The identification of protein and RNA interactors of the splicing factor Caper in the adult Drosophila nervous system

Post-transcriptional gene regulation is a fundamental mechanism that helps regulate the development and healthy aging of the nervous system. Mutations that disrupt the function of RNA-binding proteins (RBPs), which regulate post-transcriptional gene regulation, have increasingly been implicated in neurological disorders including amyotrophic lateral sclerosis, Fragile X Syndrome, and spinal muscular atrophy. Interestingly, although the majority of RBPs are expressed widely within diverse tissue types, the nervous system is often particularly sensitive to their dysfunction. It is therefore critical to elucidate how aberrant RNA regulation that results from the dysfunction of ubiquitously expressed RBPs leads to tissue specific pathologies that underlie neurological diseases. The highly conserved RBP and alternative splicing factor Caper is widely expressed throughout development and is required for the development of Drosophila sensory and motor neurons. Furthermore, caper dysfunction results in larval and adult locomotor deficits. Nonetheless, little is known about which proteins interact with Caper, and which RNAs are regulated by Caper. Here we identify proteins that interact with Caper in both neural and muscle tissue, along with neural specific Caper target RNAs. Furthermore, we show that a subset of these Caper-interacting proteins and RNAs genetically interact with caper to regulate Drosophila gravitaxis behavior

The Stellar Halos of Massive Elliptical Galaxies

We use the Mitchell Spectrograph (formerly VIRUS-P) on the McDonald Observatory 2.7m Harlan J. Smith Telescope to search for the chemical signatures of massive elliptical galaxy assembly. The Mitchell Spectrograph is an integral-field spectrograph with a uniquely wide field of view (107x107 sq arcsec), allowing us to achieve remarkably high signal-to-noise ratios of ~20-70 per pixel in radial bins of 2-2.5 times the effective radii of the eight galaxies in our sample. Focusing on a sample of massive elliptical galaxies with stellar velocity dispersions sigma* > 150 km/s, we study the radial dependence in the equivalent widths (EWs) of key metal absorption lines. By twice the effective radius, the Mgb EWs have dropped by ~50%, and only a weak correlation between sigma* and Mgb EW remains. The Mgb EWs at large radii are comparable to those seen in the centers of elliptical galaxies that are approximately an order of magnitude less massive. We find that the well-known metallicity gradients often observed within an effective radius continue smoothly to 2.5R_e, while the abundance ratio gradients remain flat. Much like the halo of the Milky Way, the stellar halos of our galaxies have low metallicities and high alpha-abundance ratios, as expected for very old stars formed in small stellar systems. Our observations support a picture in which the outer parts of massive elliptical galaxies are built by the accretion of much smaller systems whose star formation history was truncated at early times.Comment: To appear in ApJ, 15 pages, 9 figure

Host Plant Adaptation in Drosophila mettleri Populations

The process of local adaptation creates diversity among allopatric populations, and may eventually lead to speciation. Plant-feeding insect populations that specialize on different host species provide an excellent opportunity to evaluate the causes of ecological specialization and the subsequent consequences for diversity. In this study, we used geographically separated Drosophila mettleri populations that specialize on different host cacti to examine oviposition preference for and larval performance on an array of natural and non-natural hosts (eight total). We found evidence of local adaptation in performance on saguaro cactus (Carnegiea gigantea) for populations that are typically associated with this host, and to chemically divergent prickly pear species (Opuntia spp.) in a genetically isolated population on Santa Catalina Island. Moreover, each population exhibited reduced performance on the alternative host. This finding is consistent with trade-offs associated with adaptation to these chemically divergent hosts, although we also discuss alternative explanations for this pattern. For oviposition preference, Santa Catalina Island flies were more likely to oviposit on some prickly pear species, but all populations readily laid eggs on saguaro. Experiments with non-natural hosts suggest that factors such as ecological opportunity may play a more important role than host plant chemistry in explaining the lack of natural associations with some hosts

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Data from: Transcriptional variation associated with cactus host plant adaptation in Drosophila mettleri

Although the importance of host plant chemistry in plant–insect interactions is widely accepted, the genetic basis of adaptation to host plants is not well understood. Here, we investigate transcriptional changes associated with a host plant shift in Drosophila mettleri. While D. mettleri is distributed mainly throughout the Sonoran Desert where it specializes on columnar cacti (Carnegiea gigantea and Pachycereus pringleii), a population on Santa Catalina Island has shifted to chemically divergent coastal prickly pear cactus (Opuntia littoralis). We compared gene expression of larvae from the Sonoran Desert and Santa Catalina Island when reared on saguaro (C. gigantea), coastal prickly pear and laboratory food. Consistent with expectations based on the complexity and toxicity of cactus relative to laboratory food, within-population comparisons between larvae reared on these food sources revealed transcriptional differences in detoxification and other metabolic pathways. The majority of transcriptional differences between populations on the cactus hosts were independent of the rearing environment and included a disproportionate number of genes involved in processes relevant to host plant adaptation (e.g. detoxification, central metabolism and chemosensory pathways). Comparisons of transcriptional reaction norms between the two populations revealed extensive shared plasticity that likely allowed colonization of coastal prickly pear on Santa Catalina Island. We also found that while plasticity may have facilitated subsequent adaptive divergence in gene expression between populations, the majority of genes that differed in expression on the novel host were not transcriptionally plastic in the presumed ancestral state

Local preference/performance adaptation.

<p>Least square means comparisons of (a) oviposition acceptance and (b) larval survival on saguaro and three species of prickly pear. Natural hosts for each population are given in parentheses in the key. For a given host plant, points under different letters were significantly different after Tukey's adjustment (α = 0.05). Points with no letter were not included in the statistical analysis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034008#s2" target="_blank">methods</a>).</p