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Toxoplasmosis remains one of the most common opportunistic infections in immunocompromised patients, primarily in people living with HIV. An increase in the number of requests for medical care by patients with HIV infection as the disease progresses determines the need for knowledge of outpatient therapists and general practitioners of decision-making algorithms for suspected toxoplasmosis in such patients. The main clinical manifestations of toxoplasmosis in patients with immunodeficiency states, the formulation of a preliminary diagnosis, and the routing algorithm are given.

The study of variability of morphological features in red-colored varieties of amaranth and their correlations at different stages in the conditions of the Moscow region makes it possible to identify features that affect productivity, amount of amaranthine and other biologically active substances. After analyzing vegetative characteristics, the varietal features of amaranth plants were proved to have a smaller impact on root length, plant height and number of leaves characteristics than the cultivation conditions, especially at the initial stages (ISB (Influence share of the weather conditions) from 22 to 58 %). It follows from the phenotypic variability analysis that the genotypic component values varied significantly only at the last stages (Cvg 35 %). The maximum values of phenotypic variability were marked in all varieties at the stage of active growth considering the root length (Cve = 3247 %) and the number of leaves (Cve = 4885 %). The generative characteristics seemed to be significantly influenced by the varietal factor (ISA (Influence share of varietal characteristics) = 4088 %) starting from the third stage. The genotypic component of all varieties was high considering the inflorescence weight (Cvg = 7586 %). In signs of general productivity, it was studied that the leaves (93112 g/plant) contributed the most for amaranth forms, which mass in all varieties largely depended on weather conditions (ISB 55 %). The interrelation of the leaves productivity was noted high with all the vegetative characteristics on phase III-V (r = 0.710.92) and with inflorescence mass on phase V-VI.

The aim of our study was to analyze the reproduction dynamics and fertility rates of the Ayrshire cattle population in Russia and to assess the level of influence of the AH1 haplotype on the incidence of stillbirth. For an overall fertility estimate, we used 390,769 records of 67 dairy herds in Russia from 2003 to 2018. Against the background of stable population growth, the average stillbirth rate was 3.33% and the abortion rate was 0.075%. A high percentage of stillbirth (5.13%) from heifers the first fertilization event, and there was a high rate of abortions in older cows (11 calving, 1.76%). An analysis of 62,534 records of bulls with the rs475678587C>T variant of UBE3B gene (AH1 haplotype) (n = 69, of which 51 bulls were free from and 18 were carriers of AH1) for the period 2002 to 2018 showed that the proportion of female offspring of AH1-C bulls completing at least one full period of lactation was about one-third of the total livestock. An analysis of the results of mating with AH-F and AH-C bulls for the broodstock as a whole (without taking into account the female genotype) did not reveal significant differences in the number of stillbirths and abortions. Linear regression analysis showed that the status of AH1 bulls did not significantly affect stillbirth rates. An analysis of the results of calving and the reproductive ability of the offspring of AH-C bulls showed an increase in the frequency of stillbirths, confirmed by the results of linear regression analysis, which revealed a significant effect of bull fathers carrying AH1on the proportion of stillbirths experienced by their daughters. Our studies confirm that the rs475678587C>T variant of the UBE3B gene (haplotype AH1) has a significant effect on the rate of stillbirth of a cow or heifer if their father is a carrier of this genetic defect.

Our aim was to give a comparative assessment of the effectiveness of using narlaprevir in combination with pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) and interferon-free mode in patients with chronic hepatitis C (CHC).The prospective cohort study included 187 patients infected with genotype 1b of hepatitis C virus. Of these, 107 (the 1st group of patients) received narlaprevir 200 mg once a day, ritonavir 100 mg once a day, Peg-IFN-alpha-2a 180 mkg subcutaneously once a week and ribavirin at a dose depending on body weight (10001200 mg per day) for 12 weeks, and then the standart "dual" therapy (Peg-IFN-alpha-2a + ribavirin) was continued until 24 weeks. Patients of the 2nd group (n=80) received antiviral therapy in an interferon-free mode. They received narlaprevir 200 mg once daily, ritonavir 100 mg once daily, and daclatasvir 60 mg once daily for 12 weeks.With the use of an interferon-containing treatment regimen, a sustained virological response was achieved in 92.4% of previousle untreated patients with CH and in 66.7% patients with "unsuccessful" experience of the previous course of treatment. In 5.6% of cases, there was an early termination of treatment due to the development of adverse events. 80 (100%) patients completed the course of treatment with narlaprevir in the interferon-free mode. Sustained virological response was reached by 75 (90%) patients.Real clinical practice indicates that the use of narlaprevir in the non-interferon mode is not inferior in efficiency to the interferon-containing treatment regimen and demonstrates a more favorable safety profile.Цель. Дать сравнительную оценку эффективности применения нарлапревира в комбинации с пегилированным интерфероном-a2а (Пег-ИФН-a2а) и в безинтерфероновом режиме у больных хроническим гепатитом С (ХГС). Материалы и методы. В проспективное когортное исследование включены 187 пациентов, инфицированных вирусом гепатита C генотипа 1b. Из них 107 человек (группа 1) получали нарлапревир по 200 мг 1 раз в сутки, ритонавир по 100 мг 1 раз в сутки, Пег-ИФН-a2а 180 мкг подкожно 1 раз в неделю и рибавирин в дозе, зависящей от массы тела (10001200 мг/сут) на протяжении 12 нед, после чего была продолжена стандартная двойная терапия (Пег-ИФН-a2а-a2а+рибавирин) до 24 нед. Больным группы 2 (n=80) противовирусную терапию проводили в безинтерфероновом режиме. Они получали нарлапревир в дозе 200 мг 1 раз в сутки, ритонавир 100 мг 1 раз в сутки и даклатасвир 60 мг 1 раз в сутки в течение 12 нед. Результаты. При применении интерферонсодержащей схемы лечения устойчивый вирусологический ответ достигнут у 92,4% ранее не леченных больных ХГС и у 66,7% пациентов с неудачным опытом предыдущего курса лечения. В 5,6% случаев имело место досрочное прекращение терапии ввиду развития нежелательных реакций. Курс лечения нарлапревиром в безинтерфероновом режиме завершили 80 (100%) пациентов. Устойчивый вирусологический ответ зарегистрирован у 75 (90%) человек. Заключение. Реальная клиническая практика свидетельствует о том, что применение нарлапревира в безинтерфероновом режиме не уступает по эффективности интерферонсодержащей схеме лечения и демонстрирует более благоприятный профиль безопасности.

Набор новых сотрудников неизбежно влечет за собой материальные затраты и материальные потери. Поэтому задача органов управления различных уровней заключается в обеспечении приема специалистов, способных качественно выполнять должностные обязанности при оптимальных затратах на их отбор.

The discovery of insulin in the early 1900s ushered in the era of research related to peptides acting as hormones and neuromodulators, among other regulatory roles. These essential gene products are found in all organisms, from the most primitive to the most evolved, and carry important biologic information that coordinates complex physiology and behavior; their misregulation has been implicated in a variety of diseases. The evolutionary origins of at least 30 neuropeptide signaling systems have been traced to the common ancestor of protostomes and deuterostomes. With the use of relevant animal models and modern technologies, we can gain mechanistic insight into orthologous and paralogous endogenous peptides and translate that knowledge into medically relevant insights and new treatments. Groundbreaking advances in medicine and basic science influence how signaling peptides are defined today. The precise mechanistic pathways for over 100 endogenous peptides in mammals are now known and have laid the foundation for multiple drug development pipelines. Peptide biologics have become valuable drugs due to their unique specificity and biologic activity, lack of toxic metabolites, and minimal undesirable interactions. This review outlines modern technologies that enable neuropeptide discovery and characterization, and highlights lessons from nature made possible by neuropeptide research in relevant animal models that is being adopted by the pharmaceutical industry. We conclude with a brief overview of approaches/strategies for effective development of peptides as drugs. SIGNIFICANCE STATEMENT: Neuropeptides, an important class of cell-cell signaling molecules, are involved in maintaining a range of physiological functions. Since the discovery of insulin's activity, over 100 bioactive peptides and peptide analogs have been used as therapeutics. Because these are complex molecules not easily predicted from a genome and their activity can change with subtle chemical modifications, mass spectrometry (MS) has significantly empowered peptide discovery and characterization. This review highlights contributions of MS-based research towards the development of therapeutic peptides.

AIM: Evaluation of the features of the genomic architecture of Ayrshire cattle in Russia in comparison with other dairy populations of Bos taurus. MATERIALS AND METHODS: Using bioinformatic analysis of 42628 SNP markers obtained during genotyping using the BovineSNP50_v3 BeadChip medium density microarray, the features of the genomic architecture of five Bos taurus populations of different breeds were revealed. RESULTS: The domestic population of Ayrshire cattle was characterized by the lowest heterozygosity (Ho = 0.335, He = 0.339) and insignificant inbreeding (Fis = 0.010) MDS analysis. At the same time, domestic breeding animals formed a separate group within a single cluster of Ayrshirs. CONCLUSION: The Russian population of Ayrshire cattle is distinguished by a unique genome architecture, while retaining the genetic variants of the Finnish Ayrshire cattle and minor traces of Holstein gene pool.

Analytical and technological advancements in multidimensional ion mobility-mass spectrometry and molecular dynamic simulations catalyze the birth of a new precise strategy for fine-tuning Aβ42 structure and cytotoxicity.

The legal framework for the provision of medical care, its evaluation and control of quality in Russia requires the attending physician to strictly comply with the provisions of regulatory documents. At the same time, clinical practice shows that the recommended algorithms for the provision of care do not allow in all situations to provide medical care of adequate quality. Analysis of the clinical example shows that in the era of the COVID-19 pandemic, in addition to compliance with the established rules, a thorough assessment of a specific clinical situation in the dynamics of development is necessary and timely correction of treatment and diagnostic measures, including those in excess of the established requirements, are required. The methods of remote monitoring of the patients condition need to be improved, since in their current form they do not provide an objective assessment of the patients condition. Face-to-face examinations of patients with COVID-19 receiving medical care at home should be carried out at least every 72 hours, regardless of the result of the remote assessment. The absence of the effect of therapy within three days may be an indication for transferring the patient to a higher level of medical care.

The article focuses on phenological features of amaranth varieties grown in open fields as a reaction to variability of weather conditions in the Moscow region. Amaranthine is one of the promising compounds found in red-colored amaranths. It refers to a class of betalain pigments. The study revealed growth stages defined by the highest content of amarantine per plant and analyzed accumulation of the pigment in amaranth leaves and inflorescences. Phenological observations of introduced plant species under new conditions are important and determine their resistance to adverse environmental factors, ability to produce high quality fruits and seeds, and potential for cultivation. During the introduction of new amaranth varieties, the most adapted forms were selected for the conditions of the Non-Chernozem zone of the Russian Federation in 2013-2016. The studied Russian and Ecuador varieties were divided into 4 groups depending on the growth period (from germination to seed maturity). Analysis of phenological traits of plants confirmed that period of amaranth development did not depend on the variety, except the fourth stage of late-ripening cultivars - Don Pedro and Eku 17020, dependent on weather conditions. Being dependent on weather conditions, the vegetative growth period turned to be the most stable. Late cv. Eku 17020 did not form mature seeds in open ground conditions, which is explained by its origin (Ecuador). In the present study we identified growth stages when plant raw materials had the highest dye content in red-leaved amaranth varieties (Valentina, Don Pedro and Fakel). We also considered the perspective of cultivation of green-leaved varieties with red inflorescences - Pamyati Kovasa and Eku-17020 - as sources of biologically valuable compounds in the Moscow region.

Peptidergic dense-core vesicles are involved in packaging and releasing neuropeptides and peptide hormones—critical processes underlying brain, endocrine and exocrine function. Yet, the heterogeneity within these organelles, even for morphologically defined vesicle types, is not well characterized because of their small volumes. We present image-guided, high-throughput mass spectrometry-based protocols to chemically profile large populations of both dense-core vesicles and lucent vesicles for their lipid and peptide contents, allowing observation of the chemical heterogeneity within and between these two vesicle populations. The proteolytic processing products of four prohormones are observed within the dense-core vesicles, and the mass spectral features corresponding to the specific peptide products suggest three distinct dense-core vesicle populations. Notable differences in the lipid mass range are observed between the dense-core and lucent vesicles. These single-organelle mass spectrometry approaches are adaptable to characterize a range of subcellular structures.

Water conservation is vital for life in the desert. The dromedary camel (Camelus dromedarius) produces low volumes of highly concentrated urine, more so when water is scarce, to conserve body water. Two hormones, arginine vasopressin and oxytocin, both produced in the supraoptic nucleus, the core hypothalamic osmoregulatory control centre, are vital for this adaptive process, but the mechanisms that enable the camel supraoptic nucleus to cope with osmotic stress are not known. To investigate the central control of water homeostasis in the camel, we first build three dimensional models of the camel supraoptic nucleus based on the expression of the vasopressin and oxytocin mRNAs in order to facilitate sampling. We then compare the transcriptomes of the supraoptic nucleus under control and water deprived conditions and identified genes that change in expression due to hyperosmotic stress. By comparing camel and rat datasets, we have identified common elements of the water deprivation transcriptomic response network, as well as elements, such as extracellular matrix remodelling and upregulation of angiotensinogen expression, that appear to be unique to the dromedary camel and that may be essential adaptations necessary for life in the desert.

Статья посвящена проблеме сохранения и укрепления психологического здоровья детей. Необходимость решения данной проблемы возрастает особенно на данный момент, когда стремительно растет количество детей, переживающих эмоциональное неблагополучие, что приводит к соматическому ослаблению детей, развитию у них неврозов, а также появлению высокого уровня тревожности. Для предотвращения данных состояний необходимо внедрять в работу педагогов здоровьесберегающие технологии, которым в настоящее время не уделяется должного внимания.

Both the endocrine and exocrine pancreas demonstrate morphological and chemical changes associated with T2D development. Despite significant progress, chemical profiles of the islets and acinar tissue following disease progression are not well characterized. In this work we investigated isolated populations of pancreatic islets (n=18) and acinar tissues (n=7) collected from healthy and T2D affected pancreata using several mass spectrometry (MS) approaches. Samples are provided by the ADI IsletCore and the Network for Pancreatic Organ Donors with Diabetes (nPOD) . Both peptide and metabolite profiles were determined and compared via chemical profiling with matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance MS. Not surprisingly, the peptide profiles from T2D islets demonstrated lower signal intensities compared to healthy islets (ROC analysis, AUC=0.9) . Somatostatin, pancreatic icosapeptide, and insulin-related signals are most decreased. Preliminary data for acinar tissues indicate lower peptide levels in samples collected from T2D-affected (n=2) vs. healthy (n=5) pancreata. Several unique peptides are detected specifically in acinar tissue obtained from T2D-affected pancreata. Liquid chromatography-MS reveals a complex endogenous peptide complement of acinar tissue. Analysis of extracellular media for both islet types demonstrated similar differences (AUC=0.7) indicating higher levels of observed peptides in preparations from healthy islets, perhaps suggesting that peptides are released from the islets during shipment. Integrity of received islets was verified using dithizone staining prior to measurement. In contrast, almost no peptide markers of acinar tissue are found in corresponding extracellular media. Our results enhance knowledge on biochemical signature of T2D in the pancreas. Disclosure S.Rubakhin: None. E.V.Romanova: None. J.V.Sweedler: None. Funding American Diabetes Association (1-18-VSN-19)

Importance Assessment of the causative association between the COVID‐19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy‐confirmed causes of death in patients who died with COVID‐19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID‐19 (DAD). Methods Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post‐mortem SARS‐CoV‐2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. Results COVID‐19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID‐19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID‐19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID‐19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. Conclusions Vast majority of all PCR‐positive fatalities, including out‐of‐hospital deaths, during the SARS‐CoV‐2 pandemic were related to DAD caused by COVID‐19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology‐confirmed lymphocyte myocarditis was a rare finding.

Single cell analysis strives to probe molecular heterogeneity in morphologically similar cell populations through quantitative or qualitative measurements of genetic, proteomic, or metabolic products. Here, we applied mass analysis of single neurons to investigate cell-cell signaling peptides. The multiplicity of endogenous cell-cell signaling peptides is a common source of chemical diversity among cell populations. Certain peptides can undergo post-translational isomerization of select residues, which has important physiological consequences. The limited number of single cell analysis techniques that are sensitive to peptide stereochemistry make it challenging to study isomerization at the individual cell level. We performed capillary electrophoresis (CE) with mass spectrometry (MS) detection to characterize the peptide content of single cells. Using complementary trapped ion mobility spectrometry (TIMS) separations, we measured the stereochemical configurations of three neuropeptide gene products derived from the pleurin precursor in individual neurons (N = 3) isolated from the central nervous system of Aplysia californica. An analysis of the resultant mobility profiles indicated >98% of the detectable pleurin-derived peptides exist as the non-isomerized, all-L forms in individual neuron cell bodies. However, we observed 44% of the Plrn2 peptide from the pleurin precursor was present as the isomerized, D-residue-containing form in the nerve tissue. These findings demonstrate an unusual distribution of isomerized peptides in A. californica and establish CE–TIMS MS as a powerful analytical tool for investigating peptide stereochemistry at the single cell level.

Noncovalent interactions between DNA and proteins are vital for cells. DNA-protein crosslinking may occur due to various endogenous and exogenous factors, as well as chemotherapeutic agents, and often affects the performance of DNA-binding proteins. Oligodeoxyribonucleotides with a reactive group can serve as a tool to investigate the structure and action of DNA-binding proteins. Here, we report the crosslinking of MutS, which is a sensor protein of DNA mismatch repair (MMR) in Escherichia coli, via the protein’s cysteine. This was realized via DNA that harboured a 2′-deoxy-2′-[3-(2-pyridyldithio)propionamide] group as part of a nucleoside at a given position, and two fluorophores. The proposed DNA duplex consisted of complementary oligonucleotides with breaks in the top and bottom strands. This feature allowed us to introduce the reactive group at different positions and made it possible to synthesize only the central fragment of the DNA with a minimal length. The MutS-DNA conjugate was obtained by thiol-disulfide exchange with quantitative yield and separated from the unreacted DNA by size-exclusion chromatography. Fluorescence resonance energy transfer was used to show that MutS remained functionally active within the conjugate, since the protein was able to change its conformation and DNA conformation as well.

The impact of growth conditions on the fluorescent characteristics of the leaves of the vegetable and cultivated oilseed forms of soybean (Glycine max (L.) Merr.), which were introduced in central Russia for the first time, was studied. The following parameters of fluorescence induction were used: NPQ (nonphotochemical fluorescence quenching), qP (photochemical fluorescence quenching), Qy (actual quantum yield of photochemical reactions in photosystem II), Qymax (maximum quantum efficiency of photosystem II), and Rfd (vitality coefficient). Using soybean plants in the flowering and technical ripeness phases as an example a direct relationship between nonphotochemical quenching and the Rfd indicator (r = 0.95), as well as an inverse relationship between the Fv indicator with photochemical quenching (r = –0.89 and r = –0.78 in the flowering and technical ripeness phases, respectively) was shown. The biochemical parameters were studied and their correlation with the photosynthetic parameters of the leaves of vegetable forms of soybean was analyzed. As an example, the accumulation of antioxidants had approximately the same moderate degree of correlation (r = 0.40) with Qymax, Rfd, and qRstat. At the end of the growing season, the correlation of the vitality coefficient in the technical ripeness phase with the productivity of vegetable soybean in the phase of full biological ripeness, namely, the weight of the plant (including the underground part), the number of beans per plant, and the weight of seeds per plant, were analyzed. There was a stable positive correlation between these indicators from r = 0.78 (with the mass of the plant and the mass of seeds from the plant) to 0.90 (with the number of beans per plant). The vitality coefficient has practical significance, playing the role of a quantitative characteristic of plant productivity, which makes it possible to use PAM fluorimetry in the assessment of the physiological state of a plant organism and its economic efficiency.

The mismatch repair system (MMR) ensures the stability of genetic information during DNA replication in almost all organisms. Mismatch repair is initiated after recognition of a non-canonical nucleotide pair by the MutS protein and the formation of a complex between MutS and MutL. Eukaryotic and most bacterial MutL homologs function as endonucleases that introduce a single-strand break in the daughter strand of the DNA, thus activating the repair process. However, many aspects of the functioning of this protein remain unknown. We studied the ATPase and DNA binding functions of the MutL protein from the pathogenic bacterium Neisseria gonorrhoeae (NgoMutL), which exhibits endonuclease activity. For the first time, the kinetic parameters of ATP hydrolysis by the full-length NgoMutL protein were determined. Its interactions with single- and double-stranded DNA fragments of various lengths were studied. NgoMutL was shown to be able to efficiently form complexes with DNA fragments that are longer than 40 nucleotides. Using modified DNA duplexes harboring a 2-pyridyldisulfide group on linkers of various lengths, we obtained NgoMutL conjugates with DNA for the first time. According to these results, the Cys residues of the wild-type protein are located at a distance of approximately 18–50 A from the duplex. The efficiency of the affinity modification of Cys residues in NgoMutL with reactive DNAs was shown to decrease in the presence of ATP or its non-hydrolyzable analog, as well as ZnCl2, in the reaction mixture. We hypothesize that the conserved Cys residues of the C-terminal domain of NgoMutL, which are responsible for the coordination of metal ions in the active center of the protein, are involved in its interaction with DNA. This information may be useful in reconstruction of the main stages of MMR in prokaryotes that are different from γ-proteobacteria, as well as in the search for new targets for drugs against N. gonorrhoeae.

Las musáceas son muy importantes para fines de alimentación a nivel mundial, en el Ecuador estas ocupan el 20,57 % de la superficie plantada, siendo el cantón El Carmen, uno de los principales sitios dedicados a esta explotación. Por otra parte, Ralstonia solanacearum, es la causante de la enfermedad conocida como Moko de plátano, la cual puede desaparecer el 100 % de una plantación. El objetivo fue, realizar una caracterización morfológica y bioquímica de R. solanacearum Raza 2, bacteria patógena en cultivos de banano y plátano en El Carmen, Manabí, Ecuador. El análisis bioquímico y morfológico, se realizó en los laboratorios de la Universidad de las Fuerzas Armadas-ESPE considerando los protocolos establecidos por diversos autores, las muestras se tomaron de plantaciones de plátano y banano (suelo y pseudotallo georeferenciadas), con síntomas de infección del Moko. Como resultado, se identificó virulencia en la mitad de las muestras, se confirmó que la bacteria es Gram negativa, en forma de bacilo, positiva a catalasa, indol negativa, con carácter oxidativo (energía en medios anaeróbicos); y fermentativos de lactosa y glucosa, sin presencia de ácido sulfhídrico, quien no fue capaz de hidrolizar almidón, in vitro; se confirmó que la temperatura de 4°C y pH de 4,5 inhiben el aumento de estas poblaciones bacterianas, sin embargo, los rangos de 25 y 37°C con pH de 6,5 a 8,5 no resultaron ser restrictivos para su propagación, por lo que se afirma, que El Carmen cumple con los estándares requeridos, para que el patógeno prolifere de manera óptima.

The present paper explores the history of one of the Tver Kremlin cemeteries first surveyed archaeologically in 1998 (figure 1). Based on the analyses of the material gained and its dating the authors indicate the period of the studied part of necropolis functioning as the second quarter of the 16th – the border of the 16–17th centuries (figures 2–5). The cemetery existed by the wooden church which was destroyed probably in the period of “the Time of Troubles” in the early 17th century. The church stood in the western part of the Tver Kremlin, 200 meters to the west of central ensemble of stone temples including the Cathedral of Transfiguration of Our Saviour as well as constructions of Prince’s Yard and the Bishop’s one. The consecration of the necropolis’ church has been determined probably as “the Church of Life-giving Trinity over the Bishop’s Yard” [6, р. 296]. Authors came to the conclusion on the basis of studying several written and archaeological sources.

Snakes have a well-developed hematopoietic and immune system, demonstrate responses to the full range of environmental factors and are a unique object for environmental research. The issues of assessing the immune status of snakes under the influence of anthropogenic press in different biotopic environmental conditions remains poorly understood. Therefore, it is particularly relevant to search for population markers that allow us to assess the work of the effector mechanisms of the immune system determining the process of forming adaptive responses of the body. The aim of the work was a comparative assessment of the leukocyte blood system of the tesselated water snake Natrix tessellata (Laurenti, 1768) of the Northern and Eastern Pre-Caspian. The lymphocyte-granulocyte composition of peripheral blood of the water snake Natrix tessellata was characterized by a predominance of agranulocytes (70–75 %), the proportion of granulocytes was 25–30 %. The redistribution of the ratio of granulocytes to agranulocytes was established in the blood of individuals of the studied populations from different biotopes. The content of heterophiles, monocytes was increased and content of lymphocytes was reduced in individuals of the Eastern Pre-Caspian compared with individuals of the Northern Pre-Caspian. Intersex differences were observed in the content of azurophils, the proportion of which in the blood of females of the water snake from the Northern Pre-Caspian was higher compared to males. Integral indices (ISGE, ILG, ISGL) revealed the same type of variability in the parameters of the blood leukocyte system of females and males living in the areas of the Caspian lowland. The revealed differences in the parameters of the white blood cell system of water snakes may be related to their seasonal ontogenetic activity. The non-specific protective system of the blood of snakes responds faster and more effectively to a wide range of pathogenic antigens of the environment, compared with adaptive responses. Consequently, during the mating period, it is the innate defense system, characterized by higher development in ectothermic animals that provided maximum protection and stable functioning of the body.