National Repository of Grey Literature 113 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Cardioprotective effects of sodium-glucose cotransporter SGLT2 inhibitors.
Thořová, Markéta ; Horníková, Daniela (advisor) ; Vávra, Jiří (referee)
Cardiovascular diseases are one of the most common causes of death in both non-diabetic and diabetic patients. Nowadays, a large number of drugs target cardiovascular problems. One of the very promising therapies is the use of sodium-glucose cotransporter type 2 (SGLT2) inhibitors. SGLT2 inhibitors have gained a wide interest in the treatment of type 2 diabetes (DM2) due to their ability to lower blood glucose levels independently of insulin action. However, in addition to their main effect on glycemic control, there is increasing evidence of their beneficial effects on the cardiovascular system beyond their hypoglycaemic effects. These drugs reduce hyperglycemia, hypertension, and improve diabetic retinopathy through multiple mechanisms, many of which have not been fully explained. The main focus has been on identifying the mechanisms through which these drugs affect the heart and blood vessels, whether by reducing blood pressure, affecting cardiac cells, or improving metabolic processes in blood vessels. Key words: SGLT2, inhibitors of SGLT2, cardioprotective effect, diabetes mellitus, heart
Cardiotoxic effects of anthracyclines in oncological treatment
Tekáčová, Kateřina ; Horníková, Daniela (advisor) ; Vávra, Jiří (referee)
Anthracyclines are antitumor antibiotics used during chemotherapy in cancer patients. Treatment with anthracyclines has good results but a side effect is significant cardiotoxicity. This bachelor thesis describes the mechanisms of action of anthracyclines which are essential in cancer therapy and may be risky for patients. The thesis also defines the term of cardiotoxicity and summarizes factors that may increase the risk of cardiotoxicity. The most commonly used agents in the anthracycline series are briefly described. Cardiotoxicity can be detected by cardiac markers, especially particular troponin and diagnostic methods. The last chapter describes the groups of substances that reduce the cardiotoxic effects of anthracyclines. Key words: heart, anthracyclines, cardiotoxicity, chemotherapy, onkology treatment
Heme sensor proteins as potential biomarkers of cellular and oxidative stress processes induced by ionizing radiation
Vávra, Jakub ; Martínková, Markéta (advisor) ; Souček, Pavel (referee) ; Tichý, Aleš (referee)
[IN CZECH] Ionizing radiation is a potential inducer of the oxidative stress processes in cells. As a result, reactive radicals are formed in the intracellular space modifying the essential biomolecules. Ionizing radiation has either direct (radiation sickness) or indirect (malignant processes) effect on the organism. Therefore, a fast determination of the dose is required when suspected irradiation of the organism occurs. However, a method routinely applicable, fast enough and at the same time suitable for dose estimation based on biomarkers has not been developed so far. The aim of this thesis is to describe new properties of the selected heme sensor proteins and discuss their potential importance for the cellular adaptation to oxidative stress conditions. Specifically, the thesis is focused on two eukaryotic proteins, heme regulated inhibitor (HRI) and transcription factor p53. The study of functional regulation as well as the conformational changes of these proteins induced by heme is greatly emphasized. Besides, the optimization of the key experimental methods was conducted. Specifically, Phos-tag electrophoresis was applied for the kinetics study of HRI wild type and its Gly202Ser mutant form, which is a characteristics of lung cancer development. Unsurprisingly, for both HRI forms studied,...
Study of the effect of heme analogues on the structural-functional characteristics of a model representative of heme sensor proteins
Ďatko, Peter ; Martínková, Markéta (advisor) ; Vávra, Jakub (referee)
Heme sensor proteins allow bacteria to react to changes of concentration of certain molecules in their environment. This reaction depends on the coordination of the ligand to the heme iron atom. Model representative of this signaling system is a histidine kinase containing a sensor domain with a globin structure, AfGcHK. The aim of this bachelor thesis was to prepare and characterize a modified form of AfGcHK containing manganese within its protoporphyrine complex. To express the protein, E. coli BL-21 (DE3) cells were transformed using a plasmid pET21c(+)/AfGcHK. The protein was isolated and purified using affinity chromatography and gel chromatography. To determine its enyzmatic activity, polyacrylamid gel electrophoresis in the presence of sodium dodecyl sulfate with Phos-Tag was used. It was determined, that this novel form of AfGcHK is enzymatically active. Spectroscopic analysis has shown, that the modified form of AfGcHK containing manganese within its protoporphyrine complex is susceptible to reduction by sodium dithionate. Key words: heme, heme sensor proteins, oxygen sensors, signal transduction [IN CZECH]
Tcf4 transcription factor in the intestinal epithelium renewal and pathology
Müllerová, Tereza ; Janečková, Lucie (advisor) ; Vávra, Jiří (referee)
TCF4 (T-Cell Factor 4, sometimes also TCF7L2) is an important effector of the canonical Wnt signalling pathway. The transcription factor is produced in many different isoforms with tissue-specific expressionand diametricallyopposing functions.In the intestine,TCF4 is a key factor in epithelial regenerationandmaintenance of stem cell homeostasis. Its depletion causes loss of the proliferatingcrypt compartment and complete breakdown of the intestinal mucosal architecture. The processes in which it acts are therefore vital and must be strongly regulated by the Wnt signalling pathway. Disturbances in TCF4 expression or alternative splicing often lead to a wide range of complex pathologies such as colon cancer, ileal Crohn's disease and type 2 diabetes mellitus.
Structure and function of ubiquitin-activating enzyme UBA1
Pánska, Dominika ; Vávra, Jiří (advisor) ; Onhajzer, Jakub (referee)
Ubiquitin-activating enzyme, also known as UBA1, is an essential enzyme in the process of ubiquitin activation in all eukaryotic cells, and its loss, as well as complete disfunction, leads inevitably to death of an organism. In humans, nuclear (UBA1a) and cytoplasmic (UBA1b) isoforms are known. Ubiquitination, the process at the beginning of which UBA1 stands as a key player, is important for proteasomal degradation of proteins, cell cycle progression, DNA damage repairs, fertilisation, as well as antiviral response of an organism. Its impaired function is the cause of many oncological and neurodegenerative diseases or just recently discovered autoinflammatory syndrome VEXAS. This thesis includes basic and current knowledge about UBA1, its structure, functions in cells and pathologies. Key words: UBA1, ubiquitin, catalytic cysteine, proteasomal degradation, VEXAS
Model-based Clustering of Multivariate Longitudinal Data of a Mixed Type
Vávra, Jan ; Komárek, Arnošt (advisor) ; Frühwirth-Schnatter, Sylvia (referee) ; Hlávka, Zdeněk (referee)
Model-based Clustering of Multivariate Longitudinal Data of a Mixed Type Jan Vávra October 3, 2022 Abstract In many nowadays studies, the data are collected repeatedly on the same units over a certain period of time. Moreover, such longitudinal data are composed of numeric values, count variables, binary indicators, ordered or nominal categories. A few variants of statistical model capa- ble of modelling such often highly correlated data jointly are introduced. On top of that, a methodology of model-based clustering is adapted to such models to discover hidden heterogeneity within the data by dividing units into clusters of specific characteristics. Bayesian approach is taken, generative model is proposed and MCMC methodology is developed for estimation. A simulation study verifying the estimation properties is con- ducted. The methodology is applied to real datasets such as medical data on patients suffering from primary biliary cholangitis (PBC) or econom- ical dataset consisting of thousands of Czech households followed since 2005 (EU-SILC database). 1
Model-based Clustering of Multivariate Longitudinal Data of a Mixed Type
Vávra, Jan ; Komárek, Arnošt (advisor)
Model-based Clustering of Multivariate Longitudinal Data of a Mixed Type Jan Vávra October 3, 2022 Abstract In many nowadays studies, the data are collected repeatedly on the same units over a certain period of time. Moreover, such longitudinal data are composed of numeric values, count variables, binary indicators, ordered or nominal categories. A few variants of statistical model capa- ble of modelling such often highly correlated data jointly are introduced. On top of that, a methodology of model-based clustering is adapted to such models to discover hidden heterogeneity within the data by dividing units into clusters of specific characteristics. Bayesian approach is taken, generative model is proposed and MCMC methodology is developed for estimation. A simulation study verifying the estimation properties is con- ducted. The methodology is applied to real datasets such as medical data on patients suffering from primary biliary cholangitis (PBC) or econom- ical dataset consisting of thousands of Czech households followed since 2005 (EU-SILC database). 1
Tests of independence in contingency tables
Gažová, Miroslava ; Omelka, Marek (advisor) ; Vávra, Jan (referee)
This thesis deals with the problem of independence testing between two discrete ran- dom variables. At first, we define contingency table and the basic notations in the context of independence tests. We describe the most commonly used tests in this field. Next, we present the U-statistics Permutation test of independence (USP), which was first presen- ted by authors T.B.Berrett and R.J.Samworth (2021). In the next section, we focus in better detail on fourfold contingency tables and corresponding problem of testing for the equality of parameters from two independent binomial distributions. In the end, we apply the tests on the real data using the R enviroment. 1

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