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In this study, adults naïve to organic chemistry drew stereoisomers of molecules and explained their drawings. From these explanations, we identified nine strategies that participants expressed during those explanations. Five of the nine strategies referred to properties of the molecule that were explanatorily "irrelevant" to solving the problem; the remaining four referred to properties that were explanatorily "relevant" to the solution. For each problem, we tallied which of the nine strategies were expressed within the explanation for that problem and determined whether the strategy was expressed in speech only, gesture only, or in both speech and gesture within the explanation. After these explanations, all participants watched the experimenter deliver a 2-minute training module on stereoisomers. Following the training, participants repeated the drawing + explanation task on six new problems. The number of relevant strategies that participants expressed in speech (alone or with gesture) before training did "not" predict their post-training scores. However, the number of relevant strategies participants expressed "in gesture only" before training "did" predict their post-training scores. Conveying relevant information about stereoisomers uniquely in gesture prior to a brief training is thus a good index of who is most likely to learn from the training. We suggest that gesture reveals explanatorily relevant implicit knowledge that reflects (and perhaps even promotes) acquisition of new understanding.

The expanded newborn screening (NBS) program in the Russian Federation was initiated in 2023, among which severe combined immunodeficiency (SCID) is screened using TREC/KREC assays. Here, we report a rare case of a TP63-associated disease identified through this NBS program. Dried blood spots from newborns were initially screened for TREC/KREC levels, and those with values below the cut-off underwent confirmatory testing and further genetic analysis, including whole-exome sequencing (WES). A male newborn was identified with significantly reduced TREC values, indicative of T cell lymphopenia. Genetic analysis revealed a heterozygous NM_003722.5:c.1027C>T variant in TP63, leading to the p.(Arg343Trp) substitution within the DNA binding domain. This mutation has been previously associated with Ectrodactyly–Ectodermal Dysplasia–Cleft lip/palate syndrome (EEC) syndrome and shown to reduce the transactivation activity of TP63 in a dominant-negative manner. This case represents one of the few instances of immune system involvement in a patient with a TP63 mutation, highlighting the need for further investigation into the immunological aspects of TP63-associated disorders. Our findings suggest that comprehensive immunological evaluation should be considered for patients with TP63 mutations to better understand and manage potential immune dysfunctions.

Recently, cellulose and other biomass nanofibers (NFs) have been increasingly utilized in the design of sustainable materials for environmental, biomedical, and other applications. However, the past literature lacks a comparison of the macromolecular and nanofibrous states of biopolymers in various materials, and the advantages and limitations of using nanofibers (NF) instead of conventional polymers are poorly understood. To address this question, hydrogels based on interpolyelectrolyte complexes (IPECs) between carboxymethyl cellulose nanofibers (CMCNFs) and chitosan (CS) were prepared by ele+ctrostatic cross-linking and compared with the hydrogels of carboxymethyl cellulose (CMC) and CS biopolymers. The presence of the rigid CMCNF altered the mechanism of the IPEC assembly and drastically affected the structure of IPEC hydrogels. The swelling ratios of CMCNF-CS hydrogels of ca. 40% were notably lower than the ca. 100–300% swelling of CMC-CS hydrogels. The rheological measurements revealed a higher storage modulus (G′) of the CMCNF-CS hydrogel, reaching 13.3 kPa compared to only 3.5 kPa measured for the CMC-CS hydrogel. Further comparison of the adsorption characteristics of the CMCNF-CS and CMC-CS hydrogels toward Cu2+, Cd2+, and Hg2+ ions showed the slightly higher adsorption capacity of CMC-CS for Cu2+ but similar adsorption capacities for Cd2+ and Hg2+. The adsorption kinetics obeyed the pseudo-second-order adsorption model in both cases. Overall, while the replacement of CMC with CMCNF in hydrogel does not significantly affect the performance of such systems as adsorbents, CMCNF imparts IPEC hydrogel with higher stiffness and a frequency-independent loss (G″) modulus and suppresses the hydrogel swelling, so can be beneficial in practical applications that require stable performance under various dynamic conditions.

Myotonic dystrophy type 1 (DM1) is a multisystem disorder with progressive myopathy and myotonia. The clinical study was conducted in the Republic of North Ossetia-Alania (RNOA), and in it 39 individuals from 17 unrelated families were identified with DM1. Clinical presentations varied, including muscle weakness, fatigue, intellectual disability, hypersomnia, ophthalmological abnormalities, and alopecia. Using clinical and genotyping data, we confirmed the diagnosis and enabled the study of CTG-repeat anticipation and DM1 prevalence in the Ossetian and Ingush populations. CTG expansion correlated with age of onset, with clinical severity, and with offspring showing more severe symptoms than parents. In many families, the youngest child had a more severe DM1 phenotype than older siblings. The prevalence was 14.17 per 100,000 in Ossetians and 18.74 per 100,000 in Ingush people, aligning with global data. Segregation analysis showed a higher frequency of maternal transmission. The study highlights the clinical and genetic heterogeneity of DM1 and its dependence on repeat expansion and paternal and maternal age.

This study, conducted in the Republic of North Ossetia-Alania (RNOA), aimed to explore the genetic landscape of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) in the Ossetian population using data from newborn screening (NBS). Through comprehensive molecular genetic analysis of 29 patients with HPA from diverse ethnic backgrounds, two major genetic variants in the PAH gene, P281L and P211T, were identified, constituting 50% of all detected pathogenic alleles in Ossetian patients. Remarkably, these variants exhibited an exceptionally high frequency in the Ossetian population, surpassing global prevalence rates. This study unveiled a notable prevalence of mild forms of HPA (78%), underscoring the importance of genetic counseling for carriers of pathogenic variants in the PAH gene. Moreover, the findings emphasized the necessity for ongoing monitoring of patients with mild forms, as they may lack significant symptoms for diagnosis, potentially impacting offspring. Overall, this research offers valuable insights into the genetic landscape of HPA and PKU in the Ossetian population.

p.Asn1303Lys (N1303K) is a common missense variant of the CFTR gene, causing cystic fibrosis (CF). In this study, we initially evaluated the influence of CFTR modulators on the restoration of N1303K-CFTR function using intestinal organoids derived from four CF patients expressing the N1303K variant. The forskolin-induced swelling assay in organoids offered valuable insights about the beneficial effects of VX-770 + VX-661 + VX-445 (Elexacaftor + Tezacaftor + Ivacaftor, ETI) on N1303K-CFTR function restoration and about discouraging the prescription of VX-770 + VX-809 (Ivacaftor + Lumacaftor) or VX-770 + VX-661 (Ivacaftor + Tezacaftor) therapy for N1303K/class I patients. Then, a comprehensive assessment was conducted on an example of one patient with the N1303K/class I genotype to examine the ETI effect on the restoration of N1303K-CFTR function using in vitro the patient’s intestinal organoids, ex vivo the intestinal current measurements (ICM) method and assessment of the clinical status before and after targeted therapy. All obtained results are consistent with each other and have proven the effectiveness of ETI for the N1303K variant. ETI produced a significant positive effect on forskolin-induced swelling in N1303K/class I organoids indicating functional improvement of the CFTR protein; ICM demonstrated that ETI therapy restored CFTR function in the intestinal epithelium after three months of treatment, and the patient improved his clinical status and lung function, increased his body mass index (BMI) and reduced the lung pathogenic flora diversity, surprisingly without improving the sweat test results.

Three years ago, our patient, at that time a 16-month-old boy, was discovered to have bilateral kidney lesions with a giant tumor in the right kidney. Chemotherapy and bilateral nephron-sparing surgery (NSS) for Wilms tumor with nephroblastomatosis was carried out. The patient also had eye affection, including glaucoma, eye enlargement, megalocornea, severe corneal swelling and opacity, complete aniridia, and nystagmus. The diagnosis of WAGR syndrome was suspected. De novo complex chromosomal rearrangement with balanced translocation t(10,11)(p15;p13) and a pericentric inversion inv(11)(p13q12), accompanied by two adjacent 11p14.1p13 and 11p13p12 deletions, were identified. Deletions are raised through the complex molecular mechanism of two subsequent rearrangements affecting chromosomes 11 and 10. WAGR syndrome diagnosis was clinically and molecularly confirmed, highlighting the necessity of comprehensive genetic testing in patients with congenital aniridia and/or WAGR syndrome.

Despite the tremendous progress in the development of functional materials from plastic waste to promote its recycling, only a few examples of hydrogel materials from plastic waste were reported. In this study, microwave-assisted depolymerization of waste PET plastic using polyamine was performed to prepare short aminophthalamide oligomers followed by chemically cross-linking into a hydrogel material. Catalyst-free microwave-assisted aminolysis of PET was completed within 30–40 s, demonstrating high efficiency of the depolymerization reaction. Subsequent epoxy cross-linking of the oligomers yielded a hydrogel with a swelling degree of ca. 92.1 times in pure water. The application of the obtained hydrogel for the removal of copper ions (Cu2+) from water was demonstrated. Efficient complexation of NH2 groups of the hydrogel with Cu2+ resulted in high adsorption capacities of the hydrogel material toward Cu2+ removal, which were the highest at neutral pHs and reached ca. 213 mg/g. The proposed type of environmental material is beneficial owing to its waste-derived nature and functionality that can be applied for the high-efficiency removal of a broad scope of known environmental pollutants.

Inherited retinal diseases (IRDs) constitute a prevalent group of inherited ocular disorders characterized by marked genetic diversity alongside moderate clinical variability. Among these, ABCA4-related eye pathology stands as a prominent form affecting the retina. In this study, we conducted an in-depth analysis of 96 patients harboring ABCA4 variants in the European part of Russia. Notably, the complex allele c.[1622T>C;3113C>T] (p.Leu541Pro;Ala1038Val, or L541P;A1038V) and the variant c.5882G>A (p.Gly1961Glu or G1961E) emerged as primary contributors to this ocular pathology within this population. Additionally, we elucidated distinct disease progression characteristics associated with the G1961E variant. Furthermore, our investigation revealed that patients with loss-of-function variants in ABCA4 were more inclined to develop phenotypes distinct from Stargardt disease. These findings provide crucial insights into the genetic and clinical landscape of ABCA4-related retinal dystrophies in this specific population.

Radio astronomical observations at millimeter and submillimeter wavelengths are a very important tool for astrophysical research. However, there is a huge area in northeastern Eurasia, including the whole Russian territory, which lacks sufficiently large radio telescopes effectively operating at these wavelengths. In this review, we describe our long-term efforts to find suitable sites for such radio telescopes in this area, that is, sites with good atmospheric transparency at millimeter and submillimeter waves. We describe methods and instruments used for measurements and evaluations of the atmospheric opacity. They include special radiometric systems, which are used for estimations of the atmospheric opacity in the transparency windows from the sky brightness measurements. Evaluation of the precipitable water vapor from such measurements by the artificial neural network is discussed. Other approaches use water vapor radiometers, global atmospheric models and signals of the Global Navigation Satellite Systems. To date, long-term radiometric monitoring has been performed at several candidate sites, and atmospheric conditions for many sites have been evaluated using global atmospheric models. Several sites with the best atmospheric transparency at millimeter and submillimeter wavelengths have been selected. They can be effectively used for astronomical observations, at least in the major atmospheric transparency windows at 1.3 mm and 0.85 mm. In general, the results show that northeastern Eurasia is a promising area for submillimeter astronomy. These results can also be used for space communications and radar systems.

This study aims to present a clinical case involving the unique co-occurrence of congenital aniridia and Down syndrome in a young girl and to analyze the combined impact of these conditions on the patient’s phenotype. The investigation involved comprehensive pediatric and ophthalmological examinations alongside karyotyping and Sanger sequencing of the PAX6 gene. The patient exhibited distinctive features associated with both congenital aniridia and Down syndrome, suggesting a potential exacerbation of their effects. Cytogenetic and molecular genetic analysis revealed the presence of trisomy 21 and a known pathogenic nonsense variant in exon 6 of the PAX6 gene (c.282C>A, p.(Cys94*)) corresponding to the paired domain of the protein. The observation of these two hereditary anomalies offers valuable insights into the molecular pathogenetic mechanisms underlying each condition. Additionally, it provides a basis for a more nuanced prognosis of the complex disease course in this patient. This case underscores the importance of considering interactions between different genetic disorders in clinical assessments and treatment planning.

Tuberculosis (TB) remains an important public health problem and one of the leading causes of death. Individuals with latent tuberculosis infection (LTBI) have an increased risk of developing active TB. The problem of the diagnosis of the various stages of TB and the identification of infected patients in the early stages has not yet been solved. The existing tests (the tuberculin skin test and the interferon-gamma release assay) are useful to distinguish between active and latent infections. But these tests cannot be used to predict the development of active TB in individuals with LTBI. The purpose of this review was to analyze the extant data of the interaction of M. tuberculosis with immune cells and identify molecular predictive markers and markers of the early stages of TB. An analysis of more than 90 sources from the literature allowed us to determine various subpopulations of immune cells involved in the pathogenesis of TB, namely, macrophages, dendritic cells, B lymphocytes, T helper cells, cytotoxic T lymphocytes, and NK cells. The key molecular markers of the immune response to M. tuberculosis are cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17, IL-22b, IFNɣ, TNFa, and TGFß), matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), and their inhibitors (TIMP-1, TIMP-2, TIMP-3, and TIMP-4). It is supposed that these molecules could be used as biomarkers to characterize different stages of TB infection, to evaluate the effectiveness of its treatment, and as targets of pharmacotherapy.

Sarcoidosis is a complex inflammatory multisystem disease of unknown etiology that is characterised by epithelioid cell granulomatous lesions affecting various organs, mainly the lungs. In general, sarcoidosis is asymptomatic, but some cases result in severe complications and organ failure. So far, no accurate and validated modelling for clinical and pathohistological manifestations of sarcoidosis is suggested. Moreover, knowledge about disease-specific diagnostic markers for sarcoidosis is scarce. For instance, pulmonary granulomatosis is associated with the upregulated production of proinflammatory molecules: TNF-α, IL-6, CXCL1, CCL2, CCL18, CD163, serum angiotensin-converting enzyme (sACE), lysozyme, neopterin, and serum amyloid A (SAA). Quantum dots (QDs) are widely applied for molecular diagnostics of various diseases. QDs are semiconductor nanoparticles of a few nanometres in size, made from ZnS, CdS, ZnSe, etc., with unique physical and chemical properties that are useful for the labelling and detection in biological experiments. QDs can conjugate with various antibodies or oligonucleotides, allowing for high-sensitivity detection of various targets in organs and cells. Our review describes existing experimental models for sarcoidosis (in vitro, in vivo, and in silico), their advantages and restrictions, as well as the physical properties of quantum dots and their potential applications in the molecular diagnostics of sarcoidosis. The most promising experimental models include mice with TSC2 deletion and an in silico multiscale computational model of sarcoidosis (SarcoidSim), developed using transcriptomics and flow cytometry of human sarcoid biopsies. Both models are most efficient to test different candidate drugs for sarcoidosis.

Abnormal depolarization of neuronal membranes called paroxysmal depolarization shift (PDS) represents a cellular correlate of interictal spikes. The mechanisms underlying the generation of PDSs or PDS clusters remain obscure. This study aimed to investigate the role of ionotropic glutamate receptors (iGluRs) in the generation of PDS and dependence of the PDS pattern on neuronal membrane potential. We have shown that significant depolarization or hyperpolarization (by more than ±50 mV) of a single neuron does not change the number of individual PDSs in the cluster, indicating the involvement of an external stimulus in PDS induction. Based on this data, we have suggested reliable protocols for stimulating single PDS or PDS clusters. Furthermore, we have found that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors are necessary for PDS generation since AMPAR antagonist NBQX completely suppresses bicuculline-induced paroxysmal activity. In turn, antagonists of NMDA (N-methyl-D-aspartate) and kainate receptors (D-AP5 and UBP310, respectively) caused a decrease in the amplitude of the first action potential in PDSs and in the amplitude of the oscillations of intracellular Ca2+ concentration occurring alongside the PDS cluster generation. The effects of the NMDAR (NMDA receptor) and KAR (kainate receptor) antagonists indicate that these receptors are involved only in the modulation of paroxysmal activity. We have also shown that agonists of some Gi-coupled receptors, such as A1 adenosine (A1Rs) or cannabinoid receptors (CBRs) (N6-cyclohexyladenosine and WIN 55,212-2, respectively), completely suppressed PDS generation, while the A1R agonist even prevented it. We hypothesized that the dynamics of extracellular glutamate concentration govern paroxysmal activity. Fine-tuning of neuronal activity via action on Gi-coupled receptors or iGluRs paves the way for the development of new approaches for epilepsy pharmacotherapy.

The pathogenic variant E92K (c.274G > A) of the CFTR gene is rare in America and Europe, but it is common for people with cystic fibrosis from Russia and Turkey. We studied the effect of the E92K genetic variant on the CFTR function. The function of the CFTR channel was studied using the intestinal current measurements (ICM) method. The effects of CFTR modulators on the restoration of the CFTR function were studied in the model of intestinal organoids. To assess the effect of E92K on pre-mRNA splicing, the RT-PCR products obtained from patients’ intestinal organoid cultures were analyzed. Patients with the genetic variant E92K are characterized by an older age of diagnosis compared to homozygotes F508del and a high frequency of pancreatic sufficiency. The results of the sweat test and the ICM method showed partial preservation of the function of the CFTR channel. Functional analysis of CFTR gene expression revealed a weak effect of the E92K variant on mRNA-CFTR splicing. Lumacaftor (VX-809) has been shown to restore CFTR function in an intestinal organoid model, which allows us to consider the E92K variant as a promising target for therapy with CFTR correctors.

GPR55 is a non-canonical cannabinoid receptor, important for cancer proliferation. Depending on the ligand, it induces either cell proliferation or death. The objective of the study was to establish the mechanisms of this multidirectional signaling. Using the CRISPR-Cas9 system, the GPR55, CB1, CB2, and GPR18 receptor knockouts of the MDA-MB-231 line were obtained. After the CB2 receptor knockout, the pro-apoptotic activity of the pro-apoptotic ligand docosahexaenoyl dopamine (DHA-DA) slightly increased, while the pro-proliferative activity of the most active synthetic ligand of the GPR55 receptor (ML-184) completely disappeared. On the original cell line, the stimulatory effect of ML-184 was removed by the CB2 receptor blocker and by GPR55 receptor knockout. Thus, it can be confidently assumed that when proliferation is stimulated with the participation of the GPR55 receptor, a signal is transmitted from the CB2 receptor to the GPR55 receptor due to the formation of a heterodimer. GPR18 was additionally involved in the implementation of the pro-apoptotic effect of DHA-DA, while the CB1 receptor is not involved. In the implementation of the pro-apoptotic action of DHA-DA, the elimination of Gα13 led to a decrease in cytotoxicity. The obtained data provide novel details to the mechanism of the pro-proliferative action of GPR55.

Hydroxyapatite (HAP) is the most common calcium phosphate ceramic that is used in biomedical applications, e.g., as an inorganic component of bone scaffolds. Nevertheless, fluorapatite (FAP) has gained great attention in the area of bone tissue engineering in recent times. The aim of this study was a comprehensive comparative evaluation of the biomedical potential of fabricated HAP- and FAP-based bone scaffolds, to assess which bioceramic is better for regenerative medicine applications. It was demonstrated that both biomaterials had a macroporous microstructure, with interconnected porosity, and were prone to slow and gradual degradation in a physiological environment and in acidified conditions mimicking the osteoclast-mediated bone resorption process. Surprisingly, FAP-based biomaterial revealed a significantly higher degree of biodegradation than biomaterial containing HAP, which indicated its higher bioabsorbability. Importantly, the biomaterials showed a similar level of biocompatibility and osteoconductivity regardless of the bioceramic type. Both scaffolds had the ability to induce apatite formation on their surfaces, proving their bioactive property, that is crucial for good implant osseointegration. In turn, performed biological experiments showed that tested bone scaffolds were non-toxic and their surfaces promoted cell proliferation and osteogenic differentiation. Moreover, the biomaterials did not exert a stimulatory effect on immune cells, since they did not generate excessive amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS), indicating a low risk of inflammatory response after implantation. In conclusion, based on the obtained results, both FAP- and HAP-based scaffolds have an appropriate microstructure and high biocompatibility, being promising biomaterials for bone regeneration applications. However, FAP-based biomaterial has higher bioabsorbability than the HAP-based scaffold, which is a very important property from the clinical point of view, because it enables a progressive replacement of the bone scaffold with newly formed bone tissue.

The relationship between the acid-basic properties and the electronegativity of oxygen-containing compounds of Uranium, namely, oxides, hydroxide, uranates, uranyl salts and oxohalides is examined. It is shown that Uranium dioxide and Uranium trioxide exhibit amphoteric properties; they are very weakly expressed in UO2 (range of electronegativity – from 1.84 to 1.95 eВ1/2/О2-), while the basic and acid functions of UO3 are much more pronounced –from 1.52 to 2.27 eВ1/2/О2-, respectively. The availability of sufficiently reliable thermodynamic data on a number of salts containing a particle of UO2 (uranyl), namely, sulfate, nitrate, carbonate, acetate, oxalate, as well as their hydrates, made it possible to accurately estimate the average values of the electronegativity of UO3 in its main function. Assessment of the electronegativity of acetate and oxalate acids (2.34-2.36 eВ1/2/О2-), as well as acetic anhydride (2.63eВ1/2/О2-) gave quite adequate values characteristic of relatively strong organic acids. In a similar way, the electronegativities of UF6 and UCl6 were calculated from the thermodynamic parameters of UO2F2 and UO2Cl2, which are 2.65 and 2.40 eВ1/2/О2-, respectively, which indicates their stronger acidic properties compared to UO3. For the first time, the electronegativity of U2O5 was calculated based on the thermodynamic parameters of a mixed valence oxide of the composition U3O8; its value (2.10 эВ1/2/О2-) indicates less pronounced acidic properties compared to UO3, which is consistent with the general character of the oxides and the ionic radii of U5+ and U6+. So, electronegativity of Uranium oxides in the series UO2, U2O5, UO3 varies quite natural and in agreement with generally accepted views of inorganic chemistry.

The question of the quantitative determination of the amphotericity of oxides by the values of their electronegativity is considered. The approximate boundaries of the electronegativity of amphoteric oxides from 1.6 to 2.2 eВ1/2/О2- are established according to the concept of aciditybasicity of Lux-Flood. The possibility of the manifestation of amphoteric properties with a different ratio of acid and basic functions for oxides of the composition MO, M2O3, MO2, M2O5 and MO3is analyzed, and the oxides of the composition M2O3, exhibit the most balanced ratio. The limit values of electronegativity for acid and basic functions are established, which differ by 0.3-0.4 eВ1/2/О2-. The influence of the binary oxide form (oxo-, ortho-, meta-, etc.) on the value of the electronegativity of simple oxides, which they manifest during acid-base interaction, is explained. The influence of the acid-base interaction on the electronegativity of binary oxides at the formation of ternary oxides (complex sulfates, silicates and phosphates) of metals with their equalization and the acquisition of amphoteric properties is shown. The relationship between the electronegativity of simple oxides and their thermal characteristics (melting and boiling points) characterizing the strength of crystal lattices is established. It has been shown that amphoteric oxides having a predominantly covalent crystalline structure have higher thermal parameters than oxides of a predominantly ionic or molecular nature, i.e., basic or acidic oxides. On the other hand, having the most stable crystalline structure, they are less able to chemically interact with environmental components, that is, they have higher climatic stability compared to acidic or basic oxides. This indicates the possible ways of choosing simple oxides as the basis of film-forming materials, as well as creating binary and ternary oxides with the acquisition of amphoteric properties.

A fundamentally new type of materials – composites based on the Germanium- metal oxide systems – for applying interference coatings of IR spectral optics has been developed. The formation of a pair of volatile substances (one of them being Germanium monoxide), and their recombination is characteristic of compounds of Germanium and some p-metals (In, Ge, Sn), which have different volatilities in the lower and higher oxidation states. The introduction of a stabilizing additive B2O3 to systems Ge – In2O3 (-GeO2, -SnO2) is proposed. It has been shown that between B2O3, which has acidic properties and In2O3, mainly of a basic nature, an interaction occurs that results in the formation of a complex oxide compound, Indium orthoborate of the InBO3 composition. This fact is confirmed by X-ray phase analysis and IR transmission spectroscopy. It has been established that B2O3 addition not only affects the phase composition of the samples, but also the position of the In2O3 vibrational bands. In turn, the presence of elemental Germanium in the system results in an increase in InBO3 content, the reason for which remains unclear. At the same time, the formation of ternary compounds in Ge – GeO2 (SnO2) – B2O3 systems has not been established. Most likely, glass formation takes place in the first of the systems, while in the system with SnO2, immiscibility in the liquid phase and the formation of phases of unknown composition are visually observed. Partial systems GeO2 (SnO2) – B2O3 during evaporation in vacuum destroy the material of the evaporator due to very high temperatures of the processes. On the contrary, the Ge- In2O3 – B2O3 system was successfully evaporated and a fairly strong coating was obtained. Presumably the interaction between Germanium, metal oxide and B2O3 results in the formation of complex oxides such as borates of metals in various oxidation states, which stabilizes the evaporation process in vacuum and condensation of the coating with the necessary optical and operational properties.

The general nature of the relationship between the acid-base properties (electronegativity) of 3d-metal salts and their ability to form aqua and ammine complex compounds (hydrates and ammoniates) has been established. The thermal strength of metal-ligand bonds (H2O, NH3), defined as the enthalpy of formation of a complex compound per bond depends on many factors: the coordination number of the central metal ion, the nature of the metal, anion, and ligand. An increase in the electronegativity of compounds in the series nitrates – chlorides – sulfates of 3d-metals (Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, as well as its decrease when H2O is replaced by NH3 (with the same coordination number) results in an increase in strength by a decrease in enthalpy per 1 metal-ligand bond of complex compounds. In turn, the change in electronegativity is due to the size-charge parameters (metal ionic radius, counter ion charge) of the cations and anions that make up the compounds. There is a correspondence in the change in the total enthalpy of formation of aqua complex compounds (crystalline hydrates) and their diluted solutions. An explanation of this relationship is proposed, based on the recognition of the important role of the chemical component in the process of dissolution of compounds in water. Similar, albeit in a less pronounced form, processes take place in 3d-metal hydroxides, which have mainly basic properties. When water molecules are replaced by ammonia molecules, the solubility of hydroxides in the series Mn(OH)2, Fe(OH)2, Co(OH)2, Ni(OH)2, Cu(OH)2, Zn(OH)2 significantly increases, indicating, together with a change in color, the strengthening of complex compounds. Found regularities make it possible to use the electronegativity parameter to predict and control complexation in other groups of compounds (salts, hydroxides, and molecular ligands).

North Caucasus has always been a residence of a lot of different authentic ethnic groups speaking different languages and still living their traditional lifestyle. The diversity appeared to be reflected in the accumulation of different mutations causing common inherited disorders. X-linked ichthyosis represents the second most common form of genodermatoses after ichthyosis vulgaris. Eight patients from three unrelated families of different ethnic origin, Kumyk, Turkish Meskhetians, and Ossetian, with X-linked ichthyosis from the North Caucasian Republic of North Ossetia–Alania were examined. NGS technology was implied for searching for disease-causing variants in one of the index patients. Known pathogenic hemizygous deletion in the short arm of chromosome X encompassing the STS gene was defined in the Kumyk family. A further analysis allowed us to establish that likely the same deletion was a cause of ichthyosis in a family belonging to the Turkish Meskhetians ethnic group. In the Ossetian family, a likely pathogenic nucleotide substitution in the STS gene was defined; it segregated with the disease in the family. We molecularly confirmed XLI in eight patients from three examined families. Though in two families, Kumyk and Turkish Meskhetian, we revealed similar hemizygous deletions in the short arm of chromosome X, but their common origin was not likely. Forensic STR markers of the alleles carrying the deletion were defined to be different. However, here, common alleles haplotype is hard to track for a high local recombination rate. We supposed the deletion could arise as a de novo event in a recombination hot spot in the described and in other populations with a recurrent character. Defined here are the different molecular genetic causes of X-linked ichthyosis in families of different ethnic origins sharing the same residence place in the Republic of North Ossetia–Alania which could point to the existing reproductive barriers even inside close neighborhoods.

The review summarizes and systematizes data of the last twenty years on the synthetic methods and biological properties of pyrido[2,3-d]pyrimidin-7-ones, promising objects of organic and pharmaceutical chemistry. Two main approaches to the formation of the pyrido[2,3-d]pyrimidine system are considered. The first of them involves the cyclization of substituted pyridines containing functional groups in positions 2 and 3 of the heterocyclic ring. The second approach is based on the formation of a bicyclic system by adding a pyridone moiety to the pyrimidine ring. The methods developed allow to introduce various functional groups and aromatic substituents into the pyrido[2,3-d]pyrimidine system, as well as to obtain most of the target products with high yields. The effective three-component one-pot synthetic approaches to the formation of pyridine ring with the participation of functionalized pyrimidines and compounds with an active methylene group have been proposed. The analysis of the literature has shown that functionalized pyrimidines are the most common starting reagents, which structural modification is useful for the further annelation of the pyridine cycle. Much attention is paid to the biological properties of pyrido[2,3-d]pyrimidin-7-ones. The prospect of using pyrido[2,3-d]pyrimidin-7-one derivatives as tyrosine kinase inhibitors has been shown. Data on the biological effects of pyrido[2,3-d]pyrimidin-7-one derivatives indicate the possibility of detecting new biologically active compounds among pyridopyrimidines.

An increasing number of the population all around the world suffer from age-associated neurodegenerative diseases including Parkinson’s disease (PD). This disorder presents different signs of genetic, epigenetic and environmental origin, and molecular, cellular and intracellular dysfunction. At the molecular level, α-synuclein (αSyn) was identified as the principal molecule constituting the Lewy bodies (LB). The gut microbiota participates in the pathogenesis of PD and may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The most important pathogenetic link is an imbalance of Ca2+ ions, which is associated with redox imbalance in the cells and increased generation of reactive oxygen species (ROS). In this review, genetic, epigenetic and environmental factors that cause these disorders and their cause-and-effect relationships are considered. As a constituent of environmental factors, the example of organophosphates (OPs) is also reviewed. The role of endothelial damage in the pathogenesis of PD is discussed, and a ‘triple hit hypothesis’ is proposed as a modification of Braak’s dual hit one. In the absence of effective therapies for neurodegenerative diseases, more and more evidence is emerging about the positive impact of nutritional structure and healthy lifestyle on the state of blood vessels and the risk of developing these diseases.

Here, we described three affected boys from two unrelated families of Ossetian-Digor origin from the Republic of North Ossetia-Alania who were admitted to the Research Centre for Medical Genetics with unspecified muscular dystrophy. High-throughput sequencing was performed and revealed two novel frameshift variants in the COL6A2 gene (NM_001849.3) in a heterozygous state each in both cases: c.508_535delinsCTGTGG and c.1659_1660del (case 1) and c.1689del and c.1659_1660del (case 2). In two cases, the same nucleotide variant in the COL6A2 gene (c.1659_1660del) was observed. We have suggested that the variant c.1659_1660del may be common in the Ossetian-Digor population because two analyzed families have the same ancestry from the same subethnic group of Ossetians). The screening for an asymptomatic carriage of the nucleotide variant c.1659_1660del in 54 healthy donors from Ossetian-Digor population revealed that the estimated carrier frequency is 0.0093 (CI: 0.0002–0.0505), which is high for healthy carriers of the pathogenic variant. Molecular genetic, anamnestic data and clinical examination results allowed us to diagnose Ullrich muscular dystrophy in those affected boys. Genetic heterogeneity and phenotypic diversity of muscular dystrophies complicate diagnosis. It is important to make a differential diagnosis of such conditions and use HTS methods to determine the most accurate diagnosis.

Intellectual development disorder (IDD) is characterized by a general deficit in intellectual and adaptive functioning. In recent years, there has been a growing interest in studying the genetic structure of IDD. Of particular difficulty are patients with non-specific IDD, for whom it is impossible to establish a clinical diagnosis without complex genetic diagnostics. We examined 198 patients with non-specific IDD from 171 families using whole-exome sequencing and chromosome microarray analysis. Hereditary forms of IDD account for at least 35.7% of non-specific IDD, of which 26.9% are monogenic forms. Variants in the genes associated with the BAF (SWI/SNF) complex were the most frequently identified. We were unable to identify phenotypic features that would allow differential diagnosis of monogenic and microstructural chromosomal rearrangements in non-specific IDD at the stage of clinical examination, but due to its higher efficiency, exome sequencing should be the diagnostic method of the highest priority study after the standard examination of patients with NIDD in Russia.

Genome-wide sequencing metadata allows researchers to infer bias in the relative frequencies of mutational events and to predict putative mutagenic models. In addition, much less data could be useful in the evaluation of the mutational frequency spectrum and the prevalent local mutagenic process. Here we analyzed the PAX6 gene locus for mutational spectra obtained in our own and previous studies and compared them with data on other genes as well as the whole human genome. MLPA and Sanger sequencing were used for mutation searching in a cohort of 199 index patients from Russia with aniridia and aniridia-related phenotypes. The relative frequencies of different categories of PAX6 mutations were consistent with those previously reported by other researchers. The ratio between substitutions, small indels, and chromosome deletions in the 11p13 locus was within the interval previously published for 20 disease associated genomic loci, but corresponded to a higher end due to very high frequencies of small indels and chromosome deletions. The ratio between substitutions, small indels, and chromosome deletions for disease associated genes, including the PAX6 gene as well as the share of PAX6 missense mutations, differed considerably from those typical for the whole genome.

The Sn – As – P system is characterized by the presence of unlimited solid solutions (Sn4As3)x (Sn4P3) 1–х (α-phase) and solid solutions based on tin monoarsenide (β-solid solutions) and SnP3 phosphide (γ-solid solutions). The solubility of phosphorus in SnAs depends not only on temperature, but also on the direction of the polythermal cross section, i.e. from that in the form of an individual simple substance or in the form of any of the tin phosphides, the doping component is introduced. In the present work, the confi guration of the region of existence of solid solutions of phosphorus in tin monoarsenide was investigated. Alloys of SnAs – Sn4P3:SnAs – Sn0.43P0.57; SnAs – SnP3 and SnAs – P polythermal sections, annealed at 753 K, were studied by X-ray phase analysis, the concentration range of the existence of a homogeneous solid solution was established, the parameters of the crystal structure were determined. The construction of quasi-chemical schemes for the doping of tin monoarsenide showed that with the introduction of SnP3, the greatest deviation from stoichiometry towards the lack of tin is observed. The highest solubility of phosphorus, reaching 30 mol % corresponds to this cut. Thus, the region of existence of solid solutions based on tin monoarsenide has an asymmetric shape shifted toward an excess of volatile components, and the maximum solubility of phosphorus corresponds to the direction of the polythermal section SnAs – SnP3. Taking into account the phase equilibrium scheme of the Sn – As – P ternary system and the obtained data on the confi guration of the region of existence of homogeneous solid solutions of phosphorus in the tin monoarsenide, a phase subsolidus demarcation scheme of the phase diagram of this system was carried out.

Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression.

With the use of scanning electron microscopy, atomic force microscopy and X-ray diffraction the morphology, composition and structure evolution of a-Si/ZrO2 and a-SiOx/ZrO2 multilayered nanoperiodical structures subjected to high temperature annealing were investigated. Each ZrO2 layers thickness was 2 nm while for a-Si or a-SiOx layers thickness was 8 nm with total number of layers 34 (a-SiO/ZrO2) and 43 (a-SiOx/ZrO2). Annealing was performed for 30 minutes at temperature of 1100 °С. Multilayered nanoperiodical structures have grainy relief with comparable morphology and size characteristics without noticeable dependence on layers interleaving sequence and their composition. 30 minutes anneal at 1100 °С for a-SiOx/ZrO2 multilayered nanoperiodical structures did not transform their surface. Under the same temperature for a-Si/ZrO2 multilayered nanoperiodical structures we observed noticeable changes in samples surface morphology as irregularities formation with 100 nm width and height that exceeds bilayer thickness. By X-ray diffraction technique the presence of thin ZrSi2 silicide layer is demonstrated in a-Si/ZrO2 structures as the result of silicon chemical interaction with zirconium dioxide under high temperature treatment of nanoperiodical multilayers.

Various definitions (by Brǿnsted – Lauri , Lux – Flood, Lewis )of the basicity – acidity for the systems of different types have been regarded. The necessity and possibility of the establishment of a general approach to definition of the mentioned parameter for binary demonstrated. A general character of the effect of hydration of basic and acidic oxides on the interrelation of their basic-acidic properties by Lux – Flood is established. As a parameter which reflects the expression of acidic properties, a value of the effective electronegativity of oxides and hydroxides of elements is proposed. The electronegativity of 3.0 for SO3 is chosen as principal one and values of other oxides were calculated from thermochemical data for sulfates of appropriate elements in analogous to L. Pauling manner for elements. Its values are 2.2-3.1 for acidic oxides, 0.3-1.6 for basic oxides and 1.7-2.1 for amphoteric oxides. Water is known as amphoteric oxide able to react both with acid and with basic oxides. The prevalence of acidic properties over basic ones for water is shown. It is caused by difference in energetic balance of the processes of accession to and removal from the H2O molecule of O2− ions. During the processes of hydration in the series oxide – hydroxide – hydroxide hydrate – aqueous solution a decrease of electronegativity in a case of acidic oxides and its increase in a case of basic oxides are observed. It has been shown equalizing (for basic-acidic differences) role of water concerning oxides of elements. A correlation between electronegativity of oxides and hydroxides of elements and basicity and acidity of their aqueous solution is established.

Methods of luminescent spectroscopy, spectroscopy of diffuse refl ectance and IR transmittance spectroscopy were used for investigation of process of change of nanostructures of Europium (ІІ) fl uoride in stiffened saline melt NaСl – KСl. Europium (ІІ) fluoride was synthesized by high-temperature solid-phase reaction of EuF3 with elemental Germanium ground and pressed into a tablet. The process of synthesis is accompanied by volatizing of GeF2 at hightemperature annealing of the mixture. Prolonged calcinations result in a yellowish powder with a slight gray tint. IR spectrum and spectrum of diffuse refl ectance notify on the nanostructured product. Dissolution of EuF2 in saline melt is regarded as exchange reaction with one of the components, NaCl and complexion with another one, namely KСl. At rapid crystallization of the molten saline solution multiple centers forming and the stabilization of nano-structures of «core-shell» type are occurred. It is established considerable (almost in 2 times for each week) intensity falling 5d-4f photoluminescence with a maximum at ~430 nanometers. At the same time characteristic changes in a spectra of diffuse refl ectance in an UV range of a spectrum with transition from negative values of Kubelka-Munk function to positive ones, with absorption bands observed at 250, 330 and 410 nanometers. Insignifi cant by intensity peaks in a near IR spectrum at 1800-2300 nanometers testify to the small content of Eu3+ ions in the sample that practically does not change eventually. The mechanism of degradation of the nanostructures in stiffened melt and corresponding kinetic equation of the process are proposed. The degradation process is supposed to be caused by environment factors such as moisture and oxygen of an air and results in the destruction of the stabilizing shells of the nanoparticles.

Сomplexes[SnCl4(R-Ib∙Н)], where R=H (1), 4-Br (2), 4-NO2(3), 2-OCH3(4), 4-OCH3(5), -ОC7H15(6),were synthesized by interaction of SnCl4 with isonicotinoylhydrazones of R-benzoic aldehydes (R-HIb) in acetonitrile and complex [SnCl3(2-OH-Inf∙Н)](9) – by interaction of SnCl4with 2-OH- naphthaldehydeisonicotinoylhydrazone (2-OH-H2Inf). In (1-6) bidentateO(C-O)–N(N=CH)-coordination of the enol form of the ligand is realized and the coordination node {SnCl4ON}– is formed, and in (9) the enol form remains, but the composition of the node changes – {SnCl3O2N}– due to O(C-O)–N(N=CH)–О(Ph-O)- tridentate coordination.The compounds were characterized by the methods of elemental analysis, mass spectrometry, conductometry, thermogravimetry. Their structure was established by comparing the mass- and IR spectra (1-6) and (9) with previously obtained and X-ray structurally characterized complexes [SnCl4(R-Ib∙Н)]∙CH3CN (R=4-N(CH3)2(7)) and [SnCl3(R-Ib∙Н)]∙2CH3CN (R=2-OH(8))with bi- (7) and tridentate coordination (8) of isonicotinoylhydrazones, respectively. It is shown that (1-6) and (9) are complex compounds of the zwitterionic type: the negative charge on the coordination nodes of tin(IV)is delocalized by the oxyazine fragment N=C–O, and the positive charge – by the protonation of the vacant pyridine nitrogen atomof hydrazide fragment. The influence of the composition of the coordination node of complexes (1-9), as well as the nature and position of the substituents (R) in their molecules on the activity against Mycobacteriumtuberculosis was determined. It was found that the effect of complexes with tridentate hydrazones (8) and (9) on the growth of pathogen is lower (MIC = 12.5 and 25 μM/ml, respectively) compared with bidentatehydrazones (MIC (1-7) = 0,8 – 6,25 μM/ml), among which [SnCl4(2-OCH3-Ib∙Н)] (4) stand out (MIC = 0.8 μM/ml).

Neuronal calcium sensor-1 (NCS-1) is a four-EF-hand ubiquitous signaling protein modulating neuronal function and survival, which participates in neurodegeneration and carcinogenesis. NCS-1 recognizes specific sites on cellular membranes and regulates numerous targets, including G-protein coupled receptors and their kinases (GRKs). Here, with the use of cellular models and various biophysical and computational techniques, we demonstrate that NCS-1 is a redox-sensitive protein, which responds to oxidizing conditions by the formation of disulfide dimer (dNCS-1), involving its single, highly conservative cysteine C38. The dimer content is unaffected by the elevation of intracellular calcium levels but increases to 10–30% at high free zinc concentrations (characteristic of oxidative stress), which is accompanied by accumulation of the protein in punctual clusters in the perinuclear area. The formation of dNCS-1 represents a specific Zn2+-promoted process, requiring proper folding of the protein and occurring at redox potential values approaching apoptotic levels. The dimer binds Ca2+ only in one EF-hand per monomer, thereby representing a unique state, with decreased α-helicity and thermal stability, increased surface hydrophobicity, and markedly improved inhibitory activity against GRK1 due to 20-fold higher affinity towards the enzyme. Furthermore, dNCS-1 can coordinate zinc and, according to molecular modeling, has an asymmetrical structure and increased conformational flexibility of the subunits, which may underlie their enhanced target-binding properties. In HEK293 cells, dNCS-1 can be reduced by the thioredoxin system, otherwise accumulating as protein aggregates, which are degraded by the proteasome. Interestingly, NCS-1 silencing diminishes the susceptibility of Y79 cancer cells to oxidative stress-induced apoptosis, suggesting that NCS-1 may mediate redox-regulated pathways governing cell death/survival in response to oxidative conditions.

Epileptic discharges manifest in individual neurons as abnormal membrane potential fluctuations called paroxysmal depolarization shift (PDS). PDSs can combine into clusters that are accompanied by synchronous oscillations of the intracellular Ca2+ concentration ([Ca2+]i) in neurons. Here, we investigate the contribution of L-type voltage-gated calcium channels (VGCC) to epileptiform activity induced in cultured hippocampal neurons by GABA(A)R antagonist, bicuculline. Using KCl-induced depolarization, we determined the optimal effective doses of the blockers. Dihydropyridines (nifedipine and isradipine) at concentrations ≤ 10 μM demonstrate greater selectivity than the blockers from other groups (phenylalkylamines and benzothiazepines). However, high doses of dihydropyridines evoke an irreversible increase in [Ca2+]i in neurons and astrocytes. In turn, verapamil and diltiazem selectively block L-type VGCC in the range of 1–10 μM, whereas high doses of these drugs block other types of VGCC. We show that L-type VGCC blockade decreases the half-width and amplitude of bicuculline-induced [Ca2+]i oscillations. We also observe a decrease in the number of PDSs in a cluster and cluster duration. However, the pattern of individual PDSs and the frequency of the cluster occurrence change insignificantly. Thus, our results demonstrate that L-type VGCC contributes to maintaining the required [Ca2+]i level during oscillations, which appears to determine the number of PDSs in the cluster.

DNA–chitosan (DNA–CS) hydrogel was prepared by in situ complexation between oppositely charged DNA and chitosan polyelectrolytes via electrostatic cross-linking to study its adsorption characteristics. The DNA–chitosan hydrogel matrix contains (i) cationic (NH3+) and anionic (PO4−) sites for electrostatic binding with ionic species, (ii) -OH and -NH2 groups and heteroaromatic DNA nucleobases for chelation of heavy metal ions, and (iii) DNA double-helix for recognition and binding to small organic molecules of various structures and polarities. DNA–CS hydrogels efficiently bind with Hg2+, Pb2+, Cd2+, and Cu2+ metal cations of significant environmental concern. Adsorption capacities of DNA–CS hydrogels for studied metal ions depend on hydrogel composition and pH of solution and reach ca. 50 mg/g at neutral pHs. Hydrogels with higher DNA contents show better adsorption characteristics and notably higher adsorption capacity to Hg2+ ions. Because of the co-existence of cationic and anionic macromolecules in the DNA–CS hydrogel, it demonstrates an affinity to both anionic (Congo Red) and cationic (Methylene Blue) dyes with moderate adsorption capacities of 12.6 mg/g and 29.0 mg/g, respectively. DNA–CS hydrogel can also be used for adsorptive removal of pharmaceuticals on conditions that their molecules are sufficiently hydrophobic and have ionogenic group(s). Facile preparation and multitarget adsorption characteristics of DNA–CS hydrogel coupled with sustainable and environmentally friendly characteristics render this system promising for environmental cleaning applications.

Ubiquitous on Earth, DNA and other nucleic acids are being increasingly considered as promising biomass resources. Due to their unique chemical structure, which is different from that of more common carbohydrate biomass polymers, materials based on nucleic acids may exhibit new, attractive characteristics. In this study, fluorescent nanoparticles (biodots) were prepared by a hydrothermal (HT) method from various nucleic acids (DNA, RNA, nucleotides, and nucleosides) to establish the relationship between the structure of precursors and fluorescent properties of biodots and to optimize conditions for preparation of the most fluorescent product. HT treatment of nucleic acids results in decomposition of sugar moieties and depurination/depyrimidation of nucleobases, while their consequent condensation and polymerization gives fluorescent nanoparticles. Fluorescent properties of DNA and RNA biodots are drastically different from biodots synthesized from individual nucleotides. In particular, biodots synthesized from purine-containing nucleotides or nucleosides show up to 50-fold higher fluorescence compared to analogous pyrimidine-derived biodots. The polymeric nature of a precursor disfavors formation of a bright fluorescent product. The reported effect of the structure of the nucleic acid precursor on the fluorescence properties of biodots should help designing and synthesizing brighter fluorescent nanomaterials with broader specification for bioimaging, sensing, and other applications.

Peculiarities of the change of acid-basic properties of Silicon and Germanium oxy-compounds as a function of the position of elements in the periodic system are established. It is stated that Germanium dioxide possesses much lower (compared to SiO2 and SnO2) temperatures of melting and boiling as well as lower surface tension and dynamic viscosity. This fact points out more income of the molecular structure, hence, more expressed acidic properties. The higher value of the constant of acidity of the aqueous solution of GeO2 (i.e. H2GeO3) in comparison with H4SiO4 confirms the above mentioned. Systems of the GeO2 – MxOy type, where M – metal, exhibit more chemical diversity compared to the analogous systems on the basics of SiO2. For example, GeO2 forms rather stable ternary compounds with Ga2O3 or CeO2, but SiO2, contrary, does not. At the same time, compounds of SiO2 with P2O5 are much stronger, than analogous compounds of GeO2. This fact means that SiO2 has more basic properties than GeO2. Unfortunately we have no other quasi-binary systems of SiO2 or GeO2 with more acidic oxides for the comparison. The sum of these data indicates on the more expressed acidic and less expressed basic properties of GeO2 versus SiO2, which is an additional confirmation of the “Silicon – Germanium anomaly” in the series of elements of the IV group of the periodic system. This phenomenon, probably, is caused by completion of the previous 3d – electronic level in an atom of Germanium. So, some resemblance between Si–Ge and Al–Ga pairs of elements takes place.

Processes of dispersion and solubility of CeO2 and CeF3 in the melts of systems NaNO3-KNO3 which are widely used as medium for synthesis of various oxide materials are investigated. The basis of the mechanism of the specified processes is made by the acid-basic and oxidationreduction reactions between initial substances and saline melt. For identification and definition of oxidation degree of Cerium in interaction products are applied spectroscopy of diffuse reflectance in an UV range of a spectrum and the substantial chemical analysis with use as a reagent of a solution of phosphoric acid. For reduction of influence of own absorption of ions NO3– as the sample of comparison it is used stiffened melt of NaNO3-KNO3. Definition of content of Ce(III) is carried out basing on decrease of intensity of coloring of KMnO4. Content of Ce(IV) is established photometrically on intensity of absorption of a phosphate complex (at high content of Ce(IV)) and on decrease of coloring of methanyl yellow (at low content). The data of spectroscopy of diffuse reflectance specifies in prevalence of Ce(IV) with small admixture of Ce(III) in case of system CeO2-(NaNO3-KNO3) and Ce(III) with admixture of Ce(IV) in case of system CeF3-(NaNO3-KNO3). Because of influence of H3PO4 on oxidation degree of cerium in last system, definition of Ce(III) and Ce(IV) by chemical analysis was not carried out. As for system with CeO2, contents of Ce(IV) by method of the chemical analysis are established at level 8-16%масс., and they are higher at system heat treatment on air in comparison with heat treatment in an inert (He) medium. Some inconsistency in the results received by a method of spectroscopy of diffuse reflectance and the chemical analysis, which reason while up to the end is not established, is observed. The role of the superficial phenomena on border solid state – saline melt - gas in processes of dispersion of CeO2 and CeF3 is shown.

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca2+, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.

The influence of izonicotinoilhydrazone salicylic aldehyde and its complexes with germanium(IV) and stannum(IV) on the opportunistic bacteria growth has been investigated. It has been shown that studied compounds are able to suppress the test-strain biomass increase at concentrations 25, 50 and 100 pg per ml. The compound I has demonstrated the highest activity towards most used microorganisms At the concentration of this compound 100 pg/ml the biomass increase of some test-strains has been suppressed completely.

Complexes of different types: molecular chelates [SnCl4(HL1,2)]∙nCH3CN (I, II) and zwitterionic [SnCl4(L∙H3-6)] ∙ nCH3CN (III-VI) – were synthesized by interaction of SnCl4 with salicyloyl-(HL1,2), β-,γ- pyridinoyl)hydrazones (НL3-6) of 2- and 4-methoxyaldehydes. Complexes I, II, unlike III-VI, are subjected to solvolysis in DMF by the reaction: [SnCl4(HL1,2)]∙+ ДМФА → [SnCl3(HL1,2)(ДМФА)]∙+ Cl–. The mass spectra of I, II contains peaks of ions with m/z 36[HCl]+, 225[SnCl3]+ and hydrazone 270[HL1,2]+, spectra of III-VI – 36[HCl]+ and 480[120SnCl3(L3-6)]+. In the IR spectra of I, II bands ν(C=O), ν(NH) are displaced to lower frequencies as compared to hydrazones; in the spectra of III-VI they are absent; in I–VI appear new ν(Sn–О) and ν(Sn–N), retained frequency νas(СН3)/νs(СН3), νas(CAr-O-C) and ν(ОH) (I, II). This indicated, that in I–VI realized bidentate coordination of hydrazones in different forms: ketone О(С=О)–N(CH=N) (I, II) or enol О(С–О)–N(CH=N) (III–VI) in the presence of a protonated (HN+Ру) pyridine nitrogen atom. Thermolysis of I–VI begins by dehydrochlorination, which for III–VI occurs at a higher temperature:~ 230(III, V) and 275 (IV, VI) with formation of the final product SnO2. A primary screening of hydrazones and II, V, VI on the manifestation of antimicrobial activity was conducted, it is shown that depending on the concentrations of 25, 50 and 100 mcg/ml they able to significantly inhibit or induce the accumulation of biomass strains of E. coli, S. аureus, B. subtilis. It was found 100% inhibition complex II of all cultures and VI – only B. subtilis.

The influence of izonicotinoilhydrazone 2-hydroxynapht-(H2Inf, I), 4-dimethilamin-obenzaldehydes (HIdb(II)) and its complexes with tin(IV) [SnCl3(InfH)] (III), [H2InfH]2[SnCl6] (IV), [SnCl3(IdbH)] (V) on the opportunistic bacteria growth has been investigated. It has been shown that studied compounds are able to suppress the biomass increase of S. aureus, P. aeruginosa, B. subtilis, M. luteusand P. vulgaris test-strains at concentrations 25, 50 and 100 pg per ml. All compounds have demonstrated the highest activity towards P. vulgaris. The most wide spectrum of antimicrobial activity have demonstrated compounds I, IV.

Prevalence and allelic heterogeneity of hereditary diseases (HDs) could vary significantly in different human populations. Current knowledge of HDs distribution in populations is generally limited to either European data or analyses of isolated populations which were performed several decades ago. Thus, an acknowledgement of the HDs prevalence in different modern open populations is important. The study presents the results of a genetic epidemiological study of hereditary diseases (HDs) in the population of the Karachay-Cherkess Republic (KChR). Clinical screening of a population of 410,367 people for the identification of HDs was conducted. The population surveyed is represented by five major ethnic groups—Karachays, Russians, Circassians, Abazins, Nogais. The study of the populations was carried out in accordance with the proprietary protocol of genetic epidemiological examination designed to identify >3500 HDs easily diagnosed during clinical examination by qualified specialists specializing in the HDs. The protocol consists of the population genetic and medical genetic sections and is intended for comprehensive population analysis based on the data on different genetic systems, including the genes of HDs, DNA polymorphisms, demographic data collected during hospital-based survey. 8950 families (with 10,125 patients) with presumably the HDs were initially identified as a result of the survey and data collection through various sources of registration (from 1156 medical workers from 163 medical institutions). A diagnosis of hereditary pathology was established in 1849 patients (from 1295 families). Two hundred and thirty nosological forms were revealed (in 1857 patients from 1295 families). The total prevalence of HDs was 1:221. Differences between populations and ethnic groups were identified: 1:350 in Russians, 1:195 in Karachays, 1:199 in Circassians, 1:218 in Abazins, 1:135 in Nogais. Frequent diseases were determined, the presence of marked genetic heterogeneity was identified during the confirmatory DNA diagnosis. To explain the reasons for the differentiation of populations by load of HD, a correlation analysis was carried out between the FST (random inbreeding) in populations and HDs load values. This analysis showed genetic drift is probably one of the leading factors determining the differentiation of KChR populations by HDs load. For the first time, the size of the load and spectrum of HDs in the populations of the KChR are determined. We have demonstrated genetic drift to be one of the main factors of the population dynamics in studied population. A significant genetic heterogeneity of HDs, both allelic and locus, was revealed in KChR.