bluuebunny/crossref_metadata_2025_split huggingface dataset:
PrPSc-induced conformational changes and strain-specific structures of PrPScrevealed by Disulfide-crosslink scanning
Authors: Taguchi Yuzuru , Nishida Noriyuki , Schatzl Hermann S. 
Published: August 2017

ABSTRACTThere exist many phenotypically-varied prion strains, like viruses, despite the absence of conventional genetic material which codes the phenotypic information. As prion is composed solely of the pathological isoform (PrPSc) of prion protein (PrP), the strain-specific traits are hypothesized to be enciphered in the structural details of PrPSc. Identification of the structures of PrPScis therefore vital for the understanding of prion biology, though they remain unidentified due to the incompatibility of PrPScwith conventional high-resolution structural analyses. Based on our previous hypothesis that the region between the first and the second α-helix (H1∼H2) and the distal region of the third helix (Ctrm) of the cellular isoform of PrP (PrPC) have important roles for efficient interactions with PrPSc, we created series of mutant PrPs with two cysteine substitutions (C;C-PrP) which were systematically designed to form an intramolecular disulfide crosslink between H1∼H2 and Ctrm and assessed their conformational changes by prions: Specifically, a cysteine substitution in H1∼H2 from 165 to 169 was combined with cysteine-scanning along Ctrm from 220 to 229. C;C-PrPs with the crosslinks were expressed normally with the similar glycosylation patterns and subcellular localization as the wild-type PrP albeit with varied expression levels. Interestingly, some of the C;C-PrPs converted to the protease-resistant isoforms in the N2a cells persistently infected with 22L prion strain, whereas the same mutants did not convert in the cells infected with another prion strain Fukuoka1, indicating that local structures of PrPScin these regions vary among prion strains and contribute to prion-strain diversity. Moreover, patterns of the crosslinks of the convertible C;C-PrPs implied drastic changes in positional relations of H1∼H2 and Ctrm in the PrPSc-induced conformational changes by 22L prion. Thus, disulfide-crosslink scanning is a useful approach for investigation of strain-specific structures of PrPSc, and would be applicable to other types of amyloids as well.
A global envelope test to detect early and late bursts of trait evolution
Authors: Murrell D. J. 
Published: August 2017

AbstractThe joint analysis of species’ evolutionary relatedness and their morphological evolution has offered much promise in understanding the processes that underpin the generation of biological diversity. Disparity through time (DTT) is a popular method that estimates the relative trait disparity within and between subclades at each time point, and compares this to the null hypothesis that trait values follow an uncorrelated random walk along the time calibrated phylogenetic tree. A simulation envelope is normally created by calculating, at every time point, the 95% minimum and 95% maximum disparity values from multiple simulations of the null model on the phylogenetic tree. The null hypothesis is rejected whenever the empirical DTT curve falls outside of this envelope, and these time periods may then be linked to events that may have sparked non-random trait evolution. However, this method of envelope construction leads to multiple testing and a poor, uncontrolled, false positive rate. As a consequence it cannot be recommended. A recently developed method in spatial statistics is introduced that constructs a confidence envelope by giving each DTT curve a single ranking value based upon its most extreme disparity value. This method avoids the pitfalls of multiple testing whilst retaining a visual interpretation. Results using simulated data show this new test has desirable type 1 properties and is at least as powerful in correctly rejecting the null hypothesis as the morphological disparity index and node height test that lack a visual interpretation. Three example datasets are reanalyzed to show how the new test may lead to different inferences being drawn. Overall the results suggest the new rank envelope test should be used in null model testing for DTT analyses, and that there is no need to combine the envelope test with other tests such as has been done previously. Moreover, the rank envelope method can easily be adopted into recently developed posterior predictive simulation methods. More generally, the rank envelope test should be adopted when-ever a null model produces a vector of correlated values and the user wants to determine where the empirical data is different to the null model.
Solagigasbacteria: Lone genomic giants among the uncultured bacterial phyla
Authors: Becraft Eric D. , Woyke Tanja , Jarett Jessica , Ivanova Natalia , Vitorino Filipa Godoy , Poulton Nicole , Brown Julia M. , Brown Joseph , Lau C.Y.M. , Onstott Tullis , Eisen Jonathan A. , Moser Duane , Stepanauskas Ramunas 
Published: August 2017

ABSTRACTRecent advances in single-cell genomic and metagenomic techniques have facilitated the discovery of numerous previously unknown, deep branches of the tree of life that lack cultured representatives. Many of these candidate phyla are composed of microorganisms with minimalistic, streamlined genomes lacking some core metabolic pathways, which may contribute to their resistance to growth in pure culture. Here we analyzed single-cell genomes and metagenome bins to show that the “Candidate phylum SPAM” represents an interesting exception, by having large genomes (6-8 Mbps), high GC content (66%-71%), and the potential for a versatile, mixotrophic metabolism. We also observed an unusually high genomic heterogeneity among individual SPAM cells in the studied samples. These features may have contributed to the limited recovery of sequences of this candidate phylum in prior metagenomic studies. Based on these observations, we propose renaming SPAM to “Candidate phylum Solagigasbacteria”. Current evidence suggests that Solagigasbacteria are distributed globally in diverse terrestrial ecosystems, including soils, the rhizosphere, volcanic mud, oil wells, aquifers and the deep subsurface, with no reports from marine environments to date.
Modeling the emergence of antibiotic resistance in the environment: an analytical solution for the minimum selection concentration
Authors: Greenfield Ben K. , Shaked Shanna , Marrs Carl F. , Nelson Patrick , Raxter Ian , Xi Chuanwu , McKone Thomas E. , Jolliet Olivier 
Published: August 2017

AbstractEnvironmental antibiotic risk management requires an understanding of how subinhibitory antibiotic concentrations contribute to the spread of resistance. We develop a simple model of competition between sensitive and resistant bacterial strains to predict the minimum selection concentration (MSC), the lowest level of antibiotic at which resistant bacteria are selected. We present an analytical solution for the MSC based on the routinely measured minimum inhibitory concentration (MIC) and the selection coefficient (sc) that expresses fitness differences between strains. We calibrated the model by optimizing the shape of the bacterial growth dose–response curve to antibiotic or metal exposure (the Hill coefficient, κ) to fit previously published experimental growth rate difference data. The model fit varied among nine compound-taxa combinations examined, but predicted the experimentally observed MSC/MIC ratio well (R2≥ 0.95). The shape of the antibiotic response curve varied among compounds (0.7 ≤ κ ≤ 10.5), with the steepest curve for the aminoglycosides streptomycin and kanamycin. The model was sensitive to this antibiotic response curve shape and to the sc, indicating the importance of fitness differences between strains for determining the MSC. The MSC can be more than one order of magnitude lower than the MIC, typically by a factor scκ. This study provides an initial quantitative depiction and a framework for a research agenda to examine the growing evidence of selection for resistant bacteria communities at low environmental antibiotic concentrations.
A Pan-Cancer Transcriptome Analysis Reveals Pervasive Regulation through Tumor-Associated Alternative Promoters
Authors: Demircioğlu Deniz , Kindermans Martin , Nandi Tannistha , Cukuroglu Engin , Calabrese Claudia , Fonseca Nuno A. , Kahles Andre , Lehmann Kjong , Stegle Oliver , Brazma Alvis , Brooks Angela N. , Rätsch Gunnar , Tan Patrick , Göke Jonathan ,   on behalf of the PCAWG Transcriptome Working Group, and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: August 2017

ABSTRACTMost human protein-coding genes are regulated by multiple, distinct promoters, suggesting that the choice of promoter is as important as its level of transcriptional activity. While the role of promoters as driver elements in cancer has been recognized, the contribution of alternative promoters to regulation of the cancer transcriptome remains largely unexplored. Here we infer active promoters using RNA-Seq data from 1,188 cancer samples with matched whole genome sequencing data. We find that alternative promoters are a major contributor to context-specific regulation of isoform expression and that alternative promoters are frequently deregulated in cancer, affecting known cancer-genes and novel candidates. Our study suggests that a highly dynamic landscape of active promoters shapes the cancer transcriptome, opening many opportunities to further explore the interplay of regulatory mechanism and noncoding somatic mutations with transcriptional aberrations in cancer.
Genomics-Based Identification of Microorganisms in Human Ocular Body Fluid
Authors: Kirstahler Philipp , Bjerrum Søren Solborg , Friis-Møller Alice , Cour Morten la , Aarestrup Frank M. , Westh Henrik , Pamp Sünje Johanna 
Published: August 2017

AbstractAdvances in genomics have the potential to revolutionize clinical diagnostics. Here, we examine the microbiome of vitreous (intraocular body fluid) from patients who developed endophthalmitis following cataract surgery or intravitreal injection. Endophthalmitis is an inflammation of the intraocular cavity and can lead to a permanent loss of vision. As controls, we included vitreous from endophthalmitis-negative patients, balanced salt solution used during vitrectomy, and DNA extraction blanks. We compared two DNA isolation procedures and found that an ultraclean production of reagents appeared to reduce background DNA in these low microbial biomass samples. We created a curated microbial genome database (>5700 genomes) and designed a metagenomics workflow with filtering steps to reduce DNA sequences originating from: i) human hosts, ii) ambiguousness/contaminants in public microbial reference genomes, and iii) the environment. Our metagenomic read classification revealed in nearly all cases the same microorganism than was determined in cultivation‐ and mass spectrometry-based analyses. For some patients, we identified the sequence type of the microorganism and antibiotic resistance genes through analyses of whole genome sequence (WGS) assemblies of isolates and metagenomic assemblies. Together, we conclude that genomics-based analyses of human ocular body fluid specimens can provide actionable information relevant to infectious disease management.
Interactions between species introduce spurious associations in microbiome studies
Authors: Menon Rajita , Ramanan Vivek , Korolev Kirill S. 
Published: August 2017

AbstractMicrobiota contribute to many dimensions of host phenotype, including disease. To link specific microbes to specific phenotypes, microbiome-wide association studies compare microbial abundances between two groups of samples. Abundance differences, however, reflect not only direct associations with the phenotype, but also indirect effects due to microbial interactions. We found that microbial interactions could easily generate a large number of spurious associations that provide no mechanistic insight. Using techniques from statistical physics, we developed a method to remove indirect associations and applied it to the largest dataset on pediatric inflammatory bowel disease. Our method corrected the inflation of p-values in standard association tests and showed that only a small subset of associations is directly linked to the disease. Direct associations had a much higher accuracy in separating cases from controls and pointed to immunomodulation, butyrate production, and the brain-gut axis as important factors in the inflammatory bowel disease.
Discovery and whole genome sequencing of a human clinical isolate of the novel speciesKlebsiella quasivariicolasp. nov
Authors: Wesley Long S. , Linson Sarah E. , Saavedra Matthew Ojeda , Cantu Concepcion , Davis James J. , Brettin Thomas , Olsen Randall J. 
Published: August 2017

ABSTRACTOriginally thought to be a single species,Klebsiella pneumoniaehas been divided into three distinct species:K. pneumoniae,K. quasipneumoniaeandK. variicola. In a recent study of 1,777 extended-spectrum beta-lactamase (ESBL)-producingKlebsiellastrains recovered from human infections in Houston, we discovered one strain (KPN1705) causing a wound infection that was phylogenetically distinct from all currently recognizedKlebsiellaspecies. Whole genome sequencing of strain KPN1705 revealed that it was single locus variant of the multilocus sequence type ST-1155. This sequence type was reported only once previously. To further investigate the phylogeny of these two organisms, we sequenced the genome of strain KPN1705 to closure and compared its genetic features toKlebsiellareference strains. Results demonstrated strain KPN1705 extensively shares core gene content, antimicrobial resistance genes, and plasmids withK. pneumoniae,K. quasipneumoniaeandK. variicola. Since strain KPN1705 and the previously reported novel strain are phylogenetically most closely related toK. variicola,we propose the nameK. quasivariicolasp. nov.
ProphET, Prophage Estimation Tool: a standalone prophage sequence prediction tool with self-updating reference database
Authors: Reis-Cunha João L. , Bartholomeu Daniella C. , Earl Ashlee M. , Birren Bruce W. , Cerqueira Gustavo C. 
Published: August 2017

AbstractProphages are a significant force in prokaryote evolution. The remaining sequences of a bacteriophage integration event are known for altering gene expression, enabling creative destruction of the bacterial genome and to induce pathogenicity by harboring and transposing virulence and antibiotic resistance factors. In the light of the dreadful expansion of antibiotic resistance bacteriophages have gathered renewed interest from the scientific community and public health decision makers as a promising long forgotten alternative to control bacterial infections. Cataloging the repertoire of prophages and their integration sites is an important initial step in the understanding of bacteriophages either as tool or as a threat. In this work, we present ProphET (Prophage Estimation Tool), a standalone application without the limitations of their web based counterparts and which identifies prophages in bacterial genomes with higher precision than similar applications.
Study of collaborative PRM business model for sustainability
Authors: Ray Ankita , Mondal Sandeep 
Published: August 2017

PurposeSustainable development comprises three bottom line concepts, i.e. protect environment, improve economic performance, and social performance. Business organization with only profitability as the primary objective may lead to a highly competitive market which mainly focuses on financial performance and pay less attention to environmental and social performance. Companies that adopt the product recovery activities also select economic performance as the prime priority of their business objectives. The purpose of this paper is to give a brief idea about a different kind of business model other than conventional business models. Here, the authors aim to represent collaboration among firms, companies, and players within a closed-loop supply chain (CLSC) to build a leading business model that establishes three basic concepts of sustainability.Design/methodology/approachFrom literature the authors identified that the primary objective of establishing a sustainable business model is environmental issues but achieving economic performance and gaining market share increase competition among companies. The authors also identified that increasing financial performance results in the development of a competitive business model. This literature review helps to represent the concept of collaborative business model, its benefit, and its mechanism and also helps to compare it with competitive business model in terms of sustainability.FindingsIn case of the collaborative business model, the authors found that collaboration is better than competition to sustain in the market. The authors described the collaborative business model and mechanism of both competitive and collaborative business strategies in a CLSC. The authors gave an idea to adopt some well-known business model and pricing policies for the collaborating firms. The authors presented a comparison between the collaborative and competitive business model and also identified different types of collaborative and completive relationship among the players within a CLSC.Originality/valueGovernment legislations, e-waste rules, and environmental rules involve original equipment manufacturer (OEM) for taking back its end-of-life (EOL)/end-of-use products. A collaborative business model helps OEM to manage those huge amounts of used products by involving third parties within the supply chain. Here, in this paper the authors represent different collaborative parties and their purpose for collaboration, and also represent a strong belief that collaborative business model is the recent trend for establishing sustainability than competitive business model.
Measuring the supply chain risk in offshoring countries using data envelopment analysis and the analytic hierarchy process
Authors: Min Hokey , Park Heekeon , Ahn Seung Bum 
Published: August 2017

Purpose
An indiscreet strategy of offshoring from low-cost countries (LCCs) can do more harm than good, since invisible supply chain risks may increase hidden costs and subsequently more than offset cost-saving opportunities. Considering the potential impact of these risks on offshoring, the purpose of this paper is to identify risk factors that significantly hinder the efficiency of offshoring and then measure specific risks associated with offshoring in foreign countries.

Design/methodology/approach
This paper develops performance metrics for gauging the offshoring attractiveness of potential sourcing countries using data envelopment analysis and then identifies the benchmark sourcing country using the analytic hierarchy process (AHP).

Findings
This study reveals that, defying the conventional wisdom, LCCs are not necessarily the most desirable offshoring destinations. This study also discovers that LCCs tend to be less business friendly, less logistically efficient, and riskier to source than their high-income country counterparts.

Originality/value
This paper is one of the first to introduce the concept of wealth creation efficiency for an offshoring decision and consider a host of key determinants such as wealth creation efficiency, logistics efficiency, business friendliness, and various supply chain risks for selecting the most desirable offshoring destination.
Testing the market efficiency by mean absolute deviation
Authors: Ren Louie , Ren Peter 
Published: August 2017

Purpose
Numerous articles have been written to prove or to disapprove the hypothesis of market efficiency. The purpose of this paper is to apply the forecast accuracy measure, mean absolute deviation (MAD), to check the validity of the hypothesis.

Design/methodology/approach
Forecast accuracies from applying different simple moving average methods to independently identically distributed (i.i.d.) or near i.i.d. normal time series are assessed by MAD. When moving period n is greater than m, then the mean of the MADs from the MA with n moving periods will be smaller than the mean of the MADs from the MA with m moving periods.

Findings
In this study, when different MAs are applied to four near i.i.d. finance time series from Fama’s papers, the MAD cannot distinguish the differences among MA methods with various moving periods. This contradiction implies that the four finance time series in Fama’s papers may not be i.i.d and implies that the market is not efficient.

Research limitations/implications
The finding is only based on simulation and four near i.i.d. time series studied in Fama’s papers in 1965 and 1970.

Practical implications
The study shows that that the differences of the rates of returns from Johns Manville, Goodyear, Owens Illinois, and General Electric studied are not i.i.d. and that the market is not efficient. It refutes what Fama (1965, 1970) has claimed.

Social implications
When the market is not efficient, investors may gain profit from the market.

Originality/value
Based on the literature review, this is the first study to use the forecast accuracy measure, MAD, for market efficiency.
A social norms approach to changing school children’s perceptions of tobacco usage
Authors: Sheikh Afzal , Vadera Sunil , Ravey Michael , Lovatt Gary , Kelly Grace 
Published: August 2017

Purpose
Over 200,000 young people in the UK embark on a smoking career annually, thus continued effort is required to understand the types of interventions that are most effective in changing perceptions about smoking amongst teenagers. Several authors have proposed the use of social norms programmes, where correcting misconceptions of what is considered normal behaviour lead to improved behaviours. There are a limited number of studies showing the effectiveness of such programmes for changing teenagers’ perception of smoking habits, and hence this paper reports on the results from one of the largest social norms programmes that used a variety of interventions aimed at improving teenagers’ perceptions of smoking. The paper aims to discuss this issue.

Design/methodology/approach
A range of interventions were adopted for 57 programmes in year nine students, ranging from passive interventions such as posters and banners to active interventions such as student apps and enterprise days. Each programme consisted of a baseline survey followed by interventions and a repeat survey to calculate the change in perception. A clustering algorithm was also used to reveal the impact of combinations of interventions.

Findings
The study reveals three main findings: the use of social norms is an effective means of changing perceptions, the level of interventions and change in perceptions are positively correlated, and that the most effective combinations of interventions include the use of interactive feedback assemblies, enterprise days, parent and student apps and newsletters to parents.

Originality/value
The paper presents results from one of the largest social norm programmes aimed at improving young people’s perceptions and the first to use clustering methods to reveal the impact of combinations of intervention.