A role for SNX5 in the regulation of macropinocytosis

Background: The mechanisms and components that regulate macropinocytosis are poorly understood. Here we have investigated the role of sorting nexin 5 (SNX5) in the regulation of macropinocytic activity

Does the revised cardiac risk index predict cardiac complications following elective lung resection?

Background: Revised Cardiac Risk Index (RCRI) score and Thoracic Revised Cardiac Risk Index (ThRCRI) score were developed to predict the risks of postoperative major cardiac complications in generic surgical population and thoracic surgery respectively. This study aims to determine the accuracy of these scores in predicting the risk of developing cardiac complications including atrial arrhythmias after lung resection surgery in adults. Methods: We studied 703 patients undergoing lung resection surgery in a tertiary thoracic surgery centre. Observed outcome measures of postoperative cardiac morbidity and mortality were compared against those predicted by risk. Results: Postoperative major cardiac complications and supraventricular arrhythmias occurred in 4.8% of patients. Both index scores had poor discriminative ability for predicting postoperative cardiac complications with an area under receiver operating characteristic (ROC) curve of 0.59 (95% CI 0.51-0.67) for the RCRI score and 0.57 (95% CI 0.49-0.66) for the ThRCRI score. Conclusions: In our cohort, RCRI and ThRCRI scores failed to accurately predict the risk of cardiac complications in patients undergoing elective resection of lung cancer. The British Thoracic Society (BTS) recommendation to seek a cardiology referral for all asymptomatic pre-operative lung resection patients with > 3 RCRI risk factors is thus unlikely to be of clinical benefit

Silicate dust in the environment of RS Ophiuchi following the 2006 eruption

We present further Spitzer Space Telescope observations of the recurrent nova RS Ophiuchi, obtained over the period 208-430 days after the 2006 eruption. The later Spitzer IRS data show that the line emission and free-free continuum emission reported earlier is declining, revealing incontrovertible evidence for the presence of silicate emission features at 9.7 and 18microns. We conclude that the silicate dust survives the hard radiation impulse and shock blast wave from the eruption. The existence of the extant dust may have significant implications for understanding the propagation of shocks through the red giant wind and likely wind geometry.Comment: 12 pages, 4 figures, accepted for publication in ApJ (Letters

A New Model for the Spiral Structure of the Galaxy. Superposition of 2+4-armed patterns

We investigate the possibility of describing the spiral pattern of the Milky Way in terms of a model of superposition 2- and 4-armed wave harmonics (the simplest description, besides pure modes). Two complementary methods are used: a study of stellar kinematics, and direct tracing of positions of spiral arms. In the first method, the parameters of the galactic rotation curve and the free parameters of the spiral density waves were obtained from Cepheid kinematics, under different assumptions. To turn visible the structure corresponding to these models, we computed the evolution of an ensemble of N-particles, simulating the ISM clouds, in the perturbed galactic gravitational field. In the second method, we present a new analysis of the longitude-velocity (l-v) diagram of the sample of galactic HII regions, converting positions of spiral arms in the galactic plane into locii of these arms in the l-v diagram. Both methods indicate that the ``self-sustained'' model, in which the 2-armed and 4-armed mode have different pitch angles (6 arcdeg and 12 arcdeg, respectively) is a good description of the disk structure. An important conclusion is that the Sun happens to be practically at the corotation circle. As an additional result of our study, we propose an independent test for localization of the corotation circle in a spiral galaxy: a gap in the radial distribution of interstellar gas has to be observed in the corotation region.Comment: 17 pages, 9 figures, Latex, uses aas2pp4.st

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Group Polarization in the Team Dictator Game reconsidered

While most papers on team decision-making find teams to behave more selfish, less trusting and less altruistic than individuals, Cason and Mui (1997) report that teams are more altruistic than individuals in a dictator game. Using a within-subjects design we re-examine group polarization by letting subjects make individual as well as team decisions in an experimental dictator game. In our experiment teams are more selfish than individuals, and the most selfish team member has the strongest influence on team decisions. Various sources of the different findings in Cason and Mui (1997) and in our paper are discussed

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

A New Look at the Kinematics of Neutral Hydrogen in the Small Magellanic Cloud

We have used the latest HI observations of the Small Magellanic Cloud (SMC), obtained with the Australia Telescope Compact Array and the Parkes telescope, to re-examine the kinematics of this dwarf, irregular galaxy. A large velocity gradient is found in the HI velocity field with a significant symmetry in iso-velocity contours, suggestive of a differential rotation. A comparison of HI data with the predictions from tidal models for the SMC evolution suggests that the central region of the SMC corresponds to the central, disk- or bar-like, component left from the rotationally supported SMC disk prior to its last two encounters with the Large Magellanic Cloud. In this scenario, the velocity gradient is expected as a left-over from the original, pre-encounter, angular momentum. We have derived the HI rotation curve and the mass model for the SMC. This rotation curve rapidly rises to about 60 km/s up to the turnover radius of ~3 kpc. A stellar mass-to-light ratio of about unity is required to match the observed rotation curve, suggesting that a dark matter halo is not needed to explain the dynamics of the SMC. A set of derived kinematic parameters agrees well with the assumptions used in tidal theoretical models that led to a good reproduction of observational properties of the Magellanic System. The dynamical mass of the SMC, derived from the rotation curve, is 2.4x10^9 Msolar.Comment: To appear in ApJ, March 20 2004, 11 figure

Statistical and visual differentiation of subcellular imaging

<p>Abstract</p> <p>Background</p> <p>Automated microscopy technologies have led to a rapid growth in imaging data on a scale comparable to that of the genomic revolution. High throughput screens are now being performed to determine the localisation of all of proteins in a proteome. Closer to the bench, large image sets of proteins in treated and untreated cells are being captured on a daily basis to determine function and interactions. Hence there is a need for new methodologies and protocols to test for difference in subcellular imaging both to remove bias and enable throughput. Here we introduce a novel method of statistical testing, and supporting software, to give a rigorous test for difference in imaging. We also outline the key questions and steps in establishing an analysis pipeline.</p> <p>Results</p> <p>The methodology is tested on a high throughput set of images of 10 subcellular localisations, and it is shown that the localisations may be distinguished to a statistically significant degree with as few as 12 images of each. Further, subtle changes in a protein's distribution between nocodazole treated and control experiments are shown to be detectable. The effect of outlier images is also examined and it is shown that while the significance of the test may be reduced by outliers this may be compensated for by utilising more images. Finally, the test is compared to previous work and shown to be more sensitive in detecting difference. The methodology has been implemented within the iCluster system for visualising and clustering bio-image sets.</p> <p>Conclusion</p> <p>The aim here is to establish a methodology and protocol for testing for difference in subcellular imaging, and to provide tools to do so. While iCluster is applicable to moderate (<1000) size image sets, the statistical test is simple to implement and will readily be adapted to high throughput pipelines to provide more sensitive discrimination of difference.</p

Anisomycin activates JNK and sensitises DU 145 prostate carcinoma cells to Fas mediated apoptosis

Treatment of the hormone refractory prostate cancer cell line DU 145 with sublethal concentrations of chemotherapeutic drugs has been reported to sensitise these cells to Fas mediated apoptosis. However, the mechanism by which this occurs has not been determined. Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs. Using anisomycin, a potent JNK agonist, we have demonstrated a role for JNK in Fas mediated apoptosis in DU 145 cells. Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic signal. Furthermore, we have shown that inhibition of Fas mediated apoptosis is an early event in DU 145 cells, occurring upstream of Caspase 8 cleavage. It is hoped that identifying the target of JNK will allow novel therapies to be developed for the treatment of hormone refractory prostate cancer. Such therapies are especially important because no single or combined treatment to date has significantly prolonged survival in patients with hormone refractory prostate cancer