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Role of sequence context in DNA methylation
Polák, Jan ; Fischer, Lukáš (advisor) ; Širl, Marek (referee)
Cytosine methylation of DNA is a pivotal epigenetic mark, which contributes to the regulation of the gene expresion, silencing of transposable elements, and co-defines chromatine state. There are three cytosine contexts: CG, CHG and CHH (where H stands for C, A, or T). Arabidopsis thaliana (and plants in general) has an arsenal of molecular mechanisms capable of cytosine methylation in all of its contexts. That said, there are two tasks at hand: maintaining of pre-existing methylation and if need be, creating new methylated spots. The actual process of maintaining of the methylation depends on the cytosine context. Methylation of symmetrical contexts of CG and CHG can utilize the information about the methylation pattern from the second DNA strand. The aymmetrical context of CHH, and also CHG need to look for this information elsewhere: in the methylation of the lysine 9 of H3 histone. This creates a self-reinforcing loop and a crosstalk between two epigenetic mechanisms. Maintaince of methylation of CHH is also navigated by small RNA complementary to the locus in question. This mechanism of enzyme navigating by RNA is also used in establishing a new methylated site for all of the contexts. CG methylation is most prevalent in both heterochromatine and euchromatine. It also has a special functions...
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Emerging cardiovascular risk markers in diagnostics and therapy
Tůmová, Eva ; Vrablík, Michal (advisor) ; Freiberger, Tomáš (referee) ; Polák, Jan (referee)
Cardiovascular diseases (CVD) have been one of the leading causes of morbidity and mortality in developed countries with an enormous influence on individual health and significant socioeconomic impact as well. The aim of most physicians in recent decades is to seek the best possible predicative risk factor (RF) (or combination of several RF) which could help to determine the individual risk of developing CVD. This risk stratification can be used to identify the high risk patients and treatment intensification or establishment of early preventive measures. Currently, several RF of atherosclerosis and CVD are commonly used to individualize health care. However, individuals with low levels of these RF suffer of CVD, therefore the effort to find as much as possible specific RF still persists. In recent years, the inflammatory markers, crucial in the atherosclerosis development, raise great expectation In our studies, we focused on investigating the levels of inflammatory parameters in specific groups of patients (obese children and patients with metabolic syndrome) and observed the effect of weight loss following lifestyle changes. Our main concern was lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized LDL particles (ox-LDL) and myeloperoxidase (MPO). The results demonstrated significantly...
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Nutrition in pregnancy with type 1 diabetes mellitus
Dolejšová, Lenka ; Flekač, Milan (advisor) ; Polák, Jan (referee)
Pregnancy is a very important period in every woman's life, especially for women with type 1 diabetes mellitus. It brings many changes that affect the level of blood glucose, whose stabilization is the main point of a successful pregnancy. Glycemic stabilization should ideally occur at least three months before conception. Its achievement is mainly due to a properly composed diet, which also has an irreplaceable influence on healthy fetal development. Insufficiently compensated diabetes may be associated with complications for both the baby and the mother. The aim of this bachelor thesis was to summarize available information and find out the knowledge of women with type 1 diabetes mellitus in the topics of nutrition and diabetes compensation during pregnancy. Thereafter to compare the found knowledge of women with the recommendations and depending on the relationship of the respondents to pregnancy, ie whether they were pregnant, do or do not plan pregnancy. The theoretical part of the thesis summarizes the basic facts about relation of diabetes to pregnancy - recommendation for treatment in the period before conception and during pregnancy and related complications for mother and child. It also provides an overview of essential nutrients and micronutrients affecting maternal and fetal health. In...
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Effect of obstructive sleep apnea on oxidation and transport of fatty acids in skeletal muscle in patients with type 2 diabetes mellitus
Havlíková, Nikola ; Polák, Jan (advisor) ; Gojda, Jan (referee)
Sleep apnea syndrome, or sleep apneic syndrome, is a serious illness that causes a high risk of cardiovascular disease development in patients. This disease is characterized by a breathless breathing disorder and falls into a class of disorder that accompanies sleep disturbances. Sleep apnea syndrome (SAS) affects 5-15% of the population, and 50-80% of patients with type 2 diabetes mellitus (T2DM) or severe obesity. SAS has a causal contribution to the development of disorders in glucose metabolism and T2DM. Diabetes mellitus type 2 is a complex metabolic disorder in which the organism is unable to process glucose as under normal physiological conditions due to a relative insulin deficiency and simultaneous peripheral insulin resistance. Insulin resistance is eventually compensated for by increased insulin secretion, which leads to the development of hyperglycemia after failure of this compensation. T2DM is very often associated with the presence of obesity, arterial hypertension, dyslipidemia and hyperuricemia. The aim of this study is to determine if the presence of SAS in non-diabetic subjects and patients with type 2 diabetes mellitus leads to disorders in the metabolism of fatty acids in the skeletal muscle. The results of the study contribute to the understanding of the molecular mechanisms...
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The role of adrenergic signaling in cardioprotection induced by adaptation to chronic hypoxia
Hahnová, Klára ; Novotný, Jiří (advisor) ; Polák, Jan (referee) ; Babula, Petr (referee)
Cardiovascular diseases are currently one of the most common causes of morbidity and mortality in the Western world. Adaptation to chronic hypoxia can contribute to the improvement of ischemic tolerance of myocardium but exact molecular mechanisms leading to the development of a cardioprotective phenotype are still unclear. There are some indications that point to the possible role of β-adrenergic signaling in these processes. In the first part of the thesis, we examined the effect of protective continuous (CNH; 24 h/day) and nonprotective intermittent (INH; 23 h/day hypoxia, 1 h/day reoxygenation) normobaric hypoxia on β-adrenergic signaling in the right (RV) and left ventricles (LV) of Wistar rats. Both hypoxic models led to decrease in the number of β1-adrenergic receptors (β1-ARs) in the RV. There were no significant changes in β-ARs in LV preparations. Although adenylyl cyclase (AC) activity stimulated through Gs proteins was decreased in the RV and increased in the LV after adaptation to CNH and INH, there were no significant changes in the expression of dominant AC 5/6 isoforms. Expression of Gs proteins was decreased in RV in both hypoxic models. These results suggest that chronic normobaric hypoxia may have a strong effect on myocardial β-adrenergic signaling without differences between...
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The role of mitochondrial genome in cardioprotection induced by the adaptation to chronic hypoxia
Nedvědová, Iveta ; Žurmanová, Jitka (advisor) ; Polák, Jan (referee) ; Čížková, Dana (referee)
Cardiovascular intervention studies are a very important issue given that the ischaemic heart disease is one of the main mortality and morbidity causes in the Western world. Cardioprotection is mediated through a variety of signalling pathways in the cell that may directly or indirectly affect energy metabolism and mitochondria. Ischaemia-reperfusion injury of the heart significantly affect mitochondrial function revealing a potential therapeutic target. The role of mitochondria in the myocardium is not only in the field of energy homeostasis, but also in mediating the cellular response to reduced oxygen supply and in apoptosis regulation. This thesis aims to elucidate the response of the hypertrophied heart of the spontaneously hypertensive rat (SHR) and the derived conplastic strain with mitochondrial genome of normotensive Brown Norway (SHR-mtBN ) to the cardioprotective regime of adaptation to chronic normobaric hypoxia (CNH, Fi 0.1). The adaptive changes were studied at the cellular, protein and gene levels using Real-time RT-PCR, Biomark Chip Analysis, Western Blot, spectrophotometric measurements of enzyme activity and quantitative immunofluorescence analyses. The present thesis was based on a different cardioprotective phenotype between SHR and SHR-mtBN strains, i.e. a significantly smaller...
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Significance of virtue in the philosophy of Plotinus
Polák, Ján ; Svoboda, David (advisor) ; Sousedík, Prokop (referee)
The place of virtue in the philosophy of Plotinus Abstract The main intention of this thesis is to clarify some aspects of Plotinus's concept of virtue. Significant part of it is a report of J. M. Dillon's article An ethic for the late anthique sage and its comparison with P. Hadot's essay Plotinus or the simplicity of vision, which form a base for characteristics of a dualism between sensual and spiritual world, the body/soul polarity, and relation between higher and lower virtues. Consequently a relationship of a Plotinian sage towards others is being investigated. The result of this thesis confirms that Dillon's interpretation of a radical distinction between polarities mentioned above is exaggerated and his pronouncement of an absence of the element of concern for others in Plotinus's ethical reflextion is basically mistaken. Key words Plotinus, ethics, virtue, neoplatonism, J. M. Dillon, P. Hadot, higher and lower virtues, relation with other, body and soul, sensual and spiritual world, late anthique philosophy.
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The use of magnetic resonance spectroscopy for studying glucose metabolism
Kratochvílová, Simona ; Pelikánová, Terezie (advisor) ; Štich, Vladimír (referee) ; Polák, Jan (referee)
Magnetic resonance spectroscopy (MRS) is a noninvasive technique that enables to follow metabolic processes in selected tissues in vivo. Recently the attention has been focused on metabolic mapping in target organs of insulin action to describe the pathophysiology of insulin resistance. The aim of our study was to present the practical application of ³¹P (phosphorus) MRS and ¹H (proton) MRS in metabolic studies of skeletal muscle in insulin resistant subjects and in subjects with impaired fasting glucose. The third study was aimed to evaluate the brain metabolism with ¹H MRS in healthy controls and subjects with type 1 diabetes during hyperinsulinemia. ¹H and ³¹P MRS were performed using a MR Scanner Siemens Vision operating at 1,5 Tesla. To assess the parameters of glucose metabolism and insulin action oral glucose tolerance test and hyperinsulinemic euglycemic clamp were performed. The study 1 was aimed to evaluate the skeletal muscle (m. soleus) energetic metabolism in the offspring of hypertensive parents (OH) with a higher level of insulin resistance. The concentrations of selected high energy phosphates (phosphocreatine, inorganic phosphate, adenosintriphosphate, phosphomonoesters, phosphodiesters) were evaluated with ³¹P MRS. Their amount in OH was comparable to healthy controls. However we...
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The Use of Scent in Marketing Communication
Polák, Jan ; Halada, Jan (advisor) ; Klabíková Rábová, Tereza (referee)
This bachelor thesis study sense of smell as mean to enhance marketing communication. In theoretical part of the thesis I focused on function of smell on biological level. I paid extraordinary attention to the brain and its function. I explained how the brain works and especially how the scents are being perceived. It is shown how important i tis to understand this topic well. The smell signals go directly to the deepest and oldest parts of our brain called the limbic system. This is where our emotions and memory are being processed. This tight connection between the smell, emotions and memory in some of the most important pieces of information that allows us to use the scent perception in marketing praxis. In the theoretical part of the thesis I mention also psychological effects of the smell such as the Proust phenomenon. This rather poetic term describes an unexpected feeling or long forgotten memory coming on our minds after exposure to certain smells that we have connected with our past experience. The practical part of the thesis is rather descriptive. I cited number of studies from scientific magazines which deal with effects of scents on human minds, perception and emotions, especially connected with practical use in marketing field. I added also some examples of the real companies which already use...
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Functional genomic and pharmacogenomic analysis of metabolic syndrome aspects
Krupková, Michaela ; Šeda, Ondřej (advisor) ; Haluzík, Martin (referee) ; Polák, Jan (referee)
Metabolic syndrome is a prevalent disease characterized by concurrent manifestation of insulin resistance, obesity, dyslipidemia, hypertension and other hemodynamic and metabolic disorders. It has multifactorial type of inheritance and its resultant phenotype is determined by both environmental and genetic factors as well as their interactions. That is the main reason why comprehensive analysis of the genetic component of this syndrome is complicated in human population. Genetically designed experimental animal models are significant tools for analysis of genetic architecture of human complex conditions including the metabolic syndrome. The aim of this Thesis is utilization of functional and comparative genomic tools to uncover pathogenesis of metabolic syndrome aspects and their genetic determinants. We also studied pharmacogenetic interactions of these genetic determinants with drugs affecting particular components of the metabolic syndrome. Establishing and utilizing several genetically designed congenic rat strains, we undertook four different research projects focusing on pharmacogenetic interaction of all-trans retinoic acid and ondansetron with differential segment of rat chromosome 8, pharmacogenetic interaction of differential segment of rat chromosome 4 and dexamethasone, determining Plzf...
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