Features of socio-economic development of the Republic of Tatarstan and conditions for the implementation of the investment and cluster policies of the region

© 2016 Kvon et al.The relevance of the problems studied in this article due to the fact, that the conversion of business conditions in modern markets environment imposed the need for the development of new long-term engagement forms between subjects of the regional economy, aimed at their effective functioning. This is primarily due to the unevenness in this process and the weakness of the generative force of the regional base. There is a need for developing directions of a holistic and long-term impact on the investment processes in the region. All the foregoing necessitates a complex analyzing, a socio-economic analyzing of the Republic of Tatarstan and identifying conditions of realization of the investment and cluster policies. The purpose of the article consists in the identification of the preconditions for the realization of the investment and cluster policies of the region based on an analysis of the socio-economic dynamic of the development of the Republic of Tatarstan. The leading method for the researching of this issue is the statistical method, which is a method of the quantitative analysis of set of homogeneous facts that lead to the conversion of quantitative modifications to qualitative. In this article is presented a characteristic of socio-economic development of the Republic of Tatarstan for the period 2011-2015, trends in the indicators characterizing the investment activity in the region. Also here are considered the main clusters of the Republic, score of the investment activity of the region; conditions for the realization of the investment and cluster policies of the region are identified through the analyze. Sound methods of the need to cluster activation in the region are made on findings of the research. Materials of the article are providing the practical value for specialists involved in monitoring process of conditions of realization of the investment and cluster policies in the region

КОМПЛЕКСНЫЙ ХАРАКТЕР ВЛИЯНИЯ ПОЛИЦИКЛИЧЕСКИХ АРОМАТИЧЕСКИХ УГЛЕВОДОРОДОВ НА МЕТАБОЛИЧЕСКИЕ ПРОЦЕССЫ КАК ВАЖНЫЙ ФАКТОР, ОПРЕДЕЛЯЮЩИЙ ОСОБЕННОСТИ ИХ КАНЦЕРОГЕННОЙ АКТИВАЦИИ

In the article, the contribution of the monooxygenase component to the carcinogenic activation of a key procarcinogenic derivative of benzo(a)pyrene – 7,8-benzo(a)pyrenediol in lung adenocarcinoma cell line A549 was evaluated. It is shown that the contribution of the monooxygenase process under the experimental conditions in A549 cells is only 13 %, which corresponds to a relatively low level of the constitutive expression of CYP1A1 and CYP1B1. The situation changes significantly when cells are exposed to 20-methylcholanthrene. In this case, the monooxygenase component in the carcinogenic activation of 7,8-benzo(a)pyrenediol has reached 25 %. Moreover, 90 % is accounted for a "complete" carcinogen – diolepoxide-2. As 20-methylcholanthrene is a polycyclic aromatic compound and exists with a benzo(a)pyrene in the tobacco smoke, this suggests that the entry into the body a whole pool of polycyclic aromatic hydrocarbons may significantly affect not only the level but also the direction of the carcinogenic PAH activation of individual compounds.В работе оценен вклад монооксигеназной составляющей в канцерогенную активацию одного из ключевых проканцерогенных производных бензо(а)пирена – 7,8-бензо(а)пирен-диола в клеточной линии аденокарциномы легких А549. Количественное определение двух образующихся в результате монооксигеназной реакции диолэпоксидов и сопоставление с израсходованным количеством субстрата позволили заключить, что вклад монооксигеназного процесса в условиях эксперимента в клетках А549 составляет лишь 13 %, что в принципе согласуется с относительно низким уровнем конститутивной экспрессии CYP1A1 и CYP1B1. Картина существенно меняется при экспонировании клеток действию 20-метилхолантрена - полициклического ароматического углеводорода, входящего в состав табачного дыма: монооксигеназная составляющая в канцерогенной активации 7,8-бензо(а)пирен-диола достигает уже 25 %. Причем практически 90 % приходится на долю "полного" канцерогена – диолэпоксида-2. Это позволяет полагать, что попадание в организм не одного, а целого пула полициклических ароматических углеводородов может существенным образом влиять не только на уровень, но и на направление канцерогенной активации отдельных представителей полициклических ароматических соединений

Оценка уровня экспрессии и каталитической активности изоэнзимов цитохрома Р450 в опухолевой клеточной линии А549

The contribution of monooxygenase component in carcinogenic activation of a key procarcinogenic derivative of benzo(a) pyrene - 7,8-benzo(a)pyrenediol in lung adenocarcinoma cell line A549 has been evaluated. It has been shown that the contribution of monooxygenase process under the experimental conditions in A549 cells is only 13 %, which corresponds with the relatively low level of constitutive expression of CYP1A1 and CYP1B1. When cells are exposed to 20-methylcholanthrene, monooxygenase component in carcinogenic activation of 7,8-benzo(a)pyrenediol has reached 25 %. Moreover, 90 % is accounted for a "complete" carcinogen - diolepoxide-2. As 20-methylcholanthrene is a polycyclic aromatic compound and exists with a benzo(a) pyrene in the tobacco smoke, this suggests a whole pool of polycyclic aromatic hydrocarbons entering the organism may significantly affect not only the level but also the direction of carcinogenic PAH activation of individual compounds.Оценен вклад монооксигеназной составляющей в канцерогенную активацию одного из ключевых прокан-церогенных производных бензо(а)пирена - 7,8-бензо(а)пирен-диола в клеточной линии аденокарциномы легких А549. Количественное определение двух образующихся в результате монооксигеназной реакции диолэпокси-дов и сопоставление с израсходованным количеством субстрата позволило заключить, что вклад монооксиге-назного процесса в условиях эксперимента в клетках А549 составляет лишь 13 %, что в принципе согласуется с относительно низким уровнем конститутивной экспрессии CYP1A1 и CYP1B1. Картина существенно меняется при экспонировании клеток действию 20-метилхолантрена. В этом случае монооксигеназная составляющая в канцерогенной активации 7,8-бензо(а)пирен-диола достигает уже 25 %. Причем практически 90 % приходится на долю «полного» канцерогена - диолэпоксида-2. Напомним, что 20-метилхоантрен является полициклическим ароматическим соединением и наряду с бензо(а)пиреном входит в состав табачного дыма. Это позволяет полагать, что попадание в организм не одного, а целого пула полициклических ароматических углеводородов может существенным образом влиять не только на уровень, но и на направление канцерогенной активации отдельных представителей полициклических ароматических углеводородов

State-of-the-art analytical methods of viral infections in human lung organoids

Human-based organ models can provide strong predictive value to investigate the tropism, virulence, and replication kinetics of viral pathogens. Currently, such models have received widespread attention in the study of SARS-CoV-2 causing the COVID-19 pandemic. Applicable to a large set of organoid models and viruses, we provide a step-by-step work instruction for the infection of human alveolar-like organoids with SARS-CoV-2 in this protocol collection. We also prepared a detailed description on state-of-the-art methodologies to assess the infection impact and the analysis of relevant host factors in organoids. This protocol collection consists of five different sets of protocols. Set 1 describes the protein extraction from human alveolar-like organoids and the determination of protein expression of angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and FURIN as exemplary host factors of SARS-CoV-2. Set 2 provides detailed guidance on the extraction of RNA from human alveolar-like organoids and the subsequent qPCR to quantify the expression level of ACE2, TMPRSS2, and FURIN as host factors of SARS-CoV-2 on the mRNA level. Protocol set 3 contains an in-depth explanation on how to infect human alveolar-like organoids with SARS-CoV-2 and how to quantify the viral replication by plaque assay and viral E gene-based RT-qPCR. Set 4 provides a step-by-step protocol for the isolation of single cells from infected human alveolar-like organoids for further processing in single-cell RNA sequencing or flow cytometry. Set 5 presents a detailed protocol on how to perform the fixation of human alveolar-like organoids and guides through all steps of immunohistochemistry and in situ hybridization to visualize SARS-CoV-2 and its host factors. The infection and all subsequent analytical methods have been successfully validated by biological replications with human alveolar-like organoids based on material from different donors

ФАРМАКОКИНЕТИЧЕСКИЕ СВОЙСТВА И ЭНЗИМАТИЧЕСКИЙ ГИДРОЛИЗ ДИАЦИЛГЛИЦЕРОФОСФАТНЫХ ПРОИЗВОДНЫХ ФЛУДАРАБИНА

It is shown that the intragastric administration of 1,2- and 1,3-diacylglycerphosphate fludarabine derivatives to Wistar rats and ICR outbred mice leads to a prolonged circulation of fludarabine in animal serum in comparison with the analogous administration of equimolar fludarabine phosphate. The investigated compounds can be regarded as oral fludarabine prodrugs. It is found that the oral bioavalability of fludarabine from its 1,2-dimyristoylglycerophosphate derivative is close to its oral bioavalability from equimolar fludarabine phosphate. Based on the data of the model in vitro experiments, we can suppose that fludarabine can release from its diacylglycerphosphate prodrugs under the action of phospholipases A and D and phosphodiesterases.Установлено, что в результате внутрижелудочного введения 1,2- и 1,3-диацилглицерофосфатных производных флударабина крысам Вистар и аутбредным мышам наблюдается пролонгированное выделение и более длительная циркуляция нуклеозида в системном кровотоке животных, чем после введения эквимолярных количеств флударабина фосфата. Изученные фосфолипидные производные могут рассматриваться в качестве пероральных пролекарств флударабина. Показано, что оральная биодоступность флударабина из его 1,2-димиристоилглицерофосфатного производного у животных близка к его оральной биодоступности из эквимолярного количества флударабина фосфата. На основании данных, полученных в модельных экспериментах in vitro, можно предположить, что флударабин может выделяться из полученных пролекарств под действием ферментов, принадлежащих к семействам фосфолипаз А и Д, а также фосфодиэстераз

Human alveolar progenitors generate dual lineage bronchioalveolar organoids

Mechanisms of epithelial renewal in the alveolar compartment remain incompletely understood. To this end, we aimed to characterize alveolar progenitors. Single-cell RNA-sequencing (scRNA-seq) analysis of the HTII-280(+)/EpCAM(+) population from adult human lung revealed subclusters enriched for adult stem cell signature (ASCS) genes. We found that alveolar progenitors in organoid culture in vitro show phenotypic lineage plasticity as they can yield alveolar or bronchial cell-type progeny. The direction of the differentiation is dependent on the presence of the GSK-3β inhibitor, CHIR99021. By RNA-seq profiling of GSK-3β knockdown organoids we identified additional candidate target genes of the inhibitor, among others FOXM1 and EGF. This gives evidence of Wnt pathway independent regulatory mechanisms of alveolar specification. Following influenza A virus (IAV) infection organoids showed a similar response as lung tissue explants which confirms their suitability for studies of sequelae of pathogen-host interaction

Features of socio-economic development of the Republic of Tatarstan and conditions for the implementation of the investment and cluster policies of the region

© 2016 Kvon et al.The relevance of the problems studied in this article due to the fact, that the conversion of business conditions in modern markets environment imposed the need for the development of new long-term engagement forms between subjects of the regional economy, aimed at their effective functioning. This is primarily due to the unevenness in this process and the weakness of the generative force of the regional base. There is a need for developing directions of a holistic and long-term impact on the investment processes in the region. All the foregoing necessitates a complex analyzing, a socio-economic analyzing of the Republic of Tatarstan and identifying conditions of realization of the investment and cluster policies. The purpose of the article consists in the identification of the preconditions for the realization of the investment and cluster policies of the region based on an analysis of the socio-economic dynamic of the development of the Republic of Tatarstan. The leading method for the researching of this issue is the statistical method, which is a method of the quantitative analysis of set of homogeneous facts that lead to the conversion of quantitative modifications to qualitative. In this article is presented a characteristic of socio-economic development of the Republic of Tatarstan for the period 2011-2015, trends in the indicators characterizing the investment activity in the region. Also here are considered the main clusters of the Republic, score of the investment activity of the region; conditions for the realization of the investment and cluster policies of the region are identified through the analyze. Sound methods of the need to cluster activation in the region are made on findings of the research. Materials of the article are providing the practical value for specialists involved in monitoring process of conditions of realization of the investment and cluster policies in the region

Features of socio-economic development of the Republic of Tatarstan and conditions for the implementation of the investment and cluster policies of the region

© 2016 Kvon et al.The relevance of the problems studied in this article due to the fact, that the conversion of business conditions in modern markets environment imposed the need for the development of new long-term engagement forms between subjects of the regional economy, aimed at their effective functioning. This is primarily due to the unevenness in this process and the weakness of the generative force of the regional base. There is a need for developing directions of a holistic and long-term impact on the investment processes in the region. All the foregoing necessitates a complex analyzing, a socio-economic analyzing of the Republic of Tatarstan and identifying conditions of realization of the investment and cluster policies. The purpose of the article consists in the identification of the preconditions for the realization of the investment and cluster policies of the region based on an analysis of the socio-economic dynamic of the development of the Republic of Tatarstan. The leading method for the researching of this issue is the statistical method, which is a method of the quantitative analysis of set of homogeneous facts that lead to the conversion of quantitative modifications to qualitative. In this article is presented a characteristic of socio-economic development of the Republic of Tatarstan for the period 2011-2015, trends in the indicators characterizing the investment activity in the region. Also here are considered the main clusters of the Republic, score of the investment activity of the region; conditions for the realization of the investment and cluster policies of the region are identified through the analyze. Sound methods of the need to cluster activation in the region are made on findings of the research. Materials of the article are providing the practical value for specialists involved in monitoring process of conditions of realization of the investment and cluster policies in the region

Features of socio-economic development of the Republic of Tatarstan and conditions for the implementation of the investment and cluster policies of the region

© 2016 Kvon et al.The relevance of the problems studied in this article due to the fact, that the conversion of business conditions in modern markets environment imposed the need for the development of new long-term engagement forms between subjects of the regional economy, aimed at their effective functioning. This is primarily due to the unevenness in this process and the weakness of the generative force of the regional base. There is a need for developing directions of a holistic and long-term impact on the investment processes in the region. All the foregoing necessitates a complex analyzing, a socio-economic analyzing of the Republic of Tatarstan and identifying conditions of realization of the investment and cluster policies. The purpose of the article consists in the identification of the preconditions for the realization of the investment and cluster policies of the region based on an analysis of the socio-economic dynamic of the development of the Republic of Tatarstan. The leading method for the researching of this issue is the statistical method, which is a method of the quantitative analysis of set of homogeneous facts that lead to the conversion of quantitative modifications to qualitative. In this article is presented a characteristic of socio-economic development of the Republic of Tatarstan for the period 2011-2015, trends in the indicators characterizing the investment activity in the region. Also here are considered the main clusters of the Republic, score of the investment activity of the region; conditions for the realization of the investment and cluster policies of the region are identified through the analyze. Sound methods of the need to cluster activation in the region are made on findings of the research. Materials of the article are providing the practical value for specialists involved in monitoring process of conditions of realization of the investment and cluster policies in the region

Supraspinal and Afferent Signaling Facilitate Spinal Sensorimotor Network Excitability After Discomplete Spinal Cord Injury: A Case Report

© Copyright © 2020 Militskova, Mukhametova, Fatykhova, Sharifullin, Cuellar, Calvert, Grahn, Baltina and Lavrov. Objective: In this study, we evaluated the role of residual supraspinal and afferent signaling and their convergence on the sublesional spinal network in subject diagnosed with complete paralysis (AIS-A). Methods: A combination of electrophysiologic techniques with positional changes and subject-driven reinforcement maneuvers was implemented in this study. Electrical stimulation was applied transcutaneously at the T9-L2 vertebra levels and the spinal cord motor evoked potentials (SEMP) were recorded from leg muscles. To test the influence of positional changes, the subject was placed in (i) supine, (ii) upright with partial body weight bearing and (iii) vertically suspended without body weight bearing positions. Results: Increase in amplitude of SEMP was observed during transition from supine to upright position, supporting the role of sensory input in lumbosacral network excitability. Additionally, amplitudes of SEMP were facilitated during reinforcement maneuvers, indicating a supralesional influence on sub-lesional network. After initial assessment, subject underwent rehabilitation therapy with following electrophysiological testing that reviled facilitation of SEMP. Conclusion: These results demonstrate that combination of electrophysiological techniques with positional and reinforcement maneuvers can add to the diagnostics of discomplete SCI. These findings also support an idea that integration of supraspinal and afferent information on sub-lesional circuitry plays a critical role in facilitation of spinal sensorimotor network in discomplete SCI