Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations

The sub-energetic GRB 031203 as a cosmic analogue to GRB 980425

Over the six years since the discovery of the gamma-ray burst GRB 980425, associated with the nearby (distance, ~40 Mpc) supernova 1998bw, astronomers have fiercely debated the nature of this event. Relative to bursts located at cosmological distances, (redshift, z~1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed the explosion was sub-energetic by a factor of 10. Here, we report observations of the radio and X-ray afterglow of the recent z=0.105 GRB 031203 and demonstrate that it too is sub-energetic. Our result, when taken together with the low gamma-ray luminosity, suggest that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. Intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRBs 031203 and 980425) may enable us to reveal their expected large population.Comment: To Appear in Nature, August 5, 200

Astroglial pentose phosphate pathway rates in response to high-glucose environments

ROS (reactive oxygen species) play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain parenchymal cells remain unclear. The PPP (pentose phosphate pathway) and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of 14CO2 production from [1-14C]glucose and [6-14C]glucose. ROS production, mainly H2O2, and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum) stress (presumably through increased hexosamine biosynthetic pathway flux). Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase) by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein) expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke

High Energy Gamma-Ray Emission From Blazars: EGRET Observations

We will present a summary of the observations of blazars by the Energetic Gamma Ray Experiment Telescope (EGRET) on the Compton Gamma Ray Observatory (CGRO). EGRET has detected high energy gamma-ray emission at energies greater than 100 MeV from more that 50 blazars. These sources show inferred isotropic luminosities as large as $3\times 10^{49}$ ergs s$^{-1}$. One of the most remarkable characteristics of the EGRET observations is that the gamma-ray luminosity often dominates the bolometric power of the blazar. A few of the blazars are seen to exhibit variability on very short time-scales of one day or less. The combination of high luminosities and time variations seen in the gamma-ray data indicate that gamma-rays are an important component of the relativistic jet thought to characterize blazars. Currently most models for blazars involve a beaming scenario. In leptonic models, where electrons are the primary accelerated particles, gamma-ray emission is believed to be due to inverse Compton scattering of low energy photons, although opinions differ as to the source of the soft photons. Hardronic models involve secondary production or photomeson production followed by pair cascades, and predict associated neutrino production.Comment: 16 pages, 7 figures, style files included. Invited review paper in "Observational Evidence for Black Holes in the Universe," 1999, ed. S. K. Chakrabarti (Dordrecht: Kluwer), 215-23

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

The bright optical afterglow of the nearby gamma-ray burst of 29 March 2003

Many past studies of cosmological gamma-ray bursts (GRBs) have been limited because of the large distance to typical GRBs, resulting in faint afterglows. There has long been a recognition that a nearby GRB would shed light on the origin of these mysterious cosmic explosions, as well as the physics of their fireballs. However, GRBs nearer than z=0.2 are extremely rare, with an estimated rate of localisation of one every decade. Here, we report the discovery of bright optical afterglow emission from GRB 030329. Our prompt dissemination and the brilliance of the afterglow resulted in extensive followup (more than 65 telescopes) from radio through X-ray bands, as well as measurement of the redshift, z=0.169. The gamma-ray and afterglow properties of GRB 030329 are similar to those of cosmological GRBs (after accounting for the small distance), making this the nearest known cosmological GRB. Observations have already securely identified the progenitor as a massive star that exploded as a supernova, and we anticipate futher revelations of the GRB phenomenon from studies of this source.Comment: 13 pages, 4 figures. Original tex

Constraining GRB Emission Physics with Extensive Early-Time, Multiband Follow-up

Understanding the origin and diversity of emission processes responsible for Gamma-ray Bursts (GRBs) remains a pressing challenge. While prompt and contemporaneous panchromatic observations have the potential to test predictions of the internal-external shock model, extensive multiband imaging has been conducted for only a few GRBs. We present rich, early-time, multiband datasets for two \swift\ events, GRB 110205A and GRB 110213A. The former shows optical emission since the early stages of the prompt phase, followed by the steep rising in flux up to ~1000s after the burst ($t^{-\alpha}$ with $\alpha=-6.13 \pm 0.75$). We discuss this feature in the context of the reverse-shock scenario and interpret the following single power-law decay as being forward-shock dominated. Polarization measurements, obtained with the RINGO2 instrument mounted on the Liverpool Telescope, also provide hints on the nature of the emitting ejecta. The latter event, instead, displays a very peculiar optical to near-infrared lightcurve, with two achromatic peaks. In this case, while the first peak is probably due to the onset of the afterglow, we interpret the second peak to be produced by newly injected material, signifying a late-time activity of the central engine.Comment: 48 pages,11 figures, 24 tables. Accepted to The Astrophysical Journa

The host galaxies and explosion sites of long-duration gamma-ray bursts: Hubble Space Telescope near-infrared imaging

We present the results of a Hubble Space Telescope WFC3/F160WSnapshot survey of the host galaxies of 39 long-duration gamma-ray bursts (LGRBs) at z < 3. We have non-detections of hosts at the locations of four bursts. Sufficient accuracy to astrometrically align optical afterglowimages and determine the location of the LGRB within its hostwas possible for 31/35 detected hosts. In agreement with other work, we find the luminosity distribution of LGRB hosts is significantly fainter than that of a star formation rate-weighted field galaxy sample over the same redshift range, indicating LGRBs are not unbiasedly tracing the star formation rate. Morphologically, the sample of LGRB hosts is dominated by spiral-like or irregular galaxies. We find evidence for evolution of the population of LGRB hosts towards lower luminosity, higher concentrated hosts at lower redshifts. Their half-light radii are consistent with other LGRB host samples where measurements were made on rest-frame UV observations. In agreement with recent work, we find their 80 per cent enclosed flux radii distribution to be more extended than previously thought, making them intermediate between core-collapse supernova (CCSN) and superluminous supernova (SLSN) hosts. The galactocentric projectedoffset distribution confirms LGRBs as centrally concentrated, much more so than CCSNe and similar to SLSNe. LGRBs are strongly biased towards the brighter regions in their host light distributions, regardless of their offset. We find a correlation between the luminosity of the LGRB explosion site and the intrinsic column density, NH, towards the burst. © 2017 The Authors

The X-ray emission lines in GRB afterglows: the evidence for the two-component jet model

Recently, X-ray emission lines have been observed in X-ray afterglows of several $\gamma$-ray bursts. It is a major breakthrough for understanding the nature of the progenitors. It is proposed that the X-ray emission lines can be well explained by the Geometry-Dominated models, but in these models the illuminating angle is much larger than that of the collimated jet of the $\gamma$-ray bursts(GRBs). For GRB 011211, we obtain the illuminating angle is about $\theta\sim45^{\circ}$, while the angle of GRB jet is only $3.6^{\circ}$, so we propose that the outflow of the GRBs with emission lines should have two distinct components. The wide component illuminates the reprocessing material, and produces the emission lines, while the narrow one produces the $\gamma$-ray bursts. The observations show that the energy for producing the emission lines is higher than that of the GRBs. In this case, when the wide component dominates the afterglows, a bump will appear in the GRBs afterglows. For GRB 011211, the emergence time of the bump is less than 0.05 days after the GRB, it is obviously too early for the observation to catch it. With the presence of the X-ray emission lines there should also be a bright emission component between the UV and the soft X-rays. These features can be tested by the $Swift$ satellite in the near future.Comment: 10 pags, 1 figure, ChJAA in pres