The Extended Star Formation History of the Andromeda Spheroid at 35 Kpc on the Minor Axis

Using the HST ACS, we have obtained deep optical images reaching well below the oldest main sequence turnoff in fields on the southeast minor-axis of the Andromeda Galaxy, 35 kpc from the nucleus. These data probe the star formation history in the extended halo of Andromeda -- that region beyond 30 kpc that appears both chemically and morphologically distinct from the metal-rich, highly-disturbed inner spheroid. The present data, together with our previous data for fields at 11 and 21 kpc, do not show a simple trend toward older ages and lower metallicities, as one might expect for populations further removed from the obvious disturbances of the inner spheroid. Specifically, the mean ages and [Fe/H] values at 11 kpc, 21 kpc, and 35 kpc are 9.7 Gyr and -0.65, 11.0 Gyr and -0.87, and 10.5 Gyr and -0.98, respectively. In the best-fit model of the 35 kpc population, one third of the stars are younger than 10 Gyr, while only ~10% of the stars are truly ancient and metal-poor. The extended halo thus exhibits clear evidence of its hierarchical assembly, and the contribution from any classical halo formed via early monolithic collapse must be small.Comment: Accepted for publication in The Astrophysical Journal Letters. 4 pages, latex, 2 color figure

Global meteorological influences on the record UK rainfall of winter 2013-14

The UK experienced record average rainfall in winter 2013–14, leading to widespread and prolonged flooding. The immediate cause of this exceptional rainfall was a very strong and persistent cyclonic atmospheric circulation over the North East Atlantic Ocean. This was related to a very strong North Atlantic jet stream which resulted in numerous damaging wind storms. These exceptional meteorological conditions have led to renewed questions about whether anthropogenic climate change is noticeably influencing extreme weather. The regional weather pattern responsible for the extreme UK winter coincided with highly anomalous conditions across the globe. We assess the contributions from various possible remote forcing regions using sets of ocean–atmosphere model relaxation experiments, where winds and temperatures are constrained to be similar to those observed in winter 2013–14 within specified atmospheric domains. We find that influences from the tropics were likely to have played a significant role in the development of the unusual extra-tropical circulation, including a role for the tropical Atlantic sector. Additionally, a stronger and more stable stratospheric polar vortex, likely associated with a strong westerly phase of the stratospheric Quasi-Biennial Oscillation (QBO), appears to have contributed to the extreme conditions. While intrinsic climatic variability clearly has the largest effect on the generation of extremes, results from an analysis which segregates circulation-related and residual rainfall variability suggest that emerging climate change signals made a secondary contribution to extreme rainfall in winter 2013–14

Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification

© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo

An Endoribonuclease Functionally Linked to Perinuclear mRNP Quality Control Associates with the Nuclear Pore Complexes

Nuclear mRNA export is a crucial step in eukaryotic gene expression, which is in yeast coupled to cotranscriptional messenger ribonucleoprotein particle (mRNP) assembly and surveillance. Several surveillance systems that monitor nuclear mRNP biogenesis and export have been described, but the mechanism by which the improper mRNPs are recognized and eliminated remains poorly understood. Here we report that the conserved PIN domain protein Swt1 is an RNA endonuclease that participates in quality control of nuclear mRNPs and can associate with the nuclear pore complex (NPC). Swt1 showed endoribonuclease activity in vitro that was inhibited by a point mutation in the predicted catalytic site. Swt1 lacked clear sequence specificity but showed a strong preference for single-stranded regions. Genetic interactions were found between Swt1 and the THO/TREX and TREX-2 complexes, and with components of the perinuclear mRNP surveillance system, Mlp1, Nup60, and Esc1. Inhibition of the nuclease activity of Swt1 increased the levels and cytoplasmic leakage of unspliced aberrant pre-mRNA, and induced robust nuclear poly(A)+ RNA accumulation in mlp1Δ and esc1Δ strains. Overexpression of Swt1 also caused strong nuclear poly(A)+ RNA accumulation. Swt1 is normally distributed throughout the nucleus and cytoplasm but becomes concentrated at nuclear pore complexes (NPCs) in the nup133Δ mutant, which causes NPC clustering and defects in mRNP export. The data suggest that Swt1 endoribonuclease might be transiently recruited to NPCs to initiate the degradation of defective pre-mRNPs or mRNPs trapped at nuclear periphery in order to avoid their cytoplasmic export and translation