bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel regulatory element upstream ofTNFAIP3promoter may be influenced by SLE risk variants
Authors: Nair Ajay , Rao Archana S 
Published: October 2020

AbstractAlmost all of Genome Wide Association Studies (GWAS) hits come from non-coding DNA elements. Data from chromatin interaction analyses suggest a long-range interaction with a putative enhancer upstream ofTNFAIP3. Disrupting the enhancer may impairTNFAIP3expression and enhance SLE risk. Two variants, rs10499197 and rs58905141 carried on the SLE risk haplotype are situated near this enhancer and could affect its function. Cloning the regulatory region surrounding rs10499197 into an expression plasmid containing a CRISPR-Cas9 backbone, and then performing a genome editing assay, we found that the variant is located near an enhancer. And any changes to the SNP region might impair enhancer and its ability to regulateTNFAIP3expression.
Implicit counterfactual effect in partial feedback reinforcement learning: behavioral and modeling approach
Authors: Barakchian Zahra , Vahabie Abdol-hossein , Ahmadabadi Majid Nili 
Published: October 2020

AbstractContext by distorting values of options with respect to the distribution of available alternatives, remarkably affects learning behavior. Providing an explicit counterfactual component, outcome of unchosen option alongside with the chosen one (Complete feedback), would increase the contextual effect by inducing comparison-based strategy during learning. But It is not clear in the conditions where the context consists only of the juxtaposition of a series of options, and there is no such explicit counterfactual component (Partial feedback), whether and how the relativity will be emerged. Here for investigating whether and how implicit and explicit counterfactual components can affect reinforcement learning, we used two Partial and Complete feedback paradigms, in which options were associated with some reward distributions. Our modeling analysis illustrates that the model which uses the outcome of chosen option for updating values of both chosen and unchosen options, which is in line with diffusive function of dopamine on the striatum, can better account for the behavioral data. We also observed that size of this bias depends on the involved systems in the brain, such that this effect is larger in the transfer phase where subcortical systems are more involved, and is smaller in the deliberative value estimation phase where cortical system is more needed. Furthermore, our data shows that contextual effect is not only limited to probabilistic reward but also it extends to reward with amplitude. These results show that by extending counterfactual concept, we can better account for why there is contextual effect in a condition where there is no extra information of unchosen outcome.
Multiple pathways to homothallism in closely related yeast lineages in the Basidiomycota
Authors: Cabrita Alexandra , David-Palma Márcia , Brito Patrícia H. , Heitman Joseph , Coelho Marco A. , Gonçalves Paula 
Published: October 2020

AbstractSexual reproduction in fungi relies on proteins with well-known functions encoded by the mating-type (MAT) loci. In the Basidiomycota,MATloci are often bipartite, with theP/Rlocus encoding pheromone precursors and pheromone receptors and theHDlocus encoding heterodimerizing homeodomain transcription factors (Hd1/Hd2). The interplay between different alleles of these genes within a single species usually generates at least two compatible mating types. However, a minority of species are homothallic, reproducing sexually without an obligate need for a compatible partner. Here we examine the organization and function of theMATloci ofCystofilobasidium capitatum, a species in the order Cystofilobasidiales, which is unusually rich in homothallic species. We determinedMATgene content and organization inC. capitatumand found that it resembles a mating type of the closely related heterothallic speciesCystofilobasidium ferigula. To explain the homothallic sexual reproduction observed inC. capitatumwe examined HD-protein interactions in the twoCystofilobasidiumspecies and determinedC. capitatum MATgene expression both in a natural setting and upon heterologous expression inPhaffia rhodozyma, a homothallic species belonging to a clade sister toCystofilobasidium. We conclude that the molecular basis for homothallism inC. capitatumappears to be distinct from that previously established forP. rhodozyma. Unlike the latter species, homothallism inC. capitatummay involve constitutive activation or dispensability of the pheromone receptor and the functional replacement of the usual Hd1/Hd2 heterodimer by an Hd2 homodimer. Overall, our results suggest that homothallism evolved multiple times within the Cystofilobasidiales.ImportanceSexual reproduction is important for the biology of eukaryotes because it strongly impacts the dynamics of genetic variation. In fungi, although sexual reproduction is usually associated with the fusion between cells belonging to different individuals (heterothallism), sometimes a single individual is capable of completing the sexual cycle alone (homothallism). Homothallic species are unusually common in a fungal lineage named Cystofilobasidiales. Here we studied the genetic bases of homothallism in one species in this lineage,Cystofilobasidium capitatum, and found it to be different in several aspects when compared to another homothallic species,Phaffia rhodozyma, belonging to the genus most closely related toCystofilobasidium. Our results strongly suggest that homothallism evolved independently inPhaffiaandCystofilobasidium, lending support to the idea that transitions between heterothallism and homothallism are not as infrequent as previously thought. Our work also helps to establish the Cystofilobasidiales as a model lineage in which to study these transitions.
Mapping the complex transcriptional landscape of the phytopathogenic bacteriumDickeya dadantii
Authors: Forquet Raphaël , Jiang Xuejiao , Nasser William , Hommais Florence , Reverchon Sylvie , Meyer Sam 
Published: October 2020

ABSTRACTDickeya dadantiiis a phytopathogenic bacterium that causes soft rot in a wide range of plant hosts worldwide, and a model organism for studying virulence gene regulation. The present study provides a comprehensive and annotated transcriptomic map ofD. dadantiiobtained by a computational method combining five independent transcriptomic datasets: (i) paired-end RNA-seq data for a precise re-construction of the RNA landscape; (ii) DNA microarray data providing transcriptional responses to a broad variety of environmental conditions; (iii) long-read Nanopore native RNA-seq data for isoform-level transcriptome validation and determination of transcription termination sites; (iv)dRNA-seq data forthe precise mapping of transcription start sites; (v)in plantaDNA microarray data for a comparison of gene expression profiles betweenin vitroexperiments and the early stages of plant infection. Our results show that transcription units sometimes coincide with predicted operons but are generally longer, most of them comprising internal promoters and terminators that generate alternative transcripts of variable gene composition. We characterise the occurrence of transcriptional read-through at terminators, which might play a basal regulation role and explain the extent of transcription beyond the scale of operons. We finally highlight the presence of noncontiguous operons and excludons in theD. dadantiigenome, novel genomic arrangements that might contribute to the basal coordination of transcription. The highlighted transcriptional organisation may allowD. dadantiito finely adjust its gene expression programme for a rapid adaptation to fast changing environments.IMPORTANCEThis is the first transcriptomic map of aDickeyaspecies. It may therefore significantly contribute to further progress in the field of phytopathogenicity. It is also one of the first reported applications of long-read Nanopore native RNA-seq in prokaryotes. Our findings yield insights into basal rules of coordination of transcription that might be valid for other bacteria, and may raise interest in the field of microbiology in general. In particular, we demonstrate that gene expression is coordinated at the scale of transcription units rather than operons, which are larger functional genomic units capable of generating transcripts with variable gene composition for a fine-tuning of gene expression in response to environmental changes. In line with recent studies, our findings indicate that the canonical operon model is insufficient to explain the complexity of bacterial transcriptomes.
A cross-species interaction with a symbiotic commensal enables cell-density-dependent growth and in vivo virulence of an oral pathogen
Authors: Hoare Anilei , Wang Hui , Meethil Archana , Abusleme Loreto , Hong Bo-Young , Moutsopoulos Niki M. , Marsh Philip D. , Hajishengallis George , Diaz Patricia I. 
Published: October 2020

AbstractRecent studies describe in detail the shifts in composition of human-associated polymicrobial communities from health to disease. However, the specific processes that drive the colonization and overgrowth of pathogens within these communities remain incompletely understood. We used in vitro culture systems and a disease-relevant mouse model to show that population size, which determines the availability of an endogenous diffusible small molecule, limits the growth, colonization, and in vivo virulence of the human oral pathogenPorphyromonas gingivalis. This bacterial pathogen overcomes the requirement for an endogenous cue by utilizing a cell-density dependent, growth-promoting, soluble molecule provided by the symbiotic early colonizerVeillonella parvula, but not produced by other commensals tested. Our work shows that exchange of cell-density-dependent diffusible cues between specific early and late colonizing species in a polymicrobial community drives microbial successions, pathogen colonization and disease development, representing a target process for manipulation of the microbiome towards the healthy state.
An improved experimental pipeline for preparing circular ssDNA viruses for next-generation sequencing
Authors: Aimone Catherine D. , Hoyer J. Steen , Dye Anna E. , Deppong David O. , Duffy Siobain , Carbone Ignazio , Hanley-Bowdoin Linda 
Published: October 2020

AbstractWe present an optimized protocol for enhanced amplification and enrichment of viral DNA for Next Generation Sequencing of begomovirus genomes. The rapid ability of these viruses to evolve threatens many crops and underscores the importance of using next generation sequencing efficiently to detect and understand the diversity of these viruses. We combined enhanced rolling circle amplification (RCA) with EquiPhi29 polymerase and size selection to generate a cost-effective, short-read sequencing method. This optimized protocol produced short-read sequencing with at least 50% of the reads mapping to the viral reference genome. We provide other insights into common misconceptions about RCA and lessons we have learned from sequencing single-stranded DNA viruses. Our protocol can be used to examine viral DNA as it moves through the entire pathosystem from host to vector, providing valuable information for viral DNA population studies, and would likely work well with other CRESS DNA viruses.HighlightsProtocol for short-read, high throughput sequencing of single-stranded DNA viruses using random primersComparison of the sequencing of total DNA versus size-selected DNAComparison of phi29 and Equiphi29 DNA polymerases for rolling circle amplification of viral single-stranded DNA genomes
The Arabidopsis active demethylase ROS1cis-regulates immune-responsive genes by pruning DNA methylation at promoter-regulatory regions
Authors: Halter Thierry , Wang Jingyu , Amesefe Delase , Lastrucci Emmanuelle , Charvin Magali , Rastogi Meenu Singla , Navarro Lionel 
Published: October 2020

AbstractActive DNA demethylation has emerged as an important regulatory process of plant and mammalian immunity. However, very little is known about the mechanisms by which active demethylation controls transcriptional immune reprogramming and disease resistance. Here, we first show that the Arabidopsis active demethylase ROS1 promotes basal resistance towardsPseudomonas syringaeby antagonizing RNA-directed DNA methylation (RdDM). Furthermore, we found that ROS1 facilitates the flagellin-triggered induction of the disease resistance geneRMG1by limiting RdDM at the 3’ boundary of a remnant RC/Helitron transposable element (TE) embedded in its promoter. We further identify flagellin-responsive ROS1 putative primary targets, and show that at a subset of promoters, ROS1 erases methylation at discrete regions exhibiting WRKY transcription factors (TFs) binding. In particular, we demonstrate that ROS1 removes methylation at the orphan immune receptorRLP43promoter, to ensure DNA binding of WRKY TFs. Finally, we show that ROS1-directed demethylation of theRMG1andRLP43promoters is causal for both flagellin responsiveness of these genes and for basal resistance. Overall, these findings significantly advance our understanding of how active demethylases shape transcriptional immune reprogramming to enable antibacterial resistance.HIGHLIGHTSTheTNL RMG1that is regulated by ROS1 positively regulates basal resistance towardsPtoDC3000ROS1 regulates the flg22-triggered differential expression of more than 2000 thousands genes, among which 10% are demethylated by ROS1ROS1 facilitates the transcriptional activation of a subset of flg22-induced genes by antagonizing RdDM at discrete promoter regionsWRKY transcription factors (TFs) bind to the demethylated promoter regions of a subset of flg22-induced ROS1 targetsThe hypermethylation at theRLP43promoter, caused by the lack of ROS1, repels DNA binding of two PAMP-responsive WRKY TFsSpecific hypermethylation at the ROS1-targeted promoter regions ofRMG1andRLP43is causal for their silencing as well as for disease susceptibility againstPtoDC3000
Single-cell landscape of bone marrow metastases in human neuroblastoma unraveled by deep multiplex imaging
Authors: Lazic Daria , Kromp Florian , Kirr Michael , Mivalt Filip , Rifatbegovic Fikret , Halbritter Florian , Bernkopf Marie , Bileck Andrea , Ussowicz Marek , Ambros Inge M , Ambros Peter F , Gerner Christopher , Ladenstein Ruth , Ostalecki Christian , Taschner-Mandl Sabine 
Published: October 2020

ABSTRACTBone marrow commonly serves as a metastatic niche for disseminated tumor cells (DTCs) of solid cancers in patients with unfavorable clinical outcome. Single-cell assessment of bone marrow metastases is essential to decipher the entire spectrum of tumor heterogeneity in these cancers, however, has previously not been performed.Here we used multi-epitope-ligand cartography (MELC) to spatially profile 20 biomarkers and assess morphology in DTCs as well as hematopoietic and mesenchymal cells of eight bone marrow metastases from neuroblastoma patients. We developed DeepFLEX, a single-cell image analysis pipeline for MELC data that combines deep learning-based cell and nucleus segmentation and overcomes frequent challenges of multiplex imaging methods including autofluorescence and unspecific antibody binding.Using DeepFLEX, we built a single-cell atlas of bone marrow metastases comprising more than 35,000 single cells. Comparisons of cell type proportions between samples indicated that microenvironmental changes in the metastatic bone marrow are associated with tumor cell infiltration and therapy response. Hierarchical clustering of DTCs revealed multiple phenotypes with highly diverse expression of markers such as FAIM2, an inhibitory protein in the Fas apoptotic pathway, which we propose as a complementary marker to capture DTC heterogeneity in neuroblastoma.The presented single-cell atlas provides first insights into the heterogeneity of human bone marrow metastases and is an important step towards a deeper understanding of DTCs and their interactions with the bone marrow niche.
Self-Organizing 3D Human Choroid Plexus-Ventricle-Cortical Organoids
Authors: Shaker Mohammed R. , Cooper-White Justin , Wolvetang Ernst J. 
Published: October 2020

ABSTRACTBoth the choroid plexus (CP) and the cortex are derived from the rostral neural tube during early embryonic development. In addition to producing CSF, the CP secretes essential factors that orchestrate cortical development and later neurogenesis. Previous brain modeling efforts with human pluripotent stem cells (hPSCs) generated either cortical or CP tissues in 3D culture. Here, we used hPSC-derived neuroectodermal cells, the building blocks of the anterior body, to simultaneously generate CP that forms ventricles and cortical cells in organoids (CVCOs), which can be maintained as 3D organoid cultures. Large scale culture revealed reproducibility of the protocol independent of cell lines, clones or batches. CVCOs contain mature and functional CP that projects multiple cilia into the ventricle-like fluid filled cysts and is in direct contact with appropriately patterned cortical cells. CVCOs thus recapitulate key features of developing forebrain structures observed inin vivoand constitute a useful for dissecting the role of CP in human forebrain development in health and disease.
Cellular Protrusions Engage Viral Infection Enhancing EF-C Peptide Nanofibrils
Authors: Schütz Desiree , Rode Sascha , Read Clarissa , Müller Janis A. , Glocker Bernhard , Sparrer Konstantin , Fackler Oliver , Walther Paul , Münch Jan 
Published: October 2020

AbstractSelf-assembling peptide nanofibrils (PNF) have gained increasing attention as versatile molecules in material science and biomedicine. One important application of PNF is to enhance retroviral gene transfer, a technology that has been central to the development of gene therapy. The best-investigated and commercially available PNF is derived from a 12-mer peptide termed EF-C. The mechanism of transduction enhancement depends on the polycationic surface of EF-C PNF, which binds to the negatively charged membranes of viruses and cells thereby overcoming electrostatic repulsion and increasing virion attachment and fusion. Assuming an even distribution of charges at the surfaces of virions and cells would result in an evenly distributed interaction of the virions with the cell surface. However, we here report that PNF do not randomly bind at the cell surface but are actively engaged by cellular protrusions. Chemical suppression of protrusion formation in cell lines and primary CD4+ T cells greatly reduced fibril binding and hence virion binding. Thus, the mechanism of PNF-mediated viral transduction enhancement involves active engagement of virus-loaded fibrils by cellular protrusions.
Understanding the information needs and information-seeking behaviours of new-generation engineering designers for effective knowledge management
Authors: Qin Hao , Wang Hongwei , Johnson Aylmer 
Published: October 2020

PurposeThis paper aims to explore the information needs and information-seeking behaviours of the new generation of engineering designers. A survey study is used to approach what their information needs are, how these needs change during an engineering design project and how their information-seeking behaviours have been influenced by the newly developed information technologies (ITs). Through an in-depth analysis of the survey results, the key functions have been identified for the next-generation management systems.Design/methodology/approachThe paper first proposed four hypotheses on the information needs and information-seeking behaviours of young engineers. Then, a survey study was undertaken to understand their information usage in terms of the information needs and information-seeking behaviours during a complete engineering design process. Through analysing the survey results, several findings were obtained and on this basis, further comparisons were made to discuss and evaluate the hypotheses.FindingsThe paper has revealed that the engineering designers' information needs will evolve throughout the engineering design project; thus, they should be assisted at several different levels. Although they intend to search information and knowledge on know-what and know-how, what they really require is the know-why knowledge in order to help them complete design tasks. Also, the paper has shown how the newly developed ITs and web-based applications have influenced the engineers' information-seeking practices.Research limitations/implicationsThe research subjects chosen in this study are engineering students in universities who, although not as experienced as engineers in companies, do go through a complete design process with the tasks similar to industrial scenarios. In addition, the focus of this study is to understand the information-seeking behaviours of a new generation of design engineers, so that the development of next-generation information and knowledge management systems can be well informed. In this sense, the results obtained do reveal some new knowledge about the information-seeking behaviours during a general design process.Practical implicationsThis paper first identifies the information needs and information-seeking behaviours of the new generation of engineering designers. On this basis, the varied ways to meet these needs and behaviours are discussed and elaborated. This intends to provide the key characteristics for the development of the next-generation knowledge management system for engineering design projects.Originality/valueThis paper proposes a novel means of exploring the future engineers' information needs and information-seeking behaviours in a collaborative working environment. It also characterises the key features and functions for the next generation of knowledge management systems for engineering design.
Within- and between-person(s) emotional reactions toward crisis communication
Authors: Wei Lewen , Kim Nahyun 
Published: October 2020

PurposeThe study sought to explore how people's negative emotions change in a crisis situation when they get to know about the crisis and the corporate's socially responsible activities after crisis.Design/methodology/approachA 2 (crisis type: human error vs organization misdeed) × 2 (CSR fit: low vs high) × 3 (motive disclosure: no disclosure vs company-oriented disclosure vs society-oriented disclosure) between-subjects experiment was conducted online.FindingsMore anger was elicited toward organizational misdeed than human error from both within-person and between-persons perspectives. When using CSR as postcrisis strategy, within-person analyses revealed that high CSR fit in message helped to attenuate sadness (and potentially anger) to a greater extent than low CSR fit, whereas between-persons analyses did not find significant effects of either CSR fit or motive disclosure.Originality/valueOur findings demonstrate that situational dynamics in crisis situation constantly influence people's emotional states, suggesting a vertical investigation (e.g. within-individual analysis) of emotions may help both scholars and practitioners better understand the nature of crisis emotions and provide fresh insights on how to cope with them.