bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription-independent TFIIIC-bound sites cluster near heterochromatin boundaries within lamina-associated domains in C. elegans
Authors: Stutzman Alexis V. , Liang April S. , Beilinson Vera , Ikegami Kohta 
Published: October 2019

ABSTRACTBACKGROUNDChromatin organization is central to precise control of gene expression. In various eukaryotic spieces, domains of pervasive cis-chromatin interactions demarcate functional domains of the genomes. In nematode C. elegans, however, pervasive chromatin contact domains are limited to the dosage-compensated sex chromosome, leaving the principle of C. elegans chromatin organization unclear. Transcription Factor III C (TFIIIC) is a basal transcription factor complex for RNA Polymerase III, and is implicated in chromatin organization. TFIIIC binding without RNA Polymerase III co-occupancy, referred to as extra-TFIIIC binding, has been implicated in insulating active and inactive chromatin domains in yeasts, flies, and mammalian cells. Whether extra-TFIIIC sites are present and contribute to chromatin organization in C. elegans remains unknown.RESULTSWe identified 504 TFIIIC-bound sites absent of RNA Polymerase III and TATA-binding protein co-occupancy characteristic of extra-TFIIIC sites in C. elegans embryos. Extra-TFIIIC sites constituted half of all identified TFIIIC binding sites in the genome. Extra-TFIIIC sites formed dense clusters in cis. The clusters of extra-TFIIIC sites were highly over-represented within the distal arm domains of the autosomes that presented a high level of heterochromatin-associated histone H3K9 trimethylation (H3K9me3). Furthermore, extra-TFIIIC clusters were embedded in the lamina-associated domains. Despite the heterochromatin environment of extra-TFIIIC sites, the individual clusters of extra-TFIIIC sites were devoid of and resided near the individual H3K9me3-marked regions.CONCLUSIONClusters of extra-TFIIIC sites were pervasive in the arm domains of C. elegans autosomes, near the outer boundaries of H3K9me3-marked regions. Given the reported activity of extra-TFIIIC sites in heterochromatin insulation in yeasts, our observation raised the possibility that TFIIIC may also demarcate heterochromatin in C. elegans.
A cucumber green mottle mosaic virus vector for virus-induced gene silencing in cucurbit plants
Authors: Liu Mei , Liang Zhiling , Aranda Miguel A. , Hong Ni , Liu Liming , Kang Baoshan , Gu Qinsheng 
Published: October 2019

AbstractCucurbits produce fruits or vegetables that have great dietary importance and economic significance worldwide. The published genomes of at least 11 cucurbit species are boosting gene mining and novel breeding strategies, however genetic transformation in cucurbits is impractical as a tool for gene function validation due to low transformation efficiencies. Virus-induced gene silencing (VIGS) is a potential alternative tool. So far, very few ideal VIGS vectors are available for cucurbits. Here, we describe a new VIGS vector derived from cucumber green mottle mosaic virus (CGMMV), a monopartite virus that infects cucurbits naturally. We show that the CGMMV vector is competent to induce efficient silencing of the phytoene desaturase (PDS) gene in the model plant Nicotiana benthamiana and in cucurbits, including watermelon, melon, cucumber and bottle gourd. Infection with the CGMMV vector harboring PDS sequences of 69-300 bp in length in the form of sense-oriented or hairpin cDNAs resulted in photobleaching phenotypes in N. benthamiana and cucurbits by PDS silencing. Additional results reflect that silencing of the PDS gene could persist for over two months and the silencing effect of CGMMV-based vectors could be passaged. These results demonstrate that CGMMV vector could serve as a powerful and easy-to-use tool for characterizing gene function in cucurbits.One sentence summaryA CGMMV-based vector enables gene function studies in cucurbits, an extremely low efficiency species for genetic transformation.
Roq1 confers resistance to Xanthomonas,Pseudomonas syringaeandRalstonia solanacearumin tomato
Authors: Thomas Nicholas C. , Hendrich Connor G. , Gill Upinder S. , Allen Caitilyn , Hutton Samuel F. , Schultink Alex 
Published: October 2019

AbstractXanthomonasspecies,Pseudomonas syringaeandRalstonia solanacearumare bacterial plant pathogens that cause significant yield loss in many crop species. Current control methods for these pathogens are insufficient but there is significant potential for generating new disease-resistant crop varieties. Plant immune receptors encoded by nucleotide-binding, leucine-rich repeat (NLR) genes typically confer resistance to pathogens that produce a cognate elicitor, often an effector protein secreted by the pathogen to promote virulence. The diverse sequence and presence / absence variation of pathogen effector proteins within and between pathogen species usually limits the utility of a single NLR gene to protecting a plant from a single pathogen species or particular strains. The NLR protein Recognition of XopQ 1 (Roq1) was recently identified from the plantNicotiana benthamianaand mediates perception of the effector proteins XopQ and HopQ1 fromXanthomonasandP. syringaerespectively. Unlike most recognized effectors, alleles of XopQ/HopQ1 are highly conserved and present in most plant pathogenic strains ofXanthomonasandP. syringae. A homolog of XopQ/HopQ1, named RipB, is present in manyR. solanacearumstrains. We found that Roq1 also mediates perception of RipB and confers immunity toXanthomonas, P. syringae, andR. solanacearumwhen expressed in tomato. Strong resistance toXanthomonas perforanswas observed in three seasons of field trials with both natural and artificial inoculation. TheRoq1gene can therefore be used to provide safe, economical and effective control of these pathogens in tomato and other crop species and reduce or eliminate the need for traditional chemical controls.SummaryA single immune receptor expressed in tomato confers strong resistance to three different bacterial diseases.
Targeting Lysyl oxidase-like 2 in Idiopathic Pulmonary Fibrosis
Authors: Espindola Milena S. , Habiel David M , Coelho Ana Lucia , Mikels-Vigdal Amanda , Hogaboam Cory M. 
Published: October 2019

AbstractThe composition of extracellular matrix (ECM) is altered during pathologic scarring in damaged organs including the lung. One major change in the ECM involves the cross-linking of collagen, which promotes fibroblast to myofibroblast differentiation.ObjectiveWe examined the role of lysyl oxidase (LOX)-like 2 in lung fibroblasts cultured from normal or IPF lung samples and in a humanized mouse model of IPF using a monoclonal antibody (Simtuzumab).Research Design and MethodsPrimary lung fibroblasts from normal donor lungs and IPF lung explants were examined for expression of LOXL2. Targeting LOXL2 with Simtuzumab on normal and IPF fibroblasts was examined both in vitro and in vivo for synthetic, functional, and profibrotic properties.ResultsLOXL2 was increased at transcript and protein level in IPF compared with normal lung samples. In a dose-dependent manner, Simtuzumab enhanced differentiation of fibroblasts into myofibroblasts. Inhibition of LOXL2 also enhanced fibroblast invasion and accelerated the outgrowth of fibroblasts from dissociated human lung cell preparations. Finally, preventative or delayed delivery of Simtuzumab enhanced lung fibrosis in a humanized mouse model of pulmonary fibrosis.ConclusionConsistent with its failure in a Phase 2 clinical trial, Simtuzumab exhibited no therapeutic efficacy in translational in vitro and in vivo assays.
Local extirpation is pervasive among populations of Galápagos endemic tomatoes
Authors: Gibson Matthew J.S. , de Lourdes Torres Maria , Moyle Leonie C. 
Published: October 2019

AbstractThe Galápagos Islands are home to incredible endemic biodiversity that is of high conservation interest. Two such endemic species are the Galápagos tomatoes: Solanum cheesmaniae and Solanum galapagense. Both are known from historical location records, but like many endemic plant species on the Galápagos, their current conservation status is unclear. We revisited previously documented sites of endemic species on San Cristóbal, Santa Cruz, and Isabela, and document the disappearance of >80% of these populations. In contrast, we find that two invasive relatives (Solanum pimpinellifolium and Solanum lycopersicum) are now highly abundant, and in some cases—based on morphological observations—might be hybridizing with endemics. Our findings suggest that expanding human developments and putative interspecific hybridization are among the major factors affecting the prevalence of invasives and the threatened persistence of the endemic populations.
Systematic evaluation of normalization methods for glycomics data based on performance of network inference
Authors: Benedetti Elisa , Gerstner Nathalie , Pučić-Baković Maja , Keser Toma , Reiding Karli R. , Ruhaak L. Renee , Štambuk Tamara , Selman Maurice H.J. , Rudan Igor , Polašek Ozren , Hayward Caroline , Beekman Marian , Slagboom Eline , Wuhrer Manfred , Dunlop Malcolm G , Lauc Gordan , Krumsiek Jan 
Published: October 2019

AbstractGlycomics measurements, like all other high-throughput technologies, are subject to technical variation due to fluctuations in the experimental conditions. The removal of this non-biological signal from the data is referred to as normalization. Contrary to other omics data types, a systematic evaluation of normalization options for glycomics data has not been published so far. In this paper, we assess the quality of different normalization strategies for glycomics data with an innovative approach. It has been shown previously that Gaussian Graphical Models (GGMs) inferred from glycomics data are able to identify enzymatic steps in the glycan synthesis pathways in a data-driven fashion. Based on this finding, we here quantify the quality of a given normalization method according to how well a GGM inferred from the respective normalized data reconstructs known synthesis reactions in the glycosylation pathway. The method therefore exploits a biological measure of goodness. We analyzed 23 different normalization combinations applied to six large-scale glycomics cohorts across three experimental platforms (LC-ESI-MS, UHPLC-FLD and MALDI-FTICR-MS). Based on our results, we recommend normalizing glycan data using the ‘Probabilistic Quotient’ method followed by log-transformation, irrespective of the measurement platform.
Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2
Authors: Walker Rosie M. , Vaher Kadi , Bermingham Mairead L. , Morris Stewart W. , Bretherick Andrew D. , Zeng Yanni , Rawlik Konrad , Amador Carmen , Campbell Archie , Haley Chris S. , Hayward Caroline , Porteous David J. , McIntosh Andrew M. , Marioni Riccardo E. , Evans Kathryn L. 
Published: October 2019

AbstractBACKGROUNDThe Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease, while the ε2 allele confers protection. Previous studies report differential DNA methylation of APOE between ε4 and ε2 carriers, but associations with epigenome-wide methylation have not previously been characterised.METHODSUsing the EPIC array, we investigated epigenome-wide differences in whole blood DNA methylation patterns between Alzheimer’s disease-free APOE ε4 (n=2469) and ε2 (n=1118) carriers from the two largest single-cohort DNA methylation samples profiled to date. Using a discovery, replication and meta-analysis study design, methylation differences were identified using epigenome-wide association analysis and differentially methylated region (DMR) approaches. Results were explored using pathway and methylation quantitative trait loci (meQTL) analyses.RESULTSWe obtained replicated evidence for DNA methylation differences in a ~169kb region, which encompasses part of APOE and several upstream genes. Meta-analytic approaches identified DNA methylation differences outside of APOE: differentially methylated positions were identified in DHCR24, LDLR and ABCG1 (2.59 x 10−100≤P≤2.44 x 10−8) and DMRs were identified in SREBF2 and LDLR (1.63 x 10−4≤P≤3.01 x 10−2). Pathway and meQTL analyses implicated lipid-related processes and high density lipoprotein cholesterol was identified as a partial mediator of the methylation differences in ABCG1 and DHCR24.CONCLUSIONSAPOE ε4 vs. ε2 carrier status is associated with epigenome-wide methylation differences in the blood. The loci identified are located in trans as well as cis to APOE and implicate genes involved in lipid homeostasis.
Catalysis by a rigid enzyme
Authors: Bdira F. Ben , Waudby C. A. , Volkov A. N. , Schröder S. P. , AB E. , Codée J. D. C. , Overkleeft H.S. , Aerts J. M. F. G. , van Ingen H. , Ubbink M. 
Published: October 2019

AbstractMany enzymes are dynamic entities, sampling conformational states that are relevant for catalytic activity. Crystal structures of catalytic intermediates suggest, however, that not all enzymes require structural changes for activity. The single-domain enzyme xylanase fromBacillus circulans(BCX) is involved in the degradation of hemicellulose. We demonstrate that BCX in solution undergoes minimal structural changes during catalysis. NMR spectroscopy results show that the rigid protein matrix provides a frame for fast substrate binding in multiple conformations, accompanied by slow, enzyme induced substrate distortion. Therefore, we propose a model in which the rigid enzyme takes advantage of substrate flexibility to induce a conformation that facilitates catalysis.One Sentence SummaryThe rigid matrix of BCX uses substrate flexibility in Michaelis complex formation.
Growth under high light and elevated temperature affects metabolic responses and accumulation of health-promoting metabolites in kale varieties
Authors: Alegre Sara , Pascual Jesús , Trotta Andrea , Gollan Peter J. , Yang Wei , Yang Baoru , Aro Eva-Mari , Burow Meike , Kangasjärvi Saijaliisa 
Published: October 2019

AbstractPlants are highly sensitive to changes in the light environment and respond to alternating light conditions by coordinated adjustments in foliar gene expression and metabolism. Here we assessed how long-term growth under high irradiance and elevated temperature, a scenario increasingly associated with the climate change, affects foliar chemical composition of Brassicaceous plants. Transcript profiling of Arabidopsis suggested up-regulation of phenylpropanoid metabolism and down-regulation of processes related to biotic stress resistance and indole glucosinolates (GSL). These observations prompted metabolite profiling of purple (Black Magic) and pale green (Half Tall) varieties of kale, an economically important crop species. Long-term acclimation to high light and elevated temperature resulted in reduced levels of 4-methoxy-indol-3-yl-methyl GSL in both kale varieties. The total levels of aliphatic GSLs increased under these conditions, although the profiles of individual GSL structures showed cultivar-dependent differences. Black Magic became rich in 4-methylsulfinylbutyl GSL and 2-phenylethyl GSL, which have health-promoting effects in human diet. Additionally, the purple pigmentation of Black Magic became intensified due to increased accumulation anthocyanins, especially derivatives of cyanidin. These findings demonstrate that the potentially stressful combination of high light and elevated temperature can have beneficial effects on the accumulation of health-promoting metabolites in leafy vegetables.
Cell based strain stiffening of a non-fibrous matrix as organizing principle for morphogenesis
Authors: Rüdiger Daniel , Kick Kerstin , Goychuk Andriy , Vollmar Angelika M. , Frey Erwin , Zahler Stefan 
Published: October 2019

AbstractEndothelial tube formation on a reconstituted extracellular matrix (Matrigel) is a well-established in vitro model for studying the processes of angiogenesis and vasculogenesis. However, to date, the organizing principles that underlie the morphogenesis of this network, and that shape the initial process of cell-cell finding remain elusive. Furthermore, it is unclear how in vitro results extrapolate to in vivo morphogenesis. Here, we identify a mechanism that allows cells to form networks by mechanically reorganizing and stiffening their extracellular matrix, independent of chemical guidance cues. Interestingly, we find that this cellular self-organization strongly depends on the connectivity and topology of the surrounding matrix, as well as on cell contractility and cell density. Cells rearrange the matrix, and form bridges of matrix material that are stiffer than their surroundings, thus creating a durotactic track for the initiation of cell-cell contacts. This contractility-based communication via strain stiffening and matrix rearrangement might be a general organizing principle during tissue development or regeneration.Significance StatementIn addition to chemotactic gradients, biomechanical cues are important for guiding biological pattern formation. Self-assembly of cells has often been ascribed to reorganization of collagen fibres in the extracellular matrix. However, the basement membrane surrounding vascular cells, is per se non-fibrous. Here, we find that this difference in matrix topology can crucially influence cell behaviour and pattern formation. In a homogeneously elastic environment like the basement membrane, endothelial cells rearrange extracellular matrix proteins by contractile force, forming stiff intercellular bridges as tracks for cell-cell contacts. Our findings shine some light why there is a lot of merit in having multiple approaches to matrix elasticity (like continuum theories or dilated network approaches). Our observations might help to understand why vascular nets look different in different tissues and after rearrangement of the extracellular matrix during disease.
PyVOL: a PyMOL plugin for visualization, comparison, and volume calculation of drug-binding sites
Authors: Smith Ryan H.B. , Dar Arvin C. , Schlessinger Avner 
Published: October 2019

AbstractMotivationBinding pocket volumes are a simple yet important predictor of small molecule binding; however, generating visualizations of pocket topology and performing meaningful volume comparisons can be difficult with available tools. Current programs for accurate volume determination rely on extensive user input to define bulk solvent boundaries and to partition cavities into subpockets, increasing inter-user variability in measurements as well as time demands.ResultsWe developed PyVOL, a python package with a PyMOL interface and GUI, to visualize, to characterize, and to compare binding pockets. PyVOL’s pocket identification algorithm is designed to maximize reproducibility through minimization of user-provided parameters, avoidance of grid-based methods, and automated subpocket identification. This approach permits efficient, scalable volume calculations.AvailabilityPyVOL is released under the MIT License. Source code and documentation are available through github (https://github.com/schlessingerlab/pyvol/) with distribution through PyPI (bio-pyvol).Contactavner.schlessinger@mssm.edu, arvin.dar@mssm.edu
CDK1 couples proliferation with protein synthesis
Authors: Haneke Katharina , Schott Johanna , Lindner Doris , Hollensen Anne K. , Damgaard Christian K. , Mongis Cyril , Knop Michael , Palm Wilhelm , Ruggieri Alessia , Stoecklin Georg 
Published: October 2019

ABSTRACTCell proliferation exerts a high demand on protein synthesis, yet the mechanisms coupling the two processes are not fully understood. A kinase and phosphatase screen for activators of translation, based on the formation of stress granules in human cells, revealed cell cycle-associated kinases as major candidates. CDK1 was identified as a positive regulator of global translation, and cell synchronization experiments showed that this is an extra-mitotic function of CDK1. Dephosphorylation of eIF2α and S6K1 signaling were found to act downstream of CDK1. Moreover, Ribo-Seq analysis uncovered that CDK1 exerts a particularly strong effect on the translation of 5’TOP mRNAs, which includes mRNAs encoding for ribosomal proteins and several translation factors. This effect requires the 5’TOP mRNA-binding protein LARP1, concurrent to our finding that LARP1 phosphorylation is strongly dependent on CDK1. Taken together, our results show that CDK1 provides a direct means to couple cell proliferation with biosynthesis of the translation machinery and the rate of protein synthesis.
The role of working memory for bridging the gap between perception and goal-directed actions: Evidence by mu and beta oscillations in sensorimotor cortex
Authors: Schneider Daniel , Rösner Marlene , Klatt Laura-Isabelle , Wascher Edmund 
Published: October 2019

AbstractWhat mechanisms are at work when transferring a visual representation in working memory into a higher-level code for guiding future actions? We investigated the underlying attentional and motor selection processes in working memory by means of oscillatory EEG parameters. Participants stored two, three or four objects in working memory and subsequent retroactive cues indicated one or two items as task-relevant. The oscillatory response in mu (10-14 Hz) and beta (15-25 Hz) frequencies with an estimated source in sensorimotor cortex contralateral to response side was used as a correlate of motor planning. There was a stronger suppression of oscillatory power when only one item was cued. Importantly, this effect appeared although the required response could not be anticipated at this point in time. This suggests that working memory can store multiple item-specific motor plans and the selection of a stored visual item leads to an automatic updating of associated response alternatives.
From monologic to dialogic
Authors: Kingston Kylie L. , Furneaux Craig , de Zwaan Laura , Alderman Lyn 
Published: October 2019

Purpose
Informed by the critical perspective of dialogic accounting theory, the purpose of this paper is to explore the use of evaluation as a means of enhancing accountability to beneficiaries within nonprofit organisations (NPOs). As a stakeholder group frequently marginalised by traditional accounting practices, the participation of beneficiaries within a NPO’s accountability structure is presented as a means of increasing social justice.

Design/methodology/approach
The research design used case studies involving two NPOs, examining documents and conducting interviews across three stakeholder groups, within each organisation.

Findings
Findings reveal that when viewed on beneficiaries’ terms, accountability to beneficiaries, through participative evaluation, needs to consider the particular timeframe of beneficiary engagement within each organisation. This temporal element positions downwards accountability to beneficiaries within NPOs as multi-modal.

Research limitations/implications
The research poses a limit to statistical generalisability outside of the specific research context. However, the research prioritises theoretical generalisation to social forms and meanings, and as such provides insights for literature.

Practical implications
In acknowledging that beneficiaries have accountability needs dependent upon their timeframe of participation, NPOs can better target their downwards accountability structures. This research also has practical implications in its attempt to action two of the United Nation’s Sustainable Development Goals.

Originality/value
This paper makes a contribution to the limited research into nonprofit accountability towards beneficiaries. Dialogic accounting theory is enacted to explore how accountability can be practised on beneficiaries’ terms.