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Strategic Communications of Sustainable Urban Mobility Topics
Běnek, Ondřej ; Koudelková, Petra (advisor) ; Vranka, Marek (referee)
| DT Strategic Communication of Sustainable Urban Mobility Topics | Běnek The aim of the thesis is to describe and define the type and themes of communication and good practice of procedures and approaches that are effective in gaining support forsustainable (especially urban) mobility in the context of institutional strategic communication in the Czech/European context. This creates a suitable theoretical framework for strategy development at the municipal level and gives officials, practitioners, and politicians a tool that will enable them to use strategic communication effectively to improve living conditions in cities. The theoretical part discusses the function of the public urban space, especially its transport function, introduces the different modes of transport (car, pedestrian, cycling, public transport, and their combinations) and offers a description of their effects on the city and its citizens, also points out the evolution of the transport regime and discusses approaches and policies that support sustainable modes of transport. It also discusses thefield of strategic communication as a tool for promoting sustainable transport, particularly from an institutional perspective, and describes the communication of change, the stakeholders involved, and the topics to be communicated. The...
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Preparation and evaluation of potential drugs inhibiting mitochondrial enzymes
Benek, Ondřej ; Musílek, Kamil (advisor) ; Patočka, Jiří (referee) ; Opletalová, Veronika (referee)
Preparation and evaluation of potential drugs inhibiting mitochondrial enzymes Summary in English Alzheimer's disease (AD) is the most common cause of senile dementia worldwide. Despite being subject to intensive research, the pathogenic mechanisms of AD are still not fully understood and consequently an effective treatment is yet to be developed. Although the aetiology of AD is still unknown, a build-up of amyloid-beta peptide (Aβ) is considered to play an important role in disease progression. The original amyloid cascade hypothesis proposed that insoluble extracellular plaques were responsible for the majority of Aβ toxicity. This hypothesis has since been refined, as recent data indicates that soluble intracellular oligomers are now responsible for the majority of Aβ induced toxic effects. The mitochondrial dysfunction also plays an important role in the pathophysiology of AD. Aβ was detected inside mitochondria and several mitochondrial proteins were found to interact directly with Aβ. Such interactions can affect a protein's function and cause damage to the mitochondria, which finally results in progression of AD. The background for the experimental part of this dissertation thesis was literature review summarizing current knowledge on mitochondrial proteins directly interacting with Aβ in order to...
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Preparation and in vitro screening of quartenary inhibitors of acetylcholinesterase
Benek, Ondřej ; Doležal, Martin (advisor) ; Zimčík, Petr (referee)
Preparation and in vitro screening of quarternary inhibitors of acetylcholinesterase Abstract Reversible acetylcholinesterase (AChE) inhibitors are extensively used in human medicine. Among other applications they are used as a pre-exposure treatment for the prevention of organophosphorus poisoning. For this purpose carbamate inhibitors are recently used (e.g. pyridostigmine chloride). Carbamates reversibly block AChE active site and thus protect AChE against irreversible inhibition by organophosphorus compounds. However, these drugs have many undesirable side-effects and thus there are efforts to find a more suitable alternative among reversible AChE inhibitors. In this diploma thesis, 19 potential AChE inhibitors were prepared. Their ability to inhibit AChE and butyrylcholinesterase was evaluated in vitro and compared to selective standard cholinesterase inhibitors BW284c51 and ethopropazine. None of the prepared compounds was superior to used standards in inhibitory ability or selectivity. The structure activity relationship of the novel compounds was determinated from the obtained data.
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Mitochondrial protein 17β-hydroxysteroid dehydrogenase type 10 in the brain of a genetic animal model of Alzheimer's disease (McGill-R-Thy1-APP rats)
Hofmannová, Adéla ; Krištofíková, Zdena (advisor) ; Benek, Ondřej (referee)
Transgenic McGill-R-Thy1-APP rats are one of the best animal genetic models of Alzheimer's disease (AD). Significant intracellular elevation of soluble amyloid β (Aβ) and cognitive deficits are observed already in 3-month-old rats, prior to extracellular plaque deposition. Mitochondrial bioenergetic capacity appears to be altered via defects in complex I enzymatic activity in the electron transport chain already in 6-month-old rats. Nucleus-encoded mitochondrial matrix protein 17β-hydroxysteroid dehydrogenase type 10 (17βHSD10) operates via multiple enzymatic and non-enzymatic functions and is known as a binding partner of intracellular Aβ. In patients with AD, 17βHSD10 overexpression has been reported in brain and increased levels in cerebrospinal fluid. Cytoplasmic 17βHSD10 is imported via the PINK1-Parkin-TOM/TIM pathway into mitochondrial matrix, where it binds e.g. cyclophilin D (CypD) and prevents its translocation to the inner mitochondrial membrane. By this mechanism, 17βHSD10 can regulate the opening of the mitochondrial permeability transition pore mediated by CypD. It seems that accumulated mitochondrial Aβ may influence this regulation. In this study, we measured 17βHSD10 levels in mitochondria isolated from the brain of 11-month-old homozygous McGill-R Thy1-APP rats and we evaluated...
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Preparation and in vitro screening of quartenary inhibitors of acetylcholinesterase
Benek, Ondřej ; Doležal, Martin (advisor) ; Zimčík, Petr (referee)
Preparation and in vitro screening of quarternary inhibitors of acetylcholinesterase Abstract Reversible acetylcholinesterase (AChE) inhibitors are extensively used in human medicine. Among other applications they are used as a pre-exposure treatment for the prevention of organophosphorus poisoning. For this purpose carbamate inhibitors are recently used (e.g. pyridostigmine chloride). Carbamates reversibly block AChE active site and thus protect AChE against irreversible inhibition by organophosphorus compounds. However, these drugs have many undesirable side-effects and thus there are efforts to find a more suitable alternative among reversible AChE inhibitors. In this diploma thesis, 19 potential AChE inhibitors were prepared. Their ability to inhibit AChE and butyrylcholinesterase was evaluated in vitro and compared to selective standard cholinesterase inhibitors BW284c51 and ethopropazine. None of the prepared compounds was superior to used standards in inhibitory ability or selectivity. The structure activity relationship of the novel compounds was determinated from the obtained data.
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Preparation and evaluation of potential drugs inhibiting mitochondrial enzymes
Benek, Ondřej ; Musílek, Kamil (advisor) ; Patočka, Jiří (referee) ; Opletalová, Veronika (referee)
Preparation and evaluation of potential drugs inhibiting mitochondrial enzymes Summary in English Alzheimer's disease (AD) is the most common cause of senile dementia worldwide. Despite being subject to intensive research, the pathogenic mechanisms of AD are still not fully understood and consequently an effective treatment is yet to be developed. Although the aetiology of AD is still unknown, a build-up of amyloid-beta peptide (Aβ) is considered to play an important role in disease progression. The original amyloid cascade hypothesis proposed that insoluble extracellular plaques were responsible for the majority of Aβ toxicity. This hypothesis has since been refined, as recent data indicates that soluble intracellular oligomers are now responsible for the majority of Aβ induced toxic effects. The mitochondrial dysfunction also plays an important role in the pathophysiology of AD. Aβ was detected inside mitochondria and several mitochondrial proteins were found to interact directly with Aβ. Such interactions can affect a protein's function and cause damage to the mitochondria, which finally results in progression of AD. The background for the experimental part of this dissertation thesis was literature review summarizing current knowledge on mitochondrial proteins directly interacting with Aβ in order to...
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