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Supercomplexes in the respiratory chain of mitochondria
Mikulová, Tereza ; Holzerová, Kristýna (referee) ; Houštěk, Josef (advisor)
Mitochondria are very important organelles of eukaryotic cell. In mitochondria, there are located many metabolic reactions including oxidative phosphorylation (OXPHOS). In this process, respiratory chain enzyme complexes couple the oxidation of NADH and FADH2 to vectorial proton transport across the inner mitochondrial membrane. ATP synthase then uses the resulting electrochemical potential to synthesize ATP from ADP and phosphate. Recent studies of the OXPHOS demonstrate higher structures of complexes so-called supercomplexes which facilitate substrate channeling. Formation of supercomplexes plays a role in the assembly and stability of the complexes, suggesting that the supercomplexes are the functional state of the respiratory chain.
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Biochemical and mechanical processes in synovial fluid - modeling, analysis and computational simulations
Pustějovská, Petra ; Málek, Josef (advisor) ; Süli, Endré (referee) ; Jäger, Willi (referee) ; Maršík, František (referee)
vi Title: Biochemical and mechanical processes in synovial fluid - modeling, mathematical analysis and computational simulations Author: Petra Pustějovská (petra.pustejovska@karlin.mff.cuni.cz) Department: Matematický ústav UK, Univerzita Karlova v Praze Institut für Angewandte Mathematik, Universität Heidelberg Supervisors: prof. RNDr. Josef Málek CSc., DSc. (malek@karlin.mff.cuni.cz) Matematický ústav UK, Univerzita Karlova v Praze, Prof. Dr. Dr. h.c. mult. Willi Jäger (jaeger@iwr.uni-heidelberg.de) Institut für Angewandte Mathematik, Universität Heidelberg Abstract: Synovial fluid is a polymeric liquid which generally behaves as a viscoelastic fluid due to the presence of polysaccharide molecules called hyaluronan. In this thesis, we study the biological and biochemical properties of synovial fluid, its complex rheology and interaction with synovial membrane during filtration process. From the mathematical point of view, we model the synovial fluid as a viscous incompressible fluid for which we develop a novel generalized power-law fluid model wherein the power-law exponent depends on the concentration of the hyaluronan. Such a model is adequate to describe the flows of synovial fluid as long as it is not subjected to instantaneous stimuli. Moreover, we try to find a suitable linear viscoelastic model...
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Influence of autonomic nervous system in the inducibility of atrial fibrillation.
Šrutová, Martina ; Provazník, Ivo (referee) ; Kolářová, Jana (advisor)
Cílem této práce je zjištění změn předcházejícím fibrilaci síní. Pozorována je rovnováha mezi sympatikem a parasympatikem. Do experimentu výzkumného ústavu Cleavlendské kliniky bylo zapojeno šest psů různých ras. Signály EKG byly získány Holterovským 24hodinovým monitorováním. Pomocí 40 vysokofrekvenčních impulsů (TI) byla každých 30 minut vyvolávána AF. Z 24hodinového signálu byly extrahovány kratší epizody. Každá z těchto epizod obsahovala 10 minut předcházejících TI a 3 minuty následující po TI. Desetiminutové epizody byly zpracovány automaticky, byly detekovány QRS komplexy a RR intervaly a vypočteny HRV parametry. Přítomnost a délka trvání AF byly zjištěny manuálně z tříminutových intervalů následujících po TI. Byla-li vyvolána AF o délce trvání kratší než 30 sekund došlo ve srovnání s epizodami bez výskytu AF k významným změnám tří HRV parametrů. HF parametr poklesl pro epizody s výskytem AF. LF parametr byl naopak vyšší v epizodách s AF. Pro AF delší než 30 sekund nebyly významné změny pozorovány. Změny v epizodách s krátkou AF mohly být způsobeny změnami vlivu sympatiku a parasympatiku. Ke vzniku dlouhých AF je pravděpodobně zapotřebí i jiného vlivu, který nemusí nutně souviset s nervovým systémem. K dalším analýzám je zapotřebí většího množství signálů.
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Cell signalling and molecular complexes of the TRH receptor
Drastichová, Zdeňka ; Novotný, Jiří (advisor) ; Hodný, Zdeněk (referee) ; Říčný, Jan (referee)
1 Summary The first part of this thesis is preoccupied with the identification of protein alterations in the membrane fraction of HEK293-E2M11 cells after prolonged TRH treatment. The isolated membrane fraction enriched in plasma membranes contained markedly increased the amount of Na,K-ATPase, TRH receptor and G-proteins compared to the postnuclear supernatant. By using 2D electrophoresis and mass spectrometry, the levels of 42 proteins were identified to be altered in samples of PM- enriched fractions from TRH-treated (16 h; 10 μM) cells. Out of these proteins only ezrin and stomatin-like 2 are known to be localized in the plasma membrane. Five proteins (mitofilin, MTHSP75, prohibitin, stomatin like-2, peroxiredoxin III) whose levels were increased after the prolonged TRH treatment represent proteins localized in mitochondria. All of them are important for proper structure and function of mitochondria. The ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax was markedly higher in cells treated with TRH than in control untreated cells. Hence, it can be concluded that prolonged TRH treatment may significantly affect mitochondrial membrane and function of mitochondria. The second part of this thesis deals with the identification of molecular protein complexes of TRH-R and/or Gq/11 protein. The presumed...
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The role of the exocyst in development and maintaining of cell migration structures
Vaškovičová, Katarína ; Žárský, Viktor (referee) ; Brábek, Jan (advisor)
The exocyst is a hetero-octameric protein complex which mediates tethering secretory vesicles to specific sites of plasma membrane for polarized exocytosis. The exocyst was long known to contribute to processes such as yeast budding, cytokinesis, epithelia polarization and neurite outgrowth. Recently, the role of the exocyst in regulation of actin cytoskeleton and cell migration was discovered. It was shown, that the exocyst is important for formation of cell migration structures such as lamellipodia and filopodia in motile cells and invadopodia in invasive cancer cells. These structures are all actin-based membrane protrusions and the exocyst can through its Exo70 subunit interact with the Arp2/3 complex, the activator of actin nucleation. By binding and activating the Arp2/3 complex, the exocyst mediates actin polymerization resulting in formation of these membrane protrusions. Furthermore, the exocyst probably targets the Arp2/3 complex to specific sites of plasma membrane that are intended to become membrane protrusions. In addition, the exocyst mediates secretion of matrix metalloproteinases (MMPs) in invadopodia. MMPs are important for degradation of the extracellular matrix, an essential process in cancer cell invasion. The exocyst seems to be part of the cascade downstream of cytokines...
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New ligands for applications in medicine
Holá, Kateřina ; Holzhauser, Petr (referee) ; Kotek, Jan (advisor)
The aim of this Thesis was the preparation of macrocyclic ligands (Figure 1) for the complexation of lantanoides 3+ . Their complexes can be used in nuclear medicine (in case of ligand L1) or as MRI contrast agents (in case of ligand L2). Ligand L1 was designed to increase the rate of complexation due to the weakly binding pendant group based on iminodiacetic acid (IDA). The complexation mechanism was spectrophotometrically studied with Ce3+ . Spectrophotometric kinetic measurements proved that ligand L1 not only shown no improvement in the complexation rate but its complexation is rather noticeable slowed. Ligand L2 contains amino group whose protonization/coordination could be influenced by pH or temperature. It can be utilized in determination of physical status of different tissues. However, it is difficult to obtain the ligand L2 in sufficient purity for further studies N N NN COOHHOOC HOOC N COOH COOH P OH O L1 N N NN COOHHOOC HOOC NH2 L2 Figure 1: Ligands prepared in course of this Bc Thesis
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Complexes of iron(II) salts and flavonoids
Schröpferová, Tereza ; Volný, Michael (referee) ; Roithová, Jana (advisor)
This work is devoted to a study of the interaction between iron(II) ions and flavonoids (epicatechin, catechin, quercetin) by means of mass spectrometry and electrospray ionization. First, a measurement with model molecules (pyrocatechol, resorcinol, 3-hydroxy-2-methyl-4- pyrone) has been performed in order to find how iron(II) intereacts with the OH groups on the hydrocarbon rings. It has been found that Fe2+ coordinates to epicatechin and probably also catechin (the measurement with catechin was unsuccesfull because of contamination by sodium) between the OH groups at the ring B and the fragmentation of the complex can proceed via a retro-Diels-Alder's reaction and thus lead to cleavage of the pyrone ring. Quercetin has at the pyrone ring the keto function next to the OH group, therefore the iron ion binds to these functions rather than to the OH groups at the ring B. Accordingly, the retro- Diels-Alder's reaction is not possible and the complex loses only small molecules of water and carbon oxide from the side rings as it was found for the complexes of model molecules.
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Design and synthesis of selective gallium(III) chelators
Krchová, Tereza ; Lorenc, Miroslav (referee) ; Kotek, Jan (advisor)
This bachelor thesis is focused on the preparation of two new ligands (based on the 1-oxa-4,7-diazacyclononane skeleton), which would be potentially suitable for fast and selective complexation of Ga(III). Complexes of these ligands could find applications in radiodiagnostics (PET, SPECT), or as a new class of contrast agents for MRI based on proton chemical exchange saturation transfer (CEST). This thesis also describes the preparation of 1-oxa-4,7-diazacyclononane and attempts of preparation of N-benzyloxycarbonylaziridine. Thesis also includes a description of radiodiagnostic and radiotherapeutic methods of nuclear medicine. It also discusses the method of magnetic resonance tomography (MRI), especially the method using CEST contrast agents. Thesis contains an overview of the use of Ga(III) radioisotopes in radiomedicine.
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The role of caspase 2 in apoptosis induction in tumor cells.
Schmiedlová, Martina ; Horníková, Lenka (referee) ; Kovář, Jan (advisor)
Within the cell, caspase-2 probably fulfills several functions. Caspase-2 can be involved in apoptosis induction, DNA repair as well as cell cycle regulation. Caspase-2 has the character of initiator and also executioner caspase. A stimulus for caspase 2 activation can be oxidative stress or DNA damage. Caspase-2 is activated by cleavadge during an interaction with protein complexes. One of protein complexes,i.e. PIDDosome, is made of protein PIDD, RAIDD and pro-caspase-2. Withine the PIDDosome, caspase-2 is activated. Activated caspase-2 occures in a short S form and in long L form. L form of caspase-2 has proapoptotic effects and S form of caspase-2 has antiapoptotic effects. Caspase-2S has been only detected on mRNA level but not on protein level. The main role of caspase-2L is apoptosis induction in normal and tumor cells. Caspase-2 in tumour cells is activated by extrinstic as well as intristic apoptotic pathway. Apoptosis induction by caspase-2 is for example studied in connection with breast cancer treatment with taxanes. Caspase-2 ability of apoptosis induction in cancer cells independently of p53 protein is employed in cancer treatment including overcoming the resistance to apoptosis induction which is based on loosing p53 activity. Caspase-2 is involved in apoptosis induction by different...
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