bluuebunny/crossref_metadata_2025_split huggingface dataset:
TFmapper: A tool for searching putative factors regulating gene expression using ChIP-seq data
Authors: Zeng Jianming , Li Gang 
Published: February 2018

AbstractBackgroundNext-generation sequencing coupled to chromatin immunoprecipitation (ChIP-seq), DNase I hypersensitivity (DNase-seq) and the transposase-accessible chromatin assay (ATAC-seq) has generated enormous amounts of data, markedly improved our understanding of the transcriptional and epigenetic control of gene expression. To take advantage of the availability of such datasets and provide clues on what factors, including transcription factors, epigenetic regulators and histone modifications, potentially regulates the expression of a gene of interest, a tool for simultaneous queries of multiple datasets using symbols or genomic coordinates as search terms is needed.ResultsIn this study, we annotated the peaks of thousands of ChIP-seq datasets generated by ENCODE project, or ChIP-seq/DNase-seq/ATAC-seq datasets deposited in Gene Expression Omnibus and curated by CistromeDB; We built a MySQL database called TFmapper containing the annotations and associated metadata, allowing users without bioinformatics expertise to search across thousands of datasets to identify factors targeting a genomic region/gene of interest in a specified sample through a web interface. Users can also visualize multiple peaks in genome browsers and download the corresponding sequences.ConclusionTFmapper will help users explore the vast amount of publicly available ChIP-seq/DNase-seq/ATAC-seq data, and perform integrative analyses to understand the regulation of a gene of interest. The web server is freely accessible at http://www.tfmapper.org/.
KrakenHLL: Confident and fast metagenomics classification using unique k-mer counts
Authors: Breitwieser FP , Salzberg SL 
Published: February 2018

AbstractFalse positive identifications are a significant problem in metagenomic classification. We present KrakenHLL, a novel metagenomic classifier that combines the fast k-mer based classification of Kraken with an efficient algorithm for assessing the coverage of unique k-mers found in each species in a dataset. On various test datasets, KrakenHLL gives better recall and F1-scores than other methods, and effectively classifies and distinguishes pathogens with low abundance from false positives in infectious disease samples. By using the probabilistic cardinality estimator HyperLogLog (HLL), KrakenHLL is as fast as Kraken and requires little additional memory.
SMRT-Cappable-seq reveals complex operon variants in bacteria
Authors: Yan Bo , Boitano Matthew , Clark Tyson , Ettwiller Laurence 
Published: February 2018

AbstractCurrent methods for genome-wide analysis of gene expression requires shredding original transcripts into small fragments for short-read sequencing. In bacteria, the resulting fragmented information hides operon complexity. Additionally,in-vivoprocessing of transcripts confounds the accurate identification of the 5’ and 3’ ends of operons. Here we developed a novel methodology called SMRT-Cappable-seq that combines the isolation of unfragmented primary transcripts with single-molecule long read sequencing. Applied toE. coli, this technology results in an unprecedented definition of the transcriptome with 34% of the known operons being extended by at least one gene. Furthermore, 40% of transcription termination sites have read-through that alters the gene content of the operons. As a result, most of the bacterial genes are present in multiple operon variants reminiscent of eukaryotic splicing. By providing an unprecedented granularity in the operon structure, this study represents an important resource for the study of prokaryotic gene network and regulation.
Subtle left-right asymmetry of gene expression profiles in embryonic and foetal human brains
Authors: de Kovel Carolien G.F. , Lisgo Steven N. , Fisher Simon E. , Francks Clyde 
Published: February 2018

AbstractLeft-right laterality is an important aspect of human brain organization for which the genetic basis is poorly understood. Using RNA sequencing data we contrasted gene expression in left- and right-sided samples from several structures of the anterior central nervous systems of post mortem human embryos and fetuses. While few individual genes stood out as significantly lateralized, most structures showed evidence of laterality of their overall transcriptomic profiles. These left-right differences showed overlap with age-dependent changes in expression, indicating lateralized maturation rates, but not consistently in left-right orientation over all structures. Brain asymmetry may therefore originate in multiple locations, or if there is a single origin, it is earlier than 5 weeks post conception, with structure-specific lateralized processes already underway by this age. This pattern is broadly consistent with the weak correlations reported between various aspects of adult brain laterality, such as language dominance and handedness.
Specific Eph Receptor-Cytoplasmic Effector Signaling Mediated by SAM-SAM Domain Interactions
Authors: Wang Yue , Shang Yuan , Li Jianchao , Chen Weidi , Li Gang , Wan Jun , Liu Wei , Zhang Mingjie 
Published: February 2018

AbstractThe Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM-SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain numerous Eph SAM mutations identified in patients suffering from cancers and other diseases.
TCR-MHC Interaction Strength Defines Trafficking and Resident Memory Status of CD8 T cells in the Brain
Authors: Sanecka Anna , Yoshida Nagisa , Kolawole Elizabeth Motunrayo , Patel Harshil , Evavold Brian D. , Frickel Eva-Maria 
Published: February 2018

AbstractT cell receptor-Major histocompatibility complex (TCR-MHC) affinities span a wide range in a polyclonal T cell response, yet it is undefined how affinity shapes long-term properties of CD8 T cells during chronic infection with persistent antigen. Here, we investigate how the affinity of the TCR-MHC interaction shapes the phenotype of memory CD8 T cells in the chronicallyToxoplasma gondii-infectedbrain. We employed CD8 T cells from three lines of transnuclear (TN) mice that harbour in their endogenous loci different T cell receptors specific for the sameToxoplasmaantigenic epitope ROP7. The three TN CD8 T cell clones span a wide range of affinities to MHCI-ROP7. These three CD8 T cell clones have a distinct and fixed hierarchy in terms of effector function in response to the antigen measured as proliferation capacity, trafficking, T cell maintenance and memory formation. In particular, the T cell clone of lowest affinity does not home to the brain. The two higher affinity T cell clones show differences in establishing resident memory populations (CD103+) in the brain with the higher affinity clone persisting longer in the host during chronic infection. Transcriptional profiling of naïve and activated ROP7-specific CD8 T cells revealed thatKlf2encoding a transcription factor that is known to be a negative marker for T cell trafficking is upregulated in the activated lowest affinity ROP7 clone. Our data thus suggest that TCR-MHC affinity dictates memory CD8 T cell fate at the site of infection.
New insights on adaptation and population structure of cork oak using genotyping by sequencing
Authors: Pina-Martins F. , Baptista J. , Pappas G. , Paulo O. S. 
Published: February 2018

AbstractSpecies respond to global climatic changes in a local context. Understanding this process is paramount due to the pace of these changes. Tree species are particularly interesting to study in this regard due to their long generation times, sedentarism, and ecological and economic importance. Quercus suber L. is an evergreen forest tree species of the Fagaceae family with an essentially Western Mediterranean distribution. Despite frequent assessments of the species’ evolutionary history, large-scale genetic studies have mostly relied on plastidial markers, whereas nuclear markers have been used on studies with locally focused sampling strategies. The potential response of Q. suber to global climatic changes has also been studied, under ecological modelling. In this work, “Genotyping by Sequencing” (GBS) is used to derive 2,547 SNP markers to assess the species’ evolutionary history from a nuclear DNA perspective, gain insights on how local adaptation may be shaping the species’ genetic background, and to forecast how Q. suber may respond to global climatic changes from a genetic perspective. Results reveal an essentially unstructured species, where a balance between gene flow and local adaptation keeps the species’ gene pool somewhat homogeneous across its distribution, but at the same time allows variation clines for the individuals to cope with local conditions. “Risk of Non-Adaptedness” (RONA) analyses, suggest that for the considered variables and most sampled locations, the cork oak does not require large shifts in allele frequencies to survive the predicted climatic changes. However, more research is required to integrate these results with those of ecological modelling.
A critical role for Dna2 at unwound telomeres
Authors: Markiewicz-Potoczny Marta , Lisby Michael , Lydall David 
Published: February 2018

AbstractDna2 is a nuclease and helicase that functions redundantly with other proteins in Okazaki fragment processing, double strand break (DSB) resection and checkpoint kinase activation. Dna2 is an essential enzyme, required for yeast and mammalian cell viability. Here we report that numerous mutations affecting the DNA damage checkpoint suppressdna2Δ lethality inSaccharomyces cerevisiae.dna2Δ cells are also suppressed by deletion of helicases,PIF1andMPH1, and by deletion ofPOL32, a subunit of DNA polymerase δ. Alldna2Δ cells are temperature sensitive, have telomere length defects, and low levels of telomeric 3’ single stranded DNA (ssDNA). Interestingly, Rfa1, a subunit of the major ssDNA binding protein RPA, and the telomere specific ssDNA binding protein Cdc13, often co-localize indna2Δ cells. This suggests that telomeric defects often occur indna2Δ cells. There are several plausible explanations for why the most critical function of Dna2 is at telomeres. Telomeres modulate the DNA damage response (DDR) at chromosome ends, inhibiting resection, ligation and cell cycle arrest. We suggest that Dna2 nuclease activity contributes to modulating the DNA damage response at telomeres by removing telomeric C-rich ssDNA and thus preventing checkpoint activation.
Structural insights into the recognition of mono- and di-acetylated histones by the ATAD2B bromodomain
Authors: Lloyd Jonathan T. , McLaughlin Kyle , Lubula Mulu Y. , Gay Jamie C. , Dest Andrea , Gao Cong , Phillips Margaret , Tonelli Marco , Cornilescu Gabriel , Marunde Matthew R. , Evans Chiara M. , Boyson Samuel P. , Carlson Samuel , Keogh Michael-Christopher , Markley John L. , Frietze Seth , Glass Karen C. 
Published: February 2018

ABSTRACTBromodomains are chromatin reader modules that recognize acetylated lysine. Different bromodomains exhibit a preference for specific patterns of lysine acetylation marks on core and variant histone proteins, however, the functional relationships that exist between histone acetyllysine ligands and bromodomain recognition remain poorly understood. In this study, we examined the ligand specificity of the ATAD2B bromodomain and compared it to its closely related paralog in ATAD2. We show that the ATAD2B bromodomain selects for mono- and di-acetylated histones, and structural analysis identified key residues in the acetyllysine binding pocket that dictate ligand binding specificity. The X-ray crystal structure of the ATAD2B bromodomain in complex with an ATAD2 bromodomain inhibitor was solved at 2.4 Å resolution. This structure demonstrated that critical contacts required for bromodomain inhibitor coordination are conserved between the ATAD2/B bromodomains, and many of these residues play a dual role in acetyllysine recognition. We further characterized a variant of the ATAD2B bromodomain that through alternative splicing loses critical amino acids required for histone ligand and inhibitor coordination. Altogether our results outline the structural and functional features of the ATAD2B bromodomain and identify a novel mechanism important for regulating the interaction of the ATAD2B protein with chromatin.HIGHLIGHTSThe ATAD2B bromodomain recognizes mono- and di-acetylated histone ligands.Chemical shift perturbations outline the ATAD2B bromodomain acetyllysine binding pocket.An ATAD2B bromodomain-inhibitor complex reveals important binding contacts.An alternate splice variant in the ATAD2B bromodomain abolishes histone and inhibitor binding.
Postsynaptic Pannexin-1 Facilitates Anandamide Uptake to Modulate Glutamate Release and Enhance Network Excitability
Authors: Bialecki Jennifer , Weilinger Nicholas L. , Lohman Alexander W. , Vecchiarelli Haley A. , Robinson Jordan H.B. , Egaña Jon , Medizabal-Zubiaga Juan , Werner Allison C. , Grandes Pedro , Teskey G. Campbell , Hill Matthew N. , Thompson Roger J. 
Published: February 2018

AbstractProlonged neurotransmitter release following synaptic stimulation extends the time window for postsynaptic neurons to respond to presynaptic activity. This can enhance excitability and increase synchrony of outputs, but the prevalence of this at normally highly synchronous synapses is unclear. We show that the postsynaptic channel, pannexin-1 (Panx1) regulates prolonged glutamate release onto CA1 neurons. Block of postsynaptic (CA1 neuronal) Panx1 increased the frequency of glutamate neurotransmission and action potentials in these neurons following Schaffer collateral stimulation. When Panx1 was blocked, anandamide levels increase and activated transient receptor potential vanilloid 1 (TRPV1)-mediated glutamate release. This TRPV1-induced synaptic acitvity enhanced excitability and translated into a faster rate of TRPV1-dependent epileptogenesis induced by kindling. We conclude that Panx1 facilitates AEA clearance to maintain synchronous release onto CA1 neurons so that when AEA clearance is reduced, TRPV1 channels prolong glutamate neurotransmission to enhance network output to promote epileptiform activity.
Evolutionary rescue of sphericalmreBdeletion mutants of the rod-shape bacteriumPseudomonas fluorescensSBW25
Authors: Yulo P. Richard J. , Desprat Nicolas , Gerth Monica L. , Ritzl- Rinkenberger Barbara , Farr Andrew D. , Liu Yunhao , Zhang Xue-Xian , Miller Michael , Cava Felipe , Rainey Paul B. , Hendrickson Heather L. 
Published: February 2018

AbstractMaintenance of rod-shape in bacterial cells depends on the actin-like protein MreB. Deletion ofmreBfromPseudomonas fluorescensSBW25 results in viable spherical cells of variable volume and reduced fitness. Using a combination of time-resolved microscopy and biochemical assay of peptidoglycan synthesis, we show that reduced fitness is a consequence of perturbed cell size homeostasis that arises primarily from differential growth of daughter cells. A 1,000-generation selection experiment resulted in rapid restoration of fitness with derived cells retaining spherical shape. Mutations in the peptidoglycan synthesis protein Pbp1A were identified as the main route for evolutionary rescue with genetic reconstructions demonstrating causality. Compensatorypbp1Amutations that targeted transpeptidase activity enhanced homogeneity of cell wall synthesis on lateral surfaces and restored cell size homeostasis. Mechanistic explanations require enhanced understanding of why deletion ofmreBcauses heterogeneity in cell wall synthesis. We conclude by presenting two testable hypotheses, one of which posits that heterogeneity stems from non-functional cell wall synthesis machinery, while the second posits that the machinery is functional, albeit stalled. Overall, our data provide support for the second hypothesis and draw attention to the importance of balance between transpeptidase and glycosyltransferase functions of peptidoglycan building enzymes for cell shape determination.
Surface morphology studies and kinetic-thermodynamic characterization of steels treated in 5.0 M HCl medium: hot-dip galvanizing application
Authors: El Kacimi Younes , Galai Mouhsine , Alaoui Khaoula , Touir Rachid , Ebn Touhami Mohamed 
Published: February 2018

PurposeThe purpose of this paper is to study the effect of silicon and phosphorus content in steel suitable for galvanizing on its corrosion and inhibitor adsorption processes in steels/cetyltrimethylammonium bromide combined and KI (mixture)/5.0 M hydrochloric acid systems has been studied in relation to the temperature using chemical (weight loss), Tafel polarization, electrochemical impedance spectroscopy (EIS), scanning electronic microscope (SEM) analysis and Optical 3D profilometry characterization. All the methods used are in reasonable agreement. The kinetic and thermodynamic parameters for each steels corrosion and inhibitor adsorption, respectively, were determined and discussed. Results show that the adsorption capacity for Steel Classes A and B are better than Steel Class C surfaces depending on their silicon and phosphorus content. Surface analyses via SEM and Optical 3D profilometry was used to investigate the morphology of the steels before and after immersion in 5.0 M HCl solution containing mixture. Surface analysis revealed improvement of corrosion resistance of Steels Classes A and B in the presence of mixture more than Classes C. It has been determined that the adsorbed protective film on the steels surface heterogeneity markedly depends on steels compositions, that is, the heterogeneity increases with decreasing silicon and phosphorus content.Design/methodology/approachThe effect of silicon and phosphorus content in Steels Classes A, B and C on its corrosion and inhibitor mixture adsorption processes in 5.0 M HCl solution has been studied by weight loss, potentiodynamic polarization, EIS and surface analysis.FindingsThe inhibition efficiency of mixture follows the order: (Steel Class A) > (Steel Class B) > Steel Class C) and depends on their compositions in the absence of mixture according on their silicon and phosphorus content, that is, the corrosion rate increases with increasing of the silicon and phosphorus content. A potentiodynamic polarization measurement indicates that the mixture acts as mixed-type inhibitor without changing the mechanism of corrosion process for the three classes of mild steels.Originality/valueCorrosion rate mild steels in 5.0 M HCl depends on their compositions in the absence of mixture according to their silicon and phosphorus content, that is, the corrosion rate increases with increasing silicon and phosphorus content. The adsorbed protective film on the steels surface heterogeneity markedly depends on steels class’s compositions, that is, the heterogeneity increases with decreasing silicon and phosphorus content.
Entrepreneurial financing relationships: how does gender matter?
Authors: Kim Grace 
Published: February 2018

PurposeFinancing is cited as the major obstacle for entrepreneurs. However, data limitations have prevented study of entrepreneurs’ own impact on their financing relationships. Gender-based studies have concerned lender constraints and discriminatory outcomes. Others which are generally examined are borrowers’ fear of denial and non-pursuit of credit. To more fully explain the financing obstacle, the purpose of this study is to uniquely examine entrepreneurial borrowers’ evaluation of and actions in their existing financing relationship. This study also captures those businesses with equal ownership gender concentration, to contribute to a deeper understanding of gender impact.Design/methodology/approachThis study uses a cross-sectional sample of several thousand US small enterprises from the NFIB’s proprietary credit survey. The data set offers links between owners’ perceptions and financing behavior. Robust univariate analysis examines differences across gender ownership groups. Multivariate regression analyzes how gender, business environment and other factors determine the entrepreneurs’ financing relationships.FindingsThis study highlights how entrepreneurs affect their own financing outcomes. Findings suggest that switching lenders, seeking multiple relationships and other actions determine financing satisfaction. Growth intent, business performance and characteristics of the entrepreneur are among significant posited factors influencing perception and behavior of entrepreneurs in their financing relationships that drive business performance. Furthermore, equal ownership concentration firms appear to be similar to those primarily owned by men. This study indicates that researchers need to further delineate among entrepreneurs. The results of this study also have implications for policy-makers in their assessment of gender discrimination and government entrepreneurial financing initiatives.Originality/valueFinancing is cited as the major obstacle for entrepreneurs. However, data limitations have prevented study of entrepreneurs’ own impact on their financing relationships. Gender-based studies have concerned lender constraints and discriminatory outcomes. Others which are generally examined are borrowers’ fear of denial and non-pursuit of credit. To more fully explain the financing obstacle, this study uniquely examines entrepreneurial borrowers’ evaluation of and actions in their existing financing relationship. This study also captures those businesses with equal ownership gender concentration, to contribute to a deeper understanding of gender impact.
The service recovery paradox in B2B relationships
Authors: Hübner Denis , Wagner Stephan M. , Kurpjuweit Stefan 
Published: February 2018

PurposeThis study aims to explore the service recovery paradox (SRP) in business to business (B2B) relationships. Previously, this phenomenon has been identified in consumer-facing industries. The research advances the marketing literature by highlighting the ways in which the antecedents of the service recovery paradox differ between B2B and consumer markets.Design/methodology/approachThis research draws upon findings on the SRP in the consumer setting and service failure literature in business to consumer and B2B contexts. For the analysis, interview data were collected from 43 informants among clients and service providers in the aftermath of a service failure.FindingsThe authors propose an exploratory model of the SRP for B2B relationships. In the B2B setting the propensity of eliciting the SRP depends on (1) the characteristics of the service failure, (2) the attributes of the service recovery and (3) the shared subjective perceptions among boundary spanners.Practical implicationsEmpowered operating-level employees, straightforward communication, immediate responses and action plans that ensure future conformance are the key factors to turn service failures into increased customer satisfaction.Originality/valueThis study is the first to transfer the SRP from consumer marketing into the B2B domain. Moreover, it derives an exploratory model of the SRP, which can be refined by future research.