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Role of variable chains at the interface between subunits in forming ATP-binding pocket and function of P2X4 receptor
Tvrdoňová, Vendula ; Zemková, Hana (advisor) ; Novotný, Jiří (referee) ; Vlachová, Viktorie (referee)
7 ABSTRACT Crystallization of the zebrafish P2X4 receptor in both open and closed states revealed conformational differences in the ectodomain structures, including the dorsal fin and left flipper domains. The role of these domains in forming of ATP-binding pocket and receptor function was investigated by using alanine scanning mutagenesis of the R203- L214 (dorsal fin) and the D280-N293 (left flipper) sequences of the rat P2X4 receptor and by examination of the responsiveness to ATP and orthosteric analog agonists 2- (methylthio)adenosine 5'-triphosphate, adenosine 5'-(γ-thio)triphosphate, 2'(3'-O-(4- benzoylbenzoyl)adenosine 5'-triphosphate, and α,β-methyleneadenosine 5'- triphosphate. ATP potency/efficacy was reduced in 15 out of 26 alanine mutants. The R203A, N204A, and N293A mutants were essentially non-functional, but receptor function was restored by ivermectin, an allosteric modulator. The I205A, T210A, L214A, P290A, G291A, and Y292A mutants exhibited significant changes in the responsiveness to orthosteric analog agonists. In contrast, the responsiveness of L206A, N208A, D280A, T281A, R282A, and H286A mutants to analog agonists was comparable to that of the wild type receptor. These experiments, together with homology modeling, indicate that residues of the first group located in the upper part of...
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The visual representations of children in the Israel-Palestine conflict between years 2015-2021
Lusková, Martina ; Hrůzová, Andrea (advisor) ; Novotný, David Jan (referee)
The diploma thesis is focuses on the visual representation of children in the Israeli-Palestinian conflict in the online media Haaretz and Al Jazeera. The theoretical part of the thesis focuses on the historical context of the conflict, while the media theory part focuses on the media in Israel and Palestine and the representation of reality, focusing on visual representation and stereotyping. The aim of the research part is to use mixed-methods analysis to determine how children are portrayed in the photographs of the sample and what stereotypes and myths are manifested in the photographs. The set of photographs from the seven-year period was first subjected to a quantitative visual analysis, which provided a broader context for the depiction of children in conflict and allowed for differences in their portrayal between the media studied. The results are complemented by a semiotic analysis inspired by Roland Barthes. A sample of four photographs is used to examine three levels of image - the denotated image, the linguistic message and the connoted image. The main hypothesis of the whole research assumed that each medium would support a local narrative of the conflict through the choice of photographs, which was partially refuted by the results.
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Advancing efforts to improve sanitation conditions: insights from India
Ficek, František ; Novotný, Josef (advisor) ; Roubík, Hynek (referee) ; Chakraborty, Saurav (referee)
Inadequate sanitation is a significant global challenge, impacting the lives of billions of people. It has serious implications for human health and impedes progress towards development targets. Among the countries most affected, India stands out, having until recently recorded an especially low percentage of the population practicing hygienic sanitation. In response to previous underperformances of national-level campaigns, the Indian government launched the Swachh Bharat (Clean India) Mission in 2014, as the largest sanitation program worldwide, with the goal of eliminating open defecation by 2019. This dissertation project, initiated in 2016, aims to examine sanitation change in India. Through contextually sensitive case studies it analyzes national sanitation policies and trends in sanitation interventions. The research involved analyzing the situation in rural Jharkhand through repeated cross-sectional household surveys supplemented by qualitative interviews with the data collection conducted in 2016 and 2019. Additionally, the research included a qualitative study examining the perspectives of practitioners on a specific sanitation intervention and a comparative study of national sanitation policies implemented in India and Ethiopia. The research revealed that the Swachh Bharat Mission...
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The story of Josef Hasil in the miniseries The King of Šumava The Phantom of the Dark Land and its media response
Fortuníková, Jana ; Bednařík, Petr (advisor) ; Novotný, David Jan (referee)
The bachelor thesis deals with the anti-myth and myth of Josef Hasil, a smuggler from the Šumava region and the most famous bearer of the nickname "King of Šumava". The thesis reflects his image before 1989, which was fundamentally influenced by the famous propaganda film Smugglers of Death (Král Šumavy) from 1959. After the Velvet Revolution, the purification of Hasil's reputation was attempted when his life was being reinterpreted based on facts. His dramatic fate has also been featured in post communist popular culture titles. The most successful representative could be classified as a biographical novel about Josef Hasil called Návrat Krále Šumavy from 2012. The novel inspired narration of three-part miniseries King of Šumava: Phantom of the Dark Region (Král Šumavy: Fantom temného kraje) (2022) produced by a commercial TV station and distributed on its VOD platform Voyo. Both projects present their effort to straighten out the fates of Hasil's life, yet there is admitted fabrication in the story. However, an analysis of the texts of both works shows that the revision of historical reality is not neutral and corresponds to the post communist discourse on the perception of heroes of the third resistance, which can lead to their exclusive glorification and the suppression of discussion about the...
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Conservatism as a political ideology in Czech left-wing parties
Novotný, Jáchym ; Stauber, Jakub (advisor) ; Franěk, Jakub (referee)
This master thesis focuses on conservatism as a political ideology in Czech left-wing parties. The aim of the thesis is to answer several research questions. The most important one is whether elements of conservative ideology appear in the programs and other materials of selected Czech left-wing political parties. Subsequent questions build on the first one, aiming to determine in which periods conservatism appears in the programs and other materials of the examined parties and whether these parties deliberately seek to overcome the differences between conservatism and socialism, or whether they simply accept elements of conservatism that are not in conflict with left-wing ideologies. These questions are answered through content analysis of the programs and other materials of three political parties: the Czech Social Democratic Party (ČSSD), the Communist Party of Bohemia and Moravia (KSČM), and the Left. In addition to the analysis of programs and other materials, the thesis also includes a theoretically oriented chapter that deals with the individual political ideologies under study and their directions or branches. In conclusion, it is stated that elements of conservatism appear in the programs of all three analyzed parties, with clearly the fewest identified in the programs and other materials...
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Factors influencing sanitation conditions in developing countries: insights from Ethiopia and Cambodia
Humňalová, Helena ; Novotný, Josef (advisor) ; Lustigová, Michala (referee) ; Roubík, Hynek (referee)
Hygienic sanitation - the safe disposal and management of human excreta - is central to public health and has multiple non-health benefits. While its importance is recognised in global and national strategies, there remains a significant gap in achieving the sanitation targets set out in the Sustainable Development Goals. This thesis aims to investigate and understand the sanitation situation and its determinants in rural Ethiopia and Cambodia, with some attention to India for comparison. It includes the introductory text and four published academic articles. The research undertaken in this PhD project included the analysis of field-level data previously collected in rural Cambodia, participation in the design proposal, fieldwork, analysis and presentation of findings from research conducted in rural Ethiopia, and a comparative analysis of sanitation policies implemented in Ethiopia and India. The mix of research areas and designs enabled the study to address drivers of sanitation that operate at multiple levels - from the level of individual choices and behaviours to the level of communities and national policies. The research findings revealed an important role for contextual variations in the physical and social environment, including the negative effects of remoteness (both physical...
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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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