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The cell cycle and differentiation of haematopoietic stem and progenitor cells.
Páral, Petr ; Šefc, Luděk (advisor) ; Horváthová, Monika (referee) ; Kokavec, Juraj (referee)
Haematopoietic stem and progenitor cells (HSPCs) are crucial for lifelong blood cell production. We analysed the cell cycle and cell production rate in HSPCs in murine haematopoiesis. The labelling of DNA-synthesizing cells by two thymidine analogues, optimized for in-vivo use, enabled the determination of the cell cycle flow rate into the G2-phase, the duration of the S-phase and the average cell cycle time in Sca-1+ and Sca-1- HSPCs. The determination of cells with 2n DNA content and labelled during the preceding S-phase was used to establish the cell flow rates in the G1-phase. Our measurements revealed a significant difference in how Sca-1+ and Sca-1- HSPCs self-renew and differentiate. The division of Sca-1+ progenitors led to the loss of the Sca-1 marker in about half of newly produced cells, corresponding to asymmetric cell division. In contrast both Sca-1- progenitors, arising from mitotic cell division, entered a new round of the cell cycle. This corresponds to symmetric self-renewing cell division. The novel data also enabled us to estimate the cell production rates in the Sca-1+ and in three subtypes of Sca-1- HSPCs. We focused on adult murine erythroid differentiation in the next part of our study. We introduced an original flow cytometry approach for identifying and studying erythroid...
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Gravity Model Estimation of the Russian Export: The Role of FDI
Horváthová, Monika ; Svoboda, Karel (advisor) ; Vykoukal, Jiří (referee) ; Cibulková, Petra (referee)
The main objective of this thesis was to examine the determinants of Russian export directed to its 36 main trading partners. Employing the Gravity model, the standard gravity variables, such as economic masses of the trading partners and their distance, were estimated as having significant impacts on the volume of export from Russia. However, a special attention was paid to the role of FDI, studying whether FDI flows or FDI stock act as complements or substitutes of the export. Unfortunately, with the help of the Fixed-effects and the Random-effects estimation methods we came to statistically insignificant conclusions, which might have been caused by the prevalence of missing observations in the FDI variables.
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Molecular basis of clonal heterogeneity of hematological diseases
Babošová, Oľga ; Láníková, Lucie (advisor) ; Alberich Jorda, Meritxell (referee) ; Horváthová, Monika (referee)
Tumor heterogeneity has been recognized for decades. The molecular mechanisms impacting clonal heterogeneity in hematological diseases, specifically myeloproliferative neoplasms (MPN) and mantle cell lymphoma, with the focus on several inherited genetic factors, inflammation, the protective mechanisms of DNA damage response (DDR) in the leukemic transformation and the treatment strategies are the focus of this thesis. Firstly, I focus on studying germline JAK2 variants and how these may influence the initiation and progression of MPN diseases, and even contribute to further genomic alterations in the mutated clone. A study performed by our cooperating lab in Utah, USA,1 analyzing the mutational landscape of 31 JAK2 V617F-positive polycythemia vera (PV) patients identified two novel germline mutations in JAK2 gene, JAK2 T108A and JAK2 L393V. Another study2 , performed by our cooperating lab in Olomouc, Czech Republic, characterized two germline JAK2 mutations, E846D and R1063H, in a case of hereditary erythrocytosis accompanied by megakaryocytic atypia. The JAK2 R1063H variant was initially described in 3 out of 93 PV patients that were JAK2 V617F-positive.3 Our aim was to identify the role of selected inherited mutations in JAK2 gene in the initiation and progression of myeloproliferative...
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