bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introgression fromOryza meridionalisinto domesticated riceOryza sativaresults in shoot-based iron tolerance
Authors: Wairich Andriele , de Oliveira Ben Hur Neves , Wu Lin-Bo , Murugaiyan Varunseelan , Margis-Pinheiro Marcia , Fett Janette Palma , Ricachenevsky Felipe Klein , Frei Michael 
Published: June 2020

AbstractIron (Fe) toxicity is one of the most common mineral disorders affecting rice (Oryza sativa) production in flooded lowland fields.Oryza meridionalisis endemic from Northern Australia and grows in regions with Fe rich soils, making it a candidate for use in adaptive breeding. Aiming to understand tolerance mechanisms in rice, we screened a population of interspecific introgression lines (IL) from a cross betweenO. sativaandO. meridionalisfor the identification of QTLs contributing to Fe toxicity tolerance. Six putative QTLs were identified. A line carrying one introgression fromO. meridionalison chromosome 9 associated with one QTL was highly tolerant despite very high shoot Fe concentrations. Physiological, biochemical, ionomic and transcriptomic analyses showed that the IL tolerance could partly be explained by Fe retention in the leaf sheath and culm. We constructed the interspecific hybrid genomein silicofor transcriptomic analysis, and identified differentially regulated introgressed genes fromO. meridionalisthat could be involved in shoot-based Fe tolerance, such as metallothioneins, glutathione S-transferases and transporters from ABC and MFS families. This is the first work to demonstrate that introgressions ofO. meridionalisinto theO. sativagenome can confer increased tolerance to excess Fe.HighlightWe identified QTLs associated with iron tolerance derived fromO. meridionalis, and characterized their physiological basis inO. sativa.
Assessing SARS-CoV-2 spatial phylogenetic structure: Evidence from RNA and protein sequences
Authors: Jones Leandro R. , Manrique Julieta M. 
Published: June 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent RNA virus that spread around the planet in about 4 months. The consequences of this rapid dispersion are under investigation. In this work, we analyzed thousands of genomes and protein sequences from Africa, America, Asia, Europe, and Oceania. We show that the virus is a complex of slightly different variants that are unevenly distributed on Earth, and demonstrate that SARS-CoV-2 phylogeny is spatially structured. Remarkably, the virus phylogeographic patterns were associated with ancestral amino acidic mutations. We hypothesize that geographic structuring is the result of founder effects occurring as a consequence of, and local evolution occurring after, long-distance dispersal. Based on previous studies, the possibility that this could significantly affect the virus phenotype is not remote.
Large scale metagenome assembly reveals novel animal-associated microbial genomes, biosynthetic gene clusters, and other genetic diversity
Authors: Youngblut Nicholas D. , de la Cuesta-Zuluaga Jacobo , Reischer Georg H. , Dauser Silke , Schuster Nathalie , Walzer Chris , Stalder Gabrielle , Farnleitner Andreas H. , Ley Ruth E. 
Published: June 2020

AbstractLarge-scale metagenome assemblies of human microbiomes have produced a vast catalogue of previously unseen microbial genomes; however, comparatively few microbial genomes derive from other vertebrates. Here, we generated 5596 metagenome-assembled genomes from the gut metagenomes of 180 predominantly wild animal species representing 5 classes, in addition to 14 existing animal gut metagenome datasets. The MAGs comprised 1522 species-level genome bins (SGBs); most of which were novel at the species, genus, or family levels, and the majority were enriched in host versus environment metagenomes. Many traits distinguished SGBs enriched in host or environmental biomes, including the number of antimicrobial resistance genes. We identified 1986 diverse biosynthetic gene clusters; only 23 clustered with any MIBiG database references. Gene-based assembly revealed tremendous gene diversity, much of it host- or environment-specific. Our MAG and gene datasets greatly expand the microbial genome repertoire and provide a broad view of microbial adaptations to the vertebrate gut.ImportanceMicrobiome studies on a select few mammalian species (e.g.,humans, mice, and cattle) have revealed a great deal of novel genomic diversity in the gut microbiome. However, little is known of the microbial diversity in the gut of other vertebrates. We studied the gut microbiome of a large set of mostly wild animal species consisting of mammals, birds, reptiles, amphibians, and fish. Unfortunately, we found that existing reference databases commonly used for metagenomic analyses failed to capture the microbiome diversity among vertebrates. To increase database representation, we applied advanced metagenome assembly methods to our animal gut data and to many public gut metagenome datasets that had not been used to obtain microbial genomes. Our resulting genome and gene cluster collections comprised a great deal of novel taxonomic and genomic diversity, which we extensively characterized. Our findings substantially expand what is known of microbial genomic diversity in the vertebrate gut.
Irreversible sterility of workers and high-volume egg production by queens in the stingless beeTetragonula carbonaria
Authors: Bulle Bueno Francisco Garcia , Gloag Rosalyn , Latty Tanya , Ronai Isobel 
Published: June 2020

ABSTRACTSocial insect reproduction is characterised by a division of labour. Typically, the queen is the sole reproductive female in the colony and the female workers are non-reproductive. However, in the majority of social insect species the workers are only facultatively sterile and remain capable of laying eggs under some conditions, such as when the queen dies. The Australian stingless beeTetragonula carbonariais noteworthy as workers never lay eggs, even if a colony loses its queen. Here we describe the reproductive anatomy ofT. carbonariaworkers (deactivated ovaries), virgin queens (semi-activated ovaries), and mated queens (activated ovaries).T. carbonariamated queens have high-volume egg production compared to other female insects as each of their eight ovarioles (filaments of the ovary) produces approximately 40 eggs per day. We then conduct the first experimental test of absolute worker sterility in the social insects. Using a controlled microcolony environment, we investigate whether the reproductive capacity of adult workers can be rescued by manipulating the workers’ social environment (separating them from a queen) and diet (feeding them unrestricted highly nutritious honey bee royal jelly), both conditions which cause ovary activation in bee species where workers are facultatively sterile. The ovaries ofT. carbonariaworkers that are queenless and fed royal jelly remain non-functional, indicating they are irreversibly sterile and that ovary degeneration is fixed prior to adulthood. We suggest thatT. carbonariamight have evolved absolute worker sterility because colonies under natural conditions are unlikely to ever be queenless.
Pan-Cancer analysis of somatic mutations in miRNA genes
Authors: Urbanek-Trzeciak Martyna Olga , Galka-Marciniak Paulina , Nawrocka Paulina Maria , Kowal Ewelina , Szwec Sylwia , Giefing Maciej , Kozlowski Piotr 
Published: June 2020

ABSTRACTmiRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. Here, based on analysis of the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we identified and characterized over 10,000 somatic mutations in miRNA genes and showed that some of the genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. Our results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancer-driver miRNA genes.
Rapid purification and metabolomic profiling of synaptic vesicles from mammalian brain
Authors: Chantranupong Lynne , Saulnier Jessica L. , Wang Wengang , Jones Drew R. , Pacold Michael E. , Sabatini Bernardo L. 
Published: June 2020

AbstractNeurons communicate by the activity-dependent release of small-molecule neurotransmitters packaged into synaptic vesicles (SVs). Although many molecules have been identified as neurotransmitters, technical limitations have precluded a full metabolomic analysis of synaptic vesicle content. Here, we present a workflow to rapidly isolate SVs and to interrogate their metabolic contents at a high-resolution using mass spectrometry. We validated the enrichment of glutamate in SVs of primary cortical neurons using targeted polar metabolomics. Unbiased and extensive global profiling of SVs isolated from these neurons revealed that the only detectable polar metabolites they contain are the established neurotransmitters glutamate and GABA. Finally, we adapted the approach to enable quick capture of SVs directly from brain tissue and determined the neurotransmitter profiles of diverse brain regions in a cell-type specific manner. The speed, robustness, and precision of this method to interrogate SV contents will facilitate novel insights into the chemical basis of neurotransmission.
A unifying framework disentangles genetic, epigenetic, and stochastic sources of drug-response variability in anin vitromodel of tumor heterogeneity
Authors: Hayford Corey E. , Tyson Darren R. , Robbins C. Jack , Frick Peter L. , Quaranta Vito , Harris Leonard A. 
Published: June 2020

ABSTRACTTumor heterogeneity is a primary cause of treatment failure and acquired resistance in cancer patients. Even in cancers driven by a single mutated oncogene, variability of targeted therapy response is observed. Additional genetic mutations can only partially explain this variability, leading to consideration of non-genetic factors, such as “stem-like” and “mesenchymal” phenotypic states, as critical contributors to tumor relapse and resistance. Here, we show that both genetic and non-genetic factors contribute to targeted drug-response variability in an experimental tumor heterogeneity model based on multiple versions and clonal sublines of PC9, the archetypal EGFR-mutant non-small cell lung cancer cell line. We observe significant drug-response variability across PC9 cell line versions, among sublines, and within sublines. To disentangle genetic, epigenetic, and stochastic components underlying this variability, we adopt a theoretical framework whereby distinct genetic states give rise to multiple epigenetic “basins of attraction”, across which cells can transition driven by stochastic factors such as gene expression noise and asymmetric cell division. Using mutational impact analysis, single-cell differential gene expression, and semantic similarity of gene ontology terms to connect genomics and transcriptomics, we establish a baseline of genetic differences explaining drug-response variability across PC9 cell line versions. In contrast, with the same approach, we conclude that in all but one of the clonal sublines, drug-response variability is due to epigenetic rather than genetic differences. Finally, using a clonal drug-response assay and stochastic simulations, we attribute drug-response variability within sublines to intracellular stochastic fluctuations and confirm that one subline likely contains a genetic resistance mutation that emerged in the absence of selective pressures. We propose that a theoretical framework deconvolving the complex interplay among genetic, epigenetic, and stochastic sources of intratumoral heterogeneity will lead to novel therapeutic strategies to combat tumor relapse and resistance.
Accuracy of a battery-powered portable capnometer in neonates
Authors: Hirakawa Eiji , Ibara Satoshi 
Published: June 2020

AbstractEnd-tidal CO2measurement (EtCO2) is useful for confirmation of successful tracheal intubation and ensuring adequate ventilation. There are two types of EtCO2detector, i.e., single-use-only devices and capnometers. Although portable capnometers are widely used for resuscitation, there have been no reports regarding their clinical utility in neonates. Here, the correspondence between EtCO2level determined using a battery-powered portable capnometer and arterial CO2(PaCO2) was investigated using paired data obtained simultaneously from 26 neonates weighing 1262 ± 589 g at examination on mechanical ventilation. EtCO2level and PaCO2showed a strong correlation (r = 0.839,P< 0.001), and the correlation equation was: EtCO2= 0.8 × PaCO2+ 1.1. Therefore, EtCO2readings obtained with a battery-powered portable capnometer were likely to be underestimated. This became more pronounced with decreasing infant body weight at examination as the net difference in measurements of PaCO2and EtCO2was significantly positively correlated with infant body weight at examination (r = 0.451,P< 0.001). The observations presented here may be helpful in the use of battery-powered portable capnometers in neonates requiring controlled ventilation with tracheal intubation.
Improved diagnosis of viral encephalitis in adult and pediatric hematological patients using viral metagenomics
Authors: Carbo Ellen C. , Buddingh Emilie P. , Karelioti Evita , Sidorov Igor , Feltkamp Mariet C.W. , von dem Borne Peter A. , Verschuuren Jan J.G.M. , Kroes Aloys C.M. , Claas Eric C.J. , de Vries Jutte J.C. 
Published: June 2020

AbstractMetagenomic sequencing is a powerful technique that enables detection of the full spectrum of pathogens present in any specimen in a single test. Hence, metagenomics is increasingly being applied for detection of viruses in clinical cases with suspected infections of unknown etiology and a large number of relevant potential causes. This is typically the case in patients presenting with encephalitis, in particular when immunity is impaired by underlying disorders.In this study, viral metagenomics has been applied to a cohort of hematological patients with encephalitis of unknown origin.Since viral loads in cerebrospinal fluid of patients with encephalitis are generally low, the technical performance of a metagenomic sequencing protocol enriched by capture probes targeting all known vertebrate viral sequences was studied. Subsequently, the optimized viral metagenomics protocol was applied to a cohort of hematological patients with encephalitis of unknown origin.Viral enrichment by capture probes increased the viral sequence read count of metagenomics on cerebrospinal fluid samples 100 – 10.000 fold, compared to unenriched metagenomic sequencing.In five out of 41 (12%) hematological patients with encephalitis, a virus was detected by viral metagenomics which had not been detected by current routine diagnostics. BK polyomavirus, hepatitis E virus, human herpes virus-6 and Epstein Barr virus were identified by this unbiased metagenomic approach.This study demonstrated that hematological patients with encephalitis of unknown origin may benefit from early viral metagenomics testing as a single step approach.HighlightsA metagenomics protocol employing virus capture probes was validated and retrospectively applied to 41 hematological adult and pediatric patients presenting with encephalitis of unknown aetiologyViral enrichment by capture probes increased sensitivity of viral metagenomics on cerebrospinal fluid samples 100 – 10.000 fold, compared to unenriched metagenomic sequencingIn 12% of hematological patients with encephalitis of unknown origin, a virus was detected by viral metagenomics, which was not found by routine diagnosticsViral metagenomics represents a valuable addition to the diagnostics repertoire for hematological patients with suspected CNS infection
Cycling cancer persister cells arise from lineages with distinct transcriptional and metabolic programs
Authors: Oren Yaara , Tsabar Michael , Cabanos Heidie F. , Cuoco Michael S. , Zaganjor Elma , Thakore Pratiksha I. , Tabaka Marcin , Fulco Charles P , Hurvitz Sara A. , Slamon Dennis J. , Lahav Galit , Hata Aaron , Brugge Joan S. , Regev Aviv 
Published: June 2020

AbstractNon-genetic mechanisms have recently emerged as important drivers of therapy failure in cancer (Salgia and Kulkarni, 2018), where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment (Vallette et al., 2019). While most cancer persisters, like their bacterial counterparts, remain arrested in the presence of drug, a rare subset of cancer persisters can re-enter the cell cycle under constitutive drug treatment (Sharma et al., 2010). Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drug. Here, using time-lapse imaging, we found that cycling persisters emerge early in the course of treatment of EGFR-mutant lung cancer cells with the EGFR inhibitor osimertinib. To study this rare, transiently-resistant, proliferative persister population we developed Watermelon, a new high-complexity expressed barcode lentiviral library for simultaneous tracing each cell’s clonal origin, proliferative state, and transcriptional state. Analysis of Watermelon-transduced PC9 cells demonstrated that cycling and non-cycling persisters arise from different pre-existing cell lineages with distinct transcriptional and metabolic programs. The proliferative capacity of persisters is associated with an upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation in specific subpopulations of tumor cells. Mitigating oxidative stress or blocking metabolic reprograming significantly alters the fraction of cycling persister cells. In human tumors, programs associated with cycling persisters were induced in malignant cells in response to multiple tyrosine kinase inhibitors. The Watermelon system enabled the identification of rare persister lineages, that are preferentially poised through specific gene programs to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence.
CryoEM Structure ofDrosophilaFlight Muscle Thick Filaments at 7Å Resolution
Authors: Daneshparvar Nadia , Taylor Dianne W. , O’Leary Thomas S. , Rahmani Hamidreza , Yeganeh Fatemeh Abbasi , Previs Michael J. , Taylor Kenneth A. 
Published: June 2020

AbstractStriated muscle thick filaments are composed of myosin II and several non-myosin proteins. Myosin II’s long α-helical coiled-coil tail forms the dense protein backbone of filaments while its N-terminal globular head containing the catalytic and actin binding activities extends outward from the backbone. Here we report the structure of thick filaments of the flight muscle of the fruit flyDrosophila melanogasterat 7 Å resolution. Its myosin tails are arranged in curved molecular crystalline layers identical to flight muscles of the giant waterbugLethocerus indicus.Four non-myosin densities are observed, three of which correspond to ones found inLethocerus;one new density, possibly stretchin-Mlck, is found on the backbone outer surface. Surprisingly, the myosin heads are disordered rather than ordered along the filament backbone. Our results show striking myosin tail similarity within flight muscle filaments of two insect orders separated by several hundred million years of evolution.Significance StatementMyosin thick filaments are one of striated muscle’s key structures, but also one of its least understood. A key question is how the myosin a-helical coiled-coil tail is arranged in the backbone. At 7Å resolution, sufficient to resolve individual a-helices, the myosin tail arrangement in thick filaments from the flight muscle of the fruit flyDrosophila melanogasteris strikingly similar to the myosin tail arrangement in flight muscles of the giant waterbugLethocerus indicus. Nearly every other thick filament feature is different.DrosophilaandLethocerusevolved separately >245 million years ago suggesting myosin tail packing into curved molecular crystalline layers forms a highly conserved thick filament building block and different properties are obtained by alterations in non-myosin proteins.
The framework of lncRNAs and genes at early pollen developmental stage in a PTGMS wheat line
Authors: Bai Jian-fang , Liu Zi-han , Wang Yu-kun , Guo Hao-yu , Guo Li-Ping , Tan Zhao-guo , Yuan Shao-hua , Li Yan-mei , Li Ting-ting , Duan Wen-jing , Yue Jie-ru , Zhang Feng-ting , Zhao Chang-ping , Zhang Li-ping 
Published: June 2020

AbstractWheat photo-thermosensitive genic male sterile (PTGMS) line is a vital material in the two-line hybrid wheat breeding system in which functional pollen production is highly associated with temperature during early developmental stage. Understanding the potential mechanism of pollen infertility induced by low temperature in PTGMS wheat is crucial for the effective utilization of genetic resources to guide wheat breeding. Herein, we combined full-length single-molecular sequencing and Illumina short reads sequencing data to obtain the high-resolution spatio-temporal transcriptome map of pollen under low temperature stress at mother cell, dyad and tetrad stages in PTGMS line BS366. Cytological descriptions and whole transcriptome analysis revealed a global landscape of low temperature altered pollen fertility transformation via regulating the transcriptional patterns of cytoskeleton-related lncRNAs and their target genes, which involved in the calcium signaling and vesicle trafficking pathways on cytoskeleton homeostasis at different stages of meiosis. Overall, our results provided the transcriptional and cytological evidences for understanding the low temperature-induced pollen sterility deficiency in PTGMS wheat line.
Artificial scaffolds that mimic the plant extracellular environment for the culture and attachment of plant cells
Authors: Calcutt Ryan , Vincent Richard , Dean Derrick , Arinzeh Treena Livingston , Dixit Ram 
Published: June 2020

ABSTRACTPlant growth and development involves an intricate program of cell division and cell expansion to generate different cell types, tissue patterns and organ shapes. Plant cells are stuck together by their cell walls and the spatial context of cells within tissues plays a critical role in cell fate specification and morphogenesis. Anin vitromodel system to study plant development and its regulation by various extrinsic and intrinsic factors requires the ability to mimic the physical interactions between cells and their environment. Here, we present a set of artificial scaffolds to which cultured tobacco BY-2 cells adhere without causing morphological abnormalities. These scaffolds mimic native plant cell walls in terms of their fibrous nature, charge, hydrophobicity and piezoelectricity. We found that the extent of plant cell adhesion was essentially insensitive to the stiffness, fiber dimension, and fiber orientation of the scaffolds, but was affected by the piezoelectric properties of scaffolds where adhesion increased on piezoelectric materials. We also found that the plant cell wall polysaccharide, pectin, is largely responsible for adhesion to scaffolds, analogous to pectin-mediated adhesion of plant cells in tissues. Together, this work establishes biomimetic scaffolds that realistically emulate the plant tissue environment and provide the capability to develop microfluidic devices to study how cell-cell and cell-matrix interactions affect plant developmental pathways.