Packaging signals in single-stranded RNA viruses: nature’s alternative to a purely electrostatic assembly mechanism

The formation of a protective protein container is an essential step in the life-cycle of most viruses. In the case of single-stranded (ss)RNA viruses, this step occurs in parallel with genome packaging in a co-assembly process. Previously, it had been thought that this process can be explained entirely by electrostatics. Inspired by recent single-molecule fluorescence experiments that recapitulate the RNA packaging specificity seen in vivo for two model viruses, we present an alternative theory, which recognizes the important cooperative roles played by RNA–coat protein interactions, at sites we have termed packaging signals. The hypothesis is that multiple copies of packaging signals, repeated according to capsid symmetry, aid formation of the required capsid protein conformers at defined positions, resulting in significantly enhanced assembly efficiency. The precise mechanistic roles of packaging signal interactions may vary between viruses, as we have demonstrated for MS2 and STNV. We quantify the impact of packaging signals on capsid assembly efficiency using a dodecahedral model system, showing that heterogeneous affinity distributions of packaging signals for capsid protein out-compete those of homogeneous affinities. These insights pave the way to a new anti-viral therapy, reducing capsid assembly efficiency by targeting of the vital roles of the packaging signals, and opens up new avenues for the efficient construction of protein nanocontainers in bionanotechnology

A Graph-Based Approach to Topic Clustering for Online Comments to News

This paper investigates graph-based approaches to labeled topic clustering of reader comments in online news. For graph-based clustering we propose a linear regression model of similarity between the graph nodes (comments) based on similarity features and weights trained using automatically derived training data. To label the clusters our graph-based approach makes use of DBPedia to abstract topics extracted from the clusters. We evaluate the clustering approach against gold standard data created by human annotators and compare its results against LDA – currently reported as the best method for the news comment clustering task. Evaluation of cluster labelling is set up as a retrieval task, where human annotators are asked to identify the best cluster given a cluster label. Our clustering approach significantly outperforms the LDA baseline and our evaluation of abstract cluster labels shows that graph-based approaches are a promising method of creating labeled clusters of news comments, although we still find cases where the automatically generated abstractive labels are insufficient to allow humans to correctly associate a label with its cluster

Composition and evolution of the Ancestral South Sandwich Arc: implications for the flow of deep ocean water and mantle through the Drake Passage gateway

The Ancestral South Sandwich Arc (ASSA) has a short life-span of c.20 m.y. (Early Oligocene to Middle-Upper Miocene) before slab retreat and subsequent ‘resurrection’ as the active South Sandwich Island Arc (SSIA). The ASSA is, however, significant because it straddled the eastern margin of the Drake Passage Gateway where it formed a potential barrier to deep ocean water and mantle flow from the Pacific to Atlantic. The ASSA may be divided into three parts, from north to south: the Central Scotia Sea (CSS), the Discovery segment, and the Jane segment. Published age data coupled with new geochemical data (major elements, trace elements, Hf-Nd-Sr-Pb isotopes) from the three ASSA segments place constraints on models for the evolution of the arc and hence gateway development. The CSS segment has two known periods of activity. The older, Oligocene, period produced basic-acid, mostly calc-alkaline rocks, best explained in terms of subduction initiation volcanism of Andean-type (no slab rollback). The younger, Middle-Late Miocene period produced basic-acid, high-K calc-alkaline rocks (lavas and pyroclastic rocks with abundant volcanigenic sediments) which, despite being erupted on oceanic crust, have continental arc characteristics best explained in terms of a large, hot subduction flux most typical of a syn- or post-collision arc setting. Early-Middle Miocene volcanism in the Discovery and Jane arc segments is geochemically quite different, being typically tholeiitic and compositionally similar to many lavas from the active South Sandwich island arc front. There is indirect evidence for Western Pacific-type (slab rollback) subduction initiation in the southern part of the ASSA and for the back-arc basins (the Jane and Scan Basins) to have been active at the time of arc volcanism. Models for the death of the ASSA in the south following a series of ridge-trench collisions, are not positively supported by any geochemical evidence of hot subduction, but cessation of subduction by approach of progressively more buoyant oceanic lithosphere is consistent with both geochemistry and geodynamics. In terms of deep ocean water flow the early stages of spreading at the East Scotia Ridge (starting at 17-15 Ma) may have been important in breaking up the ASSA barrier while the subsequent establishment of a STEP (Subduction-Transform Edge Propagator) fault east of the South Georgia microcontinent (< 11 Ma) led to formation of the South Georgia Passage used by the Antarctic Circumpolar Current today. In terms of mantle flow, the subduction zone and arc root likely acted as a barrier to mantle flow in the CSS arc segment such that the ASSA itself became the Pacific-South Atlantic mantle domain boundary. This was not the case in the Discovery and Jane arc segments, however, because northwards flow of South Atlantic mantle behind the southern part of the ASSA gave an Atlantic provenance to the whole southern ASSA

Quantum Gravitational Corrections to the Nonrelativistic Scattering Potential of Two Masses

We treat general relativity as an effective field theory, obtaining the full nonanalytic component of the scattering matrix potential to one-loop order. The lowest order vertex rules for the resulting effective field theory are presented and the one-loop diagrams which yield the leading nonrelativistic post-Newtonian and quantum corrections to the gravitational scattering amplitude to second order in G are calculated in detail. The Fourier transformed amplitudes yield a nonrelativistic potential and our result is discussed in relation to previous calculations. The definition of a potential is discussed as well and we show how the ambiguity of the potential under coordinate changes is resolved.Comment: 27 pages, 17 figure

Developments in Rare Kaon Decay Physics

We review the current status of the field of rare kaon decays. The study of rare kaon decays has played a key role in the development of the standard model, and the field continues to have significant impact. The two areas of greatest import are the search for physics beyond the standard model and the determination of fundamental standard-model parameters. Due to the exquisite sensitivity of rare kaon decay experiments, searches for new physics can probe very high mass scales. Studies of the k->pnn modes in particular, where the first event has recently been seen, will permit tests of the standard-model picture of quark mixing and CP violation.Comment: One major revision to the text is the branching ratio of KL->ppg, based on a new result from KTeV. Several references were updated, with minor modifications to the text. A total of 48 pages, with 28 figures, in LaTeX; to be published in the Annual Review of Nuclear and Particle Science, Vol. 50, December 200

Practical guide to glucocorticoid induced hyperglycaemia and diabetes

Glucocorticoids, also known as steroids, are a class of anti-inflammatory drugs utilised widely in clinical practice for a variety of conditions. They are associated with a range of side effects including abnormalities of glucose metabolism. Multiple guidelines have been published to illustrate best management of glucocorticoid-induced hyperglycaemia and diabetes in a variety of settings. This article discusses current best clinical practice including diagnosis, investigations and ongoing management of glucocorticoid-induced dysglycaemia in both in- and outpatient settings

Vector-meson contributions do not explain the rate and spectrum in K_L -> pi0 gamma gamma

We analyze the recent NA48 data for the reaction K_L -> pi0 gamma gamma with and without the assumption of vector meson dominance (VMD). We find that the data is well described by a three-parameter expression inspired by O(p^6) chiral perturbation theory. We also find that it is impossible to fit the shape of the decay distribution and the overall rate simultaneously if one imposes the VMD constraints on the three parameters. We comment on the different fits and their implications for the CP-conserving component of the decay K_L -> pi0 e+ e-.Comment: Version accepted for publication on Phys. Rev. D. 19 pages, LaTeX, 8 figures, uses epsf.st

The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c6A

Cytochrome c 6A is a eukaryotic member of the Class I cytochrome c family possessing a high structural homology with photosynthetic cytochrome c 6 from cyanobacteria, but structurally and functionally distinct through the presence of a disulfide bond and a heme mid-point redox potential of + 71 mV (vs normal hydrogen electrode). The disulfide bond is part of a loop insertion peptide that forms a cap-like structure on top of the core α-helical fold. We have investigated the contribution of the disulfide bond to thermodynamic stability and (un)folding kinetics in cytochrome c 6A from Arabidopsis thaliana by making comparison with a photosynthetic cytochrome c 6 from Phormidium laminosum and through a mutant in which the Cys residues have been replaced with Ser residues (C67/73S). We find that the disulfide bond makes a significant contribution to overall stability in both the ferric and ferrous heme states. Both cytochromes c 6A and c 6 fold rapidly at neutral pH through an on-pathway intermediate. The unfolding rate for the C67/73S variant is significantly increased indicating that the formation of this region occurs late in the folding pathway. We conclude that the disulfide bridge in cytochrome c 6A acts as a conformational restraint in both the folding intermediate and native state of the protein and that it likely serves a structural rather than a previously proposed catalytic role. © 2011 Elsevier B.V. All rights reserved