621 |
Characterisation of cytochromes P450 in Australian marsupials /El-Merhibi, Adaweyah. Unknown Date (has links)
Australian marsupials are unique fauna that have evolved and adapted to unique environments and thus it is likely that their detoxification systems differ considerably from those of well studied eutherian mammals. This poses a problem in applying data from metabolic studies with eutherians to marsupials. Knowledge of these processes in marsupials is therefore vital to understanding the consequences of exposure to xenobiotics. As a result, there is a clear need for improved understanding of the metabolic capabilities of Australian marsupials, particularly at the molecular level. The current PhD candidature therefore focused on characterising the important xenobiotic-metabolising enzyme superfamily, cytochrome P450, with particular emphasis on the CYP3A subfamily, in Australian marsupials, namely koala (Phascolarctos cinereus), tammar wallaby (Macropus eugenii), Eastern grey kangaroo (Macropus giganteus) and the Southern hairy-nosed wombat (Lasiorhinus latifrons). / Expression of CYP3A-like protein using hepatic microsomes was detected by western blot analysis in all four marsupial species studied. Female koalas were observed to express higher levels of CYP3A-like protein than male koalas. CYP3A activity for each marsupial species was determined in hepatic microsomes using erythromycin, a known human CYP3A4 substrate. Erythromycin N-demethylation activity was detected in all marsupial hepatic microsomes, with highest activity observed in koala. Koalas displayed gender differences in activity with female koalas showing a significant 2-fold increase. Inhibition studies with troleandomycin showed decreased erythromycin activity in both female and male koalas. Erythromycin activity in wallaby and kangaroo microsomes was notably lower than observed in koala. No gender differentiation was noted in wallaby or kangaroo. This observed difference in CYP3A activity between species may be indicative of the koala's eucalyptus diet. / Full-length CYP3A cDNAs were isolated from both koala and Eastern grey kangaroo. These clones are the first CYP3A sequences to be cloned from any marsupial species. Given the significant role that CYP3A enzymes play in the metabolism of both endogenous and exogenous compounds, these clones provide an important step in elucidating the metabolic capacity of marsupials. / The CYP2C subfamily was also investigated in koala using two previously cloned CYP2C members, CYP2C47 and CYP2C48. Site-directed mutagenesis was used to engineer the CYP2C48 cDNA into a suitable form for expression. Stable cell lines were generated for both CYP2C and CYP3A full-length cDNAs using a mammalian expression system. These cell lines were used to determine catalytic activity of the marsupial CYPs. / Multiple protein alignments were used to identify substrate recognition sites and critical residues involved in the metabolism of a variety of substrates. Sequence analysis of the deduced amino acid sequence of the CYP3A clones has highlighted important species-specific features, for example a Thr residue at position 119 which has only been found in a limited number of species, including koala, and has been shown to influence steroid metabolism. / Modelling of all marsupial CYP2C and CYP3A full-length cDNAs and phylogenetic analysis of all known marsupial cDNA sequences was performed. These studies highlight the need for inclusion of marsupial information when assessing mammalian evolution. / Collectively, the work presented here provides valuable insights into the marsupial CYP2C and CYP3A subfamilies and highlights the significance of species differences in xenobiotic metabolism. / Thesis (PhDPharmacy)--University of South Australia, 2005.
|
622 |
Photoluminescence of InN with Mg and Zn DopantsSong, Young Wook January 2008 (has links)
The optical properties of Mg-doped InN thin films grown on YSZ substrates have been investigated by photoluminescence (PL). A series of InN:Mg samples with various Mg cell temperatures (TMg) were produced by molecular beam epitaxy. The effect of Mg concentration on PL emission properties have been explored by various excitation power and temperature dependent measurements. The PL spectra as a function of excitation power exhibited a pronounce blueshift, indicating prominent band filling caused by the Burstein-Moss effect. Meanwhile, a typical redshift was observed as temperature increased due to bandgap shrinkage. The samples with TMg below 210 ˚C have a dominant peak at energy of 0.68 eV. In contrast, the PL peak emissions for films with a high TMg between 210~230 ˚C were centred near 0.6 eV. No PL emission was observed from the films with TMg above 230 ˚C. By fitting with an empirical Arrhenius equation, the activation energies yield approximately 20 meV and 15 meV for the lower and higher energy transitions, respectively. The fundamental optical properties of Zn doped InN were also examined. InN:Zn films were grown under In-rich conditions. The samples showed well defined PL emission spectra implying that the quality of the film has been improved over the Mg-doped series. The PL spectra of InN:Zn exhibited prominent features containing various emission peaks. The combination of excitation power and temperature dependent measurements supports a precise determination for the origins of the observed transitions. The comparison between the optical properties of Mg and Zn doped InN provide the motivation for more precise quantitative interpretation of p-type InN.
|
623 |
Engineering an efficient cholesterol hydroxylase from a highly active fatty acid hydroxylase, CYP102A1 /Alemseghed, Mussie, January 2007 (has links)
Thesis (M.S.)--University of Texas at Dallas, 2007. / Includes vita. Includes bibliographical references (leaves 62-64)
|
624 |
A test of the interactionist theory of conflict management /Wilson, Kara Gae. January 1978 (has links)
Thesis (Ed.D.)--University of Tulsa, 1978. / Bibliography: l. 107-117.
|
625 |
A test of the interactionist theory of conflict management /Wilson, Kara Gae. January 1978 (has links)
Thesis (Ed.D.)--University of Tulsa, 1978. / Bibliography: l. 107-117.
|
626 |
Bedeutung und Intention Paul Grices Sprachphilosophie und die BedeutungsproblematikBrändle, Max January 2005 (has links)
Zugl.: Berlin, Techn. Univ., Diss., 2005
|
627 |
Genetic polymorphism and regulation of cytochrome P450 2E1 /Hu, Yin, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.
|
628 |
Genetic polymorphism of human drug metabolising enzymes : structural and functional studies /Oscarson, Mikael, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 9 uppsatser.
|
629 |
Pharmacokinetic consequences of CYP2D6 genotypes with emphasis on gene duplication/amplification /Dalén, Per, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2000. / Härtill 5 uppsatser.
|
630 |
Interindividual differences in xenobiotic-metabolising enzymes : the human genetic factor /McLellan, Roman A., January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2000. / Härtill 6 uppsatser.
|
Page generated in 0.0304 seconds