Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix.

The refinement of biomolecular crystallographic models relies on geometric restraints to help to address the paucity of experimental data typical in these experiments. Limitations in these restraints can degrade the quality of the resulting atomic models. Here, an integration of the full all-atom Amber molecular-dynamics force field into Phenix crystallographic refinement is presented, which enables more complete modeling of biomolecular chemistry. The advantages of the force field include a carefully derived set of torsion-angle potentials, an extensive and flexible set of atom types, Lennard-Jones treatment of nonbonded interactions and a full treatment of crystalline electrostatics. The new combined method was tested against conventional geometry restraints for over 22 000 protein structures. Structures refined with the new method show substantially improved model quality. On average, Ramachandran and rotamer scores are somewhat better, clashscores and MolProbity scores are significantly improved, and the modeling of electrostatics leads to structures that exhibit more, and more correct, hydrogen bonds than those refined using traditional geometry restraints. In general it is found that model improvements are greatest at lower resolutions, prompting plans to add the Amber target function to real-space refinement for use in electron cryo-microscopy. This work opens the door to the future development of more advanced applications such as Amber-based ensemble refinement, quantum-mechanical representation of active sites and improved geometric restraints for simulated annealing

Bat Occupancy Estimates and Species Richness at Cache River National Wildlife Refuge

Six bat species of special concern, threatened or endangered, may occur in one of Arkansas’ largest bottomland hardwood forests, the Cache River National Wildlife Refuge (CRNWR). However, inventory of bat species throughout the refuge has been lacking and management plans may not be adequate in promoting bat conservation. The objectives of this study were to inventory bat species in the CRNWR, and determine bat-habitat associations via occupancy estimates. From May–August 2014 and 2015, we mist-netted from sunset for 5 hours. We also deployed bioacoustic devices throughout 5 habitat types (cypress-tupelo [dominantly Taxodium distichum and Nyssa aquatica], emergent wetland, mature forest, hardwood reforestation, and managed hardwood). Mist-netting yielded 460 bat captures with Rafinesque’s big-eared bats (Corynorhinus rafinesquii; n = 156) being the most common capture, followed by eastern red bats (Lasiurus borealis; n = 104), southeastern myotis (Myotis austroriparius; n = 91), evening bats (Nycticeius humeralis; n = 58), tri-colored bats (Perimyotis subflavus; n = 54), and a big-brown bat (Eptesicus fuscus; n = 1). Based on 3,896 calls identified with 85% certainty, evening bats and rarer big-brown bats tended to occupy managed hardwood forests more than any other habitat (occupancy probabilities ± SE: Ψ = 0.75 ± 0.13 and 0.38 ± 0.19, respectively). Tri-colored bats tended to be more present in mature forest habitats (Ψ = 0.91 ± 0.09), and Myotis species tended to have highest occupancy rates in cypress-tupelo stands (Ψ = 0.59 ± 0.15). Not all species were detected with both methods. Thus, we encourage future studies to combine mist-netting and acoustic surveying methods to minimize bias in species presence estimate. This would ensure management practices that would benefit all present species

SandflyMap: leveraging spatial data on sand fly vector distribution for disease risk assessments

We feature SandflyMap (www.sandflymap.org), a new map service within VectorMap (www.vectormap.org) that allows free public online access to global sand fly, tick and mosquito collection records and habitat suitability models. Given the short home range of sand flies, combining remote sensing and collection point data give a powerful insight into the environmental determinants of sand fly distribution. SandflyMap is aimed at medical entomologists, vector disease control workers, public health officials and health planners. Data are checked for geographical and taxonomic errors, and are comprised of vouchered specimen information, and both published and unpublished observation data. SandflyMap uses Microsoft Silverlight and ESRI’s ArcGIS Server 10 software platform to present disease vector data and relevant remote sensing layers in an online geographical information system format. Users can view the locations of past vector collections and the results of models that predict the geographic extent of individual species. Collection records are searchable and downloadable, and Excel collection forms with drop down lists, and Excel charts to country, are available for data contributors to map and quality control their data. SandflyMap makes accessible, and adds value to, the results of past sand fly collecting efforts. We detail the workflow for entering occurrence data from the literature to SandflyMap, using an example for sand flies from South America. We discuss the utility of SandflyMap as a focal point to increase collaboration and to explore the nexus between geography and vector-borne disease transmission

Evolutionary Events in a Mathematical Sciences Research Collaboration Network

This study examines long-term trends and shifting behavior in the collaboration network of mathematics literature, using a subset of data from Mathematical Reviews spanning 1985-2009. Rather than modeling the network cumulatively, this study traces the evolution of the "here and now" using fixed-duration sliding windows. The analysis uses a suite of common network diagnostics, including the distributions of degrees, distances, and clustering, to track network structure. Several random models that call these diagnostics as parameters help tease them apart as factors from the values of others. Some behaviors are consistent over the entire interval, but most diagnostics indicate that the network's structural evolution is dominated by occasional dramatic shifts in otherwise steady trends. These behaviors are not distributed evenly across the network; stark differences in evolution can be observed between two major subnetworks, loosely thought of as "pure" and "applied", which approximately partition the aggregate. The paper characterizes two major events along the mathematics network trajectory and discusses possible explanatory factors.Comment: 30 pages, 14 figures, 1 table; supporting information: 5 pages, 5 figures; published in Scientometric

A Stellar Dynamical Measurement of the Black Hole Mass in the Maser Galaxy NGC 4258

We determine the mass of the black hole at the center of the spiral galaxy NGC 4258 by constructing axisymmetric dynamical models of the galaxy. These models are constrained by high spatial resolution imaging and long-slit spectroscopy of the nuclear region obtained with the {\em Hubble Space Telescope}, complemented by ground-based observations extending to larger radii. Our best mass estimate is \MBH = (3.3 \pm 0.2) \times 10^7 \MSun for a distance of 7.28 Mpc (statistical errors only). This is within 15% of (3.82\pm 0.01) \times 10^7 \MSun, the mass determined from the kinematics of water masers (rescaled to the same distance) assuming they are in Keplerian rotation in a warped disk. The construction of accurate dynamical models of NGC 4258 is somewhat compromised by an unresolved active nucleus and color gradients, the latter caused by variations in the stellar population and/or obscuring dust. These problems are not present in the $\sim 30$ other black hole mass determinations from stellar dynamics that have been published by us and other groups; thus, the relatively close agreement between the stellar dynamical mass and the maser mass in NGC 4258 enhances our confidence in the black hole masses determined in other galaxies from stellar dynamics using similar methods and data of comparable quality.Comment: 58 pages, submitted to ApJ. Some figures excluded due to size. The entire paper is at http://www.noao.edu/noao/staff/lauer/nuker_papers.htm

Spectroscopy, MOST Photometry, and Interferometry of MWC 314: Is it an LBV or an interacting binary?

MWC 314 is a bright candidate luminous blue variable that resides in a fairly close binary system, with an orbital period of 60.753$\pm$0.003 d. We observed MWC 314 with a combination of optical spectroscopy, broad-band ground- and space-based photometry, as well as with long baseline, near-infrared interferometry. We have revised the single-lined spectroscopic orbit and explored the photometric variability. The orbital light curve displays two minima each orbit that can be partially explained in terms of the tidal distortion of the primary that occurs around the time of periastron. The emission lines in the system are often double-peaked and stationary in their kinematics, indicative of a circumbinary disc. We find that the stellar wind or circumbinary disc is partially resolved in the K\prime-band with the longest baselines of the CHARA Array. From this analysis, we provide a simple, qualitative model in an attempt to explain the observations. From the assumption of Roche Lobe overflow and tidal synchronisation at periastron, we estimate the component masses to be M1 $\approx 5$ M$_\odot$ and M2$\approx 15$ M$_\odot$, which indicates a mass of the LBV that is extremely low. In addition to the orbital modulation, we discovered two pulsational modes with the MOST satellite. These modes are easily supported by a low-mass hydrogen-poor star, but cannot be easily supported by a star with the parameters of an LBV. The combination of these results provides evidence that the primary star was likely never a normal LBV, but rather is the product of binary interactions. As such, this system presents opportunities for studying mass-transfer and binary evolution with many observational techniques.Comment: 26 pages, 7 figures, 5 tables, 2 appendices with 7 additional tables and 2 additional figures. Accepted for publication in MNRA

The Panchromatic Hubble Andromeda Treasury II. Tracing the Inner M31 Halo with Blue Horizontal Branch Stars

We attempt to constrain the shape of M31's inner stellar halo by tracing the surface density of blue horizontal branch (BHB) stars at galactocentric distances ranging from 2 kpc to 35 kpc. Our measurements make use of resolved stellar photometry from a section of the Panchromatic Hubble Andromeda Treasury (PHAT) survey, supplemented by several archival Hubble Space Telescope observations. We find that the ratio of BHB to red giant stars is relatively constant outside of 10 kpc, suggesting that the BHB is as reliable a tracer of the halo population as the red giant branch. In the inner halo, we do not expect BHB stars to be produced by the high metallicity bulge and disk, making BHB stars a good candidate to be a reliable tracer of the stellar halo to much smaller galactocentric distances. If we assume a power-law profile r^(-\alpha) for the 2-D projected surface density BHB distribution, we obtain a high-quality fit with a 2-D power-law index of \alpha=2.6^{+0.3}_{-0.2} outside of 3 kpc, which flattens to \alpha<1.2 inside of 3 kpc. This slope is consistent with previous measurements but is anchored to a radial baseline that extends much farther inward. Finally, assuming azimuthal symmetry and a constant mass-to-light ratio, the best-fitting profile yields a total halo stellar mass of 2.1^{+1.7}_{-0.4} x 10^9 M_sun. These properties are comparable with both simulations of stellar halo formation formed by satellite disruption alone, and with simulations that include some in situ formation of halo stars.Comment: 15 pages, 1 table, 5 figures, accepted for publication in Ap

The SPLASH Survey: A Spectroscopic Portrait of Andromeda's Giant Southern Stream

The giant southern stream (GSS) is the most prominent tidal debris feature in M31's stellar halo. The GSS is composed of a relatively metal-rich, high surface-brightness "core" and a lower metallicity, lower surface brightness "envelope." We present Keck/DEIMOS spectroscopy of red giant stars in six fields in the vicinity of M31's GSS and one field on Stream C, an arc-like feature on M31's SE minor axis at R=60 kpc. Several GSS-related findings and measurements are presented here. We present the innermost kinematical detection of the GSS core to date (R=17 kpc). This field also contains the continuation of a second kinematically cold component originally seen in a GSS core field at R=21 kpc. The velocity gradients of the GSS and the second component in the combined data set are parallel over a radial range of 7 kpc, suggesting a possible bifurcation in the line-of-sight velocities of GSS stars. We also present the first kinematical detection of substructure in the GSS envelope. Using kinematically identified samples, we show that the envelope debris has a ~0.7 dex lower mean photometric metallicity and possibly higher intrinsic velocity dispersion than the GSS core. The GSS is also identified in the field of the M31 dSph satellite And I; the GSS in this field has a metallicity distribution identical to that of the GSS core. We confirm the presence of two kinematically cold components in Stream C, and measure intrinsic velocity dispersions of ~10 and ~4 km/s. This compilation of the kinematical (mean velocity, intrinsic velocity dispersion) and chemical properties of stars in the GSS core and envelope, coupled with published surface brightness measurements and wide-area star-count maps, will improve constraints on the orbit and internal structure of the dwarf satellite progenitor.Comment: Accepted for publication in Ap

Dissection of a Complex Disease Susceptibility Region Using a Bayesian Stochastic Search Approach to Fine Mapping.

Identification of candidate causal variants in regions associated with risk of common diseases is complicated by linkage disequilibrium (LD) and multiple association signals. Nonetheless, accurate maps of these variants are needed, both to fully exploit detailed cell specific chromatin annotation data to highlight disease causal mechanisms and cells, and for design of the functional studies that will ultimately be required to confirm causal mechanisms. We adapted a Bayesian evolutionary stochastic search algorithm to the fine mapping problem, and demonstrated its improved performance over conventional stepwise and regularised regression through simulation studies. We then applied it to fine map the established multiple sclerosis (MS) and type 1 diabetes (T1D) associations in the IL-2RA (CD25) gene region. For T1D, both stepwise and stochastic search approaches identified four T1D association signals, with the major effect tagged by the single nucleotide polymorphism, rs12722496. In contrast, for MS, the stochastic search found two distinct competing models: a single candidate causal variant, tagged by rs2104286 and reported previously using stepwise analysis; and a more complex model with two association signals, one of which was tagged by the major T1D associated rs12722496 and the other by rs56382813. There is low to moderate LD between rs2104286 and both rs12722496 and rs56382813 (r2 ≃ 0:3) and our two SNP model could not be recovered through a forward stepwise search after conditioning on rs2104286. Both signals in the two variant model for MS affect CD25 expression on distinct subpopulations of CD4+ T cells, which are key cells in the autoimmune process. The results support a shared causal variant for T1D and MS. Our study illustrates the benefit of using a purposely designed model search strategy for fine mapping and the advantage of combining disease and protein expression data.We acknowledge use of DNA from The UK Blood Services collection of Common Controls (UKBS-CC collection), which is funded by the Wellcome Trust grant 076113/C/04/Z and by the USA National Institute for Health Research program grant to the National Health Service Blood and Transplant (RP-PG-0310-1002). We acknowledge the use of DNA from the British 1958 Birth Cohort collection, which is funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. This research utilized resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Human Genome Research Institute, the National Institute of Child Health and Human Development and the JDRF and is supported by the USA National Institutes of Health grant U01-DK062418. The JDRF/Wellcome Trust Diabetes and Inflammation Laboratory is funded by the JDRF (9-2011-253), the Wellcome Trust (091157) and the National Institute for Health Research Cambridge Biomedical Centre. The research leading to these results has received funding from the European Union's 7th Framework Programme (FP7/2007-2013) under grant agreement no.241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). CW is supported by the Wellcome Trust (089989). We acknowledge the National Institute for Health Research Cambridge Biomedical Research Centre for funding.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pgen.100527