LABORATORY 12

Laboratory of Bioinformatics of Cell Processes

and Motocontrol

Head of Laboratory – Dr.Sc. (Mathematics) Alexey Chernavsky

Tel.: (095)209-42-25, (095) 952-33-03; E-mail: chernav@iitp.ru

 

The leading researchers of the laboratory include:

 

Dr.Sc. (Biology)

Yu. Arshavsky

Dr.Sc. (Biology)

 S.  Minina

Dr.Sc. (Biology)

V. Bozhkova

Dr.Sc. (Biology)

Yu. Panchin

Dr.Sc. (Math),

V. Dunin-Barkowsky,

President of the RNNS

Dr.

 M. Berkinblit

Dr.Sc. (Biology)

Z. Khashaev

Dr.

Yu. Burmistrov

Dr.Sc. (Biology)     I. Keder-Stepanova

Dr.

 L.  Kudina

Dr.Sc. (Biology)     E. Liberman

Dr.

 D.  Voronov

Dr.Sc. ( Math.)       I.  Lukashevich

Dr.

 N.  Samosudova

 

Directions of activity

 

The general theme of the scientific work in the laboratory is: analysis of the information processes in cellular systems and in motor control. The main directions of theoretical researches in this realm: developmental biology (analysis of principles for the realization of genetic information in the developmental systems), neurobiology (neural communication and biochemical modulation in neural centers), motor control (study of geometry of manipulative space and of control goal-directed moving). Also some new bioinformatical principles are worked out including the building of computerized system for the analysis of expert knowledge.

 

MAIN RESULTS

 

Developmental biology. It is known that near 1% of all babies are born with the major structural abnormalities which arise still in early embryonic development. But the mechanisms of morphogenetic embryopathies remain unrevealed. The goal of the Dr. V. P. Bozhkova’s group study is to clear what regulatory systems play the signal role in normal morphogenesis. Their recent experiments show that phosphatidylinositol (PI) cycle directs the contractions and cytoskeleton reorganization in embryogenesis. To reveal PI cycle involvement in regulation of morphogenesis at the blastula and gastrula stages GTP-gamma-S (in final concentration 80-100 mM per embryo) and GDP-beta-S (in final concentration 5-15 mM per embryo) were used, respectively, as activator and the inhibitor of PI signalling pathway at the level of G-proteins. Inositol-1,4,5-trisphosphate (IP3) as intermediate of PI cycle also was tested (in final concentration 5-10 mM per embryo) for their influence on the morphogenetic movements of gastrulation. The work was carried out with using of fish (loach, Misgurnus fossilis) embryos. The stages of development at which GTP-gamma-S induced the immediate effect after injection were tested. The cleavage divisions and the second part of gastrulation (50-70% of epiboly) proved to be such stages. The primary effect of GTP-gamma-S consisted in the overcontraction of the yolk syncytial layer and the blastoderm margin. The late blastula and the early epiboly stages were not changed after treatment of GTP-gamma-S. In addition to immediate effect GTP-gamma-S, injected at all the stages from early blastula till midgastrula, had remote contractive effect at the second part of gastrulation. The rate of epiboly was not affected by GTP-gamma-S injections although the epiboly of some embryos was reversed. In opposite to GTP-gamma-S the injections of the stable analog of GDP – GDP-beta-S which inhibit G-protein function retarded the epiboly in loach embryos. In opposite to GTP-gamma-S the injections of IP3 did not induce the blastoderm margin contraction and did not affect the epiboly. So, our results suggest that G-proteins can be involved in stimulation of local cytoskeleton reorganization and contraction at the cleavage divisions stage (perhaps, to contribute to cytokinesis) and at the late gastrula stage to promote the final phase of epiboly. Their effects on contraction can be connected not only with IP3 . As appears from these data also in fish embryogenesis the spatial-temporal regulation of G-proteins activity takes place.

Dr. Y. V. Panchin’s group has developed and perfected new methods of isolation and culturing of identified mollusk clione’s neurons. The methods permit to realize a functional transplantation of neurons from one animal into the neural system of another in vitro. Such a system serve as a good model to study mechanisms forming new interneuron connections. It was first shown that isolated neurons conserve the ability to the selective formation of electric connections, and conditions under which such selectivity is supported or disappears were studied in details. Genes which code the proteins of gap junctions in mollusks (Clione limacina) and planar worms (Girardia tigrina) were first characterized. Also, homologue genes were found in vertebrates, and in particular three genes in humans. These results make evident existence of the second, after connexines, family of gap junction genes in vertebrates. It is ascertained that intraneuron injections of the synthetic mRNA, which codes one of early discovered proteins pannexins, influences specifically on the selectivity of the electric connection formation in the clione’s neural system. It is one of the first experimental demonstrations of the dependence of this selectivity on the gap junction protein repertory in neurons. A hypotheses was also disproved that electric connections cannot be formed between parts of the same neuron.

Dr. D. A. Voronov working in the laboratory of Dr. Taber in Washington University in frame of exploration making therein of mechanical forces part in the heart morphogenesis has found that the main role in the turn of the developing chicken heart to the right side belongs to the mechanical properties of the membrane which cover the heart tube.

Neurobiology The neural system, a base of informational interaction of multi-cell animals, was studying in the laboratory at different levels.

The cerebellum studies present the traditional topic in the laboratory. Dr. W. L. Dunin-Barkowski working in the Health Centre of Texas Tech University, USA, continued studies of the climbing fiber influence upon the Purkinje cells. A hypotheses is proposed that the liana modules approximating the correlated signals could use collectively the synapses of the parallel fibers. This could make the general ensemble productivity of nodules much greater than sum of their individual productivities. Also an analysis of the neuron mechanisms of the medullary respiratory center was continued, especially the work during the cycle waking – sleep under the variation of the gas composition of respirated air and on the background of the natural and artificial breathing. In a computer simulation based on neuron ensembles it was shown that many types of the respirator neurons may be exposed in the simplest model.

Dr. I. A. Keder-Stepanova's group studies changes in the activity of the medullary respirator nuclei in ontogenesis. The neuron activity was recorded in slices from newborn mice (1-10 days). The additional data was collected which affirmed absence of the endogenous synchronized burst activity, that is, in the same slice there occur neurons with different periods of burst activity. Such activity disappears up to 7-8 day and the neurons of respiratory nuclei works continuously with different and not constant frequency. To analyze this activity it is conveyed into computer and also histograms of interimpulse intervals is derived on base of instantaneous measurements (program of V. Olshansky). In this experimental conditions one successes with discovery of implicit period types.

Drs. N. V. Samosudova and N. V. Larionova showed that the stimulation of the parallel fibers in the presence of exogenic nitric oxide (NO) initiated formation of an electron-dense precipitation including calcium ions. Its appearance was observed in structural chain going from granular cell to Purkinje cell at sites of high metabolic activity such as nucleus ( nucleolis and nuclear membrane), mitochondria of axons and dendrites, pre- and postsynaptic membranes of synaptic contact, synaptic vesicles. The precipitation was easily removed by EGTA (2o mM ), supported with the Ca in it. Thus the precipitation formed by stimulation in the presence of exogenic NO may designate the function sites of endogenic NO during the signal transmission from one neuron to another.

When an animal does not make significant behavioral changes, as measured by bodily movements, the animal may be characterized as unresponsive to a given stimulus. A study by Dr. Y. M. Burmistrov demonstrates that when behavioral movements of crayfish cannot be observed, physiological measures of heart rate and ventilator rate show dramatic changes in response to defined sensory stimuli. Since behavioral observations do not allow an internal status to be readily assessed, we suggest that heart rate and ventilator rate may serve as a useful bioindex in crustaceans to their internal drive or possibly an awareness level to environmental cues.

Dr. Z. Kh.-M. Khashaev studies the influence of the varied pharmacological media, especially the supertoxicants of the dioxin series, on the biomembrane penetrability . The study goes in collaboration with the Institute of expermental and theoretical biophysics RAS (Poushchino), and Institute of biochemical physics RAS.

Motor control. Drs. M. B. Berkinblit and S. V. Adamovich have showed that in making movements in the three-dimensional space parkinsonics appreciate the position of arm less precisely in comparison with the normal humans when they do not see the arm prior or in time of the movement. The possibility of the improving of the moving arm and finger function with intensive therapy using virtual reality is studied. In collaboration with the Universities of Ratgers and Medsini a rehabilitation system was elaborated which includes gloves having a feedback for force and displacement, and also a set of videogames for improvements different finger movement parameters: diapason and speed of movement, degree of its independence, force etc. A pilot experimental series was carried out with 4 patients after insult which occurred more than 6 months before to begin the therapy. The having data approve the possibility to elevate the movement arm function in chronic patients after insult.

Drs. L. P. Kudina and N. M. Zhoukovskaya investigated with computer simulation the motoneuron recurrent inhibition clarifying experimental data obtained earlier. The effects of motoneuron firing frequencies and inhibitory volley characteristics on efficacy of the recurrent inhibition of slow and fast model motoneurones were analyzed. The duration of "gap" in crosscorrelation functions of spike trains of pairs of motoneurones was evaluated as a measure for the recurrent inhibition efficacy. It was shown that the effectiveness decreased with an increase in the background rate of motoneurones as has been observed experimentally. At the same time, computer simulations allowed to analyze effects of the amplitude and duration on the recurrent inhibitory volleys which cannot be studied in human experiments. The model findings were used in interpreting experimental results.

Bioinformatical principles. The method of structuring the mildly formalized information and professional knowledge was elaborated by Dr. I. P. Lukashevich. It was used for building the knowledge bases in neurology, neuropsychology and electro-encephalography. In the last case the knowledge base was realized as a computer automatic diagnostic system "EEG-EXPERT". The system is designed (and used) for the practical work in neurological hospitals and policlinics, for learning young specialists and for exploratory goals. The complex analysis permitted to determine the diagnostic and prognostic criteria for the movement and speech rehabilitation in patients after ischemic insult, to investigate the influence of afferent subcortical conductive paths on the electric brain activity, and also to make the comparative valuation of the child brain in age of 5-8 years in norm and under the retardation of the psychic development. (With participation of the Institutes of Age Physiology and of Correctional Pedagogics, RA Education.) The elaborated technique and the complex approach gave a possibility to propose and validate essentially new hypotheses on the etiology and pathogenesis of the stammer syndrome and that showed a path to prophylaxy and to more effective treatment.

Dr. A. V. Chernavsky continued a work on analysis of the development in biological evolution of the principles of informational interactions, especially on the level of pre-speech intellect (with the Sector No. 1.1 of IITP RAS.)

 

Grants from:

 

·        Russian Foundation of Basic Research (No. 99-04-48147): "Основные принципы функционирования молекулярных квантовых компьютеров".

·        Russian Foundation of Basic Research (No. 00-04-49344): "Изучение механизмов взаимодействия различных мозжечковых входов".

·        Russian Foundation of Basic Research (No. 00-04-48822): "Сигнальная функция фосфатидилинозитольной системы в морфогенезе".

·        Russian Foundation of Basic Research (No. 01-50-70102): "Изучение высоко специфических нейронных ансамблей".

·         Министерство образования РФ (ROST-N-90): Русско-французский проект "Зрение роботов 11".

 

Publications in 2001

 

Articles

 

1.      Самосудова Н.В., Божкова В.П. Внутриклеточная локализация кальция в зародышах вьюна на стадии ранней гаструлы // Цитология. 2001, т. 43, № 6, с. 575-582.

2.      Воронов Д.А. Сравнительная эмбриология нематод и закон зародышевого сходства // Общая биология. 2001, 62(1): 34-48.

3.      Panchin Y.V., Kelmanson I.V. Short-circuited neuron: a note // Neuroscience. 2000, 96, 597-599.

4.      Panchin Y., Kelmanson I., Matz M., Lukyanov K., Usman N., Lukyanov S. A ubiquitous family of putative gap junction molecules // Current Biology. 2000, 10, R473-R474.

5.      Ларионова Н.П., Самосудова Н.В., Реутов В.П., Чайлахян Л.М. Сравнительное исследование изменений структуры нейрон-нейронного взаимодействия в молекулярном слое мозжечка лягушки Rana temporaria под влиянием глутамата и NO-генерирующего соединения // ДАН. 2001. Т. 376. № 5., с. 701-706.

6.      Самосудова Н.В., Реутов В.П., Ларионова Н.П., Чайлахян Л.М. Возможное участие оксида азота в межнейронном взаимодействии // ДАН. 2001. Т. 378. № 3., с.417-420.

7.      Самосудова Н.В., Реутов В.П., Ларионова Н.П. Нейрон-глиальные взаимодействия а условиях повреждения нейронной сети мозжечка под влиянием глутамата и оксида азота // Известия ТРТУ. Тематический выпуск ''Интеллектуальные САПР''. 2001, № 4, с. 369.

8.      Фомкина М.Г., Чайлахян Л.М., Хашаев З.Х.-М., Дриняев В.А. Каналообразующие свойства нейротропного препарата Абамектина на бислойные мембраны  // ДАН. 2001. Т. 378, № 6, с. 832-836.

9.      Adamovich S.V., Archambault P., Ghafouri M., Levin M.F., Poizner H., Feldman A.G. Hand trajectory invariance in reaching movements involving the trunk // Experimental Brain Research. 2001, 138: 288-303.

10. Adamovich S.V., Berkinblit M.B., Hening W., Sage J., Poizner H. The interaction of visual and proprioceptive inputs in pointing to actual and remembered targets in Parkinson Тs disease // Neuroscience. 2001, 104: 1027-1041.

11. Jack D., Boian R., Merians A., Tremaine M., Burdea G.C., Adamovich S.V., Recce M., Poizner H. Virtual Reality-Based Stroke Rehabilitation // IEEE Transactions on Neural Systems and Rehabilitation Engineering. 2001, 9: 308-318.

12. Krebs H.I., Hogan N., Hening W., Adamovich S.V., Poizner H. Procedural Motor Learning in Parkinson’s Disease // Experimental Brain Research. 2001, DOI 10.1007

13. Беркинблит М.Б., Адамович С.В. Параллельное управление суставами при целенаправленных движениях // Материалы международной конференции "Параллельные вычисления и задачи управления" (PACO 2001), Москва, 2-4 октября 2001, Институт проблем управления РАН (электронное издание).

14. Piotrkiewicz M., Kudina L., Hausmanova-Petrusewicz I., Zhoukovskaya N., Mierzejewska J. Discharge properties and afterhyperpolarization of human motoneurones supplying slow and fast muscles // Biocybernetics and Biomedical Engineering. 2001, v. 21, no. 1, pp. 53-75.

15. Шкловский В.М., Лукашевич И.П., Мачинская Р.И., Данилов А.В., Печева С.А., Фридман Т.В., Шипкова К.М. Некоторые патогенетические механизмы нарушения развития речи у детей // Дефектология. 2001, № 2, с. 20-28.

16. Кузнецов Н.А., Любецкий В.А., Чернавский А.В. К вопросу о понятии информационного взаимодействия, 2: Доречевой интеллект // Труды III международной конференции «Проблемы управления и моделирования в сложных системах», сентябрь 2001, Самара, Самарский научный центр РАН, 2001, c. 43-61.

17. Чернавский А.В. Концепция информационной параллельности в биологии и психологии // Материалы международной конференции "Параллельные вычисления и задачи управления" (PACO 2001), Москва, 2-4 октября 2001, Институт проблем управления РАН (электронное издание). С. 92-112.

 

In press

 

1.      Подладчикова Л.Н., Бондарь Г.Г., Дунин-Барковский В.Л. Особенности активности “быстрых” и “медленных” клеток Пуркинье мозжечка // Представлено в журнал “Биофизика”, 2001.

2.      Dunin-Barkowski W.L. Analysis of Output of all Purkinje Cells, Controlled by One Climbing Fiber Cell // Submitted to Neurocomputing, 2001.

3.      Dunin-Barkowski W.L., Lovering A.T., Orem J.M. A Neural Ensemble Model of the Respiratory Central Pattern Generator: Properties of the Minimal Model // Submitted to Neurocomputing, 2001.

4.      Самосудова Н.В. и Божкова В.П. Внутриклеточная локализация кальция в зародышах вьюна на стадии ранней гаструлы (сдана в печать)

5.      Krebs, H.I., Volpe, B, Aisen, M., Hening, W., Adamovich, S.V., Poizner, H., Pradeep, K., Hogan, N. Robotic Applications in Neuromotor Rehabilitation // Robotica (in press).

6.      Boian R., Sharma A., Han C., Merians A., Burdea G., Adamovich S.,. Recce M, Tremaine M., Poizner H.. Virtual Reality Based Post-Stroke Hand Rehabilitation // Proceedings of Medicine Meets Virtual Reality Conference 2002, Newport Beach CA, January 23-26 2002 (in press).

7.      Merians A., Jack D., Boian R., Tremaine M., Burdea G.C., Adamovich S.V., Recce M., Poizner H. Virtual Reality-Augmented Rehabilitation For Patients Post Stroke: Three Case Studies // Physical Therapy (under revision).

8.      Ghafouri M., Archambault P.S., Adamovich S.V., Feldman A.G. Pointing movements may be produced in different frames of reference depending on the task demand // Brain Research (under revision).

9.      Schettino L.F., Adamovich S.V., Poizner H. The effects of object shape and visual feedback on hand configuration during grasping // Submitted to Journal of Neurophysiology.

10. Лукашевич И.П., Мачинская Р.И., Шкловский В.М. Роль правого полушария при формировании речи и памяти // Физиология человека (сдана в печать).

11. Либерман Е. А., Минина С. В., Шкловский-Корди Н.Е. Хаиматика – новая наука, объединяющая биологию, физику и математику (cдана в печать).

 

Conferences reports

 

1.      Kelmanson I.V., Shagin D.A., Matz M.V., Lukyanov S.A., Panchin Y.V. Altering electrical connections in the nervous system // Abstr. Soc. Neurosc., 2001.

2.      Dunin-Barkowski W.L. Analysis of Output of all Purkinje Cells, Controlled by One Climbing Fiber Cell. – In: "Tenth Annual Computational Neuroscience Meeting, San Francisco, June 30 - July 5, 2001", p. 34.

3.      Dunin-Barkowski W.L., Lovering A.T., Orem J.M. A Neural Ensemble Model of the Respiratory Central Pattern Generator: Properties of the Minimal Model. – In: "Tenth Annual Computational Neuroscience Meeting, San Francisco, June 30 – July 5, 2001", p. 34.

4.      Lovering A.T., Dunin-Barkowski W.L., Vidruk E.H.Orem J.M. Activity of medullary inspiratory neurons during hypoxia in cat // Soc. Neurosci. Abstr., 2001, Vol. 27, Program No. 573.4.

5.      Dunin-Barkowski W.L. Re-synthesis of climbing fiber cell input at Purkinje cell output // Soc. Neurosci. Abstr., 2001, Vol. 27, Program No. 577.1

6.      Samosudova N.V., Reutov V.P. Larionova N.P. Calcium localization in cerebellum microtubules exposed by means of electric stimulation in the NO-presence // Biological Motility: New trends in research. International symposium. Pushchino. 2001. p. 126.

7.      Larionova N.P., Reutov V.P., Samosudova N.V. The Possible Role of L-glutamate and Nitric Oxide in Frog Cerebellum Cellular Fusion and Neuronal Net Functioning Control // 2nd International Conference on Glial Interfaces in the Nervous System: Development and Repair. Uppsala, Sweden. 2001, p. 25.

8.      Larionova N.P., Reutov V.P., Samosudova N.V. Convergent-Divergent Glial Cell Roles in the Cerebellum Neuro-Glial Ansamble Functioning // Myelin: Development, Disoders and Neural Repair, ISN/ASN Satellite Meeting, Colonia, Uruguay, 2001, p. 53.

9.      Хашаев З.Х-М., Шекшеев Э.М., Ким Ю.А. Поиски новых путей защиты от воздействия экотоксикантов // Тезисы доклада на IX международном Симпозиуме "Мониторинг здоровья населения и окружающей среды. Технологии и информационные базы данных", 28 апреля – 5 мая 2001 г., Греция, о. Крит. М.: 2001, т. 1, с. 78.

10. Хашаев З.Х-М. Комплексный подход к изучению молекулярного механизма действия психофармакологических препаратов и экосупертоксикантов // Материалы Международной научно-технической конференции и молодежной научной конференции "Интеллектуальные САПР’’, ИЗВЕСТИЯ ТРТУ, 2001, № 4, с. 287-295.

11. Туманова А.Л., Хашаев З.Х-М. 1. Прогнозирование глазных заболеваний в Краснодаре, их связь с общей заболеваемостью // Материалы Международной научно-технической конференции и молодежной научной конференции "Интеллектуальные САПР”, ИЗВЕСТИЯ ТРТУ, 2001, № 4, с. 310-320.

12. Туманова А.Л., Хашаев 3. Х.-М. 2. Прогнозирование глазных заболеваний в Краснодаре, их связь с общей заболеваемостью // Материалы Международной научно-технической конференции и молодежной научной конференции "Интеллектуальные САПР”, ИЗВЕСТИЯ ТРТУ, 2001, № 4, с. 371-372.

13. Хашаев З.Х-М. Исследование механизма действия экосупертоксикантов на биологические мембраны // Материалы Юбилейной научно-практической конференции Ассоциации научно-технических обществ корейцев стран СНГ. Москва, 21-23 июня 2001, с. 90-92.

14. Туманова А.Л., Хашаев З.Х.-М. Информационные факторы прогнозирования и предупреждения риска возникновения заболеваний глаз // Труды VII Международной конференции "Информационные сети, системы и технологии". ICINASTe-2001. Минск, Беларусь, 2-4 октября 2001 г. Т. 3, с. 180-183.

15. Messier, J., Adamovich S., Jack D., Poizner H. Hemispheric specialization and visuomotor adaptation // Proceedings: Society for Neuroscience, 2001.

16. Schettino L.F., Adamovich S.V., Gordon A.M., Poizner H. The role of the transport phase during grasping tactilely-defined target shapes // Proceedings: Society for Neuroscience, 2001.

17. Tunik E., Poizner H., Levin M.F., Adamovich S.V., Messier J., Lamarre Y., Feldman A.G. Role of proprioception in arm-trunk coordination during reaching with unexpected perturbation of the trunk // Proceedings: Society for Neuroscience, 2001.

18. Kudina L. Single and doublet firing of human motoneurones: two patterns or two mechanisms? // Матеpиалы Междунаpодной научно-технической конференции "Интеллектуальные САПP", Таганpог, 2001, с. 351-352.

19. Piotrkiewicz М., Kudina L., Mierzejewska J., Zhoukovskaya N. Human motoneuron firing characteristics: modal and experiment // Матеpиалы Междунаpодной научно-технической конференции "Интеллектуальные САПP", Таганpог, 2001, с. 295-299.

20. Пиотркевич М., Кудина Л., Гаусманова-Петpусевич И. Анализ ритмики двигательных единиц как способ исследования импульсной активности мотонейронов // Симпозиум "Двигательные единицы в норме и патологии". Ваpшава, октябpь 2001 г.

21. Лукашевич И.П. Роль языка описания при комплексном анализе профессиональных знаний // III Международная конференция "Проблемы управления и моделирования в сложных системах", Самара, 3-9 сентября 2001 г.

22. Шкловский В.М., Лукашевич И.П., Мачинская Р.И., Зиборова Е.В., Фридман Т.В. Нейрофизиологическая классификация психо-эмоционального состояния детей с заиканием // Конгресс по детской психиатрии с международным участием "Психическое здоровье – детям XXI века". Москва, 25-28 сентября 2001 г. C. 342.

23. Шкловский В.М., Лукашевич И.П., Руднева О.В. Некоторые патогенетические механизмы нарушения поведения детей со специфическим расстройством речи // Конгресс по детской психиатрии с международным участием "Психическое здоровье – детям XXI века". Москва, 25-28 сентября 2001 г. C. 340.