1 Abstract in English Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. However, why modern ETC-targeted compounds are tolerated on the organismal level and what are the molecular reasons for this tolerance remains unclear. Most somatic cells are in a non-proliferative state, and features associated with the ETC in quiescence might therefore contribute to specificity. Thus, we investigated the ETC status and the role of two major consequences of ETC blockade, reactive oxygen species (ROS) generation and inhibition of ATP production, in cell death induction in breast cancer cells and in proliferating and quiescent non-transformed cells. First, we characterised the effect of a newly developed ETC inhibitor mitochondria- targeted tamoxifen (MitoTam) in in vitro and in vivo tumour models of breast cancer with varying status of the Her2 oncogene. We document that Her2high cells and tumours have increased assembly of respiratory supercomplexes (SCs) and increased complex I-driven respiration in vitro and in vivo. They are also highly sensitive to MitoTam. Unlike the parental compound tamoxifen, MitoTam efficiently suppressed experimental Her2high tumours without systemic toxicity. Mechanistically, MitoTam inhibits complex I- driven respiration and disrupts respiratory...

Mood disorders are serious diseases. Nevertheless, their pathophysiology is not sufficiently clarified. Biological markers that would facilitate the diagnosis or successful prediction of pharmacotherapy are still being sought. The aim of the study was to find out whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression. Our research is based on recent hypotheses of mood disorders, the advanced monoamine hypothesis, the neurotrophic hypothesis, and the mitochondrial dysfunction hypothesis. We assume that impaired function of mitochondria leads to neuronal damage and can be related to the origin of mood disorders. Effects of antidepressants and mood stabilizers on mitochondrial functions can be related to their therapeutic or side effects. In vitro effects of pharmacologically different antidepressants and mood stabilizers on the activities of mitochondrial enzymes were measured in mitochondria isolated from pig brains (in vitro model). Activity of monoamine oxidase (MAO) isoforms was determined radiochemically, activities of other mitochondrial enzymes were measured spectrophotometrically. Overall activity of the system of oxidative phosphorylation was measured electrochemically using high- resolution respirometry. Methods were modified to measure the same...

Mitochondria are essential organelles for most eukaryotic cells, containing intricate networks of numerous proteins. These include, among others, complexes I-IV of the electron transport chain. Being at the crossroads of the tricarboxylic acid cycle and the respiratory chain, mitochondrial complex II plays a key role in cellular metabolism. The protein complex, also known as succinate dehydrogenase, is capable of not only succinate oxidation and electron transfer but also contributes to the production of reactive oxygen species. Mitochondrial complex II consists of four subunits, SDHA-D, and four dedicated protein assembly factors SDHAF1-4 that participate in complex II biogenesis. Mutations and epigenetic modulations of genes coding for succinate dehydrogenase subunits or assembly factors are associated with pathological conditions such as neurodegenerative diseases, or may result in tumor formation. However, inborn complex-II-linked mitochondrial pathologies are rather understudied, compared to diseases with causative errors of other mitochondrial complexes, presumably due to the fact that none of complex II subunits is encoded in the mitochondrial genome. Recent studies have shown that impairment of mitochondrial complex II function or assembly leads to accumulation of alternative assembly forms...

Psychopharmaca are a large group of drugs widely used not only in psychiatry. Their systemic administration affects both the main diagnosis and the organism as a whole. The subject of our experiments is the effect of psychopharmaca on the changes in mitochondrial functions, which is beneficial for understanding of molecular mechanisms of therapeutic and adverse effects of drugs. The aim of this thesis was to study the in vitro effects of selected drugs on the cell energy metabolism. Selected antipsychotics (chlorpromazine, levomepromazine, haloperidol, risperidone, ziprasidone, zotepine, aripiprazole, clozapine, olanzapine, and quetiapine), antidepressants (bupropion, fluoxetine, amitriptyline, imipramine) and mood stabilizers (lithium, valproate, valpromide, lamotrigine, carbamazepine) were tested. In vitro effects of selected psychopharmaca were measured on isolated pig brain mitochondria. The activities of citrate synthase (CS) and electron transport chain (ETC) complexes (I, II+III, IV) were measured spectrophotometrically. Drug-induced changes of mitochondrial respiration rates linked to complex I (supported by malate and pyruvate) and complex II (supported by succinate) were evaluated by high resolution respirometry. Complex I was significantly inhibited by lithium, carbamazepine, fluoxetine,...

Title: Coupling atmospheric chemistry/aerosols to regional climate models Author: Peter Huszár Department: Department of Meteorology and Environment Protection Supervisor: doc. RNDr. Tomáš Halenka, CSc. Supervisor's e-mail address: tomas.halenka@mff.cuni.cz Abstract: In this thesis, the connections between air quality and climate are studied. For this purpose, regional climate model RegCM3 and chemistry transport model CAMx has been coupled offline with one- and two-way interaction. Our work represents a first attempt to connect RegCM3 not only with CAMx, but with any other chemistry transport model. As a first step, an offline one way couple of RegCM3 and CAMx has been developed, meaning that the climate model drives the transport, emission, chemical transformation and deposition of species while the radiative feedbacks of gases and aerosols are not considered. A meteorological interface has been developed at our department in order to convert the meteorological data generated by RegCM3 to fields required by CAMx. For those parameters that are essential for CAMx but the regional climate model does not supply them, diagnostic methods were implemented into this interface. Further, it is used to calculate biogenic emissions. Regarding anthropogenic emissions, a simple utility has been developed to...

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martin Huličiak Supervisor: PharmDr. Lukáš Červený, Ph.D Title of diploma thesis: Study of interactions of antiviral drugs with intestinal drug efflux ABC transporters P-gp, MRP2 and BCRP are efflux transporters, members of the family of ATP binding cassette (ABC) transporters. These transporters are located on the apical membrane of the intestinal epithelium, where they may limit absorption of orally administered drugs. Study of drug interactions with/on intestinal efflux transporters is necessary to provide safe and effective treatment. The Caco-2 cell line is FDA recommended in vitro model of intestinal barrier and it is used for bidirectional testing of substrates and inhibitors of ABC transporters in preclinical research. However, this methodology has several shortcomings, so the need of introduction of new experimental models is increasing and the ex vivo method based on human or rat intestine is a promising option. Precision-cut intestinal slices (PCIS) represent a mini-model of the organ and contain all types of cells of the tissue. We used both in vitro model using Caco-2 cell monolayers for drug transport study and in our lab established ex vivo method of PCIS for accumulation study...

This thesis is about the design of the telescopic platform. which should be fasten on robot called Breach. Purpose of this platform is to carry another equipment like sensors, cameras or manipulator. The platform has to provide chiefly the high demands on load capacity. Another part of the thesis is design of mechanism placed on this telescopic platform, or just on the robot Breach. This mechanism has to load up small subject on the top part of the platform and then unload it on chosen place. Only thing defined for this subjekt is maximal weight of 2 kilograms, but other parameters aren´t specified. Construction is therefore focused on maximal versatility of this mechanism.

The thesis deals with the implementation of Ethernet-based network communication interface into FPGA chip. VHDL programming language is used for description of the hardware. The interface includes the implementation of link-layer Ethernet protocol and network protocols such as IPv4, ARP, ICMP and UDP. The final design allows bi-directional communication on the transport-layer level of TCP/IP model. The designed interface was implemented into Virtex5 FPGA chip on development board ML506 by Xilinx.

This diploma thesis is focused on the construction proposal of pallet hoist connected with powered section roller conveyor for transportation of europallets with loads 1200 kg. The proposed hoist is designed for vertical handling between two working positions with the distance 5 meters. The thesis contains all structural units of machine, design of all standars parts and control calculation of some parts using the finite element method (FEM). The thesis contains complete drawing documentation for designed machine.

The aim of this master´s thesis is an explanation of the problem of transport optical networks with Dense Wavelength Division Multiplexing. DWDM principle, properties and limit of transmission system. Focus of thesis is also specification properties of migration transmission system to higher speed 40G, 100G and in future to 400G. Part of thesis is outlined the basic division of multiplexing system, there are discussed the basic solutions of wavelength multiplexes CWDM and DWDM, focus for the effects of nonlinear phenomena and parasitic modulation FWM, SPM and XPM in modulation DP-QPSK and 16-QAM. In practicle part we will make measurement of properties of 10G and then experimental measurement parameters on 100G.