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The molecular evolution and epidemiology of Rubella virusCloete, Leendert J. January 2014 (has links)
>Magister Scientiae - MSc / Despite widespread rubella virus (RV) vaccination programs, annually RV still
causes severe congenital defects in an estimated 100,000 children globally. A
concerted attempt to eradicate RV is currently underway and analytical tools to
monitor the global decline of the last remaining RV lineages will be useful for
assessing the effectiveness of this endeavour. Importantly, RV evolves rapidly
enough that much of its epidemiological information might be inferable from RV
genomic sequence data.
Using BEASTv1.8.0, I analysed publically available RV sequence data to estimate
genome-wide and gene-specific nucleotide substitution rates, to test whether the
current estimates of RV substitution rates are representative of the entire RV genome.
During these investigations, I specifically accounted for possible confounders of
nucleotide substitution rate estimates, such as temporally biased sampling, sporadic
recombination, and natural selection favouring either increased or decreased genetic
diversity (estimated by the PARRIS and FUBAR methods) at nucleotide sites within
RV nucleic acid secondary structures (predicted by the NASP method).
I determined that RV nucleotide substitution rates range from 1.19×10-3
substitutions/site/year (in the E1 region) to 7.52×10-4 substitutions/site/year (in the
P150 region). I found that these differences between nucleotide substitution rate
estimates in various RV gene regions are largely attributable to temporal sampling
biases, such that datasets containing a higher proportion of recently sampled
sequences will tend to have inflated estimates of mean substitution rates. Although
there exists little evidence of positive selection or natural genetic recombination in RV, I revealed that RV genomes possess extensive biologically functional nucleic
acid secondary structures and that purifying selection acting to maintain these
structures contributes substantially to variations in estimated nucleotide substitution
rates across RV genomes.
Although both temporal sampling biases and purifying selection favouring the
conservation of RV nucleic acid secondary structures have an appreciable impact on
substitution rate estimates, I find that these biases do not preclude the use of RV
sequence data to date ancestral sequences and evaluate the associated RV
phylodynamics. The combination of uniformly high substitution rates across the RV
genome and strong temporal signal within the available sequence data enabled me to
analyse the epidemiological and demographical dynamics of this virus during these
attempts to eradicate it. By implementing a generalized linear model (GLM) and
symmetrical model of discretized phylogeographic spread, I was able to identify
several predictive variables of geographical RV spread and detect transmission
linkages between distinct geographical regions. These results suggest that, in addition
to strengthened vaccination strategies, there also needs to be an increased effort to
educate people about the effects of vaccination and risks of RV infection.
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Identification of Leishmania genes encoding proteins containing tandemly repeating peptidesWallis, Anne Elizabeth January 1987 (has links)
In order to identify Leishmania proteins which may be immunologically relevant or may play a role in interactions between Leishmania and its mammalian host, a Leishmania major genomic DNA library was constructed in the vector λgt11 and screened with antibodies raised to Leishmania major promastigote membranes. Two recombinant DNA clones were identified which encoded repetitive sequences (Clone 20 and Clone 39). Clone 20 encoded a repetitive peptide of 14 amino acids and clone 39 encoded an unrelated repetitive peptide of 10 amino acids. Analysis of one of these clones, Clone 20, indicated that there were two RNA transcripts of 9500 and 5200 nucleotides expressed which corresponded to this clone in Leishmania major and Leishmania donovani and this expression was not stage-specific. The results of genomic DNA analysis and isolation of additional clones encoding Clone 20 sequences indicated that there were two genes which corresponded to Clone 20 in both Leishmania major and Leishmania donovani and that these genes differed from one another with respect to the number of repeats which they contained. Antibodies against the fusion protein produced by Clone 20 recognized a series of Leishmania major proteins of apparent mol wt 250,000. Analysis of Clone 39 indicated that there was a single transcript of 7500 nucleotides expressed which corresponded to this clone in both Leishmania major and Leishmania donovani and that there was a single gene (or two identical genes) which encoded this transcript.
The genomes of many protozoan parasites exhibit a high degree of plasticity with respect to chromosome size and number. The presence of highly repetitive regions within their DNA may be involved in maintaining this plasticity, allowing the parasite to evolve rapidly under selective pressure. Repetitive regions have been identified within many Plasmodia antigens and have been implicated in the ability of this parasite to evade the host immune system. The presence of Leishmania genes encoding proteins containing tandemly repeating peptides may indicate that these proteins play a similar role in evading the host immune system during the course of Leishmania infections. The possible evolution and functions of repetitive proteins in protozoan parasites is discussed. / Medicine, Faculty of / Medical Genetics, Department of / Graduate
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NA2Dsearch: rychlý a snadný nástroj pro vyhledávání sekundárních struktur v databázích nukleových kyselin v paralelním režimu / NA2Dsearch: a fast and easy tool for secondary structure searches through databases of nucleic acids in parallelHlubuček, Petr January 2010 (has links)
The diploma thesis is dealing with searching in secondary structures of nucleic acids. The NA2Dsearch application was developed that allows to search databases of secondary structures for a structural motif. The application offers user-friendly graphical user interface where a query motif can be constructed in comfortable visual way using drag&drop, database and result structures can be browsed and visualized. The application contains original interactive nucleic acid structure visualization algorithm and novel search algorithm. The search algorithm can perform a motif search on structural data (unlike existing programs that can perform a motif search on sequence data). The motif search means that a query is created that describes the structure of motif of our interest with variabilities (e.g. the length of hairpin loop) that can be tolerated. Search results are ordered by the score computed according to the resemblance of hit and the query. The NA2Dsearch also supports searching in sequence data which are folded by external folding program. Searching capabilities are demonstrated on several search experiments involving HCV IRES and tRNA. Three searches for HCV IRES were performed: a search for HCV IRES structure in database of more than thousand of HCV genomic sequences, a folding analysis of HCV IRES...
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多足型DNAナノ構造体を利用した核酸医薬の標的指向化および体内動態制御に関する研究高橋, 洋介 26 March 2018 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21048号 / 薬科博第91号 / 新制||薬科||10(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 髙倉 喜信, 教授 山下 富義, 教授 小野 正博 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM
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Novel synthesis of branched nucleic acids : towards applications in chemical biology and nanotechnologyMitra, Debbie. January 2007 (has links)
No description available.
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Expanding the size and shape of nucleic acids : studies on branched and heptose based nucleic acidsSabatino, David. January 2007 (has links)
No description available.
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Part I. Studies directed towards the asymmetric synthesis of amipurimycin. Part II. The development of novel peptide-based nucleic acid surrogatesYoo, Ji Uk January 1994 (has links)
No description available.
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Synthetic Nucleic Acid Capable of Post-Polymerization Functionalization and Evolution:Wu, Kevin B. January 2023 (has links)
Thesis advisor: Jia Niu / Thesis advisor: Abhishek Chatterjee / The functions of natural nucleic acids such as DNA and RNA have transcended from serving as the primary information carrier in cells and have emerged as a new class of functional material with applications encompassing medicine, diagnosis, and research tools. While the vulnerability of natural nucleic acids to nuclease degradation as well as the lack of chemical functionality have imposed a significant constraint on their ever-expanding applications, scientists have put in the effort to develop new classes of synthetic nucleic acids (XNAs) to overcome current limitations. In this dissertation, we will describe the development of a novel XNA oligonucleotide structure, the “click handle-modified FANA” (cmFANA), as the next-generation nucleic acid-based biopolymer that is capable of post-polymerization functionalization and evolution. In this dissertation, we divide our graduate research into three chapters: the development of the essential building block for cmFANA and the synthesis of cmFANA oligonucleotide as Chapter 1; the evolution and application of cmFANA as a sugar-presenting affinity reagent that targets disease-related Carbohydrate-Binding Proteins (CBPs) as Chapter 2; and other collaboration projects as Chapter 3. Together, we described a highly potential XNA structure that goes beyond established impressions of nucleic acids and carries the ability to be a versatile platform technology. / Thesis (PhD) — Boston College, 2023. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
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Recognition and Probing of RNA Non-canonical Pair (NCP) Site Enabled by Triplex Hybridization with Bifacial Peptide Nucleic Acids (bPNA)Tang, Xue 21 July 2022 (has links)
No description available.
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Employing Functional Nucleic Acids as Molecular Recognition Elements Within Modular BiosensorsManochehry, Sepehr January 2019 (has links)
Advances in our ability to detect biological targets relevant to human health have come from the engineering of biological molecules into assemblies capable of performing target-induced signal generation. Such assemblies, known as biosensors, are composed of a molecular recognition element (MRE) and a signal generating transduction element. One MRE class that has received great attention in recent years is functional nucleic acids, which include DNA aptamers and DNAzymes. Since 1990, a large number of functional nucleic acids have been reported. However, broad commercial use of functional nucleic acids in applications that benefit human health is sparse. The goal of this thesis is to expand the usefulness of functional nucleic acids. The thesis is made of four projects. In the first project I developed a simple colorimetric biosensor for the detection of a toxic metal ion using a reported RNA-cleaving DNAzyme coupled with urease as the signal reporter. This is followed by a project where I developed a highly effective method for the synthesis and purification of the DNA-urease conjugate needed for the biosensor. I then turned my attention to the search for high-affinity DNA aptamers that bind VEGF-165, an important human protein found to be relevant in the progression of cancers. Given that VEGF-165 is a homodimeric protein, in my third project I looked into the suitability of reported DNA aptamers for this protein for the creation of dimeric aptamers with higher binding affinity. I examined multiple factors that may affect the successful engineering of dimeric aptamers and determined that none of the existing aptamers are compatible for creating a productive dimeric aptamer. With this finding, I made an effort to create our own aptamers for this protein target. I was able to isolate a new aptamer that appears to be an excellent candidate for creating a higher affinity DNA aptamer. Overall, my work adds to our increasing appreciation of the functional capability demonstrated by single-stranded DNA molecules. More importantly, I hope the methods I have developed and new functional DNA molecules I have generated in this thesis will continue to drive the development of the functional nucleic acid field and contribute to the health research community’s efforts to increase human longevity. / Thesis / Doctor of Philosophy (PhD)
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