bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection Groups Differential (IGD) Score Reveals Infection Ability Difference between SARS-CoV-2 and Other Coronaviruses
Authors: Song Ziwei , Zhou Xingchen , Cai Yuanyuan , Feng Shuo , Zhang Tingting , Wang Yun , Lai Maode , Li Jing 
Published: May 2020

AbstractThe Corona Virus Disease 2019 (COVID-19) pandemic that began in late December 2019 has resulted in millions of cases diagnosed worldwide. Reports have shown that SARS-CoV-2 shows extremely higher infection rates than other coronaviruses. This study conducted a phylogenetics analysis of 91 representative coronaviruses and found that the functional spike protein of SARS-CoV-2, which interacts with the human receptor ACE2, is actually not undergoing distinct selection pressure compared to other coronaviruses. Furthermore, we define a new measurement, infection group differential (IGD) score, in assessing the infection ability of two human coronavirus groups. There are nine extremely high IGD (ehIGD) sites in the receptor-binding domain (RBD) out of 40 high IGD (hIGD) sites that exhibit a unique infection-related pattern from the haplotype network and docking energy comparison. These 40 hIGD sites are basically conserved among the SARS-CoV-2, i.e. there are only two hIGD sites mutated in four out of 1,058 samples, defined as rare-mutation hIGD (rhIGD) sites. In conclusion, ehIGD and rhIGD sites might be of great significance to the development of vaccines.
TCF7L2Silencing Reprograms the 4D Nucleome of Colorectal Cancer Cells
Authors: Brown Markus A. , Dotson Gabrielle A. , Ronquist Scott , Emons Georg , Rajapakse Indika , Ried Thomas 
Published: May 2020

AbstractCanonical Wnt signaling is crucial for intestinal homeostasis as the major Wnt signaling effector in the intestines, TCF4, is required for stem cell maintenance. The capability of TCF4 to maintain the stem cell phenotype is contingent upon β-catenin, a potent transcriptional activator which interacts with histone acetyltransferases and chromatin remodeling complexes. In colorectal cancer, mutations result in high levels of nuclear β-catenin causing aberrant cell growth. Here, we used RNAi to explore the influence of TCF4 on chromatin structure (Hi-C) and gene expression (RNA sequencing) across a 72-hour time series in colorectal cancer. We found that TCF4 reduction results in a disproportionate upregulation of gene expression genome-wide, including a powerful induction ofSOX2. Hi-C analysis revealed a general increase in chromatin compaction across the entire time series, though this did not influence gene expression. Analysis of local chromosome organization demonstrated a TAD boundary loss which influenced the expression of a cluster ofCEACAMgenes on chromosome 19. Four-dimensional nucleome (4DN) analysis, which integrates structural (Hi-C) and functional (RNA sequencing) data, identified EMT and E2F as the two most deregulated pathways andLUM, TMPO, andAURKAas highly influential genes in these networks. Results from gene expression, chromatin structure, and centrality analyses were then integrated to generate a list of candidate transcription factors for reprogramming of colorectal cancer cells to a vulnerable state. The top ranked transcription factor in our analysis was c-JUN, an oncoprotein known to interact with TCF4 and β-catenin.
Rescuing AAV gene transfer from antibody neutralization with an IgG-degrading enzyme
Authors: Elmore Zachary C. , Oh Daniel K. , Simon Katherine E. , Fanous Marcos M. , Asokan Aravind 
Published: May 2020

AbstractPre-existing humoral immunity to recombinant adeno-associated viral (AAV) vectors restricts the treatable patient population and efficacy of human gene therapies. Approaches to clear neutralizing antibodies (NAbs), such as plasmapheresis and immunosuppression are either ineffective or cause undesirable side effects. Here, we describe a clinically relevant strategy to rapidly and transiently degrade NAbs prior to AAV administration using an IgG degrading enzyme (IdeZ). We demonstrate that recombinant IdeZ efficiently cleaves IgG in dog, monkey and human antisera. Prophylactically administered IdeZ cleaves circulating, human IgG in mice and prevents AAV neutralizationin vivo. In macaques, a single intravenous dose of IdeZ rescues AAV transduction by transiently reversing seropositivity. Importantly, IdeZ efficiently cleaves NAbs and rescues AAV transduction in mice passively immunized with individual human donor sera representing a diverse population. Our antibody clearance approach presents a new paradigm for expanding the prospective patient cohort and improving efficacy of AAV gene therapy.
Comparison of the Accula SARS-CoV-2 Test with a Laboratory-Developed Assay for Detection of SARS-CoV-2 RNA in Clinical Nasopharyngeal Specimens
Authors: Hogan Catherine A. , Garamani Natasha , Lee Andrew S. , Tung Jack K. , Sahoo Malaya K. , Huang ChunHong , Stevens Bryan , Zehnder James , Pinsky Benjamin A. 
Published: May 2020

AbstractBackgroundSeveral point-of-care (POC) molecular tests have received emergency use authorization (EUA) from the Food and Drug Administration (FDA) for diagnosis of SARS-CoV-2. The test performance characteristics of the Accula (Mesa Biotech) SARS-CoV-2 POC test need to be evaluated to inform its optimal use.ObjectivesThe aim of this study was to assess test performance of the Accula SARS-CoV-2 test.Study designThe performance of the Accula test was assessed by comparing results of 100 nasopharyngeal swab samples previously characterized by the Stanford Health Care EUA laboratory-developed test (SHC-LDT) targeting the envelope (E) gene. Assay concordance was assessed by overall percent agreement, positive percent agreement (PPA), negative percent agreement (NPA), and Cohen’s kappa coefficient.ResultsOverall percent agreement between the assays was 84.0% (95% confidence interval [CI] 75.3 to 90.6%), PPA was 68.0% (95% CI 53.3 to 80.5%) and the kappa coefficient was 0.68 (95% CI 0.54 to 0.82). Sixteen specimens detected by the SHC-LDT were not detected by the Accula test, and showed low viral load burden with a median cycle threshold value of 37.7. NPA was 100% (95% CI 94.2 to 100%).ConclusionCompared to the SHC-LDT, the Accula SARS-CoV-2 test showed excellent negative agreement. However, positive agreement was low for samples with low viral load. The false negative rate of the Accula POC test calls for a more thorough evaluation of POC test performance characteristics in clinical settings, and for confirmatory testing in individuals with moderate to high pre-test probability of SARS-CoV-2 who test negative on Accula.
Sensitivity to food and cocaine cues are independent traits in a large sample of heterogeneous stock rats
Authors: King Christopher P. , Tripi Jordan A. , Hughson Alesa R. , Horvath Aidan P. , Lamparelli Alexander C. , Holl Katie L. , Chitre Apurva , Polesskaya Oksana , Richards Jerry B. , Woods Leah C. Solberg , Palmer Abraham A. , Robinson Terry E. , Flagel Shelly B. , Meyer Paul J. 
Published: May 2020

AbstractSensitivity to cocaine and its associated stimuli (“cues”) are important factors in the development and maintenance of addiction. Rodent studies suggest that this sensitivity is related, in part, to the propensity to attribute incentive salience to food cues, which, in turn, contributes to the maintenance of cocaine self-administration, and cue-induced relapse of drug-seeking. Whereas each of these traits has established links to drug use, the relatedness between the individual traits themselves has not been well characterized in preclinical models. To this end, the propensity to attribute incentive salience to a food cue was first assessed in a large population of 2716 outbred heterogeneous stock rats. We then determined whether this was associated with performance in two paradigms (cocaine conditioned cue preference and cocaine contextual conditioning). These measure the unconditioned locomotor effects of cocaine, as well as conditioned approach and the locomotor response to a cocaine-paired floor or context. There was large individual variability and sex differences among all traits, but they were largely independent of one another in both males and females. These findings suggest that these traits may contribute to drug-use via independent underlying neuropsychological processes.
Farm yard manure enhances phosphate fertilizer use efficiency in different upland rice genotypes through mitigating aluminium toxicity
Authors: De Bauw Pieterjan , Shimamura Erina , Rakotoson Tovohery , Andriamananjara Andry , Verbeeck Mieke , Merckx Roel , Smolders Erik 
Published: May 2020

AbstractUpland rice production on weathered soils is often constrained by phosphorus (P) deficiency and soil acidity. Farmyard manure application (FYM) can sharply enhance yields and agronomic P fertilizer (TSP) efficiency. We tested the hypothesis that rice genotypes differ in the extent of using organic P and offering distinct benefits under TSP-FYM combinations. Multiple field trials were conducted in the uplands of Madagascar, with factorial combinations of six genotypes, FYM, and TSP applications, with blanket N&K additions. Rice grain yields reached 6 t ha-1after three years of TSP+FYM application, were lower when FYM or TSP were used separately, while crops failed under zero P input. Genotypic differences were inferior to the large treatment effects. Application of FYM increased soil pH and CaCl2-extractable P while decreasing CaCl2-extractable aluminium. An additional liming trial indicated that beneficial effects of FYM over TSP relate to liming effects. Genotypic ranking of yields and agronomic efficiency was inconsistent, without superior genotypes under FYM versus TSP. However, Chomrong Dhan and FOFIFA 172 showed superior yields under TSP+FYM. The FYM application lowers aluminium toxicity which overrules potential effects of organic P supply. Aluminium tolerance should be included when developing rice genotypes for low P tolerance in weathered soils.
Small interfering RNAs are highly effective inhibitors regarding Crimean-Congo hemorrhagic fever virus replicationin vitro
Authors: Földes Fanni , Madai Mónika , Papp Henrietta , Kemenesi Gábor , Zana Brigitta , Geiger Lili , Gombos Katalin , Somogyi Balázs , Bock-Marquette Ildikó , Jakab Ferenc 
Published: May 2020

AbstractCrimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of World Health Organization, considering its potential to create a public health emergency and more importantly, the absence of efficacious drugs and/or vaccines regarding treatment. The highly lethal nature characteristic to CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design siRNAs that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 hours, nucleic acid from the supernatant was extracted for Droplet Digital PCR analysis. Among the investigated siRNAs we identified four effective candidates against all three segments of CCHF genome: one for the S and M segments, whilst two for the L segment. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAsin vitro. The most active siRNAs were demonstrated a specific inhibitory effect against CCHFV in a dose-dependent manner. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replicationin vitro. This promising result can be used in future anti-CCHFV therapy developments.
Targeted mutation of barley (1,3;1,4)-β-glucan synthases reveals complex relationships between the storage and cell wall polysaccharide content
Authors: Garcia-Gimenez Guillermo , Barakate Abdellah , Smith Pauline , Stephens Jennifer , Khor Shi F. , Doblin Monika S. , Hao Pengfei , Bacic Antony , Fincher Geoffrey B. , Burton Rachel A. , Waugh Robbie , Tucker Matthew R. , Houston Kelly 
Published: May 2020

SummaryBarley (Hordeum vulgareL) grain is comparatively rich in (1,3;1,4)-β-glucan, a source of fermentable dietary fibre that protects against various human health conditions. However, low grain (1,3;1,4)-β-glucan content is preferred for brewing and distilling. We took a reverse genetics approach, using CRISPR/Cas9 to generate mutations in members of theCellulose synthase-like(Csl) gene superfamily that encode known (HvCslF6andHvCslH1) and putative (HvCslF3andHvCslF9) (1,3;1,4)-β-glucan synthases. Resultant mutations ranged from single amino acid (aa) substitutions to frameshift mutations causing premature stop codons, and led to specific differences in grain morphology, composition and (1,3;1,4)-β-glucan content. (1,3;1,4)-β-Glucan was absent in the grain ofcslf6knock-out lines whereascslf9knock-out lines had similar (1,3;1,4)-β-glucan content to WT. However,cslf9mutants showed changes in the abundance of other cell wall-related monosaccharides compared to WT. Thousand grain weight (TGW), grain length, width and surface area were altered incslf6knock-outs and to a lesser extent TGW incslf9knock-outs. cslf3andcslh1mutants had no effect on grain (1,3;1,4)-β-glucan content. Our data indicate that multiple members of theCslF/Hfamily fulfil important functions during grain development but, with the exception ofHvCslF6, do not impact the abundance of (1,3;1,4)-β-glucan in mature grain.
Pervasive non-CpG methylation at zebrafish mosaic satellite repeats
Authors: Ross Samuel E , Angeloni Allegra , de Mendoza Alex , Bogdanovic Ozren 
Published: May 2020

AbstractIn vertebrates, DNA methylation predominantly occurs at CG dinucleotides even though widespread non-CG methylation (mCH) has been reported in mammalian embryonic and neural cells. Unlike in mammals, where mCH is found enriched at CAC/G trinucleotides and is tissue-restricted, we find that zebrafish embryos as well as adult somatic and germline tissues display robust methylation enrichment at TGCT positions associated with mosaic satellite repeats. These repeats reside in H3K9me3-marked heterochromatin and display mCH reprogramming coincident with zygotic genome activation. Altogether, this work provides insight into a novel form of vertebrate mCH and highlights the substrate diversity of vertebrate DNA methyltransferases.
Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions
Authors: Molony Claire , King Damien , Di Luca Mariana , Kitching Michael , Olayinka Abidemi , Hakimjavadi Roya , Julius Lourdes A.N. , Fitzpatrick Emma , Gusti Yusof , Burtenshaw Denise , Healy Killian , Finlay Emma K. , Kernan David , Llobera Andreu , Liu Weimin , Morrow David , Redmond Eileen M. , Ducrée Jens , Cahill Paul A. 
Published: May 2020

AbstractA hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening and lesion formation. While medial SMCs contribute to vascular lesions, the involvement of resident vascular stem cells (vSCs) remains unclear. We evaluated single cell photonics as a discriminator of cell phenotypein vitrobefore the presence of vSC within vascular lesions was assessedex vivousing supervised machine learning and further validated using lineage tracing analysis. Using a novel lab-on-a-Disk (Load) platform, label-free single cell photonic emissions from normal and injured vesselsex vivowere interrogated and compared to freshly isolated aortic SMCs, cultured Movas SMCs, macrophages, B-cells, S100β+mVSc, bone marrow derived mesenchymal stem cells (MSC) and their respective myogenic progeny across five broadband light wavelengths (λ465 – λ670 ± 20 nm). We found that profiles were of sufficient coverage, specificity, and quality to clearly distinguish medial SMCs from different vascular beds (carotid vs aorta), discriminate normal carotid medial SMCs from lesional SMC-like cellsex vivofollowing flow restriction, and identify SMC differentiation of a series of multipotent stem cells following treatment with transforming growth factor beta 1 (TGF-β1), the Notch ligand Jaggedl, and Sonic Hedgehog using multivariate analysis, in part, due to photonic emissions from enhanced collagen III and elastin expression. Supervised machine learning supported genetic lineage tracing analysis of S100β+vSCs and identified the presence of S100β+vSC-derived myogenic progeny within vascular lesions. We conclude disease-relevant photonic signatures may have predictive value for vascular disease.
Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes
Authors: Guo Hua , Hu Bing-Jie , Yang Xing-Lou , Zeng Lei-Ping , Li Bei , Ouyang Song-Ying , Shi Zheng-Li 
Published: May 2020

AbstractThe Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. It is speculated that the interaction between bat ACE2 and SARSr-CoV spike proteins drives diversity. Here, we have identified a series ofR. sinicusACE2 variants with some polymorphic sites involved in the interaction with the SARS-CoV spike protein. Pseudoviruses or SARSr-CoVs carrying different spike proteins showed different infection efficiency in cells transiently expressing bat ACE2 variants. Consistent results were observed by binding affinity assays between SARS- and SARSr-CoV spike proteins and receptor molecules from bats and humans. All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with their SARS-CoV counterpart. Structure modeling revealed that the difference in binding affinity between spike and ACE2 might be caused by the alteration of some key residues in the interface of these two molecules. Molecular evolution analysis indicates that these residues were under strong positive selection. These results suggest that the SARSr-CoV spike protein andR. sinicusACE2 may have coevolved over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics. It further proves thatR. sinicusis the natural host of SARSr-CoVs.ImportanceEvolutionary arms race dynamics shape the diversity of viruses and their receptors. Identification of key residues which are involved in interspecies transmission is important to predict potential pathogen spillover from wildlife to humans. Previously, we have identified genetically diverse SARSr-CoV in Chinese horseshoe bats. Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. These ACE2 variants support SARS- and SARSr-CoV infection but with different binding affinity to different spike proteins. The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity of spillover to humans. The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests a long-term and ongoing coevolutionary dynamics between them. Continued surveillance of this group of viruses in bats is necessary for the prevention of the next SARS-like disease.
Drosophilaphosphatidylinositol-4 kinasefwdpromotes mitochondrial fission and can suppressPink1/parkinphenotypes
Authors: Terriente-Felix Ana , Wilson Emma L. , Whitworth Alexander J. 
Published: May 2020

AbstractBalanced mitochondrial fission and fusion play an important role in shaping and distributing mitochondria, as well as contributing to mitochondrial homeostasis and adaptation to stress. In particular, mitochondrial fission is required to facilitate degradation of damaged or dysfunctional units via mitophagy. Two Parkinson’s disease factors, PINK1 and Parkin, are considered key mediators of damage-induced mitophagy, and promoting mitochondrial fission is sufficient to suppress the pathological phenotypes inPink1/parkinmutantDrosophila. We sought additional factors that impinge on mitochondrial dynamics and which may also suppressPink1/parkinphenotypes. We found that theDrosophilaphosphatidylinositol 4-kinase IIIβ homologue, Four wheel drive (Fwd), promotes mitochondrial fission downstream of the pro-fission factor Drp1. Previously described only as male sterile, we identified several new phenotypes infwdmutants, including locomotor deficits and shortened lifespan, which are accompanied by mitochondrial dysfunction. Finally, we found thatfwdoverexpression can suppress locomotor deficits and mitochondrial disruption inPink1/parkinmutants, consistent with its function in promoting mitochondrial fission. Together these results shed light on the complex mechanisms of mitochondrial fission and further underscore the potential of modulating mitochondrial fission/fusion dynamics in the context of neurodegeneration.Author SummaryMitochondria are dynamic oganelles that can fuse and divide, in part to facilitate turnover of damaged components. These processes are essential to maintain a healthy mitochondrial network, and, in turn, maintain cell viability. This is critically important in high-energy, post-mitotic tissues such as neurons. We previously identifiedDrosophilaphosphatidylinositol-4 kinasefwdas a pro-fission factor in a cell-based screen. Here we show that loss offwdregulates mitochondrial fissionin vivo, and acts genetically downstream ofDrp1. We identified new phenotypes infwdmutants, similar to loss ofPink1/parkin, two genes linked to Parkinson’s disease and key regulators of mitochondrial homeostasis. Importantly,fwdoverexpression is able to substantially suppress locomotor and mitochondrial phenotypes inPink1/parkinmutants, suggesting manipulating phophoinositides may represent a novel route to tackling Parkinson’s disease.
Hyperbolic odorant mixtures as a basis for more efficient signaling between flowering plants and bees
Authors: Ghaninia Majid , Zhou Yuansheng , Knauer Anina C. , Schiestl Florian P. , Sharpee Tatyana O. , Smith Brian H. 
Published: May 2020

AbstractAnimals use odors in many natural contexts, for example, for finding mates or food, or signaling danger. Most analyses of natural odors search for either the most meaningful components of a natural odor mixture, or they use linear metrics to analyze the mixture compositions. However, we have recently shown that the physical space for complex mixtures is ‘hyperbolic’, meaning that there are certain combination of variables that have a disproportionately large impact on perception and that these variables have specific interpretation in terms of metabolic processes taking place inside the flower and fruit that produce the odors. Here we show that the statistics of odorants and odorant mixtures produced by inflorescences (Brassica rapa) are also better described with a hyperbolic rather than a linear metric, and that combinations of odorants in the hyperbolic space are better predictors of the nectar and pollen resources sought by bee pollinators than the standard Euclidian combinations. We also show that honey bee and bumble bee antennae can detect most components of theB. rapaodor space, and the strength of responses correlates with positions of odorants in the hyperbolic space. In sum, a hyperbolic representation can be used to guide investigation of how information is represented at different levels of processing in the CNS.