bluuebunny/crossref_metadata_2025 huggingface dataset:
Three Generations of the Basins of the Early Turkestan Ocean: Ediacaran–Silurian of the Southern and Middle Tien Shan
Authors: Biske Yu. S. , Алексеев Д.В.
Published: April 2024

The results of U–Pb dating of detrital zircon from volcanoterrigenous Ediacaran–Silurian deposits, mainly from grauwacke turbidites, after accretion of which the “Caledonian” basement of the Paleozoic structure was formed in Kyzylkum and in the ridges of the Southwestern Tien Shan, including Northern Fergana, allowed us to clarify the age correlation and show the dynamics of the formation of this complex. It consists of deposits associated with the opening, filling and subsequent convergent development of three generations of oceanic basins, including the emergence and destruction of island arcs. The earliest of these basins was formed at the active volcanic margin of the eastern Rodinia/Gondwana, which included the Karakum-Tajik massif. Sandy turbidites (Besapan, etc.), whose age is not younger than the beginning of the Cambrian, were deposited here on top of siliceous (Taskazgan) Ediacaran sediments. The second generation is represented by Ordovician basins, in which radiolarian flints of the Lower Ordovician form the bathyal part of the sediments, and the main filling is turbidites of the middle Ordovician–Ruddan. The newly opened Silurian oceanic basins and their margins were filled with sediments of the third Caledonian generation, mainly graptolite aleuropelites and turbidites, starting from the end of the Llandovery. Incomplete preservation of the Ediacaran–Silurian sedimentary series is due to their partial absorption (tectonic erosion) during further subduction and collision, mainly already in the Carboniferous.
Hemipelagic Deposits of the Emsian (Dzhaus Beds, Lower Devonian) in the West of the Zeravshan Range, Kitab Geological Park, Uzbekistan
Authors: Mikhailova E. D. , Tarasenko A. B. , Барабошкин Е.Ю.
Published: April 2024

The features of sedimentation of hemipelagic deposits of the Emsian (Dzhaus Beds, Zeravshan Range, Khodzha-Kurgan valley) are reconstructed and the duration of eustatic events in this area is established on the basis of tentaculite and conodont zonality. In the studied region the Emsian Khodzha-Kurgan transgression began at the end of the pireneae zone and continued until the end of the patulus zone. The transgression maximum occurs in the Dzhaus Beds. In the Dzhaus Beds, the presence of traces of two eustatic rises, accompanied by anoxic sedimentation, and one fall of the paleobasin level were revealed. The conclusions are based on the analysis of the lithology of the Dzhaus Beds and the changes in the hydrodynamic regime in the sedimentation basin. Traces of the maximum subsidence of the sea level are recorded in the interval 29–72 m of 16-th Member (elegans tentaculite zone, inversus conodont zone). Sea level rise was recorded in the intervals of the entire 15-th Member, 0–28 and 73–102 m of 16-th Member (elegans and cancellata tentaculitic zones, inversus u serotinus conodont zones). In terms of time, the Dzhaus transgressions can be compared with the Czech Late Zlichovian and Early Dalejan eustatic events. The change in the composition of the D-zhaus cephalopod, brachiopod, and ostracod associations occurs in the elegans tentaculite zone. The information obtained from the study of the section of the Dzhaus Beds in the Khodzha-Kurgan valley makes it possible to relatively accurately date the Emsian eustatic oscillations in the South Tien Shan region. This gives the studied section a certain correlation value, since the details of the Emsian transgressions revealed in it can be used in the global correlation of eustatic events and be criteria for substantiate the position of the boundaries of the Emsian substages in the South Tien Shan.
Middle Ura Association of Organic-Walled Microfossils: The Lower Vendian of the Patom Basin, Siberia
Authors: Vorob’eva N. G. , Petrov P. Yu. , Лужная Е.А.
Published: April 2024

A new assemblage of Early Vendian (Middle Ediacaran) microfossils, including acanthomorphic acritarchs and various filamentous remains, as well as sphaeromorphic striated vesicles of Valeria, which are not characteristic of deposits of this age, is described in the Ura Formation of the Dal’nyaya Taiga Group of the Patom Basin. A new species of acanthomorphs Hocosphaeridium crispum sp. nov. is described. The selective confinement of the Ediacaran eukaryotic phytoplankton taphocoenoses to the open-sea proximal facies of the inner ramp is shown.
THE HEIGHT OF CHILDREN IN RUSSIAN TOWNS IN THE 15th–17th CENTURIES
Authors: Chechetkina Olga Yu.
Published: April 2024

Fieldwork of the Institute of Archaeology RAS in recent years has made it possible to unearth several hundred children’s burials, which belong to a narrow chronological range. Comparative research into these materials enabled to refine our understanding of the life quality of Russian towns’ population during the late Middle Ages. The study sample includes the remains of children aged from new-born to 10 year-old from the 16th–17th centuries cemetery at the Church of St. John Chrysostom, Yaroslavl, and a synchronous sample from the excavations of the Tula Kremlin. For comparison, previously published materials from excavations of other contemporary necropolises were employed. In constructing growth graphs, only those cases were taken into account, where the preservation made it possible to determine the age by the teeth confirmed by microfocus radiography. The lengths of tubular bones in children from all archaeological samples were smaller (with the exception of the sample from the Novokharkovskoye cemetery) than modern standards. Children from Yaroslavl, Tula and Mozhaysk were smaller than children of the 14th–17th centuries from the Lithuanian city of Alytus. Between the ages of one to seven, they were considerably smaller than the English children from Yorkshire (Wharram Percy Cemetery), but then overtook them in size. Comparison with Polish urban samples shows an early growth acceleration in Yaroslavl and Tula children at the age of seven rather than at eight. However, the clavicle length in children under the age of 10 from archaeological samples was practically the same as in the modern group, which probably imply that this feature can be used to determine the biological age of young children in groups of similar chronology.
GENETIC DIVERSITY OF THE CENTRAL CAUCASIAN REGION POPULATION IN THE 1st millennium BC – 1st millennium AD BASED ON MITOCHONDRIAL DNA
Authors: Korobov Dmitry S. , Boulygina Eugenia S. , Slobodova Natalia V. , Sharko Fedor S. , Nedoluzhko Artem V.
Published: April 2024

This study is the first attempt to analyze the genetic diversity of the Central Ciscaucasia population during the Late Bronze Age – Early Iron Age and Early Middle Ages. The authors analyzed 120 samples from 10 burial grounds of the Koban and Alan archaeological cultures, as well as representatives of the Middle Sarmatian culture and the North Caucasian population of the Sarmatian period. Data on the variability of mitochondrial DNA (m-tDNA) of 71 individuals were obtained. An analysis of the previously collected and published information allows concluding that the analyzed populations are characterized by a significant diversity of mtDNA with a predominance of West Eurasian mitochondrial haplogroups. East Eurasian lines of inheritance can be traced in small numbers among the population of the Koban culture (5%), as well as among the Sarmatian (14%) and Alanian populations (11%). The most common lines of Western Eurasian origin are different variants of haplogroups H, U and N. At the same time, a significant diversity of mtDNA haplogroups is observed at all burial sites, except for the Kich-Malka II burial ground, where during the 7th century BC – the early 6th century AD the succession of individuals on the maternal line was recorded, represented by haplogroup H2a2a1. Study in the latter requires a more detailed approach using whole genome sequencing. Comparison of the analyzed sample with previously published data on the genetic portrait of the North Caucasus population in the Early and Middle Bronze Age makes it possible to conclude that representatives of the East Eurasian cluster of mtDNA haplogroups arrived in the Central Ciscaucasia rather late, it was probably associated with contacts between the Koban culture carriers and the nomadic steppe population.
A BURIAL OF THE 8th–9th CENTURIES AD IN ASTRAKHAN REGION AND A POT WITH A RUNIC INSCRIPTION
Authors: Lebedev Yuri S. , Popov Pavel V.
Published: April 2024

On the territory of Astrakhan Region, an unusual burial was investigated containing a molded pot with a runic inscription on the body made in the Don script. This find is unique for the Lower Volga region. The burial is dated to the late 8th–9th century AD and can be correlated with the Bulgarian tribes. In addition to this complex, about 15 more burials with a similar ritual and accompanying goods were found in the Lower Volga region. All of them also correlate with the Bulgarians and date back to the late 8th–9th century AD. These complexes are contemporary with the Sokolovo-type burials under mounds found in the Lower Volga region. The material from those sites suggests that they were synchronous; interethnic and cultural contacts are traceable. Isolation of the Bulgarian component makes it possible to clarify the ethnic and cultural situation in the Lower Volga region in the Khazar period. The found pot with a runic inscription from Kazachiy hillock in Astrakhan Region clearly testifies to its connections with the area of the Saltov-Mayaki culture.
METAL OBJECTS FROM EXCAVATIONS AT THE JOASAPH SITE (JERICHO) IN A PHOTOGRAPH OF THE 1880–1890s
Authors: Belyaev Leonid A. , Golofast Larisa A.
Published: April 2024

At the end of the 19th century, one of the Russian photographers took pictures of items collected on the site which Father Joasaph bought in 1883. Later, the area was transferred to the Imperial Orthodox Palestine Society. Now it houses the Museum and Park Complex that belongs to the Russian Federation. An analysis of ceramic objects in one of the photographs was published earlier. This article discusses the second picture, which contains objects made of bronze and iron. Their analysis made it possible to identify the liturgical function of a significant part of the objects: an incense burner on chains, high stands – candelabra for oil lamps (3 items) and one such lamp; a fragment of a libation vessel shaped as a dog. One item shown in the photo remained unattributed despite numerous consultations. In general, the composition of the finds supports the authors’ assessment of the site as belonging to a Christian community, possibly a monastery or a pilgrimage home.
METHOD FOR CREATING A GENERALIZED PORTRAIT-RECONSTRUCTION OF A PALAEOANTHROPOLOGICAL GROUP BASED ON 3D SKULL MODELS
Authors: Rasskazova Anna V.
Published: April 2024

The article presents a new method for visualizing paleoanthropological data – a generalized portrait-reconstruction based on craniological data. A generalized or composite portrait is widely used in studying modern population; it provides generalized visual information about the facial morphology of any population sample. Palaeoanthropological morphological studies also rely on group data, but often lack summarizing visual information. The method of craniofacial reconstruction provides reliable portraits of individuals from ancient groups. However, individual craniofacial reconstructions do not give insight into the morphology of the entire group or the difference between groups. The proposed method creates a craniofacial reconstruction based on a generalized three-dimensional model of the skull, built on the mean values of the coordinates of landmarks placed on the surfaces of models of all skulls in the sample. Testing this method on two morphologically different craniological samples showed that the final summary model reproduces the specific facial morphology of each group and the selected number of landmarks is sufficient. A generalized portrait-reconstruction illustrates morphological features and differences between paleoanthropological groups, and allows visual comparisons with modern populations.
GLASS OBJECTS OF THE RUS PERIOD FROM VSHCHIZH (BASED ON THE 2014–2015 WORKS IN THE POSAD AND OUTER TOWN)
Authors: Stolyarova Ekaterina K. , Minenko Vladimir V.
Published: April 2024

The town of Vshchizh in Rus has been known from chronicles since 1142. In the middle of the 12th century, it turned from a small border fortress into the capital of a small apanage principality, a vassal to Chernigov. In 1238, the city was ravaged by the troops of Batu and ceased to function as an urban settlement. The article considers glass objects of the Rus period found in the outer town and the posad (suburb) of Vshchizh (the total number is 198 objects). The overwhelming majority of this number is represented with bracelets (186 objects). In addition, there are six beads, four fragments of finger-rings and fragments of two vessels. Most of the finds (182 objects) are products of glass-making craft of Rus, the rest (16 fragments of bracelets) are attributed to Byzantine manufacture. The bulk of glassware dates back to the second half of the 12th – first third of the 13th century AD, and only a small number of items existed, possibly, in the second half of the 13th–14th century AD.
BURIAL OF A REPRESENTATIVE OF THE LOCAL ELITE IN ALTAI OF THE MIGRATION PERIOD
Authors: Seregin Nikolay N. , Tishkin Alexey A. , Matrenin Sergey S. , Parshikova Tatiana S.
Published: April 2024

The article presents the results of studying materials obtained during excavations of a female burial found in the Choburak-I necropolis of the Bulan-Koby archaeological culture. This site located in Chemal district of the Altai Republic was fully studied by the expedition of Altai State University. An analysis of the morphological characteristics of the found accompanying grave goods was conducted employing analogies from sites in adjacent territories. Together with the results of radiocarbon dating it became the basis for determining the time of construction of mound 34 within the 4th century AD. The study of the recorded features of ritual practice made it possible to establish that the burial was made by the bearers of the Dialian burial tradition, which constituted the dominant group of the population of the Northern Altai in the pre-Turkic period. Numerous goods, which included socially significant adornments in the attire of the buried, as well as items of horse gear, testify to a high status of the deceased woman in her lifetime, probably a representative of the local nomadic elite.
Structural Optimization of an α-Hairpinin Blocking Potassium Channels KV1.3
Authors: Gigolaev A. M. , Tabakmakher V. M. , Peigneur S. , Tytgat J. , Vassilevski A. A.
Published: April 2024

Obtaining compounds with specificity for certain isoforms of ion channels is a significant problem of curent physiology and pharmacology. In a series of papers, we have shown that the α-hairpinin fold can serve as a template for the rational design of peptide ligands of potassium channels. Here, we used molecular modeling to optimize the structure of the previously obtained Tk-hefu-10 peptide, a selective KV1.3 channel blocker, with a half-maximal inhibitory concentration (IC50) of ≈150 nM. Molecular dynamics simulation of the Tk-hefu-10–KV1.3 complex provided information on the interaction of individual amino acid residues of the peptide and channel, and the analysis of these interactions made it possible to propose amino acid substitutions in the structure of Tk-hefu-10 to increase its affinity. Novel Tk-hefu-12 peptide is a truncated analog of Tk-hefu-10 by one residue with five substitutions; it is characterized by an IC50 value of ≈70 nM against KV1.3. In addition, there are no methionine residues in the structure of Tk-hefu-12, which makes it possible to obtain Tk-hefu peptides using cyanogen bromide.
Evolutionary Acquisition of Multifunctionality by Glycolytic Enzymes
Authors: Shatova O. P. , Shegay P. V. , Zabolotneva A. A. , Shestopalov A. V. , Kaprin A. D.
Published: April 2024

Solving the question of the origin of life on Earth is impossible without understanding how the chemical, functional, and regulatory principles that determine cellular metabolism arose, how cells acquired the properties that determine their evolution, and how biological systems function and develop. This review is devoted to the consideration of the versatility of the functions of glycolytic enzymes, the expression of which is significantly increased in some types of cells, for example, cells with stem properties or malignant tumor cells. Almost all glycolysis enzymes have been found to have non-catalytic functions that are necessary to maintain a high rate of cell proliferation, their a-ctive migration, and the formation of a stem-like phenotype. Glycolytic enzymes arose very early during the evolution. Since the genomes of ancient life forms had a limited number of genes to encode the entire set of necessary functions, glycolytic enzymes or the products of the reactions they catalyzed could be used as ancient regulators of intercellular and intracellular communication. Subsequently, the multifunctionality of the main metabolic enzymes began to be used by tumor cells to ensure their survival and growth. In this review, we discuss some of the noncatalytic functions of glycolytic enzymes, as well as the possible evolutionary significance of acquiring such multifunctionality.
Arginine Deiminase of Streptococcus pyogenes M49-16 Disrupts the Confluence of the Monolayer and the Structure of the Actin Cytoskeleton of Endothelial Cells In Vitro
Authors: Mammedova J. T. , Karaseva A. B. , Burova L. A. , Sokolov A. V. , Perepletchikova D. A. , Malashicheva A. B. , Starikova E. A.
Published: April 2024

The actin cytoskeleton is involved in the regulation of the barrier function of the endothelium. The bioavailability of arginine is an important factor determining of actin cytoskeleton dynamics. Pathogenic microorganisms can use arginine-hydrolyzing enzymes to disrupt the confluences of the vascular endothelium for subsequent dissemination. In this study, the effect of streptococcal arginine deiminase on the human umbilical vein endothelial cells monolayer confluence and the actin cytoskeleton structure in vitro was studied. The original technique for obtaining supernatants by sonication destroyed streptococcal cells (SDSCs) of the original strain of Streptococcus pyogenes M49-16 and its isogenic mutant with the inactivated arginine deiminase gene S. pyogenes M49-16delArcA was used in this study. The changes in the L-arginine concentration were evaluated by the modified Sakaguchi colorimetric method. The structure of the actin cytoskeleton was analyzed after cells staining with fluorescent dye labeled phalloidin. The confluence of the endothelial cell monolayer was evaluated morphologically after staining the cells with crystal violet dye. It was found that in the presence of the parental strain-derived SDSC, a significant decrease in the arginine concentration in the endothelial cells culture medium caused dynamic changes in the actin cytoskeleton structure. After 48 hours, lamellae and stress fibers formed. After 72 hours, the content of F-actin decreased and the confluence of the monolayer of endothelial cells was disrupted. Such changes were not detected when cells were cultured under standard conditions and in the presence of mutant strain-derived SDSC. The results obtained show that pathogenic microbes can use arginine depletion to regulate endothelial barrier function and dissemination in the host organism.
Analysis of the Elemental Composition of Gonads, Gametes and Larvae of the Mussel Mytilus galloprovincialis in the Spawning Period
Authors: Kapranova L. L. , Ryabushko V. I. , Kapranov S. V.
Published: April 2024

In this work, we studied the elemental composition of gonads, eggs, sperm and larvae of the mussel Mytilus galloprovincialis during spawning, when the contents of biologically active compounds and minerals are maximal. A comparative analysis of the contents showed that the elements are involved in the mussel gametogenesis in different pathways. There were significant differences in the contents of Li, B, Mg, Si, P, K, Ca, V, Cr, Mn, Fe, Co, Ni, Zn, Ge, As, Se, Br, Rb, Sr, Mo, Pd, Sn, I, Ba and Ce in male and female gonads before and after spawning, gametes and larvae of mussels. It is likely that some of the listed elements are not only passively accumulated in the mollusk body, but are also essential, being directly involved in the reproduction process. Most of significant differences in the element contents were found between eggs and larvae and between male gonads before spawning and sperm. By spawning, mussel gonads accumulated mainly p- and d-elements, apparently due to the ability of their ions to form complexes and, consequently, to be included in the structure of enzymes. The contents of B, Mg, Si, P, K, Ca, Cr, Mn, Fe, Cu, Zn, As, Se, Br, Sr and Ba in male and female gonads, gametes and larvae were an order or several orders of magnitude higher than those of other elements. The contents of Ca, Fe, Sr, Sn and I in mussel larvae were significantly higher than in gonads and gametes. Sn is a technological hydropollutant, and thus, larvae can serve as a bioindicator of the aquatic environment pollution with this element. The data obtained are of practical interest for improving the biotechnology of reproduction of marine hydrobionts and obtaining functional products based on them, which is important for the optimization of aquaculture management and for addressing human health-related issues.
Immunohistochemical Study of Macrophages of Sciatic Rat Nerve after Damage and Subperineural Injection of Mesenchymal Stem Cells
Authors: Petrova E. S. , Kolos E. A.
Published: April 2024

The dynamics of the processes of Wallerian degeneration in the Wistar-Kyoto rat sciatic nerve after injury (ligation, 40 s) was studied.The density of Iba-1+ macrophages and the state of myelin fibers stained with Luxol strong blue in the distal segment of the nerve at different times after injury were studied. Parts of rats were subperineurally transplanted with MSCs from the bone marrow of Wistar-Kyoto rats. It was shown that the highest distribution density of macrophages in the distal segment of the nerve was observed 7 days after surgery. The use of cell therapy leads to a decrease in the number of macrophages during this period and to a delay in the demyelination of damaged nerve fibers. Sixty days after the operation, the macrophage population density and the number of remyelinated regenerating nerve fibers of the distal nerve segment did not differ in control (ligature) and experimental (ligature and MSC injection) animals. The molecular mechanisms of the noted changes in the early stages after injury require further research.
Tim-3, CD9 Molecule Expressions on Natural Killer (NK) and T-Lymphocytes with NK Functions (NKT) of the Peripheral Blood at Different Trimesters of Physiological Pregnancy
Authors: Orlova E. G. , Loginova О. А. , Gorbunova О. L. , Karimova N. V. , Shirshev S. V.
Published: April 2024

Natural killer cells (NK) and T-lymphocytes with NK functions (NKT) are the leading effectors of the mother’s immune tolerance to a semi-allogeneic fetus and have a fetal trophic effect during physiological pregnancy. Tim-3 (T-cell Ig and mucin domain-containing protein 3) and CD9 molecules play a critical role in the immunoregulatory and fetal trophic functions of NK and NKT, but their expression in peripheral blood cells has not been studied. The aim of this work was to study the expression of Tim-3 and CD9 in peripheral blood NK and NKT during physiological pregnancy. The object of the study was the peripheral blood of healthy women in I and III trimesters of a physiological pregnancy. The control group consisted of healthy non-pregnant women in the first phase of the menstrual cycle. Expression of Tim-3, CD9 molecules was analyzed by flow cytometry on regulatory NK (CD16–CD56bright) and NKT (CD16–CD56+), cytotoxic NK (CD16+CD56dim/–) and NKT (CD16+CD56+). It was found that in the first trimester of pregnancy, the total number and subpopulation composition of NK and NKT cells did not change. Tim-3 expression increased in all NK and NKT subpopulations, except for cytotoxic CD16+CD56dimNK. CD9 expression increased in all NK subpopulations, but in NKT did not differ from non-pregnant. At the same time, a direct correlation between CD9 and Tim-3 expressions was revealed in regulatory NK and NKT in the first trimester of pregnancy. In the third trimester, the regulatory CD16–CD56brightNK number increased, while cytotoxic CD16+CD56dimNK and regulatory CD16–CD56+NKT decreased compared to non-pregnant women. The number of CD16+CD56–NK did not change in I and III trimesters of a physiological pregnancy. Tim-3 expression was upregulated in all NK and cytotoxic NKT subpopulations, while CD9 was upregulated only in regulatory NKs. Thus, Tim-3 and CD9 molecule expressions of s on different NK and NKT subpopulations changed during I and III trimesters of a physiological pregnancy, which plays an important role in the regulation of their phenotype and functions.
Cardioprotective Effect of Soy Protein on a High-Salt Diet in Cynomolgus Monkeys
Authors: Kulikov A. N. , Beresneva O. N. , Ivanova G. T. , Parastaeva M. M. , Bogdanova E. O. , Kayukov I. G. , Kucher A. G. , Orlov S. V.
Published: April 2024

Excessive salt intake is accompanied by the development of cardiovascular disorders, not always associated with an increase in blood pressure (BP). Given the cardioprotective effect of soy proteins in chronic kidney disease, the question arose of the possibility of leveling dietary interventions, in particular soy proteins, the damaging effect of a high-salt diet on the cardiovascular system. The aim of this work is to study the effect of long-term use of a diet high in NaCl and soy protein on myocardial remodeling and skin histomorphology in monkeys. The study was performed on male Javan macaques (Macaca fascicularis). The control group received a standard diet (2 g NaCl/kg feed). The second was a high-salt diet (8 g NaCl/kg feed), the third was a high-salt diet and SUPRO760 soy protein (200 g/kg feed). Echocardiography, registration of BP and heart rate were performed at baseline, after 4 and 12 months. After 12 months, a histological examination of the musculocutaneous flap was performed. In all animals, BP and heart rate did not change significantly during 12 months. In macaques on a high-salt diet, by the end of the study, deterioration in systolic and diastolic functions of the left ventricle (LV) was noted. In animals receiving additional soy protein, these changes leveled out. After 12 months, macaques fed soy protein had LV myocardial mass smaller and higher LV contractility than animals fed excess salt without soy protein. In monkeys on a high-salt diet, accumulation of collagen fibers in the hypodermis, hyalinization of the cytoplasm of capillary smooth muscle cells, perivascular and perineural edema of the reticular dermis were revealed. In animals treated with soy protein, skin capillary remodeling was less pronounced. Thus, high salt intake leads to adverse structural and functional disorders of the heart and blood vessels in cynomolgus monkeys, not associated with an increase in blood pressure. The inclusion of soy isolate in the diet reduces the negative effects of a high-salt diet on the cardiovascular system.
The Effect of Maternal Methyl-Enriched Diet on the Number of Dopaminergic Neurons in the Ventral Tegmental Area in Adult Offspring of WAG/Rij Rats
Authors: Fedosova E. A. , Loginova N. A. , Sarkisova K. Yu.
Published: April 2024

WAG/Rij rats are genetic model of absence epilepsy with comorbid depression. Pathologic phenotype in WAG/Rij rats was shown to be associated with reduced dopamine (DA) tone within the mesolimbic DAergic brain system. Previously, it was found that maternal methyl-enriched diet (MED) in the perinatal period increases DA content in the mesolimbic DAergic brain system and reduces absence seizures and comorbid depression in adult offspring of WAG/Rij rats. Ventral tegmental area (VTA), containing DA cells bodies, is a main source of the mesolimbic DA synthesis. The aim of this study was to test the hypothesis that increases in the mesolimbic DAergic tone induced by maternal MED in offspring may be due to an increase in the number of DA-synthesizing neurons in the VTA. Immunohistochemistry for thyrosine hydroxylase (TH) was used to assess the number of TH-immunopositive cells in adult offspring of WAG/Rij rats born to mothers fed control diet or MED and subjected or not subjected to behavioral testing for 2 consecutive days in the light-dark choice, open field, elevated plus maze and forced swimming tests. One hour after the forced swimming test animals were anesthetized. Brains were fixed using transcardial perfusion. The number of DAergic neurons was determined by the number of TH-immunopositive cells on brain slices at the level of VTA. The number of TH-immunopositive cells was counted in left and right hemispheres separately. A significant effect of maternal MED on the number of cells in the VTA expressing TH has been established. Adult WAG/Rij offspring born to mothers fed MED had an increased number of TH-immunopositive cells as compared with the offspring born to mothers fed control diet. Moreover, in WAG/Rij offspring born to mothers fed MED, the number of TH-immunopositive cells was greater in animals subjected to behavioral testing compared with animals not subjected to behavioral testing. The effects of maternal MED and behavioral testing on the number of TH-immunopositive cells in the VTA were equally expressed in the left and right hemispheres of the brain. Results suggest that maternal MED in the perinatal period can affect the developing mesolimbic DAergic brain system, promoting the generation and/or maintenance of DA neurons in the VTA, and thereby prevent the occurrence of genetic absence epilepsy and comorbid depression in the offspring of WAG/Rij rats.
Reactive Changes of Rat Spinal Cord Microgliocytes after Acute Systemic Inflammation
Authors: Kolos E. A. , Korzhevskii D. E.
Published: April 2024

It is widely known that neuroinflammation is a key factor in the development of many neurological pathologies and neurodegenerative diseases. The dynamics of development and duration of neuroinflammatory responses are critical aspects in understanding the patterns of physiological, biochemical and behavioral consequences. The most common object of study is neuroinflammation that develops after experimental systemic inflammation. The effect of acute systemic inflammation on brain microgliocytes has been studied extensively, while spinal cord microglia have been studied less frequently. The purpose of this study was to assess the topographic and temporal features of morphofunctional changes in rat spinal cord microglial cells after experimental LPS-induced systemic inflammation. It has been established that in the early stages of neuroinflammation (24 hours after LPS administration), microgliocytes are activated in the ventral white and ventral gray matter of the spinal cord. At the same time, microgliocytes of the dorsal part of the spinal cord do not show morphological attribute of activation. An increase in the population density of microgliocytes in the ventral funiculus of the spinal cord was noted. Accumulations (aggregates) of reactive microgliocytes were also found in this area.
Fibrin Coating Contributes to the Retention of the Endothelial Layer in Pulsating Flow
Authors: Matveeva V. G. , Velikanova E. A. , Antonova L. V. , Barbarash L. S.
Published: April 2024

The presence of a modifying coating based on extracellular matrix proteins on the inner surface of vascular prostheses is known to enhance endothelial cell adhesion and prevent detachment under pulsating flow conditions. This coating effectively reduces the risk of thrombosis and plays a critical role in determining implantation outcomes. Although proteins like collagen, fibrin, and fibrinogen are commonly used as coatings to improve cell adhesion, their relative effectiveness remains uncertain. Objective: This study aims to identify the optimal coating, based on extracellular matrix proteins, that preserves prosthesis functionality and maintains endothelial layer integrity under pulsating flow conditions. Methods: Scaffolds and vascular prostheses were fabricated using poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(ε-caprolactonone) through an electrospinning process. These structures were then modified with collagen I, fibronectin, or fibrin. Endothelial colony-forming cells (ECFCs) were seeded onto the protein-modified electrospun samples and cultured under both static and dynamic conditions. After a 3-day incubation period under static conditions, cell viability, metabolic and proliferative activity, as well as adhesive properties, were evaluated. Adhesive properties were assessed by analyzing the area occupied by the focal adhesion protein paxillin. Cell retention was determined by comparing cell density on the inner surface of 4 mm diameter vascular prostheses after a 7-day incubation period, both under pulsating flow conditions and static conditions. Results: Cell metabolic activity, viability, number, proliferation, and the area occupied by the focal adhesion protein paxillin were found to be significantly higher in samples coated with fibrin compared to those coated with collagen I and fibrinogen. The cell density (cells/cm2) of ECFCs on the inner surface of fibrin-coated prostheses showed no significant difference between dynamic and static conditions. In contrast, collagen and fibronectin coatings resulted in approximately half the cell density under pulsating flow conditions compared to static conditions. Conclusion: The fibrin coating demonstrated superior biological activity, adhesive properties, and preservation of the endothelial layer under both static and pulsating flow conditions, as compared to collagen I and fibronectin coatings. Consequently, the utilization of fibrin coating emerges as a promising option for modifying the inner surface of vascular prostheses.
Dysregulation of GABAergic System in the Inferior Colliculi of Rats during the Development of Audiogenic Epilepsy
Authors: Nikolaeva S. D. , Ivlev A. P. , Naumova A. A. , Kulikov A. A. , Glazova M. V. , Chernigovskaya E. V.
Published: April 2024

Epilepsy is tightly associated with dysfunction of inhibitory GABA neurotransmission. In this study, Krushinsky–Molodkina (KM) rats genetically prone to audiogenic seizures (AGS) were used. KM rats are characterized by the development of audiogenic epilepsy during postnatal ontogenesis, with AGS onset at the age of 1.5–2 months and fully developed AGS expression by 3rd month. We analyzed GABAergic system of the inferior colliculi (IC) of KM rats at different stages of postnatal development. Wistar rats were used as a control. In the IC of young KM rats, Na+/K+/Cl– cotransporter 1 (NKCC1) expression was increased, while K+/Cl– cotransporter 2 (KCC2) was unchanged indicating impairment of postsynaptic GABA action at early stages of postnatal development. Moreover, we revealed also an increase in the expression of vesicular GABA transporter (VGAT) in the IC which additionally pointed on the higher activity of GABA release. In adult rats, in opposite, we revealed a decrease in the expression of KCC2 transporter indicating downregulation of GABA inhibition on the target cells. Thus, GABA dysregulation in the IC can mediate the seizure susceptibility in adult KM rats.
The Role of Tryptophan Metabolites and Short-Chain Fatty Acids in the Pathogenesis of Autoimmune Diseases
Authors: Shatova O. P. , Yagodkina E. M. , Kaydoshko S. S. , Zabolotneva A. A. , Shestopalov A. V.
Published: April 2024

Every year, the prevalence of autoimmune diseases in the world is steadily increasing. The etiology and pathogenesis of autoimmune disease are extremely complex and largely remain unclear. However, a growing body of research data in recent years points to the critical role of microorganisms in the formation of normal immune response and autoimmune reactions in the host organism. In this case, one of the leading roles is assigned to the intestinal microbiota, represented by trillions of microbes that form a wide range of signaling and immunoregulatory metabolites. Forming a complex interdependent host-microbiota system, symbiotic bacteria largely determine the development and functioning of human immune cells. In this review, we consider the role of the intestinal microbiota and its key metabolites (namely, short-chain fatty acids and tryptophan metabolites) in the pathogenesis of autoimmune disease and discuss possible mechanisms of the influence of these signaling molecules on host immune cells.
Pulmonary Arterial Hypertension Attenuates Vasoconstrictor Responses Caused by Activation of Alpha-1-Adrenoreceptors in the Systemic Circulation
Authors: Abramov A. A. , Lakomkin V. L. , Lukoshkova E. V. , Prosvirnin A. V. , Kapelko V. I. , Kuzmin V. S.
Published: April 2024

Pulmonary arterial hypertension (PAH) accompanied by an arterial pressure increase in the pulmonary circulation, remodeling of pulmonary arteries and a change in its sensitivity to regulatory factors; PAH is accompanied by activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and increased production of atrial natriuretic peptide. The change in the sensitivity of the vessels of the systemic circulation (SC) to regulatory influences in PAH has not been investigated. Vasoconstrictor reactions in SC with monocrotaline (MCT) were studied in the work models of PAH in rats (Wistar, 350 ± 50 g, 4 months). Mean arterial pressure (MAP) was recorded against the background of a double autonomous blockade with the administration of the α1-adrenergic receptor agonist (α1-AR) phenylephrine (PE) to conscious rats at the start of experiment, then 2 and 4 weeks after the induction of PAH with MCT or saline injection for control animals. Registration of MAP under the action of PE was also performed during angiotensin-II (ATII) infusion. The maximal amplitude (Amax) of the change in MAP and the longest half-return time of MAP (T∆MAP1/2) to the baseline level in rats in response to the Phe injection were estimated. It was found that in response to PE, Amah did not change in rats with PAH, whereas in control animals it significantly increased. In rats with PAH 2 (n = 6) and 4 weeks after the induction of PAH with MCT, T∆MAP1/2 is significantly less than in control rats. ATII leads to delayed changes in T∆MAP1/2 in both control rats and rats with PAH. In rats with MAP, the potentiation with angiotensin T∆MAP1/2 is significantly less than in control rats. Thus, in animals with PAH, the ability of the resistive arteries of the systemic circulation to maintain tone in response to the activation of α1-AR decreases. In addition, PAH suppresses the ability of ATII to stimulate sympathetic responses in the SC. Firstly, in vivo, it has been demonstrated remodeling and changing the functional state of the pulmonary circulation leads to changes in the regulation of vascular tone of the systemic circulation.
The Effect of Spontaneous Neuromuscular Activity on the Development of Atrophy of the Functionally Unloaded m. soleus
Authors: Sergeeva K. V. , Sharlo K. A. , Kalashnikov V. E. , Turtikova O. V. , Tyganov S. A. , Shenkman B. S.
Published: April 2024

It is well known that the inactivity of mammalian skeletal muscles leads to the cessation of their electrical activity and is accompanied by atrophic changes in muscle fibers. However, it has been repeatedly noted that starting from the 3rd day of functional unloading, spontaneous rhythmic neuromuscular activity appears, which is the result of a decrease in the expression of the potassium chloride co-transporter KCC-2 in neurons of the lumbar spinal cord. A decrease in the expression of KCC-2 and the onset of autonomous electrical activity of the unloaded muscle can be prevented by the administration of the neuroleptic prochlorperazine. Thus, the aim of this study was to evaluate the structural and signaling effects of the reduced spontaneous activity of the unloaded m.soleus. It was found that daily administration of prochlorperazine to rats under conditions of 7-day simulated gravitational unloading prevented a decrease in the content of the main markers of ribosome biogenesis (c-Myc, 18S rRNA and 28S rRNA), and also partially prevented a decrease in the cross-sectional area of fast and slow muscle fibers in the m.soleus. Morphofunctional changes caused by a decrease of spontaneous activity of the unloaded muscle were accompanied by complete or partial prevention of activation of key proteolytic markers expression (MuRF-1, MAFbx/atrogin-1, ubiquitin). Thus, we assume that spontaneous neuromuscular activity may be a factor that augments muscle atrophy during the first week of functional unloading.
Effect of Acute and Chronic Sleep Deficit on Working and Long-Term Memory in Rats
Authors: Chernyshev M. V. , Guseev M. A. , Ekimova I. V.
Published: April 2024

It is known that insufficient sleep or diurnal rhythm disturbances of sleep and wakefulness exert a detrimental effect on cognitive functions. It was thought for a long period that memory consolidation is the most vulnerable link, i.e., information transfer from short-term/working memory to long-term memory. However, there is a progressive number of studies indicating that the most negative consequences of sleep loss are observed in working memory. In our study, we undertook an effort to assess possible disturbances in working memory and long-term memory following sleep loss impact with different protocols in acute and chronic experiment in rats. Sleep in Wistar rats was deprived/restricted by swinging platform technique according to the following protocols: 1 – total sleep deprivation for 18 h; 2 – partial sleep restriction for 24 h (3 h of sleep deprivation alternated with 1 h of sleep opportunity – totally 18 h of sleep deprivation); 3 – chronic partial sleep restriction (conditions 2 for five consistent days). Total sleep deprivation in Y-maze test was shown to result in a significant decrease in spontaneous alternations of maze arms that indicates working memory impairment. This impact in Barnes test did not exert an effect on long-term memory – time spent for seeking a shelter did not change in this task. Acute and chronic sleep restriction induced no changes in working memory and long-term memory. The results obtained allow us to come to conclusion that working memory (in contrast to long-term memory) is a vulnerable component of cognitive function under total sleep deprivation conditions. This negative effect was abolished if periods of sleep deprivation alternated with short periods of sleep opportunities that indicate protective significance of short sleep periods for cognitive functions during sleep deficit. Hence, short-term sleep is helpful for cognitive health and protects working memory, whereas continuous long-term wakefulness impairs it.
Modeling Taupathies in Zebrafish (Danio rerio)
Authors: Kotova М. М. , Kolesnikova Т. О. , Kalueff A. V.
Published: April 2024

Taupathies are a group of neurodegenerative diseases characterized by the accumulation of tau-protein in the brain, causing clinical dementia. Tau protein stabilizes microtubules and regulates axonal transport, however, when hyper-phosphorylated, aggregates in the brain. Taupaties can be divided into primary and secondary (e.g., Alzheimer’s disease). Experimental animal models models are an important tool to study taupathies. Here, we discuss molecular mechanisms of taupathies and their existing experimental models in both rodents and novel alternative organisms, zebrafish (Danio rerio), as well as future novel directions of research in this field.
Pharmacological Inhibition of the AQP4 Water Channel Activity Causes an Aggravation of Alpha-Synuclein Pathology in the Substantia Nigra in a Rat Model of Parkinson’s Disease
Authors: Lapshina K. V. , Khanina M. V. , Kaismanova M. P. , Ekimova I. V.
Published: April 2024

The misfolding of the protein α-synuclein, which leads to the formation of neurototoxic oligomers and aggregates, is one of the main causes of loss of dopaminergic (DA) neurons within the substantia nigra pars compacta (SNpc) in Parkinson’s disease (PD). We previously found that pharmacological inhibition of the water channel aquaporin-4 (AQP4), participating in the mechanisms of brain clearance of amyloidogenic proteins, caused the aggravation of neurodegeneration in the nigrostriatal system and the development of motor disturbances in a lactacystin model of PD. It was hypothesized that the progression of neurodegeneration can be a result of the excessive accumulation of pathologic forms of α-synuclein due to the AQP4 inhibition. The aim of this study is to determine whether pharmacological inhibition of AQP4 activity in a rat model of preclinical PD leads to an aggravation in α-synuclein pathology. The experiments were performed on male Wistar rats. AQP4 activity was suppressed using the intracerebroventricular injection of inhibitor TGN-020. To reproduce the model of the preclinical stage of PD, a specific proteasome inhibitor lactacystin (LC) was used. It was injected bilaterally into the SNpc. Immunoblotting methods and confocal microscopy were applied. The LC model of PD was characterized by a pathologic accumulation of total water-soluble and Ser129-phosphorylated forms of α-synuclein, as well as by formation of insoluble α-synuclein aggregates in the DA-neurons of SNpc. TGN-020 caused a significant aggravation of α-synuclein pathology in the LC model of PD. It was manifested by a marked increase in the level of water-soluble and modified forms of α-synuclein and by the 1.9-fold rise in the amount of α-synuclein aggregates in SN. We suppose that the disfunction of AQP4 which is involved in glymphatic system functioning, can be one of the mechanisms leading to the neurodegeneration and accumulation of amyloidogenic proteins in brain parenchyma during PD. The water channel AQP4 might be a target for the development of new therapeutic approaches aimed at attenuation of the cytotoxicity, accumulation and distribution of α-synuclein during the development of PD-like pathology.