National Repository of Grey Literature 26 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
The expression of miRNA in HPV-associated and HPV-independent head and neck tumors
Vojtěchová, Zuzana
Head and neck cancers represent a group of tumors with two different etiologies. The first type is associated with the viral HPV infection, the second one is virus-independent and it is associated with smoking and alcohol consumption as two main risk factors. Numerous studies show that HPV-positive tumors are more frequent in younger patients, as well as that the prognosis and overall survival of these patients is remarkably better. Therefore, the modification of the treatment is considered. For this, however, specific, sensitive and clinically relevant biomarkers for accurate identification of tumor etiology is needed. Suitable candidates for such biomarkers are miRNAs, small non-coding regulatory molecules stable in archived samples, that have been shown as differentially expressed in human cancers and the expression pattern seems specific for tumors of different origin. The submitted thesis focuses on miRNA profiling in HPV-positive and HPV-negative tonsillar tumors and cervical carcinomas with the aim to find out the differences between regulation of important carcinogenetic pathways of tumors of viral and non-viral etiology. Our data have shown very large heterogeneity of the miRNA expression profiles of these tumors. Despite the well characterized and uniform samples collection, we have found...
The expression of miRNA in HPV-associated and HPV-independent head and neck tumors
Vojtěchová, Zuzana ; Tachezy, Ruth (advisor) ; Hejnar, Jiří (referee) ; Slabý, Ondřej (referee)
Head and neck cancers represent a group of tumors with two different etiologies. The first type is associated with the viral HPV infection, the second one is virus-independent and it is associated with smoking and alcohol consumption as two main risk factors. Numerous studies show that HPV-positive tumors are more frequent in younger patients, as well as that the prognosis and overall survival of these patients is remarkably better. Therefore, the modification of the treatment is considered. For this, however, specific, sensitive and clinically relevant biomarkers for accurate identification of tumor etiology is needed. Suitable candidates for such biomarkers are miRNAs, small non-coding regulatory molecules stable in archived samples, that have been shown as differentially expressed in human cancers and the expression pattern seems specific for tumors of different origin. The submitted thesis focuses on miRNA profiling in HPV-positive and HPV-negative tonsillar tumors and cervical carcinomas with the aim to find out the differences between regulation of important carcinogenetic pathways of tumors of viral and non-viral etiology. Our data have shown very large heterogeneity of the miRNA expression profiles of these tumors. Despite the well characterized and uniform samples collection, we have found...
miRNA complexes with the target RNA sequence
Homolka, Radim ; Štěpánek, Josef (advisor) ; Římal, Václav (referee)
miRNAs are short non-coding RNA molecules which play role in post-transcriptional regulation of gene expression. Thus, miRNAs are related to a variety of physiological processes and diseases, e.g. some tumours or viral infections. In this diploma thesis we studied temperature-induced dissociation of complexes that simulated pairing of miRNA with target mRNA. For these purposes we used UV absorption spectroscopy and Raman spectroscopy. Measured spectra were then treated by means of a factor analysis. The aim of the thesis was to determine thermodynamic parameters of the complexes dissociation and to clarify how inner loops and bulges affect the stability of oligonucleotide duplexes. Also, we have tested the suitability of the used approach for study of oligonucleotide complexes. We have shown that factor analysis of temperature dependent UV absorption spectra is a proper base to determine thermodynamic parameters of the duplex dissociation. Raman spectra were affected by large errors, nevertheless they enabled to observe some structural changes related to the transition. It has been shown that the bulge loop present in the studied complex reduces both its flexibility and the energetic preference of its formation.
Creating a biosensor for miRNA effector complex formation using CRISPR nucleases
Petržílek, Jan ; Svoboda, Petr (advisor) ; Petr, Jaroslav (referee)
miRNAs are small regulatory RNAs, which function as post-transcriptional mRNA regulators. They direct ribonucleoprotein complexes to cognate mRNA to repress them by translational inhibition and degradation. miRNAs regulate thousands of mRNAs in mammals and have been recognized as regulatory factors in most cellular and developmental processes. Dysregulation of the miRNA pathway can lead to severe defects and diseases. Interestingly, a unique situation exists in mouse oocytes, where all the miRNA pathway components are present, yet the pathway is dispensable and nonfunctional, the molecular foundation of this phenomenon and its significance still remain unclear. In spite of the pronounced effects of the miRNA pathway in gene regulation in somatic cells, study strategies of the pathway bare limitations. Current methods for studying the activity of the miRNA pathway employ corelative studies (such as NGS) or reporter assays, which have relatively low throughput and are prone to artifacts. Here, I present design and development of a new strategy for directly monitor global miRNA pathway activity and integrity in near physiological conditions in living cells, which could also be employed in vivo for studies of mouse oocytes. The strategy is based on fluorescently tagged endogenous proteins of the...
Postpartal expression profile of cardiovascular microRNAs with regard to occurrence of pregnancy-related complications - study on mothers 3-10 years after the delivery
Marvanová, Veronika ; Hromadníková, Ilona (advisor) ; Korabečná, Marie (referee)
The aim of this study was to investigate gene expression of cardiovascular miRNAs in peripheral blood of mothers after delivery. MiRNAs are small non-coding RNAs, which significantly modulate posttranscriptional adjustments of mRNA and thus regulate gene expression across biological processess. Dysregulation of miRNAs is associated with many pathological phenomena, thanks that we can use them for diagnosis and potentionaly we can treat these diseases by the manipulation of miRNA gene expression. We examined gene expression of circulating miRNAs associated with cardiovascular diseases, and we investigated, how the expression profile depends on pregnancy course and manifestation of pregnancy-related complications. For this purpose we examined material from 221 mothers 3-10 years after delivery. A group with identical pregnancy-related complication was always compared with a group of mothers after physiological pregnancy. Gene expression of 29 cardiovascular miRNAs in peripheral blood was studied using reverse transcription and quantitative real-time PCR. It was confirmed, that the expression profile of miRNAs differed between pregnancy-related complications and physiological controls. We also confirmed, that the profile of gene expression discovered at mothers 3-10 years after delivery was different...
Pharmacogenetics in rheumatology - role of miRNAs
Vicherková, Petra ; Pávek, Petr (advisor) ; Doseděl, Martin (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of pharmacology and toxicology Candidate: Bc. Petra Vicherková Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of master thesis: Pharmacogenetics in rheumatology - role of miRNA Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that causes progressive joint damage and can result in to life-long depreciation of life. The influence on the onset and course of the disease is not only genetic, but due to the heterogeneous character of the disease, it is also strongly influenced by lifestyle. This disease, based on the malfunction of our immune system in RA, is still incurable. The treatment of RA uses conventional synthetic drugs as well as biological treatment. To diagnose the effect of anti-rheumatic therapy, monitoring and evaluating the response to treatment is necessary. Important indicators of RA activity, functional status, quality of life, and structural progression of the disease are important. In clinical practice, we use DAS 28 composite system according to recommendation of ČRS. Recent discoveries in the area of diagnostics raise the question of whether some miRNAs could be appropriate biomarkers of RA progression. In my diploma thesis, I summarize available knowledge in this field, obtained from...
The role of small non-coding RNAs in the regulation of plant reproductive development
Hromadová, Michaela ; Honys, David (advisor) ; Rothová, Olga (referee)
Small RNAs (sRNA) are broadly defined as regulatory molecules of 21-24 nucleotides in length which belong to the class of noncoding RNAs. They usually originate in response to the presence of double-stranded RNA in the cells and facilitate transcriptional and posttranscriptional gene silencing of complementary sequences. Their role lies not only in defence against exogenous nucleic acids, but primarily in the regulation of endogenous genes. Typical target molecules of plant sRNA are transposable elements and genes encoding the transcription factors involved in the control of key developmental transitions like the initiation of the reproductive phase and the regulation of its progress. The aim of this thesis is a summary of functional roles of individual small RNA in plant reproductive development, with focus to the female and male gametophytes and in the protection against the transition of transposable elements to following generations. Both endogenous and exogenous sRNA are amply utilized in plants, because they provide an immediate and direct response of the organism to rapidly changing conditions, and thus undoubtedly belong to the key factors which contribute to their phenotypic plasticity.
Use of RNAi and CRISPR systems in genetic modifications of parasitic protists
Kaiserová, Veronika ; Votýpka, Jan (advisor) ; Stojanovová, Darja (referee)
In organisms, RNA interference serves as a defence mechanism against foreign nucleic acids. RNAi has a negative effect on translation, via the binding of small non-coding molecules to the complementary region of mRNA, resulting in its degradation. CRISPR, a new method of genetic engineering, is based upon modulating genetic expression via creating double-stranded breaks in target DNA, aided by a ribonucleoprotein complex, consisting of the prokaryotic endonuclease Cas9 and sgRNA. Both of the aforementioned methods can be utilised in functional analysis of proteins and the characterisation of metabolic pathways in organisms of interest. This work summarises the current state of knowledge regarding RNAi and CRISPR and their use in genome editing of parasitic protists.
Spectroscopic Study of miRNA Structure and Interactions
Homolka, Radim ; Štěpánek, Josef (advisor) ; Maloň, Petr (referee)
MiRNA are short RNA molecules that mediate post-transcriptional regulation of gene expression by binding to a target mRNA. In this thesis, some structural properties and thermodynamic parameters (melting temperature, enthalpy ∆H and entropy ∆S changes connected with the transition between particular conformations) of oligonucleotides simulating complex of miRNA and mRNA, were characterized by using spectroscopic methods and a gel electrophoresis. Temperature dependences of UV and Raman spectra were measured, the results treated by means of a factor analysis, and the abovementioned thermodynamic parameters determined by a fit to a feasible model. The outputs have demonstrated the capability of the used methods to determine thermodynamic and structural properties of non-canonical RNA complexes. Powered by TCPDF (www.tcpdf.org)
Molecular aspects of musculoskeletal diseases and the role of small regulatory RNAs
Pleštilová, Lenka ; Vencovský, Jiří (advisor) ; Šedivá, Anna (referee) ; Hrnčíř, Zbyněk (referee)
Rheumatic diseases are common, usually chronic, painful and to some extent invalidating medical conditions. Understanding of the disease pathogenesis is still very fragmentary. Hyperreactivity of the immune system and defect of autotolerance are probably contributed by local factors, which helps to explain, why some joints/muscles are more affected than others. All this results from a complex net of interactions between immune cells, synovial fibroblasts, chondrocytes, osteocytes, myocytes and other cells. In the submitted PhD thesis I have focused on three groups of molecules: regulatory RNAs, S100 proteins and autoantibodies. In the theoretical part, I sum up the current knowledge on their biogenesis, function and the role in rheumatology. In the investigative part, I present six original publications and one review on the role of those molecules in development of rheumatoid arthritis (RA) and idiopathic inflammatory myositis (IIM). One of the main studies was focused on expression of PIWI-interacting RNAs (piRNAs) in RA synovial fibroblasts (SF). piRNAs are small regulatory RNAs which in complex with PIWIL proteins regulate gene expression and silence transpozoms. piRNA expression was considered to be limited to germline and cancer cells. We have found 267 PIWI-interacting RNAs to be expressed...

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