Genomic landscapes of divergence among island bird populations: Evidence of parallel adaptation but at different loci?

When populations colonise new environments, they may be exposed to novel selection pressures but also suffer from extensive genetic drift due to founder effects, small population sizes and limited interpopulation gene flow. Genomic approaches enable us to study how these factors drive divergence, and disentangle neutral effects from differentiation at specific loci due to selection. Here, we investigate patterns of genetic diversity and divergence using whole‐genome resequencing (>22× coverage) in Berthelot's pipit (Anthus berthelotii), a passerine endemic to the islands of three north Atlantic archipelagos. Strong environmental gradients, including in pathogen pressure, across populations in the species range, make it an excellent system in which to explore traits important in adaptation and/or incipient speciation. First, we quantify how genomic divergence accumulates across the speciation continuum, that is, among Berthelot's pipit populations, between sub species across archipelagos, and between Berthelot's pipit and its mainland ancestor, the tawny pipit (Anthus campestris). Across these colonisation timeframes (2.1 million–ca. 8000 years ago), we identify highly differentiated loci within genomic islands of divergence and conclude that the observed distributions align with expectations for non‐neutral divergence. Characteristic signatures of selection are identified in loci associated with craniofacial/bone and eye development, metabolism and immune response between population comparisons. Interestingly, we find limited evidence for repeated divergence of the same loci across the colonisation range but do identify different loci putatively associated with the same biological traits in different populations, likely due to parallel adaptation. Incipient speciation across these island populations, in which founder effects and selective pressures are strong, may therefore be repeatedly associated with morphology, metabolism and immune defence

ELR510444 Inhibits Tumor Growth and Angiogenesis by Abrogating HIF Activity and Disrupting Microtubules in Renal Cell Carcinoma

Background: Hypoxia-inducible factor (HIF) is an attractive therapeutic target for renal cell carcinoma (RCC) as its high expression due to the loss of von Hippel-Lindau (VHL) promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC. Principal Findings: ELR510444 decreased HIF-1a and HIF-2a levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444-mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of ELR51044 promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models. These effects were associated with increased necrosis and apoptosis and inhibition of angiogenesis. Conclusions: ELR510444 is a promising new HIF inhibitor that reduced RCC cell viability, induced apoptosis, and diminished tumor burden in RCC xenograft models. ELR510444 also destabilized microtubules suggesting that it possesses vascula

Transport, optical and electronic properties of the half metal CrO2

The electronic structure of CrO_2 is critically discussed in terms of the relation of existing experimental data and well converged LSDA and GGA calculations of the electronic structure and transport properties of this half metal magnet, with a particular emphasis on optical properties. We find only moderate manifestations of many body effects. Renormalization of the density of states is not large and is in the typical for transition metals range. We find substantial deviations from Drude behavior in the far-infrared optical conductivity. These appear because of the unusually low energy of interband optical transitions. The calculated mass renormalization is found to be rather sensitive to the exchange-correlation functional used and varies from 10% (LSDA) to 90% (GGA), using the latest specific heat data. We also find that dressing of the electrons by spin fluctuations, because of their high energy, renormalizes the interband optical transition at as high as 4 eV by about 20%. Although we find no clear indications of strong correlations of the Hubbard type, strong electron-magnon scattering related to the half metallic band structure is present and this leads to a nontrivial temperature dependence of the resistivity and some renormalization of the electron spectra.Comment: 9 Revtex 2 column pages, including 8 postscript figures. Two more figures are included in the submission that are not embedded in the paper, representing DOS and bandstructure of the paramagnetic CrO

Mechanisms of photoreceptor death and survival in mammalian retina

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any other retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial "depletion" stage caused by genetic or environmental insult and a second "late" stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second "late" stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed

‘Can you recommend any good STI apps?’ A review of content, accuracy and comprehensiveness of current mobile medical applications for STIs and related genital infections

Objective Seeking sexual health information online is common, and provision of mobile medical applications (apps) for STIs is increasing. Young people, inherently at higher risk of STIs, are avid users of technology, and apps could be appealing sources of information. We undertook a comprehensive review of content and accuracy of apps for people seeking information about STIs. Methods Search of Google Play and iTunes stores using general and specific search terms for apps regarding STIs and genital infections (except HIV), testing, diagnosis and management, 10 September 2014 to 16 September 2014. We assessed eligible apps against (1) 19 modified Health on The Net (HON) Foundation principles; and (2) comprehensiveness and accuracy of information on STIs/genital infections, and their diagnosis and management, compared with corresponding National Health Service STI information webpage content. Results 144/6642 apps were eligible. 57 were excluded after downloading. 87 were analysed. Only 29% of apps met ≥6 HON criteria. Content was highly variable: 34/87 (39%) covered one or two infections; 40 (46%) covered multiple STIs; 5 (6%) focused on accessing STI testing. 13 (15%) were fully, 46 (53%) mostly and 28 (32%) partially accurate. 25 (29%) contained ≥1 piece of potentially harmful information. Apps available on both iOS and Android were more accurate than single-platform apps. Only one app provided fully accurate and comprehensive information on chlamydia. Conclusions Marked variation in content, quality and accuracy of available apps combined with the nearly one-third containing potentially harmful information risks undermining potential benefits of an e-Health approach to sexual health and well-being.The Electronic Self-Testing Instruments for Sexually Transmitted Infection (eSTI2) Consortium is funded under the UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council (Grant Number G0901608) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, the Chief Scientist Office of the Scottish Government Health Directorates and the Wellcome Trust

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Stellar parameters for the First Release of the MaStar Library: An Empirical Approach

We report the stellar atmospheric parameters for 7503 spectra contained in the first release of the MaNGA stellar library (MaStar) in SDSS DR15. The first release of MaStar contains 8646 spectra measured from 3321 unique stars, each covering the wavelength range 3622 \AA\ to 10354 \AA\ with a resolving power of $R \sim$ 1800. In this work, we first determined the basic stellar parameters: effective temperature ($\rm T_{eff}$), surface gravity ($\log g$), and metallicity ($\rm[Fe/H]$), which best fit the data using an empirical interpolator based on the Medium-resolution Isaac Newton Telescope library of empirical spectra (MILES), as implemented by the University of Lyon Spectroscopic analysis Software (Koleva et al. 2008, ULySS) package. While we analyzed all 8646 spectra from the first release of MaStar, since MaStar has a wider parameter-space coverage than MILES, not all of these fits are robust. In addition, not all parameter regions covered by MILES yield robust results, likely due to the non-uniform coverage of the parameter space by MILES. We tested the robustness of the method using the MILES spectra itself and identified a proxy based on the local density of the training set. With this proxy, we identified 7503 MaStar spectra with robust fitting results. They cover the range from 3179K to 20,517K in effective temperature ($\rm T_{eff}$), from 0.40 to 5.0 in surface gravity ($\log g$), and from $-$2.49 to $+$0.73 in metallicity ($\rm[Fe/H]$).Comment: 14 pages, 13 figure

Genomic variation, population history and within-archipelago adaptation between island bird populations

Oceanic island archipelagos provide excellent models to understand evolutionary processes. Colonization events and gene flow can interact with selection to shape genetic variation at different spatial scales. Landscape-scale variation in biotic and abiotic factors may drive fine-scale selection within islands, while long-term evolutionary processes may drive divergence between distantly related populations. Here, we examine patterns of population history and selection between recently diverged populations of the Berthelot's pipit (Anthus berthelotii), a passerine endemic to three North Atlantic archipelagos. First, we use demographic trees and f 3 statistics to show that genome-wide divergence across the species range is largely shaped by colonization and bottlenecks, with evidence of very weak gene flow between populations. Then, using a genome scan approach, we identify signatures of divergent selection within archipelagos at single nucleotide polymorphisms (SNPs) in genes potentially associated with craniofacial development and DNA repair. We did not detect within-archipelago selection at the same SNPs as were detected previously at broader spatial scales between archipelagos, but did identify signatures of selection at loci associated with similar biological functions. These findings suggest that similar ecological factors may repeatedly drive selection between recently separated populations, as well as at broad spatial scales across varied landscapes