bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Physiometric Investigation of Inflammatory Composites: Comparison of “A Priori” Aggregates, Empirically-identified Factors, and Individual Proteins
Authors: Moriarity Daniel P. , Ellman Lauren M. , Coe Christopher L. , Olino Thomas M. , Alloy Lauren B. 
Published: June 2021

AbstractMost research testing the association between inflammation and health outcomes (e.g., heart disease, diabetes, depression) has focused on individual proteins; however, some studies have used summed composites of inflammatory markers without first investigating dimensionality. Using two different samples (MIDUS-2: N = 1,255 adults, MIDUS-R: N = 863 adults), this study investigates the dimensionality of eight inflammatory proteins (C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), fibrinogen, E-selectin, and intercellular adhesion molecule (ICAM)-1) and compared the resulting factor structure to a) an “a priori”/tau-equivalent factor structure in which all inflammatory proteins equally load onto a single dimension (comparable to the summed composites) and b) proteins modeled individually (i.e., no latent variable) in terms of model fit, replicability, reliability, and their associations with health outcomes. An exploratory factor analysis indicated a two-factor structure (Factor 1: CRP and fibrinogen; Factor 2: IL-8 and IL-10) in MIDUS-2 and was replicated in MIDUS-R. Results did not clearly indicate whether the empirically-identified factor structure or the individual proteins modeled without a latent variable had superior model fit, but both strongly outperformed the “a priori”/tau-equivalent structure (which did not achieve acceptable model fit in any models). Modeling the empirically-identified factors and individual proteins (without a latent factor) as outcomes of medical diagnoses resulted in comparable conclusions. However, modeling individual proteins resulted in findings more robust to correction for multiple comparisons despite more conservative adjustments. Further, reliability for all latent variables was poor. These results indicate that modeling inflammation as a unidimensional construct equally associated with all available proteins does not fit the data well. Instead, individual inflammatory proteins or, potentially (if empirically supported and biologically-plausible) empirically-identified inflammatory factors should be used in accordance with theory.
Analysis of science journalism reveals gender and regional disparities in coverage
Authors: Davidson Natalie R. , Greene Casey S. 
Published: June 2021

AbstractScience journalism is a critical way for the public to learn about and benefit from scientific findings. Such journalism shapes the public’s view of the current state of science and legitimizes experts. Journalists can only cite and quote a limited number of sources, who they may discover in their research, including recommendations by other scientists. Biases in either process may influence who is identified and ultimately included as a source. To examine potential biases in science journalism, we analyzed 22,001 non-research articles published by Nature and compared these with Nature-published research articles with respect to predicted gender and name origin. We extracted cited authors’ names and those of quoted speakers. While citations and quotations within a piece do not reflect the entire information-gathering process, they can provide insight into the demographics of visible sources. We then predicted gender and name origin of the cited authors and speakers. We compared articles with a comparator set made up of first and last authors within primary research articles in Nature and a subset of Springer Nature articles in the same time period. In our analysis, we found a skew toward quoting men in Nature science journalism. However, quotation is trending toward equal representation at a faster rate than authorship rates in academic publishing. Gender disparity in Nature quotes was dependent on the article type. We found a significant over-representation of names with predicted Celtic/English origin and under-representation of names with a predicted East Asian origin in both in extracted quotes and journal citations but dampened in citations.
Gene editing in bacteria via SpCas9/sgRNA ribonucleoprotein complexes
Authors: Arroyo-Olarte Rubén Dario , Bravo Rodríguez Ricardo , Morales-Ríos Edgar 
Published: June 2021

AbstractGene editing has been revolutionized by CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas technology in a variety of organisms. In bacteria, however, CRISPR-Cas still holds many caveats such as high toxicity of Cas9 and off-target editing effects. In this work we develop a system for the incorporation of Cas9/single guide RNA ribonucleoprotein complexes in bacteria and their successful application for gene editing via homologous recombination. Targeting of a green fluorescent protein (GFP) reporter allows for easy verification of gene-edition via conversion to blue-fluorescent protein (BFP), mediated by the well characterized 196T > C (Tyr66His) mutation.
Timing of transcriptomic peripheral blood mononuclear cell responses of sheep to Fasciola hepatica infection differs from those of cattle, reflecting different disease phenotypes
Authors: Niedziela Dagmara A. , Naranjo-Lucena Amalia , Molina-Hernández Verónica , Browne John A. , Martínez-Moreno Álvaro , Pérez José , MacHugh David E. , Mulcahy Grace 
Published: June 2021

AbstractInfection with the zoonotic trematode Fasciola hepatica, common in many regions with a temperate climate, leads to delayed growth and loss of productivity in cattle, while infection in sheep can have more severe effects, potentially leading to death. Previous transcriptomic analyses revealed upregulation of TGFB1, cell death and Toll-like receptor signalling, T-cell activation, and inhibition of nitric oxide production in macrophages in response to infection. However, the differences between ovine and bovine responses have not yet been explored. The objective of this study was to further investigate the transcriptomic response of ovine peripheral blood mononuclear cells (PBMC) to F. hepatica infection, and to elucidate the differences between ovine and bovine PBMC responses.Sixteen male Merino sheep were randomly assigned to infected or control groups (n = 8 per group) and orally infected with 120 F. hepatica metacercariae. Transcriptomic data was generated from PBMC at 0, 2 and 16 weeks post-infection (wpi), and analysed for differentially expressed (DE) genes between infected and control animals at each time point (analysis 1), and for each group relative to time 0 (analysis 2). Analysis 2 was then compared to a similar study performed previously on bovine PBMC.A total of 453 DE genes were found at 2 wpi, and 2 DE genes at 16 wpi (FDR < 0.1, analysis 1). Significantly overrepresented biological pathways at 2 wpi included role of PKR in interferon induction and anti-viral response, death receptor signalling and RIG-I-like receptor signalling, which suggested that an activation of innate response to intracellular nucleic acids and inhibition of cellular apoptosis were taking place. Comparison of analysis 2 with the previous bovine transcriptomic study revealed that anti-inflammatory response pathways which were significantly overrepresented in the acute phase in cattle, including IL-10 signalling, Th2 pathway, and Th1 and Th2 activation were upregulated only in the chronic phase in sheep. We propose that the earlier activation of anti-inflammatory responses in cattle, as compared with sheep, may be related to the general absence of acute clinical signs in cattle. These findings offer scope for “smart vaccination” strategies for this important livestock parasite.
Mapping the invisible chromatin transactions of prophase chromosome remodelling
Authors: Samejima Itaru , Spanos Christos , Samejima Kumiko , Rappsilber Juri , Kustatscher Georg , Earnshaw William C. 
Published: June 2021

SUMMARYWe have used a combination of chemical genetics, chromatin proteomics and imaging to map the earliest chromatin transactions during vertebrate cell entry into mitosis. Chicken DT40 CDK1ascells undergo synchronous mitotic entry within 15 minutes following release from a 1NM-PP1-induced arrest in late G2. In addition to changes in chromatin association with nuclear pores and the nuclear envelope, earliest prophase is dominated by changes in the association of ribonucleoproteins with chromatin, particularly in the nucleolus, where pre-rRNA processing factors leave chromatin significantly before RNA polymerase I. Nuclear envelope barrier function is lost early in prophase and cytoplasmic proteins begin to accumulate on the chromatin. As a result, outer kinetochore assembly appears complete by nuclear envelope breakdown (NEBD). Most interphase chromatin proteins remain associated with chromatin until NEBD, after which their levels drop sharply. An interactive proteomic map of chromatin transactions during mitotic entry is available as a resource athttps://mitoChEP.bio.ed.ac.uk.
Chronic temperature stress effects on the liver proteome of two threespine stickleback (Gasterosteus aculeatus) populations using a novel DIA assay library
Authors: Levitan Bryn Bo , Kültz Dietmar 
Published: June 2021

ABSTRACTA data-independent acquisition (DIA) assay library was generated for the liver of threespine sticklebacks to evaluate alterations in protein abundance and functional enrichment of molecular pathways following either chronic warm (25°C) or cold (7°C) three-week temperature challenge in two estuarine populations. The DIA assay library was created from a data-dependent acquisition (DDA) based raw spectral library that was filtered to remove low quality or ambiguous peptides. Functional enrichment analyses using STRING identified larger networks that were significantly enriched by examining both the entire liver proteome and only significantly elevated or depleted proteins from the various comparisons. These systems level analyses revealed the unique liver proteomic signatures of two populations of threespine sticklebacks acclimated to chronic temperature stress. The Big lagoon population (BL) had a stronger response than the Klamath river population (KL). At 7°C, BL showed alterations in protein homeostasis that likely fueled a higher demand for energy, but both populations successfully acclimated to this temperature. The warm acclimation induced major increases in proteins involved in chromatin structure and transcription, while there were decreases in proteins related to translation and fatty acid metabolism. Functional enrichment analyses of the entire liver proteome uncovered differences in glycolysis and carbohydrate metabolism between the two populations and between the cold acclimated and control groups. We conclude that the synchronous regulatory patterns of many proteins observed in the liver of threespine sticklebacks provide more comprehensive insight into population-specific responses to thermal stress than the use of less specific pre-determined biomarkers.
Immunosuppressive traits of the hybrid epithelial/mesenchymal phenotype
Authors: Sahoo Sarthak , Nayak Sonali Priyadarshini , Hari Kishore , Purkait Prithu , Mandal Susmita , Kishore Akash , Levine Herbert , Jolly Mohit Kumar 
Published: June 2021

AbstractRecent preclinical and clinical data suggests enhanced metastatic fitness of hybrid epithelial/ mesenchymal (E/M) phenotypes, but mechanistic details regarding their survival strategies during metastasis remain unclear. Here, we investigate immune-evasive strategies of hybrid E/M states. We construct and simulate the dynamics of a minimalistic regulatory network encompassing the known associations among regulators of EMT (epithelial-mesenchymal transition) and PD-L1, an established immune-suppressor. Our model simulations, integrated with single-cell and bulk RNA-seq data analysis, elucidate that hybrid E/M cells can have high levels of PD-L1, similar to those seen in cells with a full EMT phenotype, thus obviating the need for cancer cells to undergo a full EMT to be immune-evasive. Specifically, in breast cancer, we show the co-existence of hybrid E/M phenotypes, enhanced resistance to anti-estrogen therapy and increased PD-L1 levels. Our results underscore how the emergent dynamics of interconnected regulatory networks can coordinate different axes of cellular fitness during metastasis.
An artificial host system enables the obligate parasitic plant Cuscuta campestris to grow and complete its life cycle in vitro
Authors: Bernal-Galeano Vivian , Westwood James H. 
Published: June 2021

AbstractCuscuta campestris is an obligate parasitic plant that requires a host to complete its lifecycle. Parasite-host connections occur via an haustorium, a unique organ that acts as a bridge for the uptake of water, nutrients and macromolecules. Research on Cuscuta is often complicated by host influences, but comparable systems for growing the parasite in the absence of a host do not exist. We developed an axenic method to grow C. campestris on an Artificial Host System (AHS). We evaluated the effects of nutrients and phytohormones on parasite haustoria development and growth. Haustorium morphology and gene expression were characterized. The AHS consists of an inert, fibrous stick that mimics a host stem, wicking water and nutrients to the parasite. It enables C. campestris to exhibit a parasitic habit and develop through all stages of its lifecycle, including production of new shoots and viable seeds. Phytohormones NAA and BA affect haustoria morphology, and increase parasite fresh weight and biomass. Gene expression in AHS haustoria reflect process similar to those in haustoria on actual host plants. The AHS is a methodological improvement for studying Cuscuta biology by avoiding specific host effects on parasite and giving researchers full control of the parasite environment.
Voltage-driven polyelectrolyte complexation inside a nanopore
Authors: Tripathi Prabhat , Jeon Byoung-jin , Muthukumar Murugappan 
Published: June 2021

ABSTRACTWe have investigated how a pair of oppositely charged macromolecules can be driven by an electric field to form a polyelectrolyte complex inside a nanopore. To observe and isolate an individual complex pair, a model protein nanopore, embedded in artificial phospholipid membrane, allowing compartmentalization (cis/trans) is employed. A polyanion in the cis and a polycation in the trans compartments are subjected to electrophoretic capture by the pore. We find that the measured ionic current across the pore has a distinguishable signature of complex formation, which is different from the signature of the passage of individual molecules through the pore. The ionic current signature allows us to detect the interaction between the two oppositely charged macromolecules and thus, enables us to measure the lifetime of the complex inside the nanopore. After showing that we can isolate a complex pair in the nanopore, we studied the effects of molecular identity on the nature of interaction in different complex pairs. In contrast to the irreversible conductance state of the alpha-hemolysin (αHL) channel in the complexation of poly-styrene-sulfonate (PSS) and poly-L-lysine (PLL), a reversible conductance state is observed during complexation between single stranded DNA (ssDNA) and PLL. This suggests that there is a weak interaction between ssDNA and PLL, when compared to the interaction in a PSS–PLL complex. Analysis of the PSS-PLL complexation events and its lifetime inside the nanopore supports a four step-mechanism: (i) The polyanion is captured by the pore, (ii) the polyanion starts threading through the pore. (iii) The polycation is captured, a complex pair is formed in the pore, and the polyanion slides along the polycation. (iv) The complex pair can be pulled through the pore into the trans compartment or it can dissociate. Additionally, we have developed a simple theoretical model, which describes the lifetime of the complex inside the pore. The observed reversible two-state conductance across αHL channel during ssDNA-PLL complexation, is described as the binding/unbinding of PLL during the translocation of ssDNA. This enables us to evaluate the apparent rate constants for association/dissociation and equilibrium dissociation constants for the interaction of PLL with ssDNA. This work throws light on the behavior of polyelectrolyte complexes in an electric field and enhances our understanding of the electrical aspects of inter-macromolecular interactions, which plays an extremely important role in the organization of macromolecules in the crowded and confined cellular environment.
Notch-dependent Abl signaling regulates cell motility during ommatidial rotation in Drosophila
Authors: Koca Yildiz , Vuong Linh T. , Singh Jaskirat , Giniger Edward , Mlodzik Marek 
Published: June 2021

AbstractA collective cell motility event that occurs during Drosophila eye development, ommatidial rotation (OR), serves as a paradigm for signaling pathway-regulated directed movement of cell clusters. OR is instructed by several signaling events, including the EGFR and Notch pathways, and planar cell polarity (PCP) signaling, all of which are associated with photoreceptor R3 and R4 specification and differentiation. Here, we show that Abl kinase negatively regulates ommatidial rotation through its activity in the R3/R4 pair. Interestingly in wild-type, Abl is localized to apical junctional regions in R4 but not in R3 during OR, and this apical enrichment requires Notch signaling. We further demonstrate that Abl and Notch genetically interact during OR, and Abl co-immunoprecipitates in complexes with Notch in the developing eye disc. Perturbations of Abl interfere with adherens junction dynamics of the ommatidial preclusters, which are critical for the OR process. Taken together, our data suggest a model in which Abl kinase acts directly downstream of the Notch receptor in R4 to fine-tune OR via its input into adherens junction complexes.
ShinyArchR.UiO: User-friendly, integrative and open-source tool for visualisation of single-cell ATAC-seq data using ArchR
Authors: Sharma Ankush , Akshay Akshay , Rogne Marie , Eskeland Ragnhild 
Published: June 2021

AbstractMotivationMapping of chromatin accessibility landscapes in single-cells and the integration with gene expression enables a better understanding of gene regulatory mechanisms defining cell identities and cell-fate determination in development and disease. Generally, raw data generated from single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq) are deposited in repositories that are inaccessible due to lack of in-depth knowledge of computational programming.ResultsWe have developed ShinyArchR.UiO, an R-based shiny app, that facilitates scATAC-seq data accessibility and visualisation in a user-friendly, interactive, and open-source web interface. ShinyArchR.UiO is a tool that can streamline collaborative efforts for interpretation of massive chromatin accessible data and promotes open access data sharing for wider audiences.Availability and implementationShinyArchR.UiO is available at https://Github.com/EskelandLab/ShinyArchRUiO and a demo server set up with a haematopoietic tutorial dataset: https://cancell.medisin.uio.no/ShinyArchR.UiOContactAnkush.Sharma@medisin.uio.no & Ragnhild.Eskeland@medisin.uio.no
Modeling the impact of data sharing on variant classification
Authors: Casaletto James , Cline Melissa , Shirts Brian 
Published: June 2021

ABSTRACTObjectiveMany genetic variants are classified, but many more are designated as variants of uncertain significance (VUS). Patient data may provide sufficient evidence to classify VUS. Understanding how long it would take to accumulate sufficient patient data to classify VUS can inform many important decisions such as data sharing, disease management, and functional assay development.Materials and MethodsOur software models accumulation of clinical data and their impact on variant interpretation to illustrate the time and probability for variants to be classified when clinical laboratories share evidence, when they silo evidence, and when they share only variant interpretations.ResultsOur models show that the probability of classifying a rare pathogenic variant with an allele frequency of 1/100,000 (1e-05) from less than 25% with no data sharing to nearly 80% after one year when labs share data, with nearly 100% classification after 5 years. Conversely, our models found that extremely rare (1/1,000,000 or 1e-06) variants have a low probability of classification using only clinical data.DiscussionThese results quantify the utility of data sharing and demonstrate the importance of alternative lines of evidence for the interpretation of rare variants. Understanding variant classification circumstances and timelines provides valuable insight for data owners, patients, and service providers. While our modeling parameters are based on assumptions of the rate of accumulation of clinical observations, users may experiment with the impact of these rates by downloading the software and rerunning the simulations with updated parameters.ConclusionThe modeling software is available at https://github.com/BRCAChallenge/classification-timelines.
The green tea catechin EGCG provides proof-of-concept for a pan-coronavirus entry inhibitor
Authors: LeBlanc Emmanuelle V. , Colpitts Che C. 
Published: June 2021

AbstractThe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emphasized the serious threat to human health posed by emerging coronaviruses. Effective antiviral countermeasures are urgently needed as vaccine development and deployment against an emerging coronavirus takes time, even in the best-case scenario. The green tea catechin, epigallocatechin gallate (EGCG), has broad spectrum antiviral activity. We demonstrate here that EGCG prevents murine and human coronavirus infection and blocks the entry of lentiviral particles pseudotyped with spike proteins from highly pathogenic coronaviruses, as well as a bat coronavirus poised to emerge into humans. We show that EGCG treatment reduces coronavirus attachment to target cell surfaces. Our results demonstrate the potential for the development of pan-coronavirus attachment inhibitors to protect against current and future emerging coronaviruses.