bluuebunny/crossref_metadata_2025_split huggingface dataset:
VC1 catalyzes a key step in the biosynthesis of vicine from GTP in faba bean
Authors: Björnsdotter Emilie , Nadzieja Marcin , Chang Wei , Escobar-Herrera Leandro , Mancinotti Davide , Angra Deepti , Khazaei Hamid , Crocoll Christoph , Vandenberg Albert , Stoddard Frederick L. , O’Sullivan Donal M. , Stougaard Jens , Schulman Alan H. , Andersen Stig U. , Geu-Flores Fernando 
Published: February 2020

AbstractFaba bean is a widely adapted and high-yielding legume cultivated for its protein-rich seeds1. However, the seeds accumulate the anti-nutritional pyrimidine glucosides vicine and convicine, which can cause haemolytic anaemia—favism—in the 400 million individuals genetically predisposed by a deficiency in glucose-6-phosphate dehydrogenase2. Here, we identify the first enzyme associated with vicine and convicine biosynthesis, which we name VC1. We show thatVC1co-locates with the major QTL for vicine and convicine content and that the expression ofVC1correlates highly with vicine content across tissues. We also show that low-vicine varieties express a version ofVC1carrying a small, frame-shift insertion, and that overexpression of wild-typeVC1leads to an increase in vicine levels.VC1encodes a functional GTP cyclohydrolase II, an enzyme normally involved in riboflavin biosynthesis from the purine GTP. Through feeding studies, we demonstrate that GTP is a precursor of vicine both in faba bean and in the distantly related plant bitter gourd. Our results reveal an unexpected biosynthetic origin for vicine and convicine and pave the way for the development of faba bean cultivars that are free from these anti-nutrients, providing a safe and sustainable source of dietary protein.
TRANSITION OF PODOSOMES INTO ZIPPER-LIKE STRUCTURES IN MACROPHAGE-DERIVED MULTINUCLEATED GIANT CELLS
Authors: Balabiyev Arnat , Podolnikova Nataly P. , Mursalimov Aibek , Lowry David , Newbern Jason M. , Roberson Robert W. , Ugarova Tatiana P. 
Published: February 2020

ABSTRACTMacrophage fusion resulting in the formation of multinucleated giant cells (MGCs) is a multistage process that requires many adhesion-dependent steps and involves the rearrangement of the actin cytoskeleton. The diversity of actin-based structures and their role in macrophage fusion is poorly understood. In this study, we revealed hitherto unrecognized actin-based zipper-like structures (ZLSs) that arise between MGCs formed on the surface of implanted biomaterials. We established anin vitromodel for the induction of these structures in mouse macrophages undergoing IL-4– mediated fusion. Using this model, we show that over time MGCs develop cell-cell contacts containing ZLSs. Live-cell imaging using macrophages isolated from mRFP- or GFP-Lifeact mice demonstrated that ZLSs are dynamic formations undergoing continuous assembly and disassembly and that podosomes are precursors of these structures. Immunostaining experiments showed that vinculin, talin, integrin αMβ2, and other components of podosomes are present in ZLSs. Macrophages deficient in WASp or Cdc42, two key molecules involved in actin core organization in podosomes, as well as cells treated with the inhibitors of the Arp2/3 complex failed to form ZLSs. Furthermore, E-cadherin and nectin-2 were found between adjoining membranes, suggesting that the transition of podosomes into ZLSs is induced by bridging plasma membranes by junctional proteins.
Characterizing Trabecular Bone Properties near the Glenohumeral Joint Following Brachial Plexus Birth Injury
Authors: Fawcett Emily B. , McCormick Carolyn M. , Murray Austin F. , Crouch Dustin L. , Saul Katherine R. , Cole Jacqueline H. 
Published: February 2020

AbstractBrachial plexus birth injury (BPBI) causes functional arm impairment in 30-40% of those affected due to altered loading on the glenohumeral joint. While gross morphological osseous deformities have been seen in the humerus and scapula, alterations in the underlying trabecular bone microstructure and mineralization are not clear. Using a murine model of BPBI, trabecular bone alterations were explored in the proximal humerus and distal scapula, which surround the articulating surface of the joint. Samples were scanned using micro-CT, reoriented, and analyzed for standard trabecular metrics. The regions of interest closest to the articulating surface showed the greatest detriments. In the scapula, the scapular neck region showed less robust trabecular bone in the neurectomy group with decreased BV/TV (p=0.001), BMD (p=0.001), Conn.D (p=0.006), Tb.N (p<0.0001), and DA (p=0.033), and increased Tb.Sp (p<0.0001) compared to sham. In the humerus, the epiphysis showed less robust trabecular bone in neurectomy group, but to a much lesser extent than the scapular neck. The neurectomy group showed reduced BMD (p=0.007) and Tb.N (p=0.029) compared to sham. Data suggest deformities are worse near the articulating surface, likely due to the greater amount of mechanical loading. The reduction in trabecular microstructure and mineralization may compromise bone strength of the affected limb following BPBI. Further investigation of the underlying trabecular bone deformities following injury are necessary to eventually inform better treatments to limit the development of deformities.
A Bayesian inference tool for identifying artifactual calls from differential transcript abundance analyses
Authors: Mangiola Stefano , Thomas Evan A , Modrák Martin , Papenfuss Anthony T 
Published: February 2020

AbstractRelative transcript abundance has proven to be a valuable tool for inferring the phenotype of biological systems from genetic material. Several methods for the analysis of differential transcript abundance have been developed, and some of the most popular are based on negative binomial models. Although most genes are fitted reasonably well by the negative binomial distribution, the presence of outlier observations that do not fit such models can lead to artifactual identification of significant changes in transcription. Identifying those transcripts for the correct interpretation of results is extremely important. A robust and automated tool for detecting sample/transcript pairs that do not fit a negative binomial regression model is currently lacking. Here we propose ppcseq, a robust statistical framework that models hierarchically sample- and gene-wise features such as sequencing depth bias, the association between mean transcript abundance and its over-dispersion, and provides a theoretical transcript abundance distribution, on which the observed transcript abundance can be tested for outliers. We show using a publicly available data set where nearly 10% of differentially abundant transcripts had fold change inflated by the presence of outliers. This method has broad utility in filtering artifactual results of differential transcript abundance analyses based on a negative binomial framework.
Glucose-mediated expansion of a gut commensal bacterium promotesPlasmodiuminfection through alkalizing mosquito midgut
Authors: Wang Mengfei , An Yanpeng , Dong Shengzhang , Feng Yuebiao , Gao Li , Wang Penghua , Dimopoulus George , Tang Huiru , Wang Jingwen 
Published: February 2020

SUMMARYDietary sugar is the major energy source for mosquitoes, but its influence on mosquitoes’ capability to transmit malaria parasite remains unclear. Here we show thatPlasmodium bergheiinfection changes global metabolism ofAnopheles stephensiwith the most significant impact on glucose metabolism. Supplementation of glucose or trehalose (the main hemolymph sugar) to mosquito increasesPlasmodiuminfection by alkalizing the mosquito midgut. The glucose/trehalose diets promote rapid growth of a commensal bacterium,Asaia bogorensis, which remodels glucose metabolism and consequently increases midgut pH. The pH increase in turn promotesPlasmodiumgametogenesis. We also demonstrate the sugar composition from different natural plants influencesA. bogorensisgrowth andPlasmodiuminfection is associated with their capability to expandA. bogorensis. Altogether, our results demonstrate that dietary glucose is an important factor that determines mosquito’s competency to transmitPlasmodiumand further highlight a key role for mosquito-microbiota metabolic interactions in regulating development of malaria parasite.
Rapid evolution in managed grasslands: different land-use regimes are associated with contrasting phenotypes inPlantago lanceolata
Authors: Gáspár Bence , Durka Walter , Bossdorf Oliver 
Published: February 2020

AbstractLand-use intensification is a major driver of biodiversity declines, and it is known to decrease species numbers and alter community composition of managed grasslands. An open question is whether similar impacts occur within species, i.e. whether grassland management affects also the genetic diversity of plant populations and alters their genetic composition, possibly reflecting adaptation to land use. To address these questions, we sampled 61 populations of the common grassland herbPlantago lanceolatathat covered a broad range of land use intensities in the German Biodiversity Exploratories, and we grew their offspring in a common environment to quantify variation in plant size, architecture, reproduction, and leaf economy. All measured traits harboured substantial heritable variation, and six out of nine traits showed population differentiation. Interestingly, several traits were significantly correlated with land use intensity, but with opposing trends for mowing versus grazing: Increased mowing intensity was associated with larger plant size and lower specific leaf area (SLA), which may reflect evolutionary responses to increased light competition and a lesser need for resource conservation in highly productive meadows. In contrast, increased grazing intensity tended to be associated with smaller plant size and higher SLA, a phenotype syndrome known from grazing lawns. Moreover, we found that land-use intensification also affected genetic diversity, again with opposing effects for mowing versus grazing: while increased mowing was associated with decreased levels of intrapopulation phenotypic variation, the opposite was true for increased grazing intensity. In summary, land use intensification has not only already caused rapid evolutionary changes in these grassland populations, it also affects their future evolutionary potential.
Investigating the effects of pre-stimulus cortical synchrony on behavior
Authors: van Es Mats W.J. , Gross Joachim , Schoffelen Jan-Mathijs 
Published: February 2020

AbstractRhythmic brain activity may provide a functional mechanism that facilitates dynamic interareal interactions and thereby give rise to complex behavior. It has been shown that low and high frequency oscillations propagate in opposite directions, but interactions between brain areas in various frequency bands are poorly understood. We investigated local and long-range synchrony in a brain-wide network and their relation to behavior, while human subjects executed a variant of the Simon task during MEG recording. We hypothesized that the behavioral difference for stimulus-response congruent (C) and incongruent (IC) trials is caused by differences in cortical synchrony, and that the relative behavioral benefit for trials following instances with the same stimulus-response contingency (i.e. the Gratton effect) is caused by contingency-induced changes in the state of the network. This would be achieved by temporarily upregulating the connectivity strength between behaviorally relevant network nodes. We identified regions-of-interest that differed in local synchrony during the response phase of the Simon task. Within this network, spectral power in none of the nodes in either of the studied frequencies was significantly different in the pre-cue window of the subsequent trial. Nor was there a significant difference in coherence between the task-relevant nodes that could explain the superior performance after compatible consecutive trials.
Genomic copy number predicts oesophageal cancer years before transformation
Authors: Killcoyne Sarah , Gregson Eleanor , Wedge David C. , Woodcock Dan J. , Eldridge Matthew , de la Rue Rachel , Miremadi Ahmad , Abbas Sujath , Blasko Adrienn , Januszewicz Wladyslaw , Varanou Jenkins Aikaterini , Gerstung Moritz , Fitzgerald Rebecca C. 
Published: February 2020

SummaryCancer arises through a process of somatic evolution and recent studies have shown that aneuploidies and driver gene mutations precede cancer diagnosis by several years to decades1–4Here, we address the question whether such genomic signals can be used for early detection and pre-emptive cancer treatment. To this end we study Barrett’s oesophagus, a genomic copy number driven neoplastic precursor lesion to oesophageal adenocarcinoma5. We use shallow whole genome sequencing of 777 biopsies sampled from 88 patients in surveillance for Barrett’s oesophagus over a period of up to 15 years. These data show that genomic signals exist that distinguish progressive from stable disease with an AUC of 0.87 and a sensitivity of 50% even ten years prior to histopathological disease transformation. These finding are validated on two independent cohorts of 75 and 248 patients. Compared against current patient management guidelines genomic risk classification enables earlier treatment for high risk patients as well as reduction of unnecessary treatment and monitoring for patients who are unlikely to develop cancer.
Correlating single-molecule characteristics of the yeast aquaglyceroporin Fps1 with environmental perturbations directly in living cells
Authors: Shashkova Sviatlana , Andersson Mikael , Hohmann Stefan , Leake Mark C 
Published: February 2020

AbstractMembrane proteins play key roles at the interface between the cell and its environment by mediating selective import and export of molecules via plasma membrane channels. Despite a multitude of studies on transmembrane channels, understanding of their dynamics directly within living systems is limited. To address this, we correlated molecular scale information from living cells with real time changes to their microenvironment. We employed super-resolved millisecond fluorescence microscopy with a single-molecule sensitivity, to track labelled molecules of interest in real time. We use as example the aquaglyceroporin Fps1 in the yeastSaccharomyces cerevisiaeto dissect and correlate its stoichiometry and molecular turnover kinetics with various extracellular conditions. In this way we shed new light on aspects of architecture and dynamics of glycerol-permeable plasma membrane channels.
Unveiling Crucivirus Diversity by Mining Metagenomic Data
Authors: de la Higuera Ignacio , Kasun George W. , Torrance Ellis L. , Pratt Alyssa A. , Maluenda Amberlee , Colombet Jonathan , Bisseux Maxime , Ravet Viviane , Dayaram Anisha , Stainton Daisy , Kraberger Simona , Zawar-Reza Peyman , Goldstien Sharyn , Briskie James V. , White Robyn , Taylor Helen , Gomez Christopher , Ainley David G. , Harding Jon S. , Fontenele Rafaela S. , Schreck Joshua , Ribeiro Simone G. , Oswald Stephen A. , Arnold Jennifer M. , Enault François , Varsani Arvind , Stedman Kenneth M. 
Published: February 2020

ABSTRACTThe discovery of cruciviruses revealed the most explicit example of a common protein homologue between DNA and RNA viruses to date. Cruciviruses are a novel group of circular Rep-encoding ssDNA (CRESS-DNA) viruses that encode capsid proteins (CPs) that are most closely related to those encoded by RNA viruses in the familyTombusviridae. The apparent chimeric nature of the two core proteins encoded by crucivirus genomes suggests horizontal gene transfer of CP genes between DNA and RNA viruses. Here, we identified and characterized 451 new crucivirus genomes and ten CP-encoding circular genetic elements throughde novoassembly and mining of metagenomic data. These genomes are highly diverse, as demonstrated by sequence comparisons and phylogenetic analysis of subsets of the protein sequences they encode. Most of the variation is reflected in the replication associated protein (Rep) sequences, and much of the sequence diversity appears to be due to recombination. Our results suggest that recombination tends to occur more frequently among groups of cruciviruses with relatively similar capsid proteins, and that the exchange of Rep protein domains between cruciviruses is rarer than gene exchange. Altogether, we provide a comprehensive and descriptive characterization of cruciviruses.IMPORTANCEViruses are the most abundant biological entities on Earth. In addition to their impact on animal and plant health, viruses have important roles in ecosystem dynamics as well as in the evolution of the biosphere. Circular Rep-encoding single-stranded (CRESS) DNA viruses are ubiquitous in nature, many are agriculturally important, and are viruses that appear to have multiple origins from prokaryotic plasmids. CRESS-DNA viruses such as the cruciviruses, have homologues of capsid proteins (CPs) encoded by RNA viruses. The genetic structure of cruciviruses attests to the transfer of capsid genes between disparate groups of viruses. However, the evolutionary history of cruciviruses is still unclear. By collecting and analyzing cruciviral sequence data, we provide a deeper insight into the evolutionary intricacies of cruciviruses. Our results reveal an unexpected diversity of this virus group, with frequent recombination as an important determinant of variability.
Decomposing Loss Aversion from Gaze Allocation and Pupil Dilation
Authors: Sheng Feng , Ramakrishnan Arjun , Seok Darsol , Zhao Wenjia Joyce , Thelaus Samuel , Cen Puti , Platt Michael Louis 
Published: February 2020

AbstractLoss-averse decisions, in which one avoids losses at the expense of gains, are highly prevalent. However, the underlying mechanisms remain controversial. The prevailing account highlights a valuation bias that overweighs losses relative to gains, but an alternative view stresses a response bias to avoid choices involving potential losses. Here we couple a computational process model with eye-tracking and pupillometry to develop a physiologicallygrounded framework for the decision process leading to accepting or rejecting gambles with equal odds of winning and losing money. Overall, loss-averse decisions were accompanied by preferential gaze towards losses and increased pupil dilation for accepting gambles. Using our model, we found gaze allocation selectively indexed valuation bias, and pupil dilation selectively indexed response bias. Finally, we demonstrated that our computational model and physiological biomarkers can identify distinct types of loss-averse decision-makers who would otherwise be indistinguishable using conventional approaches. Our study provides an integrative framework for the cognitive processes that drive loss-averse decisions and highlights the biological heterogeneity of loss aversion across individuals.Significance StatementWe revisit the concept of loss aversion by synthesizing distinct views into an integrative framework and by probing physiological biomarkers associated with the behavior. The framework decomposes loss aversion into a valuation bias, which weighs losses over gains, and a response bias, which avoids loss-related choices altogether. Further, we revealed a double dissociation in physiology underlying the decision process. Valuation bias was associated with preferential gaze allocation to losses whereas response bias was associated with pupillary dilation. Our framework exposed biological heterogeneity underlying loss aversion and distinguishes different loss-averse decision makers who are otherwise indistinguishable using conventional approaches. Our integrative approach provides a deeper analysis of the mechanisms underlying loss aversion and incorporates distinct views within a unified biological framework.
Differential Synaptic Input to External Globus Pallidus Neuronal SubpopulationsIn Vivo
Authors: Ketzef Maya , Silberberg Gilad 
Published: February 2020

SummaryThe rodent external Globus Pallidus (GPe) contains two main neuronal subpopulations, prototypic and arkypallidal cells, which differ in their cellular properties. Their functional synaptic connectivity is, however, largely unknown. Here, we studied the membrane properties and synaptic inputs to these subpopulations in the mouse GPe. We obtained in vivo whole-cell recordings from identified GPe neurons and used optogenetic stimulation to dissect their afferent inputs from the striatum and subthalamic nucleus (STN). All GPe neurons received barrages of excitatory and inhibitory input during slow wave activity. The modulation of their activity was cell-type specific and shaped by their respective membrane properties and afferent inputs. Both GPe subpopulations received synaptic input from STN and striatal projection neurons (MSNs). STN and indirect pathway MSNs strongly targeted prototypic cells while direct pathway MSNs selectively inhibited arkypallidal cells. We show that GPe subtypes are differently embedded in the basal ganglia network, supporting distinct functional roles.
RNA-protein interaction mapping via MS2 or Cas13-based APEX targeting
Authors: Han Shuo , Zhao Boxuan Simen , Myers Samuel A. , Carr Steven A. , He Chuan , Ting Alice Y. 
Published: February 2020

AbstractRNA-protein interactions underlie a wide range of cellular processes. Improved methods are needed to systematically map RNA-protein interactions in living cells in an unbiased manner. Capitalizing on the ability of the engineered peroxidase APEX2 to identify protein interaction partners via proximity-dependent biotinylation, we used two approaches to target APEX2 to specific cellular RNAs. Both an MS2-MCP system and an engineered CRISPR-Cas13 system were able to deliver APEX2 to the human telomerase RNA hTR with high specificity. One-minute proximity biotinylation captured endogenous protein interaction partners of hTR, including more than a dozen proteins not previously linked to hTR. We validated the unexpected interaction between hTR and theN6-methyladenosine (m6A) demethylase ALKBH5. Further investigation showed that endogenous hTR is modified by m6A, which can be erased by ALKBH5, and that ALKBH5 influences both telomerase complex assembly and activity. These results highlight the ability of MS2- and Cas13-targeted APEX2 to identify novel RNA-protein interactions in living cells.
Many but not all lineage-specific genes can be explained by homology detection failure
Authors: Weisman Caroline M. , Murray Andrew W. , Eddy Sean R. 
Published: February 2020

AbstractGenes for which homologs can be detected only in a limited group of evolutionarily related species, called “lineage-specific genes,” are pervasive: essentially every lineage has them, and they often comprise a sizable fraction of the group’s total genes. Lineage-specific genes are often interpreted as “novel” genes, representing genetic novelty born anew within that lineage. Here, we develop a simple method to test an alternative null hypothesis: that lineage-specific genes do have homologs outside of the lineage that, even while evolving at a constant rate in a novelty-free manner, have merely become undetectable by search algorithms used to infer homology. We show that this null hypothesis is sufficient to explain the lack of detected homologs of a large number of lineage-specific genes in fungi and insects. However, we also find that a minority of lineage-specific genes in both clades are not well-explained by this novelty-free model. The method provides a simple way of identifying which lineage-specific genes call for special explanations beyond homology detection failure, highlighting them as interesting candidates for further study.