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Anthelmintics in the environment: circulation, metabolism and effects
Navrátilová, Martina ; Matoušková, Petra (advisor) ; Pohanka, Miroslav (referee) ; Česlová, Lenka (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Biochemical Sciences Doctoral Degree Program Xenobiochemistry and Pathobiochemistry Candidate Mgr. Martina Navrátilová Supervisor Assoc. Prof. Ing. Petra Matoušková, Ph.D. Advisor PharmDr. Ivan Vokřál, Ph.D. Title of Doctoral Thesis Anthelmintics in the environment: circulation, metabolism and effects This dissertation investigates the environmental impact of anthelmintics, specifically focusing on their circulation, metabolism, and effects in the environment. The primary objective was to explore the extent to which anthelmintics, particularly albendazole, affect plants under laboratory and field conditions and the potential for these effects to contribute to drug resistance in parasites. The study used an analytical technique, UHPLC-MS/MS, to monitor the uptake and biotransformation of albendazole and biochemical assays to asses phytotoxicity in plants like alfalfa and clover. Field experiments demonstrated the circulation of albendazole and its metabolites from sheep dung to plants and back to the sheep, indicating continuous environmental exposure. Furthermore, the investigation into the parasitic nematode Haemonchus contortus revealed changes in the expression of drug-metabolizing enzymes and the...
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Reading the Post-migrant: Reinterpreting Migration Literature in Scandinavia
Calvani, Emilio ; Březinová, Helena (advisor) ; Stahr, Radka (referee) ; Ciaravolo, Massimo (referee)
Emilio Calvani Advisor: Prof. Bruno Berni Co-Advisor: Prof. Helena Březinová Abstract Reading the Post-migrant: Reinterpreting Migration Literature in Scandinavia. Throughout the 20th and 21st centuries, migration has played an increasingly important and pervasive role in Western societies. The current globalizing network that interconnects distant places allows people, information, and images to move with greater speed and ease. This varied flow of movement has also had radical demographic repercussions over time. More and more people are moving from the Global South to the Global North in search of better prospects, thus giving rise to new generations of individuals whose life experiences fade the boundaries between local and global, nation and world. This posits the very concept of migration, in the different declinations and forms in which it manifests itself daily, as one of the cornerstones for understanding contemporaneity. At the same time, the strategies by which societies themselves interpret and modulate metanarrative processes to present themselves often relegate such realities to a secondary position. Such processes, in fact, tend to marginalize all those voices that set out to narrate intertwined cultures, languages, and identities and, consequently, to include the perspective of migration in...
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Steroid metabolome and multiple pregnancy
Černý, Andrej ; Pařízek, Antonín (advisor) ; Hubka, Petr (referee) ; Kiss, Imrich (referee)
Steroid hormones can be divided into 2 groups - intracellular and extracellular, depending on location of their activity. Intracellular ones influence expression of genes while acting as transcription factors. This so-called genomic effect is very slow. Extracellular (non-genomic) steroids bind to neurotransmitter receptors located on the cytoplasmic cell membrane and thus affect ionic channels permeability. Their effect is faster. We refer to them as neuroactive steroids (produced in different body tissues or administered externally) or neurosteroids (synthetized in nervous system cells). Some neuroactive steroids and their metabolites (e.g. progesterone) are crucial in stabilizing the pregnancy. Other steroid disorders play their role in wide spectre of pregnancy complications, such as preterm labor, preeclampsia, intrahepatic cholestasis in pregnancy etc. Our scientific interest in collaboration with the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague is focused on investigation of multiple pregnancies in term of steroid metabolome. Studies conducted so far have not provided a comprehensive analysis of steroidome within mothers and fetuses of multiple pregnancies. The aim of our research is to clarify the relationship between fetuses and mother from the point...
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Identification and investigation of key biotic and abiotic factors in sewage sludge bio-drying process
Pilnáček, Vojtěch ; Innemanová, Petra (advisor) ; Najmanová, Petra (referee) ; Wrzecionko, Jakub (referee)
The work is focused on the pretreatment of sewage sludge after anaerobic stabilization by the process of biodrying. Biodrying is a process in which the organic substrate undergoes aerobic decomposition and at the same time, due to the increased temperature and the blowing air, it is dried. The aim of the work was to optimize the most important process variables, to verify whether the process is suitable for pretreatment of sewage sludge before use as fuel or fertilizer in the context of Czech legislation and to investigate which groups of organisms and how they participate in the degradation of endocrine disruptors. For these purposes, quarter- and semi- operational bio-drying reactors were designed. The results of the work show that the most important process parameters are the aeration rate and temperature as its dependent variable and the substrate composition. The setup with a fixed time interval of blower switching was found to be the optimal aeration regime. The optimal substrate composition was a 5:2 ratio of sludge:birch chips. The results of the work further show that the bio-drying process is suitable for the preparation of fuel for co-incineration with other material. It is not very suitable for mono-incineration due to exceeding emission limits. The calorific value of the resulting fuel...
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"To the Relief of Those Who Are in Distress." On the Phenomenon of Pity in the Philosophy of J.-J. Rousseau
Sváčková, Kateřina ; Novák, Aleš (advisor) ; Špelda, Daniel (referee) ; Fulka, Josef (referee)
"To the Relief of Those Who Are in Distress." On the Phenomenon of Pity in the Philosophy of J.-J. Rousseau Kateřina Sváčková The thesis attempts to thematise the philosophical composition of the phenomenon of pity (fr. pitié, compassion) as it was elaborated by J.-J. Rousseau, and on this basis, to present an "ornament of pity" as a phenomenon that is both integral and changeable. First of all, we compose this ornament from three groups of principles: firstly, affection, passion, emotion and the so-called moral sense; secondly, reason and reasoning; and thirdly, two forms of self-love (fr. amour de soi-même, amour propre). In the first part of the thesis, Rousseau's pity comes to be seen as combining these three sets of principles. The individual phenomenon thus constructed is to be applied in the moral, social and public spheres. In Rousseau's idealised theory, pity is generalised through the rational faculties and extended self-love, and extended to the level of cosmopolitan love of humanity (fr. amour de l'humanité) and (thus) love of justice (fr. amour de la justice). We reflect on pity as defined by Rousseau as the "source of moral virtues" or the "source of social relations", tracing the transformation of its original form and strength, of its "quantity" as well as its "quality". Thus, by placing...
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The influence of Romance novels and the matter of Britain in modern and contemporary German language and literature
Pulimanti, Alessandro ; Weinberg, Manfred (advisor) ; Cornejo, Renata (referee) ; Nelva, Daniela (referee)
The aim of this doctoral thesis is to reflect on the influence that the Romance tradition has had on the work of Peter Handke. One play and three novels were selected as the corpus of the thesis, all of which were analysed from a textual perspective and all of which displayed the influence of the mystical-medieval tradition in a particularly original way. The research will be divided into three macro-sections: the first macro-section will focus on the influence of the Grail-Parzival universe on Handke's work, while the second will analyse the revival of the Latin hagiographic dimension. Finally, the third macro-topic will address the re-interpretation, through a modern lens, of the Spanish mystical tradition. In view of future studies regarding the influence of the Romance cultural dimension on Handke's work, this dissertation intends to demonstrate how the chivalric-medieval tradition and the mystical tradition itself become, for the Austrian author, a tool used to re-interpret the present and his own biographical past in light of themes and elements apparently distant from the current times, yet still profoundly connected to them.
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Development of mass spectrometric methods for structural analysis of fatty acids and estolides
Cudlman, Lukáš ; Cvačka, Josef (advisor) ; Kozlík, Petr (referee) ; Lísa, Miroslav (referee)
(EN) This doctoral thesis summarizes the use of modern mass spectrometric methods for the structural identification of fatty acids and triacylglycerol estolides (TG-EST) and their subsequent characterization in the lipidome of vernix caseosa, i.e., the biofilm covering the skin of the human fetus during the last trimester of in-utero development. Vernix caseosa has mainly antimicrobial properties and the ability to heal wounds and burns. The first part of the doctoral thesis focuses on the diversity of fatty acids in the lipidome of vernix caseosa. These acids form the structural subunits of complex lipids, such as the abundant triacylglycerols and wax esters. By studying fatty acids and their structural features, this thesis has provided valuable insights into the structural variability of the vernix caseosa lipidome. Without a full understanding of the structure of these key subunits, it would be impossible to complete the analysis of this lipidome in the future. In this thesis, fatty acids using high-performance liquid chromatography (HPLC) and modern mass spectrometry methods, namely ultraviolet photodissociation (UVPD) and ozone-induced dissociation (OzID), were characterized. The coupling of HPLC and mass spectrometry (HPLC-MS) provided unambiguous information on the positions and geometry of...
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Mapping the Proliferation of Strategic Partnerships
Rosendorf, Ondřej ; Parízek, Michal (advisor) ; Karlas, Jan (referee) ; Faude, Benjamin (referee)
Since the end of the Cold War, states have increasingly resorted to the establishment of informal alignments, with "strategic partnerships" at the forefront, whereas the number of formal military alliances has been stagnating. In spite of the rapid proliferation of these partnerships-next to other forms of informal cooperation-the extant International Relations literature has paid only limited attention to this phenomenon. In this dissertation, I introduce and analyze the first dataset of Bilateral Intergovernmental Strategic Partnerships (BISPs) established by G20 members between 1993 and 2020. Utilizing insights from international alignment and institutionalist literature, I aim to: (1) provide the first empirical account of the extent to which strategic partnerships have proliferated among the G20 and over time; (2) identify factors driving states to form strategic partnerships; and (3) determine whether these partnerships operate primarily as complements to the existing alliance structures, or exist in place of them as "low-cost" alternatives. Firstly, I found that G20 members alone established approximately 382 strategic partnerships by the end of 2020, surpassing previous estimations. Secondly, I found that the onset of strategic partnerships correlates with factors such as economic...
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The effect of variations in GRIN genes on the biogenesis and functional properties of the NMDA receptor
Kuchtiak, Viktor ; Balík, Aleš (advisor) ; Rozbeský, Daniel (referee) ; Ladislav, Marek (referee)
The expression and activity of ionotropic glutamate receptors control signal transduction at the excitatory synapses in the central nervous system. The major class are the calcium-permeable NMDA receptors that are fundamental for the various forms of synaptic plasticity, a key mechanism in the process of learning and memory formation. NMDA receptors are heterotetrameric and are represented by three types of subunits: GluN1, GluN2A-D, and GluN3A-B. Each subunit consists of four domains, with the intracellular C-terminal domain accounting for up to half of the entire NMDA receptor subunit (GluN2A/2B). A body of evidence indicates that the hypofunction of the NMDA receptor plays an important role in the pathogenesis of several neuropsychiatric disorders, including schizophrenia. Schizophrenia is characterised by a high degree of heritability, but its genetic background is not yet fully understood. Previous studies have identified in the human genome several individual loci that contribute to disease susceptibility, including the GRIN genes encoding NMDA receptors. Using a sequencing approach, we identified and annotated genetic variations across all GRIN genes in a cohort of schizophrenia patients and control subjects. The submitted doctoral thesis focuses on the functional analysis of the genetic...
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Biotransformation of plant secondary metabolites and their modulatory effects on drug-metabolizing enzymes
Šadibolová, Michaela ; Boušová, Iva (advisor) ; Soukup, Ondřej (referee) ; Anzenbacherová, Eva (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Biochemical Sciences Doctoral Degree Program Xenobiochemistry and Pathobiochemistry Candidate Mgr. Michaela Šadibolová Supervisor Assoc. Prof. PharmDr. Iva Boušová, Ph.D. Advisor Title of Doctoral Thesis Biotransformation of plant secondary metabolites and their modulatory effects on drug-metabolizing enzymes Sesquiterpenes and prenylflavonoids represent two classes of plant secondary metabolites that form an inherent part of human diet. They exert many beneficial biological activities, and accordingly, they are used as active constituents of herbal products. However, as xenobiotics, they also interact with a battery of drug-metabolizing enzymes and can in turn modulate their activity and/or expression, which may lead to herb-drug interactions. Sesquiterpenes and prenylflavonoids mentioned in this dissertation have been under-researched in this aspect. Three acyclic sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol) and three cyclic sesquiterpenes (α-humulene, β-caryophyllene, β-caryophyllene oxide) activated gene transcription mediated by pregnane X receptor; however, they did not alter the mRNA or protein expression of their downstream targets, namely cytochrome P450 (CYP) 3A4 and CYP2C, neither did...
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