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Proteomics as a tool for understanding molecular mechanisms of human diseases
Pospíšilová, Jana
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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Resenzitalizace leukemických a lymfomavých buněk k trailerem indukované apoptóze
Molinský, Jan ; Klener, Pavel (advisor) ; Hyršlová Vaculová, Alena (referee) ; Vyoral, Daniel (referee)
Apoptosis serves as a natural barrier to cancer development, and the resistance to apoptosis represents one of the key capabilities acquired during tumor development or progression. Impairment of the intrinsic apoptotic pathway exemplifies one of the established mechanisms of constitutive or acquired drug resistance. As most of the currently used cytotoxic drugs initiate tumor cell death by direct or indirect triggering of the intrinsic apoptotic pathway, impairment of the intrinsic pathway is associated with therapy failure. Targeting of the death receptors, however, enables induction of apoptosis even in the chemotherapy resistant cancer cells. TRAIL is a death ligand belonging to the TNFα superfamily that specifically kills tumor cells while sparing healthy tissues. Much enthusiasm has been generated for TRAIL as a highly promising targeted anti-cancer agent. However, many primary tumors have been shown to be TRAIL resistant. In attempt to overcome such an intrinsic TRAIL resistance a wide array of agents have been shown to sensitize tumor cells to TRAIL. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. In this study we analyzed the sensitivity of diverse hematologic malignancies to TRAIL-induced apoptosis and measured the...
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Charakterizace TRAILem indukované, receptor-specifické signalizace v nádorových buňkách.
Peterka, Martin ; Anděra, Ladislav (advisor) ; Rohlena, Jakub (referee)
TNF-related apoptosis-inducing ligand (TRAIL) is a member of TNF family expressed mainly by hematopoietic cells. TRAIL brought significant attention mainly for its ability to trigger apoptosis in a number of cancer cells. In addition to apoptosis, TRAIL can induce several other signaling pathways such as activation of MAP kinases or canonical NF-B signaling. Human TRAIL can bind to five receptors but only two of them (death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5) can trigger TRAIL-mediated apoptotic and non-apoptotic signaling in target cells. Both receptors are ubiquitously expressed on normal and cancer cells, but the relative contribution of DR4 and DR5 to TRAIL-induced signaling is not well known. Using DR4/DR5-specific variants of TRAIL, we examined how individual receptor contributes to the induction of apoptosis and NF-B, JNK, p38, ERK1/2 and TAK1 signaling pathways in selected colorectal cells. We found that in DLD-1 cells, apoptosis and activation of JNKs are mainly mediated by DR4-selective ligand. In TRAIL-resistant HT-29 cells, we show that though DISC formation and activation of caspase-8 proceeds mainly via DR4-specific signaling, activation of NF-B pathway is mainly triggered by DR5 selective ligand. In other cells and analyzed signaling pathways both receptor-specific ligands triggered very...
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Ancient Trails in the area of the Otava river
Pitín, Michal ; Charvát, Petr (advisor) ; Meduna, Petr (referee)
TITLE: Ancient trails in the area of the Otava River AUTHOR: Michal Pitín DEPARTMENT: History and History Didactics Department SUPERVISOR: prof. PhDr. Petr Charvát, DrSc. ABSTRACT: The diploma thesis focuses on one of the modern science called stibology which concentrates on the human past and human's relation to the landscape and its settlement and mainly passing trails through the landscape. The aim of this work is to study settlement and possible passing of the communications through the landscape in the area of the Otava River since the Celtic settlement, but mainly at the Early and the High Middle Ages. The work focuses on realisation of the stibologic knowledge in the area of the town Strakonice at the period of the Early Middle Ages. It also shows that the theme of the old trails is missed out of education and its possible usage in the subject called The Heritage Education in School Education Programmes. The work also includes analysis of the cartographic materials and their information about trails passing the landscape. The work is completed by the picture supplement from the area of the Otava River and cartographic materials. KEYWORDS: trail, way, settlement, area of the Otava River
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Apoptosis of tumor cells : role of TRAIL and caspase 10
Truxová, Iva ; Živný, Jan (advisor) ; Anděra, Ladislav (referee)
One of the key features of cancer cells is the ability to escape programmed cell death (apoptosis). As a mechanism of apoptosis inactivation in cancer cells, somatic mutations of pro-apoptotic genes have been reported in many cancers. Caspase 10 is an initiator caspase whose physiological function remains poorly understood. Also the ability of caspase 10 to substitute for caspase 8 in the death receptors apoptotic pathway is still controversial. However, the fact that some of the mutations found in CASP10 gene was associated with apoptosis defects (79, 81) suggest that caspase 10 could be also important in apoptosis initiation. In our lab, there was found a heterozygous mutation in CASP10 gene of Jurkat (human T-acute lymphoblastic leukemia) clone resistant to TRAIL (J-TR1). This mutation influence the amino acid composition close to the active site of the enzyme. The aim of this thesis was to confirm the mutation by ARMS-PCR and to determine if an overexpression of normal (unmutated) or mutated caspase 10 D in TRAIL sensitive and/or TRAIL resistant Jurkat cells (J-WT and/or J-TR1) will influence TRAIL induced apoptosis. Mutation was confirmed. We created J-WT and J-TR1 stable clones transfected by vector with unmutated or mutated CASP10 D (CASP10 D WT or CASP10 D MUT). CASP10 D MUT overexpression in J-WT...
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Engineering design of a fullsuspension mountain bike frame
Zvozil, Ondrej ; Lošák, Petr (referee) ; Březina, Lukáš (advisor)
The aim of this bachelor thesis is designing of a full-suspension mountain bike frame. At the beginning of the thesis mountain bikes are divided into categories, the function of a shock absorber is described and issues of bike kinematics and related characteristics are clarified. The thesis also describes properties of the most used materials for bike frames manufacturing. Subsequently, the most common systems of rear wheel linkage are analysed. Next, the requirements for own design are identified in terms of geometry, construction, kinematics and a creation of its 3D model in SolidWorks software. The characteristics of designed frame are analysed by specific software Linkage X3. Then a static analysis in Ansys software is made in order to select bearings for individual pivots. The final part of the thesis is dedicated to visualisation of designed frame.
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Architecture in landscape - Winery
Grätzová, Dita ; Herzanová, Pavla (referee) ; Urbášková, Hana (advisor)
Proposes two buildings located at the top of the raised part of the resolved region. One building is positioned parallel to the access road. The shape of the building recalls the long kubus facing in the direction of the driveway and the building of accommodation is designed perpendicular to the object. Both objects are embedded into the basement terrain. Accommodation building is situated on the south, bright and warm side with a beautiful view.
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Analysis of the offer of sightseeing tours in a selected city in the Czech Republic (Česká Skalice)
Borůvková, Alžběta ; Jarolímková, Liběna (advisor) ; Bakos, Tomáš (referee)
The bachelor's thesis deals with the analysis of tourism and sightseeing tours in the town Česká Skalice. The theoretical part defines basic notions and the town potential in the field of tourism (its characteristics, history and tourist attractions of the town). The practical part gives information about institutions acting in tourism in Česká Skalice and evaluates their projects which are involved in walking tours of the town. It also includes analysis of visitors to the town, the services provided, the promotional materials and the evaluation of main walking routes (especially heritage trail of "Grandmother's valley and "City Walk"). Based on results of analysis the town potential and its utilisation is evaluated with regard to the structure of demand and a focus on suggestions and recommendations for improvement of current situation of walking routes in Česká Skalice.
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