Late Ediacaran Redox Stability and Metazoan Evolution

The Neoproterozoic arrival of animals fundamentally changed Earth's biological and geochemical trajectory. Since the early description of Ediacaran and Cambrian animal fossils, a vigorous debate has emerged about the drivers underpinning their seemingly rapid radiation. Some argue for predation and ecology as central to diversification, whereas others point to a changing chemical environment as the trigger. In both cases, questions of timing and feedbacks remain unresolved. Through these debates, the last fifty years of work has largely converged on the concept that a change in atmospheric oxygen levels, perhaps manifested indirectly as an oxygenation of the deep ocean, was causally linked to the initial diversification of large animals. What has largely been absent, but is provided in this study, is a multi-proxy stratigraphic test of this hypothesis. Here, we describe a coupled geochemical and paleontological investigation of Neoproterozoic sedimentary rocks from northern Russia. In detail, we provide iron speciation data, carbon and sulfur isotope compositions, and major element abundances from a predominantly siliciclastic succession (spanning>1000 m) sampled by the Kel'tminskaya-1 drillcore. Our interpretation of these data is consistent with the hypothesis that the $pO_2$ threshold required for diversification of animals with high metabolic oxygen demands was crossed prior to or during the Ediacaran Period. Redox stabilization of shallow marine environments was, however, also critical and only occurred about 560 million years ago (Ma), when large motile bilaterians first enter the regional stratigraphic record. In contrast, neither fossils nor geochemistry lend support to the hypothesis that ecological interactions altered the course of evolution in the absence of environmental change. Together, the geochemical and paleontological records suggest a coordinated transition from low oxygen oceans sometime before the Marinoan (~635 Ma) ice age, through better oxygenated but still redox-unstable shelves of the early Ediacaran Period, to the fully and persistently oxygenated marine environments characteristic of later Ediacaran successions that preserve the first bilaterian macrofossils and trace fossils.Earth and Planetary SciencesOrganismic and Evolutionary Biolog

Antigenic Components of Chemical Bivalent Cholera Vaccine, Methods of their Isolation and Control

The paper presents a review of the data on the methods of isolation and control of Vibrio cholerae antigens – cholerogen-anatoxin and O-antigens of Inaba and Ogawa – components of the oral bivalent chemical cholera vaccine produced by the RusRAPI “Microbe”, the only prophylactic drug against cholera registered in the territory of the Russian Federation. Currently, the vaccine is produced using the method of segregated manufacturing of cholerogenanatoxin and O-antigens Inaba and Ogawa with step-by-step control of their main properties, which ensures the production of a high-quality finished product. Ultrafiltration is an effective method for concentrating a semi-finished product, which helps to reduce losses and increases the yield of the final product. It remains promising to develop a method for gentle steril ization of O-antigens to maximize the preservation of specific activity. To control the specific activity of the antigenic components and the finished vaccine preparation, a complex of in vivo and in vitro methods is applied. However, the multi-stage process and duration, the use of several types of laboratory animals, as well as modern WHO requirements determine the need for the introduction of alternative in vitro control methods. The use of cell cultures as a replacement for the biological method appears prospective, and demonstrates a positive correlation with animal tests. To assess the activity of antigens, the use of an immunochemical method – dot-immunoassay with gold nanoparticles – is put forward, which will make it possible to harmonize the control method at all stages of the production process, as well as to determine the serovar specificity of Vibrio cholerae O-antigens. The development of molecular-genetic, microbiological, immunochemical methods is relevant for a more complete and comprehensive control of the main immunogens of industrial strains of cholera vibrio. The introduction of promising methods for obtaining antigens and monitoring their properties will allow for a more complete characterization of the component composition of the finished dosage form of the chemical cholera vaccine

Воспроизводство трудового потенциала в период депопуляции 2019–2035 гг. и компенсирующая роль миграционного фактора

Purpose of the research. To examine the dynamics of reproduction of labor potential and labor supply in Russia for the period up to 2035, depending on the impact factors of its reproduction: generation change (changes in the proportion of cohort, entering and leaving at the age composition of the labor potential), fertility and mortality rates, migration balance in the individual age cohorts.  Materials and methods. The concept of “replacement of generations” is introduced. The coefficient of replacement of generations is developed and its value for labor potential of Russia for the period up to 2035 is calculated. The influence of factors of natural population movement on the dynamics of labor potential is analyzed. The compensating role of the migration factor in the conditions of labor potential reduction is calculated. Russian regions were grouped according to the following criteria: the direction and intensity of changes in the working-age population in 2020–2035 and the proportion of young people aged 0–15 years.  Results.  – There will be the reduction and aging of labor potential during the second stage of depopulation due to demographic factors.  – The decline in the working-age population in the second wave of depopulation is expected to be smaller than in the first wave.  – In Russia there will be a decrease in the replacement of generations in the contingent of people of the working age.  – The growth of Total Fertility Rate (TFR) in the forecast period should not be expected, because until 2030 a gradual decrease in the number of women of reproductive age is expected.  – The deepest failure in the population of the working age will be in 2020–2025 accounting for 1.7 million people according to the average variant of the forecast.  – In the forecast period, the labor force in the most productive age of 25–39 years will decrease by 10.5 million people, and the employment rate will decrease from 65.5% to 63.5%.  – Regional features of the formation of demand and supply of labor force in Russia cause the allocation of six homogeneous groups of regions.  – In order to compensate for the losses, it is necessary to increase the migration gain in the average version of ROSSTAT forecast by 2–2.5 times.  Conclusion. To meet the needs of the economy in the labor force in the forecast period, it is necessary to solve two interrelated tasks: compensation for the reduction of labor potential and ensuring the quality of labor potential necessary for the introduction of new technologies and digitalization of the economy. The unfavorable situation with the formation of labor resources is exacerbated by regional imbalances in the distribution of labor potential and differences in its quality across the country. In the future, migration is once again the only source of replenishment of labor potential and replacement of generations, despite the risks of quality losses due to the emigration of highly qualified persons and young people. It is necessary to take measures to increase the compensatory role of migration in the next five – six years. At the same time, migration policy measures should be considered in close conjunction with other measures to stimulate fertility and reduce mortality, ensuring a positive impact on the components of the population growth.  Цель работы: рассмотреть динамику воспроизводства трудового потенциала и предложение рабочей силы в России на период до 2035 г. в зависимости от воздействия факторов его воспроизвод­ства: замещения поколений (изменения соотношения численности когорт, входящих и выходящих по возрасту из состава трудового потенциала), рождаемости и смертности населения, миграци­онного сальдо в отдельных возрастных когортах.  Материалы и методы. Введено понятие «замещение поколе­ний». Разработан коэффициент замещения поколений и рассчи­тано его значение для трудового потенциала России на период до 2035 года. Проанализировано влияние факторов естественного движения населения на динамику трудового потенциала. Рас­считана компенсирующая роль фактора миграции в условиях сокращения трудового потенциала. Проведена группировка регионов России по признакам: направление и интенсивность изменения численности населения трудоспособного возраста в 2020–2035 гг. и доля молодежи в возрасте 0–15 лет.  Результаты  – Сокращение и постарение трудового потенциала в период второго этапа депопуляции обусловлено демографическими факторами.  – Прогнозируемое сокращение численности населения трудо­способного возраста во вторую волну депопуляции ожидается в меньших масштабах, чем в первую волну.  – В целом в России будет отмечаться снижение замещения поколений в контингенте лиц трудоспособного возраста.  – Ожидать роста СКР в прогнозном периоде не следует, поскольку до 2030 г. предвидится постепенное сокращение численности женщин репродуктивного возраста.  – На 2020–2025 гг. приходится наиболее глубокий провал в численности населения трудоспособного возраста: по среднему варианту прогноза он составит 1,7 млн чел.  – В прогнозном периоде численность рабочей силы в наиболее продуктивном возрасте 25–39 лет сократится на 10,5 млн чел., а уровень занятости сократится с 65,5% до 63,5%.  – Выявлены региональные особенности формирования спроса и предложения рабочей силы в России по 6 однородным группам регионов.  – Чтобы компенсировать потери необходимо увеличить в 2–2,5 раза миграционный прирост, заложенный в средний вариант прогноза Росстата.  Заключение. Для обеспечения потребностей экономики в рабочей силе в прогнозном периоде необходимо решать две взаимосвязанные задачи: компенсация сокращения трудового потенциала и обеспечение качества трудового потенциала, необходимого для внедрения новых технологий и цифровиза­ции экономики. Неблагополучная ситуация с формированием трудовых ресурсов усугубляется региональными диспропорци­ями в размещении трудового потенциала и различиями в его качестве по территории страны. В перспективе миграция становится вновь единственным источником пополнения тру­дового потенциала и замещения поколений, несмотря на риски качественных потерь за счет эмиграции лиц высокой квалифи­кации и молодежи. Необходимо принятие кардинальных мер по увеличению компенсирующей роли миграции уже в ближайшие пять-шесть лет. При этом, меры миграционной политики должны рассматриваться в тесной увязке с другими мерами по стимулированию рождаемости и снижению смертности, обеспечивая положительное воздействие на компоненты роста численности населения.

Investigating the stability of the Properties of Vibrio cholerae strains – Producers of Active Components of the Chemical Cholera Vaccine

One of the key requirements to producer strains used in the manufacturing of immunobiological preparations is their stability, which consists in maintaining the main cultural, morphological, physiological, and productive properties in a series of generations. This paper describes a comprehensive methodological approach to testing strain stability using in vitro techniques.The purpose of this study was to conduct an integrated analysis of the stability in the strains that produce active components of the chemical cholera vaccine when preparing seed material and at the stage of cultivation.Materials and methods. Toxigenic strains of Vibrio сholerae 569B of the classical biovar, serovar Inaba and V. сholerae M-41 of the classical biovar, serovar Ogawa were used in the work. Cell morphology was monitored through light and transmission electron microscopy. Atomic force microscopy was applied to measure the main parameters of the bacterial cell. The strains were tested for the presence of ctxA gene in the chromosome using the “GenChol” test system with electrophoretic registration of results. Whole genome sequencing of the strains was performed on the Ion Torrent PGM platform using the Ion 318 Chip Kit and the Ion PGM Hi-Q View Chef 400 Kit. To determine the specific activity of cholera toxin and O-antigen, a DOT immunoassay with a conjugate based on staphylococcal protein A and colloidal gold nanoparticles was applied.Results and discussion. The stability of the main properties of industrial V. сholerae strains – producers of the active components of the chemical cholera vaccine has been confirmed using microbiological, immunochemical, molecular-genetic methods and microscopic analysis at all stages of cultivation, and the prospects for using the integrated methodological approach experimentally substantiated. Tailoring of these methods will make it possible to control the stability of producer strains, optimize cultivation conditions and, as a result, increase the yield of the necessary antigenic component of the vaccine

Assessment of Stability of Chemical Cholera Vaccine in a New Primary Packaging

The bivalent chemical cholera vaccine is the only drug for the prevention of cholera registered in the Russian Federation. The vaccine has been produced in glass bottles containing 210 tablets. At the same time, modern trends dictate the need to produce the drug in varying dispensing and more practical packaging for the convenience of the consumer.The aim of the work was to study the stability of the properties of the immunobiological medicinal product “Bivalent chemical cholera vaccine” with modified filling and in new primary packaging.Materials and methods. When studying the quality of bivalent chemical cholera vaccine batches, physicochemical parameters, formaldehyde content, specific activity and safety, abnormal toxicity, immunogenicity, and microbiological purity were assessed. Stability in terms of “specific activity” was evaluated using dot immunoassay.Results and discussion. As a result of this work, the use of several dispensing options and new primary packaging of cholera vaccine has been experimentally substantiated. The stability of the finished vaccine preparation has been established in the “accelerated aging” test and during long-term storage. The possibility of using dot immunoassay with a conjugate based on staphylococcal protein A, labeled with colloidal gold, to monitor the stability of cholera vaccine has been experimentally demonstrated

The labor potential reproduction in depopulation period of 2019–2035 and the compensating role of migration

Purpose of the research. To examine the dynamics of reproduction of labor potential and labor supply in Russia for the period up to 2035, depending on the impact factors of its reproduction: generation change (changes in the proportion of cohort, entering and leaving at the age composition of the labor potential), fertility and mortality rates, migration balance in the individual age cohorts.  Materials and methods. The concept of “replacement of generations” is introduced. The coefficient of replacement of generations is developed and its value for labor potential of Russia for the period up to 2035 is calculated. The influence of factors of natural population movement on the dynamics of labor potential is analyzed. The compensating role of the migration factor in the conditions of labor potential reduction is calculated. Russian regions were grouped according to the following criteria: the direction and intensity of changes in the working-age population in 2020–2035 and the proportion of young people aged 0–15 years.  Results.  – There will be the reduction and aging of labor potential during the second stage of depopulation due to demographic factors.  – The decline in the working-age population in the second wave of depopulation is expected to be smaller than in the first wave.  – In Russia there will be a decrease in the replacement of generations in the contingent of people of the working age.  – The growth of Total Fertility Rate (TFR) in the forecast period should not be expected, because until 2030 a gradual decrease in the number of women of reproductive age is expected.  – The deepest failure in the population of the working age will be in 2020–2025 accounting for 1.7 million people according to the average variant of the forecast.  – In the forecast period, the labor force in the most productive age of 25–39 years will decrease by 10.5 million people, and the employment rate will decrease from 65.5% to 63.5%.  – Regional features of the formation of demand and supply of labor force in Russia cause the allocation of six homogeneous groups of regions.  – In order to compensate for the losses, it is necessary to increase the migration gain in the average version of ROSSTAT forecast by 2–2.5 times.  Conclusion. To meet the needs of the economy in the labor force in the forecast period, it is necessary to solve two interrelated tasks: compensation for the reduction of labor potential and ensuring the quality of labor potential necessary for the introduction of new technologies and digitalization of the economy. The unfavorable situation with the formation of labor resources is exacerbated by regional imbalances in the distribution of labor potential and differences in its quality across the country. In the future, migration is once again the only source of replenishment of labor potential and replacement of generations, despite the risks of quality losses due to the emigration of highly qualified persons and young people. It is necessary to take measures to increase the compensatory role of migration in the next five – six years. At the same time, migration policy measures should be considered in close conjunction with other measures to stimulate fertility and reduce mortality, ensuring a positive impact on the components of the population growth

Difficulties in the Differential Diagnosis of Tracheobronchomegaly in Children

Tracheobronchomegaly is a rare developmental defect in children, which is characterized by the expansion of the trachea and large bronchi, the diagnosis and treatment of which are made more often in adult practice, when the clinical diagnostic picture acquires the obvious features of Mounier-Kuhn syndrome. In this connection, the need arises for the early detection of this pathology in children and its differentiation from other diseases and malformations of the tracheobronchial tree, which mask a recurrent inflammatory process in the lung and upper respiratory tract, and primarily with those, such as cystic fibrosis and primary ciliary dyskinesia.The paper describes a case of secondary tracheobronchomegaly in a child with obvious clinical manifestations of Mounier-Kuhn syndrome in the presence of bronchiectasis, pulmonary fibrosis, and signs of systemic connective tissue disease. It discusses the possibilities of chest computed tomography in the diagnosis of this defect in children, as well as its causes. The sizes of the trachea and main bronchi in this patient are compared with those in the groups of children of the same age and sex who have cystic fibrosis or diffuse pulmonary fibrosis to identify a more significant role of hereditary connective tissue diseases in the development of secondary tracheobronchomegaly. The authors propose to separate the concepts of tracheobronchomegaly and Mounier-Kuhn syndrome in children and to recognize the threshold for tracheal expansion in these patients having +3SD or more

Use of inosine pranobex in frequently ill children

The follow-up group of «frequently ill children» is formed on the basis of criteria formulated by domestic pediatricians A.A. Baranov and V.Yu. Al’bitskiy, due to the high relevance of medical, social and economic problems caused by the increased morbidity in this category of patients especially with acute respiratory infections, with likely development of severe complications or the manifestation of chronic respiratory diseases. In general, the state of the immune system in frequently ill children is characterized by decreased local immunity and increased stress of systemic immunity, and the features of the functional immunity activity in this category of patients determine the various possibilities to affect immunity during the prevention and treatment of acute respiratory infections. This article discusses the features of the functional activity of the immune system in frequently ill children, as well as the possibilities of drug management of its disorders and the benefits of using inosine pranobex to prevent and treat respiratory infections in this category of patients. According to the international classification of drugs maintained by the World Health Organization, the drug belongs to the groups of immunomodulators (L) and antimicrobial antiviral drugs (J) for systemic use. It is proved that inosine pranobex effectively increases cellular and humoral immunity, and reduces non-specifically the viral replication capacity. During clinical trials, the drug proved to be a highly effective and safe component of the complex treatment of acute respiratory infections in frequently ill children. The use of inosine pranobex reduces the duration and intensity of symptoms of infectious respiratory tract diseases. The drug can be recommended for children with concomitant chronic respiratory tract diseases