Social and Behavioral Sciences Commons^™

Activity And Molecular Dynamics Relationship Within The Family Of Human Cholinesterase, Judith Peters, Marie Trovaslet, Marcus Trapp, Florian Nachon, Flynn Hill, Etienne Royer, Frank Gabel, Lambert Van Eijck, Patrick Masson, Moeava Tehei

Faculty of Science - Papers (Archive)

The temperature dependence of the dynamics of recombinant human acetylcholinesterase (hAChE) and plasma human butyrylcholinesterase (hBChE) is examined using elastic incoherent neutron scattering. These two enzymes belong to the same family and present 50% amino acid sequence identity. However, significantly higher flexibility and catalytic activity of hAChE when compared to the ones of hBChE are measured. At the same time, the average height of the potential barrier to the motions is increased in the hBChE, e.g. more thermal energy is needed to cross it in the latter case, which might be the origin of the increase in activation energy and …

Selective Reduction Of Hydroperoxyeicosatetraenoic Acids To Their Hydroxy Derivatives By Apolipoprotein D: Implications For Lipid Antioxidant Activity And Alzheimer's Disease, Surabhi Bhatia, Bianca Knoch, Jenny Wong, Woojin Scott Kim, Paul Else, Aaron J. Oakley, Brett Garner

Faculty of Science - Papers (Archive)

ApoD (apolipoprotein D) is up-regulated in AD (Alzheimer's disease) and upon oxidative stress. ApoD inhibits brain lipid peroxidation in vivo, but the mechanism is unknown. Specific methionine residues may inhibit lipid peroxidation by reducing radical-propagating L-OOHs (lipid hydroperoxides) to non-reactive hydroxides via a reaction that generates MetSO (methionine sulfoxide). Since apoD has three conserved methionine residues (Met49, Met93 and Met157), we generated recombinant proteins with either one or all methionine residues replaced by alanine and assessed their capacity to reduce HpETEs (hydroperoxyeicosatetraenoic acids) to their HETE (hydroxyeicosatetraenoic acid) derivatives. ApoD, apoDM49-A and apoDM157-A all catalysed the reduction of HpETEs to …

Synthesis And Anti-Leukaemic Activity Of Pyrrolo[3,2,1-Hi]Indole-1,2- Diones, Pyrrolo[3,2,1-Ij]Quinoline-1,2-Diones And Other Polycyclic Isatin Derivatives, Lidia Matesic, Julie M. Locke, Kara Vine, Marie Ranson, John B. Bremner, Danielle Skropeta

Faculty of Science - Papers (Archive)

To further expand the structure–cytotoxic activity relationships of isatin derivatives and to reduce flexibility in substituent groups at nitrogen, 20 analogues incorporating a ring system between the N1 and C7 atoms of isatin were prepared using a variety of synthetic strategies. This yielded pyrroloindole-, pyrroloquinoline-, pyrroloacridine-, pyrrolophenanthridine- and benzopyrrolophenanthridine-based systems with embedded isatin moieties, the latter possessing a novel carbon skeleton. These compounds were subsequently assessed for their in vitro cytotoxicity against human U937 lymphoma cells, with the brominated pyrroloacridine dione 27 showing the most promising activity (IC50 3.01 μM) after 24 h.

The Relationship Between Particulate Pollution Levels In Australian Cities, Meteorology, And Landscape Fire Activity Detected From Modis Hotspots, Owen F. Price, Grant J. Williamson, Sarah B. Henderson, Fay Johnston, David M. J. S Bowman

Faculty of Science - Papers (Archive)

Generally, sigmoid curves are used to describe the growth of animals over their lifetime. However, because growth rates often differ over an animal's lifetime a single curve may not accurately capture the growth. Broken-stick models constrained to pass through a common point have been proposed to describe the different growth phases, but these are often unsatisfactory because essentially there are still two functions that describe the lifetime growth. To provide a single, converged model to age animals with disparate growth phases we developed a smoothly joining two-phase nonlinear function (SJ2P), tailored to provide a more accurate description of lifetime growth …

Phytochemical And Biological Activity Studies Of The Bhutanese Medicinal Plant Corydalis Crispa, Phurpa Wangchuk, Paul A. Keller, Stephen G. Pyne, Thanapat Sastraruji, Malai Taweechotipatr, Roonglawan Rattanajak, Aunchalee Tonsomboon, Sumalee Kamchonwongpaisan

Faculty of Science - Papers (Archive)

The chemical constituents and biological activities of Corydalis crispa (Fumariaceae) were investigated for the first time. The phytochemical study resulted in the isolation of nine known isoquinoline alkaloids: protopine (1), 13-oxoprotopine (2), 13-oxocryptopine (3), stylopine (4), coreximine (5), rheagenine (6), ochrobirine (7), sibiricine (8) and bicuculline (9), with complete NMR data for 2 and 3 provided here for the first time. Crude extracts exhibitedsignificant anti-inflammatory (p < 0.01) activity against TNF-alpha production in LPS activated THP-1 cells. The acetylcholinesterase inhibitory activity of compounds 2, 4 and 7 and the antiplasmodial activity of compound 5 against P. falciparum strains TM4/8.2 and K1CB1 (multidrug resistant strain) are reported here for the first time. Stylopine (4) did not show antimalarial activity against the K1CB1 strain in contrast to a previous report. This study generated a scientific basis for the use of this plant in Bhutanese traditional medicine, either individually or in combination with other medicinal ingredients to treat a broad range of disorders. This study also identified compound 5 as potential new antimalarial lead compound.

Structural Insights Into The Dehydroascorbate Reductase Activity Of Human Omega-Class Glutathione Transferases, Huina Zhou, Joseph Brock, Dan Liu, Philip G. Board, Aaron J. Oakley

Faculty of Science - Papers (Archive)

The reduction of dehydroascorbate (DHA) to ascorbic acid (AA) is a vital cellular function. The omega-class glutathione transferases (GSTs) catalyze several reductive reactions in cellular biochemistry, including DHA reduction. In humans, two isozymes (GSTO1-1 and GSTO2-2) with significant DHA reductase (DHAR) activity are found, sharing 64% sequence identity. While the activity of GSTO2-2 is higher, it is significantly more unstable in vitro. We report the first crystal structures of human GSTO2-2, stabilized through site-directed mutagenesis and determined at 1.9Å resolution in the presence and absence of glutathione (GSH). The structure of a human GSTO1-1 has been determined at 1.7Å resolution …

Wild Type And Tangier Disease Abca1 Mutants Modulate Cellular Amyloid-Beta Production Independent Of Cholesterol Efflux Activity, Kim S. Woojin, Andrew F. Hill, Michael L. Fitzgerald, Mason W. Freeman, Genevieve Evin, Brett Garner

Faculty of Science - Papers (Archive)

Cerebral amyloid-β (Aβ) deposition is a critical feature of Alzheimer’s disease. Aβ is derived from the amyloid-β protein precursor (AβPP) via two sequential cleavages that are mediated by β-secretase and the γ-secretase complex. Such amyloidogenic AβPP processing occurs in lipid raft microdomains of cell membranes and it is thought that modulating the distribution of lipids in rafts may regulate AβPP processing and Aβ production. Certain ATP-binding cassette (ABC) transporters regulate lipid transport across cell membranes and, as recent studies reveal, within membrane microdomains. ABCA1 also regulates Aβ metabolism in the brain although its direct impact on AβPP remains an open …

Citrate Synthase Activity Does Not Account For Age-Related Differences In Maximum Aerobic Performance In House Sparrows (Passer Domesticus), William A. Buttemer, C Bech, Mark A. Chappell

Faculty of Science - Papers (Archive)

We measured basal (BMR) and peak metabolic rates (PMR) in juvenile and adult House Sparrows. Juvenile birds had significantly higher BMR, but lower PMR than adult birds, despite having statistically indistinguishable body masses. We then evaluated the relation between PMR and masses of central and peripheral organs and found that pectoral muscle mass best correlated with PMR in both groups, accounting for about 35% of the variation in PMR. Because citrate synthase (CS) has such major importance in affecting the first committed step in the tricarboxylic acid cycle, we characterized CS activity levels In extracted muscles to see if this …

The Cd-Loop Of Pai-2 (Serpinb2) Is Redundant In The Targeting, Inhibition And Clearance Of Cell Surface Upa Activity, Blake J. Cochran, Lakshitha P. Gunawardhana, Kara L. Perrow, Jodi A. Lee, Sergei A. Lobov, Marie Ranson

Faculty of Science - Papers (Archive)

Background: Plasminogen activator inhibitor type-2 (PAI-2, SERPINB2) is an irreversible, specific inhibitor of the urokinase plasminogen activator (uPA). Since overexpression of uPA at the surface of cancer cells is linked to malignancy, targeting of uPA by exogenous recombinant PAI-2 has been proposed as the basis of potential cancer therapies. To this end, reproducible yields of high purity protein that maintains this targeting ability is required. Herein we validate the use in vitro of recombinant 6 × His-tagged-PAI-2 lacking the intrahelical loop between C and D alpha-helices (PAI- 2 ΔCD-loop) for these purposes.

Results: We show that PAI-2 ΔCD-loop …

Antimycobacterial Activity Of Cinnamate-Based Esters Of The Triterpenes Betulinic, Oleanolic And Ursolic Acids, Tanud Tanachatchairatana, John B. Bremner, Ratchanaporn Chokchaisiri, Apichart Suksamrarn

Faculty of Science - Papers (Archive)

Betulinic acid, oleanolic acid and ursolic acid have been modified at the C-3 position to cinnamate-based esters and in vitro antimycobacterial activity against Mycobacterium tuberculosis H₃₇Ra has been determined. The results indicated that modification of the parent structures of betulinic acid, oleanolic acid and ursolic acid to the p-coumarate and, in the case of the latter two triterpenes, the ferulate ester analogues resulted in high antimycobacterial activity. Structure–activity relationships within the lupane, oleanane and ursane analogues and between these triterpenes are discussed.

Mimicking Phosphorylation Of Alphab-Crystallin Affects Its Chaperone Activity, Heath W. Ecroyd, Sarah Meehan, J Horwitz, Andrew Aquilina, J L Benesch, C V Robinson, Cait Macphee, John Carver

Faculty of Science - Papers (Archive)

No abstract provided.

A Survey Of Martian Dust Devil Activity Using Mars Global Surveyor Mars Orbiter Camera Images, Jenny A. Fisher, Mark I. Richardson, Claire E. Newman, Mark A. Szwast, Chelsea Graf, Shabari Basu, Shawn P. Ewald, Anthony D. Toigo, R. John Wilson

Faculty of Science - Papers (Archive)

A survey of dust devils using the Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) wide- and narrow-angle (WA and NA) images has been undertaken. The survey comprises two parts: (1) sampling of nine broad regions from September 1997 to July 2001 and (2) a focused seasonal monitoring of variability in the Amazonis region, an active dust devil site, from March 2001 to April 2004. For part 1, dust devils were identified in NA and WA images, and dust devil tracks were identified in NA images. Great spatial variability in dust devil occurrence is highlighted, with Amazonis Planitia being the …

Endogenous Redox Activity In Mouse Spermatozoa And Its Role In Regulating The Tyrosine Phosphorylation Events Associated With Sperm Capacitation, Heath W. Ecroyd, Russell C. Jones, Robert J. Aitken

Faculty of Science - Papers (Archive)

We investigated the role of endogenous redox activity in regulating the signal transduction pathway leading to tyrosine phosphorylation in mouse spermatozoa. Endogenous redox activity was monitored using a luminol-peroxidase chemiluminescent probe. Chemiluminescence increased in spermatozoa that were actively undergoing cAMP-mediated tyrosine phosphorylation events associated with capacitation and was inhibited in a dose-dependent manner by addition of catalase or diphenylene iodonium, both of which also inhibited tyrosine phosphorylation within the cell at points downstream of cAMP. Excluding bicarbonate from the incubation medium reduced the redox activity of sperm by 80-90% and dramatically reduced tyrosine phosphorylation. This study provides the first evidence …