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DNA vaccination
Plachý, Jiří
We have evalueted the protective activity of v-src-derived DNA vaccines against growth of v-src-induced tumors in congenic chicken lines.
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The role of ATM in breast cancer
Soukupová, Jana ; Pohlreich, Petr (advisor) ; Souček, Pavel (referee) ; Foretová, Lenka (referee)
Incidence of breast cancer is continuously increasing in the Czech Republic. Tumor development is a result of gene alterations'accumulation, particulary associated with genes involved in regulation of cell growth and division. Hereditary carcinomas account for approximately 5-10% of all breast tumors and in 60-80% cases are caused by a germline mutation in the major predisposition genes BRCA1 and BRCA2. Nevertheless, other genes, mostly of lower penetrance, may play a role in breast pathogenesis such as the ATM tumor-suppressor gene. ATM is the apex of the repair pathway of DSB. This protein kinase activates through phosphorylation of its substrates cell cycle checkpoints, which leads either to the delay of the cell cycle progression until DSB are repaired or to the promotion of apoptosis. To sum up, the ATM gene seems to have a role in breast cancer development in a minority of the high-risk families in our population which is significantly lower compared to BRCA1/2 and it also seems to be involved in pathogenesis of sporadic breast cancer. Despite the ATM gene's length, we do not perform the preventive screening of this gene in breast cancer high-risk families. Nevertheless, we offer the molecular diagnostics of ATM to ataxia telangiectasia patients.
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Emergent properties of the G1/S network
Dražková, Jana ; Tomášek, Petr (referee) ; Palumbo,, Pasquale (advisor)
Tato práce se zabývá buněčným cyklem kvasinky Saccgaromyces cerevisiae. Oblastí našeho zájmu je přechod mezi G1 a S fází, kde je naším cílem identifikovat velikosti buňky v době počátku DNA replikace. Nejprve se věnujeme nedávno publikovanému matematickému modelu, který popisuje mechanismy vedoucí k S fázi. Práce poskytuje detailní popis tohoto modelu, stejně jako časový průběh některých důležitých proteinů či jejich sloučenin. Dále se zabýváme pravděpodobnostním modelem aktivace replikačních počátků DNA. Nově uvažujeme vliv šíření DNA replikace mezi sousedícími počátky a analyzujeme jeho důsledky. Poskytujeme také senzitivní analýzu kritické velikosti buňky vzhledem ke konstantám popisujícím dynamiku reakcí v modelu G1/S přechodu.
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Účinky xenobiotik na oxidační stres, metabolizmus lipidů, integritu DNA a životaschopnost lidských buněk a rybích spermií in vitro
LINHARTOVÁ, Pavla
Pollution of the aquatic environment by inorganic and organic chemicals is a major factor posing a serious threat to the survival of aquatic organisms including fish. In addition balancing risks and benefits of fish consumption is nowadays an intensively discussed public health topic. Spermatozoa of almost all fish species are released into water environment where they can be directly exposed to various compounds, such as xenobiotics including toxic metals, prior to fertilization. In addition, exposure of parental adults to various xenobiotics may affect gamete quality, which may subsequently reduce fertilization success. On the other hand the advantages of eating fish are well-known, not only in the point that fish is a healthy source of protein and other nutrients, but eating contaminated fish may also confer various health benefits. Research over the past few decades has shown that the nutrients and particularly the n-3 fatty acids (FA) found in fish and seafood, are for examples protective against cardiac diseases and have a positive impact on brain development. The thesis provides a focus on two different cell model types. Firstly, human hepatocellular cells (Hep G2, ATCC) were used as in vitro tool for studying the effect of the intake of cadmium (Cd2+) contaminated fish on cytotoxicity, oxidative stress and fatty acid and phospholipid class compositions. Secondly, spermatozoa of one threatened species of fish, sterlet (Acipenser ruthenus) were used as in vitro model for studying effect of potentially hazardous xenobiotic compounds' occurring in open waters. Sperm from sterlet were exposed for 2h to environmentally relevant concentrations of DQ (0-150
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Genetic aspects of posterior polymorphous corneal dystrophy
Lišková, Petra ; Filipec, Martin (advisor) ; Čejková, Jitka (referee) ; Slavčev, Antonij (referee)
Posterior polymorphous corneal dystrophy (PPCD) is regarded as a rare autosomal dominant disorder, affecting both the corneal endothelium and Descemet's membrane. However, in the Czech Republic, PPCD is one of the most prevalent corneal dystrophies. The first phase of the project involved the phenotyping of Czech patients with PPCD and the collection of samples for further genetic analysis. The second phase involved determination of the PPCD chromosomal locus in two large families by using linkage analysis followed by positional candidate gene screening. In total 20 PPCD families with two or more affected members were ascertained. PPCD was diagnosed in 104 individuals, of these 82 provided peripheral blood sample for DNA isolation. Linkage analysis was performed on 52 members in two families that lead to the delineation of the PPCD locus to a 2.7 cM interval on chromosome 20p11.2, between flanking markers D20S48 and D20S139. This resulted in the exclusion of VSX1, which had previously been associated with PPCD, as the disease-causing gene in both families. Five positional candidate genes within the 2.7 cM genetic interval were screened for mutations in two probands from these families by the direct sequencing of the coding regions and no pathogenic mutations were identified. In summary, refinement of the...
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Detection of VPS13B gene mutation responsible for trapped neutrophil syndrome in selected dog breeds used for assistance activities
Zemanová, Lucie ; Vejl, Pavel (advisor) ; Melounová, Martina (referee)
This bachelor thesis Detection of VPS13B gene mutation responsible for Trapped neutrophil syndrome in selected dog breeds used for assistance activities starts with theoretical part and continue with experimental part, which had done in Department of genetics and breeding.
The theoretical part is focused on Trapped neutrophil syndrome and Cohen syndrome. Both of theese syndromes are caused by mutation of same gene and this is the reason, why a dog is a suitable genetic model for human disease research. Based on the theoretical part is obvious that Trapped neutrophil syndrome is a autosomal recessive genetic disease and is caused by deletion of 4 bases (GTTT) on 13th chromosome in 19th exon. This mutation is only in border collie breed. The Trapped neutrophil syndrome causes very serious problems and for individuals theese problems may be letal. If they survive, they have a very poor quality life. They have diarrhoea, pyrexia, vomite and have a typical facial ferret-like snout.
The experimental part is focused on isolation DNA from buccal mucosa of border collie breed, golden retriever, labrador retriever and Nova Scotia duck tolling retriever, than it is focused on design PCR markers and sequencing PCR amplicons.
The experimental results had confirmed hypothesis that the causal mutation is affected by pedigree and it is easy to identificate it by sequencing PCR amplicons.
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The influence of the epigallokatechin gallate, elagic acid and curcumin on the cytotoxic effect of mutagens.
Tlučhořová, Drahomíra ; Hochmann, Jiří (advisor) ; Polívková, Zdeňka (referee)
Naturally occurring phenols epigallocatechin gallate (EGCG), ellagic acid and curcumin exhibit antioxidant, antimutagenic and anticarcinogenic activity in a lot of in vivo and in vitro studies. In our study we used comet assay test to determine if these compounds are capable to affect DNA damage of AA8 and HepG2 cells caused by 2-amino-3-methylimidazo [4,5-f] quinoline (IQ), N-nitroso-N-methylurea (MNU) and UVC radiation. Results should say if comet assay test is an appropriate method for antimutagenity tests. We were interested if compounds, which are able to moderate effects of mutagens, would also affect their cytotoxicity. Except MNU and UVC radiation we used also hydrogen peroxide as a reference mutagen. In comet assay curcumin was not able to protect against MNU induced DNA damage sufficiently. However, ellagic acid effectively reduced mutagenic effect of MNU. EGCG decreased the level of DNA breaks induced by IQ and UVC radiation and affected both DNA damage induction and repair of cells incubated with MNU. We chose only EGCG for cytotoxicity tests because it showed the greatest antimutagenity. EGCG increased the number of formed colonies of cells treated with hydrogen peroxide, likely to its antioxidant properties. However EGCG did not decrease cytotoxicity of MNU and UVC radiation and the...
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