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The role of PGC1 in cardioprotective mechanisms
Jeřábková, Adéla ; Horníková, Daniela (advisor) ; Kolář, David (referee)
One of the leading causes of death worldwide is cardiovascular diseases. Researchers are, therefore, dealing with the mechanisms that induce a cardioprotection. Cardioprotection is a general pathophysiological term under which we understand myocytes protection against damage by ischemia and subsequent reperfusion impairment, inflammation, hypertension, and toxic and degenerative changes, including some types of apoptosis. One of the less common ways of cardioprotection is a cold adaptation. Adaptive thermogenesis is an important part of energy homeostasis and protection against obesity, metabolic disorder threatening heart. The PGC family of proteins plays a very important role in adaptive thermogenesis. This thesis summarizes the current state of literature in cold adaptation issues, especially the role of PGC1α and its effects at the cellular and tissue level. mRNA expression of PGC-1α is strongly induced in brown fat and skeletal muscles of mice exposed to cold. PGC-1α also increases the transcriptional activity of PPAR-γ and thyroid hormone receptor protein on UCP-1 (uncoupling protein). UCPs (uncoupling proteins) are small proteins localized to the inner side of the mitochondrial membrane to facilitate the transport of protons, which they release into concentration gradient without ATP...
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Adverbial Clauses of Time with Conjunctions bis, bevor, ehe
Kolář, David ; Šemelík, Martin (advisor) ; Dovalil, Vít (referee)
This bachelor thesis deals with subordinate adverbial clauses of time in German introduced by the following conjunctions: bis, bevor and ehe. The theoretical part of the thesis concentrates on the description of adverbial clauses of time in selected grammar books. The introductory chapter of this part presents how this area is dealt with in the grammar book by Gerhard Helbig and Joachim Buscha, which is considered to be a basic handbook for German as a foreign language at an advanced level. This part also describes how these clauses are dealt with in other grammar books. An emphasis is put on comparing this description with the description by Helbig and Buscha. The practical part focuses on the occurrence of adverbial clauses of time in selected sources, namely fiction, newspapers and the DeReKo corpus. The analysis focuses on clauses introduced by bevor, ehe expressing implied negation. Furthermore, the analysis deals with adverbial clauses of time with future reference in which the analysed conjunctions, i.e. bis, bevor and ehe, are interchangeable according to some of the analyzed grammar books. Key words: grammar, subordinate clauses, conjunctions, bis, bevor, ehe, empirical research
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Calcium signalling in astrocytes under physiological and pathological conditions
Svatoňová, Petra ; Anděrová, Miroslava (advisor) ; Kolář, David (referee)
Calcium signalling in astrocytes represents an important component, which enables proper neuronal functioning under physiological conditions. Alterations in Ca2+ signalling, accompanied by an increase in intracellular calcium levels is a hallmark for numerous pathological states of central nervous system, such as traumatic and ischemic brain/spinal cord injuries, epilepsy as well as neurodegenerative diseases, such as Alzheimer's disease and psychiatric disorders, such as schizophrenia. The research analyzing the molecular components of astrocytic Ca2+ signalling can help us understand the control mechanisms used in calcium signalling and thus be greatly beneficial for further therapeutic research. Powered by TCPDF (www.tcpdf.org)
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Physiological relevance of futile cycling based on lipolysis and fatty acid re-esterification in white adipose tissue
Funda, Jiří ; Flachs, Pavel (advisor) ; Kolář, David (referee)
AJ The thesis deals with the task of futile metabolic cycling, mainly on the cycle including lipolysis and fatty acid re-esterification, which takes place in white adipose tissue. This cycle plays some essential roles in organism, including regulation of important metabolic pathways in lipid metabolism and also exhibit certain influence on the whole body energy metabolism. First part of the thesis is focused on general properties of futile metabolic cycles and shows some examples of their functions in organism. Next part presents detail view on single steps making the whole lipolysis/re-esterification cycle. Considerable part deals with the ways of regulation of futile cycle activity. This approach may increase an impact of futile cycling on processes under its influence. Physiological relevance of futile metabolic cycle based on lipolysis and fatty acid re-esterification in white adipose tissue was described in numerous studies. This thesis shows their results for a purpose to provide a summary of functions of this system in physiology of mammals. Key words futile metabolic cycle, lipolysis, re-esterification, fatty acids, adipose tissue
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The role of lactate shuttle in ischemic-reperfusion injury of rat heart adapted to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Nováková, Olga (referee)
Adaptation to hypoxia is a well-known phenomenon increasing myocardial resistance to ischemia-reperfusion (I/R) injury as an appropriate physical exercise which improves the contractile function of the heart. Lactate is a major energy substrate for the heart muscle during physical activity and hypoxia. The metabolism of lactate was and still is associated with muscle fatigue, but in the last decades it has been considered its significant modulating function of metabolism during exercise at cellular level and whole organism level. It has been shown that its effects might be similar to the effects of hypoxia and its oxidized form, pyruvate, has the cardioprotective effects. The aim of this study was to compare the expression of LDHA and LDHB isoforms between left and right ventricle in the cardioprotective scheme of adaptation to hypoxia. Another objective/goal was to determine the left ventricular response to I/R insult in the perfused heart model adapted to hypoxia compared with the normoxic controls on/at the expression level of both LDH isoforms. Our results showed differences in the LDHA expression in the left and right ventricle and an increased response of the left ventricle to I/R insult in rats adapted to hypoxia which is reflected at the expression level of both isoforms. Key words: heart,...
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The role of microRNA in hypoxic pulmonary hypertension
Tichý, Václav ; Hampl, Václav (advisor) ; Kolář, David (referee)
Pulmonary Arterial hypertension (PAH) is a devastating progressive disease that significantly decreases quality of life and has the average survival rate of only few years. One of the significant initiators of PAH is chronic hypoxia. After more than six decades of research that was initiated in 1946 by von Euler and Liljestrand, a new group of potential regulators of this pathology was discovered, that became heavily studied in the last five years. They are highly conserved molecules belonging to non-coding RNA. These 19-23 nucleotides long microRNA (miRNA) act as negative regulators of expression on various proteins. Many of them regulate traditional signalling pathways of hypoxic PAH (HIF-1, BMPR2) and miRNA is in turn regulated by other signalizations. Together, that creates an interconnected network of direct and indirect interactions and feedback loops, that we need to study in order to understand hypoxic PAH. This thesis summarizes findings about important miRNA molecules from the last few years and elucidates part of these regulatory mechanisms on several miRNA molecules (miR-17-92, miR-21, miR-210, miR-204 a miR143/145).
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Adamcová, Michaela (referee) ; Bardová, Kristina (referee)
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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Mitochondrial dysfunctions in depression
Javorská, Jana ; Stuchlík, Aleš (advisor) ; Kolář, David (referee)
Depression (major depressive disorder; MDD) is a common and chronic psychiatric disorder. MDD causes a significant reduction in the quality of life, reduces the ability to work, and thus causes a burden on disabled patients, healthcare, and all of society. The pathophysiological features of depression are often ambiguous, and therefore current treatment for depression is insufficient. Chronic stress plays an important role in the pathogenesis of depression. It causes dysregulation of the hypothalamic-pituitary-adrenal axis (HPA axis) controlling cortisol release, imbalance of neurotransmitters and neuromodulators, and imbalance between pro- inflammatory and anti-inflammatory cytokines. Another neurobiological sign of depression is a disruption of energy metabolism in the brain, for which mitochondria are responsible. In addition to ATP, mitochondria also form reactive oxygen species (ROS). ROS are in excessive amounts during chronic stress and disrupt cellular energy. Therefore, substances related to mitochondrial energy and antioxidant effects are currently being investigated. Ketamine, dizocilpine and phencyclidine are particularly effective in mitochondrial metabolism. However, the clinical use of these substances is complicated by their hallucinogenic and neurotoxic effects. Antioxidants help...
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Cable supported bridge
Kolář, David ; Koláček, Jan (referee) ; Nečas, Radim (advisor)
The topic of this bachelor thesis is design of a footbridge across a river. The final version, which has been chosen from three designs differentiating in their static behaviour of the structure, is a cable-stayed footbridge. The chosen option is designed as a parabolic monolithic prestressed deck suspended by cables anchored to two cone shaped pylons. The structure is situated perpendicularly to the riverbed and its total length is 57,465 m. Softwares, such as SCIA Egineer 20.0 and MS Excel, were used for the calculations of internal forces and modelling calculation models and its verification by hand. The design of the prestressing force, assessment of utility limit state and serviceability limit state were done by hand according to valid standards and regulations. Partially simplified bearing capacity assessment of the pylons was solved by IDEA StatiCa 9 software and some of the results were verified by hand as well. The thesis disregards stages of construction and prestress losses are estimated.
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The role of energy metabolism in cardioprotection induced by the adaptation to chronic hypoxia
Kolář, David
Cardiac energy metabolism is the one of the most complex system in the body. To sustain life, but also to respond quickly to any sudden changes (e.g. running, emotional stress), the heart has developed a unique ability and has become a metabolic "omnivore". At physiological conditions, long chain fatty acids (LCFAs) present the major energetic source for the adult myocardium. However, the cardiac energy metabolism may be compromised during pathophysiological states. One of the most dangerous is, undoubtedly, ischaemia-reperfusion injury with its acute form, myocardial infarction. However, the adaptation to chronic hypoxia has been known for decades for its cardioprotective effect against I/R. Changes of cardiac energy metabolism induced by the adaptation have not been fully explored and the system conceals still too many secrets. This thesis has aimed to determine how adaptation to chronic hypoxia affects the cardiac metabolism of the rat LVs in the following set-ups: 1. The effect of chronic normobaric hypoxia (CNH; 3 weeks, 5500m) during a brief I/R protocol in vitro on the protein kinase B/hexokinase (Akt/HK) pathway, including the expression and phosphorylation of Akt, the expression and localization of HK, the expression of mitochondrial creatine kinase (mtCKS), and the level of Bcl-2 family...
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