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Function of Zinc finger protein 644 (Zfp644) in mouse organism.
Szczerkowska, Katarzyna Izabela ; Sedláček, Radislav (advisor) ; Komrsková, Kateřina (referee) ; Blahoš, Jaroslav (referee)
ZNF644 (Zinc Finger Protein 644) is a C2H2 zinc finger gene encoding a putative transcription regulator, of which a point mutation (S672G) is associated with inherited high myopia in humans. It is also described to be a partner of the G9a/GLP (G9a- euchromatic histone- lysine N-methyltransferase 2, EHMT2; GLP - euchromatic histone-lysine N-methyltransferase 1, EHMT1) complex, known for its essential role in histone methylation, specifically H3K9me1and H3K9me2. It was reported that another transcription factor, WIZ (Widely-Interspaced Zinc Finger-Containing Protein), can bind to this complex and cooperate in gene silencing simultaneously. In order to study Zfp644 impact on myopia, we generated a mouse model, Zfp644S673G that mimics human mutation. In addition, a mouse with a persuasive truncated form of the protein, Zfp644Δ8 was created. Both mouse models went through an examination of retinal function and morphology. Moreover, with use of ultrasonography, different ocular parameters were examined. We conclude, that Zfp644 gene is causative for myopia in mice. Further examinations of Zfp644Δ8 animals show severe symptoms in metabolism and female fertility. To describe the impact of Zfp644 in mouse fertility we performed various experiments including analysis of expression of Zfp644 in reproductive...
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2nd CCP Phenogenomics Conference 2020
Sedláček, Radislav
The conference was divided into two blocks. The block focused on the theme “From chemistry via preclinical pipeline to therapeutics“, which emphasized the translation of the basic research into the application. The second block was specifically devoted to presentation of CCP users and cooperation partners projects working in the field of immunology, hematology, genetic base of diseases, and neurobiology.
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The role of ADAM17 and other metalloproteases in liver pathological processes
Žbodáková, Oľga ; Sedláček, Radislav (advisor) ; Muchová, Lucie (referee) ; Stříšovský, Kvido (referee)
1 Abstract Liver fibrosis is a condition described by extensive accumulation of scar tissue in the liver. With further progression, it leads to cirrhosis or even to hepatocellular carcinoma. Liver fibrosis accompanies every chronic liver disease and its prevalence in adult European population is estimated to be around 4%. During my dissertation work, I studied the function of three members of Metzincin family of metalloproteinases - ADAM17, ADAM10 and MMP-19, in liver fibrosis and liver regeneration using mouse genetic models. ADAM17 and ADAM10 are important regulators of signalling pathways which are involved in immune response as well as differentiation. Both proteases are able to cleave ectodomains of their substrates from cell membrane, affecting bioavailability of ligands and functionality of receptors. Several of their substrates are involved in liver pathologies. MMP-19 on the other hand, is a metalloprotease mainly involved in extracellular matrix cleavage, important process in fibrosis development, as well as resolution of fibrosis. Our results demonstrate that ablation of ADAM10 results in increased susceptibility to liver fibrosis in mice, both spontaneous and toxin induced. ADAM10 deficiency affected biliary epithelium, as we detected higher markers of biliary damage in serum of ADAM10 deficient...
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Degradation of mechanical properties of magnesium alloy
Sedláček, R. ; Suchý, Tomáš ; Padovec, Z.
In this study, biodegradation behaviour of WE43 magnesium alloy have been studied and compared during exposure to three different media commonly used to simulate the conditions of human body environment. Magnesium alloys emerged as a new class of bioresorbable implant materials. Their applications reduce certain risks associated with conventional permanent implants. Biodegradation behaviour of the WE43 magnesium alloy was observed under Dulbecco Modified Eagle Medium (DMEM, Sigma Aldrich) supplemented with 5 % fetal bovine serum and gentamicin antibiotic as standard. The samples were stored in the medium at 37 degrees C and in a 5 % CO2 atmosphere. The second type of medium was Hank's Salt Balanced Solution (HBSS, Sigma Aldrich), which simulates the inorganic composition of blood plasma. HBSS was tempered at 37 degrees C. The last solution was an acidic solution of HCl + NaCl (pH2) with pH similar to 2 (0.01M HCl and 0.14M NaCl) tempered at 37 degrees C. The acidic type of solution was used to simulate a local acidic environment associated with osteoclast activity during bone remodelling. Changes in the mechanical properties of the samples during exposure to simulated body conditions were observed.
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Newly-built of boarding house in Velke Karlovice
Sedláček, Radek ; Nováková, Eva (referee) ; Kolář, Radim (advisor)
The subject of this thesis is a design of new building boarding house with attic flat in Velké Karlovice. House has eight flats and house is designed for temporary accommodation, the capacity is maximum 20 guests. The object is situated on a large and almost a flat land at parcel no. 3640/1. Pension is detached building. The main entrance and arrival is oriented in the northern part of the building. Plan dimensions of the house are 9,5×15 m and 10×15 m. Vertical constructions are made of ceramic bricks of Porotherm, ceiling construction is designed using technology of Spiroll. Stairs construction is a precast element. The building is roofed by saddle roof with purlins.
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Conservative treatment of spinal deformities in childhood
Sedláček, Radek ; Černý, Pavel (advisor) ; Šolc, Zdeněk (referee)
Title: Conservative treatment of spinal deformities in childhood Objectives: The main aim of this work is to point out the possibility of conservative treatment of spine deformity in a comprehensive view and logical sequence. At the beginning of the theoretical parts, the anatomy and the biomechanics of the joints are adduced and briefly explained, which are necessary for understanding. Below are examples of deformity sleep and the possibility of their correction. Also, the constructional differences of the torso orthoses used for correction and stabilization of the spine, as well as their functional properties, will be mentioned. In the end, in the special parts of this work, the technological and manufacturing process for the production of fuselage orthosis will be written. Methods: To solve this problem will be drawn from specialized literature, magazines and publications, concerning in particular matters of spinal deformity and its proper position. In the chapter on the manufacturing procedure of fuselage bones, my experience will be used in practice. Results: In the conservative treatment of spinal deformities, the interdependence of the components leading to the maximization of success in the treatment of spinal deformity is very important. This is mainly the cooperation between the doctor...
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Detached house
Sedláček, Radek ; Pospíšil, Jaroslav (referee) ; Kolář, Radim (advisor)
The subject of this thesis is a design of new building detached house with attic flat in Velké Karlovice. House has three flats and house is designed for ten to twelve permanent residents. The object is situated on a slightly sloping land on the outskirts of the village Velké Karlovice. Part of the building is a garage for three cars. The main entrance is oriented towards the main street. Plan dimensions of the house are 9,5 × 25 m. Vertical constructions are made of ceramic bricks of Porotherm, ceiling construction is designed using technology of Spiroll. Stairs construction is a precast element. The building is roofed by saddle roof with purlins. Part of the thesis is a project documentation for a construction including constructional details, fire safety, thermal engineering and acoustic solutions. The project documentation had been eleborated in an AutoCAD program.
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Chemical signals and reproductive processes of the house mouse (Mus musculus)
Černá, Martina ; Stopka, Pavel (advisor) ; Petr, Jaroslav (referee) ; Sedláček, Radislav (referee)
The aim of my thesis was to identify proteins involved in chemical communication and especially those that are involved in sexual signalling. Volatile chemical signals are transported with lipocalins in their beta-barrel structure to present their ligands to receptors or out of the body. Thus, I focused on the identification of these proteins in saliva and vaginal secretion of the house mouse using proteomic and transcriptomic approaches. Due to a cyclic manner of reproduction and its hormonal control, I have also focused on the role of estradiol on sperm phenotype in the laboratory mouse. We have identified an elevated sexual dimorphism in several lipocalins (i.e. 10 out of 20) in the saliva proteome where they may play a role in sexual signalling (i.e. similar to their described roles in the mouse urine). Interestingly, vaginal secretion also contains lipocalins and they rise from proestrus to estrus and remain steady during metestrus. Such variation provides evidence that they serve sexual signalling, however, due to their elevated levels during metestrus it is most likely that their ligands function as signals and not the proteins themselves. On the level of sperm phenotype, we have provided evidence, that experimental concentrations of estradiol have differential effects on sperm. This is due...
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Expression of ubiquitin ligases in gastrointestinal tract
Pícková, Markéta ; Sedláček, Radislav (advisor) ; Čermák, Lukáš (referee)
Ubiquitin (Ub) ligases are important regulatory and signalling molecules, which are involved in majority of cellular processes such as differentiation, DNA repair, and regulation of energetic metabolism or immune response. E3 Ubiquitin ligases are also responsible for pathophysiological changes in the organism and their activity is associated with many human diseases including cancers. This makes E3 Ubiquitin ligases to be new diagnostic markers and interesting pharmaceutical targets. Based on previous studies, these enzymes evince very specific expression in the level of tissues or cell populations. Determination of this specific expression is important for a better understanding of their biological function. In this diploma thesis we systematically screened presence of 370 genes of E3-Ub ligases in gastrointestinal tract under physiological conditions and during acute inflammatory damage of distal colon. Obtained data allowed us to select genes, which can play important role in homeostasis as well as pathophysiology and regeneration of gastrointestinal tract. The screening was based on the expression profiling using qPCR, followed by in situ hybridization to determine the exact localization of the gene expression within tissues. From qPCR analysis was predicted hundred thirty seven candidates for...
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