bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Quantification of Peptide Oxidation Isomers from Complex Mixtures
Authors: Khaje Niloofar Abolhasani , Sharp Joshua S. 
Published: November 2019

AbstractHydroxyl radical protein footprinting (HRPF) is a powerful technique for probing changes in protein topography, based on quantifying the amount of oxidation of different regions of a protein. While quantification of HRPF oxidation at the peptide level is relatively common, quantification at the residue level is challenging due to the influence of oxidation on MS/MS fragmentation and the large number of complex and only partially chromatographically resolved isomeric peptide oxidation products. HRPF quantification of isomeric peptide oxidation products (where the peptide sequence is the same but isomeric oxidation products are formed at different sites) at the residue level by electron transfer dissociation tandem mass spectrometry (ETD MS/MS) has been demonstrated in both model peptides and HRPF products, but the method is hampered by the partial separation of oxidation isomers by reversed phase chromatography. This requires custom MS/MS methods to equally sample all isomeric oxidation products across their elution window, greatly increasing method development time and reducing the oxidation products quantified in a single LC-MS/MS run. Here we present a zwitterionic hydrophilic interaction capillary chromatography (ZIC-HILIC) method to ideally co-elute all isomeric peptide oxidation products while separating different peptides. This allows us to relatively quantify peptide oxidation isomers using an ETD MS/MS spectrum acquired at any point across the single peptide oxidation isomer peak, greatly simplifying data acquisition and data analysis at both the peptide and amino acid level.
Neural Responses and Perceptual Sensitivity to Sound Depend on Sound-Level Statistics
Authors: Herrmann Björn , Augereau Thomas , Johnsrude Ingrid S. 
Published: November 2019

AbstractSensitivity to sound-level statistics is crucial for optimal perception, but research has focused mostly on neurophysiological recordings, whereas behavioral evidence is sparse. We use electroencephalography (EEG) and behavioral methods to investigate how sound-level statistics affect neural activity and the detection of near-threshold changes in sound amplitude. We presented noise bursts with sound levels drawn from distributions with either a low or a high modal sound level. One participant group listened to the stimulation while EEG was recorded (Experiment I). A second group performed a behavioral amplitude-modulation detection task (Experiment II). Neural activity depended on sound-level statistical context in two different ways. Consistent with an account positing that the sensitivity of neurons to sound intensity adapts to ambient sound level, responses for higher-intensity bursts were larger in low-mode than high-mode contexts, whereas responses for lower-intensity bursts did not differ between contexts. In contrast, a concurrent slow neural response indicated prediction-error processing: The response was larger for bursts at intensities that deviated from the predicted statistical context compared to those not deviating. Behavioral responses were consistent with prediction-error processing, but not with neural adaptation. Hence, neural activity adapts to sound-level statistics, but fine-tuning of perceptual sensitivity appears to involve neural prediction-error responses.
Differential activation of G-protein-mediated signalling by synthetic cannabinoid receptor agonists
Authors: Sachdev Shivani , Banister Samuel D. , Santiago Marina , Bladen Chris , Kassiou Michael , Connor Mark 
Published: November 2019

AbstractSynthetic cannabinoid receptor agonists (SCRAs) are new psychoactive substances associated with acute intoxication and even death. However, the molecular mechanisms through which SCRAs may exert their toxic effects remain unclear - including the potential differential activation of G protein subtypes by CB1, a major target of SCRA. We measured CB1-mediated activation of Gαs and Gαi/o proteins by SCRAs by examining stimulation (PTX-treated) as well as inhibition (non-PTX treated) of forskolin-induced cAMP accumulation in HEK cells stably expressing CB1. Real-time measurements of stimulation and inhibition of cAMP levels were made using a BRET biosensor. We found that the maximum concentration of SCRAs tested (10 μM), increased cAMP levels 12 to 45% above that produced by forskolin alone, while the phytocannabinoid THC did not significantly alter cAMP levels in PTX-treated HEK-CB1 cells. All SCRAs had greater potency to inhibit of forskolin-induced cAMP levels than to stimulate cAMP levels. The rank order of potencies for SCRA stimulation of cAMP (Gαs) was PB-22 > 5F-MDMB-PICA > JWH-018 > AB-FUBINACA > XLR-11. By contrast, the potency of SCRAs for inhibition of cAMP (Gαi/o) was 5F-MDMB-PICA > AB-FUBINACA > PB-22 > JWH-018 > XLR-11. The different rank order of potency of the SCRAs to stimulate Gαs-like signalling compared to Gαi/o signalling suggests differences in G protein preference between SCRAs. Understanding the apparent differences among these drugs may contribute to unravelling their complex effects in humans.
Benchmark of tools for CNV detection from NGS panel data in a genetic diagnostics context
Authors: Moreno-Cabrera José Marcos , Valle Jesús del , Castellanos Elisabeth , Feliubadaló Lidia , Pineda Marta , Brunet Joan , Serra Eduard , Capellà Gabriel , Lázaro Conxi , Gel Bernat 
Published: November 2019

ABSTRACTMotivationAlthough germline copy number variants (CNVs) are the genetic cause of multiple hereditary diseases, detecting them from targeted next-generation sequencing data (NGS) remains a challenge. Existing tools perform well for large CNVs but struggle with single and multi-exon alterations. The aim of this work is to evaluate CNV calling tools working on gene panel NGS data with CNVs up to single-exon resolution and their suitability as a screening step before orthogonal confirmation in genetic diagnostics strategies.ResultsFive tools (DECoN, CoNVaDING, panelcn.MOPS, ExomeDepth and CODEX2) were tested against four genetic diagnostics datasets (495 samples, 231 CNVs), using the default and sensitivity-optimized parameters. Most tools were highly sensitive and specific, but the performance was dataset-dependant. In our in-house datasets, DECoN and panelcn.MOPS with optimized parameters showed enough sensitivity to be used as screening methods in genetic diagnostics.AvailabilityBenchmarking-optimization code is freely available athttps://github.com/TranslationalBioinformaticsIGTP/CNVbenchmarkeR.
Affinity of rhodopsin to raft enables the aligned oligomer formation from dimers: Coarse-grained molecular dynamics simulation of disk membranes
Authors: Kaneshige Yukito , Hayashi Fumio , Morigaki Kenichi , Tanimoto Yasushi , Yamashita Hayato , Fuji Masashi , Awazu Akinori 
Published: November 2019

AbstractThe visual photopigment protein rhodopsin (Rh) is a typical G protein-coupled receptor (GPCR) that initiates the phototransduction cascade in retinal disk membrane of rod-photoreceptor cells. Rh molecule has a tendency to form dimer, and the dimer tends to form rows, which is suggested to heighten phototransduction efficiency in single-photon regime. In addition, the dimerization confers Rh an affinity for lipid raft, i.e. raftophilicity. However, the mechanism by which Rh-dimer raftophilicity contributes to the organization of the higher order structure remains unknown. In this study, we performed coarse-grained molecular dynamics simulations of a disk membrane model containing unsaturated lipids, saturated lipids with cholesterol, and Rh-dimers. We described the Rh-dimers by two-dimensional particle populations where the palmitoyl moieties of each Rh exhibits raftophilicity. We simulated the structuring of Rh in a disk for two types of Rh-dimer, i.e., the most and second most stable Rh dimers, which exposes the raftophilic regions at the dimerization-interface (H1/H8 dimer) and two edges away from the interface (H4/H5 dimer), respectively. Our simulations revealed that only the H1/H8 dimer could form a row structure. A small number of raftophilic lipids recruited to and intercalated in a narrow space between H1/H8 dimers stabilize the side-by-side interaction between dimers in a row. Our results implicate that the nano-sized lipid raft domains act as a “glue” to organize the long row structures of Rh-dimers.
Cutting in-line with iron: ribosomal function and non-oxidative RNA cleavage
Authors: Guth-Metzler Rebecca , Bray Marcus S. , Frenkel-Pinter Moran , Suttapitugsakul Suttipong , Montllor-Albalate Claudia , Bowman Jessica C. , Wu Ronghu , Reddi Amit R. , Okafor C. Denise , Glass Jennifer B. , Williams Loren Dean 
Published: November 2019

AbstractDivalent metal cations are essential to the structure and function of the ribosome. Previous characterizations of the ribosome performed under standard laboratory conditions have implicated Mg2+ as a primary mediator of ribosomal structure and function. Possible contributions of Fe2+ as a ribosomal cofactor have been largely overlooked, despite the ribosome’s early evolution in a high Fe2+ environment, and its continued use by obligate anaerobes inhabiting high Fe2+ niches. Here we show that (i) Fe2+ cleaves RNA by in-line cleavage, a non-oxidative mechanism that has not previously been shown experimentally for this metal, (ii) the first-order rate constant with respect to divalent cations is more than 200 times greater with Fe2+ than with Mg2+, (iii) functional ribosomes are associated with Fe2+ after purification from cells grown under low O2 and high Fe2+, and (iv) a small fraction of Fe2+ that is associated with the ribosome is not exchangeable with surrounding divalent cations, presumably because it is tightly coordinated by rRNA and buried in the ribosome. In total, these results expand the ancient role of iron in biochemistry and highlight a possible new mechanism of iron toxicity.Key PointsFe2+ cleaves rRNA by a non-oxidative in-line cleavage mechanism that is more than 200 times faster than in-line cleavage with Mg2+;ribosomes purified from cells grown under low O2 and high Fe2+ retain ~10 Fe2+ ions per ribosome and produce as much protein as low O2, high Mg2+-grown ribosomes;a small fraction (~2%) of Fe2+ that is associated with the ribosome is not exchangeable.
Increased efficacy of histone methyltransferase G9a inhibitors against MYCN-amplified Neuroblastoma
Authors: Bellamy Jacob , Szemes Marianna , Melegh Zsombor , Dallosso Anthony , Kollareddy Madhu , Catchpoole Daniel , Malik Karim 
Published: November 2019

AbstractTargeted inhibition of proteins modulating epigenetic changes is an increasingly important priority in cancer therapeutics, and many small molecule inhibitors are currently being developed. In the case of neuroblastoma (NB), a paediatric solid tumour with a paucity of intragenic mutations, epigenetic deregulation may be especially important. In this study we validate the histone methyltransferase G9a/EHMT2 as being associated with indicators of poor prognosis in NB. Immunological analysis of G9a protein shows it to be more highly expressed in NB cell-lines with MYCN amplification, which is a primary determinant of dismal outcome in NB patients. Furthermore, G9a protein in primary tumours is expressed at higher levels in poorly differentiated/undifferentiated NB, and correlates with high EZH2 expression, a known co-operative oncoprotein in NB. Our functional analyses demonstrate that siRNA-mediated G9a depletion inhibits cell growth in all NB cell lines, but, strikingly, only triggers apoptosis in NB cells with MYCN amplification, suggesting a synthetic lethal relationship between G9a and MYCN. This pattern of sensitivity is also evident when using small molecule inhibitors of G9a, UNC0638 and UNC0642. The increased efficacy of G9a inhibition in the presence of MYCN-overexpression is also demonstrated in the SHEP-21N isogenic model with tet-regulatable MYCN. Finally, using RNA sequencing, we identify several potential tumour suppressor genes that are reactivated by G9a inhibition in NB, including the CLU, FLCN, AMHR2 and AKR1C1-3. Together, our study underlines the under-appreciated role of G9a in NB, especially in MYCN-amplified tumours.
The cell-wall-localised BETA-XYLOSIDASE 4 contributes to immunity of Arabidopsis against Botrytis cinerea
Authors: Guzha Athanas , McGee Robert , Hartken Denise , Scholz Patricia , Lüdke Daniel , Bauer Kornelia , Wenig Marion , Zienkiewicz Krzysztof , Feussner Ivo , Vlot A. Corina , Wiermer Marcel , Haughn George , Ischebeck Till 
Published: November 2019

ABSTRACTPlant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. The primary cell wall of multicellular plants predominantly consists of cellulose, hemicellulose and pectin. In Arabidopsis, a cell wall-localised protein, BETA-XYLOSIDASE 4 (BXL4) that belongs to a seven-member BETA-XYLOSIDASE (BXL) gene family was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea and mechanical wounding in a jasmonoyl isoleucine (JA-Ile) dependent manner. Ectopic expression of the BXL4 gene in Arabidopsis seed coat epidermal cells was able to rescue a bxl1 mutant phenotype suggesting that like BXL1, BXL4, had both xylosidase and arabinosidase activity and acts in mura on cell wall polysaccharides. bxl4 mutants show a compromised resistance to B. cinerea. Upon infection, bxl4 mutants accumulated reduced levels of JA-Ile and camalexin. Conditional overexpression of BXL4 resulted in enhanced expression of PDF1.2 and PAD3 transcripts both before and after B. cinerea infection. This was associated with reduced susceptibility of the transgenic lines to B. cinerea. These data suggest that remodelling or degradation of one or more cell wall polysaccharides is important for plant immunity against B. cinerea and plays a role in pathogen-induced JA-Ile and camalexin accumulation.One-sentence summaryBXL4 is a putative bifunctional xylosidase/arabinofuranisodase localising to the apoplast, important for immunity against the necrotrphic pathogen B. cinerea.
A whole-genome scan for association with invasion success in the fruit flyDrosophila suzukiiusing contrasts of allele frequencies corrected for population structure
Authors: Olazcuaga Laure , Loiseau Anne , Parrinello Hugues , Paris Mathilde , Fraimout Antoine , Guedot Christelle , Diepenbrock Lauren M. , Kenis Marc , Zhang Jinping , Chen Xiao , Borowieck Nicolas , Facon Benoit , Vogt Heidrun , Price Donald K. , Vogel Heiko , Prud’homme Benjamin , Estoup Arnaud , Gautier Mathieu 
Published: November 2019

AbstractEvidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here we characterized the genome response of the spotted wing drosophilaDrosophila suzukiiduring the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic variants associated with the status (invasive versus native) of the sampled populations based on a newly developed statistic, we calledC2, that contrasts allele frequencies corrected for population structure. This new statistical framework has been implemented in an upgraded version of the program BayPass. We identified a relatively small set of single nucleotide polymorphisms (SNPs) that show a highly significant association with the invasive status of populations. In particular, two genesRhoGEF64Candcpo, the latter contributing to natural variation in several life-history traits (including diapause) inDrosophila melanogaster, contained SNPs significantly associated with the invasive status in the two separate main invasion routes ofD. suzukii. Our methodological approaches can be applied to any other invasive species, and more generally to any evolutionary model for species characterized by non-equilibrium demographic conditions for which binary covariables of interest can be defined at the population level.
Maternal exposure to cigarette smoking induces immediate and durable changes in placental DNA methylation affecting enhancer and imprinting control regions
Authors: Rousseaux Sophie , Seyve Emie , Chuffart Florent , Bourova-Flin Ekaterina , Benmerad Meriem , Charles Marie-Aline , Forhan Anne , Heude Barbara , Siroux Valérie , Slama Remy , Tost Jorg , Vaiman Daniel , Khochbin Saadi , Lepeule Johanna ,   the EDEN mother-child cohort study group
Published: November 2019

AbstractObjectiveExposure to cigarette smoking during pregnancy has been robustly associated with cord blood DNA methylation. However, little is known about such effects on the placenta; in particular, whether cigarette smoking before pregnancy could also induce epigenetic alterations in the placenta of former smokers is unknown.Design and resultsPlacental DNA methylation levels were measured in 568 women and compared among non-smokers and women either smoking during their pregnancy or who had ceased smoking before pregnancy. An Epigenome Wide Association Study identified 344 Differentially Methylated Regions (DMRs) significantly associated with maternal smoking status. Among these 344 DMRs, 262 showed “reversible” alterations of DNA methylation, only present in the placenta of current smokers, whereas 44 were also found altered in former smokers, whose placenta had not been exposed directly to cigarette smoking. This observation was further supported by a significant demethylation of LINE-1 sequences in the placentas of both current (−0.43 (−0.83 to −0.02)) and former smokers (−0.55 (−1.02 to −0.08)) compared to nonsmokers. A comparative analysis of the epigenome landscape based on the ENCODE placenta data demonstrated an enrichment of all 344 DMRs in enhancers histone marks. Additionally, smoking-associated DMRs were found near and/or overlapping with 13 imprinting gene clusters encompassing 18 imprinted genes.ConclusionsDNA methylation patterns alterations were found in 344 genomic regions in the placenta of women smoking during their pregnancy, including 44 DMRs and LINE-1 elements, where methylation changes persisted in former smokers, supporting the hypothesis of an “epigenetic memory” of exposure to cigarette smoking before pregnancy. Enhancers regions, including imprinting control regions were also particularly affected by placenta methylation changes associated to smoking, suggesting a biological basis for the sensitivity of these regions to tobacco exposure and mechanisms by which fetal development could be impacted.
Like a conductor: whole-class discussion in English classrooms
Authors: Reynolds Todd 
Published: November 2019

PurposeAfter interviewing teachers about their beliefs on discussion, the author observed four English teachers as they led class discussions. The purpose of this study is to see what kinds of discussion were happening, and what teachers were doing to facilitate those discussions.Design/methodology/approachThe author observed six English class sessions with discussion as a technique and transcribed each. To analyze the discussion events (DEs), the author focused on the addressivity of the teachers’ comments, and plotted the DEs on a four-quadrant system of analysis. The quadrants helped to move beyond the value-laden dichotomy between monologic and dialogic discussion, and to better understand what teachers are doing.FindingsThe majority of class sessions were classified as convergent-active but teachers used a variety of discussions. In particular, teachers were concerned about control, so they used three techniques to keep procedural control as follows: taking over the discussion, creating specific procedures and using the Initiation-Response-Evaluation format in different ways.Originality/valueInstead of focusing on a dichotomy this method of analysis opens up the possibility for labeling different kinds of dialogic instruction, like the teacher-as-conductor form of convergent-active discussions. This can help teachers understand that addressivity and purpose matter as they create their discussions but also that various forms of discussion are necessary in the classroom. Incorporating dialogic instruction has been difficult for teachers; this method can help describe what they are doing while not devaluing the kinds of discussion that are taking place.
Emerging theory of teacher resilience: a situational analysis
Authors: Drew Sally Valentino , Sosnowski Cathy 
Published: November 2019

PurposeThis study aims to explore the construct of teacher resilience. Researchers examined the relationship among complex risk (constraining) factors leading to burnout and attrition, as well as protective (enabling) factors that allow teachers to adapt and thrive within stressful school settings.Design/methodology/approachThis paper presents results from three focus groups comprised of 33 English language arts teachers across diverse school districts. Utilizing situational analysis, developed from grounded theory, the research plan included six stages: development of initial situational map honoring theoretical sensitivity, theoretical sampling, data collection, coding, memoing, sorting, revising of the initial map based on analysis and literature review to develop the relational map.FindingsThree propositions emerged beginning to comprise a theory of teacher resilience. (1) Resilient teachers embed roots in their school communities to withstand challenges, pulling from a sense of purpose to navigate constraining factors and benefit from enabling factors. (2) Resilient teachers embrace uncertainty, reframing negative experiences into learning experiences. Reframing helps teachers retain power, not cede it to situations, which helps balance constraining and enabling factors. (3) Teachers use relationships with colleagues, students and school leaders to endure challenges. The dynamic interaction between internal and external enabling and constraining factors is depicted on the situational map illustrating how factors counterbalance to either predict positive outcomes such as resilience and agency or negative outcomes such as burnout or attrition.Originality/valueDespite a robust international evidence base, there is a dearth of US studies exploring teacher resilience. This study proposes a theory of teacher resilience relevant to US schools and recommends practical applications and future research.
Influence of transportation infrastructure on the relationship between institutions and economic performance
Authors: Wong Mei Chi , Yip Tsz Leung 
Published: November 2019

Purpose
This study aims to analyse the observation that the economics of many countries have boomed after the input of substantial investments into physical and social infrastructures.

Design/methodology/approach
A structural equation model is formulated to examine the effect of transportation infrastructure on the relationship between institutions and gross domestic product per capita (GDPPC). This study further differentiates between developed and developing economies.

Findings
The study identifies the different roles of transportation infrastructure in mediating the relationship between institutions and average income in these two types of economy. Institutions and transportation infrastructure positively influence GDPPC, whereas institutions positively influence transportation infrastructure. In addition, the results found indirect influence of institutions on GDPPC via transportation infrastructure.

Originality/value
This study provides new insights into international business studies based on institutional theory and factor-mobility theory.