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Multifunctional protein CTCF and its role in regulation of gene expression
Pokorná, Linda ; Vacík, Tomáš (advisor) ; Vopálenský, Václav (referee)
CTCF is a ubiquitously expressed nuclear protein that binds to DNA through its central zinc finger domain. Thousands of CTCF binding sites have been identified throughout the human genome at gene promoters, in intergenic regions or in non-coding sequences. CTCF can function either as a positive or as a negative regulator of gene expression and is also involved in creating and maintaining long-range chromosomal interactions. Various developmentally important genes have been shown to be regulated by CTCF and its malfunction is frequently associated with developmental defects or diseases. CTCF undergoes various posttranslational modifications such as phosphorylation or SUMOylation which also affect its function in the regulation of gene expression. Keywords: CTCF, three dimensional genome, cohesin, regulation of gene expression, insulation, HOX genes
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Molecular subgroups of medulloblastoma: the current consensus
Jarošová, Šárka ; Zíková, Martina (advisor) ; Nedvědová, Tereza (referee)
Medulloblastoma is the most common malignant brain tumor in children. In recent years, there has been a steady improvement in understanding of genetic and molecular heterogeneity of this tumor, that has led to better prognosis and improved targeted therapies. This thesis summarizes recent advances in molecular sub-grouping, and the associated gene mutation and copy number variations in medulloblastoma.
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The expression of TP53 gene at the mRNA level in patients with myelodysplastic syndrome
Šeborová, Karolína ; Beličková, Monika (advisor) ; Španielová, Hana (referee)
Myelodysplastic syndrome (MDS) is a heterogeneous group of diseases characterized by ineffective hematopoiesis which is caused by damage of differentiation of pluripotent haematopoietic stem cells. TP53 gene mutations are identified approximately in 10% of MDS and represent a negative prognostic factor. Altered TP53 gene expression may have similar effect as the mutation. Mutations or deregulated expression of this gene have an impact on many cellular processes including apoptosis, DNA repair, cell growth and angiogenesis. In this work, the expression mRNA levels of genes involved in p53 signalling pathway were studied in CD34+ pluripotent haematopoietic cells from bone marrow of patients with low- risk MDS. MDS patients showed increased expression of genes involved in apoptosis induction, regulation of cell cycle and DNA repair (BAX, BBC3, CCNE1, CDC25A, CDKN1A, FAS, GADD45A) as compared to healthy subjects. The patients with TP53 mutation had decreased expression of apoptotic genes (BAX, PIDD, TRAF2) and increased gene expression of apoptotic inhibitor (BCL2A1), indicating a reduced activity of apoptotic pathways and that way the pathological cell clone may gain a growth advantage. Deregulation of 21 genes (BAX, BBC3, EGR1, KAT2B, MDM2 etc.) was observed in patients with del (5q) compared to...
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Production and secretion of virulence factors in Bordetella pertussis
Držmíšek, Jakub ; Večerek, Branislav (advisor) ; Petráčková, Denisa (referee)
Bordetella pertussis is a strictly human pathogen and causative agent of infectious respiratory disease called whooping cough. In order to establish successful infection and colonization of the host, B. pertussis uses a broad spectrum of virulence factors such as adhesins (filamentous hemagglutinin, pertactin, and fimbriae) and toxins (adenylate cyclase and pertussis toxins). In addition, the type 3 secretion system (T3SS) was also found in the genus Bordetella. In connection to our previous characterisation of B. pertussis strain lacking the gene encoding RNA chaperone Hfq (Δhfq), which proved that Hfq is required for T3SS functionality, the recombinant T3SS proteins BopB, BopD, BopC and BopN were purified to homogeneity. Next, the specific antibodies were obtained using purified recombinant proteins in order to study the production of the T3SS components in B. pertussis. Using refined anti- BopC antibodies it was for the first time shown that laboratory-adapted B. pertussis strain secretes BopC protein into medium. The recombinant translocators BopB and BopD were also used to examine their pore-forming activity using planar black lipid membranes. Based on the characterisation of hfq deletion mutant, having impaired production of membrane proteins when compared to the wild type, mass spectrometry...
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Effect of selected endocrine disruptors on the male mouse reproductive system in vivo
Žatecká, Eva ; Pěknicová, Jana (advisor) ; Kubelka, Michal (referee) ; Kaňka, Jiří (referee)
In our environment there are many compounds which can negatively influence humans and wildlife. Every day, a vast number of environmental pollutants are released into our environment and there is no way to avoid their exposure. Some of these compounds can even mimic endogenous hormones and interfere with our endocrine system (so called endocrine disruptors), which is the key regulatory system controlling almost all physiological processes in human and animal bodies. Also the reproductive system is largely regulated by various hormones, and their proper function is crucial for gamete formation, fertilization and embryo development. Environmental pollutants are therefore considered as one of the possible causes of increased infertility in human population. This prompted us to study the effect of two endocrine disruptors (tetrabromobisphenol A - TBBPA, and zearalenone - ZEA) on the male mouse reproductive system in vivo. According to our results, TBBPA is able to induce apoptosis as well as changes in the expression of selected testicular genes and sperm protamination. Our results also suggest that permanent exposure to TBBPA slightly enhances its effect in the next generation, depending on whether the parents have been affected or not. We hypothesized that differential protamination of the sperm DNA...
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Normality test of the gene expression data
Shokirov, Bobosharif ; Klebanov, Lev (advisor) ; Hušková, Marie (referee) ; Kalina, Jan (referee)
This thesis deals with a test of normality of gene expressions data. Based on characterization theorems of the normal distribution, the test of normality is replaced by a test of spherical uniformity. Due to strong correlations between the gene expression data, the normality test is conducted with $\delta$ sequences. A new characterization theorem of the normal distribution is proven. Based on that, the normality test is conducted using Kolmogorov's test statistic. The obtained characterization results for the normal distribution are extended to the complete type of distributions and based on that, a test is conducted to verify whether the distributions of the two data sets of the gene expressions belong to the same type. Powered by TCPDF (www.tcpdf.org)
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Study of effects of prolonged administration of emtricitabine on expression of ABC efflux transporters in maternal and fetal organs
Havlová, Ivana ; Červený, Lukáš (advisor) ; Hofman, Jakub (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Ivana Havlová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Study of effects of prolonged administration of emtricitabine on expression of ABC efflux transporters in maternal and fetal organs The aim of this thesis was to evaluate the effect of chronic administration of antiretroviral substance emtricitabine (FTC) on expression of drug efflux ABC-binding cassette (ABC) transporters in the placenta, maternal and fetal organs (brain, liver, kidney, small intestine) of pregnant rats. We focused on two most important representatives of drug efflux ABC transporters, P-glycoprotein (MDR1) and Breast Cancer Resistance Protein (BCRP). Knowledge of FTC effects on gene expression of these transporters is crucial especially when using FTC in combination therapy, known as Highly Active Antiretroviral Therapy (HAART). Changes in MDR1/BCRP expression may lead to significantly altered pharmacokinetics of concomitantly administered drugs. First, bioavailability was analyzed. AUC of FTC (3,5 mg/kg) following i.m. administration was comparable to that one after i.v. administration allowing us to use i.m. application as a route of FTC administration to rats. Subsequently,...
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Gene expression of specific parts of CNS in a rat model for transgenerational transmission of drug addiction.
Radilová, Kateřina ; Černá, Marie (advisor) ; Rothová, Olga (referee)
Methamphetamine (MA) is a drug often abused by drug-addicted women and also is the mostly used drug in the Czech Republic. This drug crosses the placental and hematoencephalic barriers easily and therefore it can negatively affect not just mother herself, but also the development of the fetus. Even though there have been several published studies evincive negative effects of MA to posterity of drug-addicted mothers, the most critical term during pregnancy for the fetus remains unknown. In this study are examined CNS structures, which are directly influenced by methamphetamine action. Their function may lead to drug addiction through pleasurable feelings, such as reward feeling evoking. In the next chapter are analysed neurotransmitters and their transporters, which are related to methamphetamine effects. Studying their structure, localization or development during life may help to bring near the drug functioning in different life periods. Methamphetamine itself and its effects are closer described in the last part of this study. The problem of methamphetamine exposed fetus is outlined there - prenatal and postnatal so far known differences, but also sex differences in methamphetamine pharma- cokinetics.
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