Gene of DC2 protein, a novel unknown gene, was identified previously in our laboratory while studying the death progression in the rat brain stem. According to the search results of bioinformatics database, both human DC2 and house mouse DC2 are 149 amino acids long and 16.8 kDa. The entire sequence of human DC2 differs from house mouse DC2 by only a single amino acid substitution. The bioinformatics revealed that human DC2 and house mouse DC2 had three predicted transmembrane regions. These results suggest human DC2 and house mouse are highly homologous. DC2 protein expresses differentially between organs. Human liver is the top fourth DC2-expressed organ, while house mouse liver is ranked 23rd DC2-expressed organ. Shibatani et al (Shibatani et al¡A2005) proposed DC2 protein as a potential subunit of mammalian Oligosaccharyltransferase (OST) after mass spectrometry analysis and suggested DC2 might involve in glycosylation. House mouse liver fibrosis was induced by giving 300mg/L thioacetamide (TAA) in the drinking water for different periods of time, and then gene expression of house mouse DC2 of liver was analyzed. mRNA expression was found in normal house mouse liver and mRNA expression increased gradually after TAA administration. DC2 protein also found in normal house mouse liver and DC2 protein of house mouse liver increased after TAA administration.

Steroid hormones, such as estrogen, are produced in one tissue and carried through the blood stream to target tissues in which they bind to highly specific nuclear receptors and trigger changes in gene expression and metabolism. Industrial chemicals, such as bisphenol A and many agricultural chemicals, including permethrin and fervalerate, are known to have estrogenic potential and therefore are estrogen mimics. Widely used agricultural chemicals, Enable (fungicide) and Diazinon (insecticide), were evaluated to examine their toxicity and estrogenicity. MCF-7 cells, an estrogen-dependent human breast cancer line, were utilized for this purpose. MCF-7 cells were treated with 0.033-3.3 ppb (ng/ml) of Enable and 0.3-67 ppm of Diazinon and gene expression was compared to that in untreated cells. Microarray analysis showed down-regulation of eight genes and up-regulation of thirty four genes in cells treated with 3.3 ppb of Enable, compared to untreated cells. Similarly, in cells treated with 67 ppm of Diazinon, there were three genes down-regulated and twenty seven genes up-regulated. For both chemicals, specific genes were selected for special consideration. RT-PCR confirmed results obtained from analysis of the microarray. These studies were designed to provide base-line data on gene expression-altering capacity of specific chemicals and will allow assessment of the deleterious effects caused by exposure to the aforementioned chemicals.

The horned condition in cattle is believed to be the wild type with morphogenesis primarily occurring after birth. The polled condition has existed since domestication and has been selected for its economic importance. The polled locus has previously been mapped by genetic linkage analysis to the proximal region of bovine chromosome 1. In order to help us eventually identify the causative mutation, the objective of the study was to structurally and functionally characterize the polled interval from IFNAR1 to SOD1 on BTA1. Our hypothesis was that the polled locus is a tissue specific transcription factor that is expressed in the developing horn buds and acts directly or indirectly upon SOX9. A 2.5 Mb BAC contig and STS content map of the polled interval was constructed. Three candidate genes encoding transcription factors were identified within this region but only C21orf66 was expressed in the horn buds from 1 d old Bos indicus influenced calves. The C21orf66 gene has 18 exons, spans 30,976 bp of genomic DNA, and 144 SNP were identified. No single SNP discovered in C21orf66 can be attributed as the causative mutation. None of the genes from the polled interval were differentially expressed in skin and horn from 1 d old Bos indicus influenced calves. However, there were significant differences in the levels of expression of RUNX2, SOX9, BMP4, PRKCA, and FOXL2 in these samples. Expression of RUNX2 was localized to the osteoblasts, and both RUNX2 and SOX9 were expressed in sebaceous glands of the horn at 1 d of age. Histological examination of horns and scurs from newborn, 5 to 6 mo, and ~1.5 yr old Bos indicus influenced cattle suggest that horns form through intramembranous ossification. Based on the data presented herein, we propose that the polled locus is upstream of RUNX2 and SOX9 in the osteogenic pathway, and could have its primary effect on the differentiation of mesenchymal condensations. The genes IL10RB, SFRS15, C21orf66, OLIG1, OLIG2 and HUNK remain candidates for the polled locus and warrant further investigation.

<p>Today one of the greatest aims within the area of bioinformatics is to gain a complete understanding of the functionality of genes and the systems behind gene regulation. Regulatory relationships among genes seem to be of a complex nature since transcriptional control is the result of complex networks interpreting a variety of inputs. It is therefore essential to develop analytical tools detecting complex genetic relationships.</p><p>This project examines the possibility of the data mining technique artificial neural network (ANN) detecting regulatory relationships between genes. As an initial step for finding regulatory relationships with the help of ANN the goal of this project is to train an ANN to predict the expression of an individual gene. The genes predicted are the nuclear receptor PPAR-g and the insulin receptor. Predictions of the two target genes respectively were made using different datasets of gene expression data as input for the ANN. The results of the predictions of PPAR-g indicate that it is not possible to predict the expression of PPAR-g under the circumstances for this experiment. The results of the predictions of the insulin receptor indicate that it is not possible to discard using ANN for predicting the gene expression of an individual gene.</p>

<p>Gene expression analysis has evolved as an extensive toolfor elucidation of various biological and molecular eventsoccurring in different organisms. A variety of techniques andsoftware tools have been developed to enable easier and morerapid means of exploring the genetic information. A moreeffective approach than exploring the whole content of genesexpressed under certain conditions is to study fingerprintassays or to use subtracted cDNA libraries to identify onlydifferentially expressed genes.</p><p>The objective for the work in this thesis has been toexplore differentially expressed genes in atherosclerosis. Thiswas done by applying and modifying a protocol for thesubtractive approach RDA (Representational Difference Analysis)in different model systems.</p><p>Initially, the molecular effects of an anti-atheroscleroticdrug candidate were elucidated. In addition, two alternativeapproaches to identify differentially expressed genes obtainedafter iterative rounds of RDA subtraction cycles wereevaluated. This revealed that in most cases, the shotgunapproach in which the obtained gene fragments are clonedwithout any prior selection has clear advantages compared tothe more commonly used selection strategy, whereby distinctbands are excised after gel electrophoresis.</p><p>A key process in the atherosclerotic plaque initiation isthe phenotypic change of macrophages into foam cells, which canbe triggered in a model system by using macrophages exposed tooxidised LDL. To investigate the genes expressed in thisprocess, the RDA technique was combined with microarrayanalysis, which allows for selectivity and sensitivity throughRDA, as well as rapid high-throughput analysis usingmicroarrays. The combination of these techniques enablessignificant differences in gene expression to be detected, evenfor weakly expressed genes and the results to be reliablyvalidated in a high throughput manner.</p><p>Finally, investigation of the focal nature ofatherosclerotic lesions and gene expression profiling werestudied using in vivo aortic tissues from ApoE-/- and LDLR -/-mice. The study was based on a comparison between localisationsthat are likely, and others that are unlikely, to developatherosclerotic plaques, and the RDA technique was employed toexplore differential gene expression.</p><p><b>Keywords:</b>Representational Difference Analysis,atherosclerosis, gene expression profiling</p>

An experienced dermatopathologist can reliably diagnose most cutaneous malignant melanomas based on well-established morphologic characteristics. However, in a minority of cases, traditional histopathologic evaluation and immunohistochemistry (IHC) are inadequate to confidently distinguish melanoma from benign melanocytic lesions such as Spitz nevi and dysplastic nevi. The advent of high-throughput gene expression array technology has resulted in the identification of hundreds of potential molecular diagnostic biomarkers, but no single chromosomal, DNA, RNA or protein marker has yet been shown to differentiate melanoma from nevus with sensitivity and specificity approaching 100%. We selected the protein products of 11 genesATP1B1, CYCLIN D1, DLX-1, HOXB13, LIF, MEIS2, MITF, MYC, PHACTR1, PTPRF and TWISTup-regulated in melanoma cell-culture and tissue-based expression arrays as candidate diagnostic biomarkers for preliminary investigation. Based on the results of our pilot studies, we proposed that increased expression of Phactr1 protein, as measured by IHC, could be used to differentiate malignant melanomas from nevi. We applied Phactr1 monoclonal antibody to a 480-core tissue microarray that included samples from 28 nevi and 62 primary melanomas. A simple scoring algorithm derived from this data distinguished primary melanoma from nevus in the training set with 92% sensitivity and 100% specificity. These data suggest that Phactr1 immunohistochemical staining is a potentially useful aid in the clinical diagnosis of primary cutaneous melanoma.

Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 114-129). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--University of Toledo, 2009. / "In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences (Cancer Biology)." Title at OhioLINK ETD site: Investigation of common bases of sympathetic nervous system and neuroblastoma development. Title from title page of PDF document. Includes bibliographical references (p. 72-75, 119-125, 152-192).

Thesis (M.A.)--York University, 2007. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 74-77). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR29562

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 114-124). Also available in print.