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Posttranlational protein modifications in response to DNA damage
Kroupa, Michal ; Hodný, Zdeněk (advisor) ; Novotný, Marian (referee)
- 5 - Abstract Thousands of DNA lessions occur in each cell every day of which the most toxic are double-strand breaks (DSBs). Signaling of their presence and subsequent repair are mediated by so-called DNA-damage response mechanism (DDR), which involves accumulation of many effector proteins into DSBs sites. These molecular accumulation at DSBs are termed DNA damage foci. Depending on presence of sister chromatid, DSBs are repaired by two major mechanisms: by homologous recombination and by non-homologous end joining. Both pathways lead to activation of checkpoint kinases (Chk1 or Chk2) which iniciate checkpoints in cell cycle and allow repair of damaged DNA. Signaling of DNA damage and activation of these pathways are regulated by posttranslational protein modifications. These enzymatic reactions involve mainly phosphorylation, ubiquitination and sumoylation. Recently it was shown that ubiquitination of damaged chromatin is a prerequisite for sumoylation of tumor supressors BRCA1 and 53BP1. Failure in DNA damage recognizing mechanisms caused by disorders such as modifications or mutations of 53BP1 and BRCA1 genes can lead to subsequent disruption of genomic integrity and then a high risk for selection of cell clones with tumorigenic potencial. Current research is focused on regulation of posttranslational...
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Chromosomal damage and DNA repair capacity in blood lymphocytes as transient markers in carcinogenesis.
Kroupa, Michal ; Vodička, Pavel (advisor) ; Štětina, Rudolf (referee)
Recent knowledge suggests that the onset of cancer is modulated by the interplay of internal and external environmental factors along with numerous gene variants. Structural chromsomal aberrations in peripheral blood lymphocytes are considered as biomarkers of effect of genotoxic carcinogens and reflect elevated risk of cancer. Incomplete or deficient repair of double-strand breaks in DNA underlie chromosomal aberrations and the measurement of cytogenetic alterations may reflect interindividual differences in the response towards the mutagen. In this study the expected deficiences in the DNA repair capacity have been determined in incident oncological patients with breast, colorectal and urogenital cancers. The determination of chromosomal aberrations have been supplemented by the measurement of variants in genes involved in double-strand breaks repair (XRCC3, rs861539; RAD54L, rs1048771). Methodologically, we employed conventional cytogenetic analysis, cytogenetic analysis following the induction of chromocomal damage by bleomycin ("Challenge assay"), TaqMan discrimination analysis for the detection of allelic variants and statistical analyses. By using these methods we did not observe statistically signifiant differences either in chromosomal breaks (p=0,354) or in a percentage of cells with...
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Reform of the IMF Real empowerment of developing countries or just a gesture?
Kroupa, Michal ; Plechanovová, Běla (advisor) ; Parízek, Michal (referee)
Recently implemented reform of the IMF was motivated by empowering smaller developing and emerging countries. My work has an ambition to assess the countries were empowered and whether there would be a more efficient way for IMF reform. I analyse of role and power of countries using well-established methodology of Voting Power Indices. Apart from the immediate change a longer perspective covering last 20 years would be implemented. My aim is not only assess the power of countries as isolated variables but also to assess them in context of other indicators such as economic development. Lastly, I would suggest a new way of reform proposal for the IMF. Currently countries are represented in the locus of executive power through constituencies. Constituencies are formed arbitrary often reflecting power-seeking behaviour of developed countries. The result is composition of constituencies that often further marginalize the developing countries. My proposal is to restructure these constituencies in line with regional international organizations, which can enhance the position of developing countries in two ways. By providing institutional capacity of already existing organizations the consensus within the constituency would be better facilitated. By formation constituencies in line with regional...
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Chromosomal damage and shortening of telomeres in cancer patients and healthy subjects
Kroupa, Michal ; Vodička, Pavel (advisor) ; Kmoníčková, Eva (referee) ; Rössner, Pavel (referee)
Impaired chromosome segregation during mitosis, inaccurate DNA damage response and excessive telomere shortening may all modulate the frequency of chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBL). There is evidence that increased frequency of structural CAs in PBL may be considered as a marker of enhanced cancer risk. In the present Thesis, an effect of variants in genes involved in mitotic checkpoint and DNA damage response on the inter-individual differences in CAs frequency in PBL was investigated. Considering the importance of disrupted telomere structure and its function in cancer biology, a link between telomere length and clinicopathological and molecular features of cancer patients was analysed. Furthermore, the relevance of telomere length and CAs frequency as markers of patients' survival was examined. The major outcomes of the Thesis, fully reported in detail in seven attached Manuscripts, are: I) Increased frequency of structural CAs and/or disrupted telomere length in PBL may be considered as risk factors for the different types of solid cancer; II) Telomere shortening in PBL of healthy subjects increased the frequency of structural CAs; III) Binary interactions of gene variants in mitotic checkpoint and DNA repair pathways may modulate the frequency of structural...
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Chromosomal damage and shortening of telomeres in cancer patients and healthy subjects
Kroupa, Michal ; Vodička, Pavel (advisor) ; Kmoníčková, Eva (referee) ; Rössner, Pavel (referee)
Impaired chromosome segregation during mitosis, inaccurate DNA damage response and excessive telomere shortening may all modulate the frequency of chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBL). There is evidence that increased frequency of structural CAs in PBL may be considered as a marker of enhanced cancer risk. In the present Thesis, an effect of variants in genes involved in mitotic checkpoint and DNA damage response on the inter-individual differences in CAs frequency in PBL was investigated. Considering the importance of disrupted telomere structure and its function in cancer biology, a link between telomere length and clinicopathological and molecular features of cancer patients was analysed. Furthermore, the relevance of telomere length and CAs frequency as markers of patients' survival was examined. The major outcomes of the Thesis, fully reported in detail in seven attached Manuscripts, are: I) Increased frequency of structural CAs and/or disrupted telomere length in PBL may be considered as risk factors for the different types of solid cancer; II) Telomere shortening in PBL of healthy subjects increased the frequency of structural CAs; III) Binary interactions of gene variants in mitotic checkpoint and DNA repair pathways may modulate the frequency of structural...
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Suggestion of a workshop lift for garden machines
Kroupa, Martin ; Kašpárek, Jaroslav (referee) ; Hloušek, David (advisor)
This bachelor thesis deals with the design of workshop lifting equipment for garden equipment. The parameters for lifting equipment were set at a load capacity of 100 kg, working table dimensions of 1200x800 mm and minimum working table height of 1200 mm. In the thesis, the static and strength calculation of the mechanism is performed and the drive is calculated, which is realized by means of a motion screw.
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Intentional act and ideality of linguistic meaning in Husserl's thought
Kroupa, Martin ; Čapek, Jakub (advisor) ; Švec, Ondřej (referee)
Gottlob Frege made in his famous article "Über Sinn und Bedeutung" an distinction between meaning and referent of an expression. Meaning has an ideal charakter. Referent is than an object of the expression. Later in his study "Der Gedanke" he extended this distincion of the hole sentence. The meanings are in this case understood as thoughts of the senteces. Referent than Frege called as truth value. The question is, how is it possible for human mind to access this region of ideality of meanigs and thoughts. Frege wrote, that we are able to grasp an thought by force of thinking. Few years later Edmund Husserl made in his Logical investigations similar distinction between ideal sense and object of intention. In many ways is it possible to compare both conceptions. But for Husserl "grasping" of ideality is a form of an abstraction from the intentional act. It is not an abstraction in empirical sense, but ideation, where are ideas are "seen" in original intuition. The main topic of this study is is the attempt to analyse Husserl's ideative abstraction in special case of ideal meaning of an expression.
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Frequency Characteristic of the Induction Machine
Kroupa, Martin
The paper focuses on the induction machine as the transfer member and on its behavior in the frequency domain. The linearized mathematical model of induction machine is introduced and the issue of its frequency transmissions is discussed. Finally, the appropriateness of the motor use as diagnostic tool for analysis of time-varying load torque is mentioned.
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Reform of the IMF Real empowerment of developing countries or just a gesture?
Kroupa, Michal ; Plechanovová, Běla (advisor) ; Parízek, Michal (referee)
Recently implemented reform of the IMF was motivated by empowering smaller developing and emerging countries. My work has an ambition to assess the countries were empowered and whether there would be a more efficient way for IMF reform. I analyse of role and power of countries using well-established methodology of Voting Power Indices. Apart from the immediate change a longer perspective covering last 20 years would be implemented. My aim is not only assess the power of countries as isolated variables but also to assess them in context of other indicators such as economic development. Lastly, I would suggest a new way of reform proposal for the IMF. Currently countries are represented in the locus of executive power through constituencies. Constituencies are formed arbitrary often reflecting power-seeking behaviour of developed countries. The result is composition of constituencies that often further marginalize the developing countries. My proposal is to restructure these constituencies in line with regional international organizations, which can enhance the position of developing countries in two ways. By providing institutional capacity of already existing organizations the consensus within the constituency would be better facilitated. By formation constituencies in line with regional...
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