No description available.

The class B scavenger receptor CD36, or fatty acid translocase (FAT), is an 88 kDa plasma membrane glycoprotein that is the founding member of the class B scavenger receptor family. It has a number of natural ligands and has different functions at various locations in the body. It contributes to adhesion of platelets via its binding to thrombospondin-1. In monocytes and macrophages, it contributes to recognition and phagocytosis of apoptotic cells and it mediates the binding and uptake of oxidatively damaged low-density lipoproteins (oxLDL). In adipose and muscle tissues, FAT/CD36 mediates high-affinity binding and uptake of long-chain fatty acids (LCFAs) and is therefore a key regulator of lipid storage (particularly in adipocytes) and mitochondrial beta oxidation (particularly in muscle). Interestingly FAT/CD36 also binds native lipoproteins (including high-density lipoproteins [HDL]) with high affinity in vitro, although the physiological significance of this is unclear at present. Expression of FAT/CD36 by hepatocytes has not been recognised until recently, mainly because it is gender-regulated in both humans, and rats. However, the primary function of FAT/CD36 in the liver is unknown. The work described in this thesis has used various transfected cell lines to examine the possibility that FAT/CD36 contributes to hepatic LCFA uptake and/or the uptake of cholesteryl esters (and other lipids) from HDL. The subcellular localization of FAT/CD36 has been explored in rat liver and in cell lines of hepatic and non-hepatic origin, especially with respect to its association with specialized plasma membrane lipid raft microdomains known as caveolae. Furthermore, the importance of the cytoplasmic carboxyl-terminus of FAT/CD36 in both subcellular localization of the molecule and its activity as a LCFA transporter has been examined using truncated mutants and chimeric variants of FAT/CD36. The results indicate that FAT/CD36 contributes to LCFA uptake by hepatocyte-derived cell lines. In these cells it resides in both non-raft and lipid raft domains of the plasma membrane that may not always include caveolae. The studies also indicate that the cytoplasmic C-terminus of FAT/CD36 contributes to the attachment of FAT/CD36 to membranes, including raft-derived detergent-resistant membranes. This domain is necessary also for correct targeting of the receptor to the plasma membrane and for its activity as a LCFA transporter. Finally, DNA constructs have been prepared and tested, with the objective of producing transgenic mice in which expression of FAT/CD36 can be induced and over-expressed specifically in the liver. This model could be used to confirm whether FAT/CD36 has a role as a LCFA transporter in the liver and to explore whether it has additional significance as a hepatic transporter of HDL-derived cholesteryl esters or as a scavenger of oxidised LDL. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1294862 / Thesis (Ph.D.) -- School of Molecular and Biomedical Science, 2007

Bibliography: leaves 187-202 / 204 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Organic Chemistry, 1991

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

No description available.

Two studies concerning low molecular weight organic acids in soils were conducted. In the first study, anion exclusion chromatography was used to separate and identify 12 common organic acids, and the accuracy, precision and detection limits of the method were determined. The method was found to be sensitive and accurate to between 1.5 and 9 ��M, depending on the acid in question. The stability of the selected acids was examined, and the large concentration changes observed underscore the importance of timely analysis of soil solutions. No significant interferences were encountered in the analysis of two soil solutions. In the second study, the reaction of a forest soil with oxalic acid at four concentrations was monitored for a period of 96 hours. A large release of aluminum, sulfate, and phosphate was observed, with the greatest release occurring with the highest concentration of added oxalate. Solution aluminum increased by up to a factor of twenty, and though [Al�����] values were consistent with control by thermodynamic equilibrium with an amorphous aluminum oxide phase, exchangeable Al appeared to be the source of the increase. Sulfate increased abruptly at the start of the reaction and continued to rise, though more slowly, throughout the study. Solution phosphate was increased by up to four times and was maintained at the elevated level throughout the study. Changes in both sulfate and phosphate concentrations were attributed directly to exchange with oxalate. The persistence of elevated phosphate concentrations after 96 hours indicates that the effects of oxalate production by mycorrhizae could have lasting effects on the nutrient status of a soil. / Graduation date: 2000

A novel protocol for the study of protein-nucleic acid interactions is presented and demonstrated to be feasible. The protocol combines photochemical crosslinking techniques and mass spectrometric methods into a new strategy for identifying protein domains or amino acid residues that are in close contact with nucleic acid in protein-nucleic acid complexes. Identifying nucleic acid binding domains in proteins provides a starting point for understanding structure-function relationships in protein-nucleic acid complexes. The protocol can be divided into three parts: 1) Cross linking of the protein-nucleic acid complex by irradiation with ultraviolet light and subsequently verifying the crosslinking by mass spectrometry; 2) Mass spectrometric peptide mapping of crosslinked protein-nucleic acid complexes to identify crosslinked peptide-nucleic acid hybrids; 3) Tandem mass spectrometric sequencing of peptide-nucleic acid hybrids to localize the crosslinked amino acid residue(s). The experimental data described in this dissertation documents our efforts to establish and implement this analytical protocol. Using several different protein-nucleic acid systems and different crosslinking techniques, we have demonstrated the feasibility of a mass spectrometric based approach to structurally characterize UV-crosslinked protein-nucleic acid complexes. Matrix-assisted laser desorption/ionization mass spectrometry was for the first time demonstrated to be highly effective for detection and molecular weight determination of intact, UV-crosslinked protein-nucleic acid complexes and for molecular weight determination of synthetic and UV-crosslinked peptide-nucleic acid hybrids. Electrospray ionization mass spectrometry and tandem mass spectrometry was demonstrated to be effective for analysis of synthetic peptide-nucleic acid hybrids and, in conjunction with HPLC, for peptide mapping of a protein. The first application of MALDI mass spectrometry to the characterization of crosslinked peptide-nucleic acid hybrids isolated from a photochemically crosslinked protein-nucleic acid complex demonstrate that the new protocol can be used to identify nucleic acid binding domains in proteins. / Graduation date: 1995

Thesis (M.S.)--Oregon State University, 2007. / Printout. Includes bibliographical references (leaves 101-107). Also available on the World Wide Web.

Patients diagnosed with malignant glioma tumours have median survivals of 1.6 yrs and 5 months, respectively, highlighting the deadly nature of this disease. Despite aggressive multimodal treatment, patients with malignant glioma often present with secondary brain tumours at sites distal to the primary tumour mass. These secondary tumours are a consequence of renegade neoplastic cells that infiltrate the surrounding normal brain, a hallmark feature of malignant glioma. Brain fatty acid-binding protein (FABP7), which binds omega-3 docosahexaenoic acid (DHA) and omega-6 arachidonic acid (AA), is overexpressed and associated with a poor prognosis in patients with malignant glioma compared with normal brain. These data suggest that FABP7 plays an important role in gliomagenesis; however, the mechanism(s) underlying a role for FABP7 in malignant glioma has, until now, been unexplored. Here, we demonstrate that expression of FABP7 in malignant glioma cells is accompanied by increased cell migration. Consistent with our in vitro results, we show that expression of FABP7 in astrocytoma tumours is associated with sites of tumour infiltration and tumour recurrence. Furthermore, we demonstrate that the fatty-acid ligands of FABP7 affect cell migration in an FABP7-dependent manner. More specifically, DHA inhibits migration, whereas AA stimulates cell migration. Finally, we reveal that uptake and incorporation of DHA and AA in the phospholipids of malignant glioma cells is enhanced by FABP7 expression, suggesting a mechanism by which DHA and AA may affect cell migration by altering signal transduction at the cell membrane. We propose that the inherent ability of malignant glioma cells to express the radial glial marker FABP7 underlies their infiltrative capacity, allowing tumour cells to migrate long distances from the main tumour mass. We propose a model whereby FABP7 expression and relative levels of DHA and AA determine tumour infiltrative potential. Our findings provide insight into the role of FABP7 and its fatty acid ligands in controlling the migration of malignant glioma cells and point to the potential use of DHA as a natural anti-infiltrative agent in the treatment of malignant glioma. We believe that targeting FABP7-expressing cells may make a significant impact on the treatment of high grade astrocytomas. / Experimental Oncology

Three studies were conducted to determine the effects of cyclopropenoid fatty acids (CPFA) on the membrane components of livers of rainbow trout (Salmo gairdneri). In the first study, ¹⁴C-sterculic acid was administered by intraperitoneal injection into rainbow trout and the trout maintained for 72 hours. The labelled sterculic acid was found in choline phospholipids (CP) and ethanolamine phospholipids (EP). Smaller amounts of label were found in other microsomal membrane lipid components. No label was found associated with the proteins of the microsomal membrane. Phospholipase A₂ treatment of isolated CP and EP showed ¹⁴C-sterculic acid to be preferentially esterified to the 1-position of the glycerol backbone. In the second study, the cleavable bifunctional protein crosslinking reagent dimethyl 3,3'-dithiobispropionimidate-2HCl (DTBP) was used in an attempt to study alterations in the spatial arrangement of proteins in liver microsomal and plasma membranes that might be induced by dietary CPFA. The use of this reagent failed to yield a clear picture of protein-protein interactions in the microsomal membrane due to the formation of high molecular weight aggregates that were not resolvable on polyacrylamide gels. On the other hand, the use of DTBP failed to crosslink the proteins of the plasma membrane. In the third study, two-dimensional polyacrylamide gel electrophoresis was used to assess the effects of dietary CPFA on protein composition of trout liver microsomal and plasma membranes. Proteins were separated in the first dimension on the basis of their isoelectric points and in the second dimension on the basis of their molecular weights. No major alterations in the composition of liver microsomal or plasma membranes were found to be induced by dietary CPFA. / Graduation date: 1983