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Modulation of human telomerase activity by nucleoside and nucleotide analogues
Hájek, Miroslav ; Votruba, Ivan (advisor) ; Fajkus, Jiří (referee) ; Hejnar, Jiří (referee)
CONCLUSIONS Considering human telomerase as a promising target of anti-cancer therapy, the thesis deals with the study of inhibitory potency of selected ANP diphosphates towards telomerase, and the capability of nucleoside-type DNA methylation inhibitors to inhibit hTERT expression, knowing that hTERT expression closely correlates with telomerase activity in vitro and in vivo. The results can be summarized as follows: All the purine ANP diphosphates except for (S)-PMPApp and 6-Me2PMEDAPpp show dose- dependent inhibition of human telomerase in cell-free assay, the adenine derivatives are less effective inhibitors than the guanine derivatives. The only two pyrimidine ANP diphosphates tested (PMECpp and PMETpp) do not show any significant inhibitory potency towards telomerase. Activity of tested ANPs on telomerase is limited to their diphosphates (ANPpp) only. (R)-enantiomers are more inhibitory compared to (S)-enantiomers. This indicates that absolute configuration plays an important role in the telomerase inhibition and that the enzyme distinguishes between the (R)- and (S)-enantiomers. PMEGpp is the most potent human telomerase inhibitor among all ANPs studied with the IC50 value of 12.7 ± 0.5 mol.l-1 at 125 M dNTPs. Its inhibitory potency towards telomerase is comparable to that of ddGTP (IC50...
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Dynamics of de novo DNA methylation and its impact on transgene expression and CRISPR/Cas9 mutagenesis
Přibylová, Adéla ; Fischer, Lukáš (advisor) ; Pečinka, Aleš (referee) ; Fajkus, Jiří (referee)
Genetic information must be protected, maintained and copied from cell to daughter cells, from generation to generation. In plants, most of the cells contain complete genetic information, and many of these cells can regenerate to a whole new plant. Such a feature leads to the need for precise control of which genes will be active and which not because in growth and differentiation, only the activity of specific genes for the individual cells, tissues, organs are required. One of the mechanisms controlling the gene activity is RNA interference (RNAi), which down- regulates or blocks the expression of specific genes at the transcriptional or post-transcriptional level. The crucial part of the RNAi is guiding the RNAi machinery to the target. It is mediated via sequence complementarity of the target with a small RNA (sRNA), which is diced from a double- stranded RNA (dsRNA) precursor. The molecular mechanism of dsRNA and sRNA formation and also the target origin predestinates the subsequent silencing pathway. In transcriptional gene silencing (TGS), the gene expression is regulated through chromatin epigenetic modifications. One of the epigenetic marks is cytosine methylation, which is established mainly by RNA-directed DNA-methylation (RdDM) pathway. Although the protein machinery was relatively...
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Modulation of human telomerase activity by nucleoside and nucleotide analogues
Hájek, Miroslav ; Votruba, Ivan (advisor) ; Fajkus, Jiří (referee) ; Hejnar, Jiří (referee)
CONCLUSIONS Considering human telomerase as a promising target of anti-cancer therapy, the thesis deals with the study of inhibitory potency of selected ANP diphosphates towards telomerase, and the capability of nucleoside-type DNA methylation inhibitors to inhibit hTERT expression, knowing that hTERT expression closely correlates with telomerase activity in vitro and in vivo. The results can be summarized as follows: All the purine ANP diphosphates except for (S)-PMPApp and 6-Me2PMEDAPpp show dose- dependent inhibition of human telomerase in cell-free assay, the adenine derivatives are less effective inhibitors than the guanine derivatives. The only two pyrimidine ANP diphosphates tested (PMECpp and PMETpp) do not show any significant inhibitory potency towards telomerase. Activity of tested ANPs on telomerase is limited to their diphosphates (ANPpp) only. (R)-enantiomers are more inhibitory compared to (S)-enantiomers. This indicates that absolute configuration plays an important role in the telomerase inhibition and that the enzyme distinguishes between the (R)- and (S)-enantiomers. PMEGpp is the most potent human telomerase inhibitor among all ANPs studied with the IC50 value of 12.7 ± 0.5 mol.l-1 at 125 M dNTPs. Its inhibitory potency towards telomerase is comparable to that of ddGTP (IC50...
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Mechanisms of DNA repair in the moss Physcomitrella patens
Holá, Marcela ; Angelis, Karel (advisor) ; Bříza, Jindřich (referee) ; Fajkus, Jiří (referee)
Over the course of an organism's life, its genome is exposed to endogenous and exogenous chemical, physical and biological agents - genotoxins. These genotoxins alter its basic structural components - sugar residues, phosphodiester bonds, and nitrogenous bases. Organisms have therefore evolved a plethora of different strategies to both repair DNA lesions and maintain genomic stability. These DNA repair pathways are linked with several other cell pathways, including chromatin remodelling, DNA replication, transcription, cell cycle control, apoptosis - programmed cell death (PCD), thereby providing a coordinated cellular response to DNA damage. Biochemical mechanisms of DNA repair are relatively well understood in yeast and mammals, however, far less so in plants. While these repair mechanisms are evolutionary conserved, significant differences still remain. Therefore, further investigation is required. This thesis summarises the introduction of a novel plant model - the moss, Physcomitrella patens (Physcomitrella). As a haploid gametophyte with unique characteristics of high frequency of homologous recombination (HR), and apical growth of filaments, it is an ideal organism to study DNA repair in plants. Previous research on Physcomitrella regarding mechanisms of DNA lesion repair induced by...
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Identification and characterization of transcription facotrs affecting late stages of male gametophyte development in Arabidopsis thaliana
Dupľáková, Nikoleta ; Honys, David (advisor) ; Bříza, Jindřich (referee) ; Fajkus, Jiří (referee)
Conclusions My thesis was devoted to the investigation of a complex regulatory network of transcription factors in the Arabidopsis thaliana male gametophyte. In addition to the abovementioned objective, the second aim of the thesis was the creation of a web-based transcriptome database and data mining tool characterized by an innovative concept of presentation and evaluation of the data from DNA chips. The results of my thesis can be summarized as follows: 1. We created a database called Arabidopsis Gene Family Profiler (arabidopsisGFP) (http://agfp.ueb.cas.cz/) which was made available on-line. This database was developed in order to provide a new tool for presentation of gene expression data (transcriptome), allowing the user to display the data in a quick and intuitive way using the innovative and when launched also unique concept of a virtual plant. The database employs a progressive idea "from simple to complex", but also provides the user with more traditional data presenting options. The aGFP database can serve as a reference manual for the expression of individual genes and gene families in Arabidopsis thaliana under physiological conditions at different phases of the life cycle and in individual organs and tissues or cell types. 2. A chapter reviewing available servers for deposition of the...
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Comparative Analysis of New Developments Around the City of Brno
Uličný, Karel ; Fajkus, Jiří (referee) ; Kledus, Robert (advisor)
This master’s thesis deals with analysis of documents for the realization of the new buildings the wider area of Brno. It is divided into the theoretical part and the empirical part. The theoretical part describes defines and characterize different stages of implementation of building plots in the framework of utility lines and roads on agricultural land (greenfields), designated for residential housing. In the empirical part goals and methodology of the research project are mentioned and it is divided into two parts. The first part is devoted to case studies comparing and analyzing the costs and revenues of the developer selected localities of satellite towns. The second part is focused on the actual development of land prices. It points to items affecting profit or loss of the developer. In the last chapter the author of this thesis describes creating a preliminary calculation, which the developer can determine whether a satellite town of the selected project will be successful or not. In conclusion, the thesis points out important factors affecting the project success of the satellite town.
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Modern methods of QRS detection
Fajkus, Jiří ; Kozumplík, Jiří (referee) ; Vítek, Martin (advisor)
This bachelor’s thesis deals with methods, which are used for processing of ECG signals, specifically for the detection of QRS complexes. The QRS detection is an essential part of every ECG analysis because it is a source of points with timing information, which are used for classification and measurement of other waves and intervals required for diagnostics. Some ways of QRS detection are described in this work and there is also a description of detector implemented in programming environment MATLAB, which is based on zero crossing counts. This QRS detector was then tested CSE database and signals from Holter examination.
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Proposal of Method for the Administration of Logistics Centres in the Conditions of the Czech Republic
Karafiátová, Hana ; Fajkus, Jiří (referee) ; Kledus, Robert (advisor)
This thesis deals with facility management. The first part handles facility management as such, its nature, basic concepts, historical development, instruments, ways of providing services and participants. Level of provided services in the Czech Republic is analyzed. Based on received knowledge of the field the other part is focused on detailed specification of facility management services provided in the area of logistic centers management. On the example of individual services there are described differences in management of logistic centres and possible solutions of these situations. The benefit of this thesis consists in providing a comprehensive view of logistics centres management and suggesting possible improvements.
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A Critical Analysis of Investment Opportunities in the Property Market
Matha, Jan ; Fajkus, Jiří (referee) ; Škapa, Stanislav (advisor)
The thesis is dedicated to the issue of the real estate market,considering it in the context of before, during and after the crisis. It deals with the property invesments through mutual funds, investment companies and unit trusts, with tax and legal benefits of these investments and their financing. It monitors all the segments of the real estate market development. Its models will cover future optimistic, pesimistic and realistic scenario of the real estate markets.
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