bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surveillance of airborne plant disease dissemination at continental scale using air mass trajectory analysis and network theory
Authors: Radici Andrea , Martinetti Davide , Bevacqua Daniele 
Published: June 2021

AbstractSustainable management of plant disease outbreaks in agriculture is one of the main challenges of the next years to restore economic and environmental viability of farming practices. Improving early-detection capabilities and disease surveillance is increasingly seen as an obligate step to design appropriate and effective prophylactic measures. In this context, plant diseases caused by wind-dispersed pathogens represent an interesting case of study, since they are particularly complex and hard to observe directly, especially if compared to other dissemination means, and demand for a multidisciplinary approach to be dealt with. Wind dispersal could imply a geographic differentiation in pathogens spreading potential, due to the emerging of local meteorological features. In this work we analyze the spatio-temporal patterns of wind connectivity in Europe and the Mediterranean basin in order to identify possible pathways of Puccinia graminis spores, the causal agent of stem rust of wheat. By running backwards Lagrangian simulations merging a biological layer coupled with a pathogen viability model, we investigate possible long-distance connections between regions in the study area across different seasons. We characterized these regions in terms of network centrality indicators to identify possible spreaders of stem rust of wheat, founding that Central and Western European regions appears to provide highest connectivity for the spread of P. graminis.
C. elegansTFIIH subunit GTF-2H5/TTDA is a non-essential transcription factor indispensable for DNA repair
Authors: Thijssen Karen L. , van der Woude Melanie , Davó-Martínez Carlota , Sabatella Mariangela , Vermeulen Wim , Lans Hannes 
Published: June 2021

AbstractThe 10-subunit TFIIH complex is vital to both transcription initiation and nucleotide excision repair. Hereditary mutations in its smallest subunit, TTDA/GTF2H5, cause a photosensitive form of the rare developmental brittle hair disorder trichothiodystrophy (TTD). Some TTD features are thought to be caused by subtle transcription or gene expression defects. Strikingly, TTDA/GTF2H5 knockout mice are not viable, which makes it difficult to investigate how TTDA/GTF2H5 promotes transcriptionin vivo. Here, we show that deficiency of theC. elegansTTDA ortholog GTF-2H5 is, however, compatible with viability and growth, in contrast to depletion of other TFIIH subunits. We also show that GTF-2H5 promotes the stability of TFIIH in multiple tissues and is indispensable for nucleotide excision repair, in which it facilitates recruitment of the TFIIH complex to DNA damage. Strikingly, when transcription is challenged,gtf-2H5embryos die due to the intrinsic TFIIH fragility in the absence of GTF-2H5. These results support the idea that TTDA/GTF2H5 mutations cause transcription impairment underlying trichothiodystrophy and establishC. elegansas potential model for studying the pathogenesis of this disease.
Detection of an unstable minor QTL linked to fire blight resistance on linkage group 16 of Malus fusca
Authors: Emeriewen Ofere Francis , Richter Klaus , Wensing Annette , Malnoy Mickael , Peil Andreas 
Published: June 2021

AbstractObjectiveErwinia amylovora causes fire blight disease in Malus. A strong resistance QTL (Mfu10) was previously detected on linkage group 10 of Malus fusca accession MAL0045, using several strains of the bacterium. As no strain capable of breaking the resistance of MAL0045 has been found, it was hypothesized that a second resistance factor contributes to the fire blight resistance of MAL0045. However, to date, no minor locus has been detected with previously published strains of the bacterium. We detected a minor QTL only on a subset of a population following inoculation with strain Ea1038, which heterologously expresses an effector in a derivative of isolate Ea3049. Two genetic maps of MAL0045, one scarce, the other dense with markers, were used for QTL analyses.ResultsMfu10 was detected on LG10 with Ea1038, as was previously with Ea3049. Although no other QTLs of significant LOD was previously detected in other linkage groups with Ea3049, a QTL of significant LOD was detected on LG16 (Mfu16) after inoculation of a subset of 76 individuals with Ea1038, but only using the dense genetic map. Mfu16 improved the effect of Mfu10. However, when the number of individuals inoculated with Ea1038 was increased to 121, Mfu16 was no longer detected in the dense genetic map. We hypothesize some factors, which might be responsible for the instability of this QTL.
Desiccation-driven senescence and its repression in Xerophyta schlechteri are regulated at extremely low water contents
Authors: Radermacher Astrid L. , Williams Brett , Iranzadeh Arash , Dace Halford , Mundree Sagadevan , Hilhorst Henk W.M. , Farrant Jill M. 
Published: June 2021

SummaryVegetative desiccation tolerance, the ability to survive loss of over 90% of cellular water, is an extremely rare trait in Angiosperms. Xerophyta schlechteri survives such extreme water deficit by entering prolonged quiescence and suppressing drought-induced senescence in most of the leaf area, except the apical tip. Information on the molecular regulation of senescence in such plants is scarce and this is the first study to investigate such regulation in senescing and non-senescing tissues of the same leaf.Genome-wide RNA sequencing enabled comparison of senescent and non-senescent tissues during desiccation and early rehydration, establishment of the water content range in which senescence is initiated and identification of molecular mechanisms employed to bring about cellular death.Senescence-associated genes (XsSAG) specific to this species were identified and two potential regulatory sites were enriched in regions upstream to these XsSAGs, allowing us to create a model of senescence regulation in X. schlechteri based on homology with known Arabidopsis senescence regulators.We hypothesise that desiccation-driven senescence occurs as a result of a convergence of signals around MAPK6 to trigger WRKY-mediated ethylene synthesis and XsSAG expression, not unlike aging and stress-related senescence in Arabidopsis, but at remarkably lower water contents (<35% RWC).
Topological and Structural Plasticity of the single Ig fold and the double Ig fold present in CD19
Authors: Youkharibache Philippe 
Published: June 2021

ABSTRACTThe Ig-fold has had a remarkable success in vertebrate evolution, with a presence in over 2% of human genes. The Ig-fold is not just the elementary structural domain of antibodies and TCRs, it is also at the heart of a staggering 30% of immunologic cell surface receptors, making it a major orchestrator of cell-cell-interactions. While BCRs, TCRs, and numerous Ig-based cell surface receptors form homo or heterodimers on the same cell surface (in cis), many of them interface as ligand-receptors (checkpoints) on interacting cells (in trans) through their Ig domains. New Ig-Ig interfaces are still being discovered between Ig-based cell surface receptors, even in well known families such as B7. What is largely ignored however is that the Ig-fold itself is pseudo-symmetric, a property that makes the Ig-domain a versatile self-associative 3D structure and may in part explain its success in evolution, especially through its ability to bind in cis or in trans in the context of cell surface receptor-ligand interactions. In this paper we review the Ig domains tertiary and quaternary pseudo symmetries, with a particular attention to the newly identified double Ig fold in the solved CD19 molecular structure to highlight the underlying fundamental folding elements of Ig domains, i.e. Ig protodomains. This pseudosymmetric property of Ig domains gives us a decoding frame of reference to understand the fold, relate all Ig-domain forms, single or double, and suggest new protein engineering avenues.
Peptide-based inhibitors of Tau aggregation as a potential therapeutic for Alzheimer’s disease and other Tauopathies
Authors: Aggidis Anthony , Chatterjee Shreyasi , Townsend David , Fullwood Nigel J. , Ortega Eva Ruiz , Tarutani Airi , Hasegawa Masato , Lucas Hannah , Mudher Amritpal , Allsop David 
Published: June 2021

ABSTRACTThere are currently no disease altering drugs available for Tauopathies such as Alzheimer’s disease, which alone is predicted to affect ~88 million people worldwide by 2050. As Tau aggregation underpins its toxicity, aggregation inhibitors are likely to have disease-modifying potential. Guided by in-silico mutagenesis studies, we developed a potent retro-inverso peptide inhibitor of Tau aggregation, RI-AG03 [Ac-rrrrrrrrGpkyk(ac)iqvGr-NH2], based on the306VQIVYK311hotspot. Aggregation of recombinant Tau was reduced by >90% with equimolar RI-AG03 and no fibrils were observed by EM. When added during the growth phase, RI-AG03 blocked seeded aggregation. Fluorescein-tagged RI-AG03 efficiently penetrated HEK-293 cells over 24 hours and was non-toxic at doses up to 30 μM. In transgenicDrosophila, RI-AG03 significantly improves neurodegenerative and behavioural phenotypes caused by expression of human Tau. Collectively this shows that RI-AG03 can effectively reduce Tau aggregationin vitroand block aggregation-dependent phenotypesin vivo, raising possibilities for exploring its translational potential.
Targeted anti-BCR-ABL+ ALL therapy may benefit the heart
Authors: Kirchhoff Hanna , Ricke-Hoch Melanie , Wohlan Katharina , Pietzsch Stefan , Karsli Ümran , Erschow Sergej , Zweigerdt Robert , Ganser Arnold , Eder Matthias , Scherr Michaela , Hilfiker-Kleiner Denise 
Published: June 2021

AbstractTargeted therapies are currently considered the best cost-benefit anti-cancer treatment. In hematological malignancies, however, relapse rates and non-hematopoietic side effects including cardiotoxicity remain high. We here describe significant heart damage due to advanced acute lymphoblastic leukemia with t(9;22) encoding the bcr-abl oncogene (BCR-ABL+ ALL) in murine xenotransplantation models. Echocardiography reveals severe cardiac dysfunction with impaired left ventricular function and reduced heart and cardiomyocyte dimensions associated with increased apoptosis. This cardiac damage is fully reversible, but cardiac recovery depends on the therapy used to induce ALL remission. Chemotherapy-free therapy with dasatinib and venetoclax (targeting the BCR-ABL oncoprotein and mitochondrial Bcl2, respectively), as well as dexamethasone can fully revert cardiac defects whereas depletion of otherwise identical ALL in a genetic model using HSV-TK cannot. Mechanistically, dexamethasone induces pro-apoptotic BIM expression and apoptosis in ALL cells but enhances pro-survival BCLXL expression in cardiomyocytes and clinical recovery with reversion of cardiac atrophy. These data demonstrate that therapies designed to optimize apoptosis induction in ALL may circumvent cardiac on-target side effects and may even activate cardiac recovery. In the future, combining careful clinical monitoring of cardiotoxicity in leukemic patients with further characterization of organ-specific side effects and signaling pathways activated by malignancy and/or anti-tumor therapies seems reasonable.
CRISPR-Cas systems are widespread accessory elements across bacterial and archaeal plasmids
Authors: Pinilla-Redondo Rafael , Russel Jakob , Mayo-Muñoz David , Shah Shiraz A. , Garrett Roger A. , Nesme Joseph , Madsen Jonas S. , Fineran Peter C. , Sørensen Søren J. 
Published: June 2021

ABSTRACTMany prokaryotes encode CRISPR-Cas systems as immune protection against mobile genetic elements (MGEs), yet, a number of MGEs also harbor CRISPR-Cas components. With a few exceptions, CRISPR-Cas loci encoded on MGEs are uncharted and a comprehensive analysis of their distribution, prevalence, diversity, and function is lacking. Here, we systematically investigated CRISPR-Cas loci across the largest curated collection of natural bacterial and archaeal plasmids. CRISPR-Cas loci are widely but heterogeneously distributed across plasmids and, in comparison to host chromosomes, their mean prevalence per Mbp is higher and their distribution is markedly distinct. Furthermore, the spacer content of plasmid CRISPRs exhibits a strong targeting bias towards other plasmids, while chromosomal arrays are enriched with virus-targeting spacers. These contrasting targeting preferences dominate across the diversity of CRISPR-Cas subtypes and host taxa, highlighting the genetic independence of plasmids and suggesting a major role of CRISPR-Cas for mediating plasmid-plasmid conflicts. Altogether, CRISPR-Cas are frequent accessory components of many plasmids, which is an overlooked phenomenon that possibly facilitates their dissemination across microbiomes.
A novel Fiji/ImageJ plugin for the rapid analysis of blebbing cells
Authors: Vosatka Karl W. , Lavenus Sandrine B. , Logue Jeremy S. 
Published: June 2021

AbstractWhen confined, cells have recently been shown to undergo a phenotypic switch to what has been termed, fast amoeboid (leader bleb-based) migration. However, as this is a nascent area of research, few tools are available for the rapid analysis of cell behavior. Here, we demonstrate that a novel Fiji/ImageJ-based plugin, Analyze_Blebs, can be used to quickly obtain cell migration parameters and morphometrics from time lapse images. As validation, we show that Analyze_Blebs can detect significant differences in cell migration and morphometrics, such as the largest bleb size, upon introducing different live markers of F-actin, including F-tractin and LifeAct tagged with green and red fluorescent proteins. We also demonstrate, using flow cytometry, that live markers increase total levels of F-actin. Furthermore, that F-tractin increases cell stiffness, which was found to correlate with a decrease in migration, thus reaffirming the importance of cell mechanics as a determinant of Leader Bleb-Based Migration (LBBM).Highlight summaryA new plugin, Analyze_Blebs, enables the rapid analysis of cell migration and morphometrics of fast amoeboid cells. Morphometrics combined with cell stiffness are found to be predictive of confined, fast amoeboid (leader bleb-based), migration.
A hybridin silicoapproach reveals novel inhibitors of multiple SARS-CoV-2 variants
Authors: Jain Sankalp , Talley Daniel C. , Baljinnyam Bolormaa , Choe Jun , Hanson Quinlin , Zhu Wei , Xu Miao , Chen Catherine Z. , Zheng Wei , Hu Xin , Shen Min , Rai Ganesha , Hall Matthew D. , Simeonov Anton , Zakharov Alexey V. 
Published: June 2021

AbstractThe National Center for Advancing Translational Sciences (NCATS) has been actively generating SARS-CoV-2 high-throughput screening data and disseminates it through the OpenData Portal (https://opendata.ncats.nih.gov/covid19/). Here, we provide a hybrid approach that utilizes NCATS screening data from the SARS-CoV-2 cytophatic effect reduction assay to build predictive models, using both machine learning and pharmacophore-based modeling. Optimized models were used to perform two iterative rounds of virtual screening to predict small molecules active against SARS-CoV-2. Experimental testing with live virus provided 100 (~16% of predicted hits) active compounds (Efficacy > 30%, IC50≤ 15 μM). Systematic clustering analysis of active compounds revealed three promising chemotypes which have not been previously identified as inhibitors of SARS-CoV-2 infection. Further analysis identified allosteric binders to host receptor angiotensin-converting enzyme 2, which were able to inhibit the entry of pseudoparticles bearing spike protein of wild type SARS-CoV-2 as well as South African B.1.351 and UK B.1.1.7 variants.
Maize Brittle Stalk2-Like3, encoding a COBRA protein, functions in cell wall formation and carbohydrate partitioning
Authors: Julius Benjamin T. , McCubbin Tyler J. , Mertz Rachel A. , Baert Nick , Knoblauch Jan , Grant DeAna G. , Conner Kyle , Bihmidine Saadia , Chomet Paul , Wagner Ruth , Woessner Jeff , Grote Karen , Peevers Jeanette , Slewinski Thomas L. , McCann Maureen C. , Carpita Nicholas C. , Knoblauch Michael , Braun David M. 
Published: June 2021

ABSTRACTCarbohydrate partitioning from leaves to sink tissues is essential for plant growth and development. The maize (Zea mays) recessive carbohydrate partitioning defective28 (cpd28) and cpd47 mutants exhibit leaf chlorosis and accumulation of starch and soluble sugars. Transport studies with 14C-sucrose (Suc) found drastically decreased export from mature leaves in cpd28 and cpd47 mutants relative to wild-type siblings. Consistent with decreased Suc export, cpd28 mutants exhibited decreased phloem pressure in mature leaves, and altered phloem cell wall ultrastructure in immature and mature leaves. We identified the causative mutations in the Brittle Stalk2-Like3 (BK2L3) gene, a member of the COBRA family, which is involved in cell wall development across angiosperms. None of the previously characterized COBRA genes are reported to affect carbohydrate export. Consistent with other characterized COBRA members, the BK2L3 protein localized to the plasma membrane, and the mutants condition a dwarf phenotype in dark-grown shoots and primary roots, as well as the loss of anisotropic cell elongation in the root elongation zone. Likewise, both mutants exhibit a significant cellulose deficiency in mature leaves. Therefore, BK2L3 functions in tissue growth and cell wall development, and this work elucidates a unique connection between cellulose deposition in the phloem and whole-plant carbohydrate partitioning.Funding InformationThe research was supported by US National Science Foundation Plant Genome Research Program grants (IOS-1025976 and IOS-1444448) to DMB.
Targeting DNA topoisomerases or checkpoint kinases results in an overload of chaperone systems, triggering aggregation of a metastable subproteome
Authors: Huiting Wouter , Dekker Suzanne L. , van der Lienden Joris C. J. , Mergener Rafaella , Furtado Gabriel V. , Gerrits Emma , Musskopf Maiara K. , Oghbaie Mehrnoosh , Di Stefano Luciano H. , van Waarde-Verhagen Maria A.W.H. , Couzijn Suzanne , Barazzuol Lara , LaCava John , Kampinga Harm H. , Bergink Steven 
Published: June 2021

ABSTRACTA loss of the checkpoint kinase ATM leads to impairments in the DNA damage response, and in humans causes cerebellar neurodegeneration, and a high risk to cancer. A loss of ATM is also associated with increased protein aggregation. The relevance and characteristics of this aggregation are still incompletely understood. Moreover, it is unclear to what extent other genotoxic conditions can trigger protein aggregation as well. Here, we show that targeting ATM, but also ATR or DNA topoisomerases result in a similar, widespread aggregation of a metastable, disease-associated subfraction of the proteome. Aggregation-prone model substrates, including Huntingtin exon1 containing an expanded polyglutamine repeat, aggregate faster under these conditions. This increased aggregation results from an overload of chaperone systems, which lowers the cell-intrinsic threshold for proteins to aggregate. In line with this, we find that inhibition of the HSP70 chaperone system further exacerbates the increased protein aggregation. Moreover, we identify the molecular chaperone HSPB5 as a potent suppressor of it. Our findings reveal that various genotoxic conditions trigger widespread protein aggregation in a manner that is highly reminiscent of the aggregation occurring in situations of proteotoxic stress and in proteinopathies.
Improved draft reference genome for the Glassy-winged Sharpshooter (Homalodisca vitripennis), a vector for Pierce’s disease
Authors: Ettinger Cassandra L. , Byrne Frank J. , Collin Mathew A. , Carter-House Derreck , Walling Linda L. , Atkinson Peter W. , Redak Rick A. , Stajich Jason E. 
Published: June 2021

AbstractHomalodisca vitripennis(Hemiptera: Cicadellidae), known as the glassy-winged sharpshooter, is a xylem feeding leafhopper and an important agricultural pest as a vector ofXylella fastidiosa,which causes Pierce’s disease in grapes and a variety of other scorch diseases. The currentH. vitripennisreference genome from the Baylor College of Medicine’s i5k pilot project is a 1.4-Gb assembly with 110,000 scaffolds, which still has significant gaps making identification of genes difficult. To improve on this effort, we used a combination of Oxford Nanopore long-read sequencing technology combined with Illumina sequencing reads to generate a better assembly and first-pass annotation of the whole genome sequence of a wild-caught Californian (Tulare County) individual ofH. vitripennis. The improved reference genome assembly forH. vitripennisis 1.93-Gb in length (21,254 scaffolds, N50 = 650 Mb, BUSCO completeness = 94.3%), with 33.06% of the genome masked as repetitive. In total, 108,762 gene models were predicted including 98,296 protein-coding genes and 10,466 tRNA genes. As an additional community resource, we identified 27 orthologous candidate genes of interest for future experimental work including phenotypic marker genes likewhite. Further, as part of the assembly process, we generated four endosymbiont metagenome-assembled genomes (MAGs), including a high-quality near complete 1.7-MbWolbachiasp. genome (1 scaffold, CheckM completeness = 99.4%). The improved genome assembly and annotation forH. vitripennis, curated set of candidate genes, and endosymbiont MAGs will be invaluable resources for future research ofH. vitripennis.
Real-time environmental monitoring of contaminants using living electronic sensors
Authors: Atkinson Joshua T. , Su Lin , Zhang Xu , Bennett George N. , Silberg Jonathan J. , Ajo-Franklin Caroline M. 
Published: June 2021

ABSTRACTReal-time chemical sensing is needed to counter the global threats posed by pollution. We combine synthetic biology and materials engineering to develop a living bioelectronic sensor platform with minute detection times.Escherichia coliwas programmed to reduce an electrode in a chemical-dependent manner using a modular, eight-component, synthetic electron transport chain. This strain produced significantly more current upon exposure to thiosulfate, an anion that causes microbial blooms. Incorporating a protein switch into the synthetic pathway and encapsulation of microbes with electrodes and conductive nanomaterials yielded a living bioelectronic sensor that could detect an endocrine disruptor within two minutes in riverine water, implicating the signal as mass transfer limited. These findings provide a new platform for miniature, low-power sensors that safeguard ecological and human health.One Sentence SummaryChemicals are detected electrically using an allosterically-regulated electron transfer pathway in designer microbes.