bluuebunny/crossref_metadata_2025 huggingface dataset:
EPS: an empirical Bayes approach to integrating pleiotropy and tissue-specific information for prioritizing risk genes
Authors: Liu Jin , Wan Xiang , Ma Shuangge , Yang Can
Published: February 2016

Motivation: Researchers worldwide have generated a huge volume of genomic data, including thousands of genome-wide association studies (GWAS) and massive amounts of gene expression data from different tissues. How to perform a joint analysis of these data to gain new biological insights has become a critical step in understanding the etiology of complex diseases. Due to the polygenic architecture of complex diseases, the identification of risk genes remains challenging. Motivated by the shared risk genes found in complex diseases and tissue-specific gene expression patterns, we propose as an Empirical Bayes approach to integrating Pleiotropy and Tissue-Specific information (EPS) for prioritizing risk genes.

Results: As demonstrated by extensive simulation studies, EPS greatly improves the power of identification for disease-risk genes. EPS enables rigorous hypothesis testing of pleiotropy and tissue-specific risk gene expression patterns. All of the model parameters can be adaptively estimated from the developed expectation–maximization (EM) algorithm. We applied EPS to the bipolar disorder and schizophrenia GWAS from the Psychiatric Genomics Consortium, along with the gene expression data for multiple tissues from the Genotype-Tissue Expression project. The results of the real data analysis demonstrate many advantages of EPS.

Availability and implementation: The EPS software is available on https://sites.google.com/site/liujin810822.

Contact:  eeyang@hkbu.edu.hk

Supplementary information: Supplementary data are available at Bioinformatics online.
A quantitative model for oxygen uptake and release in a family of hemeproteins
Authors: Bustamante Juan P. , Szretter María E. , Sued Mariela , Martí Marcelo A. , Estrin Darío A. , Boechi Leonardo
Published: February 2016

Motivation: Hemeproteins have many diverse functions that largely depend on the rate at which they uptake or release small ligands, like oxygen. These proteins have been extensively studied using either simulations or experiments, albeit only qualitatively and one or two proteins at a time.

Results: We present a physical–chemical model, which uses data obtained exclusively from computer simulations, to describe the uptake and release of oxygen in a family of hemeproteins, called truncated hemoglobins (trHbs). Through a rigorous statistical analysis we demonstrate that our model successfully recaptures all the reported experimental oxygen association and dissociation kinetic rate constants, thus allowing us to establish the key factors that determine the rates at which these hemeproteins uptake and release oxygen. We found that internal tunnels as well as the distal site water molecules control ligand uptake, whereas oxygen stabilization by distal site residues controls ligand release. Because these rates largely determine the functions of these hemeproteins, these approaches will also be important tools in characterizing the trHbs members with unknown functions.

Contact:  lboechi@ic.fcen.uba.ar

Supplementary information:  Supplementary data are available at Bioinformatics online.
Isoform-level ribosome occupancy estimation guided by transcript abundance with Ribomap
Authors: Wang Hao , McManus Joel , Kingsford Carl
Published: February 2016

Summary: Ribosome profiling is a recently developed high-throughput sequencing technique that captures approximately 30 bp long ribosome-protected mRNA fragments during translation. Because of alternative splicing and repetitive sequences, a ribosome-protected read may map to many places in the transcriptome, leading to discarded or arbitrary mappings when standard approaches are used. We present a technique and software that addresses this problem by assigning reads to potential origins proportional to estimated transcript abundance. This yields a more accurate estimate of ribosome profiles compared with a naïve mapping.

Availability and implementation: Ribomap is available as open source at http://www.cs.cmu.edu/∼ckingsf/software/ribomap.

Contact:  carlk@cs.cmu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
KiT: a MATLAB package for kinetochore tracking
Authors: Armond Jonathan W. , Vladimirou Elina , McAinsh Andrew D. , Burroughs Nigel J.
Published: February 2016

Summary: During mitosis, chromosomes are attached to the mitotic spindle via large protein complexes called kinetochores. The motion of kinetochores throughout mitosis is intricate and automated quantitative tracking of their motion has already revealed many surprising facets of their behaviour. Here, we present ‘KiT’ (Kinetochore Tracking)—an easy-to-use, open-source software package for tracking kinetochores from live-cell fluorescent movies. KiT supports 2D, 3D and multi-colour movies, quantification of fluorescence, integrated deconvolution, parallel execution and multiple algorithms for particle localization.

Availability and implementation: KiT is free, open-source software implemented in MATLAB and runs on all MATLAB supported platforms. KiT can be downloaded as a package from http://www.mechanochemistry.org/mcainsh/software.php. The source repository is available at https://bitbucket.org/jarmond/kit and under continuing development.

Supplementary information:  Supplementary data are available at Bioinformatics online.

Contact:  jonathan.armond@warwick.ac.uk
Informational and emotional elements in online support groups: a Bayesian approach to large-scale content analysis
Authors: Deetjen Ulrike , Powell John A
Published: February 2016

Objective This research examines the extent to which informational and emotional elements are employed in online support forums for 14 purposively sampled chronic medical conditions and the factors that influence whether posts are of a more informational or emotional nature.

Methods Large-scale qualitative data were obtained from Dailystrength.org. Based on a hand-coded training dataset, all posts were classified into informational or emotional using a Bayesian classification algorithm to generalize the findings. Posts that could not be classified with a probability of at least 75% were excluded.

Results The overall tendency toward emotional posts differs by condition: mental health (depression, schizophrenia) and Alzheimer’s disease consist of more emotional posts, while informational posts relate more to nonterminal physical conditions (irritable bowel syndrome, diabetes, asthma). There is no gender difference across conditions, although prostate cancer forums are oriented toward informational support, whereas breast cancer forums rather feature emotional support. Across diseases, the best predictors for emotional content are lower age and a higher number of overall posts by the support group member.

Discussion The results are in line with previous empirical research and unify empirical findings from single/2-condition research. Limitations include the analytical restriction to predefined categories (informational, emotional) through the chosen machine-learning approach.

Conclusion Our findings provide an empirical foundation for building theory on informational versus emotional support across conditions, give insights for practitioners to better understand the role of online support groups for different patients, and show the usefulness of machine-learning approaches to analyze large-scale qualitative health data from online settings.
Development and validation of a predictive model for detection of colorectal cancer in primary care by analysis of complete blood counts: a binational retrospective study
Authors: Kinar Yaron , Kalkstein Nir , Akiva Pinchas , Levin Bernard , Half Elizabeth E , Goldshtein Inbal , Chodick Gabriel , Shalev Varda
Published: February 2016

Objective The use of risk prediction models grows as electronic medical records become widely available. Here, we develop and validate a model to identify individuals at increased risk for colorectal cancer (CRC) by analyzing blood counts, age, and sex, then determine the model’s value when used to supplement conventional screening.

Materials and Methods Primary care data were collected from a cohort of 606 403 Israelis (of whom 3135 were diagnosed with CRC) and a case control UK dataset of 5061 CRC cases and 25 613 controls. The model was developed on 80% of the Israeli dataset and validated using the remaining Israeli and UK datasets. Performance was evaluated according to the area under the curve, specificity, and odds ratio at several working points.

Results Using blood counts obtained 3–6 months before diagnosis, the area under the curve for detecting CRC was 0.82 ± 0.01 for the Israeli validation set. The specificity was 88 ± 2% in the Israeli validation set and 94 ± 1% in the UK dataset. Detecting 50% of CRC cases, the odds ratio was 26 ± 5 and 40 ± 6, respectively, for a false-positive rate of 0.5%. Specificity for 50% detection was 87 ± 2% a year before diagnosis and 85 ± 2% for localized cancers. When used in addition to the fecal occult blood test, our model enabled more than a 2-fold increase in CRC detection.

Discussion Comparable results in 2 unrelated populations suggest that the model should generally apply to the detection of CRC in other groups. The model’s performance is superior to current iron deficiency anemia management guidelines, and may help physicians to identify individuals requiring additional clinical evaluation.

Conclusions Our model may help to detect CRC earlier in clinical practice.
A method for comparing non-nested models with application to astrophysical searches for new physics
Authors: Algeri Sara , Conrad Jan , van Dyk David A.
Published: February 2016

Searches for unknown physics and decisions between competing astrophysical models to explain data both rely on statistical hypothesis testing. The usual approach in searches for new physical phenomena is based on the statistical likelihood ratio test and its asymptotic properties. In the common situation, when neither of the two models under comparison is a special case of the other i.e. when the hypotheses are non-nested, this test is not applicable. In astrophysics, this problem occurs when two models that reside in different parameter spaces are to be compared. An important example is the recently reported excess emission in astrophysical γ-rays and the question whether its origin is known astrophysics or dark matter. We develop and study a new, simple, generally applicable, frequentist method and validate its statistical properties using a suite of simulations studies. We exemplify it on realistic simulated data of the Fermi-Large Area Telescope γ-ray satellite, where non-nested hypotheses testing appears in the search for particle dark matter.
Vibrio
bacteria in raw oysters: managing risks to human health
Authors: Froelich Brett A. , Noble Rachel T.
Published: February 2016

The human-pathogenic marine bacteria
Vibrio vulnificus
and
V. parahaemolyticus
are strongly correlated with water temperature, with concentrations increasing as waters warm seasonally. Both of these bacteria can be concentrated in filter-feeding shellfish, especially oysters. Because oysters are often consumed raw, this exposes people to large doses of potentially harmful bacteria. Various models are used to predict the abundance of these bacteria in oysters, which guide shellfish harvest policy meant to reduce human health risk.
Vibrio
abundance and behaviour varies from site to site, suggesting that location-specific studies are needed to establish targeted risk reduction strategies. Moreover, virulence potential, rather than simple abundance, should be also be included in future modeling efforts.
annotatr: Genomic regions in context
Authors: Cavalcante Raymond G. , Sartor Maureen A.
Published: February 2016

Motivation:

Analysis of next-generation sequencing data often results in a list of genomic regions. These may include differentially methylated CpGs/regions, transcription factor binding sites, interacting chromatin regions, or GWAS-associated SNPs, among others. A common analysis step is to annotate such genomic regions to genomic annotations (promoters, exons, enhancers, etc.). Existing tools are limited by a lack of annotation sources and flexible options, the time it takes to annotate regions, an artificial one-to-one region-to-annotation mapping, a lack of visualization options to easily summarize data, or some combination thereof.

Results:

We developed the annotatr Bioconductor package to flexibly and quickly summarize and plot annotations of genomic regions. The annotatr package reports all intersections of regions and annotations, giving a better understanding of the genomic context of the regions. A variety of graphics functions are implemented to easily plot numerical or categorical data associated with the regions across the annotations, and across annotation intersections, providing insight into how characteristics of the regions differ across the annotations. We demonstrate that annotatr is up to 27x faster than comparable R packages. Overall, annotatr enables a richer biological interpretation of experiments.

Availability:

http://bioconductor.org/packages/annotatr/

Contact:

rcavalca@umich.edu

Supplementary information:

Supplementary data are available atBioinformaticsonline.
Two-Dimensional NMR Lineshape Analysis
Authors: Waudby Christopher Andrew , Ramos Andres , Cabrita Lisa D. , Christodoulou John
Published: February 2016

NMR titration experiments are a rich source of structural, mechanistic, thermodynamic and kinetic information on biomolecular interactions, which can be extracted through the quantitative analysis of resonance lineshapes. However, applications of such analyses are frequently limited by peak overlap inherent to complex biomolecular systems. Moreover, systematic errors may arise due to the analysis of two-dimensional data using theoretical frameworks developed for one-dimensional experiments. Here we introduce a more accurate and convenient method for the analysis of such data, based on the direct quantum mechanical simulation and fitting of entire two-dimensional experiments, which we implement in a new software tool, TITAN (TITration ANalysis). We expect the approach, which we demonstrate for a variety of protein-protein and protein-ligand interactions, to be particularly useful in providing information on multi-step or multi-component interactions.
Mutation of cancer driverMLL2results in transcription stress and genome instability
Authors: Kantidakis Theodoros , Saponaro Marco , Mitter Richard , Horswell Stuart , Kranz Andrea , Boeing Stefan , Aygün Ozan , Kelly Gavin P. , Matthews Nik , Stewart Aengus , Stewart A. Francis , Svejstrup Jesper Q.
Published: February 2016

Genome instability is a recurring feature of tumorigenesis. Mutation inMLL2, encoding a histone methyltransferase, is a driver in numerous different cancer types, but the mechanism is unclear. Here, we present evidence thatMLL2mutation results in genome instability. Mouse cells in whichMLL2gene deletion can be induced display elevated levels of sister chromatid exchange, gross chromosomal aberrations, 53BP1 foci, and micronuclei. HumanMLL2knockout cells are characterized by genome instability as well. Interestingly, MLL2 interacts with RNA polymerase II (RNAPII) and RECQL5, and, althoughMLL2mutated cells have normal overall H3K4me levels in genes, nucleosomes in the immediate vicinity of RNAPII are hypomethylated. Importantly,MLL2mutated cells display signs of substantial transcription stress, and the most affected genes overlap with early replicating fragile sites, show elevated levels of γH2AX, and suffer frequent mutation. The requirement for MLL2 in the maintenance of genome stability in genes helps explain its widespread role in cancer and points to transcription stress as a strong driver in tumorigenesis.
Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation
Authors: Marhavý Peter , Montesinos Juan Carlos , Abuzeineh Anas , Van Damme Daniel , Vermeer Joop E.M. , Duclercq Jerôme , Rakusová Hana , Nováková Petra , Friml Jiři , Geldner Niko , Benková Eva
Published: February 2016

To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved proliferation capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endodermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots.
On the possibility of using X-ray Compton scattering to study magnetoelectrical properties of crystals
Authors: Collins S. P. , Laundy D. , Connolley T. , van der Laan G. , Fabrizi F. , Janssen O. , Cooper M. J. , Ebert H. , Mankovsky S.
Published: February 2016

This paper discusses the possibility of using Compton scattering – an inelastic X-ray scattering process that yields a projection of the electron momentum density – to probe magnetoelectrical properties. It is shown that an antisymmetric component of the momentum density is a unique fingerprint of such time- and parity-odd physics. It is argued that polar ferromagnets are ideal candidates to demonstrate this phenomenon and the first experimental results are shown, on a single-domain crystal of GaFeO3. The measured antisymmetric Compton profile is very small (≃ 10−5of the symmetric part) and of the same order of magnitude as the statistical errors. Relativistic first-principles simulations of the antisymmetric Compton profile are presented and it is shown that, while the effect is indeed predicted by theory, and scales with the size of the valence spin–orbit interaction, its magnitude is significantly overestimated. The paper outlines some important constraints on the properties of the antisymmetric Compton profile arising from the underlying crystallographic symmetry of the sample.
Crystal structure of bis(2-methyl-1H-imidazol-3-ium) dihydroxidobis(oxalato-κ2O1,O2)stannate(IV) monohydrate
Authors: Diop Mouhamadou Birame , Diop Libasse , Plasseraud Laurent , Maris Thierry
Published: February 2016

In the structure of the hydrated title salt, (C4H7N2)2[Sn(C2O4)2(OH)2]·H2O, the asymmetric unit comprises one stannate(IV) dianion, two organic cations and one water molecule of crystallization. The [Sn(C2O4)2(OH)2]2−dianion consists of an SnIVatom chelated by two oxalate anions and coordinated by two OH−ligands in acisoctahedral arrangement. Neighbouring anions are connected through O—H...O hydrogen bonds between hydroxide groups and non-coordinating oxalate O atoms into layers expanding parallel to (100). In addition, cations and anions are linked through N—H...O hydrogen bonds, and the water molecule bridges two anions with two O—H...O hydrogen bonds and is also the acceptor of an N—H...O hydrogen bond with one of the cations. Weak C—H...O hydrogen bonds are also observed. The intricate hydrogen bonding leads to the formation of a three-dimensional network.
Crystal structure of ethyl 2-[2-(4-methylbenzoyl)-5-p-tolyl-1H-imidazol-1-yl]acetate
Authors: Prabha E. Arockia Jeya Yasmi , Kumar S. Suresh , Padala Anil K. , Ahmed Qazi Naveed , Athimoolam S.
Published: February 2016

In the title compound, C22H22N2O3, the plane of the five-membered ring is oriented at dihedral angles of 45.4 (1) and 52.5 (1)° to the phenyl rings. Furthermore, this ring makes an angle of 85.2 (2)° with the plane of the ethyl acetate substituent. The molecular structure is affected by an intramolecular C—H...O hydrogen bond between an H atom from thep-tolyl group and the carbonyl O atom of the acetate. The methyl group of the ethyl acetate residue is disordered over two sites with equal occupancies. The crystal structure features intermolecular C—H...O and C—H...N interactions. One of the C—H...O hydrogen bonds forms aC(5) chain motif extending along theaaxis. In addition, C—H...N contacts form inversion dimers withR22(12) ring motifs, linking the imidazole ring system to the benzene ring of thep-tolyl substituent.
Design engineers’ perception of health and safety and its impact in the design process
Authors: Morrow Susan , Hare Billy , Cameron Iain
Published: February 2016

Purpose

– The purpose of this paper is to consider design engineers’ perception of health and safety and its impact on their behaviour during design activity. The study presents three types of design engineers each, exhibiting particular tendencies when faced with health and safety considerations during design. The discovery of these tendencies pose important implications for education and professional institutions and practical measures are suggested to help design engineers manage their tendencies to be more conducive to ensuring improved health and safety performance.

Design/methodology/approach

– An exploratory design method was used – grounded theory, to include 13, in-depth, one-to-one interviews with design engineers, representing junior staff, middle and senior management.

Findings

– The paper provides empirical insights about how designers think and behave when asked to consider health and safety issues during the design process. It identifies three group types of designers: doers, receivers and givers, who will exhibit their particular tendencies based on how they view and understand the term health and safety.

Research limitations/implications

– The data obtained were from design engineers only, and therefore the research results may lack generalisability. Therefore, researchers are encouraged to test the proposed propositions.

Practical implications

– The paper includes implications for those involved in the creation and development of designers e.g., educators and professional bodies. The data forms the basis for helping designers to manage their perceptions towards the term health and safety and thus, their tendencies exhibited in their behaviour.

Originality/value

– This paper contributes to new understanding of designers’ behaviour and considers the significance of how designers’ views of health and safety will influence their behaviour.
Embeddedness of codes of ethics in construction organizations
Authors: Oladinrin Olugbenga Timo , Ho Christabel Man-Fong
Published: February 2016

Purpose

– The existence of codes of ethics in most organizations does not seem to have reduced unethical behaviour especially in the construction organizations due to lack of effective ethics management such as embeddedness of ethical codes. The purpose of this paper is to bridge the current knowledge gap by highlighting the principal factors determining the embeddedness of codes of ethics in construction organizations.

Design/methodology/approach

– Questionnaires detailing 30 factors determining ethical code embeddedness were sent to professionals in construction organizations in Hong Kong. In total, 160 valid responses were analysed by mean score and exploratory factor analysis.

Findings

– Based on the mean score, “protecting anyone who exposes alleged wrongdoing”, “managers acting as role models” and “giving code standards with explanation to new employees” are the three factors that ranked highest. From the results of factor analysis, six factors were extracted, including; process of code internalization, identification and remover of barriers, process of enacting value, process of accountability, process of coding and process of monitoring. These are processes that enable proper integration of codes of ethics within construction organization.

Research limitations/implications

– While this study has provided useful information regarding ethical codes, the limitation is inherent in the population of the study in that, percentage representation of construction organizations in Hong Kong could not be presented. This was due to the sensitivity of ethics as perceived by construction practitioners. The authors, at the initial stage, sent invitation letters to several organizations inviting them to participate in the research but they all declined. Therefore, the data collection approach discussed earlier was adopted and the questionnaire was made strictly anonymous which made it difficult to classify organizations that are represented. Nevertheless, it is hoped that this paper will engineer a change in research direction and open up new discussion channels.

Originality/value

– The results presented in this study provide sufficient evidence and useful pointers to clarify some misconceptions about factors determining code embeddedness. These findings help to clarify what the high-prioritized factors are, and could also be used as an assessment tool to evaluate performance of an organization regarding codes of ethics and thus help to identify areas requiring improvement.
Rapid lactate oxidase‐based assay for lactate content in milk to ascertain its hygienic quality
Authors: Kumar Brajesh , Sharma Rajan , Thakur Rahul , Barui Amit Kumar , Rajput Yudhishthir S , Mann Bimlesh
Published: February 2016

A rapid method for qualitative and quantitative assaying of l‐lactate in milk is described. The method is based on oxidation of lactate by lactate oxidase with the simultaneous formation of H2O2 which subsequently oxidises 2, 4, 6‐tribromo 3‐hydroxy benzoic acid (TBHBA) in the presence of peroxidase. Oxidised TBHBA then reacts with 4‐amino antipyrine to obtain magenta colour (λmax = 523 nm). In the qualitative assay, colour change becomes visible in raw milk samples spiked with 300 mg lactate/L. The absorbance increases linearly up to 1000 mg/L. The method can be used for rapid assessment of the hygienic quality of milk.
Low serum albumin and advanced age predict early mortality in Asian patients with extreme elevations of serum aminotransferase
Authors: Chang Pik Eu , Goh George Boon‐Bee , Tan Chee Kiat
Published: February 2016

Objective

Extreme elevations of serum aminotransferases (EESAT), defined as alanine transaminase (ALT) or aspartate transaminase (AST) level of above 3000 U/L, reflect severe liver injury and poor outcomes of the patients. This study aimed to evaluate the prevalence, etiology and clinical outcomes of EESAT in Asian patients and to identify the predictors of early mortality.

Methods

Medical records of patients with EESAT over a 1‐year period were retrospectively analyzed for disease prevalence, etiology and clinical outcome. The primary outcome was 28‐day mortality (defined as death occurring within 28 days of the onset of EESAT). A logistic regression was performed to identify independent predictors of mortality.

Results

A total of 101 patients with a mean age of 57.4 ± 18.0 years met the criteria for EESAT, resulted in a prevalence of 1.4 per 1000 admissions. Altogether 63.4% of the patients were men. The etiologies of EESAT were hypoxic hepatitis (74.2%), viral hepatitis (20.8%), rhabdomyolysis (3.0%), drug‐induced hepatitis (1.0%) and choledocholithiasis (1%). The 28‐day mortality of EESAT was 53.5%. EESAT due to hypoxic hepatitis was associated with high mortality (70.7%) whereas the mortality risk was low in EESAT from viral hepatitis (9.5%). Serum albumin <28 g/L (HR 5.78, 95% CI 1.41–23.62) and age >55 years (HR 4.81, 95% CI 1.29–17.90) were independent predictors of mortality.

Conclusions

The main etiology of EESAT is hypoxic hepatitis, which carries a high mortality. EESAT due to viral hepatitis is common in Asians and has a good outcome. Low serum albumin and elder age are independent predictors of early mortality in EESAT patients.
Biocontrol agents promote growth of potato pathogens, depending on environmental conditions
Authors: Cray Jonathan A. , Connor Mairéad C. , Stevenson Andrew , Houghton Jonathan D. R. , Rangel Drauzio E. N. , Cooke Louise R. , Hallsworth John E.
Published: February 2016

There is a pressing need to understand and optimize biological control so as to avoid over‐reliance on the synthetic chemical pesticides that can damage environmental and human health. This study focused on interactions between a novel biocontrol‐strain, Bacillus sp. JC12GB43, and potato‐pathogenic Phytophthora and Fusarium species. In assays carried out in vitro and on the potato tuber, the bacterium was capable of near‐complete inhibition of pathogens. This Bacillus was sufficiently xerotolerant (water activity limit for growth = 0.928) to out‐perform Phytophthora infestans (~0.960) and challenge Fusarium coeruleum (~0.847) and Fusarium sambucinum (~0.860) towards the lower limits of their growth windows. Under some conditions, however, strain JC12GB43 stimulated proliferation of the pathogens: for instance, Fusarium coeruleum growth‐rate was increased under chaotropic conditions in vitro (132 mM urea) by >100% and on tubers (2‐M glycerol) by up to 570%. Culture‐based assays involving macromolecule‐stabilizing (kosmotropic) compatible solutes provided proof‐of‐principle that the Bacillus may provide kosmotropic metabolites to the plant pathogen under conditions that destabilize macromolecular systems of the fungal cell. Whilst unprecedented, this finding is consistent with earlier reports that fungi can utilize metabolites derived from bacterial cells. Unless the antimicrobial activities of candidate biocontrol strains are assayed over a full range of field‐relevant parameters, biocontrol agents may promote plant pathogen infections and thereby reduce crop yields. These findings indicate that biocontrol activity, therefore, ought to be regarded as a mode‐of‐behaviour (dependent on prevailing conditions) rather than an inherent property of a bacterial strain.
Stimulating soil microorganisms for mineralizing the herbicide isoproturon by means of microbial electroremediating cells
Authors: Rodrigo Quejigo Jose , Dörfler Ulrike , Schroll Reiner , Esteve‐Núñez Abraham
Published: February 2016

The absence of suitable terminal electron acceptors (TEA) in soil might limit the oxidative metabolism of environmental microbial populations. Microbial electroremediating cells (MERCs) consist in a variety of bioelectrochemical devices that aim to overcome electron acceptor limitation and maximize metabolic oxidation with the purpose of enhancing the biodegradation of a pollutant in the environment. The objective of this work was to use MERCs principles for stimulating soil bacteria to achieve the complete biodegradation of the herbicide 14C‐isoproturon (IPU) to 14CO2 in soils. Our study concludes that using electrodes at a positive potential [+600 mV (versus Ag/AgCl)] enhanced the mineralization by 20‐fold respect the electrode‐free control. We also report an overall profile of the 14C‐IPU metabolites and a 14C mass balance in response to the different treatments. The remarkable impact of electrodes on the microbial activity of natural communities suggests a promising future for this emerging environmental technology that we propose to name bioelectroventing.
The effects of cannabis intoxication on motor vehicle collision revisited and revised
Authors: Rogeberg Ole , Elvik Rune
Published: February 2016

Aims

To determine whether and to what extent acute cannabis intoxication increases motor vehicle crash risk.

Design

Study 1 replicates two published meta‐analyses, correcting for methodological shortcomings. Study 2 is an updated meta‐analysis using 28 estimates from 21 observational studies. These included studies from three earlier reviews, supplemented by results from a structured search in Web of Science and Google Scholar, and by the personal libraries of the research team. Risk estimates were combined using random‐effects models and meta‐regression techniques.

Setting

Study 1 replicates the analysis of Asbridge et al., based on nine studies from five countries, published 1982–2007; and Li et al., based on nine studies from six countries, published 2001–10. Study 2 involves studies from 13 countries published in the period 1982–2015.

Participants

In study 1, total counts extracted totalled 50 877 (27 967 cases, 22 910 controls) for Asbridge et al. and 93 229 (4236 cases and 88 993 controls) for Li et al. Study 2 used confounder‐adjusted estimates where available (combined sample size of 222 511) and crude counts from the remainder (17 228 total counts), giving a combined sample count of 239 739.

Measurements

Odds ratios (OR) were used from case–control studies and adjusted OR analogues from culpability studies. The impact of the substantial variation in confounder adjustment was explored in subsample analyses.

Findings

Study 1 substantially revises previous risk estimates downwards, with both the originally reported point estimates lying outside the revised confidence interval. Revised estimates were similar to those of study 2, which found cannabis‐impaired driving associated with a statistically significant risk increase of low‐to‐moderate magnitude [random‐effects model OR 1.36 (1.15–1.61), meta‐regression OR 1.22 (1.1–1.36)]. Subsample analyses found higher OR estimates for case–control studies, low study quality, limited control of confounders, medium‐quality use data and not controlling for alcohol intoxication.

Conclusions

Acute cannabis intoxication is associated with a statistically significant increase in motor vehicle crash risk. The increase is of low to medium magnitude. Remaining selection effects in the studies used may limit causal interpretation of the pooled estimates.
From the Panama Canal to Post‐Fordism: Producing Temporary Labor Migrants Within and Beyond Agriculture in the United States (1904–2013)
Authors: Clark Gabrielle E.
Published: February 2016

In the historical study of modern American capitalism, labor unfreedom in agriculture has been conceptualized as an exception to liberal labor relations in the post‐slavery polity, from debt peonage to the threat of deportation from workplaces populated by non‐citizen migrants. At the same time, state‐enforced labor compulsions and restrictions are increasingly part and parcel of what scholars call neoliberal exceptionalism. This article argues that agricultural and neoliberal exceptionalisms are related, by tracing the historical genealogy and juridical production of a restrictive work status, the deportable temporary labor migrant, across political economies in the modern United States, from imperial construction in the Panama Canal Zone, to agriculture, to the knowledge economy. Contrary to existing notions of temporary work visas as a new form of unfreedom in neoliberalized advanced capitalist states, I show how the threat of deportation is older and rooted in the rise of the liberal regulatory state in a post‐slavery, yet persistently racial capitalist political economy. The import of understanding this history of government intervention increases as the liberal regulatory state's coercive logics and practices intensify and circulate in agriculture and under a post‐Fordist regime of accumulation, reproducing racial capitalism in the labor process.
Digoxin reduces atherosclerosis in apolipoprotein E‐deficient mice
Authors: Shi Huairui , Mao Xiaobo , Zhong Yucheng , Liu Yuzhou , Zhao Xiaoqi , Yu Kunwu , Zhu Ruirui , Wei Yuzhen , Zhu Jianghao , Sun Haitao , Mao Yi , Zeng Qiutang
Published: February 2016

Background and Purpose

Numerous in vitro studies have suggested that digoxin suppresses inflammation and alters lipid metabolism. However, the effect of dioxin on atherosclerosis is poorly understood. The present study was conducted to determine whether digoxin affects the development of atherosclerosis in a murine model of atherosclerotic disease.

Experimental Approach

Apolipoprotein E‐deficient mice maintained on a Western‐type diet were administered PBS (control), low‐dose digoxin (1 mg·kg−1· day−1) or high‐dose digoxin (2 mg·kg−1 · day−1) via i.p. injection for 12 weeks.

Key Results

Digoxin dose‐dependently reduced atherosclerotic lesion formation and plasma lipid levels (reductions of 41% in total cholesterol, 54% in triglycerides and 20% in low‐density lipoprotein cholesterol in the high‐dose digoxin‐treated group). Moreover, treatment with digoxin markedly attenuated IL‐17A expression and IL‐17A‐related inflammatory responses and increased the abundance of regulatory T cells (Tregs).

Conclusions and Implications

Our data demonstrate that digoxin acts as a specific antagonist of retinoid‐related orphan receptor‐γ to decrease atherosclerosis by suppressing lipid levels and IL‐17A‐related inflammatory responses.
CD44 variant 9 is a potential biomarker of tumor initiating cells predicting survival outcome in hepatitis C virus‐positive patients with resected hepatocellular carcinoma
Authors: Kakehashi Anna , Ishii Naomi , Sugihara Eiji , Gi Min , Saya Hideyuki , Wanibuchi Hideki
Published: February 2016

This study investigated whether the expression of CD44 variant 9 (CD44v9) might be a functional marker of tumor‐initiating stem‐like cells in primary hepatocellular carcinomas (HCCs) of hepatitis C virus (HCV)+ patients and provide an indicator of patient survival, as well as associated mechanisms. A total of 90 HCV+ HCC patients who underwent surgery from 2006 to 2011 were enrolled and monitored for 2–8 years. Expression of CD44v9 was validated immunohistochemically in all HCCs, followed by comparative proteome, survival, and clinicopathological analyses. CD44 variant 8–‐10 was further evaluated in diethylnitrosamine‐induced HCCs of C57Bl/6J mice. Focally localized CD44v+ cells with a membranous staining pattern were detected in human HCV+ and mouse HCCs. CD44v9+ cells of HCCs were predominantly negative for Ki67 and P‐p38, indicating decrease of cell proliferation in the CD44v9+ tumor cell population, likely to be related to suppression of intracellular oxidative stress due to activation of Nrf2‐mediated signaling, DNA repair, and inhibition of xenobiotic metabolism. CD44v9 IHC evaluation in 90 HCV+ HCC cases revealed that positive expression was significantly associated with poor overall and recurrence‐free survival, a younger age, poor histological differentiation of HCCs, and high alkaline phosphatase levels compared with patients with negative expression. CD44v9 is concluded to be a potential biomarker of tumor‐initiating stem‐like cells and a prognostic marker in HCV+ HCC patients associated with Nrf2‐mediated resistance to oxidative stress.
Determining prevalence of maltreatment among children in the kingdom of Saudi Arabia
Authors: Al‐Eissa M. A. , Saleheen H. N. , AlMadani S. , AlBuhairan F. S. , Weber A. , Fluke J. D. , Almuneef M. , Casillas K. L.
Published: February 2016

Purpose

The aim of this study is to find out the overall prevalence rates for the major forms of abuse among adolescents in the Kingdom of Saudi Arabia and the differences in prevalence by age, gender and living arrangement.

Methods

The cross‐sectional study was conducted in secondary high schools in five of the 13 main regions of Kingdom of Saudi Arabia during 2012. Through a multistage stratified sampling technique, a sample (n = 16 939) of adolescents (15‐19 years) were identified and invited to participate. The ISPCAN Child Abuse Screening Tool ‐ Child was used for data collection. The previous year's occurrence of violence exposure, psychological, physical and sexual abuse, and neglect were assessed.

Results

Nearly 90% of the adolescents were between 16 and 18 years of age, and over 80% were cared for by both of their biological parents. Annual prevalence of various forms of abuse in the year before the 2012 assessment ranged between 0.10 and 0.65, with the lowest rate for sexual abuse and the highest for psychological abuse. Significantly, greater rates of all forms of abuse/exposure were found when participants lived with their mother or father only (versus with both), and even greater rates for all when they lived with their biological parent and a step‐parent. Rates for violence exposure, psychological abuse and neglect were significantly greater for girls, and rate of sexual abuse was greater for boys.

Conclusions

More attention should be given to the effect of adolescent maltreatment particularly among girls. In addition, sexual abuse prevention programme should be targeted among boys.
A common variant association study reveals novel susceptibility loci for low HDL‐cholesterol levels in ethnic Arabs
Authors: Wakil S. M. , Ram R. , Muiya N. P. , Andres E. , Mazhar N. , Hagos S. , Alshahid M. , Meyer B. F. , Morahan G. , Dzimiri N.
Published: February 2016

The genetic susceptibility to acquiring low high density lipoprotein‐cholesterol (LHDLC) levels is not completely elucidated yet. In this study, we performed a common variant association study for harboring this trait in ethnic Arabs. We employed the Affymetrix high‐density Axiom Genome‐Wide ASI Array (Asian population) providing a coverage of 598,000 single nucleotide variations (SNPs) to genotype 5495 individuals in a two‐phase study involving discovery and validation sets of experiments. The rs1800775 [1.31 (1.22–1.42); p = 3.41E‐12] in the CETP gene and rs359027 [1.26 (1.16–1.36); p = 2.55E‐08] in the LMCD1 gene were significantly associated with LHDLC levels. Furthermore, rs3104435 [1.26 (1.15–1.38); p = 1.19E‐06] at the MATN1 locus, rs9835344 [1.16 (1.08–1.26); p = 8.75E‐06] in the CNTN6 gene, rs1559997 [1.3 (1.14–1.47); p = 9.48E‐06] in the SDS gene and rs1670273 [1.2 (1.1–1.31); p = 4.81E‐06] in the DMN/SYNM gene exhibited suggestive association with the disorder. Seven other variants including rs1147169 in the PLCL1 gene, rs10248618 in the DNAH11, rs476155 in the GLIS3, rs7024300 in the ABCA1, intergenic rs10836699, rs11603691 in P2RX3 and rs750134 in CORO1C gene exhibited borderline protective properties. Validation and joint meta‐analysis resulted in rs1800775, rs3104435 and rs359027 retaining their predisposing properties, while rs10836699 and rs11603691 showed protective properties. Our data show several predisposing variants across the genome for LHDLC levels in ethnic Arabs.
Selecting stage ypT0–1N0 for locally advanced rectal cancer following preoperative chemoradiotherapy: implications for potential candidates of organ‐sparing management
Authors: Huang S. H. , Chi P. , Lin H. M. , Lu X. R. , Huang Y. , Xu Z. B. , Sun Y. W. , Ye D. X. , Wang X. J. , Wang X.
Published: February 2016

Aim

Local excision or a wait‐and‐see policy may offer the possibility of organ preservation for locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (CRT). Identifying associated factors of good responders (GR) with stage ypT0–1N0 would probably influence the selection of potential candidates who were theoretically eligible for organ‐sparing management. This study was to establish a scoring system to select stage ypT0–1N0 for LARC following preoperative CRT.

Method

Between 2009 and 2014, 262 patients with middle and low LARC were treated with CRT and radical surgery. Clinicopathological data which were found to be significantly associated with GR were incorporated into a scoring system.

Results

Fifty‐seven (21.8%) patients were GR with stage ypT0–1N0 in the operative specimen. Multivariate analyses indicated that a low level of pretreatment carcinoembryonic antigen (CEA) and post‐treatment CEA <2.55 ng/ml (P = 0.008 and P = 0.009 respectively) and long‐axis diameter of residual tumours (P = 0.006) were independently associated with stage ypT0–1N0. The three factors were incorporated into a scoring system. Using receiver operating characteristic curve analysis, we determined a cutoff value of −0.3 for scores, at which the system's sensitivity was 71.9% and specificity 73.1%. When applied to testing samples, the sensitivity was 74.1% and specificity 76.2%.

Conclusion

We demonstrated that low levels of pretreatment and post‐treatment CEA and the long‐axis diameter of residual tumours were associated with stage ypT0–1N0 for LARC after CRT. Therefore, the three‐factor scoring system may be used to select potential candidates for organ‐sparing management.
Endocannabinoid regulation of β‐cell functions: implications for glycaemic control and diabetes
Authors: Jourdan T. , Godlewski G. , Kunos G.
Published: February 2016

Visceral obesity is a major risk factor for the development of insulin resistance which can progress to overt type 2 diabetes (T2D) with loss of β‐cell function and, ultimately, loss of β‐cells. Insulin secretion by β‐cells of the pancreatic islets is tightly coupled to blood glucose concentration and modulated by a large number of blood‐borne or locally released mediators, including endocannabinoids. Obesity and its complications, including T2D, are associated with increased activity of the endocannabinoid/CB1 receptor (CB1R) system, as indicated by the therapeutic effects of CB1R antagonists. Similar beneficial effects of CB1R antagonists with limited brain penetrance indicate the important role of CB1R in peripheral tissues, including the endocrine pancreas. Pancreatic β‐cells express all of the components of the endocannabinoid system, and endocannabinoids modulate their function via both autocrine and paracrine mechanisms, which influence basal and glucose‐induced insulin secretion and also affect β‐cell proliferation and survival. The present brief review will survey available information on the modulation of these processes by endocannabinoids and their receptors, with an attempt to assess the contribution of such effects to glycaemic control in T2D and insulin resistance.
How accessible are coral reefs to people? A global assessment based on travel time
Authors: Maire Eva , Cinner Joshua , Velez Laure , Huchery Cindy , Mora Camilo , Dagata Stephanie , Vigliola Laurent , Wantiez Laurent , Kulbicki Michel , Mouillot David
Published: February 2016

The depletion of natural resources has become a major issue in many parts of the world, with the most accessible resources being most at risk. In the terrestrial realm, resource depletion has classically been related to accessibility through road networks. In contrast, in the marine realm, the impact on living resources is often framed into the Malthusian theory of human density around ecosystems. Here, we develop a new framework to estimate the accessibility of global coral reefs using potential travel time from the nearest human settlement or market. We show that 58% of coral reefs are located < 30 min from the nearest human settlement. We use a case study from New Caledonia to demonstrate that travel time from the market is a strong predictor of fish biomass on coral reefs. We also highlight a relative deficit of protection on coral reef areas near people, with disproportional protection on reefs far from people. This suggests that conservation efforts are targeting low‐conflict reefs or places that may already be receiving de facto protection due to their isolation. Our global assessment of accessibility in the marine realm is a critical step to better understand the interplay between humans and resources.