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Naegleria: from free-living protist to brain eating deadly pathogen
Matějková, Magdalena ; Mach, Jan (advisor) ; Marková, Lenka (referee)
N. fowleri is mostly a free-living amoeboflagellate which, in favorable conditions, can occasionally adopt a parasitic lifestyle. In such cases, the amoeba becomes causative agent of primary amoebic meningoencephalitis, a severe and largely fatal disease occurring in several mammals including humans. The treatment of this disease is complicated by many unwanted side-effects of available drugs and a lack of prompt diagnostic methods. Within the Naegleria genus, N. fowleri is the only human pathogen. According to up-to-date knowledge, the pathogenicity of this species is due to its metabolic properties as well as to a particular set of proteins expressed by this protist. Besides a wide scale of enzymes, some of these proteins participate in the formation of cellular structures which are crucial for the pathogenesis. All these particularities should be targeted in a search for a better treatment. The thesis is focusing on a comparison of N. fowleri with related species N. gruberi and N. lovaniensis, stressing out the differences of N. fowleri from these non-pathogenic species. Key words: Naegleria fowleri, primary amoebic meningoencephalitis, immune response, pathogenesis, facultative parasitism
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Current options of treatment for parasitic kinetoplastids
Čadková, Aneta ; Mach, Jan (advisor) ; Richterová, Lenka (referee)
Chagas disease, sleeping sickness and leishmaniasis are diseases occurring mainly in developing areas of Africa, America and Asia. They are caused by parasitic kinetoplastids from the genus Trypanosoma and Leishmania. These protozoans undergo morphologic transformations during their development leading to changes of their properties. They are characterized by complex mechanisms that allow them to evade the host's immunity. At the same time, because of these mechanisms and selection pressures, they are able to subsequently develop resistance to used drugs. The diseases caused by protozoa are classified as "neglected tropical diseases". The research and development of drugs against them is heavily underfunded. Currently used drugs are expensive, have a number of side effects, and due to lack of usage regulation develop resistance. The work first generally presents human parasites of the class Kinetoplastida. It further describes the treatment of diseases caused by the characterized species and focuses on a summary of currently used drugs, their mechanism, resistance and potential new drugs in clinical phases. Key words: kinetoplastids, Trypanosoma, Leishmania, treatment, disease, mechanism of action, resistance, nitroreductase
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Legal regulation of weapons and ammunition in the Czech Republic and implementation of EU regulations
Mach, Jan ; Staša, Josef (advisor) ; Prášková, Helena (referee)
in English The introduction of this thesis explains the basic concepts of the legislative regulation of weapons and ammunition in the Czech Republic and their use in specific cases. This part also briefly presents the legal history of selected institutes of weapons legislation in the Czech Republic with EU law, in particular conditions and possession of weapons, business in the field of weapons and categorization of weapons. The next part analyzes Act No. 288/1995 Coll. again focusing on selected institutes important in the context of the implementation of EU law. The following are comparisons of Council Directive 91/477 / EEC in its original version with Act No. 119/2002 Coll. in the original wording and Council Directive 91/477 / EEC as amended by Directive 2008/51 / EC of the European Parliament and of the Council with Act No. 119/2002 Coll. as amended by Act No. 222/2017 Coll., with an overlap into certain legal regulations. The thesis also describes and analyzes the reasons for the adoption of Directive (EU) 2017/853 of the European Parliament and of the Council, the process of its adoption and the Czech Republic's lawsuit for its invalidity and describes the subsequent proceedings in front of the EU Court of Justice. Due to the lawsuit rejection, Czech Republic was forced to adopt an...
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Biogenesis of mitochondria in parasitic protist Trypanosoma brucei
Mach, Jan
In last decade, investigations of mitochondria including their various reduced forms such as hydrogenosomes and mitosomes revealed unexpected diversity of this indispensable organelle. Interestingly, the single mitochondrion of parasitic protist Trypanosoma brucei is able to undergo remarkable functional and structural changes reflecting available carbon sources. Moreover, it was proposed that trypanosomes belong among the most ancient eukaryotes and as such, their mitochondria raised high attention of biologists. To contribute to the knowledge of mitochondrial biogenesis and function, we focused on studies of two key mitochondrial processes, the processing of preproteins that are imported to the mitochondria, and mechanism of pyruvate transport to these organelles. Moreover, we also investigated uptake of iron by T. brucei. This metal is essential for function of numerous proteins, particularly for iron-sulfur proteins in mitochondria. Evolutionary history of trypanosomes and their mitochondrion is a question of debates. According to some reports, mitochondrion of trypanosomes represent an ancient form of this organelle, which is supported by identification of putative "archaic" translocase of the outer mitochondrial membrane (ATOM) and finding of only a single type of translocation pore in...
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Iron metabolism of parasitic protist Trypanosoma brucei
Krejbichová, Lucie ; Mach, Jan (advisor) ; Pyrih, Jan (referee)
Trypanosoma brucei is a parasite most frequently occurring in Sub-Saharan Africa that causes sleeping sickness in humans and various similar illnesses in animals. The bloodsucking tsetse flies (Glossina) transfer the parasite to humans, their final hosts. Throughout its complex life cycle, Trypanosoma occurs in different environments and undergoes various morphological and metabolic changes. Iron is an important element for all living organisms, including Trypanosoma. The metal plays a crucial role in the host-parasite interaction since trypanosomes are dependent on the iron they acquire from the host or vector. Trypanosomes use iron in metabolic reactions, such as energy metabolism, respiration, nucleic acid synthesis, detoxification, and cellular homeostasis. It is an important element in the synthesis of iron-sulfur clusters which function as cofactors during the above-mentioned reactions. The understanding of iron metabolism in the cell can facilitate the development of new medicaments, an example being iron chelators.
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Temporary agency employment - legal theory and application practice
Mach, Jan ; Pichrt, Jan (advisor) ; Morávek, Jakub (referee)
Temporary agency employment - legal theory and application practice The title of this diploma thesis is "Temporary agency employment - Legal theory and application practice ", where temporary agency employment being is characterized as flexible form or provision of labor force. The main aim of this work is to summarize the regulations of temporary agency employment and to point out problematic its most critical flaws. The thesis additionally highlights the most important differences compared to regulations in force in neighboring countries. The first chapter defines the central attributes of temporary agency employment, including flexibility and secondment. It further formalizes how temporary agency employment differs from similar concept of outsourcing. The main law text sources are subsequently presented and set to the historical law context of the Czech Republic. The third chapter defines the main players partaking in temporary agency employment, with focus on how permissions are obtained, the deposit obligation and the bankruptcy insurance. The fourth chapter deals with interplay of labor and commercial law, including the definition of individual terms of the contract. Next, the liabilities of all parties are explained, with particular focus on regulation of salary and employment terms,...
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Marketing communication of Česká zbrojovka Uherský Brod after 1992
Mach, Jan ; Halada, Jan (advisor) ; Švec, Kamil (referee)
The first part of this thesis is focused on the history of traditional marketing and arms marketing, defining the key marketing concepts of this sector and most importantly it deals with the influence of legislation on individual elements of the marketing mix in the Czech Republic since 1992 until the forthcoming amendment to the Weapons Act during 2019. Furthermore, this part covers the terms and conditions of social media and web browsers that regulate content involving weapons and their accessories. In its second, practical part, this thesis deals with the traditional Czech manufacturer of weapons, a company named Česká zbrojovka. It presents its rich history and development of its manufactured assortment up to the present. In addition, this part contains an analysis of individual marketing activities and their development since 1992. In particular, it characterizes the development of advertising in selected professional media, PR activities directed towards the general public, state apparatus and employees, discusses the history and achievements of the shooting team of Česká zbrojovka, event marketing, communication in point of sale including analysis of product catalogs. Furthermore, it deals with the communication of Česká zbrojovka at trade fairs and exhibitions, namely at the IWA, IDET and...
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Alcohol dehydrogenases in parasitic protists
Šipková, Anna ; Mach, Jan (advisor) ; Smutná, Tamara (referee)
Bachelor's thesis summarizes alcohol dehydrogenases mainly in parasitic protists. These widespread enzymes have been identified in several organisms ranging from bacteria to human. Thanks to the diversity of the enzyme's structure and substrate specificity is its function variable. Structure of the model zinc-containing Adh1 Saccharomyces cerevisiae is tetrameric. Enzymes are responsible for reversible oxidation of alcohols to aldehydes or ketones with concomitant reduction of NAD(P)+ as a cofactor. In most organisms, Adh appears in several types. Classification of Adhs is quite difficult and incomplete due to the investigation progress. The current classification includes three groups: MDR ("medium chain" Adh), SDR ("small chain" Adh) and iron-containing Adh. Adhs in parasitic protists have a specific role in the flexibility of metabolism and the adaptability to environmental changes in the host. This thesis deals especially with anaerobic parasites, where Adh is important in fermentation metabolism. Adh also figures in the resistance to drugs like in Trypanosoma cruzi or Tritrichomonas foetus. Recently, Adh has become a promising enzyme for a biotechnological application like in pharmaceutical or chemical industry. Keywords: Alcohol dehydrogenases, classification, parasitic protists, resistance
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Iron-sulphur cluster synthesis in anaerobic protists
Zelená, Marie ; Hampl, Vladimír (advisor) ; Mach, Jan (referee)
Iron-sulpur clusters are small ubiquitous cofactors of proteins present in all cells. These proteins participate in many important processes such as gene expression or respiratory chain. In vivo synthesis of iron-sulphur clusters requires complex biosynthetic pathways. In eukaryotic cells these pathways are localized inside mitochondria and plastids and in the cytosol. Cytosolic synthesis depends on a product of the mitochondrial pathway. Mitochondria of anaerobic protists in most cases went through reductive evolution, which is associated with the reduction of mitochondrial iron-sulphur cluster biosynthetic pathway. In many cases, these organisms acquired alternative pathways via lateral gene transfer, which act either as a complement to the mitochondrial pathway, or as its complete functional substitution. Replacement of the mitochondrial pathway might have been a key event for secondary loss of mitochondria. Key words: Iron-sulphur clusters, anaerobic protists, ISC, CIA, SUF, mitochondrion
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