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From the search for new oncogenes to the effort of redefining the cancerogenesis phenomenon
Pajer, Petr ; Dvořák, Michal (advisor) ; Vodička, Pavel (referee) ; Eckschlager, Tomáš (referee)
The described experimental model of clonal tumors induced through the insertional mutagenesis with MAV-2 proved to be a valid and rich source of information describing the process of transformation of normal into tumor cell. We have mapped more than 2000 individual clonal VISs from several hundreds of tumor tissue samples. We have analyzed five tumor types of different histology and tissue of origin along with their derivative tissue cultures. Furthermore, we have discovered the industasis phenomenon and described it during the course of the study. The goal of my study was to uncover common reasons for neoplastic transformation of the cell. The results of my study led me to the paradoxical conclusion that the significance of genetic changes as the primary cause of induction of neoplastic transformation is being overestimated. Although studying the functions of individual genes and search for new tumor markers and therapeutical targets are still beneficial, I believe that the traditional perception of tumor formation as a function/result of mutation accumulation and selection is becoming a serious drawback in further investigations. These conclusions are further discussed in the last section of the presented Ph.D. thesis.
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The biological importance of CAS SH3 domain tyrosine phosphorylation
Janoštiak, Radoslav ; Brábek, Jan (advisor) ; Dvořák, Michal (referee)
Protein CAS is a major tyrosine-phosphorylated protein in cells transformed by v-crk and v-src oncogenes. It is a multidomain adaptor protein, which serves as a scaffold for assembly of signalling complexes which are important for migration and invasiveness of Src-transformed cells. A novel phosphorylation site in N-terminal SH3 domain was identified - tyrosine 12 located on binding surface of CAS SH3 domain. To study biological importance of tyrosine 12 phosphorylation, non-phosphorylable (Y12F) and phosphomimicking ( Y12E) mutant of CAS were prepared. We found that phosphomimicking mutation Y12E leads to decreased interaction of CAS SH domain with kinase FAK a phosphatase PTP-PEST and also reduce tyrosine phosphorylation of FAK. Using GFP-tagged CAS protein, we show that Y12E mutation caused delocalization of CAS from focal adhesion but has no effect on localization of CAS to podosome-type adhesion. Non-phosphorylable mutation Y12F cause hyperphosphorylation of CAS substrate domain and decrease turnover of focal adhesion and associated cell migration of mouse embryonal fibroblasts (MEFs) independent to integrin singalling. Analogically to migration, CAS Y12F decrease invasiveness of Src-transformed MEF. The results of this diploma thesis show that phosphorylation of Tyr12 in CAS SH3 domain is...
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French Muses of Jindřich Štyrský
Dvořák, Michal ; Listíková, Renáta (advisor) ; Ébert-Zeminová, Catherine (referee)
Jindřich Štýrský est né le 11 aot 1899 dans le village appelé Černá en Bohme de l'est ; ses parents y avaient une grande propriété. Štýrský avait une relation difficile avec ses parents. Son pre, enseignant atteint d'alcoolisme chronique, était assez exigeant et obligeait son fils de devenir l'enseignant. Sa mre était trs croyante et l'a peu materné. Sa soeur aînée du premier mariage de sa mre s'appelait Marie et Štýrský enfant était amoureux d'elle. Cette relation platonique a fortement marqué Štýrský et elle a évoqué chez lui de premires fantaisies érotiques. Les témoignages décrivent Štýrský comme un jeune homme élégant et bien élevé. Il était connu comme un séducteur des femmes. Il détestait ses études d'enseignant et il préférait la peinture et la littérature. Parmi ses auteurs aimés se trouvaient les écrivains français. La mort de sa mre lui a libéré et aprs ses études, un an de service mititaire et deux ans de la profession du maître, il a quitté la campagne et s'est installé Prague. Malgré l'opposition de son pre il y a fréquenté l'Académie d'art plastique et il rencontrait des artistes connus. A cause de sa personnalité compliquée il a bientôt abandonné ses études l'Académie et grâce aux moyens obtenus de la succession de sa mre il a décidé voyager. Štýrský a voulu aller en Polynésie mais il s'est...
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Cytokine expression in chemically-induced senescence
Nováková, Zora ; Hodný, Zdeněk (advisor) ; Hampl, Aleš (referee) ; Dvořák, Michal (referee)
AbstractJanderova-Rossmeislova L., Novakova Z., Vlasakova J., Philimonenko V., Hozak P., Hodny Z., 2007. PML protein association with specific nucleolar structures differs in normal, tumor and senescent human cells. J. Struct. Biol. 159, 56-70. Cellular senescence, widely recognized as a potent suppressor of tumorigenesis, represents response to cellular stress and DNA damage which results in irreversible cell growth arrest. Growing evidence signalizes crucial role of cytokine production in senescence phenomenon. Recently, many research groups have efforted to define exact character of senescence-associated secretory phenotype and its function in senescence development and maintentance. Factors secreted by senescent cells, mainly of proiflammatory character, were found to have pronounced effects on their environment as well as on its own producer. These observations were obtained preferentially on models of replicative senescence and oncogene-induced senescence. Vlasakova J, Novakova Z, Rossmeislova L, Kahle M, Hozak P, Hodny Z. 2007. Histone deacetylase inhibitors suppress IFNalpha-induced up-regulation of promyelocytic leukemia protein. Blood 109: 1373-80 Novakova Z, Man P, Novak P, Hozak P, Hodny Z. 2006. Separation of nuclear protein complexes by blue native polyacrylamide gel electrophoresis....
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Interactive flexible program - Sulfur chemistry and its impact to acquiring of curriculum
Dvořák, Michal
UNIVERZITA cká fakulta KARLOVA V PRAZE, Přírodověde Katedra učitelství a didaktiky chemie CHA ce RLES UNIVERSITY IN PRAGUE, Faculty of Scien Department of Teaching and Didactic of Chemistry Interaktivní flexibilní program - Chemie síry a jeho vliv na efektivitu osvojování učiva Interactive flexible program - Sulfur chemistry and its impact to acquiring of curriculum Mgr. Michal Dvořák Souhrn disertační práce Summary of PhD. Thesis 1 Praha/Praque 2009 2 KEYWORDS Interactive flexible program; electronic materials; digital textbook; education software; effectiveness; process of acquiring curriculum; key competencies; chemistry xperiments, personal computer; technology. e INTRODUCTION We live in an era of information technology where the revolutionary way of acquiring new information is available. The new information deepen and widen acknowledge in individual branches of science. Most of the new information contradicts the validity of the existing data. Huge increase and still rising difficulty of the new information require the fundamental changes in the organization of process of acquiring curriculum. But the existing education tools specified for self-studying pupils do not reflect these...
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Interactive flexible program - Sulfur chemistry and its impact to acquiring of curriculum
Dvořák, Michal ; Čipera, Jan (advisor) ; Bílek, Martin (referee) ; Havlíček, David (referee)
13. Summary At the end I have found out that all the main and partial goals identified at the beginning of the work have been fulfilled and the stated hypothesis has been confirmed. The results of the educational material analysis show that there is no any satisfactory complex educational program on the market. The questionnaire investigation between teachers and pupils acknowledged the present trend of using computers in education. It was explicitly demonstrated the interest at the both side oť the utilization in education system. The most of teachers appreciate the possibility to edit the Program according to the current needs. The chosen technology DHTML allows any user with the basic computer literacy and at least elementary knowledge of HTML to modify and adjust the Program in compliance with the actual conditions. On the basis of the facts established by enquiry I have created the Interactive Flexible Program "Chemistry of Sulfur" in order to all requirements on the modern didactic instrument specified for self-study. I have verified the created IFp during the study on some secondary schools in the Czech Republic. The results proofed the main research hypothesis of this work that the self-study with IFP contributes to the better results within learning of chernistry. I only did not succeed in the...
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The influence of employment policy measures on employing persons with disability
Dvořák, Michal ; Tomeš, Igor (advisor) ; Hutař, Jan (referee)
The object of the thesis - The influence of employment policy measures on employing persons with disabilites - is set of employment policy measures applying to emplyoing persons with disabilites in the Czech Republic, and the influence of the measures on employing such persons from 1997 through 2007. The thesis describes development of the measures, analyses the measures costs, and considers the measures influence on the progress of the unemployment rate among persons with disabilites.
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The VoIP protocols real time analyzer
Dvořák, Michal ; Jirovský, Václav (advisor) ; Kvítek, Petr (referee)
This thesis goal is to desing an application which would allow real-time monitoring and analyzing of services for transferring voice over the Internet network, based on the study of the relevant standards. The thesis focuses on monitoring the H.323 standard. An implementation is a part of this thesis.
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