Structural insights into omega-class glutathione transferases: a snapshot of enzyme reduction and identification of a non-catalytic ligandin site

Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot of the enzyme in the process of regeneration. GSSG occupies both the G (GSH-binding) and H (hydrophobic-binding) sites and causes re-arrangement of some H-site residues. In the same structure we demonstrate the existence of a novel "ligandin" binding site deep within in the dimer interface of this enzyme, containing S-(4-nitrophenacyl)glutathione, an isozyme-specific substrate for hGSTO1-1. The ligandin site, conserved in Omega class GSTs from a range of species, is hydrophobic in nature and may represent the binding location for tocopherol esters that are uncompetitive hGSTO1-1 inhibitors.This work was supported by National Health and Medical Research Council Project Grant 366731. AJO is supported by an Australian Research Council Future Fellowship FT0990287

Flight range, fuel load and the impact of climate change on the journeys of migrant birds

Collection of biometric data was supported by the Natural Environment Research Council (NE/I028068/1) to JAT and the USUK Fulbright Commission and the Oxford Clarendon Fund to C.S. This research was funded by a Durham University Seedcorn grant to SGW. Production of the underlying SDMs was funded by a National Environment Research Council training grant (NE/J500215/1).Climate change is predicted to increase migration distances for many migratory species, but the physiological and temporal implications of longer migratory journeys have not been explored. Here, we combine information about species' flight range potential and migratory refuelling requirements to simulate the number of stopovers required and the duration of current migratory journeys for 77 bird species breeding in Europe. Using tracking data, we show that our estimates accord with recorded journey times and stopovers for most species. We then combine projections of altered migratory distances under climate change with models of avian flight to predict future migratory journeys. We find that 37% of migratory journeys undertaken by long-distance migrants will necessitate an additional stopover in future. These greater distances and the increased number of stops will substantially increase overall journey durations of many long-distance migratory species, a factor not currently considered in climate impact studies.Publisher PDFPeer reviewe

Ariel - Volume 4 Number 6

Editors David A. Jacoby Eugenia Miller Tom Williams Associate Editors Paul Bialas Terry Burt Michael Leo Gail Tenikat Editor Emeritus and Business Manager Richard J. Bonnano Movie Editor Robert Breckenridge Staff Richard Blutstein Mary F. Buechler J.D. Kanofsky Rocket Weber David Maye

A survey of weather information possessed by thirty-two pupils randomly selected from sixth and eleventh grades and from special classes

Thesis (Ed.M.)--Boston Universit

Spitzer, Near-Infrared, and Submillimeter Imaging of the Relatively Sparse Young Cluster, Lynds 988e

We present {\it Spitzer} images of the relatively sparse, low luminosity young cluster L988e, as well as complementary near-infrared (NIR) and submillimeter images of the region. The cluster is asymmetric, with the western region of the cluster embedded within the molecular cloud, and the slightly less dense eastern region to the east of, and on the edge of, the molecular cloud. With these data, as well as with extant H$\alpha$ data of stars primarily found in the eastern region of the cluster, and a molecular $^{13}$CO gas emission map of the entire region, we investigate the distribution of forming young stars with respect to the cloud material, concentrating particularly on the differences and similarities between the exposed and embedded regions of the cluster. We also compare star formation in this region to that in denser, more luminous and more massive clusters already investigated in our comprehensive multi-wavelength study of young clusters within 1 kpc of the Sun.Comment: 21 pages, 6 tables, 13 figures. Full resolution figures at: http://astro.pas.rochester.edu/~tom/Preprints/L988e.pd

THE IMPACT OF A CORONARY ARTERY DISEASE GENETIC RISK SCORE ON MYOCARDIAL INFARCTION RISK IN A MULTI-ETHNIC POPULATION: AN INTERHEART STUDY

Background: Genome wide association studies (GWAS) performed in Caucasian populations have identified several single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD), although their cumulative impact in other ethnicities is unknown. Using a genetic risk score (GRS), we examined the impact of CAD related SNPs on myocardial infarction (MI) in a multi-ethnic population. Methods: We included 4083 MI cases and 4473 controls from the INTERHEART case: control study, stratified by six ethnic groups: European, South Asian, other Asian, Arab, Latin American, and African. We created a GRS comprised of 25 SNPS, and tested its association with MI in individual ethnicities using logistic regression, and across ethnic groups through meta-analyses. Results were adjusted for age, sex, and modifiable risk factors. Results: The GRS was significantly associated with MI in Europeans (odds ratio [OR] = 1.08, 95% confidence interval [CI] 1.04-1.12 per risk allele), South Asians (OR = 1.09, 95% CI 1.05-1.14), other Asians (OR = 1.09, 95% CI 1.04-1.15), and Arabs (OR = 1.07, 95% CI 1.03-1.12). In Latin Americans and Africans the GRS was not significant. Meta-analysis of ethnic groups demonstrated a 1.06 (95% CI 1.03-1.09) increase in the odds of MI with the GRS per risk allele. Significant heterogeneity was observed, which was reduced by exclusion of Latin Americans (I2=63% to 0%). Above clinical risk factors, the GRS modestly increased population attributable risk (PAR) (0.92 to 0.94), concordance statistic (0.73 to 0.74), net reclassification improvement (0.14), and integrated discriminatory improvement (0.007). Conclusions: The GRS was associated with a significant increase in the odds of MI in multiple ethnic groups. Improvements in PAR, discrimination and reclassification were modest above clinical factors.Master of Science (MSc

Strong field ionization to multiple electronic states in water

High harmonic spectra show that laser-induced strong field ionization of water has a significant contribution from an inner-valence orbital. Our experiment uses the ratio of H2O and D2O high harmonic yields to isolate the characteristic nuclear motion of the molecular ionic states. The nuclear motion initiated via ionization of the highest occupied molecular orbital (HOMO) is small and is expected to lead to similar harmonic yields for the two isotopes. In contrast, ionization of the second least bound orbital (HOMO-1) exhibits itself via a strong bending motion which creates a significant isotope effect. We elaborate on this interpretation by simulating strong field ionization and high harmonic generation from the water isotopes using the time-dependent Schr\"odinger equation. We expect that this isotope marking scheme for probing excited ionic states in strong field processes can be generalized to other molecules