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Synthesis and characterization of new insulin derivatives with altered selectivity for insulin and IGF-1 receptors.
Halamová, Tereza ; Jiráček, Jiří (advisor) ; Dračínská, Helena (referee)
Insulin receptor (IR) exists in two isoforms (IR-A and IR-B), which differ in the tissue distribution and probably also in their function, i.e. in their response to insulin binding. It is supposed that IR-A activates mainly mitogenic processes and that IR-B triggers mainly metabolic effects resulting in the uptake of glucose by muscle and fat cells. Insulin can also weakly bind to the receptor for IGF-1 (IGF-1R), a growth factor involved in the regulation of growth and development. Insulin derivatives selectively binding only to one of the receptors would be interesting for the study of the receptors but also potentially for the treatment of diseases such as diabetes or cancer. Here we used our experience in the structure-activity studies of insulin for the design, synthesis and biological characterization of 4 new insulin derivatives in order to modify their selectivity towards the individual receptors. We systematically modified insulin by amidation of the C-terminus of its B-chain or by prolongation of the B-chain by 1-3 carboxyamidated glycine residues. Binding affinities of all new analogues for IR-A and IR-B were determined and for some of the analogues binding affinities for IGF-1R as well. Finally, abilities of analogues to activate autophosphorylation of intracellular subunits of IR-A and...
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Structural characterization of human Aichi virus RNA replication
Dubánková, Anna ; Bouřa, Evžen (advisor) ; Teisinger, Jan (referee)
Viral RNA dependent RNA polymerases (RdRps) are enzymes which enable RNA viruses to replicate their genome and to prepare mRNA for translation of viral proteins. Due to its relative evolutionary conservation RdRps are good targets for drug design. In this work we present a structure of the RdRp (3Dpol ) of Aichi virus, which has not been solved yet. Aichi virus is a human pathogen that causes gastroenteritis. Aichi virus is also used as a model organism for studying cognate viruses which virulence is more dangerous, for example: Rhinovirus, Hepatitis A virus, SARS virus, hepatitis C virus, yellow fever, and West-Nile virus. In addition to structural studies of Aichi virus 3Dpol we also tested a previously published hypothesis that, 3Dpol is recruited to the membrane through phosphatidylinositol 4 phosphate (PI4P) - an important regulatory lipid. Membranes highly enriched in PI4P are formed in cells infected by single stranded positive sense RNA (plus ssRNA) viruses. Finally we tested the influence of ribonucleotides on the 3Dpol protein stability. (In Czech)
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New analogues of prolactin-releasing peptide with prolonged effect on food intake
Tichá, Anežka ; Ryšlavá, Helena (advisor) ; Konvalinka, Jan (referee)
Prolactin-releasing peptide (PrRP) is a member of the family of RF-amide peptides. These peptides have typical C-terminal sequence -Arg-Phe-NH2 and similar biological effects. PrRP was discovered as an endogenous ligand of an orphan receptor GPR10 while searching for a factor responsible for a prolactin secretion. This effect was not later confirmed and nowadays, PrRP is mainly considered as an anorexigenic peptide. This is supported by a fact that PrRP and GPR10 deficient mice suffer from hyperphagia and late-onset obesity. Besides GPR10, PrRP is bound to NPFF2 receptor whose endogenous ligand is neuropeptide FF (NPFF). In this study, the PrRP's analogues modified at the N-terminus with fatty acids of different lenghts were tested in vitro on binding and activation MAPK/ERK1/2 signalling pathway. In in vivo experiments on food intake, the central anorexigenic effects of lipidized PrRP-analogues were tested provided their crossing blood brain barrier. Binding studies showed that all analogues bound to rat pituitary RC-4B/C cells with high affinity, analogues containing fatty acid with Ki of one order of magnitude lower than native PrRP. High affinity was also confirmed for binding to cells overexpressing GPR10 receptor and cell membranes with overexpressed NPFF2 receptor. All tested analogues...
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Production of adjustable in-line skates
Sulovský, Marek ; Kandus, Bohumil (referee) ; Žák, Ladislav (advisor)
The thesis is focused on design of adjustable in-line skates. Using this design, users can set its length to their shoes. Adjustable length can cover up to three shoe length sizes. Traditional wood and steel designs are now almost fully replaced by plastic. Plastics are modern materials that have a lot of useful features. They have lower density than steel, while maintaining acceptable stiffness. Major part of the design can be manufactured using plastic injection molding and wheels are made by casting technology. Remaining parts include standardized stainless steel bolts with threaded inserts and aluminum rivets. Major features, setting this design apart include stable 3-wheel platform, fast Velcro fixing and built-in hex driver.
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Sevices WCF
ENINGER, Boris
The main goal of this thesis is to acquaint readers with the modern technology Windows Communication Foundation. People who are interested in it can learn via several tutorial lessons how to create and set WCF services. In addition to it, the work describes some techniques of the security service and gives the basic look into hosting area. The problems are explained through visual aids. The sample of audiovisual presentation is available.
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Functions of French articles as a part of the text in comparison with the means of Czech language
KUNCOVÁ, Martina
The aim of this work is to analyse functions of French articles as a part of the text in comparison with the means of Czech language. The theoretical part defines determinants as a word class in French language as well as its function in conjunction with nominal group, ways of linking in the text and structure of the text. All of this is based on the works of French and Czech authors concerned in the question of articles. The comparative part was done on the text accessible in both languages. The texts were analysed in the same way and then they studied all the questions from the theoretical part i.e. functions of the article in the text and its language means in Czech. The results were put into two tables. First table presents Czech equivalents of nominal group. Second table presents Czech equivalents of the way of linking in the text.
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