bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct imaging of anthrax intoxication in animals reveals shared and individual functions of CMG-2 and TEM-8 in cellular toxin entry
Authors: Merritt Carly , Chun Elizabeth M. , Fattah Rasem J. , Moayeri Mahtab , Paliga Dennis , Neumann Sebastian , Heumann Rolf , Leppla Stephen H. , Bugge Thomas H. 
Published: January 2021

SUMMARYThe virulence ofBacillus anthracisis linked to the secretion of anthrax lethal toxin and anthrax edema toxin. These binary toxins consist of a common cell-binding moiety, protective antigen (PA), and the enzymatic moieties, lethal factor (LF) and edema factor (EF). PA binds either of two specific cell surface receptors, capillary morphogenesis protein-2 (CMG-2) or tumor endothelial marker-8 (TEM-8), which triggers the binding, endocytosis, and cytoplasmic translocation of LF and EF. The cellular distribution of functional TEM-8 and CMG-2 receptors during anthrax toxin intoxication in animals is not fully elucidated. Herein, we describe a novel assay to image anthrax toxin intoxication in live animals, and we use the assay to visualize TEM-8- and CMG-2-dependent intoxication. Specifically, we generated a chimeric protein consisting of the N-terminal domain of LF fused to a nuclear localization signal-tagged Cre recombinase (LFn-NLS-Cre). When PA and LFn-NLS-Cre were co-administered to transgenic mice that ubiquitously express a red fluorescent protein in the absence of Cre activity and a green fluorescent protein in the presence of Cre activity, anthrax toxin intoxication could be visualized at single-cell resolution by confocal microscopy. By using this assay, we show that CMG-2 is critical for intoxication in the liver and heart, whereas TEM-8 is required for full intoxication in the kidney and spleen. Other tissues examined were largely unaffected by single deficiences in either receptor, suggesting extensive overlap in TEM-8 and CMG-2 expression. The novel assay will be useful for basic and clinical/translational studies ofBacillus anthracisinfection and for identifying on- and off-targets for reengineered toxin variants in the clinical development of cancer treatments.BackgroundAssays for imaging of anthrax toxin intoxication in animals are not available.ResultsAnthrax toxin-Cre fusions combined with fluorescent Cre reporter mice enabled imaging of anthrax toxin intoxication in animals.ConclusionShared and distinct functions of toxin receptors in cellular entry were uncovered. Significance. A simple and versatile assay for anthrax toxin intoxication is described.
Human genetic analyses of organelles highlight the nucleus in age-related trait heritability
Authors: Gupta Rahul , Karczewski Konrad J. , Howrigan Daniel , Neale Benjamin M. , Mootha Vamsi K. 
Published: January 2021

AbstractMost age-related human diseases are accompanied by a decline in cellular organelle integrity, including impaired lysosomal proteostasis and defective mitochondrial oxidative phosphorylation. An open question, however, is the degree to which inherited variation in or near genes encoding each organelle contributes to age-related disease pathogenesis. Here, we evaluate if genetic loci encoding organelle proteomes confer greater-than-expected age-related disease risk. As mitochondrial dysfunction is a “hallmark” of aging, we begin by assessing nuclear and mitochondrial DNA loci near genes encoding the mitochondrial proteome and surprisingly observe a lack of enrichment across 24 age-related traits. Within nine other organelles, we find no enrichment with one exception: the nucleus, where enrichment emanates from nuclear transcription factors. In agreement, we find that genes encoding several organelles tend to be “haplosufficient,” while we observe strong purifying selection against heterozygous protein-truncating variants impacting the nucleus. Our work identifies common variation near transcription factors as having outsize influence on age-related trait risk, motivating future efforts to determine if and how this inherited variation then contributes to observed age-related organelle deterioration.
Burkholderiafrom fungus gardens of fungus-growing ants produce antifungals that inhibit the specialized parasiteEscovopsis
Authors: Francoeur Charlotte B. , May Daniel S. , Thairu Margaret W. , Hoang Don Q. , Panthofer Olivia , Bugni Tim S. , Pupo Mônica T. , Clardy Jon , Pinto-Tomás Adrián A. , Currie Cameron R. 
Published: January 2021

ABSTRACTWithin animal associated microbiomes, the functional roles of specific microbial taxa are often uncharacterized. Here, we use the fungus-growing ant system, a model for microbial symbiosis, to determine the potential defensive roles of key bacterial taxa present in the ants’ fungus gardens. Fungus gardens serve as an external digestive system for the ants, with mutualistic fungi in the genusLeucoagaricusspp. converting plant substrate into energy for the ants. The fungus garden is host to specialized parasitic fungi in the genusEscovopsis. Here, we examine the potential role ofBurkholderiaspp. that occur within ant fungus gardens in inhibitingEscovopsis.We isolated members of the bacterial generaBurkholderiaspp. andParaburkholderiaspp. from 50% of the 52 colonies sampled, indicating that the familyBurkholderiaceaeare common fungus garden inhabitants of a diverse range of fungus-growing ant genera. Using antimicrobial inhibition bioassays, we found that 28 out of 32 isolates inhibited at least oneEscovopsisstrain with a zone of inhibition greater than 1 cm. Genomic assessment ofBurkholderiaceaeisolates indicated that isolates with strong inhibition all belonged to the genusBurkholderiaand contained biosynthetic gene clusters that encoded the production of two antifungals: burkholdine1213 and pyrrolnitrin. Organic extracts of cultured isolates confirmed these compounds as responsible for antifungal activity that inhibitEscovopsisbut, at low concentrations, notLeucoagaricusspp. Overall, these new findings, combined with previous evidence, suggest that members of the fungus garden microbiome play an important role in maintaining the health and function of the fungus-farming ant colony.IMPORTANCEMany organisms partner with microbes to defend themselves against parasites and pathogens. Fungus-growing ants must protectLeucoagaricusspp., the fungal mutualist that provides sustenance for the ants, from a specialized fungal parasite,Escovopsisspp. The ants take multiple approaches, including weeding their fungus gardens to removeEscovopsisspores, as well as harboringPseudonocardiathat produce antifungals that inhibitEscovopsis.In addition, a genus of bacteria commonly found in fungus gardens,Burkholderiaspp., is known to produce secondary metabolites that inhibitEscovopsisspp. In this study, we isolatedBurkholderiaspp. from fungus-growing ants, assessed the isolates’ ability to inhibitEscovopsisspp., and identified two compounds responsible for inhibition. Our findings suggest thatBurkholderiaspp. are often found in fungus gardens, adding another possible mechanism within the fungus-growing ant system to suppress the growth of the specialized parasiteEscovopsis.
Fine-scale Population Structure of North AmericanArabidopsis thalianaReveals Multiple Sources of Introduction from Across Eurasia
Authors: Shirsekar Gautam , Devos Jane , Latorre Sergio M. , Blaha Andreas , Dias Maique Queiroz , González Hernando Alba , Lundberg Derek S. , Burbano Hernán A. , Fenster Charles B. , Weigel Detlef 
Published: January 2021

AbstractLarge-scale movement of organisms across their habitable range, or migration, is an important evolutionary process that can contribute to observed patterns of genetic diversity and our understanding of the adaptive spread of alleles. While human migrations have been studied in great detail with modern and ancient genomes, recent anthropogenic influence on reducing the biogeographical constraints on the migration of non-native species has presented opportunities in several study systems to ask the questions about how repeated introductions shape genetic diversity in the introduced range. We present here the most comprehensive view of population structure of North AmericanArabidopsis thalianaby studying a set of 500 (whole-genome sequenced) and over 2800 (RAD-seq genotyped) individuals in the context of global diversity represented by Afro-Eurasian genomes. We use haplotype-sharing, phylogenetic modeling and rare-allele sharing based methods to identify putative sources of introductions of extant N. AmericanA. thalianafrom the native range of Afro-Eurasia. We find evidence of admixture among the introduced lineages that has resulted in the increased haplotype diversity and reduced mutational load. Further, we also present signals of selection in the immune-system related genes that impart qualitative disease resistance to pathogens of bacterial and oomycete origins. Thus, multiple introductions to a non-native range can quickly increase adaptive potential of a colonizing species by increasing haplotypic diversity through admixture. The results presented here lay the foundation for further investigations into the functional significance of admixture.
The Arabidopsis pattern recognition receptor EFR enhances fire blight resistance in apple
Authors: Piazza Stefano , Campa Manuela , Pompili Valerio , Costa Lorenza Dalla , Salvagnin Umberta , Nekrasov Vladimir , Zipfel Cyril , Malnoy Mickael 
Published: January 2021

AbstractFire blight disease, caused by the bacteriumErwinia amylovora(E. amylovora), is responsible for substantial losses in cultivated apple worldwide. An important mechanism of plant immunity is based on the recognition of conserved microbial molecules, named pathogen- or microbe-associated molecular patterns (PAMPs or MAMPs), through pattern recognition receptors (PRRs), leading to pattern-triggered immunity (PTI). The interspecies transfer of PRRs represents a promising strategy to engineer broad spectrum and durable disease resistance in crops. EFR, theArabidopsis thalianaPRR for the PAMP elf18 derived from the elongation factor thermal unstable (EF-Tu) proved to be effective in improving bacterial resistance when expressed into Solanaceae and other plant species,. In this study, we tested whether EFR can affect the interaction of apple withE. amylovoraby its ectopic expression in the susceptible apple rootstock M.26. StableEFRexpression led to the activation of PAMP-triggered immune response in apple leaves upon treatment with supernatant ofE. amylovora, as measured by production of reactive oxygen species and the induction of known defense genes. The amount of tissue necrosis associated withE. amylovorainfection was significantly reduced in theEFRtransgenic rootstock compared to the wild-type. Our results show that the expression ofEFRin apple rootstock may be a valuable biotechnology strategy to improve the resistance of apple to fire blight.
Deciphering the differential physiological and molecular requirements for conidial anastomosis tube fusion and germ tube formation inColletotrichum gloeosporioides
Authors: Mehta Nikita , Patil Ravindra , Baghela Abhishek 
Published: January 2021

AbstractThe conidia of a hemibiotrophic fungusColletotrichum gloeosporioidescan conventionally form germ tube (GT) and develop in to a fungal colony, while under certain conditions, they tend to get connected with each other through conidial anastomosis tube (CAT) so as to share the nutrients. CAT fusion is believed to be responsible for generation of genetic variations in few asexual fungi, which appears problematic for effective fungal disease management. The physiological and molecular mechanism underlying the GT versus CAT formation remained unexplored. In the present study, we have deciphered the decision switch responsible for GT formation versus CAT fusion inC. gloeosporioides. GT formation occurred at high frequency in the presence of nutrients, while CAT fusion was found to be higher in absence of nutrients. Younger conidia were found to form GT efficiently, whilst older conidia preferentially formed CAT. Whole transcriptome analysis of GT and CAT fusion revealed differential molecular requirements for these two processes. We identified 11050 and 9786 differentially expressed genes (DEGs) in GT and CAT, respectively. A total 1567 effector candidates were identified, of them 103 and 101 were uniquely secreted during GT and CAT formation respectively. Genes coding for cell wall degrading enzymes, germination, hyphal growth, host-fungus interaction and virulence were up-regulated during GT formation. Whilst, genes involved in stress response, cell wall remodelling, membrane transport, cytoskeleton, cell cycle, and cell rescue were highly up-regulated during CAT fusion. To conclude, the GT and CAT fusion were found to be mutually exclusive processes, requiring differential physiological conditions and sets of DEGs inC. gloeosporioides. This will help to understand the basic CAT biology in the genusColletotrichum.
Quantifying and cataloguing unknown sequences within human microbiomes
Authors: Modha Sejal , Robertson David L. , Hughes Joseph , Orton Richard J. 
Published: January 2021

AbstractAdvances in genome sequencing technologies and lower costs have enabled the exploration of a multitude of known and novel environments and microbiomes. This has led to an exponential growth in the raw sequence data that is deposited in online repositories. Metagenomic and metatranscriptomic data sets are typically analysed with regards to a specific biological question. However, it is widely acknowledged that these data sets are comprised of a proportion of sequences that bear no similarity to any currently known biological sequence, and this so-called ‘dark matter’ is often excluded from downstream analyses. In this study, a systematic framework was developed to assemble, identify, and measure the proportion of unknown sequences present in distinct human microbiomes. This framework was applied to forty distinct studies, comprising 963 samples, and covering ten different human microbiomes including fecal, oral, lung, skin and circulatory system microbiomes. The framework was used to determine the proportion of taxonomically unknown sequences present within samples, and to compare such sequences both within and across assembled metagenomes. We found that whilst the human microbiome is one of the most extensively studied, on average 2% of assembled sequences have not yet been taxonomically defined. However, this proportion varied extensively among different microbiomes and was as high as 25% for skin and oral microbiomes that have more interactions with the environment. The publicly available data sets used have not previously been systematically mined to quantify and compare such dark matter. Typically, these unknown sequences are found in several microbiomes and potentially belong to unidentified novel microbes that we interact with on a daily basis. A cross-study comparison led to the identification of similar unknown sequences in different samples and/or microbiomes. A rate of taxonomic characterisation of 1.64% of unknown sequences being characterised per month was calculated from these taxonomically unknown sequences discovered in this study. Additionally, the approach led to the discovery of several potentially novel viral genomes that bear no similarity to sequences in the public databases. Both our computational framework and the novel unknown sequences produced are publicly available for future cross-referencing.
Insights from Genomes and Genetic Epidemiology of SARS-CoV-2 isolates from the state of Andhra Pradesh
Authors: Rani Pallavali Roja , Imran Mohamed , Lakshmi J. Vijaya , Jolly Bani , Afsar S. , Jain Abhinav , Divakar Mohit Kumar , Suresh Panyam , Sharma Disha , Rajesh Nambi , Bhoyar Rahul C. , Ankaiah Dasari , Kumari Sanaga Shanthi , Ranjan Gyan , Lavanya Valluri Anitha , Rophina Mercy , Umadevi S. , Sehgal Paras , Devi Avula Renuka , Surekha A. , Sekhar Pulala Chandra , Hymavathy Rajamadugu , Vanaja P.R. , Scaria Vinod , Sivasubbu Sridhar 
Published: January 2021

AbstractCoronavirus disease (COVID-19) emerged from a city in China and has now spread as a global pandemic affecting millions of individuals. The causative agent, SARS-CoV-2 is being extensively studied in terms of its genetic epidemiology using genomic approaches. Andhra Pradesh is one of the major states of India with the third-largest number of COVID-19 cases with limited understanding of its genetic epidemiology. In this study, we have sequenced 293 SARS-CoV-2 genome isolates from Andhra Pradesh with a mean coverage of 13,324X. We identified 564 high-quality SARS-CoV-2 variants, out of which 15 are novel. A total of 18 variants mapped to RT-PCR primer/probe sites, and 4 variants are known to be associated with an increase in infectivity. Phylogenetic analysis of the genomes revealed the circulating SARS-CoV-2 in Andhra Pradesh majorly clustered under the clade A2a (94%), while 6% fall under the I/A3i clade, a clade previously defined to be present in large numbers in India. To the best of our knowledge, this is the most comprehensive genetic epidemiological analysis performed for the state of Andhra Pradesh.
Nucleotide limitation results in impaired photosynthesis, reduced growth and seed yield together with massively altered gene expression
Authors: Bellin Leo , Melzer Michael , Hilo Alexander , Amaya Diana Laura Garza , Keller Isabel , Meurer Jörg , Möhlmann Torsten 
Published: January 2021

ABSTRACTNucleotide limitation and imbalance is a well described phenomenon in animal research but understudied in the plant field. A peculiarity of pyrimidine de novo synthesis in plants is the complex subcellular organization. Here, we studied two organellar localized enzymes in the pathway, with chloroplast aspartate transcarbamoylase (ATC), and mitochondrial dihydroorotate dehydrogenase (DHODH).ATCknockdowns were most severely affected, exhibiting low levels of pyrimidine nucleotides, a low energy state, reduced photosynthetic capacity and accumulation of reactive oxygen species (ROS). Furthermore, altered leaf morphology and chloroplast ultrastructure were observed inATCmutants. Although less affected,DHODHknockdown mutants showed impaired seed germination and altered mitochondrial ultrastructure. Transcriptome analysis of anATC-amiRNA line revealed massive alterations in gene expression with central metabolic pathways being downregulated and stress response and RNA related pathways being upregulated. In addition, genes involved in central carbon metabolism, intracellular transport and respiration were mainly downregulated in ATC mutants, being putatively responsible for the observed impaired growth.ONE-SENTENCE SUMMARYImpaired pyrimidine nucleotide synthesis results in nucleotide limitation and imbalance, resulting in impaired photosynthesis, reduced growth, reproduction, and seed yield together with massively altered gene expression
The developmental stage of the medulloblastoma cell-of-origin restricts Hedgehog pathway usage and drug sensitivity
Authors: Smit Marlinde J. , Armandari Inna , Bockaj Irena , Martini Tosca E.I. , Zomerman Walderik W. , Siragna Zillah , Meeuwsen Tiny G.J. , Scherpen Frank J.G. , Schoots Mirthe H. , Ritsema Martha , den Dunnen Wilfred F.A. , Hoving Eelco W. , Paridaen Judith T.M.L. , de Haan Gerald , Guryev Victor , Bruggeman Sophia W.M. 
Published: January 2021

SummarySonic Hedgehog (SHH) medulloblastoma originates from the cerebellar granule neuron progenitor (CGNP) lineage that depends on Hedgehog signaling for its perinatal expansion. While SHH tumors exhibit overall deregulation of this pathway, they also show patient age-specific aberrations.To investigate if the developmental stage of the CGNP can account for these age-specific lesions, we analyzed developing murine CGNP transcriptomes and observed highly dynamic gene expression as function of age. Cross-species comparison with human SHH medulloblastoma showed partial maintenance of these expression patterns, and highlighted low primary cilium expression as hallmark of infant medulloblastoma and early embryonic CGNPs. This coincided with reduced responsiveness to upstream Shh pathway component Smoothened, while sensitivity to downstream components Sufu and Gli was retained.Together, these findings can explain the preference forSUFUmutations in infant medulloblastoma and suggest that drugs targeting the downstream SHH pathway will be most appropriate for infant patients.
Facilitation and biodiversity jointly drive mutualistic networks
Authors: Losapio Gianalberto , Norton Hasday Elizabeth , Espadaler Xavier , Germann Christoph , Ortiz‐Sánchez Francisco Javier , Pont Adrian , Sommaggio Daniele , Schöb Christian 
Published: January 2021

AbstractFacilitation by nurse plants increases understorey diversity and supports ecological communities. In turn, biodiversity shapes ecological networks and enhances ecosystem functioning. However, whether and how facilitation and increased biodiversity jointly influence community structure and ecosystem functioning remains unclear.We performed a field experiment disentangling the relative contribution of nurse plants and increasing understorey plant diversity in driving pollination interactions. Both the presence of nurse shrubs and increased understorey plant diversity increased pollinator diversity and visitation rates. While nurse and understorey diversity effects on pollinator visitation rates did not interact, the effects of increasing understorey plant diversity on pollinator diversity were stronger in the absence than in the presence of shrubs, meaning that nurse shrubs attenuated the effects of high understorey diversity and buffered the effects of low understorey diversity.We also found positive complementarity effects among understorey species as well as complementarity between nurse plants and understorey species at high diversity. Results also indicate negative selection effects, suggesting that species with generally few pollinators benefit the most in the polyculture while a species (possibly the nurse plant) with generally lots of pollinators does not. The corresponding changes in pollination networks with the experimental treatments were due to both changes in the frequency of visits and turnover in pollinator community composition.Synthesis. Plant–plant facilitative systems, where a nurse plant increases understorey plant diversity, are common in stressful environments. Here, we show that these facilitative systems positively influence mutualistic interactions with pollinators via both direct nurse effects and indirect positive effects of increasing plant diversity. Conserving and supporting nurse plant systems is crucial not only for maintaining plant diversity but also for supporting ecosystem functions and services.
Re‐Embodying History's ‘Lady’: Women's History, Materiality and Public Space in Early‐Twentieth‐Century Vienna
Authors: Motyl Katya 
Published: January 2021

AbstractIn ‘The Disembodied Lady’, neurologist Oliver Sacks recounts the case of Christina, a woman who suddenly lost her corporeal sense of self. This article uses this case as a metaphor for the state of women's history at the turn of the millennium. With the turn to discourse, even the so‐called ‘lady’ within the academy had become disembodied. As Christina mouthed to Sacks, however, to be disembodied is awful. The purpose of this article is to follow the more recent trend in scholarship that has sought to re‐embody the ‘lady’ of history. The article begins by tracing the development of women's history and how its subject, the ‘lady’, came to disappear. It then draws on the ‘material’ turn in feminist theory to consider the implications of this vanishing act by looking, first, to lived experience, and second, to materiality/discursive production. I argue that Women are not only a matter of language, but a matter of matter, and further, that matter itself must be re‐evaluated as agential and entangled with discourse. Finally, an example from my research on street walking in early‐twentieth‐century Vienna illustrates how to bring this new women's history to life.