|
|
Low-temperature biogas purification
Hřebíček, Martin ; Fiedler, Jan (referee) ; Pospíšil, Jiří (advisor)
The aim of this thesis is the issue of low-temperature cleaning of biogas. He briefly acquaint the reader with the technology of production of biogas and its possible use. Provide requirements for low-temperature treatment and purification of biogas to the needs of downstream equipment. Provide an overview of the possibilities of suitable production systems applicable cold. Develop your own design facilities for low-temperature treatment of biogas
|
|
|
Meter run for servo-actuator test
Hřebíček, Martin ; Bogdálek, Jan (referee) ; Novotný, Zdeněk (advisor)
The aim of this bachelor´s thesis is projecting a metering and regulating run for servo-actuator test, choosing a suitable choice of the soft and accurate regulation of pulsing oil and projecting a suitable armature for holding an constant pressure of an overflow oil. Further to project a suitable kind of pump for supply of operative oil. To verify by calculation of an fitness of a choice of a given armature and choose these elements, which are accessible on Czech market. A projecting of a suitable machine for a detection of lifting of a spindle and a pressure of an impulsive oil to be able to analyze a results and electronically note on a PC output. To draw up a description of process soft measuring and correction of a given servo-actuator.
|
|
| |
|
|
Molecular genetic analysis in Niemann-Pick type C disease
Marešová, Ivona ; Dvořáková, Lenka (advisor) ; Hřebíček, Martin (referee)
Niemann-Pick disease type C (NPC) is a rare, severe disease with autosomal recessive inheritance. Disease is caused by pathogenic mutations located in genes NPC1/NPC2. These genes encode lysosomal non enzymatic NPC1/NPC2 proteins that are part of lipid transport. As a result of malfunction of these proteins intracellular accumulation of lipids occurs, in particular free cholesterol and glycolipids. Causal therapy is currently still unsatisfactory therefore new therapies are evolved. However these therapies depend on whether the patient cells contain at least residual amount of transcript NPC1 gene. In a group of patiens, for which a fibroblast culture was available, I analyzed the effect of pathogenic mutations on the expression level of the transcript. Results showed that for all pathogenic mutations transcript level is low, but detectable. Moreover, I characterized the structure of the NPC1 gene promoter. By sequence analysis I found polymorphisms rs8099071, rs28403610, rs2981422, rs1652354, rs1788774, rs1788772 in promoter. On the basis of the composition of polymorphisms in individual patiens, I estimate six different haplotypes. I performed mutation analysis in DNA of recently diagnosed patient. I found only one pathogenic mutation p.I1061T (c.3182T> C) in the NPC1 gene. Therefore I tested...
|
|
|
Optimization of newborn screening for cystic fibrosis in the Czech Republic
Krulišová, Veronika ; Macek, Milan (advisor) ; Vrtěl, Radek (referee) ; Hřebíček, Martin (referee)
Newborn screening for cystic fibrosis allows diagnosing patients with cystic fibrosis during asymptomatic stage of their disease or when the symptoms had not fully developed. Due to early diagnosis, patients with cystic fibrosis have the possibility to be treated prior to the occurrence of irreversible changes in the relevant organs, which leads to significantly improved quality of life and patient survival. Commented version of the doctoral thesis presents issues concerning the selection of a suitable newborn screening programme for cystic fibrosis in neonates born in the Czech Republic and establishes requirements for particular analytical and molecular genetics tiers in the tested screening schemes. The aim of this thesis is to nominate newborn screening protocol for cystic fibrosis that leads to optimal parameters in terms of its high sensitivity and specificity, including acceptable costs in the conditions of the Czech Republic health care system. Powered by TCPDF (www.tcpdf.org)
|
|
| |
|
|
Recombination between the gene and pseudogene for glucocerebrosidase as a mechanism of mutation generation in Gaucher disease
Peková, Barbora ; Hřebíček, Martin (advisor) ; Schierová, Michaela (referee)
Gaucher disease is an autosomal recessive disorder caused by the deficiency of β-glucocerebrosidase. Some Gaucher patients carry in their β-glucocerebrosidase genes complex mutations which apparently arose by a recombination with the non-functional β-glucocerebrosidase pseudogene. Recombination between genes and their corresponding pseudogenes plays a role in the development of other hereditary human diseases. Mutant alleles formed in male and female meiosis are a source of these variations in the gene pool. The study of frequency and scope of recombination events in human disease-associated genes in the gametes is of importance for evaluation of the disease burden in the population. The evaluation of the scope of single recombination events in the β-glucocerebrosidase gene in human gametes is technically challenging. Novel technologies such as next-generation sequencing, nanopore sequencing or droplet digital PCR may have advantages over previously used techniques in this application. Key words: recombination, gene conversion, pseudogene, β-glucocerebrosidase, complex alleles, Gaucher disease
|
|
|
Biochemical and molecular studies of the congenital disorders of glycosylation
Ondrušková, Nina ; Hansíková, Hana (advisor) ; Stiborová, Marie (referee) ; Hřebíček, Martin (referee)
Congenital disorders of glycosylation (CDG) represent a rapidly growing group of rare inherited metabolic diseases with estimated prevalence as high as 1:20 000, which are caused by genetic defects that impair the process of glycosylation, i.e. the enzymatic addition of a specific saccharide structure onto a protein or lipid backbone. Due to non-specificity and variability of clinical symptoms in the patients, the medical diagnosis of CDG remains extremely challenging and significantly relies on accurate biochemical and genetic analyses. The overall goal of the present dissertation thesis was to study CDG at the biochemical and molecular genetic level in the context of the Czech and Slovak Republic, which involved three specific aims: A.) to introduce and optimize laboratory screening methods for CDG detection in a group of clinically suspected patients, B.) to determine the corresponding genetic defect in the positive patients selected via CDG screening and to study the pathobiochemical aspects of specific CDG types at the cellular level, and C.) to analyze glycosylation disturbances of non- CDG etiology. Contributions of this work include optimization of isoelectric focusing of apolipoprotein C-III (ApoC-III) as a screening method for O-glycosylation abnormalities, as well as the description of...
|
|
|
Molecular genetic and biochemical studies of selected inherited metabolic disorders, development and applications of new methods
Mušálková, Dita ; Hřebíček, Martin (advisor) ; Adam, Tomáš (referee) ; Macek, Milan (referee)
Inherited metabolic disorders (IMD) form a diverse group of several hundred different diseases with a relatively high cumulative incidence (stated up to 1:600). They are associated with accumulation of the substrates and lack of the products in specific metabolic pathways, which is caused by deficiency of the enzyme or its activator, or dysfunction of the transport protein. However, the underlying cause is at the DNA level. The grounds for different phenotype manifestation in patients with the same genotype are often not known. During my work at the Institute of Inherited Metabolic Disorders, I designed several new methods for the research of IMD and applied them in the patients and their families. I created procedures for the isolation of lysosomal membranes that are used for the research of lysosomal storage disorders and general properties of lysosomes. Next, I introduced several novel assays for determination of the X-inactivation ratio, which led to a significant increase of informative women. Nowadays, we use these methods in heterozygous women with X-linked diseases in order to study the influence of X-inactivation on the manifestation of the diseases. The cases of a girl with mucopolysaccharidosis type II, a girl with OTC deficiency and a family with the mutation in HPRT1 gene are described...
|
|
|
Characterization of promoter regions of HGSNAT and GBA genes, and a contribution to the study of pathogenesis of MPS IIIC and Gaucher disease
Richtrová, Eva ; Hřebíček, Martin (advisor) ; Macek, Milan (referee) ; Adam, Tomáš (referee)
Pathogenesis of mucopolysaccharidosis type IIIC (MPS IIIC) and Gaucher disease has not been yet fully clarified, and the causes of phenotypical variability between the patients with the same genotype in Gaucher disease remain obscure. Because the variants in the regulatory regions of genes can cause phenotypical differences mentioned above, I have studied promoter regions of HGSNAT and GBA genes mutated in these lysosomal disorders. I have shown that there is an alternative promoter of GBA (P2). Additional studies were aimed to elucidate possible physiological functions of P2, and its possible role in the pathogenesis of Gaucher disease. I have found that P2 is not tissue specific, and that its variants do not influence the variability of phenotype in Gaucher patients with the same genotype. P2 is used differentially neither during the differentiation of monocytes to macrophages nor in macrophages from controls and Gaucher patients, in whom there is a prominent storage only in cells of macrophage origin. We have thus not found any changes that would suggest a role for P2 in the pathogenesis of Gaucher disease. I have characterized the promoter region of HGSNAT and shown that the binding of Sp1 transcription factor is important for its expression. Sequence variants found in HGSNAT promoter in...
|
guest ::
RSS feed.