bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulated linear test applied to quantitative proteomics
Authors: Pham TV , Jimenez CR
Published: September 2016

Motivation

Omics studies aim to find significant changes due to biological or functional perturbation. However, gene and protein expression profiling experiments contain inherent technical variation. In discovery proteomics studies where the number of samples is typically small, technical variation plays an important role because it contributes considerably to the observed variation. Previous methods place both technical and biological variations in tightly integrated mathematical models that are difficult to adapt for different technological platforms. Our aim is to derive a statistical framework that allows the inclusion of a wide range of technical variability.

Results

We introduce a new method called the simulated linear test, or the s-test, that is easy to implement and easy to adapt for different models of technical variation. It generates virtual data points from the observed values according to a pre-defined technical distribution and subsequently employs linear modeling for significance analysis. We demonstrate the flexibility of the proposed approach by deriving a new significance test for quantitative discovery proteomics for which missing values have been a major issue for traditional methods such as the t-test. We evaluate the result on two label-free (phospho) proteomics datasets based on ion-intensity quantitation.

Availability and Implementation

Available at http://www.oncoproteomics.nl/software/stest.html.

Contact

t.pham@vumc.nl
PRED-TMBB2: improved topology prediction and detection of beta-barrel outer membrane proteins
Authors: Tsirigos Konstantinos D , Elofsson Arne , Bagos Pantelis G
Published: September 2016

Motivation

The PRED-TMBB method is based on Hidden Markov Models and is capable of predicting the topology of beta-barrel outer membrane proteins and discriminate them from water-soluble ones. Here, we present an updated version of the method, PRED-TMBB2, with several newly developed features that improve its performance. The inclusion of a properly defined end state allows for better modeling of the beta-barrel domain, while different emission probabilities for the adjacent residues in strands are used to incorporate knowledge concerning the asymmetric amino acid distribution occurring there. Furthermore, the training was performed using newly developed algorithms in order to optimize the labels of the training sequences. Moreover, the method is retrained on a larger, non-redundant dataset which includes recently solved structures, and a newly developed decoding method was added to the already available options. Finally, the method now allows the incorporation of evolutionary information in the form of multiple sequence alignments.

Results

The results of a strict cross-validation procedure show that PRED-TMBB2 with homology information performs significantly better compared to other available prediction methods. It yields 76% in correct topology predictions and outperforms the best available predictor by 7%, with an overall SOV of 0.9. Regarding detection of beta-barrel proteins, PRED-TMBB2, using just the query sequence as input, achieves an MCC value of 0.92, outperforming even predictors designed for this task and are much slower.

Availability and Implementation

The method, along with all datasets used, is freely available for academic users at http://www.compgen.org/tools/PRED-TMBB2.

Contact

pbagos@compgen.org
TANDEM: a two-stage approach to maximize interpretability of drug response models based on multiple molecular data types
Authors: Aben Nanne , Vis Daniel J , Michaut Magali , Wessels Lodewyk FA
Published: September 2016

Motivation

Clinical response to anti-cancer drugs varies between patients. A large portion of this variation can be explained by differences in molecular features, such as mutation status, copy number alterations, methylation and gene expression profiles. We show that the classic approach for combining these molecular features (Elastic Net regression on all molecular features simultaneously) results in models that are almost exclusively based on gene expression. The gene expression features selected by the classic approach are difficult to interpret as they often represent poorly studied combinations of genes, activated by aberrations in upstream signaling pathways.

Results

To utilize all data types in a more balanced way, we developed TANDEM, a two-stage approach in which the first stage explains response using upstream features (mutations, copy number, methylation and cancer type) and the second stage explains the remainder using downstream features (gene expression). Applying TANDEM to 934 cell lines profiled across 265 drugs (GDSC1000), we show that the resulting models are more interpretable, while retaining the same predictive performance as the classic approach. Using the more balanced contributions per data type as determined with TANDEM, we find that response to MAPK pathway inhibitors is largely predicted by mutation data, while predicting response to DNA damaging agents requires gene expression data, in particular SLFN11 expression.

Availability and Implementation

TANDEM is available as an R package on CRAN (for more information, see http://ccb.nki.nl/software/tandem).

Contact

m.michaut@nki.nl or l.wessels@nki.nl

Supplementary information

Supplementary data are available at Bioinformatics online.
Optimization of signal-to-noise ratio for efficient microarray probe design
Authors: Matveeva Olga V. , Nechipurenko Yury D. , Riabenko Evgeniy , Ragan Chikako , Nazipova Nafisa N. , Ogurtsov Aleksey Y. , Shabalina Svetlana A.
Published: September 2016

Motivation: Target-specific hybridization depends on oligo-probe characteristics that improve hybridization specificity and minimize genome-wide cross-hybridization. Interplay between specific hybridization and genome-wide cross-hybridization has been insufficiently studied, despite its crucial role in efficient probe design and in data analysis.

Results: In this study, we defined hybridization specificity as a ratio between oligo target-specific hybridization and oligo genome-wide cross-hybridization. A microarray database, derived from the Genomic Comparison Hybridization (GCH) experiment and performed using the Affymetrix platform, contains two different types of probes. The first type of oligo-probes does not have a specific target on the genome and their hybridization signals are derived from genome-wide cross-hybridization alone. The second type includes oligonucleotides that have a specific target on the genomic DNA and their signals are derived from specific and cross-hybridization components combined together in a total signal. A comparative analysis of hybridization specificity of oligo-probes, as well as their nucleotide sequences and thermodynamic features was performed on the database. The comparison has revealed that hybridization specificity was negatively affected by low stability of the fully-paired oligo-target duplex, stable probe self-folding, G-rich content, including GGG motifs, low sequence complexity and nucleotide composition symmetry.

Conclusion: Filtering out the probes with defined ‘negative’ characteristics significantly increases specific hybridization and dramatically decreasing genome-wide cross-hybridization. Selected oligo-probes have two times higher hybridization specificity on average, compared to the probes that were filtered from the analysis by applying suggested cutoff thresholds to the described parameters. A new approach for efficient oligo-probe design is described in our study.

Contact:  shabalin@ncbi.nlm.nih.gov or olga.matveeva@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
PanTools: representation, storage and exploration of pan-genomic data
Authors: Sheikhizadeh Siavash , Schranz M. Eric , Akdel Mehmet , de Ridder Dick , Smit Sandra
Published: September 2016

Motivation

Next-generation sequencing technology is generating a wealth of highly similar genome sequences for many species, paving the way for a transition from single-genome to pan-genome analyses. Accordingly, genomics research is going to switch from reference-centric to pan-genomic approaches. We define the pan-genome as a comprehensive representation of multiple annotated genomes, facilitating analyses on the similarity and divergence of the constituent genomes at the nucleotide, gene and genome structure level. Current pan-genomic approaches do not thoroughly address scalability, functionality and usability.

Results

We introduce a generalized De Bruijn graph as a pan-genome representation, as well as an online algorithm to construct it. This representation is stored in a Neo4j graph database, which makes our approach scalable to large eukaryotic genomes. Besides the construction algorithm, our software package, called PanTools, currently provides functionality for annotating pan-genomes, adding sequences, grouping genes, retrieving gene sequences or genomic regions, reconstructing genomes and comparing and querying pan-genomes. We demonstrate the performance of the tool using datasets of 62 E. coli genomes, 93 yeast genomes and 19 Arabidopsis thaliana genomes.

Availability and Implementation

The Java implementation of PanTools is publicly available at http://www.bif.wur.nl.

Contact

sandra.smit@wur.nl
Logical model specification aided by model-checking techniques: application to the mammalian cell cycle regulation
Authors: Traynard Pauline , Fauré Adrien , Fages François , Thieffry Denis
Published: September 2016

Motivation

Understanding the temporal behaviour of biological regulatory networks requires the integration of molecular information into a formal model. However, the analysis of model dynamics faces a combinatorial explosion as the number of regulatory components and interactions increases.

Results

We use model-checking techniques to verify sophisticated dynamical properties resulting from the model regulatory structure in the absence of kinetic assumption. We demonstrate the power of this approach by analysing a logical model of the molecular network controlling mammalian cell cycle. This approach enables a systematic analysis of model properties, the delineation of model limitations, and the assessment of various refinements and extensions based on recent experimental observations. The resulting logical model accounts for the main irreversible transitions between cell cycle phases, the sequential activation of cyclins, and the inhibitory role of Skp2, and further emphasizes the multifunctional role for the cell cycle inhibitor Rb.

Availability and Implementation

The original and revised mammalian cell cycle models are available in the model repository associated with the public modelling software GINsim (http://ginsim.org/node/189).

Contact

thieffry@ens.fr

Supplementary information

Supplementary data are available at Bioinformatics online.
A weighted exact test for mutually exclusive mutations in cancer
Authors: Leiserson Mark DM , Reyna Matthew A , Raphael Benjamin J
Published: September 2016

Motivation

The somatic mutations in the pathways that drive cancer development tend to be mutually exclusive across tumors, providing a signal for distinguishing driver mutations from a larger number of random passenger mutations. This mutual exclusivity signal can be confounded by high and highly variable mutation rates across a cohort of samples. Current statistical tests for exclusivity that incorporate both per-gene and per-sample mutational frequencies are computationally expensive and have limited precision.

Results

We formulate a weighted exact test for assessing the significance of mutual exclusivity in an arbitrary number of mutational events. Our test conditions on the number of samples with a mutation as well as per-event, per-sample mutation probabilities. We provide a recursive formula to compute P-values for the weighted test exactly as well as a highly accurate and efficient saddlepoint approximation of the test. We use our test to approximate a commonly used permutation test for exclusivity that conditions on per-event, per-sample mutation frequencies. However, our test is more efficient and it recovers more significant results than the permutation test. We use our Weighted Exclusivity Test (WExT) software to analyze hundreds of colorectal and endometrial samples from The Cancer Genome Atlas, which are two cancer types that often have extremely high mutation rates. On both cancer types, the weighted test identifies sets of mutually exclusive mutations in cancer genes with fewer false positives than earlier approaches.

Availability and Implementation

See http://compbio.cs.brown.edu/projects/wext for software.

Contact

braphael@cs.brown.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
iReMet-flux: constraint-based approach for integrating relative metabolite levels into a stoichiometric metabolic models
Authors: Sajitz-Hermstein Max , Töpfer Nadine , Kleessen Sabrina , Fernie Alisdair R , Nikoloski Zoran
Published: September 2016

Motivation

Understanding the rerouting of metabolic reaction fluxes upon perturbations has the potential to link changes in molecular state of a cellular system to alteration of growth. Yet, differential flux profiling on a genome-scale level remains one of the biggest challenges in systems biology. This is particularly relevant in plants, for which fluxes in autotrophic growth necessitate time-consuming instationary labeling experiments and costly computations, feasible for small-scale networks.

Results

Here we present a computationally and experimentally facile approach, termed iReMet-Flux, which integrates relative metabolomics data in a metabolic model to predict differential fluxes at a genome-scale level. Our approach and its variants complement the flux estimation methods based on radioactive tracer labeling. We employ iReMet-Flux with publically available metabolic profiles to predict reactions and pathways with altered fluxes in photo-autotrophically grown Arabidopsis and four photorespiratory mutants undergoing high-to-low CO2 acclimation. We also provide predictions about reactions and pathways which are most strongly regulated in the investigated experiments. The robustness and variability analyses, tailored to the formulation of iReMet-Flux, demonstrate that the findings provide biologically relevant information that is validated with external measurements of net CO2 exchange and biomass production. Therefore, iReMet-Flux paves the wave for mechanistic dissection of the interplay between pathways of primary and secondary metabolisms at a genome-scale.

Availability and Implementation

The source code is available from the authors upon request.

Contact

nikoloski@mpimp-golm.mpg.de

Supplementary information

Supplementary data are available at Bioinformatics online.
MetaProb: accurate metagenomic reads binning based on probabilistic sequence signatures
Authors: Girotto Samuele , Pizzi Cinzia , Comin Matteo
Published: September 2016

Motivation

Sequencing technologies allow the sequencing of microbial communities directly from the environment without prior culturing. Taxonomic analysis of microbial communities, a process referred to as binning, is one of the most challenging tasks when analyzing metagenomic reads data. The major problems are the lack of taxonomically related genomes in existing reference databases, the uneven abundance ratio of species and the limitations due to short read lengths and sequencing errors.

Results

MetaProb is a novel assembly-assisted tool for unsupervised metagenomic binning. The novelty of MetaProb derives from solving a few important problems: how to divide reads into groups of independent reads, so that k-mer frequencies are not overestimated; how to convert k-mer counts into probabilistic sequence signatures, that will correct for variable distribution of k-mers, and for unbalanced groups of reads, in order to produce better estimates of the underlying genome statistic; how to estimate the number of species in a dataset. We show that MetaProb is more accurate and efficient than other state-of-the-art tools in binning both short reads datasets (F-measure 0.87) and long reads datasets (F-measure 0.97) for various abundance ratios. Also, the estimation of the number of species is more accurate than MetaCluster. On a real human stool dataset MetaProb identifies the most predominant species, in line with previous human gut studies.

Availability and Implementation

https://bitbucket.org/samu661/metaprob

Contacts

cinzia.pizzi@dei.unipd.it or comin@dei.unipd.it

Supplementary information

Supplementary data are available at Bioinformatics online.
A program for verification of phylogenetic network models
Authors: Gunawan Andreas DM , Lu Bingxin , Zhang Louxin
Published: September 2016

Motivation

Genetic material is transferred in a non-reproductive manner across species more frequently than commonly thought, particularly in the bacteria kingdom. On one hand, extant genomes are thus more properly considered as a fusion product of both reproductive and non-reproductive genetic transfers. This has motivated researchers to adopt phylogenetic networks to study genome evolution. On the other hand, a gene’s evolution is usually tree-like and has been studied for over half a century. Accordingly, the relationships between phylogenetic trees and networks are the basis for the reconstruction and verification of phylogenetic networks. One important problem in verifying a network model is determining whether or not certain existing phylogenetic trees are displayed in a phylogenetic network. This problem is formally called the tree containment problem. It is NP-complete even for binary phylogenetic networks.

Results

We design an exponential time but efficient method for determining whether or not a phylogenetic tree is displayed in an arbitrary phylogenetic network. It is developed on the basis of the so-called reticulation-visible property of phylogenetic networks.

Availability and Implementation

A C-program is available for download on http://www.math.nus.edu.sg/∼matzlx/tcp_package.

Contact

matzlx@nus.edu.sg

Supplementary information

Supplementary data are available at Bioinformatics online.
Towards a flexible Decision Support Tool for MSY-based Marine Protected Area design for skates and rays
Authors: Dedman Simon , Officer Rick , Brophy Deirdre , Clarke Maurice , Reid David G.
Published: September 2016

It is recommended that demersal elasmobranchs be managed using spatial proxies for Maximum Sustainable Yield. Here we combine escapement biomass—the percentage of the stock which must be retained each year to conserve it—with maps of predicted Catch Per Unit Effort (CPUE) of four ray species [cuckoo (Leucoraja naevus), thornback (Raja clavata), blonde (Raja brachyura), and spotted (Raja montagui)], created using Boosted Regression Tree modelling. We then use a Decision Support Tool to generate location and size options for Marine Protected Areas to protect these stocks, based on the priorities of the various stakeholders, notably the minimisation of fishing effort displacement. Variations of conservation/fishing priorities are simulated, as well as differential priorities for individual species, with a focus on protecting nursery grounds and spawning areas. Prioritizing high CPUE cells results in a smaller closed area that displaces the most fishing effort, whereas prioritizing low fishing effort results in a larger closed area that displaces the least fishing effort. The final result is a complete software package that produces maps of predicted species CPUE from limited survey data, and allows disparate stakeholders and policymakers to discuss management options within a mapping interface.
Barley (Hordeum vulgare ) circadian clock genes can respond rapidly to temperature in an EARLY FLOWERING 3 -dependent manner
Authors: Ford Brett , Deng Weiwei , Clausen Jenni , Oliver Sandra , Boden Scott , Hemming Megan , Trevaskis Ben
Published: September 2016

An increase in global temperatures will impact future crop yields. In the cereal crops wheat and barley, high temperatures accelerate reproductive development, reducing the number of grains per plant and final grain yield. Despite this relationship between temperature and cereal yield, it is not clear what genes and molecular pathways mediate the developmental response to increased temperatures. The plant circadian clock can respond to changes in temperature and is important for photoperiod-dependent flowering, and so is a potential mechanism controlling temperature responses in cereal crops. This study examines the relationship between temperature, the circadian clock, and the expression of flowering-time genes in barley ( Hordeum vulgare ), a crop model for temperate cereals. Transcript levels of barley core circadian clock genes were assayed over a range of temperatures. Transcript levels of core clock genes CCA1 , GI , PRR59 , PRR73, PRR95 , and LUX are increased at higher temperatures. CCA1 and PRR73 respond rapidly to a decrease in temperature whereas GI and PRR59 respond rapidly to an increase in temperature. The response of GI and the PRR genes to changes in temperature is lost in the elf3 mutant indicating that their response to temperature may be dependent on a functional ELF3 gene.
Addressing the Challenges of Pathogen Evolution on the World’s Arable Crops
Authors: Burdon Jeremy J. , Zhan Jiasui , Barrett Luke G. , Papaïx Julien , Thrall Peter H.
Published: September 2016

Advances in genomic and molecular technologies coupled with an increasing understanding of the fine structure of many resistance and infectivity genes, have opened up a new era of hope in controlling the many plant pathogens that continue to be a major source of loss in arable crops. Some new approaches are under consideration including the use of nonhost resistance and the targeting of critical developmental constraints. However, the major thrust of these genomic and molecular approaches is to enhance the identification of resistance genes, to increase their ease of manipulation through marker and gene editing technologies and to lock a range of resistance genes together in simply manipulable resistance gene cassettes. All these approaches essentially continue a strategy that assumes the ability to construct genetic-based resistance barriers that are insurmountable to target pathogens. Here we show how the recent advances in knowledge and marker technologies can be used to generate more durable disease resistance strategies that are based on broad evolutionary principles aimed at presenting pathogens with a shifting, landscape of fluctuating directional selection.
Negative mood influences default mode network functional connectivity in patients with chronic low back pain: implications for functional neuroimaging biomarkers
Authors: Letzen Janelle E. , Robinson Michael E.
Published: September 2016

The default mode network (DMN) has been proposed as a biomarker for several chronic pain conditions. Default mode network functional connectivity (FC) is typically examined during resting-state functional neuroimaging, in which participants are instructed to let thoughts wander. However, factors at the time of data collection (eg, negative mood) that might systematically impact pain perception and its brain activity, influencing the application of the DMN as a pain biomarker, are rarely reported. This study measured whether positive and negative moods altered DMN FC patterns in patients with chronic low back pain (CLBP), specifically focusing on negative mood because of its clinical relevance. Thirty-three participants (CLBP = 17) underwent resting-state functional magnetic resonance imaging scanning before and after sad and happy mood inductions, and rated levels of mood and pain intensity at the time of scanning. Two-way repeated-measures analysis of variances were conducted on resting-state functional connectivity data. Significant group (CLBP > healthy controls) × condition (sadness > baseline) interaction effects were identified in clusters spanning parietal operculum/postcentral gyrus, insular cortices, anterior cingulate cortex, frontal pole, and a portion of the cerebellum (P
FDR < 0.05). However, only 1 significant cluster covering a portion of the cerebellum was identified examining a two-way repeated-measures analysis of variance for happiness > baseline (P
FDR < 0.05). Overall, these findings suggest that DMN FC is affected by negative mood in individuals with and without CLBP. It is possible that DMN FC seen in patients with chronic pain is related to an affective dimension of pain, which is important to consider in future neuroimaging biomarker development and implementation.
Radiation and hybridization of the Little Devil poison frog (Oophaga sylvatica) in Ecuador
Authors: Roland Alexandre B. , Santos Juan C. , Carriker Bella C. , Caty Stephanie N. , Tapia Elicio E. , Coloma Luis A. , O’Connell Lauren A.
Published: September 2016

Geographic variation of color pattern in the South American poison frogs (Dendrobatidae) is an intriguing evolutionary phenomenon. These chemically defended anurans use bright aposematic colors to warn potential predators of their unpalatibility. However, aposematic signals are frequency-dependent and individuals deviating from a local model are at a higher risk of predation. The well-known examples of Batesian and Müllerian mimics, hymenopterans (wasps and bees) andHeliconiusbutterflies, both support the benefits of unique models with relatively high frequencies. However, extreme diversity in the aposematic signal has been documented in the poison frogs of the genusDendrobates, especially in theOophagasubgenus. Here we investigate the phylogenetic and genomic differentiations among populations ofOophaga sylvatica, which exhibit one of the highest phenotypic diversification among poison frogs. Using a combination of PCR amplicons (mitochondrial and nuclear markers) and genome wide markers from a double-digested RAD data set, we characterize 13 populations (12 monotypic and 1 polytypic) across theO. sylvaticadistribution. These populations are mostly separated in two lineages distributed in the Northern and the Southern part of their range in Ecuador. We found relatively low genetic differentiation within each lineage, despite considerable phenotypic variation, and evidence suggesting ongoing gene flow and genetic admixture among some populations of the Northern lineage. Overall these data suggest that phenotypic diversification and novelty in aposematic coloration can arise in secondary contact zones even in systems where phenotypes are subject to strong stabilizing selection.
QCAT: testing causality of variants using only summary association statistics
Authors: Lee Donghyung , Bigdeli T. Bernard , Vladimirov Vladimir I. , Fanous Ayman H. , Bacanu Silviu-Alin
Published: September 2016

Genome-wide and, very soon, sequencing association studies, might yield multiple regions harbouring interesting association signals. Given that each region encompasses numerous variants in high linkage disequilibrium, it is not clear which are i) truly causal or ii) just reasonably close to the causal ones. Researchers proposed many methods to predict, albeit not test, the causal SNPs in a region, a process commonly denoted as fine-mapping. Unfortunately, all existing fine-mapping methods output posterior causality probabilities assuming that causal SNPs are among those already measured in the study, or have been catalogued elsewhere. However, due to technological and computational obstacles in calling many types of genetic variants, such assumption is not realistic. We propose a novel method/software, denoted as Quasi-CAausality Test (QCAT), for testing (not just predicting) the causality of any catalogued genetic variant. QCAT i) makes no assumption that causal variants are among catalogued variants, and ii) makes use of easily available summary statistics from genetic studies, e.g. variant association Z-scores, to make statistical inferences. The proposed statistical test controls the type I error at or below the desired level. Its practical application to well-known smoking association signals provide some insightful results. The QCAT software is publically available at:http://dleelab.github.io/qcat/
A novel TP53-KPNA3 translocation defines a de novo treatment-resistant clone in osteosarcoma
Authors: Chen Kenneth S. , Kwon Woo Sun , Kim Jiwoong , Heo Su Jin , Kim Hyo Song , Kim Hyo Ki , Kim Soo Hee , Lee Won Suk , Chung Hyun Cheol , Rha Sun Young , Hwang Tae Hyun
Published: September 2016

Osteosarcoma is the most common primary bone cancer. It can be cured by aggressive surgery and chemotherapy, but outcomes for metastatic or chemoresistant disease remain dismal. Cancer sequencing studies have shown that the p53 pathway is dysregulated in nearly every case, often by translocation; however, no studies of osteosarcoma evolution or intratumor heterogeneity have been done to date. We studied a patient with chemoresistant, metastatic disease over the course of 3 years. We performed exome sequencing on germline DNA and DNA collected from tumor at three separate time points. We compared variant calls and variant allele frequencies between different samples. We identified subclonal mutations in several different genes in the primary tumor sample and found that one particular subclone dominated subsequent tumor samples at relapse. This clone was marked by a novel TP53-KPNA3 translocation and loss of the opposite-strand wild-type TP53 allele. Future research must focus on the functional significance of such clones and strategies to eliminate them.
Design and Generation of Donor Constructs for Genome Engineering in Drosophila
Authors: Housden Benjamin E. , Perrimon Norbert
Published: September 2016

The generation of precise alterations to the genome using CRISPR requires the combination of CRISPR and a donor construct containing homology to the target site. A double-strand break is first generated at the target locus using CRISPR. It is then repaired using the endogenous homologous recombination (HR) pathway. When a donor construct is provided, it can be used as a template for HR repair and can therefore be exploited to introduce alterations in the genomic sequence with single base-pair precision. Here we describe a protocol for the generation of donor constructs using Golden Gate assembly and discuss some key considerations for donor construct design for use in Drosophila.
Systematic Mapping of Chemical–Genetic Interactions in Saccharomyces cerevisiae
Authors: Suresh Sundari , Schlecht Ulrich , Xu Weihong , Bray Walter , Miranda Molly , Davis Ronald W. , Nislow Corey , Giaever Guri , Lokey R. Scott , St.Onge Robert P.
Published: September 2016

Chemical–genetic interactions (CGIs) describe a phenomenon where the effects of a chemical compound (i.e., a small molecule) on cell growth are dependent on a particular gene. CGIs can reveal important functional information about genes and can also be powerful indicators of a compound’s mechanism of action. Mapping CGIs can lead to the discovery of new chemical probes, which, in contrast to genetic perturbations, operate at the level of the gene product (or pathway) and can be fast-acting, tunable, and reversible. The simple culture conditions required for yeast and its rapid growth, as well as the availability of a complete set of barcoded gene deletion strains, facilitate systematic mapping of CGIs in this organism. This process involves two basic steps: first, screening chemical libraries to identify bioactive compounds affecting growth and, second, measuring the effects of these compounds on genome-wide collections of mutant strains. Here, we introduce protocols for both steps that have great potential for the discovery and development of new small-molecule tools and medicines.
New insight on cubic–tetragonal–monoclinic phase transitions in ZrO2: ab initio study and symmetry analysis
Authors: Evarestov R. A. , Kitaev Yu. E.
Published: September 2016

A group-theory analysis of temperature-induced phase transitions in ZrO2 has been performed in the framework of the group–subgroup relationship tree (Bärnighausen tree) with the computer tools of the Bilbao Crystallographic Server. The transition paths including symmetry-allowed intermediate phases have been established. The active irreducible representations corresponding to soft phonon modes and spontaneous deformation strains responsible for the phase transitions have been determined. The phonon mode frequencies at the symmetry points of the Brillouin zones of cubic, tetragonal and monoclinic phases have been calculated using the ab initio density functional theory method. As a result, the soft modes and their symmetries have been revealed, which are in a complete agreement with the group-theoretical predictions.
Phase-targeted X-ray diffraction
Authors: Hansford G. M.
Published: September 2016

A powder X-ray diffraction (XRD) method to enhance the signal of a specific crystalline phase within a mixture is presented for the first time. Specificity to the targeted phase relies on finding coincidences in the ratios of crystal d spacings and the ratios of elemental characteristic X-ray energies. Such coincidences can be exploited so that the two crystal planes diffract through the same scattering angle at two different X-ray energies. An energy-resolving detector placed at the appropriate scattering angle will detect a significantly enhanced signal at these energies if the target mineral or phase is present in the sample. When implemented using high scattering angles, for example 2θ > 150°, the method is tolerant to sample morphology and distance on the scale of ∼2 mm. The principle of the method is demonstrated experimentally using Pd Lα1 and Pd Lβ1 emission lines to enhance the diffraction signal of quartz. Both a pure quartz powder pellet and an unprepared mudstone rock specimen are used to test and develop the phase-targeted method. The technique is further demonstrated in the sensitive detection of retained austenite in steel samples using a combination of In Lβ1 and Ti Kβ emission lines. For both these examples it is also shown how the use of an attenuating foil, with an absorption edge close to and above the higher-energy characteristic X-ray line, can serve to isolate to some degree the coincidence signals from other fluorescence and diffraction peaks in the detected spectrum. The phase-targeted XRD technique is suitable for implementation using low-cost off-the-shelf components in a handheld or in-line instrument format.
Carry‐over effects on the annual cycle of a migratory seabird: an experimental study
Authors: Fayet Annette L. , Freeman Robin , Shoji Akiko , Kirk Holly L. , Padget Oliver , Perrins Chris M. , Guilford Tim
Published: September 2016

Long‐lived migratory animals must balance the cost of current reproduction with their own condition ahead of a challenging migration and future reproduction. In these species, carry‐over effects, which occur when events in one season affect the outcome of the subsequent season, may be particularly exacerbated. However, how carry‐over effects influence future breeding outcomes and whether (and how) they also affect behaviour during migration and wintering is unclear.

Here we investigate carry‐over effects induced by a controlled, bidirectional manipulation of the duration of reproductive effort on the migratory, wintering and subsequent breeding behaviour of a long‐lived migratory seabird, the Manx shearwaterPuffinus puffinus. By cross‐fostering chicks of different age between nests, we successfully prolonged or shortened by ∼25% the chick‐rearing period of 42 breeding pairs. We tracked the adults with geolocators over the subsequent year and combined migration route data with at‐sea activity budgets obtained from high‐resolution saltwater‐immersion data. Migratory behaviour was also recorded during non‐experimental years (the year before and/or two years after manipulation) for a subset of birds, allowing comparison between experimental and non‐experimental years within treatment groups.

All birds cared for chicks until normal fledging age, resulting in birds with a longer breeding period delaying their departure on migration; however, birds that finished breeding earlier did not start migrating earlier. Increased reproductive effort resulted in less time spent at the wintering grounds, a reduction in time spent resting daily and a delayed start of breeding with lighter eggs and chicks and lower breeding success the following breeding season. Conversely, reduced reproductive effort resulted in more time resting and less time foraging during the winter, but a similar breeding phenology and success compared with control birds the following year, suggesting that ‘positive’ carry‐over effects may also occur but perhaps have a less long‐lasting impact than those incurred from increased reproductive effort.

Our results shed light on how carry‐over effects can develop and modify an adult animal's behaviour year‐round and reveal how a complex interaction between current and future reproductive fitness, individual condition and external constraints can influence life‐history decisions.
Microbial diversity within the Trichodesmium holobiont
Authors: Rouco Mónica , Haley Sheean T. , Dyhrman Sonya T.
Published: September 2016

Nitrogen‐fixing cyanobacteria in the genus Trichodesmium play a critical role in the productivity of the tropical and subtropical oligotrophic oceans. The ecological success of these populations is likely associated with the diverse microbial interactions occurring within the Trichodesmium holobiont, especially between Trichodesmium and heterotrophic bacterial epibionts. Yet, the composition of the Trichodesmium holobiont and the processes governing microbial assemblage are not well documented. Here, we used high‐resolution 16S rDNA amplicon sequencing to examine the diversity of Trichodesmium and associated epibionts across different ocean regions and colony morphologies (puffs and rafts). Trichodesmium Clade I (i.e., T. thiebautii‐like) dominated the colonies in all ocean basins regardless of morphology, although the Trichodesmium community structure significantly varied between morphologies in some regions. On average, Alphaproteobacteria (i.e., Thalassobius), Gammaproteobacteria (i.e., Pseudoalteromonas), Sphingobacteria (i.e., Microscilla and Vibrio) and Flavobacteria dominated the epibiont communities, but community composition and structure significantly differed between regions. Epibionts from the two colony morphologies were taxonomically and functionally distinct in the North Atlantic and North Pacific. These findings suggest that the colony types might define two distinct niches and that epibiont assemblage might be driven in part by selective processes, where epibionts are selected according to their influence on colony metabolism.
Heterogeneous Treatment Effects? An Examination of Australian Non‐Government Primary Schools
Authors: Rodgers Joan , Neri Frank , Moran Ian
Published: September 2016

On average, students in Australian non‐government schools consistently outperform their counterparts in government schools on standardised tests of literacy and numeracy. However, when differences across school sectors in student characteristics are taken into account, this performance differential largely disappears. Nevertheless, non‐government schools may have heterogeneous effects; that is, they may benefit particular groups of students. This study investigates the extent of non‐government‐school advantage for specific primary‐school student groups using data from National Assessment Program–Literacy and Numeracy and the Longitudinal Study of Australian Children. We find no evidence that non‐government primary schools have a positive effect on academic outcomes of children, categorised by sex or socioeconomic status.
Taxation of Housing
Authors: Freebairn John
Published: September 2016

The effects of taxation on housing market outcomes, and implications for efficiency and distribution, are assessed. Current consumption, income and asset taxes are evaluated. Effects of the taxes on decisions to purchase own home versus rent for housing services and for investment of household savings in own home, other property or other options, such as bank deposits and superannuation, are considered. Replacing conveyance duty and the current narrow‐base land tax with a broad‐based land tax is advocated. A more radical reform proposal for a larger land tax and lower income tax‐mix change is assessed.
The Inexorable Rise in House Prices in Australia since 1970: Unique or Not?
Authors: Stapledon Nigel
Published: September 2016

The period since 1970 has seen a very significant rise in house prices and rents in real terms in Australia. The geographical variance in house prices in the United States over the same period provides an insight into the rising value attached to amenity and the impact of supply constraints in explaining the rise. Financial deregulation and low interest rates are the key factors that, after 1991, boosted prices but at the same time limited rent growth. These factors are a one‐off and not a guide to the future. The decline in home‐ownership rates requires a more nuanced debate.
The Costs of Fall‐Related Injuries among Older Adults: Annual Per‐Faller, Service Component, and Patient Out‐of‐Pocket Costs
Authors: Hoffman Geoffrey J. , Hays Ron D. , Shapiro Martin F. , Wallace Steven P. , Ettner Susan L.
Published: September 2016

Objective

To estimate expenditures for fall‐related injuries (FRIs) among older Medicare beneficiaries.

Data Sources

The 2007–2009 Medicare claims and 2008 Health and Retirement Study (HRS) data for 5,497 (228 FRI and 5,269 non‐FRI) beneficiaries.

Study Design

FRIs were indicated by inpatient/outpatient ICD‐9 diagnostic codes for fractures, trauma, dislocations, and by e‐codes. A pre‐post comparison group design was used to estimate the differential change in pre‐post expenditures for the FRI relative to the non‐FRI cohort (FRI expenditures). Out‐of‐pocket (OOP) costs, service category total annual FRI‐related Medicare expenditures, expenditures related to the type of initial FRI treatment (inpatient, ED, outpatient), and the risk of persistently high expenditures (4th quartile for each post‐FRI quarter) were estimated.

Principal Findings

Estimated FRI expenditures were $9,389 (95 percent CI: $5,969–$12,808). Inpatient, physician/outpatient, skilled nursing facility, and home health comprised 31, 18, 39, and 12 percent of the total. OOP costs were $1,363.0 (95 percent CI: $889‐$1,837). Expenditures for FRIs initially treated in inpatient/ED/outpatient settings were $21,424/$6,142/$8,622. The FRI cohort had a 64 percent increased risk of persistently high expenditures. Total Medicare expenditures were $13 billion (95 percent CI: $9–$18 billion).

Conclusions

FRIs are associated with substantial, persistent Medicare expenditures. Cost‐effectiveness of multifactorial falls prevention programs should be assessed using these expenditure estimates.
Developmental Times of Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) at Constant Temperatures and Applications in Forensic Entomology
Authors: Yang Yong‐qiang , Li Xue‐bo , Shao Ru‐yue , Lyu Zhou , Li Hong‐wei , Li Gen‐ping , Xu Lyu‐zi , Wan Li‐hua
Published: September 2016

The characteristic life stages of infesting blowflies (Calliphoridae) such as Chrysomya megacephala (Fabricius) are powerful evidence for estimating the death time of a corpse, but an established reference of developmental times for local blowfly species is required. We determined the developmental rates of C. megacephala from southwest China at seven constant temperatures (16–34°C). Isomegalen and isomorphen diagrams were constructed based on the larval length and time for each developmental event (first ecdysis, second ecdysis, wandering, pupariation, and eclosion), at each temperature. A thermal summation model was constructed by estimating the developmental threshold temperature D0 and the thermal summation constant K. The thermal summation model indicated that, for complete development from egg hatching to eclosion, D0 = 9.07 ± 0.54°C and K = 3991.07 ± 187.26 h °C. This reference can increase the accuracy of estimations of postmortem intervals in China by predicting the growth of C. megacephala.
Synthesis of Common Management Concerns Associated with Dam Removal
Authors: Tullos Desirée D. , Collins Mathias J. , Bellmore J. Ryan , Bountry Jennifer A. , Connolly Patrick J. , Shafroth Patrick B. , Wilcox Andrew C.
Published: September 2016

Managers make decisions regarding if and how to remove dams in spite of uncertainty surrounding physical and ecological responses, and stakeholders often raise concerns about certain negative effects, regardless of whether these concerns are warranted at a particular site. We used a dam‐removal science database supplemented with other information sources to explore seven frequently raised concerns, herein Common Management Concerns (CMCs). We investigate the occurrence of these concerns and the contributing biophysical controls. The CMCs addressed are the following: degree and rate of reservoir sediment erosion, excessive channel incision upstream of reservoirs, downstream sediment aggradation, elevated downstream turbidity, drawdown impacts on local water infrastructure, colonization of reservoir sediments by nonnative plants, and expansion of invasive fish. Biophysical controls emerged for some of the concerns, providing managers with information to assess whether a given concern is likely to occur at a site. To fully assess CMC risk, managers should concurrently evaluate site conditions and identify the ecosystem or human uses that will be negatively affected if the biophysical phenomenon producing the CMC occurs. We show how many CMCs have one or more controls in common, facilitating the identification of multiple risks at a site, and demonstrate why CMC risks should be considered in the context of other factors such as natural watershed variability and disturbance history.
Evaluating Flow Diversion Impacts to Groundwater‐Dependent Riparian Vegetation with Flow Alteration and Groundwater Model Analysis
Authors: Hathaway Deborah L. , Barth Gilbert , Kirsch Katie
Published: September 2016

An approach for assessing the potential ecologic response of groundwater‐dependent riparian vegetation to flow alteration is developed, focusing on change to groundwater. Groundwater requirements for riparian vegetation are reviewed in conjunction with flow alteration statistics. Where flow alteration coincides with groundwater‐related vegetation sensitivities, scenarios are developed for groundwater simulation. Groundwater depths and recession rates in the riparian zone are simulated for baseline and altered stream hydrographs, with changes to river stage and width represented with a transient, flow‐dependent boundary condition. Potential flow diversion from the Upper Gila River in New Mexico is examined. Statistical flow alteration analysis, applying prospective diversions to a 76‐year record of daily flow, shows that flows in the winter‐spring months and within the high‐pulse to small flood range are subject to greatest potential change. Groundwater simulation scenarios are developed for these flow conditions in representative dry, near‐average, and wet years. Differences in groundwater elevations, generally less than 0.25 m during the flow alteration period, dissipate rapidly following cessation of diversion. Relating groundwater depth, recession rates and range of fluctuations to riparian vegetation needs, we find adverse ecological response is not expected from groundwater impacts for the flow alteration examined.