bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Advanced Neoplasia Using the National Cancer Institute’s Colorectal
Cancer Risk Assessment Tool
Authors: Imperiale Thomas F , Yu Menggang , Monahan Patrick O , Stump Timothy E , Tabbey Rebeka , Glowinski Elizabeth , Ransohoff David F
Published: September 2016

Background: There is no validated, discriminating, and easy-to-apply tool for estimating risk of colorectal neoplasia. We studied whether the National Cancer Institute’s (NCI’s) Colorectal Cancer (CRC) Risk Assessment Tool, which estimates future CRC risk, could estimate current risk for advanced colorectal neoplasia among average-risk persons.

Methods: This cross-sectional study involved individuals age 50 to 80 years undergoing first-time screening colonoscopy. We measured medical and family history, lifestyle information, and physical measures and calculated each person’s future CRC risk using the NCI tool’s logistic regression equation. We related quintiles of future CRC risk to the current risk of advanced neoplasia (sessile serrated polyp or tubular adenoma ≥ 1 cm, a polyp with villous histology or high-grade dysplasia, or CRC). All statistical tests were two-sided.

Results: For 4457 (98.5%) with complete data (mean age = 57.2 years, SD = 6.6 years, 51.7% women), advanced neoplasia prevalence was 8.26%. Based on quintiles of five-year estimated absolute CRC risk, current risks of advanced neoplasia were 2.1% (95% confidence interval [CI] = 1.3% to 3.3%), 4.8% (95% CI = 3.5% to 6.4%), 6.4% (95% CI = 4.9% to 8.2%), 10.0% (95% CI = 8.1% to 12.1%), and 17.6% (95% CI = 15.5% to 20.6%; P < .001). For quintiles of estimated 10-year CRC risk, corresponding current risks for advanced neoplasia were 2.2% (95% CI = 1.4% to 3.5%), 4.8% (95% CI = 3.5% to 6.4%), 6.5% (95% CI = 5.0% to 8.3%), 9.3% (95% CI = 7.5% to 11.4%), and 18.4% (95% CI = 15.9% to 21.1%; P < .001). Among persons with an estimated five-year CRC risk above the median, current risk for advanced neoplasia was 12.8%, compared with 3.7% among those below the median (relative risk = 3.4, 95 CI = 2.7 to 4.4).

Conclusions: The NCI’s Risk Assessment Tool, which estimates future CRC risk, may be used to estimate current risk for advanced neoplasia, making it potentially useful for tailoring and improving CRC screening efficiency among average-risk persons.
Surveying for Virus-vectoring Nematodes in Container-grown Blueberry Plants in Oregon
Authors: Sharma-Poudyal D. , Fraley C. , Osterbauer N. K.
Published: September 2016

The goal of this study was to determine the risk of finding virus-vectoring nematodes in containerized blueberry plants placed on gravel. To detect dagger nematode, soil, and potting media samples were collected from blueberry nurseries growing plants in containers using soilless potting media, with the containers placed on a gravel bed or, for one nursery, on a plastic sheet placed on the soil surface. Potting media samples were collected from containers holding plants and soil samples were collected from beneath the gravel or plastic barrier. Nematodes were extracted from all of the samples using sucrose centrifugation. No dagger or other plant parasitic nematodes were detected in any of the samples tested. These results suggest no treatment of soilless potting media is necessary before planting blueberries into containers. Similarly, the gravel layer seems to be an effective barrier for suppressing dagger and other plant parasitic nematodes.

Accepted for publication 25 July 2016. Published 8 August 2016.
An immuno-suppressive aphid saliva protein is delivered into the cytosol of plant mesophyll cells during feeding
Authors: Mugford Sam T. , Barclay Elaine , Drurey Claire , Findlay Kim C. , Hogenhout Saskia A.
Published: September 2016

Herbivore selection of plant hosts and plant responses to insect colonization have been subjects of intense investigations. A growing body of evidence suggests that for successful colonization to occur, (effector/virulence) proteins in insect saliva must modulate plant defense responses to the benefit of the insect. A range of insect saliva proteins that modulate plant defense responses have been identified, but there is no direct evidence that these proteins are delivered into specific plant tissues and enter plant cells. Aphids and other sap-sucking insects of the order Hemiptera use their specialized mouthparts (stylets) to probe plant mesophyll cells, until they reach the phloem cells for long-term feeding. Here we show by immunogold-labeling of ultrathin sections of aphid feeding sites that an immuno-suppressive aphid effector localizes in the cytoplasm of mesophyll cells near aphid stylets, but not in cells further away from aphid feeding sites. In contrast, another aphid effector protein localizes in the sheaths composed of gelling saliva that surround the aphid stylets. Thus, insects deliver effectors directly into plant tissue. Moreover, different aphid effectors locate extracellularly in the sheath saliva or are introduced into the cytoplasm of plant cells.
Epigenetic switching as a strategy for quick adaptation while constraining biochemical noise
Authors: Gómez-Schiavon Mariana , Buchler Nicolas E
Published: September 2016

Epigenetic switches are bistable, molecular systems built from self-reinforcing feedback loops that can spontaneously switch between heritable phenotypes in the absence of DNA mutation. It has been hypothesized that epigenetic switches first evolved as a mechanism of bet-hedging and adaptation, but the evolutionary trajectories and conditions by which an epigenetic switch can outcompete adaptation through genetic mutation remain unknown. Here, we used computer simulations to evolve a mechanistic, biophysical model of a self-activating genetic circuit, which can both adapt genetically through mutation and exhibit epigenetic switching. We evolved these genetic circuits under a fluctuating environment that alternatively selected for low and high protein expression levels. In all tested conditions, the population first evolved by genetic mutation to regimes of high nonlinearity to decrease the genetic adaptation time after each environmental transition. Once at high nonlinearity, epigenetic switching became accessible and could start competing with genetic adaptation as a possible strategy. We show the existence of a trade-off between either minimizing the adaptation time or increasing the robustness of the phenotype to biochemical noise. Epigenetic switching was superior in a fast fluctuating environment because it adapted faster than genetic mutation after an environmental transition. Conversely, genetic adaptation was favored in a slowly fluctuating environment because it minimized the noise load during the constant environment between transitions. These simple trade-offs reliably predict the conditions and trajectories under which an epigenetic switch evolved to outcompete genetic adaptation, shedding light on possible mechanisms by which bet-hedging strategies might emerge and persist in natural populations.
Disentangling the Relative Strength of Niche Competition from Grazing-Induced Phytoplankton Mortality
Authors: Beckett Stephen J. , Weitz Joshua S.
Published: September 2016

The dilution method is the principal tool used to inferin situmicrozooplankton grazing rates. However, grazing is the only mortality process considered in the theoretical model underlying the interpretation of dilution method experiments. Here we evaluate the robustness of mortality estimates inferred from dilution experiments when there is concurrent niche competition amongst phytoplankton. Using a combination of mathematical analysis and numerical simulations, we find that grazing rates may be overestimated – the degree of overestimation is related to the importance of niche competition relative to microzooplankton grazing. In response, we propose a conceptual method to disentangle the effects of niche competition and grazing by diluting out microzooplankton, but not phytoplankton. Our theoretical results suggest this revised “Z-dilution” method can robustly infer grazing mortality, regardless of the dominant phytoplankton mortality driver in our system. Further, we show it is possible to independently estimate both grazing mortality and niche competition if the classical and Z-dilution methods can be used in tandem. We discuss the significance of these results for quantifying phytoplankton mortality rates; and the feasibility of using the Z-dilution method in practice.
Factors contributing to the accumulation of reproductive isolation: a mixed model approach
Authors: Castillo Dean M.
Published: September 2016

The analysis of large data sets describing reproductive isolation between species that vary in their degrees of relatedness has been extremely influential in the study of speciation. However, several limitations make it difficult to test specific hypotheses about which factors predict the evolution of reproductive isolation. In particular, the statistical methods typically used are limited in their ability to test complex hypotheses involving multiple predictor variables or interactions between variables; at least one method, the Mantel Test, has also been found to be unreliable. In this paper, I describe a framework to determine which factors contribute to the evolution of reproductive isolation using phylogenetic linear mixed models. Phylogenetic linear mixed models do not suffer from the same statistical limitations as other methods and I demonstrate the flexibility of this framework to analyze data collected at different evolutionary scales, to test both categorical and continuous predictor variables, and to test the effect of multiple predictors simultaneously, all of which cannot be achieved using any other single statistical method. I do so by re-analyzing several classic data sets and explicitly testing hypotheses that had previously been untested directly, including differences in accumulation of reproductive isolation between sympatric and allopatric species pairs.
A Neural Oscillatory Signature of Reference
Authors: Nieuwland Mante S. , Martin Andrea E.
Published: September 2016

The ability to use words to refer to the world is vital to the communicative power of human language. In particular, the anaphoric use of words to refer to previously mentioned concepts (antecedents) allows dialogue to be coherent and meaningful. Psycholinguistic theory posits that anaphor comprehension involves reactivating a memory representation of the antecedent. Whereas this implies the involvement of recognition memory, the neural processes for reference resolution are largely unknown. Here, we report time-frequency analysis of four EEG experiments to reveal the increased coupling of functional neural systems associated with referentially coherent expressions compared to referentially ambiguous expressions. Despite varying in modality, language, and type of referential expression, all experiments showed larger gamma-band power for coherence compared to ambiguity. Beamformer analysis in high-density Experiment 4 localised this increase to posterior parietal cortex around 400-600 ms after anaphor-onset and to frontal-temporal cortex around 500-1000 ms. We argue that the observed gamma-band power increases reflect successful referential binding and resolution, which links incoming information to antecedents through an interaction between the brain’s recognition memory networks and frontal-temporal language network. We integrate these findings with previous results from patient and neuroimaging studies, and outline a nascent cortico-hippocampal theory of reference.
GAVIN - Gene-Aware Variant INterpretation for medical sequencing
Authors: van der Velde K. Joeri , de Boer Eddy N. , van Diemen Cleo C. , Sikkema-Raddatz Birgit , Abbott Kristin M. , Knopperts Alain , Franke Lude , Sijmons Rolf H. , de Koning Tom J. , Wijmenga Cisca , Sinke Richard J. , Swertz Morris A.
Published: September 2016

Here, we present GAVIN, a new method that delivers accurate classification of variants for next-generation sequencing molecular diagnostics. It is based on gene-specific calibrations of allele frequencies (from the ExAC database), effect impact (using SnpEff) and estimated deleteriousness (CADD scores) for >3,000 genes. In a benchmark on 18 clinical gene sets, we achieved a sensitivity of 91.6%, with a specificity of 78.2%. This accuracy was unmatched by 12 other tools we tested. We provide GAVIN as an online MOLGENIS service to annotate VCF files, and as open source executable for use in bioinformatic pipelines. It can be found athttp://molgenis.org/gavin.
Evolution of cell-to-cell variability in stochastic, controlled, heteroplasmic mtDNA populations
Authors: Johnston Iain G. , Jones Nick S.
Published: September 2016

Populations of physiologically vital mitochondrial DNA (mtDNA) molecules evolve in cells under control from the nucleus. The evolution of populations of mixed mtDNA types is complicated and poorly understood, and variability of these controlled admixtures plays a central role in the inheritance and onset of genetic disease. Here, we develop a mathematical theory describing the evolution and variability in these stochastic populations for any type of cellular control, showing that cell-to-cell variability in mtDNA, and mutant load, inevitably increases with time, according to rates which we derive and which are notably independent of the mechanistic details of feedback signalling. We show with a set of experimental case studies that this theory explains disparate quantitative results from classical and modern experimental and computational studies on heteroplasmy variance in different species. We demonstrate that our general model provides a host of specific insights, including a modification of the often-used but hard-to-interpret Wright formula to correspond directly to biological observables, the ability to quantify selective and mutational pressure in mtDNA populations, and the pronounced variability inevitably arising from the action of possible mtDNA quality-control mechanisms. Our general theoretical framework, supported by existing experimental results, thus helps understand and predict the evolution of stochastic mtDNA populations in cell biology.
Zika infection of neural progenitor cells perturbs transcription in neurodevelopmental pathways
Authors: Yi Lynn , Pimentel Harold , Pachter Lior
Published: September 2016

Background

A recent study of the gene expression patterns of Zika virus (ZIKV) infected human neural progenitor cells (hNPCs) revealed transcriptional dysregulation and identified cell-cycle-related pathways that are affected by infection. However deeper exploration of the information present in the RNA-Seq data can be used to further elucidate the manner in which Zika infection of hNPCs affects the transcriptome, refining pathway predictions and revealing isoform-specific dynamics.

Methodology/Principal Findings

We analyzed data published by Tanget al.using state-of-the-art tools for transcriptome analysis. By accounting for the experimental design and estimation of technical and inferential variance we were able to pinpoint Zika infection affected pathways that highlight Zika’s neural tropism. The examination of differential genes reveals cases of isoform divergence.

Conclusions/Significance

Transcriptome analysis of Zika infected hNPCs has the potential to identify the molecular signatures of Zika infected neural cells. These signatures may be useful for diagnostics and for the resolution of infection pathways that can be used to harvest specific targets for further study.
De novo PHIP-predicted deleterious variants are associated with developmental delay, intellectual disability, obesity, and dysmorphic features
Authors: Webster Emily , Cho Megan T. , Alexander Nora , Desai Sonal , Naidu Sakkubai , Bekheirnia Mir Reza , Lewis Andrea , Retterer Kyle , Juusola Jane , Chung Wendy K.
Published: September 2016

Using whole-exome sequencing, we have identified novel de novo heterozygous pleckstrin homology domain-interacting protein (PHIP) variants that are predicted to be deleterious, including a frameshift deletion, in two unrelated patients with common clinical features of developmental delay, intellectual disability, anxiety, hypotonia, poor balance, obesity, and dysmorphic features. A nonsense mutation in PHIP has previously been associated with similar clinical features. Patients with microdeletions of 6q14.1, including PHIP, have a similar phenotype of developmental delay, intellectual disability, hypotonia, and obesity, suggesting that the phenotype of our patients is a result of loss-of-function mutations. PHIP produces multiple protein products, such as PHIP1 (also known as DCAF14), PHIP, and NDRP. PHIP1 is one of the multiple substrate receptors of the proteolytic CUL4-DDB1 ubiquitin ligase complex. CUL4B deficiency has been associated with intellectual disability, central obesity, muscle wasting, and dysmorphic features. The overlapping phenotype associated with CUL4B deficiency suggests that PHIP mutations cause disease through disruption of the ubiquitin ligase pathway.
Morphological Analysis of Cell Death by Cytospinning Followed by Rapid Staining
Authors: Crowley Lisa C. , Marfell Brooke J. , Waterhouse Nigel J.
Published: September 2016

Identifying and characterizing different forms of cell death can be facilitated by staining internal cellular structures with dyes such as hematoxylin and eosin (H&E). These dyes stain the nucleus and cytoplasm, respectively, and optimized reagents (e.g., Rapi-Diff, Rapid Stain, or Quick Dip) are commonly used in pathology laboratories. Fixing and staining adherent cells with these optimized reagents is a straightforward procedure, but apoptotic cells may detach from the culture plate and be washed away during the fixing and staining procedure. To prevent the loss of apoptotic cells, cells can be gently centrifuged onto glass slides by cytospinning before fixing and staining. In addition to apoptotic cells, this procedure can be used on cells in suspension, or adherent cells that have been trypsinized and removed from the culture dish. This protocol describes cytospinning followed by Rapi-Diff staining for morphological analysis of cell death.
Analyzing Cell Death by Nuclear Staining with Hoechst 33342
Authors: Crowley Lisa C. , Marfell Brooke J. , Waterhouse Nigel J.
Published: September 2016

The nuclei of healthy cells are generally spherical, and the DNA is evenly distributed. During apoptosis the DNA becomes condensed, but this process does not occur during necrosis. Nuclear condensation can therefore be used to distinguish apoptotic cells from healthy cells or necrotic cells. Dyes that bind to DNA, such as Hoechst 33342 or 4′,6-diamidino-2-phenylindole (DAPI), can be used to observe nuclear condensation. These dyes fluoresce at 461 nm when excited by ultraviolet light and can therefore be visualized using conventional fluorescent microscopes equipped with light sources that emit light at ∼350 nm and filter sets that permit the transmission of light at ∼460 nm. This protocol describes staining and visualization of cells stained with Hoechst 33342, but it can be adapted for staining with DAPI or other dyes.
Measuring Ca2+-Dependent Modulation of Voltage-Gated Ca2+ Channels in HEK-293T Cells
Authors: Thomas Jessica R. , Lee Amy
Published: September 2016

Voltage-gated Ca2+ (Cav) channels regulate a variety of biological processes, such as muscle contraction, gene expression, and neurotransmitter release. Cav channels are subject to diverse forms of regulation, including those involving the Ca2+ ions that permeate the pore. High voltage-activated Cav channels undergo Ca2+-dependent inactivation (CDI) and facilitation (CDF), which can regulate processes such as cardiac rhythm and synaptic plasticity. CDI and CDF differ slightly between Cav1 (L-type) and Cav2 (P/Q-, N-, and R-type) channels. Human embryonic kidney cells transformed with SV40 large T-antigen (HEK-293T) are advantageous for studying CDI and CDF of a particular type of Cav channel. HEK-293T cells do not express endogenous Cav channels, but Cav channels can be expressed exogenously at high levels in these cells by transient transfection. This protocol describes how to characterize and analyze Ca2+-dependent modulation of recombinant Cav channels in HEK-293T cells.
Identification of Chemical–Genetic Interactions via Parallel Analysis of Barcoded Yeast Strains
Authors: Suresh Sundari , Schlecht Ulrich , Xu Weihong , Miranda Molly , Davis Ronald W. , Nislow Corey , Giaever Guri , St.Onge Robert P.
Published: September 2016

The Yeast Knockout Collection is a complete set of gene deletion strains for the budding yeast,Saccharomyces cerevisiae. In each strain, one of approximately 6000 open-reading frames is replaced with a dominant selectable marker flanked by two DNA barcodes. These barcodes, which are unique to each gene, allow the growth of thousands of strains to be individually measured from a single pooled culture. The collection, and other resources that followed, has ushered in a new era in chemical biology, enabling unbiased and systematic identification of chemical–genetic interactions (CGIs) with remarkable ease. CGIs link bioactive compounds to biological processes, and hence can reveal the mechanism of action of growth-inhibitory compounds in vivo, including those of antifungal, antibiotic, and anticancer drugs. The chemogenomic profiling method described here measures the sensitivity induced in yeast heterozygous and homozygous deletion strains in the presence of a chemical inhibitor of growth (termed haploinsufficiency profiling and homozygous profiling, respectively, or HIPHOP). The protocol is both scalable and amenable to automation. After competitive growth of yeast knockout collection cultures, with and without chemical inhibitors, CGIs can be identified and quantified using either array- or sequencing-based approaches as described here.
Designing Polymerase Chain Reaction Primers Using Primer3Plus
Authors: Hung Jui-Hung , Weng Zhiping
Published: September 2016

Designing oligonucleotide primers is a crucial step for successful molecular biology experiments that require the use of the polymerase chain reaction (PCR). PCR involves cycles of three steps: denaturation, annealing, and extension. During denaturation, double-stranded DNA (dsDNA) molecules (templates) are separated into single strands. During annealing, a pair of primers is annealed to the complementary regions of the single-stranded molecules. In the extension step, DNA polymerase extends the primers to produce DNA molecules that correspond to the region bracketed by the primers (the amplicons). All of these steps are temperature sensitive, and the common choice of temperatures is 94°C, 60°C, and 70°C, respectively. Poorly designed primers may lead to no amplification product or additional undesired amplified fragments. The goals of primer design include good primer specificity, high annealing efficiency, appropriate melting temperature, proper GC content, and the prevention of primer hairpins or primer dimers.
Azido{1-[(2-diethylaminoethylimino)methyl]naphthalato}copper(II). Erratum
Authors: Qiu Xiao-Yang
Published: September 2016

In the paper by Qiu [Acta Cryst. (2006), E62, m849–m850], the metal atom was reported incorrectly.
Content analysis of comparative claims in drug advertisements
Authors: Boudewyns Vanessa , Williams Pamela A.
Published: September 2016

Purpose

The purpose of this study is to describe the trends and practices of comparative prescription drug advertising by examining the types of comparative claims made in direct-to-consumer (DTC) and direct-to-physician (DTP) print advertisements.

Design/methodology/approach

The authors conducted a content analysis of 54 DTC and DTP print prescription drug advertisements (published between 1997 and 2014) with comparative claims.

Findings

Efficacy-based comparisons appeared in 64 per cent of advertisements, and attribute-based comparisons appeared in 37 per cent of advertisements. Most advertisements made direct (vs indirect) references to competitors (85 per cent), compared the advertised drug to a single (vs multiple) competitor (78 per cent), focused exclusively on one type of comparison claim (i.e. efficacy-, risk- or attribute-based) (70 per cent) and did not contain data-driven visual aids (82 per cent). Some differences between DTC and DTP advertisements emerged. More DTP than DTC advertisements included data-driven visual aids (82 per cent vs 0 per cent, respectively), included numerical data (88 per cent vs 53 per cent) and conveyed statistical significance (52 per cent vs 12 per cent).

Research limitations/implications

The study used a convenience sample rather than a random sample of advertisements; thus, the findings might not be generalizable to all pharmaceutical DTC and DTP advertisements. Examining the tactics that advertisers use to educate and influence consumers and physicians sets the foundation for future studies that examine the effects of their exposure to comparative claims. Suggestions for future research are discussed.

Originality/value

This study is the first to examine and statistically compare the comparative advertising tactics used in both consumer and physician prescription drug advertisements.
Causes and effects of wine tourism development in wineries
Authors: Lavandoski Joice , Pinto Patrícia , Silva João Albino , Vargas-Sánchez Alfonso
Published: September 2016

Purpose

This study aims to propose that the institutional environment exerts pressure on the behavior of wineries toward wine tourism development (WTD) and the effect of this influence confers legitimacy to the business of wine tourism.

Design/methodology/approach

Structural equation modeling through partial least squares was applied to estimate and validate a model using data from a quantitative survey in the universe of 62 wineries with a wine tourism component along the Alentejo Wine Route in Portugal. The proposed model is based on institutional theory through an inter-organizational perspective of wineries.

Findings

The results show that WTD coexists with a highly institutionalized environment, exerting distinctive mechanisms of external pressure together with the search for social legitimacy through actions and practices on the part of the involved wineries. However, the relationship between legitimacy and organizational performance in wineries with wine tourism is not validated.

Research limitations/implications

The specific sample of the Alentejo wine companies does not allow the results to be generalized. Future studies should replicate the proposed research model using other geographic areas.

Practical implications

The results are particularly interesting for managers of wineries and should be considered in the decision-making and strategic processes regarding wine tourism.

Originality/value

The use of institutional theory in the wine tourism context is novel and original. This study fills a research gap by conducting an empirical investigation of wine tourism based on institutional theory, which allows the identification of exogenous factors that can influence and impose restrictions on the organizational behavior of winery companies toward wine tourism.
Mechanical compaction in heterogeneous clastic formations from plastic–poroelastic deformation principles: theory and applications
Authors: Bachrach Ran
Published: September 2016

Mechanical compaction or loss of porosity due to increase in effective stress is a fundamental geological process that governs many of the rock elastic and transport parameters, all of great importance in exploring and developing subsurface reservoirs. The ability to model the compaction process enables us to improve our understanding of the seismic signature of the basin and better relate the geology of deposition to current porosity, velocity, pore pressure, and other mechanical parameters that depend on the state of compaction of the sediment. In this paper, a set of mathematical equations that can be used to model the plastic deformation associated with primary and secondary loading curves is presented. Compaction laws are posed in terms of natural strain increment formulation often used in plasticity theory to model large deformation. Laboratory and field estimates of constitutive plastic deformation relations for sand–shale mixtures are used in a numerical model that generates estimates of porosity under various pore pressures, shale content, and loading scenarios. These estimates can be used in a variety of settings to predict various basin and reservoir properties associated with different loading conditions and/or sedimentation processes.
Bone morphogenetic protein 6—a possible new player in pathophysiology of heart failure
Authors: Banach Joanna , Gilewski Wojciech , Słomka Artur , Buszko Katarzyna , Błażejewski Jan , Karasek Danuta , Rogowicz Daniel , Żekanowska Ewa , Sinkiewicz Wadyslaw
Published: September 2016

Derangement of bone morphogenetic protein (BMP) signalling was observed in cardiovascular disorders. The present study assesses the diagnostic and prognostic value of BMP6 plasma concentration in chronic heart failure (CHF). 130 CHF patients and 32 controls participated in the study. BMP6 plasma level was measured at baseline. During 12‐month follow‐up death and hospitalisation with CHF exacerbation were recorded. BMP6 was significantly increased in CHF patients with highest concentration in most advanced disease. Individuals with pulmonary congestion or peripheral oedema had higher levels of BMP6 than isovolemic patients. BMP6 was not a predictor of all‐cause mortality or CHF hospitalisation. BMP6 may be involved in pathophysiology of systolic CHF. BMP6 plasma level is related to the disease severity and signs of exacerbation.
Fungal community composition in soils subjected to long‐term chemical fertilization is most influenced by the type of organic matter
Authors: Sun Ruibo , Dsouza Melissa , Gilbert Jack A. , Guo Xisheng , Wang Daozhong , Guo Zhibin , Ni Yingying , Chu Haiyan
Published: September 2016

Organic matter application is a widely used practice to increase soil carbon content and maintain soil fertility. However, little is known about the effect of different types of organic matter, or the input of exogenous species from these materials, on soil fungal communities. In this study, fungal community composition was characterized from soils amended with three types of organic matter over a 30‐year fertilization experiment. Chemical fertilization significantly changed soil fungal community composition and structure, which was exacerbated by the addition of organic matter, with the direction of change influenced by the type of organic matter used. The addition of organic matter significantly increased soil fungal richness, with the greatest richness achieved in soils amended with pig manure. Importantly, following addition of cow and pig manure, fungal taxa associated with these materials could be found in the soil, suggesting that these exogenous species can augment soil fungal composition. Moreover, the addition of organic matter decreased the relative abundance of potential pathogenic fungi. Overall, these results indicate that organic matter addition influences the composition and structure of soil fungal communities in predictable ways.
Tax Compliance and Data: What Is Available and What Is Needed
Authors: Torgler Benno
Published: September 2016

After first providing an overview of useful survey data sources and commonly studied variables in the area of tax compliance, this article outlines the major tools and exploratory methods used in the field, including laboratory and field experiments, simulations and surveys. It also discusses future possibilities and the data required to progress in this area. It is thus particularly useful as a guide for those planning or just beginning to work in the tax compliance field.
The Attrition Rate, Lifetime and Hoarding of Australian Decimal Coins
Authors: Frazer Eric J. , van der Touw John
Published: September 2016

Samples of Australian decimal coinage were taken in 2008 and 2012 from a major currency processing centre in Melbourne. A generic model was developed to analyse the pooled data and give separate estimates of loss, hoarding and return rates, as well as the numbers of coins in circulation, hoarded and permanently lost. For standard design coins, no particular trend in attrition rate with denomination was observed and average lifetimes were generally more than 30 years. Higher attrition rates were observed for the commemorative 20 cent and 50 cent coins versus the standard design. Hoarding was quantified for the 5 cent and 50 cent coins.
Retirees, Creatives and Housing Market Complexity: Challenges for Policy‐Makers
Authors: de Silva Ashton , Sinclair Sarah , Angelopoulos Sveta
Published: September 2016

Retirees and creatives, significant cohorts in the Australian economy, are used in this article to demonstrate the challenges faced by policy‐makers when addressing the housing environment. The housing market is characterised by many participants, often with competing needs and wants, all contributing to the complexity of housing policy. As a result, policy can be difficult to define with multi‐directional interdependencies. We identify five characteristics of complexity—uniqueness, layers of government, dynamism, actors and knowledge spheres—that if duly considered in the policy formation process could contribute to a more integrated approach that minimises negative and conflicting policy consequences.
Corporate Mobility and Company Law
Authors: Ferran Eilís
Published: September 2016

Globalisation has given commercial parties more freedom to choose the company law system that best suits their private needs. The growing range of techniques to facilitate choice between systems of company law reshapes the mandatory/enabling debate in countries where corporate mobility is a relatively new business phenomenon and where the past focus has mostly been on degrees of flexibility within domestic law. This article examines relocations, both out of and into the UK, as a source of learning on market preferences with respect to company law and on vulnerabilities. It considers the wider policy implications for the development of company law of more freedom of choice between company law systems. It concludes with a call to explore the potential for more optionality within company law to counter the rise of choice between systems of company law.
The Power of Policy: Reinforcing the Paris Trajectory
Authors: Figueres Christiana
Published: September 2016

The Paris Agreement is a critical global response that enables a transition toward human and planetary wellbeing. It articulates a new trajectory toward a low‐carbon economic system. It encompasses all countries, in the global North and South, and engages public and private sectors at local and global levels. Every country has stepped up to contribute to addressing the challenge of climate change. Governments, civil society, businesses, investors, academics expressed commitment to tackling climate change not as an end in itself, but as a means to a resilient society, to sustainable development and to more fulfilling and enriching lifestyles and livelihoods.
Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder
Authors: Lasek Amy W.
Published: September 2016

The brain extracellular matrix (ECM) occupies the space between cells and is involved in cell–matrix and cell–cell adhesion. However, in addition to providing structural support to brain tissue, the ECM activates cell signaling and controls synaptic transmission. The expression and activity of brain ECM components are regulated by alcohol exposure. This review will discuss what is currently known about the effects of alcohol on the activity and expression of brain ECM components. An interpretation of how these changes might promote alcohol use disorder (AUD) will be also provided. Ethanol (EtOH) exposure decreases levels of structural proteins involved in the interstitial matrix and basement membrane, with a concomitant increase in proteolytic enzymes that degrade these components. In contrast, EtOH exposure generally increases perineuronal net components. Because the ECM has been shown to regulate both synaptic plasticity and behavioral responses to drugs of abuse, regulation of the brain ECM by alcohol may be relevant to the development of alcoholism. Although investigation of the function of brain ECM in alcohol abuse is still in early stages, a greater understanding of the interplay between ECM and alcohol might lead to novel therapeutic strategies for treating AUD.
Information linkages between emission allowance and energy markets
Authors: Schultz Emma , Swieringa John
Published: September 2016

We employ a rational expectations framework similar to that proposed by Fleming et al. (1998) to examine the source, and nature of, information linkages between the emission allowance and energy markets as gauged by the correlation of return volatilities. Estimating the model for bivariate pairings of securities suggests that market linkages arise from sensitivities to common information rather than from indirect spillovers, with emission allowances most strongly linked to the crude oil market.
Pre‐exposure prophylaxis for people who inject drugs and their sex partners
Authors: Beyrer Chris
Published: September 2016

Commentary to: ‘PrEP is not ready for our community, and our community is not ready for PrEP’: pre‐exposure prophylaxis for HIV for people who inject drugs and limits to the HIV prevention response
Rethinking recovery
Authors: Lancaster Kari
Published: September 2016

Commentary to: Making the hard work of recovery more attractive for those with substance use disorders
Heterogeneous survival between stage IIA and stage IIIA colon cancer when different numbers of lymph nodes are harvested
Authors: Huang Ben , Feng Yang , Ni Mengdong , Chen Chen , Cai Guoxiang
Published: September 2016

Background

We aim to compare the prognosis between patients with stage IIA and stage IIIA colon cancer.

Methods

We analysed patients with stage IIA or stage IIIA colon cancer based on data from the US Surveillance, Epidemiology, and End Results (SEER) database. Survival data were generated as Kaplan–Meier curves and were compared by log‐rank tests. A multivariate Cox proportional hazards model was used to analyze the risk factors.

Results

In total, 43 379 patients (38 784 stage IIA and 4595 stage IIIA) were included from the SEER database. A Kaplan–Meier analysis showed no significant difference between patients with stage IIA and IIIA colon cancer (P = 0.547). In the subgroup of patients with number of lymph nodes harvested (LNH) ≥12, a multivariate analysis showed that compared with stage IIA patients, stage IIIA patients were more likely to have a poorer cancer‐specific survival (CSS) (hazard ratio (HR) 1.252, 95% confidence interval (CI) 1.095–1.431, P = 0.001). In the subgroup of patients with LNH <12, a multivariate analysis showed that compared with stage IIA patients, stage IIIA patients were more likely to have a better CSS (HR 0.820, 95% CI 0.731–0.919, P = 0.001).

Conclusions

Patients with stage IIA colon cancer had a CSS comparable with that of patients with stage IIIA disease. When adequate lymph nodes were retrieved (LNH ≥12), stage IIA patients had a greater CSS than stage IIIA patients. On the contrary, when inadequate lymph nodes were retrieved (LNH <12), stage IIA patients had a poorer CSS than stage IIIA patients.
Functional insulin‐like factor 3 (INSL3) hormone‐receptor system in the testes and spermatozoa of domestic ruminants and its potential as a predictor of sire fertility
Authors: Pitia Ali M. , Uchiyama Kyoko , Sano Hiroaki , Kinukawa Masashi , Minato Yoshiaki , Sasada Hiroshi , Kohsaka Tetsuya
Published: September 2016

Insulin‐like factor 3 (INSL3) is essential for fetal testis descent, and has been implicated in the testicular and sperm functions in adult males; however, similar functions in domestic ruminants remain largely unknown. This study investigated the functional INSL3 hormone‐receptor system in adult ruminant testes and spermatozoa, and explored its potential to diagnose the fertility of sires. Testes and spermatozoa were obtained from fertile bulls, rams and he‐goats, whereas subfertile testes and spermatozoa were obtained only from bulls. As expected, INSL3 was visualized in Leydig cells, while we clearly demonstrated that the functional receptor, relaxin family peptide receptor 2 (RXFP2), enabling INSL3 to bind was identified in testicular germ cells and in the sperm equatorial segment of bulls, rams and he‐goats. In comparison to fertile bulls, the percentage of INSL3‐ and RXFP2‐expressing cells and their expression levels per cell were significantly reduced in the testes of subfertile bulls. In addition, the population of INSL3‐binding spermatozoa was also significantly reduced in the semen of subfertile bulls. These results provide evidence for a functional INSL3 hormone‐receptor system operating in ruminant testes and spermatozoa, and its potential to predict subfertility in sires.
Adenosine A2A receptor promotes collagen type III synthesis via β‐catenin activation in human dermal fibroblasts
Authors: Shaikh Gibran , Zhang Jin , Perez‐Aso Miguel , Mediero Aranzazu , Cronstein Bruce
Published: September 2016

Background and Purpose

Adenosine A2A receptor stimulation promotes the synthesis of collagen type I and type III (Col1 and Col3), mediators of fibrosis and scarring. The A2A receptor modulates collagen balance via cAMP/PKA/p38‐MAPK/Akt pathways. Wnt signalling is important in fibrosis and the cAMP and Wnt pathways converge. Because the A2A receptor is Gs‐linked and increases cAMP, we determined whether A2A receptors and Wnt signalling interact.

Experimental Approach

Total β‐catenin, de‐phosphorylated β‐catenin (canonical activation, de‐phospho β‐catenin) and phosphorylated β‐catenin at Ser552 (non‐canonical activation, p‐Ser552 β‐catenin) levels were determined in primary human dermal fibroblasts, cytosol and nucleus, by western blot analysis and fluorescence microscopy, before and after stimulation by A2A receptor‐selective agonist CGS21680, with/without A2A receptor‐selective antagonist (SCH56261) pretreatment. β‐Catenin was knocked down by transfection with scrambled‐siRNA or specific‐siRNA, and Col1 and Col3 levels determined by western blots.

Key Results

CGS21680 stimulation rapidly (15 min) increased cellular β‐catenin levels. Both de‐phospho β‐catenin and p‐Ser552 β‐catenin levels were also increased. CGS21680 stimulated the translocation of total de‐phospho and p‐Ser552 β‐catenin to the nucleus. A2A receptor‐stimulation increased Col1 synthesis similarly in β‐catenin knockeddown and scrambled cells. However, β‐catenin knockdown abolished the increase in Col3 synthesis induced in A2A receptor‐stimulated fibroblasts.

Conclusions and Implications

A2A receptor stimulation promotes Col3 synthesis via the activation of canonical and non‐canonical β‐catenin, consistent with a role for A2A receptors in dermal fibrosis and scarring.
Fisheries, invasive species, and the formation and fracturing of the Great Lakes system
Authors: Knight William , Bocking Stephen
Published: September 2016

Key Messages

Invasive and introduced fish species highlight tensions between systemic and jurisdictional visions of the Great Lakes during the 20th century.

Different jurisdictions shared the Great Lakes and acknowledged its status as a single biological and hydrological system, yet often took divergent approaches to managing their fisheries.

Alewife and splake demonstrate how Ontario and Michigan differed in their respective approaches to fisheries management on Lake Huron.
Reassessment of the cosyntropin stimulation test in the confirmatory diagnosis and subtype classification of primary aldosteronism
Authors: Umakoshi Hironobu , Xiaomei Yang , Ichijo Takamasa , Kamemura Kohei , Matsuda Yuichi , Fujii Yuichi , Kai Tatsuya , Fukuoka Tomikazu , Sakamoto Ryuichi , Ogo Atsushi , Suzuki Tomoko , Ogasawara Tatsuki , Tsuiki Mika , Naruse Mitsuhide ,   WAVES‐J Study Group
Published: September 2016

Objective

Although corticotropin is a representative secretagogue of aldosterone, the utility of the cosyntropin stimulation test (C‐ST) in diagnosing primary aldosteronism (PA) has not been elucidated. Aim of the study was to evaluate the clinical utility of C‐ST for confirmatory testing and subtype classification of PA.

Design, Setting and Patients

In this retrospective study, we identified patients with hypertension and positive case‐detection results for PA who underwent C‐ST and saline infusion testing (SIT) between 2006 and 2013 at eight referral centres in Japan. PA and essential hypertension (EH) were distinguished based on SIT results. PA subtype classification was determined by adrenal venous sampling (AVS). Plasma aldosterone concentration (PAC) was measured before and 30 and 60 min after intravenous cosyntropin administration. The ability of C‐ST to distinguish PA from EH and to distinguish unilateral from bilateral disease was assessed by the area under the receiver operating characteristic curve.

Results

Of 205 patients with hypertension and positive case‐detection results, 139 (68%) had PA based on SIT results. Eighteen patients in whom AVS was unsuccessful were excluded from analysis. The baseline PAC before C‐ST was significantly higher (P < 0·01) in patients with PA than in those with EH. However, the degree of difference in PAC between patients with PA and EH was not enhanced by the administration of cosyntropin. In addition, the administration of cosyntropin did not improve the distinction between bilateral and unilateral PA subtypes.

Conclusions

C‐ST has no utility as a confirmatory and subtype testing of PA when the diagnosis of PA is based on the positive results in SIT.
Investigation of brain GABA+ in primary hypothyroidism using edited proton MR spectroscopy
Authors: Liu Bo , Yang Huan , Gao Fei , Wang Qing , Zhao Bin , Gong Tao , Wang Zhensong , Chen Weibo , Wang Guangbin , Edden Richard A.E.
Published: September 2016

Objective

Evidence indicates that thyroid hormones have effects on the inhibitory GABAergic system. The aim of this study was to investigate whether brain GABA levels are altered in patients with hypothyroidism compared with healthy controls.

Design/Methods

Fifteen patients with primary hypothyroidism and 15 matched healthy controls underwent single‐voxel MEGA‐PRESS magnetic resonance spectroscopy at 3T, to quantify GABA levels in the median prefrontal cortex (mPFC) and posterior cingulate cortex (PCC). All participants underwent thyroid function test. Neuropsychological performances were evaluated by administration of the Montreal Cognitive Assessment (MoCA) and the 21‐item Beck Depression Inventory‐II (BDI‐II).

Results

The patients with hypothyroidism had significantly lower GABA+ levels in the mPFC compared with healthy controls (P = 0·016), whereas no significant difference (P = 0·214) was observed in the PCC. Exploratory analyses revealed that mPFC GABA+ levels were negatively correlated with the BDI‐II scores in patient group (r = −0·60, P = 0·018). No correlations were found between GABA+ levels and TSH or fT3 or fT4 levels in either region (all P > 0·05).

Conclusion

This study suggests that alteration of GABAergic neurotransmission may play an important role in the pathophysiology of primary hypothyroidism, providing intriguing neurochemical clues to understand thyroid–brain interactions.