College of Agriculture & Natural Resources
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The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item CHARACTERIZATION OF LIVER X RECEPTORS IN PROSTATE CANCER CHOLESTEROL METABOLISM AND PULMONARY IMMUNE RESPONSE(2011) Trasino, Steven E.; Lei, David K; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Liver x receptors (LXRs) are central regulators cholesterol homeostasis and the innate immune response. As modulators of inflammation and cholesterol metabolism LXRs might diminish dyslipidemia and inflammation related pathologies caused by high fat (HF) diets or obesity. There is also data demonstrating that LXRs can protect against progression of prostate cancer (PCa), but little is known about the cholesterol modulating effects of LXRs in transformed cells. The goal of this project is to characterize the cholesterol modulating properties of LXRs in two models of PCa and the anti-inflammatory properties of LXRs in swine bronchial alveolar macrophages (AMs). This project will also examine whether the anti-inflammatory and lipid lowering properties of the dietary probiotic bacteria Lactobacillus casei (L. casei), can interact with the LXR axis in AMs. Studies in two PCa cell lines, LNCaP and PC-3, revealed that LXR ligands regulate the LXR responsive genes, ABCA1 and ABCG1 through the LXR&beta isoform and not LXR&alpha in PC-3 cells, but only ABCG1 in LNCaP. LXR- ABCA1 mediated reverse cholesterol transport (RCT) resulted in a decrease in plasma membrane lipid raft cholesterol domains in PC-3 cells, suggesting a potential anti-cancer axis for LXR activation. Studies in LNCaP and PC-3 cells also demonstrated that soy isoflavones can activate transcriptional activation of ABCA1 and ABCG1 in LNCaP and PC-3 cells through the LXR&beta isoform, but did not lead to an increase in RCT. Metabolic and anti-inflammatory studies of LXR in AM from Ossabaw pigs fed either a control (C) diet, HF, HF plus L casei (HFPB) or L. casei alone (CPB) diet revealed that AM from HF fed pigs had significantly higher concentrations of cholesteryl-esters (CE) compared with AM from control (C) diet fed pigs. Ex-vivo activation of LXR with the LXR ligand T0901317 opposed LPS mediated upregulation of IL-1&beta , IL-6, IL-8 and IL-10 mRNA levels in AM from HF, HFPB and CPB fed pigs. Finally, it was observed that LPS stimulation lead to significant inhibition of LXR transcription of LXR&alpha, ABCA1, ABCG1, cholesterol 25 hydroxylase (CH25H) and PPAR&gamma in AM. This effect was abrogated by L. casei for ABCA1, CH25H and PPAR&gamma mRNA expressionItem Novel surface proteins in the pathogenesis and diagnosis of Lyme disease(2010) Coleman, Adam Steven; Pal, Utpal; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Lyme disease is caused by an infection with the spirochete Borrelia burgdorferi. Transmitted between mammal reservoirs by the bite of an Ixodes tick, the pathogen exists in a complex life cycle that requires long-term persistence in arthropod and mammal hosts. The mechanisms responsible for persistence and the pathogenesis of Lyme disease are not well understood, but may involve interactions between bacterial surface proteins and the host. Previous experiments have shown that differential gene expression of surface proteins assists the pathogen in adaptation and persistence in a new host. Most B. burgdorferi surface proteins have no homology to known proteins, making the identification of virulence factors difficult. Gene expression analyses can be used to identify potentially important gene products for further study, based on the conditions under which they are expressed. To this end, the B. burgdorferi in vivo transcriptome of selected potential surface proteins was analyzed to identify promising targets for further study. Based on these analyses and other observations from the literature, the lipoproteins BbCRASP-2 and BBK07 were selected for further characterization. My hypothesis is that these proteins are important for B. burgdorferi virulence and persistence in the murine host. The surface exposure of each protein was assessed, as well as a detailed transcriptional profile of each gene. Using specific antibody-mediated interference and gene inactivation, I show that neither BbCRASP-2 nor BBK07 is essential for infectivity or pathogenesis in the murine model of Lyme disease. My results also indicate that BBK07 is a novel immunodominant antigen of B. burgdorferi that could be used as a serodiagnostic marker for human Lyme disease. Using a peptide library, the most immunodominant epitopes of BBK07 were identified, and shown to improve the diagnostic accuracy over that of the full-length recombinant BBK07. Finally, I show that BBK07-based diagnosis was sensitive even in the early stages of Lyme disease, and that the addition of BBK07 epitopes to current serodiagnostic assays could improve their sensitivity.