Species trees from consensus single nucleotide polymorphism (SNP) data: Testing phylogenetic approaches with simulated and empirical data

Datasets of hundreds or thousands of SNPs (Single Nucleotide Polymorphisms) from multiple individuals per species are increasingly used to study population structure, species delimitation and shallow phylogenetics. The principal software tool to infer species or population trees from SNP data is currently the BEAST template SNAPP which uses a Bayesian coalescent analysis. However, it is computationally extremely demanding and tolerates only small amounts of missing data. We used simulated and empirical SNPs from plants (Australian Craspedia, Asteraceae, and Pelargonium, Geraniaceae) to compare species trees produced (1) by SNAPP, (2) using SVD quartets, and (3) using Bayesian and parsimony analysis with several different approaches to summarising data from multiple samples into one set of traits per species. Our aims were to explore the impact of tree topology and missing data on the results, and to test which data summarising and analyses approaches would best approximate the results obtained from SNAPP for empirical data. SVD quartets retrieved the correct topology from simulated data, as did SNAPP except in the case of a very unbalanced phylogeny. Both methods failed to retrieve the correct topology when large amounts of data were missing. Bayesian analysis of species level summary data scoring the two alleles of each SNP as independent characters and parsimony analysis of data scoring each SNP as one character produced trees with branch length distributions closest to the true trees on which SNPs were simulated. For empirical data, Bayesian inference and Dollo parsimony analysis of data scored allele-wise produced phylogenies most congruent with the results of SNAPP. In the case of study groups divergent enough for missing data to be phylogenetically informative (because of additional mutations preventing amplification of genomic fragments or bioinformatic establishment of homology), scoring of SNP data as a presence/absence matrix irrespective of allele content might be an additional option. As this depends on sampling across species being reasonably even and a random distribution of non-informative instances of missing data, however, further exploration of this approach is needed. Properly chosen data summary approaches to inferring species trees from SNP data may represent a potential alternative to currently available individual-level coalescent analyses especially for quick data exploration and when dealing with computationally demanding or patchy datasets.This study was partly supported by a Centre of Biodiversity Analysis Ignition Grant to A.N.S.-L. and Justin Borevitz in 2013/14

Early pH Changes in Musculoskeletal Tissues upon Injury-Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release

A Composite Seyfert 2 X-ray Spectrum: Implications for the Origin of the Cosmic X-ray Background

We present a composite 1-10 keV Seyfert 2 X-ray spectrum, derived from ASCA observations of a distance-limited sample of nearby galaxies. All 29 observed objects were detected. Above ~3 keV, the composite spectrum is inverted, confirming that Seyfert 2 galaxies as a class have the spectral properties necessary to explain the flat shape of the cosmic X-ray background spectrum. Integrating the composite spectrum over redshift, we find that the total emission from Seyfert 2 galaxies, combined with the expected contribution from unabsorbed type 1 objects, provides an excellent match to the spectrum and intensity of the hard X-ray background. The principal uncertainty in this procedure is the cosmic evolution of the Seyfert 2 X-ray luminosity function. Separate composite spectra for objects in our sample with and without polarized broad optical emission lines are also presented.Comment: 11 pages (AASTeX), including 3 figures. Accepted for publication in ApJ Letter

Sequential conformational rearrangements in flavivirus membrane fusion

The West Nile Virus (WNV) envelope protein, E, promotes membrane fusion during viral cell entry by undergoing a low-pH triggered conformational reorganization. We have examined the mechanism of WNV fusion and sought evidence for potential intermediates during the conformational transition by following hemifusion of WNV virus-like particles (VLPs) in a single particle format. We have introduced specific mutations into E, to relate their influence on fusion kinetics to structural features of the protein. At the level of individual E subunits, trimer formation and membrane engagement of the threefold clustered fusion loops are rate-limiting. Hemifusion requires at least two adjacent trimers. Simulation of the kinetics indicates that availability of competent monomers within the contact zone between virus and target membrane makes trimerization a bottleneck in hemifusion. We discuss the implications of the model we have derived for mechanisms of membrane fusion in other contexts. DOI: http://dx.doi.org/10.7554/eLife.04389.00

Changes in the gut microbiome and fermentation products concurrent with enhanced longevity in acarbose-treated mice.

BACKGROUND: Treatment with the α-glucosidase inhibitor acarbose increases median lifespan by approximately 20% in male mice and 5% in females. This longevity extension differs from dietary restriction based on a number of features, including the relatively small effects on weight and the sex-specificity of the lifespan effect. By inhibiting host digestion, acarbose increases the flux of starch to the lower digestive system, resulting in changes to the gut microbiota and their fermentation products. Given the documented health benefits of short-chain fatty acids (SCFAs), the dominant products of starch fermentation by gut bacteria, this secondary effect of acarbose could contribute to increased longevity in mice. To explore this hypothesis, we compared the fecal microbiome of mice treated with acarbose to control mice at three independent study sites. RESULTS: Microbial communities and the concentrations of SCFAs in the feces of mice treated with acarbose were notably different from those of control mice. At all three study sites, the bloom of a single bacterial taxon was the most obvious response to acarbose treatment. The blooming populations were classified to the largely uncultured Bacteroidales family Muribaculaceae and were the same taxonomic unit at two of the three sites. Propionate concentrations in feces were consistently elevated in treated mice, while the concentrations of acetate and butyrate reflected a dependence on study site. Across all samples, Muribaculaceae abundance was strongly correlated with propionate and community composition was an important predictor of SCFA concentrations. Cox proportional hazards regression showed that the fecal concentrations of acetate, butyrate, and propionate were, together, predictive of mouse longevity even while controlling for sex, site, and acarbose. CONCLUSION: We observed a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in the longevity-enhancing properties of acarbose. Treatment modulated the taxonomic composition and fermentation products of the gut microbiome, while the site-dependence of the responses illustrate the challenges facing reproducibility and interpretation in microbiome studies. These results motivate future studies exploring manipulation of the gut microbial community and its fermentation products for increased longevity, testing causal roles of SCFAs in the observed effects of acarbose

Early pH changes in musculoskeletal tissues upon injury-aerobic catabolic pathway activity linked to inter-individual differences in local pH

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release

Crepuscular Rays from the Highly Inclined Active Galactic Nucleus in IC 5063

On Earth near sunset, the sun may cast "crepuscular rays" such that clouds near the horizon obscure the origin of light scattered in bright rays. In principle, AGN should be able to produce similar effects. Using new Hubble Space Telescope (HST) near-infrared and optical observations, we show that the active galaxy IC 5063 contains broad radial rays extending to $\gtrsim$11 kpc from the nucleus. We argue that the bright rays may arise from dusty scattering of continuum emission from the active nucleus, while the dark rays are due to shadowing near the nucleus, possibly by a warped torus. We also consider alternative AGN-related and stellar origins for the extended light.Comment: Accepted for publication to ApJ Letters. 13 pages, 5 figures. Facilitated by Twitter discussion (see https://twitter.com/SpaceGeck/status/1201350966945017856). This version corrects figure labels and includes other more minor update

The Farthest Known Supernova: Support for an Accelerating Universe and a Glimpse of the Epoch of Deceleration

We present photometric observations of an apparent Type Ia supernova (SN Ia) at a redshift of ~1.7, the farthest SN observed to date. SN 1997ff, was discovered in a repeat observation by the HST of the HDF-), and serendipitously monitored with NICMOS on HST throughout the GTO campaign. The SN type can be determined from the host galaxy type:an evolved, red elliptical lacking enough recent star formation to provide a significant population of core-collapse SNe. The class- ification is further supported by diagnostics available from the observed colors and temporal behavior of the SN, both of which match a typical SN Ia. The photo- metric record of the SN includes a dozen flux measurements in the I, J, and H bands spanning 35 days in the observed frame. The redshift derived from the SN photometry, z=1.7+/-0.1, is in excellent agreement with the redshift estimate of z=1.65+/-0.15 derived from the U_300,B_450,V_606,I_814,J_110,J_125,H_160, H_165,K_s photometry of the galaxy. Optical and near-infrared spectra of the host provide a very tentative spectroscopic redshift of 1.755. Fits to observations of the SN provide constraints for the redshift-distance relation of SNe~Ia and a powerful test of the current accelerating Universe hypothesis. The apparent SN brightness is consistent with that expected in the decelerating phase of the preferred cosmological model, Omega_M~1/3, Omega_Lambda~2/3. It is inconsistent with grey dust or simple luminosity evolution, candidate astro- physical effects which could mimic past evidence for an accelerating Universe from SNe Ia at z~0.5.We consider several sources of possible systematic error including lensing, SN misclassification, selection bias, and calibration errors. Currently, none of these effects appears likely to challenge our conclusions.Comment: Accepted to the Astrophysical Journal 38 pages, 15 figures, Pretty version available at http://icarus.stsci.edu/~stefano/ariess.tar.g

Evaluating Systematic Dependencies of Type Ia Supernovae: The Influence of Deflagration to Detonation Density

We explore the effects of the deflagration to detonation transition (DDT) density on the production of Ni-56 in thermonuclear supernova explosions (type Ia supernovae). Within the DDT paradigm, the transition density sets the amount of expansion during the deflagration phase of the explosion and therefore the amount of nuclear statistical equilibrium (NSE) material produced. We employ a theoretical framework for a well-controlled statistical study of two-dimensional simulations of thermonuclear supernovae with randomized initial conditions that can, with a particular choice of transition density, produce a similar average and range of Ni-56 masses to those inferred from observations. Within this framework, we utilize a more realistic "simmered" white dwarf progenitor model with a flame model and energetics scheme to calculate the amount of Ni-56 and NSE material synthesized for a suite of simulated explosions in which the transition density is varied in the range 1-3x10^7 g/cc. We find a quadratic dependence of the NSE yield on the log of the transition density, which is determined by the competition between plume rise and stellar expansion. By considering the effect of metallicity on the transition density, we find the NSE yield decreases by 0.055 +/- 0.004 solar masses for a 1 solar metallicity increase evaluated about solar metallicity. For the same change in metallicity, this result translates to a 0.067 +/- 0.004 solar mass decrease in the Ni-56 yield, slightly stronger than that due to the variation in electron fraction from the initial composition. Observations testing the dependence of the yield on metallicity remain somewhat ambiguous, but the dependence we find is comparable to that inferred from some studies.Comment: 15 pages, 13 figures, accepted to ApJ on July 6, 201