bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of YKL-40 on angiogenic potential of HUVECs are partly mediated by syndecan-4
Authors: Zheng Jianlei , Xue Qi , Zhao Yan , Sun WeiJun 
Published: April 2020

AbstractObjectiveYKL-40, a secreted glycoprotein, has a role in promoting tumor angiogenesis through syndecan-1 receptor. As one of the members of syndecans family, syndecan-4 is also an important mediator for tube formation. However, the effects of YKL-40 on migration and tube formation of human umbilical vein cells (HUVECs) mediated by syndecan-4 receptor are unknown.MethodsHUVECs were transfected with lentivirus encoding syndecan-4 short hairpin (sh) RNA (lenti-synd4 shRNA) and the efficiency of transfection was measured using reverse transcription quantitative real time polymerase chain reaction (qRT-PCR) and flow cytometry. The effects of recombinant protein of YKL-40 on migration and angiogenesis of HUVECs adjusted by syndecan-4 were determined by wound healing and tube formation assay. The expression of protein kinase Cα (PKCα) and extracellular signal regulated kinases (ERKs) 1 and 2 (ERK1/2) in HUVECs was measured using western blotting.ResultsTransfection of lenti-synd4 shRNA significantly decreased the membrane protein expression of syndecan-4 in HUVECs. HUVECs transfected with lenti-synd4 shRNA remarkably inhibited the migration and tube formation of endothelial cells stimulated by recombinant protein of YKL-40. The levels of PKCα and ratio of p-ERK1/2 to ERK1/2 in HUVECs were also down-regulated by silencing syndecan-4.ConclusionThe effects of YKL-40-induced on migration and tube formation of HUVECs may partly be inhibited by knock-downing syndecan-4 through suppressing PKCα and ERK1/2 signaling pathways.
Natural variation in autumnFLClevels, rather than epigenetic silencing, aligns vernalization to different climates
Authors: Hepworth Jo , Antoniou-Kourounioti Rea L , Berggren Kristina , Selga Catja , Tudor Eleri , Yates Bryony , Cox Deborah , Collier Harris Barley R , Irwin Judith , Howard Martin , Säll Torbjörn , Holm Svante , Dean Caroline 
Published: April 2020

AbstractPlants monitor temperatures over long timescales to assess seasons and time developmental transitions. InArabidopsis thaliana, winter is registered during vernalization through the temperature-dependent repression and epigenetic silencing of floral repressorFLOWERING LOCUS C (FLC). Natural Arabidopsis accessions show considerable variation in vernalization, however which aspect of theFLCrepression mechanism is most important for adaptation to different climates is not clear. By analyzingFLCsilencing in natural variants throughout winter in three field sites, we find thatFLCstarting levels and early phases of silencing are the major variables underlying vernalization response, rather than establishment of epigenetic silencing. This results in an intricate interplay between promotion and delay of flowering to balance survival, and through a post-vernalization effect ofFLC, reproductive effort via branch production. These data reveal how non-codingFLCvariation aligns vernalization response to different climatic conditions and year-on-year fluctuations in natural temperature profiles.Impact StatementAlleles of the major floral repressor vary in their initial expression to underpin the ability of Arabidopsis to survive year-on-year climatic fluctuations.
A visual encoding model links magnetoencephalography signals to neural synchrony in human cortex
Authors: Kupers Eline R. , Benson Noah C. , Winawer Jonathan 
Published: April 2020

AbstractSynchronization of neuronal responses over large distances is hypothesized to be important for many cortical functions. However, no straightforward methods exist to estimate synchrony non-invasively in the living human brain. MEG and EEG measure the whole brain, but the sensors pool over large, overlapping cortical regions, obscuring the underlying neural synchrony. Here, we developed a model from stimulus to cortex to MEG sensors to disentangle neural synchrony from spatial pooling of the instrument. We find that synchrony across cortex has a surprisingly large and systematic effect on predicted MEG spatial topography. We then conducted visual MEG experiments and separated responses into stimulus-locked and broadband components. The stimulus-locked topography was similar to model predictions assuming synchronous neural sources, whereas the broadband topography was similar to model predictions assuming asynchronous sources. We infer that visual stimulation elicits two distinct types of neural responses, one highly synchronous and one largely asynchronous across cortex.
Impact of lossy compression of nanopore raw signal data on basecalling and consensus accuracy
Authors: Chandak Shubham , Tatwawadi Kedar , Sridhar Srivatsan , Weissman Tsachy 
Published: April 2020

AbstractMotivationNanopore sequencing provides a real-time and portable solution to genomic sequencing, enabling better assembly, structural variant discovery and modified base detection than second generation technologies. The sequencing process generates a huge amount of data in the form of raw signal contained in fast5 files, which must be compressed to enable efficient storage and transfer. Since the raw data is inherently noisy, lossy compression has potential to significantly reduce space requirements without adversely impacting performance of downstream applications.ResultsWe explore the use of lossy compression for nanopore raw data using two state-of-the-art lossy time-series compressors, and evaluate the tradeoff between compressed size and basecalling/consensus accuracy. We test several basecallers and consensus tools on a variety of datasets at varying depths of coverage, and conclude that lossy compression can provide 35-50% further reduction in compressed size of raw data over the state-of-the-art lossless compressor with negligible impact on basecalling accuracy (≲0.2% reduction) and consensus accuracy (≲0.002% reduction). In addition, we evaluate the impact of lossy compression on methylation calling accuracy and observe that this impact is minimal for similar reductions in compressed size, although further evaluation with improved benchmark datasets is required for reaching a definite conclusion. The results suggest the possibility of using lossy compression, potentially on the nanopore sequencing device itself, to achieve significant reductions in storage and transmission costs while preserving the accuracy of downstream applications.AvailabilityThe code is available athttps://github.com/shubhamchandak94/lossy_compression_evaluation.Supplementary informationSupplementary data are available atBioinformaticsonline.Contactschandak@stanford.edu
A novel framework for characterizing genomic haplotype diversity in the human immunoglobulin heavy chain locus
Authors: Rodriguez O. L. , Gibson W. S. , Parks T. , Emery M. , Powell J. , Strahl M. , Deikus G. , Auckland K. , Eichler E. E. , Marasco W. A. , Sebra R. , Sharp A. J. , Smith M. L. , Bashir A. , Watson C. T. 
Published: April 2020

AbstractAn incomplete ascertainment of genetic variation within the highly polymorphic immunoglobulin heavy chain locus (IGH) has hindered our ability to define genetic factors that influence antibody and B cell mediated processes. To date, methods for locus-wide genotyping of all IGH variant types do not exist. Here, we combine targeted long-read sequencing with a novel bioinformatics tool, IGenotyper, to fully characterize genetic variation within IGH in a haplotype-specific manner. We apply this approach to eight human samples, including a haploid cell line and two mother-father-child trios, and demonstrate the ability to generate high-quality assemblies (>98% complete and >99% accurate), genotypes, and gene annotations, including 2 novel structural variants and 16 novel gene alleles. We show that multiplexing allows for scaling of the approach without impacting data quality, and that our genotype call sets are more accurate than short-read (>35% increase in true positives and >97% decrease in false-positives) and array/imputation-based datasets. This framework establishes a foundation for leveraging IG genomic data to study population-level variation in the antibody response.
Rice lectin proteinOsr40c1imparts drought tolerance by modulatingOsSAM2,OsSAP8 and chromatin-associated proteins
Authors: Sahid Salman , Roy Chandan , Paul Soumitra , Datta Riddhi 
Published: April 2020

AbstractLectin proteins play an important role in biotic and abiotic stress responses in plants. Although the rice lectin protein,Osr40c1, has been reported to be regulated by drought stress, the mechanism of its drought tolerance activity has not been studied so far. In this study, it has been depicted that expression ofOsr40c1gene correlates with the drought tolerance potential of various rice cultivars. Transgenic rice plants overexpressingOsr40c1were significantly more tolerant to drought stress over the wild-type plants. Furthermore, ectopic expression of theOsr40c1gene in tobacco yielded a similar result. Interestingly, the protein displayed a nucleo-cytoplasmic localization and was found to interact with a number of drought-responsive proteins likeOsSAM2,OsSAP8,OsMNB1B, andOsH4. Fascinatingly, silencing of each of these protein partners led to drought susceptibility in the otherwise tolerantOsr40c1 expressing transgenic tobacco lines indicating that these partners were crucial for theOsr40c1-mediated drought tolerancein planta. Together, the present investigation delineated the novel role ofOsr40c1 protein in imparting drought tolerance by regulating the chromatin proteins,OsMNB1B andOsH4, which presumably enablesOsSAP8 to induce downstream gene expression. In addition, its interaction withOsSAM2 might induce polyamine biosynthesis thus further improving drought tolerance in plants.HighlightsA rice lectin protein,Osr40c1, plays a crucial role in imparting drought stress tolerance in plants by modulatingOsSAM2 as well as the transcriptional regulatorsOsSAP8,OsMNB1B andOsH4.
Jacalin domain-containing protein OsSalT interacts with OsDREB2A and OsNAC1 to impart drought stress tolerance in planta
Authors: Sahid Salman , Roy Chandan , Shee Dibyendu , Datta Riddhi , Paul Soumitra 
Published: April 2020

AbstractWith the changing climatic conditions, drought has become one of the most threatening abiotic stress factors that adversely affect rice cultivation and productivity. Although the involvement of the jacalin domain-containing protein, OsSalT, has been reported in drought and salinity tolerance, its functional mechanism still remains largely unexplored. In this study, expression of the OsSalT gene was found to be positively correlated with the drought tolerance potential with its higher transcript abundance in the tolerant indica rice cultivar, Vandana and lower abundance in the susceptible cultivar, MTU1010. Moreover, the ectopic expression of OsSalT in tobacco imparted drought stress tolerance in the transgenic lines. The transgenic lines exhibited significantly improved growth and higher osmolyte accumulation over the wild-type (WT) plants together with the induction in the OsSalT expression under drought stress. Fascinatingly, the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) analyses confirmed the interaction of OsSalT protein with two interesting transcription factors (TFs), OsNAC1 and OsDREB2A. In silico analysis further revealed that the OsSalT protein interacted with the regulatory domain of OsDREB2A and the C-terminal domain of OsNAC1 leading to their activation and induction of their downstream drought-responsive genes. Together, this study unravels a novel model for OsSalT-mediated regulation of drought tolerance in plants.
An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity
Authors: Luna Lucas A. , Lesecq Zachary , White Katharine A. , Hoang An , Scott David A. , Zagnitko Olga , Bobkov Andrey A. , Barber Diane L. , Schiffer Jamie M. , Isom Daniel G. , Sohl Christal D. 
Published: April 2020

ABSTRACTIsocitrate dehydrogenase 1 (IDH1) catalyzes the reversible NADP+-dependent conversion of isocitrate to α-ketoglutarate (α-KG) to provide critical cytosolic substrates and drive NADPH-dependent reactions like lipid biosynthesis and glutathione regeneration. In biochemical studies, the forward reaction is studied at neutral pH, while the reverse reaction is typically characterized in more acidic buffers. This led us to question whether IDH1 catalysis is pH-regulated, which would have functional implications under conditions that alter cellular pH, like apoptosis, hypoxia, cancer, and neurodegenerative diseases. Here, we show evidence of catalytic regulation of IDH1 by pH, identifying a trend of increasingkcatvalues for α-KG production upon increasing pH in the buffers we tested. To understand the molecular determinants of IDH1 pH sensitivity, we used the pHinder algorithm to identify buried ionizable residues predicted to have shifted pKavalues. Such residues can serve as pH sensors, with changes in protonation states leading to conformational changes that regulate catalysis. We identified an acidic residue buried at the IDH1 dimer interface, D273, with a predicted pKavalue upshifted into the physiological range. D273 point mutations had decreased catalytic efficiency and, importantly, loss of pH-regulated catalysis. Based on these findings, we conclude that IDH1 activity is regulated, at least in part, by pH. We show this regulation is mediated by at least one buried acidic residue ∼12 Å from the IDH1 active site. By establishing mechanisms of regulation of this well-conserved enzyme, we highlight catalytic features that may be susceptible to pH changes caused by cell stress and disease.
MpsLDA-ProSVM: predicting multi-label protein subcellular localization by wMLDAe dimensionality reduction and ProSVM classifier
Authors: Zhang Qi , Li Shan , Yu Bin , Li Yang , Zhang Yandan , Ma Qin , Zhang Yusen 
Published: April 2020

ABSTRACTProteins play a significant part in life processes such as cell growth, development, and reproduction. Exploring protein subcellular localization (SCL) is a direct way to better understand the function of proteins in cells. Studies have found that more and more proteins belong to multiple subcellular locations, and these proteins are called multi-label proteins. They not only play a key role in cell life activities, but also play an indispensable role in medicine and drug development. This article first presents a new prediction model, MpsLDA-ProSVM, to predict the SCL of multi-label proteins. Firstly, the physical and chemical information, evolution information, sequence information and annotation information of protein sequences are fused. Then, for the first time, use a weighted multi-label linear discriminant analysis framework based on entropy weight form (wMLDAe) to refine and purify features, reduce the difficulty of learning. Finally, input the optimal feature subset into the multi-label learning with label-specific features (LIFT) and multi-label k-nearest neighbor (ML-KNN) algorithms to obtain a synthetic ranking of relevant labels, and then use Prediction and Relevance Ordering based SVM (ProSVM) classifier to predict the SCLs. This method can rank and classify related tags at the same time, which greatly improves the efficiency of the model. Tested by jackknife method, the overall actual accuracy (OAA) on virus, plant, Gram-positive bacteria and Gram-negative bacteria datasets are 98.06%, 98.97%, 99.81% and 98.49%, which are 0.56%-9.16%, 5.37%-30.87%, 3.51%-6.91% and 3.99%-8.59% higher than other advanced methods respectively. The source codes and datasets are available athttps://github.com/QUST-AIBBDRC/MpsLDA-ProSVM/.
NAT8LmRNA oxidation is linked to neurodegeneration in multiple sclerosis
Authors: Kharel Prakash , Singhal Naveen Kumar , West Nicole , Rana Joram , Smith Lindsey , Freeman Ernest , Chattopadhyay Ansuman , McDonough Jennifer , Basu Soumitra 
Published: April 2020

AbstractRNA oxidation has been implicated in neurodegeneration, but the underlying mechanism for such effects is unclear. Recently, we demonstrated extensive RNA oxidation within the neurons in multiple sclerosis (MS) brain. In this report we identified selectively oxidized mRNAs in neuronal cells that pertained to neuropathological pathways. N-acetyl aspartate transferase 8 like (NAT8L) mRNA is one such transcript, whose translated product enzymatically synthesizes N-acetyl aspartic acid (NAA), a neuronal metabolite important for myelin synthesis. We reasoned that impediment of translation of an oxidizedNAT8LmRNA will result in reduction in its cognate protein, thus lowering NAA level. This assertion is directly supported by our studies on a model cellular system, an MS animal model and postmortem human MS brain. Reduced NAA level in the brain hampers myelin integrity making neuronal axons more susceptible to damage, which contributes in MS neurodegeneration. Overall, this work provides a framework for mechanistic understanding of the link between RNA oxidation and neurodegenerative diseases.
Cell-intrinsic differences between human airway epithelial cells from children and adults
Authors: Maughan Elizabeth F. , Hynds Robert E. , Pennycuick Adam , Nigro Ersilia , Gowers Kate H.C. , Denais Celine , Gómez-López Sandra , Lazarus Kyren A. , Orr Jessica C. , Pearce David R. , Clarke Sarah E. , Lee Dani Do Hyang , Woodall Maximillian N. J. , Masonou Tereza , Case Katie-Marie , Teixeira Vitor H. , Hartley Benjamin E. , Hewitt Richard J. , Yaghchi Chadwan Al , Sandhu Gurpreet S. , Birchall Martin A. , O’Callaghan Christopher , Smith Claire M. , De Coppi Paolo , Butler Colin R. , Janes Sam M. 
Published: April 2020

SummaryThe airway epithelium is a key protective barrier, the integrity of which is preserved by the self-renewal and differentiation of basal stem cells. Epithelial cells are central to the pathogenesis of multiple lung diseases. In chronic lung diseases, increasing age is a principle risk factor. Few studies have explored the differences between airway epithelial cells in children and adults and how the function of basal stem cells changes during ageing is poorly understood. Here, we analyze airway epithelial cells from children and adults in homeostatic conditions (laser capture-microdissected whole epithelium and fluorescence-activated cell-sorted basal cells) and in proliferation-inducing cell culture conditions. We find that, while the cellular composition of the pediatric and adult tracheobronchial epithelium is broadly similar, in cell culture, pediatric airway epithelial cells displayed higher colony-forming ability, sustainedin vitrogrowth and outcompeted adult cells in competitive proliferation assays. In RNA sequencing experiments, we observed potentially important differences between epithelium from children and adults, including higher baseline interferon-associated gene expression in pediatric epithelium. Our results demonstrate cell-intrinsic differences in transcriptional profile and regenerative capacity between proximal airway epithelial cells of children and adults.Graphical abstract
Chimpanzee Brain Morphometry Utilizing Standardized MRI Preprocessing and Macroanatomical Annotations
Authors: Vickery Sam , Hopkins William D. , Sherwood Chet C. , Schapiro Steven J. , Latzman Robert D. , Caspers Svenja , Gaser Christian , Eickhoff Simon B. , Dahnke Robert , Hoffstaedter Felix 
Published: April 2020

AbstractChimpanzees are among the closest living relatives to humans and, as such, provide a crucial comparative model for investigating primate brain evolution. In recent years, human brain mapping has strongly benefited from enhanced computational models and image processing pipelines that could also improve data analyses in animals by using species-specific templates. In this study, we use structural MRI data from the National Chimpanzee Brain Resource (NCBR) to develop the chimpanzee brain reference template Juna.Chimp for spatial registration and the macro-anatomical brain parcellation Davi130 for standardized whole-brain analysis. Additionally, we introduce a ready-to-use image processing pipeline built upon the CAT12 toolbox in SPM12, implementing a standard human image preprocessing framework in chimpanzees. Applying this approach to data from 178 subjects, we find strong evidence for age-related GM atrophy in multiple regions of the chimpanzee brain, as well as, a human-like anterior-posterior pattern of hemi-spheric asymmetry in medial chimpanzee brain regions.
Reprogramming acetogenic bacteria with CRISPR-targeted base editingviadeamination
Authors: Xia Peng-Fei , Casini Isabella , Schulz Sarah , Klask Christian-Marco , Angenent Largus T. , Molitor Bastian 
Published: April 2020

AbstractAcetogenic bacteria are rising in popularity as chassis microbes in biotechnology due to their capability of converting inorganic one-carbon (C1) gases to organic chemicals. To fully uncover the potential of acetogenic bacteria, synthetic-biology tools are imperative to either engineer designed functions or to interrogate the physiology. Here, we report a genome-editing tool at a one-nucleotide resolution, namely base editing, for acetogenic bacteria based on CRISPR-targeted deamination. This tool combines nuclease deactivated Cas9 with activation-induced cytidine deaminase to enable cytosine-to-thymine substitution without DNA cleavage, homology-directed repair, and donor DNA, which are generally the bottlenecks for applying conventional CRISPR-Cas systems in bacteria. We designed and validated a modularized base-editing tool in the model acetogenic bacteriumClostridium ljungdahlii. The editing principles were investigated, and anin-silicoanalysis revealed the capability of base editing across the genome. Moreover, genes related to acetate and ethanol production were disrupted individually by installing premature STOP codons to reprogram carbon flux towards improved acetate production. This resulted in engineeredC. ljungdahliistrains with the desired phenotypes and stable genotypes. Our base-editing tool promotes the application and research in acetogenic bacteria and provides a blueprint to upgrade CRISPR-Cas-based genome editing in bacteria in general.SignificanceAcetogenic bacteria metabolize one-carbon (C1) gases, such as industrial waste gases, to produce fuels and commodity chemicals. However, the lack of efficient gene-manipulation approaches hampers faster progress in the application of acetogenic bacteria in biotechnology. We developed a CRISPR-targeted base-editing tool at a one-nucleotide resolution for acetogenic bacteria. Our tool illustrates great potential in engineering other A-T-rich bacteria and links designed single-nucleotide variations with biotechnology. It provides unique advantages for engineering industrially relevant bacteria without creating genetically modified organisms (GMOs) under the legislation of many countries. This base-editing tool provides an example for adapting CRISPR-Cas systems in bacteria, especially those that are highly sensitive to heterologously expressed Cas proteins and have limited ability of receiving foreign DNA.