bluuebunny/crossref_metadata_2025 huggingface dataset:
2D Pulses using spatially dependent frequency sweeping
Authors: Jang Albert , Kobayashi Naoharu , Moeller Steen , Vaughan J. Thomas , Zhang Jianyi , Garwood Michael
Published: November 2015

Purpose

To introduce a method of designing two‐dimensional (2D) frequency‐modulated pulses that produce phase coherence in a spatiotemporal manner. Uniquely, this class of pulses provides the ability to compensate for field inhomogeneity using a spatiotemporally dependent trajectory of maximum coherence in a single‐shot.

Theory and Methods

A pulse design method based on a k‐space description is developed. Bloch simulations and phantom experiments are used to demonstrate sequential spatiotemporal phase coherence and compensation for
and B0 inhomogeneity.

Results

In the presence of modulated gradients, the 2D frequency‐modulated pulses were shown to excite a cylinder in a selective manner. With a surface coil transmitter, compensation of the effect of
inhomogeneity was experimentally verified, in agreement with simulation results. In addition, simulations were used to demonstrate partial compensation for B0 inhomogeneity.

Conclusion

The 2D frequency‐modulated pulses are a new class of pulses that generate phase coherence sequentially along a spatial trajectory determined by gradient‐ and frequency‐modulated functions. By exploiting their spatiotemporal nature, 2D frequency‐modulated pulses can compensate for spatial variation of the radiofrequency field in a single‐shot excitation. Preliminary results shown suggest extensions might also be used to compensate for static field inhomogeneity. Magn Reson Med 76:1364–1374, 2016. © 2015 International Society for Magnetic Resonance in Medicine
Synergistic flame retardant effect of BiFeO3 in intumescent flame‐retardant polypropylene composites
Authors: Han Lijing , Wu Weihong , Qi Yanxia , Qu Hongqiang , Xu Jianzhong
Published: November 2015

The BiFeO3 was used to intumescent flame retardant (IFR) polypropylene (PP) composites as a synergist. The limiting oxygen index (LOI) and UL‐94 tests indicated that there is an optimum synergistic concentration of BiFeO3 in the PP/IFR composites. Thermogravimetric analysis (TG) results of flame retardant PP showed that the moderate of BiFeO3 can reduce the decomposition rate of sample at high temperatures. TG of APP/PER/BiFeO3 showed that BiFeO3 main affects the third mass loss stage of APP/PER. So the morphology and composition of the char residue of APP/PER/BiFeO3 composites were characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), and laser Raman spectroscopy (LRS). An appropriate amount of BiFeO3 can react with APP/PER forming BiOP and FeOP bond, and so more P elements was involved in a crosslinking reaction to form more stable char residue, which can effectively increase the flame retardant properties of PP. POLYM. COMPOS., 38:2771–2778, 2017. © 2015 Society of Plastics Engineers
Highly redox‐stable and electrochromic aramids with morpholinyl‐substituted triphenylamine units
Authors: Hsiao Sheng‐Huei , Hsiao Ying‐Hsiu , Kung Yu‐Ruei
Published: November 2015

A novel morpholinyl‐substituted, triphenylamine‐based diamine monomer, namely 4,4′‐diamino‐4″‐(4‐morpholinyl)triphenylamine, was synthesized and polymerized with various aromatic dicarboxylic acids via the phosphorylation polyamidation reaction leading to a series of electroactive aromatic polyamides (aramids). All aramids were readily soluble in polar organic solvents and could be solution cast into tough and flexible films with high thermal stability. Cyclic voltammograms of the aramid films on the indium‐tin oxide‐coated glass substrate exhibited a pair of reversible oxidation waves with very low onset potentials of 0.36 − 0.41 V (vs. Ag/AgCl) in acetonitrile solution. The polymer films showed reversible electrochemical oxidation accompanied by strong color changes with high coloration efficiency, high contrast ratio, and rapid switching time. The optical transmittance change (Δ%T) at 650 nm between the neutral state and the fully oxidized state is up to 90%. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1289–1298
A History of Greece
Authors: Bury J. B. , Meiggs Russell
Published: November 2015

This book, originally published in 1900, was the major work of the classical historian J. B. Bury. It became a standard textbook on the topic of ancient Greek history to the death of Alexander the Great for almost a century, and in its updated form is still studied today. Bury had studied philosophy as well as classics at Trinity College, Dublin, and had travelled widely in Greece, but until the publication of this work was better known for his two-volume History of the Later Roman Empire (also reissued in this series), and many of his other works also deal with the Byzantine period. He describes in the preface his decision to limit the extent of his history: ‘compression into a single volume often produces a more useful book’. This magisterial and very readable synthesis of political and military history encompasses nearly three millennia and the whole of the Mediterranean and Near East.
Charles I
Authors: Young Michael B.
Published: November 2015

Students of early Stuart politics face a bewildering array of books and articles published in recent years. The purpose of the present book is to guide readers through this maze of writings, clarify the issues at stake, and ultimately determine who has been right and wrong about Charles I. While this book is distinguished by its frank discussion of current scholarship, it is organised around a dramatic narrative of events intended to hold the interest of students and acquaint them with the basic events of Charles's reign.
Correspondence in Stakeholder Assessment of Health, Work Capacity and Sick Leave in Workers with Comorbid Subjective Health Complaints? A Video Vignette Study
Authors: Maeland Silje , Magnussen Liv Heide , Eriksen Hege R. , Werner Erik L. , Helle-Valle Anna , Hensing Gunnel
Published: November 2015

Purpose The purpose of this study is to test if there is correspondence in stakeholders’ assessments of health, work capacity and sickness certification in four workers with comorbid subjective health complaints based on video vignettes. Methods A cross sectional survey among stakeholders (N = 514) in Norway in 2009/2010. Logistic regression and multinomial logistic regression was used to obtain the estimated probability of stakeholders choosing 100 % sick leave, partial sick leave or work and the estimation of odds ratio of stakeholder assessment compared to the other stakeholders for the individual worker. Results The supervisors were less likely to assess poor health and reduced work capacity, and more likely to suggest partial sick leave and full time work compared to the GPs for worker 1. The public was less likely to assess comorbidity and reduced work capacity, and 6 and 12 times more likely to suggest partial sick leave and full time work compared to the GPs for worker 1. Stakeholders generally agreed in their assessments of workers 2 and 3. The public was more likely to assess poor health, comorbidity and reduced work capacity, and the supervisors more likely to assess comorbidity and reduced work capacity, compared to the GPs for worker 4. Compared to the GPs, all other stakeholders were less likely to suggest full time work for this worker. Conclusions Our results seem to suggest that stakeholders have divergent assessments of complaints, health, work capacity, and sickness certification in workers with comorbid subjective health complaints.
Solvent and Extraction Conditions Control the Assayable Phenolic Content and Antioxidant Activities of Seeds of Black Beans, Canola and Millet
Authors: Chandrasekara Anoma , Rasek Omar Abdel , John Jenny Ann , Chandrasekara Neel , Shahidi Fereidoon
Published: November 2015

The effects of extraction solvent and conditions on the total phenolic content (TPC) and antioxidant activity of black beans, canola and foxtail millet were investigated. The antioxidant activity was assayed using 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging activity (DRSA) and oxygen radical absorbance capacity (ORAC). Four solvent systems, namely 70 % acetone, 80 % ethanol, 80 % methanol and a mixture of acetone/methanol/water (7:7:6, v/v/v) were used. The extraction methods adopted in this study included refluxing, homogenization, cold extraction and sonication. The TPC as measured using the Folin Ciocalteu's method were 12.35–28.39, 2.43–16.73, and 1.78–5.06 µmol catechin equivalents/g dry matter (dm) for canola, black beans and foxtail millet, respectively. Aqueous acetone afforded the highest TPC for black beans and canola. Within the same solvent system used, the TPC, DRSA and ORAC obtained from different extraction techniques differed for black beans, canola and foxtail millet. The results demonstrated that the solvent system as well as method influenced the extraction of phenolic compounds and their antioxidant activities, depending on the type of matrix in which phenolics were embedded.
Validation of the Everyday Technology Use Questionnaire in a Japanese Context
Authors: Malinowsky Camilla , Kottorp Anders , Tanemura Rumi , Asaba Eric , Nagao Toru , Noda Kazue , Sagara Jiro , Bontje Peter , Rosenberg Lena , Nygård Louise
Published: November 2015

Background/Objective

The Everyday Technology Use Questionnaire (ETUQ), which evaluates the perceived relevance of and the perceived ability in everyday technology (ET) use, has demonstrated acceptable psychometric properties in Swedish studies of older adults. The aim of this study was to examine the reliability and validity of the ETUQ in a Japanese context in older Japanese adults.

Methods

A sample of older Japanese adults (n = 164) including persons with (n = 32) and without (n = 132) cognitive impairment was interviewed with the ETUQ, including original items (ETs) and added Japanese context-specific items. Data were analyzed using a Rasch measurement model.

Results

The analysis demonstrated acceptable functioning of the rating scale, internal scale validity, person response validity, and person-separation reliability of the Japanese ETUQ according to the Rasch model. However, evidence supporting unidimensionality in the Japanese ETUQ was not consistent in this sample. The added Japanese items did not significantly change the estimated individual person measures of perceived ability to use ET.

Conclusion

The Japanese ETUQ seems to be a sensitive tool to evaluate perceived ability in ET use among elderly people in Japan with and without cognitive impairment. Therefore, it could be used in research and clinical practice.
Endoplasmic reticulum pathology and stress response in neurons precede programmed necrosis after neonatal hypoxia‐ischemia
Authors: Chavez‐Valdez Raul , Flock Debbie L. , Martin Lee J. , Northington Frances J.
Published: November 2015

The endoplasmic reticulum (ER) is tasked, among many other functions, with preventing excitotoxicity from killing neurons following neonatal hypoxia‐ischemia (HI). With the search for delayed therapies to treat neonatal HI, the study of delayed ER responses becomes relevant. We hypothesized that ER stress is a prominent feature of delayed neuronal death via programmed necrosis after neonatal HI. Since necrostatin‐1 (Nec‐1), an inhibitor of programmed necrosis, provides delayed neuroprotection against neonatal HI in male mice, Nec‐1 is an ideal tool to study delayed ER responses. C57B6 male mice were exposed to right carotid ligation followed by exposure to FiO2 = 0.08 for 45 min at p7. Mice were treated with vehicle or Nec‐1 (0.1 μl of 8 μmol) intracerebroventricularly with age‐matched littermates as controls. Biochemistry assays at 3 and 24 h and electron microscopy (EM) and immunohistochemistry at 96 h after HI were performed. EM showed ER dilation and mitochondrial swelling as apparent early changes in neurons. With advanced neurodegeneration, large cytoplasmic fragments containing dilated ER “shed” into the surrounding neuropil and calreticulin immunoreactivity was lost concurrent with nuclear features suggestive of programmed necrosis. Nec‐1 attenuated biochemical markers of ER stress after neonatal HI, including PERK and eIF2α phosphorylation, and unconventional XBP‐1 splicing, consistent with the mitigation of later ER pathology. ER pathology may be an indicator of severity of neuronal injury and potential for recovery characterized by cytoplasmic shedding, distinct from apoptotic blebbing, that we term neuronal macrozeiosis. Therapies to attenuate ER stress applied at delayed stages may rescue stressed neurons after neonatal HI.
Improvement and retention of emergency obstetrics and neonatal care knowledge and skills in a hospital mentorship program in Lilongwe, Malawi
Authors: Tang Jennifer H. , Kaliti Charlotte , Bengtson Angela , Hayat Sumera , Chimala Eveles , MacLeod Rachel , Kaliti Stephen , Sisya Fanny , Mwale Mwawi , Wilkinson Jeffrey
Published: November 2015

Objective

To evaluate whether a hospital‐based mentoring program could significantly increase short‐ and longer‐term emergency obstetrics and neonatal care (EmONC) knowledge and skills among health providers.

Methods

In a prospective before‐and‐after study, 20 mentors were trained using a specially‐created EmONC mentoring and training program at Bwaila Hospital in Lilongwe, Malawi. The mentors then trained an additional 114 providers as mentees in the curriculum. Mentors and mentees were asked to complete a test before initiation of the training (Pre‐Test), immediately after training (Post‐Test 1), and at least 6 months after training (Post‐Test 2) to assess written and practical EmONC knowledge and skills. Mean scores were then compared.

Results

Scores increased significantly between the Pre‐Test and Post‐Test 1 for both written (n = 134; difference 22.9%, P < 0.001) and practical (n = 125; difference 29.5%, P < 0.001) tests. Scores were still significantly higher in Post‐Test 2 than in the Pre‐Test for written (n = 111; difference 21.0%, P < 0.001) and practical (n = 103; difference 29.3%, P < 0.001) tests.

Conclusion

A hospital‐based mentoring program can result in both short‐ and longer‐term improvement in EmONC knowledge and skills. Further research is required to assess whether this leads to behavioral changes that improve maternal and neonatal outcomes.
Kinetic analysis of structural influences on the susceptibility of peroxiredoxins 2 and 3 to hyperoxidation
Authors: Poynton Rebecca A. , Peskin Alexander V. , Haynes Alexina C. , Lowther W. Todd , Hampton Mark B. , Winterbourn Christine C.
Published: November 2015

Mammalian 2-cysteine peroxiredoxins (Prxs) are susceptible to hyperoxidation by excess H2O2. The cytoplasmic family member Prx2 hyperoxidizes more readily than mitochondrial Prx3 due to slower dimerization of the sulfenic acid (SpOH) intermediate. Four variant amino acids near the C-terminus have been shown to contribute to this difference. We have performed kinetic analysis of the relationship between hyperoxidation and disulfide formation, using whole-protein MS and comparing wild-type (WT) Prx2 and Prx3 with tail-swap mutants in which the four amino acids were reversed. These changes make Prx3 more sensitive and Prx2 less sensitive to hyperoxidation and accounted for ∼70% of the difference between the two proteins. The tail swap mutant of Prx3 was also more susceptible when expressed in the mitochondria of HeLa cells. The hyperoxidized product at lower excesses of H2O2 was a semi-hyperoxidized dimer with one active site disulfide and the other a sulfinic acid. For Prx2, increasing the H2O2 concentration resulted in complete hyperoxidation. In contrast, only approximately half the Prx3 active sites underwent hyperoxidation and, even with high H2O2, the predominant product was the hyperoxidized dimer. Size exclusion chromatography (SEC) showed that the oligomeric forms of all redox states of Prx3 dissociated more readily into dimeric units than their Prx2 counterparts. Notably the species with one disulfide and one hyperoxidized active site was decameric for Prx2 and dimeric for Prx3. Reduction and re-oxidation of the hyperoxidized dimer of Prx3 produced hyperoxidized monomers, implying dissociation and rearrangement of the subunits of the functional homodimer.
Stoichiometry of the eIF2B complex is maintained by mutual stabilization of subunits
Authors: Wortham Noel C. , Stewart Joanna D. , Harris Sean , Coldwell Mark J. , Proud Christopher G.
Published: November 2015

The eukaryotic translation initiation factor eIF2B is a multi-subunit complex with a crucial role in the regulation of global protein synthesis in the cell. The complex comprises five subunits, termed α through ε in order of increasing size, arranged as a heterodecamer with two copies of each subunit. Regulation of the co-stoichiometric expression of the eIF2B subunits is crucial for the proper function and regulation of the eIF2B complex in cells. We have investigated the control of stoichiometric eIF2B complexes through mutual stabilization of eIF2B subunits.

 Our data show that the stable expression of the catalytic eIF2Bε subunit in human cells requires co-expression of eIF2Bγ. Similarly, stable expression of eIF2Bδ requires both eIF2Bβ and eIF2Bγ+ε. The expression of these subunits decreases despite there being no change in either the levels or the translation of their mRNAs. Instead, these subunits are targeted for degradation by the ubiquitin–proteasome system.

 The data allow us to propose a model for the formation of stoichiometric eIF2B complexes which can ensure their stoichiometric incorporation into the holocomplex.
The cancer-promoting gene fatty acid-binding protein 5 (FABP5) is epigenetically regulated during human prostate carcinogenesis
Authors: Kawaguchi Koichiro , Kinameri Ayumi , Suzuki Shunsuke , Senga Shogo , Ke Youqiang , Fujii Hiroshi
Published: November 2015

FABPs (fatty-acid-binding proteins) are a family of low-molecular-mass intracellular lipid-binding proteins consisting of ten isoforms. FABPs are involved in binding and storing hydrophobic ligands such as long-chain fatty acids, as well as transporting these ligands to the appropriate compartments in the cell. FABP5 is overexpressed in multiple types of tumours. Furthermore, up-regulation of FABP5 is strongly associated with poor survival in triple-negative breast cancer. However, the mechanisms underlying the specific up-regulation of the FABP5 gene in these cancers remain poorly characterized. In the present study, we determined that FABP5 has a typical CpG island around its promoter region. The DNA methylation status of the CpG island in the FABP5 promoter of benign prostate cells (PNT2), prostate cancer cells (PC-3, DU-145, 22Rv1 and LNCaP) and human normal or tumour tissue was assessed by bisulfite sequencing analysis, and then confirmed by COBRA (combined bisulfite restriction analysis) and qAMP (quantitative analysis of DNA methylation using real-time PCR). These results demonstrated that overexpression of FABP5 in prostate cancer cells can be attributed to hypomethylation of the CpG island in its promoter region, along with up-regulation of the direct trans-acting factors Sp1 (specificity protein 1) and c-Myc. Together, these mechanisms result in the transcriptional activation of FABP5 expression during human prostate carcinogenesis. Importantly, silencing of Sp1, c-Myc or FABP5 expression led to a significant decrease in cell proliferation, indicating that up-regulation of FABP5 expression by Sp1 and c-Myc is critical for the proliferation of prostate cancer cells.
Making Sustainability Tangible: Land O'Lakes and the Dairy Supply Chain
Authors: Boland Michael , Cooper Brendan , White James M.
Published: November 2015

This case study examines the challenges of implementing a vaguely defined concept called sustainability in a large organization that also has a cooperative structure. Stakeholder theory is described and applied to a multinational dairy firm. The case firm, Land O'Lakes, must balance the needs of multiple constituencies: the general public, employees, cooperative members, external funding organizations, and the management team. One challenge is to define sustainability for the entire dairy industry. The case discusses the strategies used by firms in developing a sustainability response where the tradeoffs between different strategies are between credibility and autonomy and using an industry rather than a firm‐level response.
Identification of drug–target interaction from interactome network with ‘guilt-by-association’ principle and topology features
Authors: Li Zhan-Chao , Huang Meng-Hua , Zhong Wen-Qian , Liu Zhi-Qing , Xie Yun , Dai Zong , Zou Xiao-Yong
Published: November 2015

Motivation: Identifying drug–target protein interaction is a crucial step in the process of drug research and development. Wet-lab experiment are laborious, time-consuming and expensive. Hence, there is a strong demand for the development of a novel theoretical method to identify potential interaction between drug and target protein.

Results: We use all known proteins and drugs to construct a nodes- and edges-weighted biological relevant interactome network. On the basis of the ‘guilt-by-association’ principle, novel network topology features are proposed to characterize interaction pairs and random forest algorithm is employed to identify potential drug–protein interaction. Accuracy of 92.53% derived from the 10-fold cross-validation is about 10% higher than that of the existing method. We identify 2272 potential drug–target interactions, some of which are associated with diseases, such as Torg-Winchester syndrome and rhabdomyosarcoma. The proposed method can not only accurately predict the interaction between drug molecule and target protein, but also help disease treatment and drug discovery.

Contacts:  zhanchao8052@gmail.com or ceszxy@mail.sysu.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
SVD-phy: improved prediction of protein functional associations through singular value decomposition of phylogenetic profiles
Authors: Franceschini Andrea , Lin Jianyi , von Mering Christian , Jensen Lars Juhl
Published: November 2015

Summary: A successful approach for predicting functional associations between non-homologous genes is to compare their phylogenetic distributions. We have devised a phylogenetic profiling algorithm, SVD-Phy, which uses truncated singular value decomposition to address the problem of uninformative profiles giving rise to false positive predictions. Benchmarking the algorithm against the KEGG pathway database, we found that it has substantially improved performance over existing phylogenetic profiling methods.

Availability and implementation: The software is available under the open-source BSD license at https://bitbucket.org/andrea/svd-phy

Contact:  lars.juhl.jensen@cpr.ku.dk

Supplementary information:  Supplementary data are available at Bioinformatics online.
MetaQUAST: evaluation of metagenome assemblies
Authors: Mikheenko Alla , Saveliev Vladislav , Gurevich Alexey
Published: November 2015

Summary: During the past years we have witnessed the rapid development of new metagenome assembly methods. Although there are many benchmark utilities designed for single-genome assemblies, there is no well-recognized evaluation and comparison tool for metagenomic-specific analogues. In this article, we present MetaQUAST, a modification of QUAST, the state-of-the-art tool for genome assembly evaluation based on alignment of contigs to a reference. MetaQUAST addresses such metagenome datasets features as (i) unknown species content by detecting and downloading reference sequences, (ii) huge diversity by giving comprehensive reports for multiple genomes and (iii) presence of highly relative species by detecting chimeric contigs. We demonstrate MetaQUAST performance by comparing several leading assemblers on one simulated and two real datasets.

Availability and implementation:  http://bioinf.spbau.ru/metaquast.

Contact:  aleksey.gurevich@spbu.ru

Supplementary information:  Supplementary data are available at Bioinformatics online.
Mechanics and thermal management of stretchable inorganic electronics
Authors: Song Jizhou , Feng Xue , Huang Yonggang
Published: November 2015

Stretchable electronics enables lots of novel applications ranging from wearable electronics, curvilinear electronics to bio-integrated therapeutic devices that are not possible through conventional electronics that is rigid and flat in nature. One effective strategy to realize stretchable electronics exploits the design of inorganic semiconductor material in a stretchable format on an elastomeric substrate. In this review, we summarize the advances in mechanics and thermal management of stretchable electronics based on inorganic semiconductor materials. The mechanics and thermal models are very helpful in understanding the underlying physics associated with these systems, and they also provide design guidelines for the development of stretchable inorganic electronics.
Suzaku study on the ejecta of the supernova remnant G272.2−3.2
Authors: Kamitsukasa Fumiyoshi , Koyama Katsuji , Nakajima Hiroshi , Hayashida Kiyoshi , Mori Koji , Katsuda Satoru , Uchida Hiroyuki , Tsunemi Hiroshi
Published: November 2015

We report reanalyses of the Suzaku observations of the Galactic supernova remnant (SNR) G272.2−3.2, for which previous studies were limited below 3 keV. With careful data reduction and background subtraction, we discover the K-shell lines of Ar, Ca, and Fe above 3 keV. The X-ray spectrum of G272.2−3.2 consists of two components, a low-temperature collisional ionization equilibrium (CIE) plasma (kTe ∼ 0.2 keV) and a high-temperature non-equilibrium ionization (NEI) plasma (kTe = 0.6–3 keV). The CIE plasma has solar abundances over the entire area, hence it originates from the interstellar medium. On the other hand, the abundances of the NEI plasma increase toward the inner region, suggesting ejecta origin. The line center energy of the Fe K-shell emission (∼6.4 keV) suggests that the ejecta are recently heated by reverse shock, a common feature in Type Ia SNRs.
BAGEL: A computational framework for identifying essential genes from pooled library screens
Authors: Hart Traver , Moffat Jason
Published: November 2015

Background

The adaptation of the CRISPR-Cas9 system to pooled library gene knockout screens in mammalian cells represents a major technological leap over RNA interference, the prior state of the art. New methods for analyzing the data and evaluating results are needed.

Results

We offer BAGEL (Bayesian Analysis of Gene EssentiaLity), a supervised learning method for analyzing gene knockout screens. Coupled with gold-standard reference sets of essential and nonessential genes, BAGEL offers significantly greater sensitivity than current methods, while computational optimizations reduce runtime by an order of magnitude.

Conclusions

Using BAGEL, we identify ~2,000 fitness genes in pooled library knockout screens in human cell lines at 5% FDR, a major advance over competing platforms. BAGEL shows high sensitivity and specificity even across screens with highly variable reagent quality.
Novel Intronic Non-Coding RNAs Contribute to Maintenance of Phenotype inSaccharomyces Cerevisiae
Authors: Hooks Katarzyna B , Naseeb Samina , Griffiths-Jones Sam , Delneri Daniela
Published: November 2015

TheSaccharomyces cerevisiaegenome has undergone extensive intron loss during its evolutionary history. It has been suggested that the few remaining introns (in only 5% of protein-coding genes) are retained because of their impact on function under stress conditions. Here, we explore the possibility that novel non-coding RNA structures (ncRNAs) are embedded within intronic sequences and are contributing to phenotype and intron retention in yeast. We employedde novoRNA structure prediction tools to screen intronic sequences inS. cerevisiaeand 36 other fungi. We identified and validated 19 new intronic RNAs via RNAseq and RT-PCR. Contrary to common belief that excised introns are rapidly degraded, we found that, in six cases, the excised introns were maintained intact in the cells. In other two cases we showed that the ncRNAs were further processed from their introns. RNAseq analysis confirmed higher expression of introns in the ribosomial protein genes containing predicted RNA structures. We deleted the novel intronic RNA structure within theGLC7intron and showed that this predicted ncRNA, rather than the intron itself, is responsible for the cell’s ability to respond to salt stress. We also showed a direct association between the presence of the intronic ncRNA andGLC7expression. Overall, these data support the notion that some introns may have been maintained in the genome because they harbour functional ncRNAs.
Unearthing New Genomic Markers of Drug Response by Improved Measurement of Discriminative Power
Authors: Dang Cuong C. , Peón Antonio , Ballester Pedro J.
Published: November 2015

Background

Oncology drugs are only effective in a small proportion of cancer patients. Our current ability to identify these responsive patients before treatment is still poor in most cases. Thus, there is a pressing need to discover response markers for marketed and research oncology drugs in order to improve patient survival, reduce healthcare costs and enhance success rates in clinical trials. Screening these drugs against a large panel of cancer cell lines has been employed to discover new genomic markers ofin vitrodrug response, which can now be further evaluated on more accurate tumour models. However, while the identification of discriminative markers among thousands of candidate drug-gene associations in the data is error-prone, an appraisal of the effectiveness of such detection task is currently lacking.

Results

Here we present a new non-parametric method to measuring the discriminative power of a drug-gene association. This is enabled by the identification of an auxiliary threshold posing this task as a binary classification problem. Unlike parametric statistical tests, the adopted non-parametric test has the advantage of not making strong assumptions about the data distorting the identification of genomic markers. Furthermore, we introduce a new benchmark to further validate these markersin vitrousing more recent data not used to identify the markers. The application of this new methodology has led to the identification of 128 new genomic markers distributed across 61% of the analysed drugs, including 5 drugs without previously known markers, which were missed by the MANOVA test initially applied to analyse data from the Genomics of Drug Sensitivity in Cancer consortium.

Abbreviation

(WT)

wild-type

(GDSC)

Genomics of Drug Sensitivity in Cancer

(TP)

true positive

(TN)

true negative

(FP)

false positive

(FN)

false negative

(MCC)

Matthews Correlation Co-efficient.
Sequenceserver: a modern graphical user interface for custom BLAST databases
Authors: Priyam Anurag , Woodcroft Ben J. , Rai Vivek , Munagala Alekhya , Moghul Ismail , Ter Filip , Gibbins Mark Anthony , Moon HongKee , Leonard Guy , Rumpf Wolfgang , Wurm Yannick
Published: November 2015

The dramatic drop in DNA sequencing costs has created many opportunities for novel biological research. These opportunities largely rest upon the ability to effectively compare newly obtained and previously known sequences. This is commonly done with BLAST, yet using BLAST directly on new datasets requires substantial technical skills or helpful colleagues. Furthermore, graphical interfaces for BLAST are challenging to install and largely mimic underlying computational processes rather than work patterns of researchers.

We combined a user-centric design philosophy with sustainable software development approaches to create Sequenceserver (http://sequenceserver.com), a modern graphical user interface for BLAST. Sequenceserver substantially increases the efficiency of researchers working with sequence data. This is due to innovations at three levels. First, our software can be installed and used on custom datasets extremely rapidly for personal and shared applications. Second, based on analysis of user input and simple algorithms, Sequenceserver reduces the amount of decisions the user must make, provides interactive visual feedback, and prevents common potential errors that would otherwise cause erroneous results. Finally, Sequenceserver provides multiple highly visual and text-based output options that mirror the requirements and work patterns of researchers. Together, these features greatly facilitate BLAST analysis and interpretation and thus substantially enhance researcher productivity.
Diversity of immune strategies explained by adaptation to pathogen statistics
Authors: Mayer Andreas , Mora Thierry , Rivoire Olivier , Walczak Aleksandra M
Published: November 2015

Biological organisms have evolved a wide range of immune mechanisms to defend themselves against pathogens. Beyond molecular details, these mechanisms differ in how protection is acquired, processed and passed on to subsequent generations -- differences that may be essential to long-term survival. Here, we introduce a mathematical framework to compare the long-term adaptation of populations as a function of the pathogen dynamics that they experience and of the immune strategy that they adopt. We find that the two key determinants of an optimal immune strategy are the frequency and the characteristic timescale of the pathogens. Depending on these two parameters, our framework identifies distinct modes of immunity, including adaptive, innate, bet-hedging and CRISPR-like immunities, which recapitulate the diversity of natural immune systems.
Meiotic interactors of a mitotic geneTAO3revealed by functional analysis of its rare variant
Authors: Gupta Saumya , Radhakrishnan Aparna , Nitin Rachana , Raharja-Liu Pandu , Lin Gen , Steinmetz Lars M. , Gagneur Julien , Sinha Himanshu
Published: November 2015

Studying the molecular consequences of rare genetic variants has the potential of identifying novel and hereto uncharacterized pathways causally contributing to phenotypic variation. Here we characterize the functional consequences of a rare coding variant ofTAO3, previously reported to significantly contribute to sporulation efficiency variation inSaccharomyces cerevisiae. During mitosisTAO3interacts withCBK1, a conserved NDR kinase and a component of RAM network. The RAM network genes are involved in regulation cell separation and polarization. We demonstrate that the role of the rare alleleTAO3(4477C)in meiosis is distinct from its role in mitosis by being independent ofACE2, which is a RAM network target gene. By quantitatively measuring cell morphological dynamics and conditionally expressingTAO3(4477C)allele during sporulation, we show thatTAO3has an early role in meiosis. This early role ofTAO3coincides with entry of cells into meiotic division. Time-resolved transcriptome analyses during early sporulation phase identified regulators of carbon and lipid metabolic pathways as candidate mediators. We experimentally show that during sporulation theTAO3allele genetically interacts withERT1andPIP2, the regulators of tricarboxylic acid cycle and gluconeogenic enzymes, respectively. We thus uncover meiotic functions ofTAO3, a mitotic gene and proposeERT1andPIP2as novel regulators of sporulation efficiency. Our results demonstrate that study of causal effects of genetic variation on the underlying molecular network has the potential to provide more extensive comprehension of the pathways driving a complex trait. This can help identify prospective personalized targets for intervention in complex diseases.
Sex‐specific and individual preferences for hunting strategies in white sharks
Authors: Towner Alison V. , Leos‐Barajas Vianey , Langrock Roland , Schick Robert S. , Smale Malcolm J. , Kaschke Tami , Jewell Oliver J. D. , Papastamatiou Yannis P.
Published: November 2015

Fine‐scale predator movements may be driven by many factors including sex, habitat and distribution of resources. There may also be individual preferences for certain movement strategies within a population which can be hard to quantify.

Within top predators, movements are also going to be directly related to the mode of hunting, for example sit‐and‐wait or actively searching for prey. Although there is mounting evidence that different hunting modes can cause opposing trophic cascades, there has been little focus on the modes used by top predators, especially those in the marine environment.

Adult white sharks (Carcharhodon carcharias) are well known to forage on marine mammal prey, particularly pinnipeds. Sharks primarily ambush pinnipeds on the surface, but there has been less focus on the strategies they use to encounter prey.

We applied mixed hidden Markov models to acoustic tracking data of white sharks in a coastal aggregation area in order to quantify changing movement states (area‐restricted searching (ARS) vs. patrolling) and the factors that influenced them. Individuals were re‐tracked over multiple days throughout a month to see whether state‐switching dynamics varied or if individuals preferred certain movement strategies.

Sharks were more likely to use ARS movements in the morning and during periods of chumming by ecotourism operators. Furthermore, the proportion of time individuals spent in the two different states and the state‐switching frequency, differed between the sexes and between individuals.

Predation attempts/success on pinnipeds were observed for sharks in both ARS and patrolling movement states and within all random effects groupings. Therefore, white sharks can use both a ‘sit‐and‐wait’ (ARS) and ‘active searching’ (patrolling) movements to ambush pinniped prey on the surface.

White sharks demonstrate individual preferences for fine‐scale movement patterns, which may be related to their use of different hunting modes. Marine top predators are generally assumed to use only one type of hunting mode, but we show that there may be a mix within populations. As such, individual variability should be considered when modelling behavioural effects of predators on prey species.
Silicon in aquatic vegetation
Authors: Schoelynck Jonas , Struyf Eric
Published: November 2015

Silicon (Si) use by plants has not always received the research attention of other elements. Yet today, the importance of Si for plant functioning is slowly becoming better understood. Si is a crucial element for many terrestrial plant species (especially grasses), yet a recent surge of research has shown that some species of aquatic plants contain significant amounts of Si too.

We argue that degree of Si accumulation is a functional trait in aquatic vegetation, with plants adapting to environmental conditions. Aquatic vegetation can show apparent plasticity regarding Si uptake, adaptive to water and wind dynamics, light interception, herbivory and nutrient stress. Beyond a plant physiological viewpoint, high Si uptake results in high BSi in plant litter, which can impact on aquatic decomposition processes. Si content in aquatic vegetation shows intriguing relations with other strength components such as cellulose and lignin. Si content has also been linked to fungal and microbial community, litter stoichiometry and invertebrate shredders: all factors that potentially influence organic turnover in aquatic sediments.

Uptake of Si by aquatic vegetation is thus not only an important transient sink for Si in the global biogeochemical Si cycle, it can also affect carbon turnover in aquatic ecosystems. Experimental and field studies should be conducted to elucidate controls on aquatic plant Si uptake, especially focusing on interactive effects of multiple biotic and abiotic factors. This review provides an overview of the state‐of‐the‐art knowledge on silicon in aquatic vegetation.
Above‐ground and below‐ground responses to long‐term nutrient addition across a retrogressive chronosequence
Authors: Wardle David A. , Jonsson Micael , Mayor Jordan R. , Metcalfe Daniel B.
Published: November 2015

There is much interest in understanding ecosystem responses to local‐scale soil fertility variation, which has often been studied using retrogressive chronosequences that span thousands of years and show declining fertility and plant productivity over time. There have been few attempts to experimentally test how plant nutrient limitation changes during retrogression.

We studied a well‐characterized system of 30 forested lake islands in northern Sweden that collectively represent a 5350‐year post‐fire retrogressive chronosequence, with fertility and productivity decreasing as time since fire increases. For each island, we set up four plots on understorey vegetation, each subjected to a different fertilizer treatment over 6 years: no additions, nitrogen (N) only, phosphorus (P) only and N + P.

We found that both N and P additions reduced feather moss and thus total plant biomass. Meanwhile, the three dominant vascular plant species showed contrasting biomass responses, but similar responses of foliar nutrient concentrations to nutrient additions. Fertilization reduced most microbial groups and altered CO2 fluxes, most likely through feather moss reduction. Against expectations, the majority of interactive effects of N and P were antagonistic.

Changes in effects of nutrient additions during retrogression were usually modest. Empetrum hermaphroditum biomass was increasingly promoted by P and N + P addition, while vascular plant N‐to‐P ratios were increasingly reduced by P addition, indicating increasing plant limitation by nutrients (notably P) during retrogression. Below‐ground, positive effects of N addition on soil mineral N increased, while negative effects of N addition on soil fungi decreased during retrogression; no other below‐ground effects of fertilization changed along the gradient.

Synthesis. Our results show that forest understorey communities on islands of different fire history and thus stages of retrogression show relatively modest differences in how they respond to nutrient addition despite large changes in ecosystem productivity and soil fertility, probably because of high species turnover and adaptation of communities to infertile conditions. While increased nutrient availability (as expected through global change) may have important ecological consequences, these effects are likely, especially below‐ground, to be rather similar across ecosystems that differ greatly in nutrient availability and productivity.
Effects of spatial plant–soil feedback heterogeneity on plant performance in monocultures
Authors: Wubs E. R. Jasper , Bezemer T. Martijn
Published: November 2015

Plant–soil feedback (PSF) effects have almost exclusively been quantified on homogeneous soils, but as different plant species will influence their local soil differently, in reality PSF effects will be spatially heterogeneous. Whether plant performance in soils with spatially heterogeneous PSF can be predicted from pot experiments with homogeneous soils is unclear.

In a glasshouse experiment, we tested the response of monocultures of six grassland species (two grasses, two legumes and two forbs) to three spatially explicit treatments (fine‐grained heterogeneity, coarse‐grained heterogeneity and homogeneous). Sixteen patches of conditioned soil (˜6 × 6 cm) were placed within each container. For homogeneous treatments, all patches contained the same conditioned soil within a container. The fine‐grained heterogeneous treatment contained four differently conditioned soils that were applied following a Latin square design, while for the coarse‐grained heterogeneous treatment, four contiguous square blocks of four cells each were created in each container.

In general, species grew worse on soil conditioned by conspecifics. However, when the biomass production on all homogeneous soil treatments (own and foreign soils) was averaged and compared to the heterogeneous treatments, we found that biomass production was lower than expected in the heterogeneous soils. This effect of heterogeneity depended on both the conditioning and test species, but most heterogeneity effects were negative. The grain of the heterogeneity (coarse vs. fine: at the chosen spatial scale) did not affect plant performance.

We hypothesize that a more diverse soil community is present in spatially heterogeneous soils. This increases (i) the chance of plants to encounter its antagonists, which may then rapidly increase in numbers; and (ii) the scope for synergistic co‐infections. Together, this may lead to non‐additive responses of plants to spatial heterogeneity in PSF.

Synthesis. Plant performance was lower in spatially heterogeneous soils than predicted by spatially homogeneous soils. In natural grasslands that have mixed plant communities conditioning the soil, plant–soil feedback (PSF) effects on plant performance may therefore be more negative than what is predicted from pot experiments. Our results emphasize the need to incorporate the spatial dynamics of PSF both in empirical and modelling studies if we are to understand the role of PSF in plant–plant interactions and plant community dynamics.
Public Pressure and Corporate Tax Behavior
Authors: DYRENG SCOTT D. , HOOPES JEFFREY L. , WILDE JARON H.
Published: November 2015

We use a shock to the public scrutiny of firm subsidiary locations to investigate whether that scrutiny leads to changes in firms’ disclosure and corporate tax avoidance behavior. ActionAid International, a nonprofit activist group, levied public pressure on noncompliant U.K. firms in the FTSE 100 to comply with a rule requiring U.K. firms to disclose the location of all of their subsidiaries. We use this setting to examine whether the public pressure led scrutinized firms to increase their subsidiary disclosure, decrease tax avoidance, and reduce the use of subsidiaries in tax haven countries compared to other firms in the FTSE 100 not affected by the public pressure. The evidence suggests that the public scrutiny sufficiently changed the costs and benefits of tax avoidance such that tax expense increased for scrutinized firms. The results suggest that public pressure from outside activist groups can exert a significant influence on the behavior of large, publicly traded firms. Our findings extend prior research that has had little success documenting an empirical relation between public scrutiny of tax avoidance and firm behavior.
Effect of renal function on serum concentration of 1,5‐anhydroglucitol in type 2 diabetic patients in chronic kidney disease stages I–III: A comparative study with HbA1c and glycated albumin
Authors: Hasslacher Christoph , Kulozik Felix
Published: November 2015

Background

1,5‐Anhydroglucitol (1,5‐AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5‐AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5‐AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA).

Methods

The following parameters were measured in 377 patients with type 2 diabetes: HbA1c, serum concentrations of 1,5‐AG, GA and creatinine, hemoglobin, urinary albumin/creatinine ratio, and urinary excretion of α1‐microglobulin (A1M). Estimated glomerular filtration rate (eGFR) was calculated according to the Cockgroft–Gault formula.

Results

There was a negative correlation between 1,5‐AG and renal function (r = −0.18; P < 0.001). Concentrations of 1,5‐AG were, on average, 27.2% lower in patients with glomerular hyperfiltration (eGFR >120 mL/min) compared with patients with moderate renal impairment (eGFR 30–59 mL/min; P = 0.016). In contrast, HbA1c, GA levels and urinary A1M excretion did not differ between the two patient groups. The mean age of patients with eGFR 30–59 mL/min was substantially higher than that of patients with glomerular hyperfiltration (P < 0.001). Thus, an age‐related change in the renal glucose threshold could be the reason for the observed correlation between 1,5‐AG and renal function.

Conclusions

In clinical practice, age and renal function must be taken into consideration when interpreting 1,5‐AG levels, even in the absence of advanced renal impairment.