs, facilitating direct communication between the brain and machines, hold great promise for brain-AI interaction. Therefore, a comprehensive understanding of ErrPs is crucial to ensure reliable BCI outcomes. In this study, we investigated ErrPs in the context of the “guess what I am thinking” paradigm. 23 healthy participants were instructed to imagine an object from a predetermined set, while an algorithm randomly selected another object that was either the same as or different from the imagined object. We recorded and analyzed the participants’ EEG activity to capture their mental responses to the algorithm’s “predictions”. The study identified components distinguishing correct from incorrect responses. It discusses their nature and how they differ from ErrPs extensively studied in other BCI paradigms. We observed pronounced variations in the shape of ErrPs across different stimulus sets, underscoring the significant influence of visual stimulus appearance on ErrP peaks. These findings have implications for designing effective BCI systems, especially considering the less conventional BCI paradigm employed. They emphasize the necessity of accounting for stimulus factors in BCI development. [ABSTRACT FROM AUTHOR]

Pure single crystal diamond is a superior material for electronic, quantum, and detection applications. The state-of-the-art level of background concentrations of boron and nitrogen in such diamonds is about 1 ppb, which is quite close to the detection limit of the best chemical analysis techniques. In this work, we show that the boron concentration of ∼0.1 ppb causes conductivity of ∼5 kΩ cm of the single crystal diamond if the nitrogen concentration is lower. In such a case, the temperature dependent Hall effect measurement provides ∼100 times better detection limit for the concentration of the impurities in diamond compared to the conventional optical techniques. As a result, we have found the background concentrations of boron and nitrogen at the level of 0.07 and 0.02 ppb, respectively. This fact leads to a conclusion that growth of the insulating diamond is possible only when the nitrogen concentration is higher than the boron concentration. [ABSTRACT FROM AUTHOR]

For the first time, we have prepared non-aggregating phthalocyanine cobalt complexes as a set of resolved positional isomers. These compounds comprise a unique test bed for the structure–properties studies, as their optical and electrochemical properties are influenced by the planarity of the phthalocyanine macrocycle, which can be controlled by the positional isomerism of the bulky aromatic substituents at the α-phthalo sites. We support our conclusions with molecular modelling studies, which show a perfect match between the calculated and experimentally determined spectral/electrochemical values. We challenge a common perception that the NMR spectra of cobalt phthalocyanines cannot be measured due to the paramagnetic nature of Co(II). We suggest instead that the key factors affecting the NMR spectral resolution are molecular aggregation and π–π stacking. These interactions are suppressed by the bulky peripheral substituents on the cobalt phthalocyanines prepared, making these isomeric compounds an excellent tool for paramagnetic NMR studies. [ABSTRACT FROM AUTHOR]

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.

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.

The paper provides initial materials characterizing the complicated history of formation, natural soils and lithological-geomorphological conditions of the Jizzakh steppe before the beginning of reclamation development. It is shown that on the basis of soil-lithological and geomorphological zoning, the Jizzakh steppe is divided into a number of natural regions belonging to different levels (altitude levels) of the piedmont plain. In total, 22 districts have been identified within the Jizzakh steppe, including the foothill margins. On the piedmont plain itself, the regions are combined into two high-altitude levels: the upper step and the lower step or blanket zone. These two levels differ sharply in terms of drainage conditions and soil salinity. The upper level, covering the upper and middle parts of the alluvial fan, the high interconal Zaamin-Sanzar plain and the Lomakino plateau, is characterized by a weak manifestation of salinity due to relatively good drainage, except for the sloping depressions of the Lomakino plateau. In contrast to the upper level, the lower level, located in the blanket zone of the piedmont plain, is characterized by active natural salinization because of the poor drainage. The saline sediments of the Zaamin cone delta are characterized by the greatest thickness. To a lesser extent, the rocks of the Sanzar cone delta, which are drained by deep gullies, are salinized. The Khavast sloping plain is characterized by a strongly saline upper two-meter layer, with salt and gypsum content decreasing with depth. Thus, it is shown that high salinity and gypsum bearing rocks, as well as high groundwater salinity of the cone delta zone are the source of modern salt accumulation in soils of foothill Golodnostepskaya plain, as well as in soils of the cone delta zone of Djizak steppe.