bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stochastic sensing of Angiotensin II with lysenin channels
Authors: Shrestha Nisha , Bryant Sheenah L. , Thomas Christopher , Richtsmeier Devon , Pu Xinzhu , Tinker Juliette , Fologea Daniel 
Published: May 2017

AbstractThe ability of pore-forming proteins to interact with various analytes has found vast applicability in single molecule sensing and characterization. In spite of their abundance in organisms from all kingdoms of life, only a few pore-forming proteins have been successfully reconstituted in artificial membrane systems for sensing purposes. Lysenin, a pore-forming toxin extracted from the earthworm E. fetida, inserts large conductance nanopores in lipid membranes containing sphingomyelin. Here we show that single lysenin channels may function as stochastic nanosensors by allowing the short cationic peptide angiotensin II to be electrophoretically driven through the conducting pathway. Long-term translocation experiments performed using large populations of lysenin channels allowed unequivocal identification of the unmodified analyte by Liquid Chromatography-Mass Spectrometry. However, application of reverse voltages or irreversible blockage of the macroscopic conductance of lysenin channels by chitosan addition prevented analyte translocation. This investigation demonstrates that lysenin channels have the potential to function as nano-sensing devices capable of single peptide molecule identification and characterization, which may be further extended to other macromolecular analytes.
Proteomic comparisons of opaque and transparent variants of Streptococcus pneumoniae by two dimensional-differential gel electrophoresis
Authors: Chai Melissa H. , Weiland Florian , Harvey Richard M. , Hoffmann Peter , Ogunniyi Abiodun D. , Paton James C. 
Published: May 2017

AbstractStreptococcus pneumoniae (the pneumococcus) is a human pathogen, accounting for massive global morbidity and mortality. Although asymptomatic colonization of the nasopharynx almost invariably precedes disease, the critical determinants enabling pneumococcal progression from this niche to cause invasive disease are poorly understood. One mechanism proposed to be central to this transition involves opacity phase variation, whereby pneumococci harvested from the nasopharynx are typically transparent, while those simultaneously harvested from the blood are opaque. Here, we used two dimensional-differential gel electrophoresis (2D-DIGE) to compare protein expression profiles of transparent and opaque variants of 3 pneumococcal strains, D39 (serotype 2), WCH43 (serotype 4) and WCH16 (serotype 6A) in vitro. One spot comprising a mixture of capsular polysaccharide biosynthesis protein and other proteins was significantly up-regulated in the opaque phenotype in all 3 strains; other proteins were differentially regulated in a strain-specific manner. We conclude that pneumococcal phase variation is a complex and multifactorial process leading to strain-specific pathogenicity.
Dependence of Solidification for Bi2Te3−xSex Alloys on Their Liquid States
Authors: Yu Yuan , Wu Zhan , Cojocaru-Mirédin Oana , Zhu Bin , Wang Xiao-Yu , Gao Na , Huang Zhong-Yue , Zu Fang-Qiu 
Published: May 2017

AbstractThe resistivity versus temperature (ρ-T) behaviours of liquid n-type Bi2Te3−x
Se
x
(x = 0.3, 0.45 and 0.6) alloys are explored up to 1050 °C. A clear hump is observed on all ρ-T curves of the three studied Bi2Te3−x
Se
x
melts during the heating process, which suggests that a temperature-induced liquid-liquid structural transition takes place in the melts. Based on this information, the solidification behaviours and microstructures of the alloys with different liquid states are investigated. The samples that experienced liquid structural transition show that the nucleation and growth undercooling degrees are conspicuously enlarged and the solidification time is shortened. As a result, the solidified lamellae are refined and homogenized, the prevalence of low-angle grain boundaries between these lamellae is increased, and the Vicker Hardness is enhanced. Atom probe tomography analyses prove that there is no segregation or nanoprecipitation within the grains, but the Te-rich eutectic structure and the evolution of composition near the Te-matrix phase boundary are investigated in a sample that experienced liquid structural transition. Our work implies that the solidification behaviours of Bi2Te3−xSex alloys are strongly related to their parent liquid states, providing an alternative approach to tailor the thermoelectric and mechanical properties even when only a simple solidification process is performed.
Reducing mitochondrial reads in ATAC-seq using CRISPR/Cas9
Authors: Montefiori Lindsey , Hernandez Liana , Zhang Zijie , Gilad Yoav , Ober Carole , Crawford Gregory , Nobrega Marcelo , Jo Sakabe Noboru 
Published: May 2017

AbstractATAC-seq is a high-throughput sequencing technique that identifies open chromatin. Depending on the cell type, ATAC-seq samples may contain ~20–80% of mitochondrial sequencing reads. As the regions of open chromatin of interest are usually located in the nuclear genome, mitochondrial reads are typically discarded from the analysis. We tested two approaches to decrease wasted sequencing in ATAC-seq libraries generated from lymphoblastoid cell lines: targeted cleavage of mitochondrial DNA fragments using CRISPR technology and removal of detergent from the cell lysis buffer. We analyzed the effects of these treatments on the number of usable (unique, non-mitochondrial) reads and the number and quality of peaks called, including peaks identified in enhancers and transcription start sites. Both treatments resulted in considerable reduction of mitochondrial reads (1.7 and 3-fold, respectively). The removal of detergent, however, resulted in increased background and fewer peaks. The highest number of peaks and highest quality data was obtained by preparing samples with the original ATAC-seq protocol (using detergent) and treating them with CRISPR. This strategy reduced the amount of sequencing required to call a high number of peaks, which could lead to cost reduction when performing ATAC-seq on large numbers of samples and in cell types that contain a large amount of mitochondria.
Dynamics and ligand-induced conformational changes in human prolyl oligopeptidase analyzed by hydrogen/deuterium exchange mass spectrometry
Authors: Tsirigotaki Alexandra , Elzen Roos Van , Veken Pieter Van Der , Lambeir Anne-Marie , Economou Anastassios 
Published: May 2017

AbstractProlyl oligopeptidase (PREP) is conserved in many organisms across life. It is involved in numerous processes including brain function and neuropathology, that require more than its strict proteolytic role. It consists of a seven-bladed β-propeller juxtaposed to a catalytic α/β-hydrolase domain. The conformational dynamics of PREP involved in domain motions and the gating mechanism that allows substrate accessibility remain elusive. Here we used Hydrogen Deuterium eXchange Mass Spectrometry (HDX-MS) to derive the first near-residue resolution analysis of global PREP dynamics in the presence or absence of inhibitor bound in the active site. Clear roles are revealed for parts that would be critical for the activation mechanism. In the free state, the inter-domain interface is loose, providing access to the catalytic site. Inhibitor binding “locks” the two domains together exploiting prominent interactions between the loop of the first β-propeller blade and its proximal helix from the α/β-hydrolase domain. Loop A, thought to drive gating, is partially stabilized but remains flexible and dynamic. These findings provide a conformational guide for further dissection of the gating mechanism of PREP, that would impact drug development. Moreover, they offer a structural framework against which to study proteolysis-independent interactions with disordered proteins like α-synuclein involved in neurodegenerative disease.
Adaptive stochastic resonance for unknown and variable input signals
Authors: Krauss Patrick , Metzner Claus , Schilling Achim , Schütz Christian , Tziridis Konstantin , Fabry Ben , Schulze Holger 
Published: May 2017

AbstractAll sensors have a threshold, defined by the smallest signal amplitude that can be detected. The detection of sub-threshold signals, however, is possible by using the principle of stochastic resonance, where noise is added to the input signal so that it randomly exceeds the sensor threshold. The choice of an optimal noise level that maximizes the mutual information between sensor input and output, however, requires knowledge of the input signal, which is not available in most practical applications. Here we demonstrate that the autocorrelation of the sensor output alone is sufficient to find this optimal noise level. Furthermore, we demonstrate numerically and analytically the equivalence of the traditional mutual information approach and our autocorrelation approach for a range of model systems. We furthermore show how the level of added noise can be continuously adapted even to highly variable, unknown input signals via a feedback loop. Finally, we present evidence that adaptive stochastic resonance based on the autocorrelation of the sensor output may be a fundamental principle in neuronal systems.
The distribution of reflexive intensifiers in learner English
Authors: Rankin Tom 
Published: May 2017

AbstractThis study investigates the use of reflexive intensifiers by L1 German-speaking learners of L2 English against the background of previous research which has identified non-target-like distribution of such features which are sensitive to discourse constraints and/or register variation. Occurrences of intensified NPs are compared between theLouvain Corpus of Native English Essaysand the German component of theInternational Corpus of Learner English.In line with previous research, it is found that learners overuse this lexico-grammatical means of information highlighting. However, there is only significant overuse of a specific sub-type of intensifier, the inclusive adverbial intensifier. These results are discussed in terms of (i) general learnability considerations which may account for learners’ problems in mastering the use of register-sensitive information-structural patterns, and (ii) pedagogical issues which arise in connection with addressing residual non-target performance in written production beyond the stage at which target properties of lexico-grammar have generally been acquired.
Quantitative research methods and study quality in learner corpus research
Authors: Paquot Magali , Plonsky Luke 
Published: May 2017

AbstractThis study aims to provide the first empirical assessment of quantitative research methods and study quality in learner corpus research. We systematically review quantitative primary studies referenced in theLearner Corpus Bibliography(LCB), a representative bibliography of learner corpus research maintained by theLearner Corpus Associationwhich contained 1,276 references when the current study began. Each primary study in the LCB was coded for over fifty features representing six dimensions: (a) publication type (i.e. conference paper, book chapter, journal article), (b) research focus (e.g. lexis, grammar), (c) methodological features (e.g. keyword analysis, error analysis, use of reference corpus), (d) statistical analyses (e.g. X²,t-test, regression analysis), and (e) reporting practices (e.g. reliability coefficients, means). Results point to several systematic strengths as well as many flaws, such as the absence of research questions, incomplete and inconsistent reporting practices (e.g. means without standard deviations), and lack of statistical literacy (i.e. LCR studies generally overrely on tests of statistical significance, do not report effect sizes, rarely check or report whether statistical assumptions have been met, and rarely use multivariate analyses). Improvements over time, however, are clearly noted and there are signs that, like other related disciplines, learner corpus research is slowly undergoing methodological reform.
Long-Term PM2.5 Exposure and Respiratory, Cancer, and Cardiovascular Mortality in Older US Adults
Authors: Pun Vivian C , Kazemiparkouhi Fatemeh , Manjourides Justin , Suh Helen H 
Published: May 2017

Abstract
The impact of chronic exposure to fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5)) on respiratory disease and lung cancer mortality is poorly understood. In a cohort of 18.9 million Medicare beneficiaries (4.2 million deaths) living across the conterminous United States between 2000 and 2008, we examined the association between chronic PM2.5 exposure and cause-specific mortality. We evaluated confounding through adjustment for neighborhood behavioral covariates and decomposition of PM2.5 into 2 spatiotemporal scales. We found significantly positive associations of 12-month moving average PM2.5 exposures (per 10-μg/m3 increase) with respiratory, chronic obstructive pulmonary disease, and pneumonia mortality, with risk ratios ranging from 1.10 to 1.24. We also found significant PM2.5-associated elevated risks for cardiovascular and lung cancer mortality. Risk ratios generally increased with longer moving averages; for example, an elevation in 60-month moving average PM2.5 exposures was linked to 1.33 times the lung cancer mortality risk (95% confidence interval: 1.24, 1.40), as compared with 1.13 (95% confidence interval: 1.11, 1.15) for 12-month moving average exposures. Observed associations were robust in multivariable models, although evidence of unmeasured confounding remained. In this large cohort of US elderly, we provide important new evidence that long-term PM2.5 exposure is significantly related to increased mortality from respiratory disease, lung cancer, and cardiovascular disease.
MetaSRA: normalized human sample-specific metadata for the Sequence Read Archive
Authors: Bernstein Matthew N , Doan AnHai , Dewey Colin N 
Published: May 2017

AbstractMotivationThe NCBI’s Sequence Read Archive (SRA) promises great biological insight if one could analyze the data in the aggregate; however, the data remain largely underutilized, in part, due to the poor structure of the metadata associated with each sample. The rules governing submissions to the SRA do not dictate a standardized set of terms that should be used to describe the biological samples from which the sequencing data are derived. As a result, the metadata include many synonyms, spelling variants and references to outside sources of information. Furthermore, manual annotation of the data remains intractable due to the large number of samples in the archive. For these reasons, it has been difficult to perform large-scale analyses that study the relationships between biomolecular processes and phenotype across diverse diseases, tissues and cell types present in the SRA.ResultsWe present MetaSRA, a database of normalized SRA human sample-specific metadata following a schema inspired by the metadata organization of the ENCODE project. This schema involves mapping samples to terms in biomedical ontologies, labeling each sample with a sample-type category, and extracting real-valued properties. We automated these tasks via a novel computational pipeline.Availability and implementationThe MetaSRA is available at metasra.biostat.wisc.edu via both a searchable web interface and bulk downloads. Software implementing our computational pipeline is available at http://github.com/deweylab/metasra-pipelineSupplementary informationSupplementary data are available at Bioinformatics online.
Cholinergic Grb2-Associated-Binding Protein 1 Regulates Cognitive Function
Authors: Lu Nan-Nan , Tan Chao , Sun Ning-He , Shao Ling-Xiao , Liu Xiu-Xiu , Gao Yin-Ping , Tao Rong-Rong , Jiang Quan , Wang Cheng-Kun , Huang Ji-Yun , Zhao Kui , Wang Guang-Fa , Liu Zhi-Rong , Fukunaga Kohji , Lu Ying-Mei , Han Feng 
Published: May 2017

AbstractGrb2-associated-binding protein 1 (Gab1) is a docking/scaffolding molecule known to play an important role in cell growth and survival. Here, we report that Gab1 is decreased in cholinergic neurons in Alzheimer’s disease (AD) patients and in a mouse model of AD. In mice, selective ablation of Gab1 in cholinergic neurons in the medial septum impaired learning and memory and hippocampal long-term potentiation. Gab1 ablation also inhibited SK channels, leading to an increase in firing in septal cholinergic neurons. Gab1 overexpression, on the other hand, improved cognitive function and restored hippocampal CaMKII autorphosphorylation in AD mice. These results suggest that Gab1 plays an important role in the pathophysiology of AD and may represent a novel therapeutic target for diseases involving cholinergic dysfunction.
A transcriptional serenAID: the role of noncoding RNAs in class switch recombination
Authors: Yewdell William T. , Chaudhuri Jayanta 
Published: May 2017

AbstractDuring an immune response, activated B cells may undergo class switch recombination (CSR), a molecular rearrangement that allows B cells to switch from expressing IgM and IgD to a secondary antibody heavy chain isotype such as IgG, IgA or IgE. Secondary antibody isotypes provide the adaptive immune system with distinct effector functions to optimally combat various pathogens. CSR occurs between repetitive DNA elements within the immunoglobulin heavy chain (Igh) locus, termed switch (S) regions and requires the DNA-modifying enzyme activation-induced cytidine deaminase (AID). AID-mediated DNA deamination within S regions initiates the formation of DNA double-strand breaks, which serve as biochemical beacons for downstream DNA repair pathways that coordinate the ligation of DNA breaks. Myriad factors contribute to optimal AID targeting; however, many of these factors also localize to genomic regions outside of the Igh locus. Thus, a current challenge is to explain the specific targeting of AID to the Igh locus. Recent studies have implicated noncoding RNAs in CSR, suggesting a provocative mechanism that incorporates Igh-specific factors to enable precise AID targeting. Here, we chronologically recount the rich history of noncoding RNAs functioning in CSR to provide a comprehensive context for recent and future discoveries. We present a model for the RNA-guided targeting of AID that attempts to integrate historical and recent findings, and highlight potential caveats. Lastly, we discuss testable hypotheses ripe for current experimentation, and explore promising ideas for future investigations.
Activation of group 2 innate lymphoid cells exacerbates and confers corticosteroid resistance to mouse nasal type 2 inflammation
Authors: Morikawa Taiyo , Fukuoka Ayumi , Matsushita Kazufumi , Yasuda Koubun , Iwasaki Naruhito , Akasaki Shoko , Fujieda Shigeharu , Yoshimoto Tomohiro 
Published: May 2017

Abstract
Both Th2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders are unclear. In this study, we investigated the cooperation of Th2 cells and ILC2s in a mouse model of nasal allergic disorder. To differentially activate Th2 cells and/or ILC2s in nasal mucosa, mice were intra-nasally administered ovalbumin (OVA) antigen, papain, an ILC2-activator, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 h after the final challenge. Intra-nasal administration of OVA and papain preferentially activated Th2 cells and ILC2s, respectively, in the nose. Both OVA and papain increased the nasal epithelial thickness and number of eosinophils, and their coadministration significantly enhanced the symptoms. Although T-/B-cell-deficient mice showed severely decreased nasal symptoms induced by OVA or OVA-plus-papain, the mice still showed slight papain-induced nasal symptoms. In ILC2-deficient mice, OVA-plus-papain-induced nasal symptoms were suppressed to the same level as OVA-alone. Similarly, IL-33- and ST2-deficient mice showed decreased OVA-plus-papain-induced nasal symptoms. IL-5 induced eosinophilia only, but IL-13 contributed to both nasal epithelial thickening and eosinophilia induced by OVA-plus-papain. Dexamethasone ameliorated OVA-alone-induced nasal epithelial thickening. However, OVA-plus-papain-induced nasal epithelial thickening was only partially controlled by dexamethasone. These results demonstrate that IL-33/ST2-pathway-mediated ILC2 activation exacerbated Th2-cell-induced nasal inflammation by producing IL-13. Although Th2-cell-alone-induced nasal inflammation was controlled by corticosteroid treatment, the activation of ILC2s conferred treatment resistance. Therefore, ILC2s and their activators could be therapeutic targets for treatment-refractory nasal allergic disorders.
On the level of cluster assembly bias in SDSS
Authors: Zu Ying , Mandelbaum Rachel , Simet Melanie , Rozo Eduardo , Rykoff Eli S. 
Published: May 2017

Abstract
Recently, several studies have discovered a strong discrepancy between the large-scale clustering biases of two subsamples of galaxy clusters at the same halo mass, split by their average projected membership distances 〈Rmem〉. The level of this discrepancy significantly exceeds the maximum halo assembly bias predicted by Λ cold dark matter (ΛCDM). We explore whether some of the large-scale bias differences could be caused by projection effects in 〈Rmem〉 due to other systems along the line of sight. We thoroughly investigate the assembly bias of the redMaPPer clusters in Sloan Digital Sky Survey (SDSS), by defining a new variant of the average membership distance estimator $\tilde{R}_{\mathrm{mem}}$ that is robust against projection effects in the cluster membership identification. Using the angular mark correlation functions, we show that the large-scale bias differences when splitting by 〈Rmem〉 can be mostly attributed to projection effects. After splitting by $\tilde{R}_{\mathrm{mem}}$, the anomalously large signal is reduced, giving a ratio of 1.02 ± 0.14 between the two clustering biases as measured from weak lensing. Using a realistic mock cluster catalogue, we predict that the bias ratio between two $\tilde{R}_{\mathrm{mem}}$-split subsamples should be ≃1.10, which is &gt;60 per cent weaker than the maximum halo assembly bias (1.24) when split by halo concentration. Therefore, our results demonstrate that the level of halo assembly bias exhibited by clusters in SDSS is consistent with the ΛCDM prediction. With a 10-fold increase in cluster numbers, deeper ongoing surveys will enable a more robust detection of halo assembly bias. Our findings also have important implications for quantifying the impact of projection effects on cosmological constraints using photometrically selected clusters.
New hard X-ray sources discovered in the ongoing INTEGRAL Galactic plane survey after 14 yr of observations
Authors: Krivonos Roman A. , Tsygankov Sergey S. , Mereminskiy Ilya A. , Lutovinov Alexander A. , Sazonov Sergey Yu. , Sunyaev Rashid A. 
Published: May 2017

Abstract
The International Gamma-Ray Astrophysics Laboratory (INTEGRAL) continues to successfully work in orbit after its launch in 2002. The mission provides the deepest ever survey of hard X-ray sources throughout the Galaxy at energies above 20 keV. We report on a catalogue of new hard X-ray source candidates based on the latest sky maps comprising 14 yr of data acquired with the IBIS telescope onboard INTEGRAL in the Galactic Plane (|b| &lt; 17.5°). The current catalogue includes in total 72 hard X-ray sources detected at S/N &gt; 4.7σ and not known to previous INTEGRAL surveys. Among them, 31 objects have also been detected in the on-going all-sky survey by the BAT telescope of the Swift observatory. For 26 sources on the list, we suggest possible identifications: 21 active galactic nuclei, two cataclysmic variables, two isolated pulsars or pulsar wind nebulae and one supernova remnant; 46 sources from the catalogue remain unclassified.