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Cell cycle regulation and genome integrity protection in the early mammalian embryos
Knoblochová, Lucie ; Drutovič, David (advisor) ; Carr, Antony M. (referee) ; Fulková, Helena (referee)
(English version) Infertility is a major health problem, as it affects one in every six people worldwide (Njagi et al., 2023). One of the major reasons for infertility are aneuploidies, additions or losses of an entire or partial chromosome during cell division. Aneuploidies thus negatively influence cellular processes and potentially lead to developmental problems or embryo loss. It has been thought for a long time that aneuploidies arise mostly during oocyte development, and these mechanisms have been well studied. However, recent evidence has shown that aneuploidies arise also de novo after fertilisation and during the early embryonic development; but the molecular mechanisms of these abnormalities still remains elusive. Aneuploidies often originate during cell cycle division from unrepaired DNA damage in mitosis. DNA damage is sensed by DNA damage response (DDR) signalling pathways, which slow down or arrest cell cycle progression until it is resolved. An essential DDR factor during typical cell cycle progression is checkpoint kinase 1 (CHK1). However, the role of DDR factors in the early embryos, and especially CHK1, have not been well studied. Early embryonic development is regulated by maternal factors stored in the oocyte until the transcription of the embryonic genome begins. To study...
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Gold nanoparticles as a tool of targeted therapy of cancer
Knoblochová, Lucie ; Hodný, Zdeněk (advisor) ; Brábek, Jan (referee)
Nanomaterials have caught the interest of biomedical science because of their size (which enables them to interact with cellular structures), high surface area, and unique physical properties. Gold nanoparticles (GNPs) can be synthesised in various shapes. Their common property is surface plasmon resonance, which makes it possible to detect these particles with high resolution using dark field microscopy. GNPs can be efficiently modified with various ligands such as drugs, antibodies, or aptamers; this can be utilized to selectively bind GNPs to tissues, e.g. for drug delivery. Conjugated GNPs can also be used in diagnostics of tumor cells as well. Photothermal therapy consists of GNPs selectively binding to the tumor tissue, where they transform light into heat upon irradiation by near-infrared (NIR) light, thereby damaging nearby cells. The toxicity of GNPs is currently unclear. Research into modified gold nanoparticles is of great interest for targeted tumor therapy, as it may yield a tool for the selective destruction of tumor cells.
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Gold nanoparticles as a tool of targeted therapy of cancer
Knoblochová, Lucie ; Hodný, Zdeněk (advisor) ; Brábek, Jan (referee)
Nanomaterials have caught the interest of biomedical science because of their size (which enables them to interact with cellular structures), high surface area, and unique physical properties. Gold nanoparticles (GNPs) can be synthesised in various shapes. Their common property is surface plasmon resonance, which makes it possible to detect these particles with high resolution using dark field microscopy. GNPs can be efficiently modified with various ligands such as drugs, antibodies, or aptamers; this can be utilized to selectively bind GNPs to tissues, e.g. for drug delivery. Conjugated GNPs can also be used in diagnostics of tumor cells as well. Photothermal therapy consists of GNPs selectively binding to the tumor tissue, where they transform light into heat upon irradiation by near-infrared (NIR) light, thereby damaging nearby cells. The toxicity of GNPs is currently unclear. Research into modified gold nanoparticles is of great interest for targeted tumor therapy, as it may yield a tool for the selective destruction of tumor cells.
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Role of the tumour suppressor PML in DNA damage response and cellular senescence after genotoxic stress
Knoblochová, Lucie ; Hodný, Zdeněk (advisor) ; Horníková, Lenka (referee)
The promyelocytic leukemia protein (PML) is a tumour suppressor. It has been reported that PML interaction with the p53 protein is involved in the activation of cell cycle checkpoints and, when persistent, may lead to the premature onset of cellular senescence. Cellular senescence is a state of permanent cell growth arrest that is associated with characteristic morphological and metabolic changes and persistent DNA damage signalling. Importantly, PML nuclear bodies coassociate with persistent DNA damage foci in senescent cells; however, the role of this interaction is still obscure. My goal was to characterize the role of PML in DNA damage response (DDR) and the induction of premature cellular senescence after genotoxic stress, namely X-radiation, using both siRNA-mediated PML knock down (PML KD) and complete PML knock out (PML KO) in human cells. The dynamics of DNA damage foci, levels of various proteins involved in DDR, and proliferation rate were measured in both PML KD and KO cells. No significant changes in the formation of DNA damage foci, activated DDR (p53 and Chk2), activated p21CIP1/WAF1 cyclin-dependent kinase inhibitor, senescent morphology, and SA-β-galactosidase activity in PML KO cells were observed. However, PML KO cells displayed higher levels of retinoblastoma protein (Rb) and...
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Evidence a oceňování zásob ve výrobním podniku
Knoblochová, Lucie ; Nováčková, Zdenka (advisor) ; Chodora, Jiří (referee)
Diplomová práce je zaměřena na teoretické vymezení zásob, jejich oceňování a na praktickou část, která popisuje problematiku na konkrétním podniku, který se zabývá z převážné většiny výrobou nástrojů a výrobků pro automobilový průmysl. Cílem diplomové práce bylo poznat realitu na konkrétním podniku a popsat obecně problematiku evidence a účetní ocenění zásob.
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