A humoral factor elaborated by tumor tissue has been suggested as the etiological agent which causes the systemic effects accompanying malignant disease. Because of the important role of the nucleic acids in the metabolism of the cell, it was postulated that the tumor factor might produce the systemic effects by altering the nucleic acid metabolism of the host tissues. With these considerations in mind, a study has been made of the effect of several transplantable tumors on the incorporation of formate-C¹⁴ and tritiated thymidine into the nucleic acids of the host tissues. Studies on the incorporation of thymidine into the host tissues have been emphasized since this compound is a specific precursor of DNA thymine. Liquid scintillation counting methods were developed in order to assay the radioactivity of the tritium-labelled thymine. Methods for the liquid scintillation counting of carbon-¹⁴ labelled purines and pyrimidines were also established. The presence of the ascitic and subcutaneous forms of the Ehrlich tumor was found to have little effect on the incorporation of formate-C¹⁴ into the nucleic acids of the host tissues. In contrast an increased uptake of tritiated thymidine by the DNA of the host tissues was observed in animals bearing the Ehrlich ascites tumor, Novikoff hepatoma and the Walker 256 carcinosarcoma. This effect was particularly striking in the case of the liver and spleen of animals bearing the Walker 256 tumor. Other investigators have isolated a substance known as toxohormone from tumor tissue which has been shown to produce certain systemic effects similar to those of tumor tissue. It was postulated that the increased incorporation of thymidine into the DNA of the host tissues might be the result of the action of toxohormone. In order to test this hypothesis, the effect of toxohormone on the incorporation of tritiated thymidine into the DNA of rat liver and spleen was studied. Crude toxohormone caused an increased uptake of thymidine by the DNA of spleen, but the results obtained for liver were equivocal. A highly purified fraction of toxohormone was prepared by ion-exchange chromatography and gel filtration. However this fraction had no effect on the incorporation of thymidine into the DNA of rat liver and spleen. These results suggested that tumor tissue might contain a factor which stimulates DNA synthesis and which could be isolated in company with crude toxohormone. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

RNA molecules that can fold into two or more predefined alternative metastable structures can be designed rationally. We outline an algorithm for this task that reduces the problem to vertex coloring the union of all prescribed outerplanar secondary structure graphs. Starting from an ear decomposition of this composite graph colorings are produced by a dynamic programming procedure. Sequences can then be optimized for particular properties by means of standard optimization heuristics.

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Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

Thesis (Ph. D.)--Virginia Commonwealth University, 2010. / Prepared for: Dept. of Human Genetics. Title from title-page of electronic thesis. Includes bibliographical references . Record unavailable until 5/13/2015.

Thesis (Ph. D.)--University of Wisconsin, 1967. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

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Many different experimental approaches were attempted to achieve carbon-carbon bond formation by nucleic acid template-directed reactions and ribozyme catalysis as potential lipid synthesizing machineries in the RNA world. A novel biomimetic condition for decarboxylative Claisen condensation in polyketide biosynthesis was discovered. The reaction of a malonic acid half oxyester with a Nhydroxysuccinmidyl ester forming reagent resulted in self-condensation to provide the corresponding 1,3-acetonedicarboxylic acid diester in the absence of a divalent metal chelator or a coordinating solvent. The decarboxylative Claisen condensation of malonyl adenosine using a poly-U template in solution or with immobilized poly-U was attempted. Various analytical methods demonstrated that malonyl adenosine underwent an exclusive hydrolysis reaction instead of condensation in the given conditions. Similar results were observed for the reaction of malonyl-CoA with acetyl-CoA on poly-U templates. No evidence for the decarboxylative Claisen condensation was observed by a DNA-templated system although a double helical structure of DNA duplex was proven to facilitate a bimolecular reaction by offering a favorable proximity effect. Therefore, it seems that the unsuccessful condensation resulted not from the bad template effect but from the intrinsic properties of the decarboxylative Claisen condensation reaction itself. Two tRNA molecules loaded with a malonic acid were prepared by ligation of truncated tRNAs with malonylated dinucletides. Our initial attempts to probe carbon-carbon bond formation by subjecting malonylated tRNAs to the in vitro translational machinery were not successful. Novel carbon isosteres of α-amino acids are suggested as a potential source of a more stable and reactive carbanion for future experiments. Isoprenoid conjugates of nucleoside 5??-diphosphates, which were proposed as either an initiator nucleotide or substrate molecule for in vitro selection of prenyl-transferase ribozyme were prepared by one step nucleophilic displacement reactions. A random DNA pool was constructed for selection of a ketosynthase ribozyme. A substrate bearing a biotin tag was prepared by one-step conjugation. Hig-tagged T7 RNA polymerase was expressed and purified for a large scale transcription reaction. In vitro transcription of the random DNA pool with a 5??-thiol modified GMP analogue as an initiator nucleotide produced a thiol-modified random RNA library.