bluuebunny/crossref_metadata_2025_split huggingface dataset:
DivBrowse – interactive visualization and exploratory data analysis of variant call matrices
Authors: König Patrick , Beier Sebastian , Mascher Martin , Stein Nils , Lange Matthias , Scholz Uwe 
Published: September 2022

AbstractBackgroundThe sequencing of whole genomes is becoming increasingly affordable. In this context large-scale sequencing projects are generating ever larger datasets of species-specific genomic diversity. As a consequence, more and more genomic data needs to be made easily accessible and analyzable to the scientific community.FindingsWe present DivBrowse, a web application for interactive visualization and exploratory analysis of genomic diversity data stored in Variant Call Format (VCF) files of any size. By seamlessly combining BLAST as an entry point together with interactive data analysis features such as principal component analysis in one graphical user interface, DivBrowse provides a novel and unique set of exploratory data analysis capabilities for genomic biodiversity datasets. The capability to integrate DivBrowse into existing web applications supports interoperability between different web applications. Built-in interactive computation of principal component analysis allows users to perform ad-hoc analysis of the population structure based on specific genetic elements such as genes and exons. Data interoperability is supported by the ability to export genomic diversity data in VCF and General Feature Format (GFF3) files.ConclusionDivBrowse offers a novel approach for interactive visualization and analysis of genomic diversity data and optionally also gene annotation data by including features like interactive calculation of variant frequencies and principal component analysis. The use of established standard file formats for data input supports interoperability and seamless deployment of application instances based on the data output of established bioinformatics pipelines.
Histone lactylation: A new epigenetic axis for host-parasite signalling in malaria?
Authors: Merrick Catherine J. 
Published: September 2022

ABSTRACTEpigenetic marks such as histone acetylation and methylation play important roles in the biology and virulence of malaria parasites. Here I report that histone lactylation is also found in these parasites, and speculate on its potential functions. Lactylation is a new epigenetic modification, discovered only in 2019 in human cells. This nascent field has since focussed largely on human biology, but lactyl epigenetic marks could be particularly important in malaria parasites, which are exposed to high and fluctuating lactate levels in their host environment. This is because parasites in the bloodstream respire by glycolysis, producing lactate, and hyperlactataemia is characteristic of severe malarial disease. Therefore, blood lactate could be a signal for the status of the infected host, which could be directly translated to virulence responses via histone lactylation and modulation of parasite gene expression. Responses could include the rate of conversion into sexual transmission stages, the expression of cytoadherence genes – which enhance immune evasion by the parasite but can exacerbate pathology in the host – and the modulation of parasite stress-resistance. Lactylation may soon join acetylation and methylation as a key tool in the epigenetic arsenal of Plasmodium.
Synthesis of natural history collections data reveals patterns of US freshwater mussel diversity and decline
Authors: Pfeiffer John , Dubose Traci P. , Keogh Sean M. 
Published: September 2022

AbstractNatural history collections are uniquely positioned to chronicle biodiversity changes across time and space and are a fundamental data source in taxon-based research and conservation. With over 90 species listed under the Endangered Species Act, freshwater mussels are one of the most imperiled animal assemblages in the United States and are the focus of considerable conservation efforts (e.g., species status assessments, listing decisions, and recovery plans). Unfortunately, natural history collections data is often underleveraged in such efforts, in part, because much of the data are decentralized and nonstandard, and thus, difficult to access and analyze. Our objective herein is to synthesize, standardize, and enrich digitized US freshwater mussel collections data to better suit the needs of conservation stakeholders. We aggregated specimen records from 45 US natural history collections and enriched these records by programmatically standardizing taxonomic information, flagging potentially problematic records, and joining records with freshwater-specific spatial frameworks (e.g., hydrological units and stream segments) and their associated metadata (e.g., area, stream order, discharge, velocity). The assembled dataset includes 410,665 records, 302 species, and 1,494 hydrological units (8 digit-level). Using these enriched records, we estimated ecological attributes for over 280 freshwater mussel species including aspects of range size (i.e., area of occupancy and change in area of occupancy) and habitat preferences (i.e., stream order size, discharge, slope, and velocity). Listed species had significantly fewer occurrences (p<0.001) and smaller area of occupancy (p<0.001) in comparison to non-listed listed species. Listed species also tended to have a higher stream order preference (p<0.001) and discharge preference than non-listed species (p<0.001). These important ecological attributes have not been incorporated into freshwater mussel conservation efforts in a quantitative way and our novel estimates can be used to make more data-driven ecological and conservation inferences.
Commercial influenza vaccines vary in both the structural arrangements of HA complexes and in induction of antibodies to cross-reactive HA epitopes
Authors: Myers Mallory L. , Gallagher John R. , Kim Alexander J. , Payne Walker H. , Bock Kevin W. , Torian Udana , Moore Ian N. , Harris Audray K. 
Published: September 2022

AbstractInfluenza virus infects millions of people annually and can cause global pandemics. Hemagglutinin (HA) is the primary component of commercial influenza vaccines (CIV), and antibody to HA is a primary correlate of protection. Persistent antigenic variation of HA requires that CIV be reformulated for new strains yearly. Differences in structural organization of HA has not been correlated with induction of broadly reactive antibodies, and CIV formulations can vary in how HA is organized. Using electron microscopy to study four current CIV, we found that these different formulations contained a variety of structures including: individual HAs, starfish-like structures with up to 12 HA molecules, and novel “spiked nanodisc” structures that displayed over 50 HA molecules along the complex’s perimeter. These spiked nanodiscs uniquely exposed conserved stem epitopes and elicited the highest levels of heterosubtypic cross-reactive antibodies. Overall, we found that HA structural organization can be an important CIV parameter and can be associated with the induction of cross-reactive antibodies to conserved HA epitopes.
Systematic analysis of transcriptional and epigenetic effects of genetic variation in Kupffer cells enables discrimination of cell intrinsic and environment-dependent mechanisms
Authors: Bennett Hunter , Troutman Ty D. , Zhou Enchen , Spann Nathanael J. , Link Verena M. , Seidman Jason S. , Nickl Christian K. , Abe Yohei , Sakai Mashito , Pasillas Martina P. , Marlman Justin M. , Guzman Carlos , Hosseini Mojgan , Schnabl Bernd , Glass Christopher K. 
Published: September 2022

ABSTRACTNoncoding genetic variation is a major driver of phenotypic diversity but determining the underlying mechanisms and the cell types in which it acts remain challenging problems. Here, we investigate the impact of natural genetic variation provided by phenotypically diverse inbred strains of mice on gene expression and epigenetic landscapes of Kupffer cells. Analysis of gene expression in Kupffer cells and other liver cell types derived from C57BL/6J, BALB/cJ and A/J mice provided evidence for strain-specific differences in environmental factors influencing Kupffer cell phenotypes, including preferential Leptin signaling in BALB/cJ Kupffer cells. Systematic analysis of transcriptomic and epigenetic data from F1 hybrids of these mice, and transcriptomic data from strain-specific Kupffer cells engrafted into a common host enabled quantitative assessment of cis versus trans effects of genetic variation on gene expression and an estimate of cell autonomous versus non cell autonomous effects. Under homeostatic conditions, trans effects of genetic variation were dominant, with the majority of trans regulation being non cell autonomous. In contrast, strain specific responses to acutely administered LPS were primarily associated with genetic variation acting in cis to modify response elements for lineage determining and signal dependent transcription factors. Collectively, these findings reveal cell intrinsic and environmental effects of natural genetic variation on gene expression, demonstrate the use of enhancers as detectors of trans effects of genetic variation, and provide a new resource for understanding the impact of genetic variation on gene expression in Kupffer cells.
Motif2Site: a Bioconductor package to detect accurate transcription factor binding sites from ChIP-seq
Authors: Zarrineh Peyman , Darieva Zoulfia , Bobola Nicoletta 
Published: September 2022

AbstractTranscription factors (TFs) binding are in the core of the Regulatory networks studies. ChIP-seq experiments are available for many TFs in various species. As TFs co-bind in cis-regulatory elements regions to control gene expression, studying the existing relation among co-binding TFs such as distance of binding sites or co-occupancy are highly important to understand the regulatory mechanisms. Currently, to detect binding sites of each TF in cis-regulatory elements, first binding regions of each TF are detected by standard peak calling methods, and at the second step the best candidate binding sites are prioritized by motif detection methods in binding regions. However, it is well-known that the best prioritized candidate motifs are not necessarily the actual binding sites of TFs. Furthermore, motif prioritizing methods that consider more genomic features complexities of TFs bindings are usually computationally expensive methods. Here, we tend to improve the TF binding sites accuracy detection by using the original ChIP-seq signal. The motifs which are located closer to the summits of binding region peaks are more likely to be the actual binding sites. Therefore, We developed a novel post-processing Bioconductor package called Motif2Site to detect TFs binding sites from user provided motif sets and recenter them across experiments. We applied Motif2Site method to detect TF binding sites for major mouse embryonic stem cell (mESC) as well as mouse fetal and birth time (P0) heart TFs. Motif2Site could detect binding regions with comparable accuracy to the existing state-of-the-art while it substantially increased the accuracy of the detected binding sites. Motif2Site could future improve the accuracy of binding sites prediction by recentering binding sites across developmental conditions (fetal/P0 heart) and across homologous TFs (ex. GATA4/GATA6 and MEF2A/MEF2C). Purifying high-confidence binding sites in mouse fetal heart, enabled us to study the co-binding properties of TFs in cis-regulatory elements. We could also traced TFs footprints in selected heart-specific VISTA enhancers chromatin accessible regions.
Imbalanced Unfolded Protein Response Signaling Contributes to 1-Deoxysphingolipid Retinal Toxicity
Authors: Rosarda Jessica D. , Giles Sarah , Harkins-Perry Sarah , Mills Elizabeth A , Friedlander Martin , Wiseman R. Luke , Eade Kevin T. 
Published: September 2022

SUMMARY1-Deoxysphingolipids (1-dSLs) are atypical cytotoxic sphingolipids formed through the substitution of alanine for serine in de novo sphingolipid biosynthesis. Accumulation of 1-dSLs has been linked to diseases of the eye such as diabetic retinopathy and Macular Telangiectasia Type 2 (MacTel). However, the molecular mechanisms by which 1-dSLs induce toxicity in retinal cells remains poorly understood. Here, we integrate bulk and single-nucleus RNA-sequencing to define the biological pathways that contribute to toxicity caused by the 1-dSL species, 1-deoxysphinganine (1-dSA), in human retinal organoids. Our results demonstrate that 1-dSA preferentially and differentially activates signaling arms of the unfolded protein response (UPR) in photoreceptor cells and Müller glia within retinal organoids. Using a combination of pharmacologic inhibitors and activators, we define the roles for individual arms of the UPR in 1-dSL-mediated toxicity. We show that sustained PERK signaling through the integrated stress response (ISR) promotes 1-dSL-induced apoptosis in photoreceptors. In contrast, deficiencies in signaling through the ATF6 arm of the UPR contribute to photoreceptor toxicity. These results indicate that imbalanced signaling between the pro-apoptotic PERK/ISR and protective ATF6 arms of the UPR contributes to 1-dSL-induced photoreceptor toxicity. Further, our results identify new opportunities to intervene in 1-dSL linked diseases through targeting different signaling arms of the UPR.
Transcriptionally defined morphological subtypes of pancreatic ductal adenocarcinoma
Authors: Krieger Teresa G , Sudy Alexander , Schicktanz Felix , Tosti Luca , Liebig Johannes , Konukiewitz Björn , Rouault Morgane , Niesnerová Anežka , Qian Xiaoyan , Weichert Wilko , Eils Roland , Steiger Katja , Conrad Christian 
Published: September 2022

AbstractTumour heterogeneity remains a major obstacle to effective and precise therapy for pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer. Several transcriptional subtypes of PDAC with differential prognosis have been described, but they co-occur within tumours and are difficult to distinguish in routine clinical workflows. To investigate the relationship between transcriptional PDAC subtypes, local tissue morphology and the tumour microenvironment, we employed in situ sequencing to profile single cells in their spatial tissue context. We identify five transcriptional subtypes of PDAC cells occurring in three distinct morphological patterns, including secretory tumour cell monolayers, invasive tumour cells with high expression of cell adhesion molecules CEACAM5 and CEACAM6, and spatially distributed tumour cells associated with inflammatory-type fibroblasts. Analysis of bulk RNA-sequencing datasets of the TCGA-PAAD and PACA-AU cohorts according to these spatio-transcriptional subtypes confirmed their prognostic significance. Our results thus indicate an automatable substratification based on spatially-resolved transcriptomics of PDAC and identify distinct subtypes of ‘classical’ PDAC, representing most cases of this devastating malignancy.
Requirement for STAT3 and its target, TFCP2L1, in self-renewal of naïve pluripotent stem cellsin vivoandin vitro
Authors: Kraunsoe Sophie , Azami Takuya , Pei Yihan , Martello Graziano , Jones Kenneth , Boroviak Thorsten , Nichols Jennifer 
Published: September 2022

AbstractWe previously demonstrated gradual loss of epiblast during diapause in embryos lacking components of the LIF/IL6 receptor. Here we explore requirement for the downstream signalling transducer and activator of transcription, STAT3 and its target, TFCP2L1, in maintenance of naïve pluripotency. Unlike conventional markers, such as NANOG, which remains high in epiblast until implantation, both STAT3 and TFCP2L1 proteins decline during blastocyst expansion, but intensify in the embryonic region after induction of diapause, as observed visually and confirmed using our novel image analysis tool, consistent with our previous transcriptional expression data. Embryos lacking STAT3 or TFCP2L1, underwent catastrophic loss of most of the inner cell mass during the first few days of diapause, implicating involvement of signals in addition to LIF/IL6 for sustaining naïve pluripotencyin vivo. By blocking MEK/ERK signalling from the morula stage we could derive embryonic stem cells with high efficiency from STAT3 null embryos, but not those lacking TFCP2L1, suggesting a hitherto unknown additional role for this essential STAT3 target in transition from embryo to embryonic stem cellsin vitro.Summary StatementInducing diapause in mouse embryos demonstrates that STAT3 and TFCP2L1 are essential for self-renewal of the epiblast, but only TFCP2L1 is required for derivation of embryonic stem cells.
The transcriptome of acute dehydration in Myeloid Leukemia cells
Authors: Mark Welch David B. , Gould Travis J. , Olins Ada L. , Olins Donald E. 
Published: September 2022

AbstractLive human myeloid leukemia (HL-60/S4) cells exposed to acute hyperosmotic stress with sucrose undergo dehydration and cell shrinkage. Interphase chromatin and mitotic chromosomes congeal, and exhibit altered phase separation (demixing) of chromatin-associated proteins. To investigate concurrent changes in the transcriptome, we exposed exponentially growing HL-60/S4 cells to acute hyperosmotic stress (∼600 milliOsmolar) for 30 and 60 minutes by addition of sucrose to the culture medium. We employed RNA-Seq of polyA mRNA to identify genes with significantly increased or decreased transcript levels relative to untreated control cells (i.e., differential gene expression). These identified genes were examined for over-representation of Gene Ontology (GO) terms. In hyperosmotically-stressed cells, multiple GO terms associated with transcription, translation, mitochondrial function and proteosome activity, as well as the gene set “replication-dependent histones”, were over-represented among genes with increased transcript levels; whereas, genes with decreased transcript levels were over-represented in various GO terms for transcription repressors. The overall transcriptome profiles of these stressed cells suggest a rapid acquisition of cellular rebuilding, a futile homeostatic response, as these cells are ultimately doomed to a dehydrated death.“Do not go gentle into that good nightRage, rage against the dying of the light”Dylan Thomas (1914-1953)
Policy, regulation, and institutional approaches to digital innovation in the wine sector: a cross-country comparison
Authors: Waye Vicki Catherine , Rocca Laura , Veneziani Monica , Helliar Christine , Suryawathy I. Gusti Ary 
Published: September 2022

PurposeThis study explores the impact of institutions, policies, and regulations at the global, national, and sectoral levels on digitalisation within the Italian and Australian wine industries.Design/methodology/approachDrawing on qualitative research data collected from interviews with key personnel in the wine industry, this study shows that both jurisdictions are at a similar stage of emergent digital development despite very different settings.FindingsAccordingly, the authors find that digitalisation is constrained by common policy and regulatory issues emanating at the global and national levels, such as a lack of data infrastructure and data governance, and the need for institutions at the local and regional levels to spur innovation, especially with SMEs.Originality/valueThis is the first study to analyse the role of policy, regulation, and institutional arrangements in digital diffusion using a cross-country comparison of the wine sector.
Let's talk about straw: the effect of information provision on consumers' attitudes towards pig husbandry systems
Authors: Weingarten Nina , Hartmann Monika 
Published: September 2022

PurposeThe type of flooring in stalls is an important factor that shapes consumers' overall perception of animal husbandry. Although slatted and straw floors have benefits and drawbacks, consumers strongly prefer slatted over straw floors in pig husbandry. The present study investigates whether information provision can depolarise consumers' implicit and explicit attitudes towards both floor types to enable a more realistic evaluation of pig husbandry systems. Furthermore, this study examines the effectiveness of information depending on different frames and consumers' personality traits.Design/methodology/approachAn experimental laboratory study with 185 German consumers was conducted to investigate the effect of information on implicit and explicit attitudes towards different flooring types. Participants received information on straw and slatted floors in a cognitive or affective frame or about a control topic. Furthermore, it was analysed whether certain consumer groups respond differently to the cognitive or affective frame.FindingsThe results demonstrated that information provision is a successful tool for depolarising consumers' implicit and explicit attitudes regarding straw and slatted floors. Although consumers continued to prefer straw floors after receiving information, the magnitude of this preference considerably decreased. Mediation analysis illustrated that implicit and explicit attitudes are highly interconnected. The study found no evidence that the personality traits of consumers moderated the effectiveness of the cognitive or affective frame.Originality/valueThe study proposes that information provision can be a potential avenue for increasing the societal acceptance of conventional methods in pig husbandry and provides recommendations for communicating conditions related to animal husbandry. Furthermore, through the inclusion of an implicit measure, this study overcomes biases of other studies in an agricultural context which usually rely only on explicit measures.
Aiming for bullseye: a novel gameplan for circular economy in the construction industry
Authors: Zandee Diane , Zutshi Ambika , Creed Andrew , Nijhof André 
Published: September 2022

PurposeThe paper aims to provide managerial recommendations for implementing circular economy (CE) principles in both organizational and interorganizational contexts, including when using digital tools, such as building information modeling (BIM) and blockchain. Drawn from the construction sector in the Netherlands, the findings can be generalized to similar sectors where a company may receive multiple inputs as part of its supply chain augmented by digital technologies.Design/methodology/approachDesign addresses the research question: what are the strategic and tactical approaches of organizations on the CE pathway? Sub-questions target initiatives pursued by participants, and look toward information, roles and functions for supporting the CE process. Applying a multiple-case study approach (21 semi-structured interviews with 29 participants) the paper explores strategic initiatives of construction companies implementing CE pathways. The strength of the research design comes from facilitation of rich and deep qualitative insights from Netherlands-based managers embedded within global supply chains contributing to conceptual mapping. A limitation is data from one country (though representing both national and multinational companies).FindingsInterviewed managers share guidance for production-related construction companies anchored in materials and product design. Recommendations include to (1) develop both internally and externally the awareness of CE amongst leaders, (2) communicate with internal and external stakeholders for shared vision across the supply chain, (3) start with pilot projects, and (4) ensure product data-integration for CE business models through computer modeling and blockchain for decision-making processes, choices of materials, business model coordination and product (re)design. Continuous learning about CE roles and responsibilities amidst organizational process restructuring is required throughout linear to CE transitions. Extending the time for the CE principles evaluation process would allow for reconsideration of decisions made for CE implemented projects.Originality/valueA novel CE gameplan with a hurdles and recommendations checklist provides an operational interface with decision making points between internal factors for the host organization and external supply chain partners.