No description available.

No description available.

Endogenous retroviruses (ERVs) comprise a significant portion of the genome of all mammals and have been implicated in placental development in multiple species. The ovine genome contains approximately 27 copies of endogenous betaretroviruses (enJSRVs) that are related to the exogenous Jaagsiekte sheep retrovirus (JSRV), an oncogenic retrovirus tropic to the lung. The enJSRV loci are abundantly expressed in the female reproductive tract and the conceptus, and they are essential to conceptus development. Studies were conducted to determine: 1) the effect of exogenous progesterone administration on conceptus development after loss of enJSRV Env; 2) the specific enJSRV env expressed in the developing conceptus; and 3) if the uterus produces enJSRV viral particles that are capable of transducing the conceptus. Study One determined the effects of exogenous progesterone on development of the conceptus in which enJSRV Env was ablated. Despite rescuing conceptus survival, the conceptuses were morphologically fragile and had reduced binucleate cell (BNC) numbers. These results suggest that mononuclear trophectoderm cell (MTC) proliferation and differentiation is dependent on enJSRV Env, even in a uterine environment supported by exogenous progesterone. Study Two assessed the enJSRV loci transcribed in the ovine conceptus during elongation before (day 13) and after (day 18) onset of BNC differentiation. The most represented loci in both day 13 and day 18 conceptuses encoded truncated Env proteins that did not contain membrane-spanning domains. Conceptuses from both time points contained evidence of the transcription of full-length, biologically active enJSRV Env, as well as completely intact proviral loci with the ability to produce viral particles in vitro. Study Three utilized a transpecies embryo transfer experiment to determine if the intact enJSRVs loci could produce viral particles in vivo. The presence of enJSRV viral particles in the uterus was confirmed, as was their ability to transduce the conceptus. Collectively, these studies provide evidence of truncated Env proteins, intact biologically active Env proteins, and enJSRVs viral particles within the ovine uterus and conceptus that are necessary to stimulate proliferation and differentiation of MTCs even in a uterine environment supported by exogenous progesterone.

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xix, 165 p.; also includes graphics (some col.). Includes abstract and vita. Advisor: Kathleen Boris-Lawrie, Dept. of Molecular, Cellular and Developmental Biology. Includes bibliographical references (p. 148-165).

Tp1 is a long highly-abundant repetitive element found in the genome of <i>Physarum polycephalum</i>. It predominates in a hypermethylated, high molecular weight HpaII-resistant domain. The structural properties of this element resemble those of eukaryotic retrotransposons such as <i>copia</i> in <i>Drosophila melanogaster</i>. Preliminary evidence has indicated that segments of Tp1 are transcribed in both plasmodia and amoebae. Hence, from the structural analogy with retrotransposons it was supposed that the long terminal repeats (LTRs) of Tp1 may serve as transcriptional promoters. A plasmid (pE1oriCAT) was constructed which contains a CAT reporter gene located 3' to the Tp1 LTR and a <i>Physarum</i> origin of replication. CAT activity observed in cell lysates prepared from pE1oriCAT-transfected amoebae suggested that the Tp1 LTR can function as a transcriptional promoter. Nucleotide sequence information was obtained for the right-hand end of a copy of Tp1. From its predicted amino acid sequence a high degree of homology was found with the reverse transcriptase domain in the C-terminal half of the <i>pol</i> polypeptide in <i>copia</i> from <i>Drosophila melanogaster</i>, Ty912 from <i>Saccharomyces cerevisiae</i> and Ta1 from <i>Arabidopsis thaliana</i>. The high degree of identity between the reverse transcriptase domains in all of the above elements suggests that they may share a common ancestor. A preliminary search for Tp1 virus-like particles (VLPs) was carried out. Fractions collected from sucrose density gradients, prepared from amoebal cell lysates, were examined for VLP structures by transmission electron microscopy. Although putative VLPs were observed, which were morphologically similar to VLPs associated with the yeast retrotransposon Ty, they did not react immunologically with an antibody prepared against Ty VLPs. A member of another transposon-like family, designated Tp2, has also been identified in the genome of <i>Physarum</i>. Tp2 is 1.68kb in length, has 180bp LTR sequences at its termini and is blanked by 5bp direct repeats. Analysis of the predicted amino acid sequence of Tp2 identified an amino acid motif that is homologous to a highly conserved RNA binding domain in the <i>gag</i> polypeptide of retroviruses and retrotransposons.

Thesis (Ph. D.)--University of Sydney, 2000. / Includes tables. Title from title screen (viewed Apr. 22, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Dept. of Animal Science, Faculty of Agriculture. Includes bibliography. Also available in print form.

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xiii, 111 p.; also includes graphics Includes bibliographical references (p. 102-111). Available online via OhioLINK's ETD Center

No description available.

No description available.

The epidermal growth factor receptor (EGFR) gene was examined as a proto-oncogene. Initially, the cellular homolog of the retroviral oncogene erb-B was shown to be localized to the same region of human chromosome 7 as the EGFR gene, giving support to the idea that these genes are closely related. To determine how some cells can over-express the EGFR gene, somatic cell hybrids constructed between a human EGFR-overproducing cell line and a mouse EGFR-deficient cell line were examined. EGFR gene amplification was observed in one of these hybrids along with EGFR gene rearrangement, which is thought to generate an abnormal mRNA. When examining tumor tissue, the EGF receptor (EGFR) was found to be elevated relative to normal adjacent tissue in 9 out of 15 primary human squamous cell carcinomas. Only 2 of these 9 tumors had EGFR gene amplification, suggesting alternative mechanisms potentially involved in increasing EGFR levels. Because placental tissue expresses high levels of EGFR, it was thought that some tissues may normally possess high EGFR levels and that some cancerous tissues inappropriately mimic the mechanisms active in the placenta. From the examination of several tissue samples, EGFR mRNA levels and EGFR protein half-life were also postulated as contributing factors regulating the EGFR levels. The EGFR gene was implicated as a proto-oncogene by evidence which suggests that either a qualitative or a quantitative change in the receptor may be involved in tumorigenesis. Finally, to begin to better understand what role EGFR hyperproduction plays in tumorigenesis, a DNA vector was constructed which produces antisense-RNA for inhibiting EGFR expression.