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Investigation of changes in epigenetic modofications in rat brain induced by morphine treatment
Hronová, Anna ; Novotný, Jiří (advisor) ; Roubalová, Lenka (referee)
This study addressed the impact of varying lengths of abstinence periods on the epitranscriptomic modification of m6 A and the enzymes involved in this modification as well as on transcription factors in the brains of morphine-dependent rats. The methods used included a colorimetric kit to determine m6 A levels and Western blotting to quantify the levels of enzymes and transcription factors. The results showed that different lengths of morphine abstinence did not have a significant effect on m6 A modification, suggesting that this pathway was likely not influenced by morphine abstinence. However, significant changes were observed in the levels of enzymes involved in the regulation of m6 A, which were localized and time-specific, without a clear trend. Examination of transcriptional regulators ∆FosB and MeCP2 also revealed significant changes only in certain parts of the brain and at specific times, but without a clear trend in changes in levels. The outcome of this study is that the dynamics of transcriptional regulators, N6 -methyl-adenosine, and enzymes involved in m6 A modification are localized and time-specific, opening new questions regarding the mechanisms that govern neurobiological processes during the abstinence period.
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The effect of opioids on the immune system
Miniariková, Nina ; Novotný, Jiří (advisor) ; Cimermanová, Veronika (referee)
The use of opioids in medicine is necessary as they serve to suppress pain as a part of anesthesia notably during surgical procedures. After that, they help suppress pain during postoperative care and they are also prescribed to patients with chronic pain, for example in the final stages of cancer. However, opioids are among the most abused substances worldwide. The United States of America is facing an opioid epidemic, also called the opioid crisis, which began mainly with the excessive prescription of opioids and their subsequent misuse. It is clear that opioids affect the immune system which has been the subject of many recent studies. Different opioids have variable effects on the immune system. The understanding of their impact on the immune system could mean improvement of health care, and at the same time could present a basis for proposals of new treatment methods for some of the diseases. This bachelor thesis summarizes the available studies dealing with the influence and effects of various opioids on the cells of the immune system in order to better understand their importance and their use in practice. Keywords: opioids, immune system, inhibition, immunomodulation, phagocytes, lymphocytes
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The role of SGIP1 protein in the control of cannabinoid receptor
Gazdarica, Matej ; Blahoš, Jaroslav (advisor) ; Jakubík, Jan (referee) ; Novotný, Jiří (referee)
Two regions within the cannabinoid receptor 1 (CB1R) C-tail, 425 SMGDS429 and 460 TMSVSTDTS468 , contain clusters of serine and threonine residues that can be phosphorylated and collectively play an essential role in the desensitization and internalization of activated CB1R. First, I studied the role of phosphorylation of the aforementioned serine/threonine clusters in protein-protein interaction between CB1R and molecules relevant to the receptor desensitization and internalization using the Bioluminescence Resonance Energy Transfer method in tandem with pharmacological inhibitors. I show that CB1R interaction with G protein-coupled receptor kinases 3 (GRK3) and β-arrestin2 depends on distinct C-tail phosphorylation patterns. Furthermore, the activation of GRK3 is required for its interaction with CB1R. Second, I studied the impact of Src homology 3-domain growth factor receptor-bound 2-like endophilin interacting protein 1 (SGIP1) on the dynamics of CB1R signalosome and CB1R desensitization. SGIP1 altered CB1R interactions with GRK3, β-arrestin2 and GRK3-Gβγ coupling. Further, I characterize newly identified splice variants of SGIP1 and demonstrate that alternative splicing-based alterations in SGIP1 domains do not affect the inhibitory effect of SGIP1 on CB1R internalization. This study's...
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Neurobiology of food addiction
Cíbiková, Sofia Anna ; Novotný, Jiří (advisor) ; Petríková, Ivana (referee)
This work deals with food addiction, mainly its neurobiological basis. The fact that highly processed food high in calories can have effects similar to those of addictive substances has been known for decades, however with the rapidly increasing prevalence of obesity in the last few years, there is more and more research being done in this area. Food addiction very often correlates with obesity and eating disorders, such as binge eating disorder, and naturally has a negative impact on the health of an increasing number of people. Excessive consumption of highly caloric foods causes changes in the neural pathways in the brain, especially those connected to dopamine and the reward system which, similarly to substance use disorders, leads to addiction, which manifests itself in loss of control over the consumption, developed tolerance and withdrawal symptoms. Stress together with various mental health disorders such as depression and anxiety are often factors contributing to the development of addiction. Understanding the similarities between food addiction and substance use disorders can be beneficial for finding an appropriate treatment. Cognitive intervention and therapeutic methods seem to be the most effective, on the other hand strict diets and efforts to make major lifestyle changes often bring...
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The role of epigenetic mechanisms in the development of drug dependence
Durdilová, Marie ; Novotný, Jiří (advisor) ; Janoušková, Alena (referee)
The abuse of addictive substances is widely spread and carries numerous negative impacts, both on individuals and their surroundings. Some substances can lead to addiction after just a few doses, while for others, it may be a more prolonged process. However, the result is generally similar, with the prioritization of the drug or activity becoming the individual's main focus in life. This shift in priorities is linked to increased dopamine production due to the substance's effects, and the modulation of reward circuits in the brain. Changes in the connectivity and excitability of neurons in the mesolimbic and mesocorticolimbic dopamine systems lead to the development and maintenance of addiction. These neuronal changes are maintained in the body through epigenetic remodeling of chromatin. The pattern of epigenetic modifications, characteristic for a specific type of abused substance, can be passed on to the next generation, thereby increasing the potential for addiction development in offspring. Research on epigenetic modifications associated with addiction provides us with a deeper understanding of the neurophysiological changes accompanying drug addiction. At the same time, it raises the question of further treatment possibilities for drug addiction by targeting the epigenetic modifications that...
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Evaluation of Economic Effeciency and Risk of Investment Project
Novotný, Jiří ; Hromádka, Vít (referee) ; Korytárová, Jana (advisor)
The bachelor thesis deals with the evaluation of economic efficiency and risks of an investment project. This is the construction of a multifunctional building in Brno. The theoretical part of the thesis explains the basics concepts, defines the phases of the project life cycle, describes cash flows, economic indicators and deals with project efficiency management. The practical part is devoted to the investment project, especially the creation of cash flows and the resulting evaluation of the economic efficiency of the project. At the end of the work, a sensitivity analysis is demonstrated.
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Impact of Drivers' Working Regimes in Freight Road Transport on Transport Safety
Máša, Vojtěch ; Novotný, Jiří (referee) ; Libertín, Josef (advisor)
Working arrangements are restrictive limits for drivers important for both motor carriers and drivers. Have a major impact on the logistical arrangements of manufacturing companies that transport their goods by road. Failure to comply with these limits, is recently one of the major problems in road transport and leads to unfair competition between road hauliers. Carrier's failure to obtain such social legislation crucial competitive advantage. Recently the problem devoted much time from the perspective of politicians. States, violations of social legislation by the carrier and the driver severely punished and often the articles we read on the operating modes of drivers and their associated hazards of freight transport, road safety hazard, danger for drivers of cars. For 10 years devoted to the issue and participate in the creation of training materials on the subject of Logistics and. In my work I wanted to examine the issue of working arrangements drivers from professional point of view - how the limits are set and working arrangements whether they comply with road safety. Next, consider the statistics of accidents in the CR in relation to drivers' working arrangements and to propose changes that would contribute to the improvement of social legislation in relation to road safety.
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An Arrhytmia Classifiication Based on RR Interval
Novotný, Jiří ; Škutková, Helena (referee) ; Kozumplík, Jiří (advisor)
This bachelor’s thesis deals with automatic classification of cardiac rhytm based on the sequence of RR intervals. The theoretical part deals both with characteristics of arrhytmias, which have been classified and the principles of the detectors and classificators used in this thesis. In the practical part, the QRS detector based on the calculation of the envelope of the ECG signal was realized in Matlab. Furthermore, the algoritm classifying arrhytmias based on the analysis of RR intervals was created. The reliability of the detector and the efficiency of the classificator was tested on the standard database CSE. The sensitivity of the detector was 98,28% and its positive predictive value was 98,38%. The diagnoses of the implemented classificator concurred in 73,17% with the cardiologists‘ diagnoses.
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