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A Long-Term Neuroepigenomic Profile Of Prenatal Alcohol Exposure, Benjamin I. Laufer

Electronic Thesis and Dissertation Repository

Fetal Alcohol Spectrum Disorders (FASD) represent the largest preventable cause of cognitive deficits in the western world. The mechanism(s) of how prenatal alcohol exposure (PAE) results in FASD remain unknown. Towards this end, mouse models of PAE have successfully recreated endophenotypes that are characteristic of FASD. This doctoral thesis examines the long-term epigenomic alterations associated with PAE. I have examined both mice with PAE and human patients with FASD.

In the first set of experiments, mice with PAE and matched controls were raised to adulthood and then their whole brains were examined for alterations to gene expression, non-coding RNA (ncRNA) …

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse model …

Comprehensive Assessment Of Cnv Calling Algorithms: A Family Based Study Involving Monozygotic Twins Discordant For Schizophrenia, Sujit Maiti

Electronic Thesis and Dissertation Repository

Genetic variability is essential to human individuality. Genetic variation includes differences in sequence at the single nucleotide level to structural variations of large segments of DNA called copy number variations (CNVs). CNVs within a genome can be identified using microarray technology; however, the analysis of microarray results resulting in the “calling” of CNVs is not always precise. The research included in this manuscript describes the identification and analysis of CNVs using three commercially-available packages, Affymetrix^® Genotyping Console^TM, Partek^® Genome Suite^TM and PennCNV, that are most commonly used in the analysis of SNP and CNV data. …

Modulatory Effects Of North American Ginseng Extracts On Human Innate And Adaptive Immune Responses, Holly Rebecca Lemmon

Electronic Thesis and Dissertation Repository

Ginseng has played a vital role in traditional Chinese medicine for thousands of years. There are 22 variants of ginseng including North American ginseng (Panax quinquefolius) and Asian ginseng (Panax ginseng). The use of North American ginseng has increased dramatically and there is a strong need to understand its immunomodulatory effects. This is because the majority of current research focusing on the Asian ginseng variant. Human peripheral blood mononuclear cells (PBMC) were used to test the immunomodulatory properties of 3 North American ginseng extracts, COLD-FX^® and deglycosylated individual ginsenosides. Microarray analysis of PBMC exposed to …

The Intracellular Behaviour Of Burkholderia Cenocepacia In Murine Macrophages, Jennifer S. Tolman

Electronic Thesis and Dissertation Repository

Burkholderia cenocepacia is an opportunistic pathogen causing life-threatening infections in cystic fibrosis and other immunocompromised patients. The bacterium survives within macrophages by interfering with typical endocytic trafficking, resulting in delayed maturation of a B. cenocepacia-containing phagosome. We hypothesize that B. cenocepacia alters gene expression after internalization by macrophages, inducing genes involved in intracellular survival and host adaptation. Furthermore, we hypothesize that specialized bacterial secretion systems are involved in the interactions between intracellular bacteria and macrophages. In this work, we characterize later-stage infection of macrophages by B. cenocepacia, showing replication within an acidified endosomal compartment suggestive of a phagolysosome. …

Survival Analysis Of Microarray Data With Microarray Measurement Subject To Measurement Error, Juan Xiong

Electronic Thesis and Dissertation Repository

Microarray technology is essentially a measurement tool for measuring expressions of genes, and this measurement is subject to measurement error. Gene expressions could be employed as predictors for patient survival, and the measurement error involved in the gene expression is often ignored in the analysis of microarray data in the literature. Efforts are needed to establish statistical method for analyzing microarray data without ignoring the error in gene expression. A typical microarray data set has a large number of genes far exceeding the sample size. Proper selection of survival relevant genes contributes to an accurate prediction model. We study the …

Dna-Damage-Independent Mitochondrial Dysfunction Drives A Loss Of Retina Function Prior To Neuron Death In The Harlequin Mouse Model Of Aging, Alex Michael Laliberte

Digitized Theses

Although there are many aging-associated retinal diseases, the aging mechanisms which initiate retinal disease remain elusive. To investigate this problem, a model of premature aging, the harlequin mouse, was examined for deficits in retinal function, anatomy and histology, as well as changes in retinal oxidative stress, gene expression and mitochondrial DNA damage. Retinal function of the harlequin mouse, as assessed by electroretinography, was compromised in advance of change in retinal anatomy and histology. Functional deficits occurred in parallel with increased oxidative stress, assessed by in situ dihydroethidium staining. Furthermore, microarray transcriptome analysis of harlequin mice identified markers of mitochondrial stress, …

A Microarray Study On Gene Expression Of Drosophila Melanogaster 'M Response To Multiple Cold Exposures, Jian Zhang

Digitized Theses

In the field, insects suffer multiple cold exposures during winter. When exposed to repeated low temperatures, Drosophila melanogaster females show an increase in survival, but a reduction in reproduction. In this study, microarrays were used to analyze the gene expression of female D. melanogaster after multiple, single sustained (or single prolonged) and single short cold treatments, which exposed the flies at 0 °C for repeated 2 h, single 10 h and single 2 h respectively. Candidate genes involved in the 6 h recovery from different types of cold exposures were identified. After repeated cold exposures, candidate genes particularly included those …

Brassinosteroid-Mediated Stress Tolerance: Hormone Pathways, Genes And Function, Uday K. Divi

Digitized Theses

Brassinosteroids (BRs) are naturally occurring plant steroid derivatives that play crucial roles in plant development and also promote tolerance to a range of abiotic stresses. Although much has been learned about their roles in plant development, the mechanisms by which BRs control plant stress responses and regulate stress-responsive gene expression are not fully known. It is also likely that the stress tolerance conferring ability of BRs is in part due to their interactions with other stress hormones. In the present study the stress tolerance effects of BR, interactions of BR with other plant hormones, and global genomic responses of BR …

Transcriptional Profiling Of Myeloid Dendritic Cells Generated In Vitro, Karly Lycett-Lambert

Digitized Theses

Myeloid dendritic cells (DC) such as Langerhans cells (LC) and dermal DC (MDDC) are among the most potent professional antigen presenting cells. Their phenotypical and positional differences in vivo suggest that LC and MDDC may perform distinct functions. To gain insights into functional differences, we performed a genome-wide analysis of the transcriptome of LC and MDDC in immature and mature states, generated in vitro from CD34+ and CD14+ progenitors. Transcripts displaying statistically significant differences in expression between the cell types were separated into twelve functional categories. Partitioning has revealed that there are substantial differences in DC transcriptional activity. DC subsets …