bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrocortical Evidence for Long-Term Incidental Spatial Learning Through Modified Navigation Instructions
Authors: Wunderlich Anna , Gramann Klaus 
Published: March 2018

AbstractThe use of Navigation Assistance Systems for spatial orienting has become increasingly popular. Such automated navigation support, however, comes with a reduced processing of the surrounding environment and often with a decline of spatial orienting ability. To prevent such deskilling and to support spatial learning, the present study investigated incidental spatial learning by comparing standard navigation instructions with two modified navigation instruction conditions. The first modified instruction condition highlighted landmarks and provided additional redundant information regarding the landmark (contrast condition), while the second highlighted landmarks and included personal relevant information regarding the landmark (personal-reference condition). Participants’ spatial knowledge of the previously unknown virtual city was tested three weeks later. Behavioral and electroencephalographic (EEG) data demonstrated enhanced memory performance for participants in the modified navigation instruction conditions without further differentiating between modified instructions. Recognition performance of landmarks was better and the late positive complex of the event-related potential (ERP) revealed amplitude differences reflecting an increased amount of recollected information for modified navigation instructions. The results indicate a significant long-term spatial learning effect when landmarks are highlighted during navigation instructions.
An eQTL landscape of kidney tissue in human nephrotic syndrome
Authors: Gillies Christopher E. , Putler Rosemary , Menon Rajasree , Otto Edgar , Yasutake Kalyn , Nair Viji , Hoover Paul , Lieb David , Li Shuqiang , Eddy Sean , Fermin Damian ,   Nephrotic Syndrome Study Network (NEPTUNE), Hacohen Nir , Kiryluk Krzysztof , Wen William , Kretzler Matthias , Sampson Matthew G. 
Published: March 2018

AbstractExpression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTLs studies of human kidney. Here, we used whole genome sequencing (WGS) and microdissected glomerular (GLOM) & tubulointerstitial (TI) transcriptomes from 187 patients with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures.Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n=136) and TI (n=166). We used the Bayesian “Deterministic Approximation of Posteriors” (DAP) to fine-map these signals, eQtlBma to discover GLOM-or TI-specific eQTLs, and single cell RNA-Seq data of control kidney tissue to identify cell-type specificity of significant eQTLs. We integrated eQTL data with an IgA Nephropathy (IGAN) GWAS to perform a transcriptome-wide association study (TWAS).We discovered 894 GLOM eQTLs and 1767 TI eQTLs at FDR <0.05. 14% and 19% of GLOM & TI eQTLs, respectively, had > 1 independent signal associated with its expression. 12% and 26% of eQTLs were GLOM-specific and TI-specific, respectively. GLOM eQTLs were most significantly enriched in podocyte transcripts and TI eQTLs in proximal tubules. The IGAN TWAS identified significant GLOM & TI genes, primarily at the HLA region.In this study of NS patients, we discovered GLOM & TI eQTLs, identified those that were tissue-specific, deconvoluted them into cell-specific signals, and used them to characterize known GWAS alleles. These data are publicly available for browsing and download at http://nephqtl.org.
PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data
Authors: Hernández-de-Diego Rafael , Tarazona Sonia , Martínez-Mira Carlos , Balzano-Nogueira Leandro , Furió-Tarí Pedro , Pappas Georgios J , Conesa Ana 
Published: March 2018

ABSTRACTThe increasing availability of multi-omic platforms poses new challenges to data analysis. Joint visualization of multi-omics data is instrumental to understand interconnections across molecular layers and to fully leverage the biology discovery power offered by the multi-omics approach.We present here PaintOmics 3, a web-based resource for the integrated visualization of multiple omic data types onto KEGG pathway diagrams. PaintOmics 3 combines server-end capabilities for data analysis with the potential of modern web resources for data visualization, providing researchers with a powerful framework for interactive exploration of their multi-omics information.Unlike other visualization tools, PaintOmics 3 covers a complete pathway analysis workflow, including automatic feature name/identifier conversion, multi-layered feature matching, pathway enrichment, network analysis, interactive heatmaps, trend charts, etc. It accepts a wide variety of omic types, including transcriptomics, proteomics and metabolomics, as well as region-based approaches such as ATAC-seq or ChIP-seq data. The tool is freely available at http://bioinfo.cipf.es/paintomics/.
Effects of CEPA and 1-MCP on flower bud differentiation of apple cv. ‘Nagafu No.2’ grafted on different rootstocks
Authors: Li Wenfang , Chen Baihong , Mao Juan , Li Xinwen , Su Jing , Dawuda Mohammed Mujitaba , Ma Zonghuan , Zuo Cunwu , An Zeshan 
Published: March 2018

AbstractThe apple (Malus domestica Borkh.) has a relatively long juvenile period which prevent the fruit breeding. The understanding of the flowering system is important to improve breeding efficiency in the apple. In this context, 2-year-old “Fuji” apple cv. “Nagafu No.2” trees that were grafted on dwarf self-rooted rootstock M.26, vigorous rootstock M. sieversii and interstock M.26/M. sieversii, respectively. Spraying with clean water (as controls), 800 mg·L−1 2-Chloroethylphosphonic acid (CEPA) and 2 μL·L−1 1-methylcyclopropene (1-MCP). The results showed that CEPA significantly repressed the vegetative growth attributed to the increase of the ABA and ZT synthesis, and the decrease of IAA synthesis in leaves and buds. However, there was no significant difference or significant inverse effect between 1-MCP and control. Furthermore, CEPA promoted flower formation, increased the flowering rate and advanced the blossom period for 2 days compared with the control, which accompanied by the accumulation of soluble sugar, glucose and sucrose, and the increase of α-amylase (α-AMY) and sucrose phosphate synthase (SPS) activities, and the decrease of the starch contents and sucrose synthase (SS) activities in leaves and buds. However, the blossom period was delayed for 2 days after spraying with 1-MCP. Finally, the expression of TFL1 was significantly repressed while the AP1 was significantly promoted in buds from M.26 and M.26/M. sieversii after spraying with CEPA, while the effect was not significant from M. sieversii. However, the expression levels of TFL1 and AP1 were not significantly different from the control after the application of 1-MCP. In spite of this, CEPA was more susceptible to easy-flowering M26, followed by M26/M. sieversii, and still less susceptible to difficult-flowering rootstock M. sieversii.Abbreviations1-MCP1-methylcyclopropeneα-amylase(α-AMY)ABAabscisic acidCEPA2-Chloroethylphosphonic acidCTKcytokininsETHethyleneGAgibberellinSPSsucrose phosphate synthaseSSsucrose synthaseZTzeatin.
Evolutionary analysis implicates RNA polymerase II pausing and chromatin structure in nematode piRNA biogenesis
Authors: Beltran T. , Barroso C. , Birkle T.Y. , Stevens L. , Schwartz H. T. , Sternberg P.W. , Fradin H. , Gunsalus K. , Piano F. , Cotton J. , Martínez-Pérez E. , Blaxter M. , Sarkies P. 
Published: March 2018

AbstractPiwi-interacting RNAs (piRNAs) control transposable elements widely across metazoans but have rapidly evolving biogenesis pathways. In Caenorhabditis elegans, almost all piRNA loci are found within two 3Mb clusters on Chromosome IV. Each piRNA locus possesses an upstream motif that recruits RNA polymerase II to produce a ∼28 nt precursor transcript. Here, we use comparative epigenomics across nematodes to gain insight into piRNA biogenesis. We show that the piRNA upstream motif is derived from core promoter elements controlling snRNA biogenesis. We describe two alternative modes of piRNA organisation in nematodes: in C. elegans and closely related nematodes, piRNAs are clustered within repressive H3K27me3 chromatin, whilst in other species, typified by Pristionchus pacificus, piRNAs are distributed genome-wide within introns of actively transcribed genes. In both groups, piRNA production depends on downstream sequence signals associated with RNA polymerase II pausing, which synergise with the chromatin environment to control piRNA precursor transcription.
Functional analysis of a hypomorphic allele shows that MMP14 catalytic activity is the prime determinant of the Winchester syndrome phenotype
Authors: de Vos Ivo J.H.M. , Tao Evelyn Yaqiong , Ong Sheena Li Ming , Goggi Julian L. , Scerri Thomas , Wilson Gabrielle R. , Low Chernis Guai Mun , Wong Arnette Shi Wei , Grussu Dominic , Stegmann Alexander P.A. , van Geel Michel , Janssen Renske , Amor David J. , Bahlo Melanie , Dunn Norris R. , Carney Thomas J. , Lockhart Paul J. , Coull Barry J. , van Steensel Maurice A.M. 
Published: March 2018

AbstractWinchester syndrome (WS, MIM #277950) is an extremely rare autosomal recessive skeletal dysplasia characterized by progressive joint destruction and osteolysis. To date, only one missense mutation inMMP14, encoding the membrane-bound matrix metalloprotease 14, has been reported in WS patients. Here, we report a novel hypomorphic MMP14 p.Arg111His (R111H) allele, associated with a mitigated form of WS. Functional analysis demonstrated that this mutation, in contrast to previously reported human and murineMMP14mutations, does not affect MMP14’s transport to the cell membrane. Instead, it partially impairs MMP14’s proteolytic activity. This residual activity likely accounts for the mitigated phenotype observed in our patients. Based on our observations as well as previously published data, we hypothesize that MMP14’s catalytic activity is the prime determinant of disease severity. Given the limitations of ourin vitroassays in addressing the consequences of MMP14 dysfunction, we generated a novelmmp14a/bknockout zebrafish model. The fish accurately reflected key aspects of the WS phenotype including craniofacial malformations, kyphosis, short-stature and reduced bone density due to defective collagen remodeling. Notably, the zebrafish model will be a valuable tool for developing novel therapeutic approaches to a devastating bone disorder.
Measuring Endoplasmic Reticulum Signal Sequences Translocation Efficiency Using the Xbp1 Arrest Peptide
Authors: Kriegler Theresa , Magoulopoulou Anastasia , Marchal Rocio Amate , Hessa Tara 
Published: March 2018

SummarySecretory proteins translocate across the mammalian ER membrane co-translationally via the ribosome-sec61 translocation channel complex. Signal sequences within the polypeptide, which guide this event, are diverse in their hydrophobicity, charge, length, and amino acid composition. Despite the known sequence diversity in the ER-targeting signals, it is generally assumed that they have a dominant role in determining co-translational targeting and translocation initiation process. We have analyzed co-translational events experienced by secretory proteins carrying efficient, versus inefficient (poorly hydrophobic) signal sequences, using an assay based on Xbp1 peptide-mediated translational arrest. With this method we were able to measure the functional efficiency of ER signal sequences. We show that an efficient signal sequence experiences a two-phases event in which the nascent chain is pulled from the ribosome during its translocation, thus resuming translation and yielding full-length products. Conversely, the inefficient signal sequence experiences a single weaker pulling event, suggesting inadequate engagement by the translocation machinery of these marginally hydrophobic signal sequences.
Escher-FBA: A web application for interactive flux balance analysis
Authors: Rowe Elliot , Palsson Bernhard O. , King Zachary A. 
Published: March 2018

AbstractBackgroundFlux balance analysis (FBA) is a widely-used method for analyzing metabolic networks. However, most existing tools that implement FBA require downloading software and writing code. Furthermore, FBA generates predictions for metabolic networks with thousands of components, so meaningful changes in FBA solutions can be difficult to identify. These challenges make it difficult for beginners to learn how FBA works.ResultsTo meet this need, we present Escher-FBA, a web application for interactive FBA simulations within a pathway visualization. Escher-FBA allows users to set flux bounds, knock out reactions, change objective functions, upload metabolic models, and generate high-quality figures without downloading software or writing code. We provide detailed instructions on how to use Escher-FBA to replicate several FBA simulations that generate real scientific hypotheses.ConclusionsWe designed Escher-FBA to be as intuitive as possible so that users can quickly and easily understand the core concepts of FBA. The web application can be accessed at https://sbrg.github.io/escher-fba.
Comprehensive profiling of the fission yeast transcription start site activity during stress and media response
Authors: Thodberg Malte , Thieffry Axel , Bornholdt Jette , Boyd Mette , Holmberg Christian , Azad Ajuna , Workman Christopher T. , Chen Yun , Ekwall Karl , Nielsen Olaf , Sandelin Albin 
Published: March 2018

AbstractFission yeast, Schizosaccharomyces pombe, is an attractive model organism for transcriptional and chromatin biology research. Such research is contingent on accurate annotation of transcription start sites (TSSs). However, comprehensive genome-wide maps of TSSs and their usage across commonly applied laboratory conditions and treatments for S. pombe are lacking. To this end, we profiled TSS activity genome-wide in S. pombe cultures exposed to heat shock, nitrogen starvation, hydrogen peroxide and two commonly applied media, YES and EMM2, using Cap Analysis of Gene Expression (CAGE). CAGE-based annotation of TSSs is substantially more accurate than existing PomBase annotation; on average, CAGE TSSs fall 50-75 bp downstream of PomBase TSSs and co-localize with nucleosome boundaries. In contrast to higher eukaryotes, S. pombe does not show sharp and dispersed TSS distributions. Our data recapitulate known S. pombe stress expression response patterns and identify stress- and mediaresponsive alternative TSSs. Notably, alteration of growth medium induces changes of similar magnitude as some stressors. We show a link between nucleosome occupancy and genetic variation, and that the proximal promoter region is genetically diverse between S. pombe strains. Our detailed TSS map constitute a central resource for S. pombe gene regulation research.
smCounter2: an accurate low-frequency variant caller for targeted sequencing data with unique molecular identifiers
Authors: Xu Chang , Gu Xiujing , Padmanabhan Raghavendra , Wu Zhong , Peng Quan , DiCarlo John , Wang Yexun 
Published: March 2018

AbstractMotivationLow-frequency DNA mutations are often confounded with technical artifacts from sample preparation and sequencing. With unique molecular identifiers (UMIs), most of the sequencing errors can be corrected. However, errors before UMI tagging, such as DNA polymerase errors during end-repair and the first PCR cycle, cannot be corrected with single-strand UMIs and impose fundamental limits to UMI-based variant calling.ResultsWe developed smCounter2, a UMI-based variant caller for targeted sequencing data and an upgrade from the current version of smCounter. Compared to smCounter, smCounter2 features lower detection limit at 0.5%, better overall accuracy (particularly in non-coding regions), a consistent threshold that can be applied to both deep and shallow sequencing runs, and easier use via a Docker image and code for read pre-processing. We benchmarked smCounter2 against several state-of-the-art UMI-based variant calling methods using multiple datasets and demonstrated smCounter2’s superior performance in detecting somatic variants. At the core of smCounter2 is a statistical test to determine whether the allele frequency of the putative variant is significantly above the background error rate, which was carefully modeled using an independent dataset. The improved accuracy in non-coding regions was mainly achieved using novel repetitive region filters that were specifically designed for UMI data.AvailabilityThe entire pipeline is available at https://github.com/qiaseq/qiaseq-dna under MIT license.
Topographic effects on dispersal patterns ofPhytophthora cinnamomiat a stand scale in a Spanish heathland
Authors: Cardillo Enrique , Acedo Angel , Abad Enrique 
Published: March 2018

AbstractPhytophthora cinnamomiis one of the most important plant pathogens in the world, causing root rot in more than a thousand plant species. This observational study was carried out on aP. cinnamomiinfected heathland ofErica umbellataused as goat pasture. The patterns and shapes of disease foci and their distribution were described in a spatial and temporal context using an aerial photograph record. A set of topographic traits was selected on the basis of a disease dynamic hypothesis and their effects on observed spatial disease patterns were analyzed. Incipient infections situated in flat terrain expanded as compact circular front patterns with a low growth rate. On slopes, disease patches developed more rapidly down slope, forming parabolic shapes. The axis direction of the parabolas was highly correlated with terrain aspect, while the parabolic amplitude was associated with land curvature and slope. New secondary foci appeared over the years producing an accelerated increase of the affected surface. These new foci were observed in sites where disease density was higher or near sites more frequently visited by animals such as the stable or the forage crop. In contrast, a smaller number of disease foci occur in areas which animals are reluctant to visit, such as where they have a short range of vision. Our results suggest that 1) the growth of existingP. cinnamomifoci is controlled by a combination of root-to-root contact and water flows, 2) the increase in the diseased area arises mainly from the multiplication of patches, 3) the formation of new foci is mediated by long-distance transport due to the movement of animals and humans along certain preferential pathways, and 4) geomorphology and topography traits are associated with the epidemiology of this soil-borne pathogen.
Dectin-3 recognizes cryptococcal glucuronoxylomannan to initiate host defense against cryptococcosis
Authors: Huang Hua-Rong , Li Fan , Han Hua , Lv Quan-Zhen , Xu Xia , Li Ning , Wang Shunchun , Xu Jin-Fu , Jia Xin-Ming 
Published: March 2018

AbstractCryptococcus neoformansandCryptococcus gattiicause life-threatening meningoencephalitis and pneumonia in immunosuppressed and immunocompetent individuals. Given the structural differences of major polysaccharide glucuronoxylomannan (GXM) betweenC. neoformansandC. gattii, it remains unclear that how innate immune system recognizes GXM. Here, we report that C-type lectin receptor Dectin-3 (MCL encoded by Clec4d) is a direct receptor for GXMs fromC. neoformansserotype AD (C.n-AD) andC. gattiiserotype B (C.g-B). GXMs fromC.n-AD andC.g-B activated both NF-κB and ERK pathways to induce the pro-inflammatory cytokine production, whereas it was completely abolished due to deficiency of Dectin-3 or its downstream adaptor protein CARD9. Upon pulmonaryC.n-AD andC.g-B infection, Dectin-3- and CARD9-deficient mice were highly susceptible and showed augmented lung injury due to impairment of alveolar macrophage accumulation and killing activities. These results demonstrate that Dectin-3 contributes to host immunity againstCryptococcusinfection through selectively recognizingGXM.
CREBBPandWDR 24Affects Quantitative Variation in Red Colouration in the Chicken
Authors: Fogelholm J. , Henriksen R. , Höglund A. , Huq N. , Johnsson M. , Lenz R. , Jensen P. , Wright D. 
Published: March 2018

AbstractPlumage colouration in birds is important for a plethora of reasons, ranging from camouflage, sexual signaling, and species recognition. The genes underlying colour variation have been vital in understanding how genes can affect a phenotype. Multiple genes have been identified that affect plumage variation, but research has principally focused on major-effect genes (such as those causing albinism, barring, and the like), rather than the smaller effect modifier loci that more subtly influence colour. By utilizing a domestic x wild advanced intercross with a combination of classical QTL mapping of red colouration as a quantitative trait and a targeted genetical genomics approach, we have identified five separate candidate genes (CREBBP, WDR24, ARL8A, PHLDA3, LAD1) that putatively influence quantitative variation in red colouration in chickens. Such small effect loci are potentially far more prevalent in wild populations, and can therefore potentially be highly relevant to colour evolution.
Human Puf-A, a Novel Component of 90S Pre-ribosome, Links Ribosome Biogenesis to Cancer Progression
Authors: Cho Huan-Chieh , Huang Yenlin , Hung Jung-Tung , Lai Li-Chun , Wang Sheng-Hung , Liu Yun-Hen , Cho I-Ming , Kuo Ming-Wei , Cheng Pei-Yi , Ho Ming-Yi , Lin Rey-Jin , Yu Alice L. , Yu John 
Published: March 2018

AbstractWe describe a novel biogenesis factor of the 90S pre-ribosome, Puf-A, which is a negative transcriptional target of p53. The expression of Puf-A is not only upregulated in advanced human lung cancer and tumors of patients especially with TP53 mutation, but also is highly prognostic for stage I lung cancer. Loss of Puf-A expression prevents KrasG12D/p53-/-–induced tumor progression in the lungs and induces apoptosis in TP53– mutated cancers and c-Myc/p53-/-–transformed cells as well. Overexpression of Puf-A enhances proliferation of normal cells after c-Myc induction and overcomes the cell-cycle checkpoints incurred by p53 expression. Mechanistically, Puf-A interacts with double-stranded structures of the 5.8S sequence within pre-rRNA and maintains the integrity of 90S pre-ribosomes, thereby impacting early ribosome assembly and export of ribosomes from nuclei. Silencing of Puf-A disrupts the assembly of 90S pre-ribosomes and induces the translocation of its associated nucleophosmin (NPM1) from nucleoli to the nucleoplasm, resulting in impairment of ribosome synthesis. Thus, Puf-A is crucial for over-activation of ribosome biogenesis and contributes to tumor progression and cancer growth.
Impulsive choice in mice lacking paternal expression of Grb10 suggests intra-genomic conflict in behavior
Authors: Dent Claire L. , Humby Trevor , Lewis Katie , Ward Andrew , Fischer-Colbrie Reiner , Wilkinson Lawrence S. , Wilkins Jon F , Isles Anthony R. 
Published: March 2018

AbstractImprinted genes are expressed from one parental allele only as a consequence of epigenetic events that take place in the mammalian germ line and are thought to have evolved through intra-genomic conflict between parental alleles. We demonstrate, for the first time, oppositional effects of imprinted genes on brain and behavior. Specifically, here we show that mice lacking paternal Grb10 make fewer impulsive choices, with no dissociable effects on a separate measure of impulsive action. Taken together with previous work showing that mice lacking maternal Nesp55 make more impulsive choices this suggests that impulsive choice behavior is a substrate for the action of genomic imprinting. Moreover, the contrasting effect of these two genes suggests impulsive choices are subject to intra-genomic conflict and that maternal and paternal interests pull this behavior in opposite directions. Finally, these data may also indicate that an imbalance in expression of imprinted genes contributes to pathological conditions such as gambling and drug addiction, where impulsive behavior becomes maladaptive.