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Structural biochemistry of human NK cell receptor complex NKp30 and B7-H6
Skořepa, Ondřej ; Vaněk, Ondřej (advisor) ; Šulc, Miroslav (referee) ; Schneider, Bohdan (referee)
Natural killer cells (NK cells for short) are lymphocytes of the non-specific (innate) immune system. They excel in the ability to recognise and eliminate infected or cancerous cells rapidly. Although their role in immune surveillance of malignant transformation was confirmed years ago, ongoing research shows that this process is far from simple. NKp30 is one of the central activating receptors of NK cells with a potential for use in targeted immunotherapy. The oligomerisation of the extracellular ligand-recognition domain of NKp30 in solution depends on the presence of a C-terminal stalk region. However, the structure and role in signal transduction of these oligomers are still unclear. Moreover, the interaction of NKp30 with ligands is influenced by the presence of N-linked glycosylation. In this work, we investigated whether and how the oligomerisation of NKp30 depends on its glycosylation. Our results show that NKp30 forms oligomers, regardless of whether glycosylation is complex or uniform (acquired by expression in the HEK293S GnTI- cell line). In contrast, NKp30 was found to form only monomers when enzymatically deglycosylated. Furthermore, we characterised the interaction with the ligand B7-H6, again concerning oligomerisation and glycosylation. We solved the crystal structure of its...
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Timing of egg laying in obligate brood parasites
Studecký, Jan ; Šulc, Michal (advisor) ; Pipek, Pavel (referee)
Obligate brood parasitism has evolved in 109 bird species around the world, which is approximately 1 % of all bird species. This alternative reproductive strategy is associated with complex evolution of the relationships between parasite and host(s) which is responsible for many adaptations on both sides. One of the important adaptations is the timing of egg laying either within a season, time of a day, or nesting stage of an individual host pair. The speed of laying itself is also no less important adaptation. Because brood parasitism is present worldwide in many different bird orders and parasites use variable species as their hosts, this adaptation is expected to be variable as well. My thesis will review information about timing of egg laying in all main taxonomical groups of brood parasites and will compare this adaptation between specialists and generalists, between closely related parasites with different hosts or between sedentary and migratory parasitic species. The main focus is on the question of coevolution with the host in relation to different timing strategies and an attempt to explain the differences in these strategies. Keywords: birds, coevolution, brood parasitism, egg laying, timing
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Automimicry-intraspecific variation in antipredatory defences
Stránská, Anna ; Exnerová, Alice (advisor) ; Šulc, Michal (referee)
Aposematic prey is characterized by the fact that individuals are warningly-coloured and unpalatable to predators. However, variability in antipredator defence may occur within one species. The presence of intraspecific variation in antipredator defences is called automimicry. Automimics can be palatable or have a different level of quantity or quality of chemical defence. One of the ways through which the variability arises is for instance consumption of specific plants which defence against predators by means of sequestration. Intraspecific variation in antipredator defence affects the behaviour of predators that can distinguish between palatable of unpalatable prey. Chemical defence is costly for unpalatable individuals. Palatable individuals on the other hand save much energy by simply resembling unpalatable individuals of the same species.
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Evaluation of the Financial Situation of Company and Proposals to its Improvement
Šulc, Michal ; Lisický, Adam (referee) ; Hornungová, Jana (advisor)
This bachelor thesis is based on the financial situation of OK PYRUS, s.r.o. in 2015-2019 for supporting methods of financial analysis. In theoretical studies, there are several relevant analyzes of financial analysis, which are based on analytical studies. Analytics has a fixed number of overheads and no charts. This practice is based on the fact that it is a very promising and successful solution, as it is a real estate agent, because it is a real-time application of prostitution in the field of financial support.
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Protein-protein interaction mapping of cytochrome P-450 by methods using /chemical modification and mass spectrometry
Ječmen, Tomáš ; Šulc, Miroslav (advisor)
Mapping of protein-protein interactions in the system of cytochrom P-450 by chemical modification and mass spectrometry Abstract Cytochromes P-450 (P450s) belong to haemoprotein superfamily and they are responsible for metabolism of a wide variety of compounds, among others many drugs and carcinogens. P450s serve as the terminal oxidases in the mixed function oxidase system in cooperation with a redox partner NADPH: cytochrome P450 reductase (CPR) providing input of two electrons to the reaction cycle of P450. The CPR can be substituted by other redox partner of P450, cytochrome b5 (cyt b5), to deliver the second electron. Three dimensional structure of P450 is required in order to fully understand its reaction mechanism. At the present time, a homology model of cytochrome P-450 2B4 (CYP 2B4) is available in our laboratory. In this study, the mapping of interaction domain between CYP 2B4 and cyt b5 employing a crosslinking agent EDC to form amide bonds between close complementary charged amino acid side chains was the first goal. We have identified five interacting amino acid pairs in total using mass spectrometry (MS). The second research interest was to verify and refine the CYP 2B4 model using a photoaffinity labelling with N-(p-azidobenzyl)-N-methyl-p-aminophenylamine probe. This photoreactive probe is...
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Proteomics as a tool for understanding molecular mechanisms of human diseases
Pospíšilová, Jana ; Petrák, Jiří (advisor) ; Šulc, Miroslav (referee) ; Kovářová, Hana (referee)
Proteomics is a set of analytical methods which enable qualitative and quantitative characterization of the proteome. Expression proteomics quantitatively compares proteomes of cells, tissues, body fluids or other biological materials to find differencies in protein expression and, based on these differencies, to describe the biological processes occuring in investigated organisms. An initial material for expression proteomic studies are complex mixtures containing thousands of proteins, which are analyzed using separation (electrophoretic and chromatographic) methods, and identified, possibly quantified using mass spectrometry. The aim of this Thesis is to demonstrate the application of the tools of expression proteomics in solving diverse challenges in biomedicine. We employed various proteomic approaches and tools for studying molecular mechanisms of human diseases using pacient biological samples, or a model organism and a cell culture. We were conducting three different research projects, namely: A quest for potencial molecular targets for selective elimination of TRAIL-resistant mantle cell lymphoma cells; Investigation of molecular mechanisms of heart failure using a rat model of the disease induced by volume overload; and Searching for diagnostically usable serum biomarkers of ovarian...
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Excitation of molecules by cold electrons
Šulc, Miroslav ; Horáček, Jiří (advisor)
Title: Excitation of molecules by cold electrons Author: Miroslav Šulc Department / Institute: Institute of Theoretical Physics, Charles University in Prague Supervisor of the doctoral thesis: prof. RNDr. Jiří Horáček, DrSc., Institute of Theoretical Physics, Charles University Abstract: Several methods for low energy collisional processes are investigated. In the first part, attention is especially devoted to examination of applicability of the R-matrix method combined with the Schwinger-Lanczos (SL) variational principle for potential scattering with long-range forces. Next sections deal with the development of the interaction correlation-polarization (CP) potential in the framework of the Dis- crete Momentum Representation (DMR) method on the grounds of the Local Density Approximation in the Density Functional Theory (DFT) context. Obtained results are then utilized in body-frame (BF), static exchange + polarization (SEP), calcula- tions within an analysis of experimental data for e−-N2 scattering comprising a part of a larger project addressing theoretical examination of rotational excitations of small molecules in the gas phase induced by electron impact. For N2, a new phenomenon consisting in suppression of backward cross-section below 95 meV is observed and con- sequently attributed to...
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Proteomic approaches in cancer biology
Lorková, Lucie ; Petrák, Jiří (advisor) ; Šulc, Miroslav (referee) ; Kovářová, Hana (referee)
Proteomics as a modern comprehensive approach to the analysis of proteomes was applied in three projects aimed at diagnosis and therapy of cancer. The aim of the first the project was to find a new diagnostic biomarker for ovarian cancer. Two different comparative proteomic approaches were used for comparative analysis of sera from patients diagnosed with ovarian cancer and from healthy age-matched women. We identified -1-antitrypsin with increased concentration in patien sera, and apolipoprotein A4 and retinol-binding protein 4 (RBP4) with significantly decreased concentration in patients. The significantly decerased concentration of RBP4 in patients is a new observation. We propose that RBP4 is either decreased in ovarian cancer patients as a result of its reduced production by ovary or it may reflect less specific systemic changes, for instance early onset of cancer cachexia. The second project was focused on gaining insight into the molecular mechanism of cytarabine resistance in mantle cell lymphoma (MCL). Proteomic and transcriptomic analyses of cytarabine-resistant cells revealed marked downregulation of deoxycytidine kinase (DCK) - a protein essential to intracellular activation of purine and pyrimidine nucleosides and their analogues including cytarabine. The cytarabine-resistant MCL...
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Evolution and function of polymorphism in warningly coloured prey
Fárová, Monika ; Exnerová, Alice (advisor) ; Šulc, Michal (referee)
Polymorphism can be expected in warningly colored prey if the prey is protected from predation by nothing else but its coloration. On the contrary, in defended prey, polymorphism was only until recently considered a controversial phenomenon due to its longer and costly avoidance learning. Individual moprhs can vary in different components of warning coloration: color, pattern, melanization degree, and internal and external contrast of colour patterns. This makes it difficult for predators to learn and remember warning signals of defended prey and avoid it in the future. Predator selection pressures and mechanisms leading to polymorphism differ between defended and undefended prey. For undefended prey, it is a negative frequency-depended selection that supports rare morphs or the multiple models hypothesis for one mimetic species. For defended prey, the polymorphism can occur temporarily (i. e., be unstable) and it also can be allowed by spatial heterogeneity of morphs or, as for undefended prey, one species can mimic multiple models. Quasi-Batesian mimesis could also contribute to the existence of the polymorphism, due to mechanisms similar to those in unprotected prey. Apart from selection by predators, there are other factors, that contribute to the existence of polymorhism in prey warning...
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Principles of market economy in Civics
Šulc, Martin ; Zicha, Zbyněk (advisor) ; Tichá, Milena (referee)
The diploma thesis will be devoted to the principles of market economy and its teaching in Civics classes at primary school. The work is divided into two parts, theoretical and practical. The theoretical part introduces the basic principles of market economy, explains the concepts of market, market mechanism, supply, demand, competition, monopoly, price and profit, including the interrelationships. The following is an insight to the curriculum and the theory of didactics. At the end of the theoretical part, space is set aside for introduction to the basic issues of teaching economic topics at primary school. In the practical part I present project teaching, a didactic analysis of the principles of market economy is performed, a teaching unit was designed and evaluated, which was implemented at the primary school and kindergarten Kralupy nad Vltavou, Třebízského 523. The diploma thesis is ended with self-evaluation.
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