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Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC50) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC50 was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC50. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC50 from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity. [ABSTRACT FROM AUTHOR]

The cytosolic calcium concentration ([Ca2+]cyt) in yeast cells is maintained at a low level via the action of different transporters sequestrating these cations in the vacuole. Among them, the vacuolar Ca2+ ATPase Pmc1 crucially contributes to this process. Its inactivation in Ogataea yeasts was shown to cause sodium dodecyl sulfate (SDS) hypersensitivity that can be alleviated by the inactivation of the plasma membrane high-affinity Ca2+ channel Cch1. Here, we show that SDS at low concentrations induces a rapid influx of external Ca2+ into cells, while the plasma membrane remains impermeable for propidium iodide. The inactivation of Pmc1 disturbs efficient adaptation to this activity of SDS. The inactivation of Cch1 partially restores the ability of pmc1 mutant cells to cope with an increased [Ca2+]cyt that correlates with the suppression of SDS hypersensitivity. At the same time, Cch1 is unlikely to be directly involved in SDS-induced Ca2+ influx, since its inactivation does not decrease the amplitude of the rapid [Ca2+]cyt elevation in the pmc1-Δ mutant. The obtained data suggest that the effects of CCH1 inactivation on SDS sensitivity and coping with increased [Ca2+]cyt are related to an additional Cch1 function beyond its direct involvement in Ca2+ transport. [ABSTRACT FROM AUTHOR]

Victory Day celebrations in Russia have frequently been characterized as a vehicle for state militarism, particularly in the context of the full‐scale invasion of Ukraine. This article challenges the notion that the state is the sole proprietor of this national holiday. Drawing on recent ethnographies of Victory Day, the article argues that a trend towards patriotic performativity increasingly defines public celebrations. This trend has two outcomes: strengthening participants' sense of national community while reinforcing statist discourse – even among the holiday's critics. By examining the relationship between the Russian state and Victory Day, the article illuminates the crucial distinction between a reiterated, performative victory and the realities of actual warfare. This analysis contributes to broader discussions on collective memory, state power and the role of public celebrations in shaping national identity in post‐Soviet contexts. [ABSTRACT FROM AUTHOR]

Results of studying the catalytic properties of systems based on complexes with [Pd(Cp)(L)n]m[BF4]m (where Cp = η5-C5H5; n = 2, m = 1: L = tris(ortho-methoxyphenyl)phosphine, triphenylphosphine, tris(2-furyl)phosphine (TFP); n = 1, m = 1: L = 1,1'-bis(diphenylphosphino)ferrocene, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,5-bis(diphenylphosphino)pentane; n = 1, m = 2 or 3: L = 1,6-bis(diphenylphosphino)hexane) in the addition homo- and copolymerization of norbornene (NB) and NB derivatives have been described. It has been found that these complexes can be activated with Lewis acids (BF3⋅OEt2 or AlCl3). The productivity of the [Pd(Cp)(PPh3)2][BF4]/BF3⋅OEt2 catalyst system in NB polymerization can achieve 188 800 molNB . The homopolymerization of 5-methoxycarbonylnorbornene and the copolymerization of NB with 5-methoxycarbonylnorbornene or 5-phenylnorbornene in the presence of BF3⋅OEt2 and [Pd(Cp)(L)2][BF4] (L = PPh3 or TFP) has been studied. A hypothesis for the formation of the catalyst via the intramolecular rearrangement of the η5-Cp ligand into the η1-Cp form upon interaction with a Lewis acid has been proposed. The structure of the [Pd(Cp)(TFP)2]BF4 complex (I) has been determined by X-ray diffraction (XRD) analysis. In the crystal structure of complex I, the coordination sphere of palladium is characterized by a slight distortion of the square planar geometry of the central atom, while the cyclopentadiyl moiety is in an eclipsed conformation. Based on XRD data, the steric hindrance of the TFP ligand has been determined (cone angle is 149°). [ABSTRACT FROM AUTHOR]

The reactive spark plasma sintering (R-SPS) method was compared in this work with the two-step SHS–SPS route, based on the combination of the self-propagating high-temperature synthesis (SHS) with the SPS process, for the fabrication of dense (Hf0.2Mo0.2Ti0.2Ta0.2Nb0.2)B2–SiC and (Hf0.2Mo0.2Ti0.2Ta0.2Zr0.2)B2–SiC ceramics. A multiphase and inhomogeneous product, containing various borides, was obtained at 2000 °C/20 min by R-SPS from transition metals, B4C, and Si. In contrast, if the same precursors were first reacted by SHS and then processed by SPS under the optimized condition of 1800 °C/20 min, the desired ceramics were successfully attained. The resulting sintered samples possessed relative densities above 97% and displayed uniform microstructures with residual oxide content <2.4 wt.%. The presence of SiC made the sintering temperature milder, i.e., 150 °C below that needed by the corresponding additive-free system. The fracture toughness was also markedly improved, particularly when considering the Nb-containing system processed at 1800 °C/20 min, whereas the fracture toughness progressively decreased (from 7.35 to 5.36 MPa m1/2) as the SPS conditions became more severe. SiC addition was found to inhibit the volatilization of metal oxides like MoO3 formed during oxidation experiments, thus avoiding mass loss in the ceramics. The benefits above also likely took advantage of the fact that the two composite constituents were synthesized in parallel, according to the SHS–SPS approach, rather than being produced separately and combined subsequently, so that strong interfaces between them were formed. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaze (Bovhyaluronidase Azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaze was administered at different doses by intranasal and intramuscular routes. Histology, hematology, and enzyme-linked immunosorbent assay were used in the study. The use of Longidaze reduced pulmonary fibrosis, as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue, and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaze inhibited the inflammatory response in pulmonary fibrosis, and decreased the levels of IL-6, TNF-α, and hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaze at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaze is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease. [ABSTRACT FROM AUTHOR]

Long-period eclipsing binaries (variables) are a valuable source of data for calculating stellar masses. Such objects have a sufficient amount of both photometric and spectral data for determining their parameters and further analysis. We began a project to study long-period massive eclipsing binaries in order to determine their component masses and refine the mass-luminosity relation for stars of high and intermediate masses. We describe our project in general terms, focusing in more detail on the use of large photometric surveys as an important base in our research. We will talk about almost all avaliable large sky surveys, from which we collected all available photometric data on our objects and constructed light curves. We present the results of photometric data analysis for the objects we study using existing and specially constructed software packages. In particular we demonstrate several cases, where application of the surveys' data to our objects allows us to obtain new orbital period for eclipsing binaries. The paper is based on a talk presented at the astrophysical memorial seminar "Novelties in Understanding the Evolution of Binary Stars", dedicated to the 90th anniversary of Professor M.A. Svechnikov. [ABSTRACT FROM AUTHOR]

Mobile phone–based engagement approaches provide potential platforms for improving access to primary healthcare (PHC) services for underserved populations. We held two focus groups (February 2020) with residents (n = 25) from a low-income urban neighbourhood (downtown Vancouver, Canada), to assess recent healthcare experiences and elicit interest in mobile phone–based healthcare engagement for underserved residents. Note-based analysis, guided by interpretative description, was used to explore emerging themes. Engagement in PHC was complicated by multiple, intersecting personal-level and socio-structural factors, and experiences of stigma and discrimination from care providers. Perceived inadequacy of PHC services and pervasive discrimination reported by participants indicate a significant and ongoing need to improve client–provider relationships to address unmet health needs. Mobile phone–based engagement was endorsed, highlighting phone ownership and client–provider text-messaging, facilitated by non-clinical staff such as peers, as helpful to strengthening retention and facilitating care team connection. Concerns raised included reliability, cost, and technology and language accessibility. [ABSTRACT FROM AUTHOR]

Resolved spectroscopic binaries are unique among other types of binaries. They provide the only possibility (aside from trigonometric parallaxes) to accurately determine distances to objects, which is one of the most important characteristics in astronomy. Such binaries are not numerous, but an exhaustive catalog of them still does not exist. The authors have developed a pilot version of a new catalog of resolved spectroscopic binaries. It contains information about orbital elements, component masses, parallaxes, and other parameters for 107 stars. Thus, the catalog represents the most extensive list of resolved spectroscopic binaries known to date. A preliminary analysis of the distributions of the stellar parameters of the objects in the catalog has been carried out, as well as a comparison of the trigonometric parallaxes from Gaia DR3 with the orbital parallaxes. The article is partly based on a report presented at the conference "Modern Stellar Astronomy-2022," which was held at the Caucasian Mountain Observatory of the Astronomical institute of Lomonosov Moscow State University on November 8–10, 2022. [ABSTRACT FROM AUTHOR]

CoSb 3 belongs to the skutterudite family of compounds and serves as a crucial platform for the exploration of thermoelectric materials, however, its importance is equally high for studies of strong correlations at high pressures. Under compression it undergoes a 'self-insertion' isostructural transition resulting in a peculiar redistribution of large Sb atoms between different crystallographic sites. We conducted a comprehensive investigation of the structural phase stability of CoSb 3 up to 70 GPa using single crystal samples characterized employing conventional single crystal X-ray diffraction and X-ray scattering focused on measuring Bragg peak at high resolution (including elements of Bragg Coherent Diffraction Imaging). We explore the compression behavior of CoSb 3 in three different pressure transmitting media (PTM) and address several important, but previously unexplored topics: the influence of various PTMs and nonhydrostatic stresses on the strongly correlated system of CoSb 3 , including the 'self-insertion' crossover, the phase stability of CoSb 3 , the compound's polymorphism, its crystal chemistry, and its peculiar evolution under pressure at ambient temperature. Among other important observations, we track the population of Sb atoms within the dodecahedral sites of CoSb 3 on compression, during the process of 'self-insertion', and on decompression. We detect that 'self-insertion' may not only reduce the solid's compressibility, but also make it negative. Finally, but not least, we report that the 'self-insertion' crossover is an important step preceding a previously unknown phase transformation from cubic Im 3 ̅ CoSb 3 into trigonal R 3 ̅ occurring above 40 GPa, and discuss the distinctive behavior of CoSb 3 phases and their structural frameworks. • High-pressure study resolves intricate behavior of CoSb 3 crystal chemistry. • Multiple phase transitions, including 'self-insertion,' characterized structurally. • 'Self-insertion' precedes cubic-to-trigonal transition in unfilled skutterudites. • Unique application of Bragg coherent diffraction imaging in high-pressure research. [ABSTRACT FROM AUTHOR]

Sodium chloride is expected to be found on many of the surfaces of icy moons like Europa and Ganymede. However, spectral identification remains elusive as the known NaCl-bearing phases cannot match current observations, which require higher number of water of hydration. Working at relevant conditions for icy worlds, we report the characterization of three “hyperhydrated” sodium chloride (SC) hydrates, and refined two crystal structures [2NaCl·17H2O (SC8.5); NaCl·13H2O (SC13)]. We found that the dissociation of Na+ and Cl− ions within these crystal lattices allows for the high incorporation of water molecules and thus explain their hyperhydration. This finding suggests that a great diversity of hyperhydrated crystalline phases of common salts might be found at similar conditions. Thermodynamic constraints indicate that SC8.5 is stable at room pressure below 235 K, and it could be the most abundant NaCl hydrate on icy moon surfaces like Europa, Titan, Ganymede, Callisto, Enceladus, or Ceres. The finding of these hyperhydrated structures represents a major update to the H2O–NaCl phase diagram. These hyperhydrated structures provide an explanation for the mismatch between the remote observations of the surface of Europa and Ganymede and previously available data on NaCl solids. It also underlines the urgent need for mineralogical exploration and spectral data on hyperhydrates at relevant conditions to help future icy world exploration by space missions. [ABSTRACT FROM AUTHOR]

The effect of ketanserin on inflammation, liver fibrosis, and microviscosity of the plasma and mitochondrial membranes of hepatocytes was studied on young (3 months) and old (9 months) male Wistar rats with experimental liver cirrhosis. Ketanserin reduced inflammation, area of the connective tissue, and liver damage and improved serum biochemical parameters in rats of both age groups; in old rats, the effects were more pronounced than in young animals. In old rats, ketanserin reduced polarity of hepatocyte plasma and mitochondrial membranes in the area of protein-lipid contacts, which determined higher effectiveness of ketanserin during the treatment of liver cirrhosis in aged animals. [ABSTRACT FROM AUTHOR]

This correction notice addresses a mistake in Figure 10 of the original publication titled "High-Entropy Diborides-Silicon Carbide Composites by Reactive and Non-Reactive Spark Plasma Sintering: A Comparative Study." The incorrect subfigure (g) Nb has been replaced with the correct subfigure (g) Zr. The authors assure that this correction does not affect the scientific conclusions of the study. The original publication has been updated accordingly. [Extracted from the article]

Organosilicon varnishes, such as polymethylphenylsiloxane and polyaluminomethylphenylsiloxane, filled with modified clay minerals are the object of research. The most vulnerable place of the organosilicon coating is insufficient mechanical properties (hardness, impact strength, etc.) and low adhesive strength of the film to the surface, especially when operating at elevated temperatures. Various oxides, ceramic compounds, natural and synthetic silicate materials are introduced into organosilicon compositions to improve the specified properties. But only individual units can comprehensively improve both the mechanical and heat-resistant properties of organosilicon compounds although the range of such materials is quite wide. The clay minerals palygorskite, which is classified as an intermediate type between strip and layered silicates, and montmorillonite from the subclass of layered silicates, which have a natural high dispersion, were used as fillers during the study. The choice of palygorskite and montmorillonite is explained by the sufficient study of their behavior in organic environments by a number of scientists, availability and economic advantages for introduction into production. Existing clay minerals, which are traditionally used to solve the problem of improving the physical and mechanical properties of organosilicon coatings, are not sufficiently active due to the hydrophilic properties of the particles surface. Based on this, a modifier that has proven itself well in this field was used for the study. A number of compositions of heat-resistant organosilicon varnishes with modified fillers based on the abovementioned clay minerals were obtained. It was established that the introduction of modified forms of natural aluminosilicates contributes to the increase of temperature resistance in filled coatings, compared to coatings made of pure polymer. At the same time, the best effect is achieved when using montmorillonite. This is related with the fact that the proposed compositions of polymethylphenylsiloxane varnish and montmorillonite have a number of features, in particular, the highest comprehensive result of simultaneous improvement of the physical, mechanical and thermal properties of the specified coatings. It is possible to obtain compositions with stable physico-mechanical properties, as they withstood heat treatment at 400 °C for 100 hours without visible changes in integrity, due to the introduction of the optimal amount of modified montmorillonite into organosilicon varnishes KO-08K and KO-921. Compared to similar heat-resistant polymethylphenylsiloxane varnishes, longer service life at elevated temperatures is ensured. [ABSTRACT FROM AUTHOR]

Abstract—Two classical theories of synchronization of main-sequence components in binary systems developed by J.P. Zahn and J.-L. Tassoul are considered. These two theories predict significantly different synchronization time scales. Within the framework of this study, the times and probabilities of synchronization for a set of O–G-type model stars are estimated and compared with the results based on recent observational data from the catalog of detached eclipsing binaries by G. Torres. For each of the catalog objects, the maximum period of axial rotation is computed and compared with the known orbital period. A conclusion about the synchronization of each of the systems is then made based on the above theoretical estimates. Zahn's theory, which yields longer synchronization time scales, is found to describe the observational data better than Tassoul's theory. The results of this analysis will be useful for estimating the probability of synchronization in binary systems. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) therapy is a new method for the treatment of androgenetic alopecia (AGA), the effectiveness and safety of which continues to be studied. Information on comparative efficacy when combining PRP with other methods of treatment is limited. The aim of the study was a comparative evaluation of the clinical efficacy of minoxidil, PRP therapy, and their combination in the treatment of men with AGA. Materials and Methods: The study included 69 men. The patients were divided into three observation groups: the main group (25 people, received applications of a 5% solution of minoxidil in combination with PRP injections), the comparison group (22 people, received intradermal injections of PRP), and the control group (22 people, received applications of a 5% solution of minoxidil). The clinical efficacy of the therapy was evaluated by the dynamics of morphometric indicators of hair growth using a digital camera and the software. Results: It was established that after complex therapy in the form of minoxidil applications and injections of PRP, the hair density increased by 32% (P = 0.00004), the diameter of the hair shafts by 26% (P = 0.00004), the share of vellus hair decreased by 30% (P = 0.00082), and the proportion of telogen hair decreased by 39% (P = 0.00008). The results of using complex therapy significantly exceeded the clinical effect of platelet-rich plasma and topical applications of a 5% solution of minoxidil. Conclusions: The data obtained allows suggesting that PRP and minoxidil potentiate each other's action when used together and their complex application seems promising for the treatment of androgenetic alopecia. [ABSTRACT FROM AUTHOR]

The article examines the content and features of the public interest as a category of administrative and legal science. The main features of public interest are clarified, namely: (i) it is a set of certain needs (values); (ii) there may be needs of the whole society, as well as its groups or individual citizens; (iii) is provided at the initiative of the directly interested subject or public administration; (iv) these interests are recognized by the state, can be normatively fixed; (v) aimed at ensuring human rights and freedoms; (vi) are provided by subjects of public administration. It is established that the content of public interest as an administrative-legal category follows from the essence of general interest and is individualized by the content of administrative-legal relations. Public interest is defined as a set of certain needs (values) of a person or society, aimed at ensuring and protecting human rights and freedoms and implemented in the activities of public administration. It is established that the public interest reflects the interests of society as a whole or an individual, but its needs may become significant for society as a whole. The types of public interests are distinguished depending on the sphere of realization, territory of distribution and number of persons expressing public interest. [ABSTRACT FROM AUTHOR]

The topic of the study is especially relevant because of the non-standard form of employment (NFE) ‘volunteering’ has acquired across the global. Similarly, NFE ‘voluntourism’ has recently been acquiring the form of a social movement and the development of mechanisms for public administration of these activities is far from complete. The aim of the article is to summarise the world experience of the project approach of public authorities to youth policy and the introduction of NFE of youth ‘volunteering’, as well as to analyse the experience of the micro-project approach of public authorities in Mariupol, Ukraine. The study is based on a comprehensive and systematic approach to public management of youth employment and uses methods to describe, summarise, analyse and synthesise the results of observations and experiments. The generalisation of the world experience of the project approach of public authorities to the introduction of non-standard forms of youth employment ‘volunteering’ and ‘voluntourism’ and the modern experience of its use is supported by UNESCO, which allows expanding its scope. It established that experience of the project approach of public authorities on creation of NFE ‘volunteering’ in the city of Mariupol, Ukraine, can be considered as innovative technology of information education. Thus, the project approach of public authorities with the use of NFE ‘volunteering’ and ‘voluntourism’ plays a specific useful role in professional and life situations of young people and allows them to perform social functions of professional, community and personal goals and competencies. [ABSTRACT FROM AUTHOR]

Based on the results from previous high‐pressure experiments on the gadolinite‐type mineral datolite, CaBSiO4(OH), the behavior of the isostructural borates β‐HfB2O5 and β‐ZrB2O5 have been studied by synchrotron‐based in situ high‐pressure single‐crystal X‐ray diffraction experiments. On compression to 120 GPa, both borate layer‐structures are preserved. Additionally, at ≈114 GPa, the formation of a second phase can be observed in both compounds. The new high‐pressure modification γ‐ZrB2O5 features a rearrangement of the corner‐sharing BO4 tetrahedra, while still maintaining the four‐ and eight‐membered rings. The new phase γ‐HfB2O5 contains ten‐membered rings including the rare structural motif of edge‐sharing BO4 tetrahedra with exceptionally short B−O and B⋅⋅⋅B distances. For both structures, unusually high coordination numbers are found for the transition metal cations, with ninefold coordinated Hf4+, and tenfold coordinated Zr4+, respectively. These findings remarkably show the potential of cold compression as a low‐energy pathway to discover metastable structures that exhibit new coordinations and structural motifs. [ABSTRACT FROM AUTHOR]

We studied the formation of injuries in lung endothelium and the response of angiogenesis cells during modeling of pulmonary emphysema in male and female C57BL/6 mice with metabolic disorders. Hemodynamic disturbances and reduction in the area of the microvasculature caused by combined pathology in male mice were more pronounced than in females. Mobilization and migration of angiogenic precursors were impaired in both male and female mice. In males, activity of recruiting endothelial progenitor cells, vascular smooth muscle cells, luminal cells of nascent vessels and pericytes into the lungs was additionally reduced. In females, accumulation of endothelial progenitor cells (CD45—CD31+CD34+), vascular smooth muscle cells, and pericytes in the lungs was observed, which indicated activation of endothelial regeneration. Sex differences in the reaction of the lung endothelium and angiogenesis cells can be explained by genetic factors of lipid and glucose metabolism. [ABSTRACT FROM AUTHOR]

Methods are proposed for the extraction of amino acids histidine, methionine, and proline from aqueous media with water-soluble polymers for their subsequent determination by capillary electrophoresis. Regularities of the interphase distribution of analytes in water–salt extraction systems based on poly-N-vinyl formamide and its copolymer with N-vinylimidazole are revealed and their efficiency is proved. The rate of formation of a two-phase system water-soluble polymer–aqueous salt solution of amino acid is substantially affected by the molecular weight and intrinsic viscosity of the extractant. The effect of the volume ratio of water and organic phases on the efficiency of extraction of histidine, methionine, and proline is studied, also on their simultaneous presence; quantitative characteristics of the process are calculated. Homo- and copolymers of N-vinylformamide are used for the efficient extraction and extraction separation of a histidine−methionine mixture. Partition coefficients and the recoveries of amino acids are specified in the systems containing poly-N-vinylformamide and its copolymer with N-vinylimidazole in the presence of an ammonium sulfate salting-out agent. The conditions for the electrophoretic determination of amino acids are optimized, i.e., the composition of the buffer solution and the type and concentration of the micelle-forming agent. The developed method for the electrophoretic separate determination of amino acids with the preliminary extraction of the target components with water-soluble polymers can be recommended for routine analyses in determining the safety of foodstuffs, energy drinks, and pharmaceuticals. [ABSTRACT FROM AUTHOR]

It is now known that the possibility of conceiving and carrying a pregnancy is largely due to the interaction of a woman's macroorganism with microorganisms involved in the formation of the microbiome of the intestine, vagina and other organs. Attempts to treat infertility using in vitro fertilization (IVF) are not always successful. Probably, the disruption of the vaginal and intestinal microbiome can significantly reduce the effectiveness of IVF programs. The aim of our work was to study the vaginal and intestinal microbiome in women with infertility in preparation for IVF programs. Materials and research methods. 40 women suffering from infertility were examined. Primary infertility was in 12 women and secondary in 28 patients. Of these, the 1st group consisted of 20 women suffering from infertility who had 2-4 unsuccessful IVF attempts in history; Group 2 consisted of 20 women who, after infertility treatment, had a pregnancy that ended in premature birth. The control group consisted of 20 healthy women. Bacteriological studies of the vaginal and intestinal microbiome were carried out using the method of light microscopy. The level of proinflammatory and anti-inflammatory cytokines in the blood serum was determined by the enzyme immunoassay. Results. When conducting bacteriological examination in the 1st and 2nd groups of patients, it was found that the vaginal microbiome is characterized by a sharp decrease in normal flora (lacto-, bifidobacteria) and a significant increase in opportunistic flora (eubacteria, prevotella, peptostreptococcus). In the intestinal microbiome, a decrease in species diversity, an increase in the number of enterococci, Klebsiella, proteobacteria, characteristic of intestinal dysbiosis associated with inflammation, were found. Thus, in both groups of women, a violation of the vaginal microbiome was found in 71.7%, a violation of the intestinal microbiome - in 86.7% of patients. While in the control group, there was no violation of the vaginal microbiome, and the violation of the intestinal microbiome occurred in 10% of women. Conclusions. According to the results of the study, it can be considered that the risk factors for failed IVF attempts and premature birth are a violation of the microbiome of the vagina and intestines, as well as an imbalance of pro-inflammatory and anti-inflammatory cytokines in women with infertility. To develop individual fertility treatment programs, it is necessary to include an assessment of the vaginal and intestinal microbiome in the examination. In addition, drugs that normalize the microbiome of these organs should be included in IVF programs and for the prevention of preterm birth in women with a history of infertility, which will increase the effectiveness of IVF programs and reduce reproductive losses. [ABSTRACT FROM AUTHOR]

Growth of the external migration within the Russian Federation draws the attention of scientists to this problem. During the latest decade, the majority of foreign migrants (coming for work, study, or residence) are representatives of the Central Asian countries. The objective of this research is studying ethnic identity and personal helplessness in migrants coming from the Central Asian countries. The data obtained as a result of the conducted research allow making conclusions about orientation to interaction with other ethnic groups being stronger in migrants from the Central Asia who feature personal helplessness than in the ones characterized by independence and tending to shut themselves off communication with other ethnoses. According to the obtained data, the respondents with independence feature significantly higher indicators of ethnic nihilism, ethnic fanaticism, and ethnic isolationism than the tested ones with personal helplessness do. The found particularities of ethnic identity in migrants having different personal features allow integrating results of the research conducted into the ethnopsychological domain of knowledge. Similarly, they allow creating the theoretical basis for solving applied problems in social and psychological adaptation support rendered to migrants. [ABSTRACT FROM AUTHOR]

Behaviour of hingganite-(Y), Y2□Be2Si2O8(OH)2, on compression to 47 GPa has been studied by synchrotron-based in situ high-pressure single-crystal X-ray diffraction at room temperature in a diamond anvil cell. In the studied pressure range no obvious phase transitions have been observed. The compression of hingganite-(Y) crystal structure is anisotropic, with b axis showing the maximal compressibility. A fit of the experimental pressure–volume data by the Birch-Murnaghan third-order equation of state yielded the bulk modulus of 131(2) GPa and its pressure first derivative of 3.5(2). The difference between high-pressure behaviour of hingganite-(Y) and structurally related datolite is governed by the different chemical nature of interlayer cations. [ABSTRACT FROM AUTHOR]

The changes in endothelial progenitor cells and progenitor cells of angiogenesis, pericytes and smooth muscle cells, were studied in female C57BL/6 mice with a combination of metabolic impairments induced by injections of sodium glutamate and lung emphysema modeled by the administration of cigarette smoke extract. It was observed that sodium glutamate significantly enhances pathological changes in the lungs (inflammation and lung emphysema) induced by the administration of cigarette smoke extract. Recruiting of endothelial progenitor cells (CD45—CD31+CD34+ and CD31+CD34+CD146—) and progenitor cells of angiogenesis (CD45—CD117+CD309+) was registered in the injured lungs. Angiogenesis impairment induced by combined exposure is related to altered migration of pericytes (CD31—CD34—CD146+) and smooth muscle cells (CD31—CD34+CD146+) in emphysema-like enlarged lung tissue. [ABSTRACT FROM AUTHOR]

The Education of people of the “third age” is based on the fact that their ability of self-development and understanding of the surrounding world is reduced to the application of previously acquired knowledge in a certain period of time. At the same time, it is believed that a decrease in cognitive abilities and an increase in inaccuracies in motor skills leads to the fact that it is almost impossible to master new knowledge. Determining the extent to which this statement corresponds to psychological and educational attitudes shapes the relevance of the study. The novelty of the research is determined by the fact that, for the first time, it is proposed to approach the topic of education for people of “third age” not only as a problem, which is determined solely for increasing the employment of the population and raising the retirement age, but the authors also offer to consider the topic of the research as a factor in improving the standard of living and social adaptability of "third age" citizens. Models of university and distance education are considered in the article. The practical significance of the research is determined by the need to develop the issue outlined in the face of crisis and the desire of public administration to identify priorities for the formation of a qualitatively new social model. A model of comparative analysis with foreign models is used in the research, as well as the experience of implementation is offered. [ABSTRACT FROM AUTHOR]

Abstract A series of cationic acetylacetonate palladium complexes were demonstrated to be active for the polymerization and oligomerization of phenylacetylene. Catalyst screening and optimization have determined the superior activity of complex [(acac)Pd(TOMPP) 2 ]BF 4 (TOMPP – tris (2-methoxyphenyl)phosphine) for the stereospecific polymerization of phenylacetylene in non-coordinating solvents as well as in an aqueous emulsion. Catalyst turnover frequencies of 100–160 h−1 were observed (M w = (10–27)·104 with PDI = 1.7–2.3, cis double bond content in PPA up to 95%). The effect of temperature, solvent nature, and the use of cocatalyst, BF 3 ·OEt 2 , have been studied. Graphical abstract Unlabelled Image Highlights • Cationic acetylacetonate Pd complexes catalyzed polymerization of phenylacetylene. • Pd precursor affects activity, selectivity, and M w in the polymerization. • [Pd(acac)(L) 2 ]BF 4 (L = tris (2-methoxyphenyl)phosphine) showed superior activity. • The high stereoregularity of polyphenylacetylene (>95% cis) was observed. • The effect of temperature, solvent, and the use of BF 3 ·OEt 2 cocatalyst were studied. [ABSTRACT FROM AUTHOR]

The effects of the pegylated form of glucagon-like peptide 1 (pegGLP-1) on oligopotent β cell precursors (CD45—TER119—CD133+CD49flow) in the pancreas were studied in C57Bl/6 mice. Under conditions of streptozotocin-induced type 1 diabetes mellitus, intraperitoneal injection of pegGLP1 increased the content of β cell precursors and dithizone-stained cells in the pancreas. β Cell precursors of mice with diabetes demonstrated high self-maintenance potential. In contrast to pegGLP-1, native GLP-1 did not affect β cell precursors in diabetic animals. Treatment of a culture of β cell precursors from mice with diabetes induced the yield of dithizone-stained mononuclears. In conditioned mediums of dithizone-positive cells obtained as a result of differentiation of β cell precursors from mice with diabetes, insulin was detected after administration of pegGLP-1 (10—7 M) and glucose (3 mmol/liter); the level of insulin increased with increasing glucose concentration (to 20 mmol/liter). The in vitro effect of pegGLP-1 did not differ from the effect of GLP-1 (10—7 M). [ABSTRACT FROM AUTHOR]

In the automation systems of sorting process the use of computer networks of Ethernet technology is possible. But its traditional drawback is a probabilistic nature of the network access, which does not guarantee the information transmission in specified time intervals. However, there are other technologies that are free from this defect, for example, the Token Ring technology. A methodology, for determination of the network parameters in the automation system on marshalling yard at the restriction of the average time for application waiting in the queue at the station network has worked out. Using the token method of access to the ring, the state diagram of network stations was compiled. This is the basis for simulation model of the Token Ring network, which was developed in the GPSS environment. As a result of simulation the dependencies of the maximum queue length at the network station on the frame length, intensity, and distribution of time for application receipt from the station were obtained. [ABSTRACT FROM AUTHOR]

The low quality of transplants having undergone hypoxic injury can lead to postoperative complications. The aim of the present research is to estimate, by means of mathematical modeling, how the process of oxygen uptake through the liver surface influences the metabolism of ex vivo perfused liver under hypoxia. The value of oxygen uptake through the surface was established to depend on the degree of oxygenation of the perfusion medium. A decrease in the oxygenation of the perfusion medium resulted in a decreased oxygen uptake through the liver surface. Stoichiometric modeling of the liver metabolism shows that upon the decreased oxygenation of the perfusion medium more energy is required for the process of oxygen uptake through the surface even at a lower level as compared to the normal oxygen supply. The application of the Pareto optimality allows estimating the optimum distribution of the energy resources in liver under ex vivo conditions. Both upon the normal and decreased oxygenation of the perfusion medium, the phenomenon of "free competition" for the resource was observed, with the energy being optimally distributed among all the metabolic fluxes. Moreover, this energy is also spent on the accompanying processes, e.g. for the transport of interstitial fluid. • Oxygen uptake through the liver surface was estimated by means of mathematical modeling. • Oxygen uptake through the liver surface depends on the degree of perfusate oxygenation. • There is correlation between perfusate oxygenation and oxygen uptake through the liver surface. • Distribution of energy in ex vivo perfused liver under normoxia and hypoxia is carried out optimally. [ABSTRACT FROM AUTHOR]

Biogeochemical structures of three permanently stratified waterbodies were studied: a sea water basin (the Black Sea), an estuary (Hunnbunn fjord), and a freshwater lake (Nordbytjernet), with focus on the distributions of methylmercury (MeHg) and total mercury (THg). THg concentrations were similar in the sea water basin (0.2-1.8 ng/L) and the freshwater lake (0.8-1.2 ng/L), but significantly higher in the estuary (0.6-9.4 ng/L). An increase in the MeHg concentration and MeHg/THg ratio were found in the redox zone in all three basins, indicating bacterial production of MeHg in the aqueous phase. In the lake and estuary, the maximum MeHg concentration and MeHg/THg ratio were found in samples located closest to the bottom sediments, likely due to the formation of MeHg in surface sediments and subsequent diffusion to the overlying waters. [ABSTRACT FROM AUTHOR]

Course administration streptozotocin to male C57Bl/6 mice induces a complex of symptoms typical of type 1 diabetes mellitus: hyperglycemia and insulin deficiency, focal inflammatory infiltration of the pancreas, destructive changes in the Langerhans islets, damage to the insular apparatus (reduced number of PDX1 cells and insulin expression by the secreting cells). Male reproductive disorder are serious complications of type 1 diabetes mellitus. In 'diabetic' mice, interstitial edema with inflammatory infiltration and microvascular disorders in the testicular tissue are observed, the number of endothelial precursors (CD45/CD31) and the total number and percentage of motile spermatozoa decreased, immature spermatogenic epithelium cells are desquamated of into the lumen of the tubules. Disturbances in the proliferation and differentiation of various spermatogonial stem cell populations (c-kit/CD90, c-kit/CD90, and CD51/CD24/CD52) in diabetes can be explained by the inhibitory influence of inflammatory factors on testosterone-producing Leydig cells. [ABSTRACT FROM AUTHOR]

Antifreeze proteins (AFPs) enhance the survival of organisms inhabiting cold environments by affecting the formation and/or structure of ice. We report the crystal structure of the first multi-domain AFP that has been characterized. The two ice binding domains are structurally similar. Each consists of an irregular β-helix with a triangular cross-section and a long α-helix that runs parallel on one side of the β-helix. Both domains are stabilized by hydrophobic interactions. A flat plane on the same face of each domain’s β-helix was identified as the ice binding site. Mutating any of the smaller residues on the ice binding site to bulkier ones decreased the antifreeze activity. The bulky side chain of Leu174 in domain A sterically hinders the binding of water molecules to the protein backbone, partially explaining why antifreeze activity by domain A is inferior to that of domain B. Our data provide a molecular basis for understanding differences in antifreeze activity between the two domains of this protein and general insight on how structural differences in the ice-binding sites affect the activity of AFPs. [ABSTRACT FROM AUTHOR]

The properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90 and epithelial progenitors CD45-CD31-Sca-1CD49f derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro. In contrast, spermatogonial stem cells with immune phenotype CD51-CD24CD52 had reduced selfrenewal capacity. Spermatogonial stem cells CD117-CD90 and CD117CD90 as well as endothelial progenitors CD45-CD31 derived from the testes of donor mice with metabolic disorders demonstrated high transplantation capacity in C57Bl/6 mouse testes damaged by cytostatic busulfan. [ABSTRACT FROM AUTHOR]

Synchrotron-based high-pressure single-crystal X-ray diffraction experiments were conducted on synthetic pure clinoferrosilite, Fe2Si2O6, at room temperature to a maximum pressure of 45 GPa. In addition to the previously described P21/ c → C2/ c phase transition between 1.48 and 1.75 GPa (), we observe further transition between 30 and 36 GPa into the high-pressure P21/c phase (HP- P21/ c). The C2/ c → HP- P21/ c transition is induced by rearrangement of half of the layers of corner-sharing SiO4 tetrahedra into layers of edge-sharing SiO6 octahedra. The new configuration of VISi layers suggests a possibility of a progressive transformation of the pyroxene into an ilmenite-type structure. The persistence of metastable pyroxene up to pressures higher than expected and its feasible direct transformation to ilmenite are of special interest for understanding the dynamics of cold-subducting slabs. We report on structural and compressibility features of both high-pressure phases as well as address thermal stability of HP- P21/ c. [ABSTRACT FROM AUTHOR]

Efficient application of veterinary blood transfusion approaches for small companion animals requires readily available supply of the donor material. This can be achieved by developing of effective biobanking technologies allowing long-term storage of donor blood components via cryopreservation. Transfusion of an erythrocyte concentrate allows the successful correction of various hematological pathologies, severe bleeding, and etc. While in the past there were several approaches to cryopreserve red blood cells of dogs, to our knowledge there is virtually no data on cryopreservation of feline erythrocytes. In this paper, we performed a comprehensive parameter optimization for low temperature storage of RBCs of both species. Here, the efficiency of single-component and multicomponent cryoprotective media as well as necessary time of pre-incubation with penetrating and non-penetrating cryoprotectants prior to rapid freezing is analyzed. This study showed that glycerol was not sufficient for cryopreservation of red blood cells of the studied species under the investigated conditions. Application of 10% (v/v) ME2SO allowed for a significant reduction of canine and feline erythrocytes hemolysis after thawing. 17.5% hydroxyethyl starch demonstrated the highest cryoprotective activity for both species. It was found that dog RBCs should be incubated in cryoprotective media for 30 min at 22°C prior to freezing, while for cat RBCs 20 min is sufficient. Combination of CPAs was less effective. Presented data may be considered in further studies in veterinary transfusion and blood banking optimization. [ABSTRACT FROM AUTHOR]

The regenerative potential of stem and progenitor cells from ischemic testes of C57Bl/6 mice was studied in vitro (cell culture) and in vivo (mouse model of busulfan-induced suppression of spermatogenesis). Spermatogonial stem cells with phenotypes CD117CD90 and CD51CD24CD52 from ischemic testes demonstrated 33-fold and 7-fold increments of cell mass and generated colonies in vitro. Epithelial (CD45CD31Sca-1CD49f) and endothelial (CD45CD31) precursors exhibited lower self-renewal capacity. On day 30 after injection of stem and progenitor cells from ischemic testes to the rete testis zone of the testes of busulfantreated animals, an increase in the count of CD117CD90 spermatogonial stem cells, total count, and mobile sperm count in the testes of recipient mice was observed. In addition, we observed an increase in Sca-1 cell count, recovery of the spermatogenic epithelium in the seminiferous tubules, and appearance of immature Leydig cells in 'busulfan' testes; the level of tissue testosterone and fertility index also increased. [ABSTRACT FROM AUTHOR]

Using the model of hypogonadism in C57Bl/6 male mice, we showed that injection of streptozotocin to newborn animals and high-fat diet induced serum IFN-γ and IL-17 elevation, glucose metabolism disturbances, insulin resistance, destructive changes of the Langerhans islets (deficit of PDX1β cells), while the number of oligopotent β cell precursors (CD45TER119CD133CD49f) increased. Diabetes played the role of an inducer of testicular tissue inflammation (pan-hemopoietic cell infiltration, increase of IL-2, IL-17, and IL-23 content) and reproductive system disturbances in mice (decrease in free testosterone concentration, suppression of spermatogenesis, and infertility). The development of hypogonadism was paralleled by an increase in the count of spermatogonial stem cells (CD117CD29CD90), multipotent mesenchymal stromal cells (CD45CD31CD90CD106), hemangiogenesis precursors (CD45CD117Flk1), and epithelial cells (CD45CD31CD49fCD326). [ABSTRACT FROM AUTHOR]

Stem and progenitor cells were studied on mouse model of testicular ischemia. Testicular ischemia led to a decrease in free testosterone concentration. Hemodynamic changes, interstitial edema, and destruction of spermatogenic epithelium, Leydig, and Sertoli cells were observed in the testicular tissue. Accumulation of degenerative germ cells was accompanied by reduction in the count of spermatogonial stem cells with immunophenotype CD117CD29CD90 and CD117CD29CD90. Simultaneously with pathomorphological changes in the testes and suppression of spermatogenesis, ischemia reduced the count of hematopoietic progenitor cells, hematopoietic stem cells with immunophenotype LinCD117Sca-1c-kitCD34 and LinCD117Sca-1c-kitCD34, and multipotent mesenchymal stromal cells (CD45CD31 CD90CD106) in the testicular tissue. The population of CD45CD31-endothelial cells in ischemic testicular tissue increased. [ABSTRACT FROM AUTHOR]

Inflammation, extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, and fibronectin), stem and progenitor cells (multipotent mesenchymal stromal cells, Clara cells, angiogenesis, precursors, endothelial and epithelial cells) were studied in female C57Bl/6 mice with experimental elastase-induced emphysema. Diffuse emphysema reduced the number of endothelial (CD45CD31CD34) and epithelial (CD45CD117CD49f) cells, induced microcirculation disturbances, and decreased the area occupied by the connective tissue. Emphysematous changes in the lungs were accompanied by infiltration of the alveolar septa with macrophages and lymphocytes, increase in the serum and lung concentrations of transforming growth factor-β, IL-1β, IL-2, IL-5, IL-10, and IL-13, and lung concentration of IL-17. In the lungs, inflammation was associated with marked increase in the number of multipotent mesenchymal stromal cells CD90CD73CD106CD44) and Clara cells (CD45CD34CD31Sca1) and overexpression of extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, fibronectin) and Clara cells protein. On the other hand, elastase reduced the number of angiogenic precursor cells (CD45CD117Flk1). [ABSTRACT FROM AUTHOR]

Electroporation-induced cell sensitization was described as the occurrence of a delayed hypersensitivity to electric pulses caused by pretreating cells with electric pulses. It was achieved by increasing the duration of the electroporation treatment at the same cumulative energy input. It could be exploited in electroporation-based treatments such as electrochemotherapy and tissue ablation with irreversible electroporation. The mechanisms responsible for cell sensitization, however, have not yet been identified. We investigated cell sensitization dynamics in five different electroporation buffers. We split a pulse train into two trains varying the delay between them and measured the propidium uptake by fluorescence microscopy. By fitting the first-order model to the experimental results, we determined the uptake due to each train (i.e. the first and the second) and the corresponding resealing constant. Cell sensitization was observed in the growth medium but not in other tested buffers. The effect of pulse repetition frequency, cell size change, cytoskeleton disruption and calcium influx do not adequately explain cell sensitization. Based on our results, we can conclude that cell sensitization is a sum of several processes and is buffer dependent. Further research is needed to determine its generality and to identify underlying mechanisms. [ABSTRACT FROM AUTHOR]

The responses of tumor stem cells and various populations of CD4 and CD8 T cells of young and aged C57BL/6 mice were studied in a lung cancer model. Using Lewis lung carcinoma cell line, an orthotopic model of lung cancer was modeled. Cancer stem cells, circulating tumor cells, and various populations of CD4 and CD8 T cells in the blood and lung tissue were studied by cytometry. We revealed age-related differences in the content of various populations of CD4 and CD8 T cells in the blood and lungs of intact young and aged mice. Age-related features of the reaction of various populations of cancer stem cells and CD4 and CD8 T cells in the blood and lungs of animals in the Lewis lung carcinoma were shown. [ABSTRACT FROM AUTHOR]

A synthetic CaCO 3 – SrCO 3 solid solution with composition Ca 0.82 Sr 0.18 CO 3 was investigated by single-crystal X-ray diffraction in the pressure range between 0 and 22 GPa using different pressure-transmitting media. The samples were compressed in DACs using Ne up to ∼ 9 GPa and Ar up to ∼ 22 GPa. At ambient conditions, Ca 0.82 Sr 0.18 CO 3 crystallizes in a monoclinic structure, isostructural to CaCO 3 -II, Sr-calcite-II (Sr-CC-II), with space group P 2 1 / c , 4 formula units per unit cell, Z, a = 6.4237 (7) Å, b = 5.0176 (1) Å, c = 8.1129 (1) Å, β = 108.064 (1) ∘ and V = 248.60 (1) Å 3 (where the number in parenthesis is 1 σ uncertainties on the last digit). At 1.72(5) GPa, a structural phase transition is observed to a new monoclinic structure, Sr-calcite-IIIc (Sr-CC-IIIc), with space group P 2 1 / m and Z = 8 ( a = 6.2683 (2) Å, b = 9.9220 (5) Å, c = 7.6574 (6) Å, β = 103.856 (6) ∘ and V = 462.39 (5) Å 3 ), different from any pure CaCO 3 polymorph. At 12 GPa, the sample transformed to a triclinic structure, Sr-calcite-IIIb (Sr-CC-IIIb), with space group P 1 ¯ and Z = 4 ( a = 6.059 (5) Å, b = 6.280 (2) Å, c = 6.331 (2) Å, α = 95.20 (3) ∘ , β = 108.89 (5) ∘ , γ = 110.52 (5) ∘ and V = 207.7 (2) Å 3 ), isostructural to end-member CaCO 3 -IIIb. Finally, at 17 GPa, a transition is observed to Sr-calcite-VI (Sr-CC-VI), with space group P 1 ¯ and Z = 2 ( a = 3.444 (3) Å, b = 4.985 (4) Å, c = 5.761 (5) Å, α = 77.05 (7) ∘ , β = 84.92 (7) ∘ , γ = 89.00 (7) ∘ and V = 96.0 (1) Å 3 ), isostructural to end-member CaCO 3 -VI, which is preserved up to the maximum investigated pressure of 22 GPa. The results of this study show the effect of Sr/Ca cationic substitution on the high-pressure behavior and physical properties of a CaCO 3 – SrCO 3 solid solution. The phase evolution of Ca 0.82 Sr 0.18 CO 3 and the crystallization of a new phase, Sr-CC-IIIc, different from the high-pressure polymorphs of end-member CaCO 3 , point to the importance of extending the study of carbonates to more complex systems than pure end-member compositions. [ABSTRACT FROM AUTHOR]

The article focuses on the examination of a synthetic moissanite coated with diamond film imitating rough diamond at the Far East Geological Institute (FEGI). Topics include thermal conductivity testing indicated diamond, tests for electrical conductivity were not convincing, and only small parallel needle-like inclusions, typical for synthetic moissanite, were found using a gemological microscope.

Acetyl-CoA carboxylase catalyzes the first and regulated step in fatty acid synthesis. In most Gram-negative and Gram-positive bacteria, the enzyme is composed of three proteins: biotin carboxylase, a biotin carboxyl carrier protein (BCCP), and carboxyltransferase. The reaction mechanism involves two half-reactions with biotin carboxylase catalyzing the ATP-dependent carboxylation of biotin-BCCP in the first reaction. In the second reaction, carboxyltransferase catalyzes the transfer of the carboxyl group from biotin-BCCP to acetyl-CoA to form malonyl-CoA. In this report, high-resolution crystal structures of biotin carboxylase from Haemophilus influenzae were determined with bicarbonate, the ATP analogue AMPPCP; the carboxyphosphate intermediate analogues, phosphonoacetamide and phosphonoformate; the products ADP and phosphate; and the carboxybiotin analogue Nl'-methoxycarbonyl biotin methyl ester. The structures have a common theme in that bicarbonate, phosphate, and the methyl ester of the carboxyl group of Nl'-methoxycarbonyl biotin methyl ester all bound in the same pocket in the active site of biotin carboxylase and as such utilize the same set of amino acids for binding. This finding suggests a catalytic mechanism for biotin carboxylase in which die binding pocket that binds tetrahedral phosphate also accommodates and stabilizes a tetrahedral dianionic transition state resulting from direct transfer of CO2 from the carboxyphosphate intermediate to biotin. [ABSTRACT FROM AUTHOR]