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162. Differential effects of formoterol on thrombin- and PDGF-induced proliferation of human pulmonary arterial vascular smooth muscle cells

Author

Goncharova Elena A, Khavin Irene S, Goncharov Dmitry A, and Krymskaya Vera P

Subjects
(R, R) formoterol, ERK1/2, Pulmonary hypertension, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Increased pulmonary arterial vascular smooth muscle (PAVSM) cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH). The long-acting β2-adrenergic receptor (β2AR) agonist formoterol, a racemate comprised of (R,R)- and (S,S)-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD). PH, a common complication of COPD, increases patients’ morbidity and reduces survival. Recent studies demonstrate that formoterol has anti-proliferative effects on airway smooth muscle cells and bronchial fibroblasts. The effects of formoterol and its enantiomers on PAVSM cell proliferation are not determined. The goals of this study were to examine effects of racemic formoterol and its enantiomers on PAVSM cell proliferation as it relates to COPD-associated PH. Methods Basal, thrombin-, PDGF- and chronic hypoxia-induced proliferation of primary human PAVSM cells was examined by DNA synthesis analysis using BrdU incorporation assay. ERK1/2, mTORC1 and mTORC2 activation were determined by phosphorylation levels of ERK1/2, ribosomal protein S6 and S473-Akt using immunoblot analysis. Results We found that (R,R) and racemic formoterol inhibited basal, thrombin- and chronic hypoxia-induced proliferation of human PAVSM cells while (S,S) formoterol had lesser inhibitory effect. The β2AR blocker propranolol abrogated the growth inhibitory effect of formoterol. (R,R), but not (S,S) formoterol attenuated basal, thrombin- and chronic hypoxia-induced ERK1/2 phosphorylation, but had little effect on Akt and S6 phosphorylation levels. Formoterol and its enantiomers did not significantly affect PDGF-induced DNA synthesis and PDGF-dependent ERK1/2, S473-Akt and S6 phosphorylation in human PAVSM cells. Conclusions Formoterol inhibits basal, thrombin-, and chronic hypoxia-, but not PDGF-induced human PAVSM cell proliferation and ERK1/2, but has little effect on mTORC1 and mTORC2 signaling. Anti-proliferative effects of formoterol depend predominantly on its (R,R) enantiomer and require the binding with β2AR. These data suggest that (R,R) formoterol may be considered as potential adjuvant therapy to inhibit PAVSM cell proliferation in COPD-associated PH.

Published
2012
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164. Deaf Children after Cochlear Implantation: Transformation of the Speech Therapist Professional Competencies.

Author

Kukuskina, Olga I., Goncharova, Elena L., Malofeev, Nikolay N., and Satayeva, Albina I.

Subjects
*DEAF children, *COCHLEAR implants, *SPEECH therapists, *COMMUNICATION, *AUDITORY perception
Abstract

The purpose of the article is to present the method developed for triggering the natural and spontaneous mastering of communication and speech in a deaf child after cochlear implant (CI) surgery, which is typical for a normally hearing child. The article also aims at demonstrating the need for revision of professional competencies of the present-day teachers of deaf children and speech therapists. The ideas on the social nature of secondary developmental disorders in children with severe hearing and the ideas on the role of normal child's affective interaction with close adults for triggering the development of child's auditory perception and speech during the first year of life served the theoretical basis of the study. Also, the ideas on the triggering point of the natural development of auditory perception and speech in children after CI surgery and the ideas proposed in the Galperin theory constituted the theoretical ground of the research. The results of the study: a) method of 3R rehabilitation aimed at transferring a child with CI to the path of the natural development of auditory perception, communication and speech, typical for a normally hearing young child; b) evidence of the effectiveness of the 3R rehabilitation method of a family and a child with CI; c) practical professional skills of a specialist, necessary for implementing a 3R rehabilitation of a family and a child with CI, are identified, their differences from those traditionally taught for the teachers of deaf children and speech therapists are shown. [ABSTRACT FROM AUTHOR]

Published
2020
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165. Повышение качества работы по формированию здорового образа жизни дошкольников через игровую деятельность

Author

Pertseva Liubov Vasilevna, Musina Alesia Nikolaevna, and Goncharova Elena Anatolevna

Subjects
игровые технологии, инновационные технологии, квест-игры
Abstract

авторы отмечают, что в соответствии с требованиями ФГОС одной из основных задач физического развития детей дошкольного возраста является становление ценностей здорового образа жизни, овладение его элементарными нормами и правилами. Важным подспорьем в этой работе служат игровые технологии.

Published
2018

169. Инновационные факторы экономического развития России

Author

Goncharova Elena Viacheslavovna and Starovoitov Mikhail Karpovich

Subjects
инновационный потенциал, инновации, стратегия, экономическое развитие, малые предприятия
Abstract

в представленной статье авторы рассматривают основные факторы формирования стратегии экономического развития с точки зрения инновационной составляющей. Особо выделена роль малых предприятий. В работе анализируется процесс адаптационного воздействия и прогнозирования устойчивого функционирования предприятий. Проанализирован опыт мировой практики на примере Европейской карты инновационного развития и выделены важнейшие ее направления.

Published
2018

170. Факторы формирования инновационного потенциала промышленных предприятий

Author

Goncharova Elena Viacheslavovna and Starovoitov Mikhail Karpovich

Subjects
рынок, инновационный потенциал, технопарк, инновационные инфраструктуры, управление инновационным потенциалом, научно-техническая продукция
Abstract

в статье рассматриваются основные факторы формирования инновационного потенциала предприятий на современном этапе российской экономики. Рассмотрены особенности управления инновационным потенциалом. Обоснована роль инновационных инфраструктур в развитии российских предприятий. Приведен практический пример развития промышленности города Волжского.

Published
2017

176. Metformin Therapy for Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction versus Pulmonary Arterial Hypertension

Author

Goncharov, Dmitry A., primary, Goncharova, Elena A., additional, Tofovic, Stevan P., additional, Hu, Jian, additional, Baust, Jeff J., additional, Pena, Andressa Z., additional, Ray, Arnab, additional, Rode, Analise, additional, Vanderpool, Rebecca R., additional, Mora, Ana L., additional, Gladwin, Mark T., additional, and Lai, Yen-Chun, additional

Published
2018
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183. Инновационные факторы экономического развития России

Author

Гончарова Елена Вячеславовна, Волжский политехнический институт (филиал) ФГБОУ ВО «Волгоградский государственный технический университет», Goncharova Elena Viacheslavovna, Volzhskii politekhnicheskii institut (filial) FGBOU VO "Volgogradskii gosudarstvennyi tekhnicheskii universitet", Старовойтов Михаил Карпович, Starovoitov Mikhail Karpovich, Гончарова Елена Вячеславовна, Волжский политехнический институт (филиал) ФГБОУ ВО «Волгоградский государственный технический университет», Goncharova Elena Viacheslavovna, Volzhskii politekhnicheskii institut (filial) FGBOU VO "Volgogradskii gosudarstvennyi tekhnicheskii universitet", Старовойтов Михаил Карпович, and Starovoitov Mikhail Karpovich

Abstract

В представленной статье авторы рассматривают основные факторы формирования стратегии экономического развития с точки зрения инновационной составляющей. Особо выделена роль малых предприятий. В работе анализируется процесс адаптационного воздействия и прогнозирования устойчивого функционирования предприятий. Проанализирован опыт мировой практики на примере Европейской карты инновационного развития и выделены важнейшие ее направления.

Published
2018

184. Повышение качества работы по формированию здорового образа жизни дошкольников через игровую деятельность

Author

Перцева Любовь Васильевна, МБДОУ «Д/С №62 «Золотой улей», Pertseva Liubov Vasilevna, MBDOU "D/S 62 "Zolotoi ulei", Мусина Алеся Николаевна, Musina Alesia Nikolaevna, Гончарова Елена Анатольевна, Goncharova Elena Anatolevna, Перцева Любовь Васильевна, МБДОУ «Д/С №62 «Золотой улей», Pertseva Liubov Vasilevna, MBDOU "D/S 62 "Zolotoi ulei", Мусина Алеся Николаевна, Musina Alesia Nikolaevna, Гончарова Елена Анатольевна, and Goncharova Elena Anatolevna

Abstract

Авторы отмечают, что в соответствии с требованиями ФГОС одной из основных задач физического развития детей дошкольного возраста является становление ценностей здорового образа жизни, овладение его элементарными нормами и правилами. Важным подспорьем в этой работе служат игровые технологии.

Published
2018

186. Automated Measurement of Blood Vessels in Tissues from Microscopy Images

Author

Kelly, Neil J, Dandachi, Nadine, Goncharov, Dmitry A, Pena, Andressa Z, Radder, Josiah E, Gregory, Alyssa D, Lai, Yen-Chun, Leme, Adriana S, Gladwin, Mark T, Goncharova, Elena A, St Croix, Claudette M, and Shapiro, Steven D

Subjects
Male, Microscopy, Image Processing, Reproducibility of Results, Bioengineering, Vascular Remodeling, Inbred C57BL, Rats, Mice, Automation, Computer-Assisted, pulmonary hypertension, Blood Vessels, Animals, Sprague-Dawley, wall thickness, morphometry
Abstract

The quantification of tunica media thickness in histological cross sections is a ubiquitous exercise in cardiopulmonary research, yet the methods for quantifying medial wall thickness have never been rigorously examined with modern image analysis tools. As a result, inaccurate and cumbersome manual measurements of discrete wall regions along the vessel periphery have become common practice for wall thickness quantification. The aim of this study is to introduce, validate, and facilitate the use of an improved method for medial wall thickness quantification. We describe a novel method of wall thickness calculation based on image skeletonization and compare its results to those of common techniques. Using both theoretical and empirical approaches, we demonstrate the accuracy and superiority of the skeleton-based method for measuring wall thickness while discussing its interpretation and limitations. Finally, we present a new freely available software tool, the VMI Calculator, to facilitate wall thickness measurements using our novel method. © 2016 by John Wiley & Sons, Inc.

Published
2016

187. Tumor suppressors TSC1 and TSC2 differentially modulate actin cytoskeleton and motility of mouse embryonic fibroblasts.

Author

Goncharova, Elena A, Hotchin, Neil A1, Goncharova, Elena A, James, Melane L, Kudryashova, Tatiana V, Goncharov, Dmitry A, Krymskaya, Vera P, Goncharova, Elena A, Hotchin, Neil A1, Goncharova, Elena A, James, Melane L, Kudryashova, Tatiana V, Goncharov, Dmitry A, and Krymskaya, Vera P

Abstract

TSC1 and TSC2 mutations cause neoplasms in rare disease pulmonary LAM and neuronal pathfinding in hamartoma syndrome TSC. The specific roles of TSC1 and TSC2 in actin remodeling and the modulation of cell motility, however, are not well understood. Previously, we demonstrated that TSC1 and TSC2 regulate the activity of small GTPases RhoA and Rac1, stress fiber formation and cell adhesion in a reciprocal manner. Here, we show that Tsc1(-/-) MEFs have decreased migration compared to littermate-derived Tsc1(+/+) MEFs. Migration of Tsc1(-/-) MEFs with re-expressed TSC1 was comparable to Tsc1(+/+) MEF migration. In contrast, Tsc2(-/-) MEFs showed an increased migration compared to Tsc2(+/+) MEFs that were abrogated by TSC2 re-expression. Depletion of TSC1 and TSC2 using specific siRNAs in wild type MEFs and NIH 3T3 fibroblasts also showed that TSC1 loss attenuates cell migration while TSC2 loss promotes cell migration. Morphological and immunochemical analysis demonstrated that Tsc1(-/-) MEFs have a thin protracted shape with a few stress fibers; in contrast, Tsc2(-/-) MEFs showed a rounded morphology and abundant stress fibers. Expression of TSC1 in either Tsc1(-/-) or Tsc2(-/-) MEFs promoted stress fiber formation, while TSC2 re-expression induced stress fiber disassembly and the formation of cortical actin. To assess the mechanism(s) by which TSC2 loss promotes actin re-arrangement and cell migration, we explored the role of known downstream effectors of TSC2, mTORC1 and mTORC2. Increased migration of Tsc2(-/-) MEFs is inhibited by siRNA mTOR and siRNA Rictor, but not siRNA Raptor. siRNA mTOR or siRNA Rictor promoted stress fiber disassembly in TSC2-null cells, while siRNA Raptor had little effect. Overexpression of kinase-dead mTOR induced actin stress fiber disassembly and suppressed TSC2-deficient cell migration. Our data demonstrate that TSC1 and TSC2 differentially regulate actin stress fiber formation and cell migration, and that only TSC2 loss promotes mTOR- an

Published
2014

188. Folliculin controls lung alveolar enlargement and epithelial cell survival through E-cadherin, LKB1, and AMPK.

Author

Goncharova, Elena A, Goncharova, Elena A, Goncharov, Dmitry A, James, Melane L, Atochina-Vasserman, Elena N, Stepanova, Victoria, Hong, Seung-Beom, Li, Hua, Gonzales, Linda, Baba, Masaya, Linehan, W Marston, Gow, Andrew J, Margulies, Susan, Guttentag, Susan, Schmidt, Laura S, Krymskaya, Vera P, Goncharova, Elena A, Goncharova, Elena A, Goncharov, Dmitry A, James, Melane L, Atochina-Vasserman, Elena N, Stepanova, Victoria, Hong, Seung-Beom, Li, Hua, Gonzales, Linda, Baba, Masaya, Linehan, W Marston, Gow, Andrew J, Margulies, Susan, Guttentag, Susan, Schmidt, Laura S, and Krymskaya, Vera P

Abstract

Spontaneous pneumothoraces due to lung cyst rupture afflict patients with the rare disease Birt-Hogg-Dubé (BHD) syndrome, which is caused by mutations of the tumor suppressor gene folliculin (FLCN). The underlying mechanism of the lung manifestations in BHD is unclear. We show that BHD lungs exhibit increased alveolar epithelial cell apoptosis and that Flcn deletion in mouse lung epithelium leads to cell apoptosis, alveolar enlargement, and an impairment of both epithelial barrier and overall lung function. We find that Flcn-null epithelial cell apoptosis is the result of impaired AMPK activation and increased cleaved caspase-3. AMPK activator LKB1 and E-cadherin are downregulated by Flcn loss and restored by its expression. Correspondingly, Flcn-null cell survival is rescued by the AMPK activator AICAR or constitutively active AMPK. AICAR also improves lung condition of Flcn(f/f):SP-C-Cre mice. Our data suggest that lung cysts in BHD may result from an underlying defect in alveolar epithelial cell survival, attributable to FLCN regulation of the E-cadherin-LKB1-AMPK axis.

Published
2014

191. Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction

Author

Alvarez, Roger A., primary, Miller, Megan P., additional, Hahn, Scott A., additional, Galley, Joseph C., additional, Bauer, Eileen, additional, Bachman, Timothy, additional, Hu, Jian, additional, Sembrat, John, additional, Goncharov, Dmitry, additional, Mora, Ana L., additional, Rojas, Mauricio, additional, Goncharova, Elena, additional, and Straub, Adam C., additional

Published
2017
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193. Pharmacological Inhibition of mTOR Kinase Reverses Right Ventricle Remodeling and Improves Right Ventricle Structure and Function in Rats

Author

Pena, Andressa, primary, Kobir, Ahasanul, additional, Goncharov, Dmitry, additional, Goda, Akiko, additional, Kudryashova, Tatiana V., additional, Ray, Arnab, additional, Vanderpool, Rebecca, additional, Baust, Jeffrey, additional, Chang, Baojun, additional, Mora, Ana L., additional, Gorcsan, John, additional, and Goncharova, Elena A., additional

Published
2017
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197. HDAC6: A Novel Histone Deacetylase Implicated in Pulmonary Arterial Hypertension

Author

Boucherat, Olivier, primary, Chabot, Sophie, additional, Paulin, Roxane, additional, Trinh, Isabelle, additional, Bourgeois, Alice, additional, Potus, François, additional, Lampron, Marie-Claude, additional, Lambert, Caroline, additional, Breuils-Bonnet, Sandra, additional, Nadeau, Valérie, additional, Paradis, Renée, additional, Goncharova, Elena A., additional, Provencher, Steeve, additional, and Bonnet, Sébastien, additional

Published
2017
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200. Development of a Mouse Model of Metabolic Syndrome, Pulmonary Hypertension, and Heart Failure with Preserved Ejection Fraction

Author

Meng, Qingqing, primary, Lai, Yen-Chun, additional, Kelly, Neil J., additional, Bueno, Marta, additional, Baust, Jeffrey J., additional, Bachman, Timothy N., additional, Goncharov, Dmitry, additional, Vanderpool, Rebecca R., additional, Radder, Josiah E., additional, Hu, Jian, additional, Goncharova, Elena, additional, Morris, Alison M., additional, Mora, Ana L., additional, Shapiro, Steven D., additional, and Gladwin, Mark T., additional

Published
2017
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