bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudo-Location: A novel predictor for predicting pseudo-temporal gene expression patterns using spatial functional regression
Authors: Ahn Kyungmin , Fujiwara Hironobu 
Published: June 2020

Statement of withdrawalThe authors have withdrawn version 1 of this manuscript because a draft manuscript, which was still in the early stages of preparation and required major revisions including the replacement of the source RNA-seq datasets, was erroneously submitted. The authors do not wish this version to be cited as reference for this study. We will post a revised manuscript in the future. If you have any questions, please contact the corresponding author.
Prediction of complex phenotypes using theDrosophilametabolome
Authors: Rohde Palle Duun , Kristensen Torsten Nygaard , Sarup Pernille , Muñoz Joaquin , Malmendal Anders 
Published: June 2020

ABSTRACTUnderstanding the genotype – phenotype map and how variation at different levels of biological organization are associated are central topics in modern biology. Fast developments in sequencing technologies and other molecular omic tools enable researchers to obtain detailed information on variation at DNA level and on intermediate endophenotypes; such as RNA, proteins and metabolites. This can facilitate our understanding of the link between genotypes and molecular and functional organismal phenotypes. Here, we use theDrosophilaGenetic Reference Panel and nuclear magnetic resonance (NMR) metabolomics to investigate the ability of the metabolome to predict organismal phenotypes. We performed NMR metabolomics on four replicate pools of male flies from each of 170 different isogenic lines. Our results show that metabolite profiles are variable among the investigated lines and that this variation is highly heritable. Secondly, we identify genes associated with metabolome variation. Thirdly, using the metabolome gave better prediction accuracies than genomic information for four of five quantitative traits analysed. Our comprehensive characterization of population-scale diversity of metabolomes and its genetic basis illustrates that metabolites have large potential as predictors of organismal phenotypes. This finding is of great importance e.g. in human medicine and animal and plant breeding.
Insertion of an endogenous Jaagsiekte Sheep Retrovirus element into theBCO2 -gene abolishes its function and leads to yellow discoloration of adipose tissue in Norwegian Spælsau (Ovis aries)
Authors: Kent Matthew , Moser Michel , Boman Inger Anne , Lindtveit Kristine , Árnyasi Mariann , Sundsaasen Kristil Kindem , Våge Dag Inge 
Published: June 2020

AbstractBackgroundThe accumulation of carotenoids in adipose tissue leading to yellow fat is, in sheep, a heritable recessive trait that can be attributed to a nonsense mutation in thebeta-carotene oxygenase 2 (BCO2)gene. However, not all sheep breeds suffering from yellow fat have this nonsense mutation, meaning that other functional mechanisms must exist. We investigated one such breed, the Norwegian spælsau.ResultsIn spælsau we detected an aberration inBCO2mRNA. Nanopore sequencing of genomic DNA revealed the insertion of a 7.9 kb endogenous Jaagsiekte Sheep Retrovirus (enJSRV) sequence in the first intron of theBCO2gene. Close examination of its cDNA revealed that theBCO2genes first exon was spliced together with enJSRV-sequence immediately downstream of a potential - AG splice acceptor site at enJSRV position 415. The hybrid protein product consists of 29 amino acids coded by theBCO2exon 1, followed by 29 amino acids arbitrary coded for by the enJSRV-sequence, before a translation stop codon is reached.ConclusionsConsidering that the functional BCO2 protein consists of 575 amino acids, it is unlikely that the 58 amino acid BCO2/enJSRV hybrid protein can display any enzymatic function. The existence of this novelBCO2allele represents an alternative functional mechanism accounting forBCO2inactivation and is a perfect example of the potential benefits for searching for structural variants using long-read sequencing data.
Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells
Authors: Wong Candida , Darby Jocelyn M. , Murphy Peter R. , Pinfold Terry L. , Lennard Patrick R. , Woods Gregory M , Lyons A. Bruce , Flies Andrew S. 
Published: June 2020

AbstractImmune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis. Similarly, CD28 can capture CD80 and CD86 via trogocytosis and retain the captured ligands on the surface of the CD28-expressing cells. The wild Tasmanian devil (Sarcophilus harrisii) population has declined by 77% due to transmissible cancers that evade immune defenses despite genetic mismatches between the host and tumours. We used a live cell-based assay to demonstrate that devil CTLA4 and CD28 can capture CD80 and CD86. Mutation of evolutionarily conserved motifs in CTLA4 altered functional interactions with CD80 and CD86 in accordance with patterns observed in other species. These results suggest that checkpoint immunotherapies can be translated to evolutionarily divergent species.HighlightsKey immune checkpoint receptor-ligand interactions are conserved in marsupials.Live cell-based assays show Tasmanian devil CD28 and CTLA4 can capture CD80 and CD86in transfrom adjacent cells.Mutation of the conserved CTLA4MYPPPYligand binding motif to CTLA4MYPPPAreduces binding to CD80 and intercellular protein transfer.Removal of conserved CTLA4YVKMprotein recycling binding motif in CTLA4 results in bidirectional intercellular protein transfer between CTLA4 and CD80.Highly successful human immune checkpoint immunotherapies have the potential to be translated for veterinary and conservation medicine.
Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs
Authors: Zhang Meng , Gui Miao , Wang Zi-Fu , Gorgulla Christoph , Yu James J , Wu Hao , Sun Zhen-yu , Klenk Christoph , Merklinger Lisa , Morstein Lena , Hagn Franz , Plückthun Andreas , Brown Alan , Nasr Mahmoud L , Wagner Gerhard 
Published: June 2020

AbstractG protein coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals1,2. Although several structures have been solved for GPCR-G protein complexes3–17, structural studies of the complex in a physiological lipid membrane environment are lacking. Additionally, most previous studies required additional antibodies/nanobodies and/or engineered G proteins for complex stabilization. In the absence of a native complex structure, the underlying mechanism of G protein activation leading to GDP/GTP exchange remains unclear. Here, we report cryo-EM structures of lipid bilayer-bound complexes of neurotensin, neurotensin receptor 1, and Gαi1β1γ1 protein in two conformational states, resolved to 4.1 and 4.2 Å resolution. The structures were determined without any stabilizing antibodies/nanobodies, and thus provide a native-like platform for understanding the structural basis of GPCR-G protein complex formation. Our structures reveal an extended network of protein-protein interactions at the GPCR-G protein interface compared to in detergent micelles, defining roles for the lipid membrane in modulating the structure and dynamics of complex formation, and providing a molecular explanation for the stronger interaction between GPCR and G protein in lipid bilayers. We propose a detailed allosteric mechanism for GDP release, providing new insights into the activation of G proteins for downstream signaling under near native conditions.
Not quite human, not quite machine: Electrophysiological responses to robot faces
Authors: Geiger Allie R. , Balas Benjamin 
Published: June 2020

AbstractFace recognition is supported by selective neural mechanisms that are sensitive to various aspects of facial appearance. These include ERP components like the P100, N170, and P200 which exhibit different patterns of selectivity for various aspects of facial appearance. Examining the boundary between faces and non-faces using these responses is one way to develop a more robust understanding of the representation of faces in visual cortex and determine what critical properties an image must possess to be considered face-like. Here, we probe this boundary by examining how face-sensitive ERP components respond to robot faces. Robot faces are an interesting stimulus class because they can differ markedly from human faces in terms of shape, surface properties, and the configuration of facial features, but are also interpreted as social agents in a range of settings. In two experiments, we examined how the P100 and N170 responded to human faces, robot faces, and non-face objects (clocks). We found that robot faces elicit intermediate responses from face-sensitive components relative to non-face objects and both real and artificial human faces (Exp. 1), and also that the face inversion effect was only partly evident in robot faces (Exp. 2). We conclude that robot faces are an intermediate stimulus class that offers insight into the perceptual and cognitive factors that affect how social agents are identified and categorized.
Molecular Dynamics Simulations of Bacterial Outer Membrane Lipid Extraction: Adequate Sampling?
Authors: Shearer Jonathan , Marzinek Jan K. , Bond Peter J. , Khalid Syma 
Published: June 2020

AbstractThe outer membrane of Gram-negative bacteria is almost exclusively composed of lipopolysaccharide in its outer leaflet, whereas the inner leaflet contains a mixture of phospholipids. Lipopolysaccharide diffuses at least an order of magnitude slower than phospholipids, which can cause issues for molecular dynamics simulations in terms of adequate sampling. Here we test a number of simulation protocols for their ability to achieve convergence with reasonable computational effort using the MARTINI coarse-grained force-field. This is tested in the context both of potential of mean force (PMF) calculations for lipid extraction from membranes, and of lateral mixing within the membrane phase. We find that decoupling the cations that cross-link the lipopolysaccharide headgroups from the extracted lipid during PMF calculations is the best approach to achieve convergence comparable to that for phospholipid extraction. We also show that lateral lipopolysaccharide mixing/sorting is very slow and not readily addressable even with Hamiltonian replica exchange. We discuss why more sorting may be unrealistic for the short (microseconds) timescales we simulate and provide an outlook for future studies of lipopolysaccharide-containing membranes.
An ABA Synthesis Enzyme AlleleOsNCED2Promotes the Aerobic Adaption in Upland Rice
Authors: Huang Liyu , Bao Yachong , Qin Shiwen , Ning Min , Lyu Jun , Zhang Shilai , Huang Guangfu , Zhang Jing , Wang Wensheng , Fu Binying , Hu Fengyi 
Published: June 2020

ABSTRACTThere are two ecotypes, upland rice and irrigate rice, during its evolution in rice. Upland rice exhibits aerobic adaptive phenotype via its stronger root system and more rapid drought responses compared with its counterpart, irrigated rice. We assessed the functional variation and applications of the aerobic adaptive alleleOsNCED2Tcloned from IRAT104 which is a cultivar of upland rice.OsNCED2-overexpressing transgenic rice andOsNCED2T-NILs exhibited significantly higher ABA contents at the seedling and reproductive stages, which can improve root development (RD) and drought tolerance (DT) to promote aerobic adaptation in upland rice. RNA-Seq-based expression profiling of transgenic versus wild-type rice identifiedOsNCED2-mediated pathways that regulate RD and DT. Meanwhile,OsNCED2-overexpressing rice exhibited significantly increased reactive oxygen species (ROS)-scavenging abilities and transcription levels of many stress- and development-related genes, which regulate RD and DT. A SNP mutation (C to T) from irrigated rice to upland rice, caused the functional variation ofOsNCED2, and the enhanced RD and DT mediated by this site under aerobic conditions could promote higher yield of upland rice. These results show thatOsNCED2T, through ABA synthesis, positively modulates RD and DT which confers aerobic adaptation in upland rice and might serve as a novel gene for breeding aerobic adaptive or water-saving rice.
Phytohormone production by the arbuscular mycorrhizal fungusRhizophagus irregularis
Authors: Pons Simon , Fournier Sylvie , Chervin Christian , Bécard Guillaume , Rochange Soizic , Frey Nicolas Frei Dit , Pagès Virginie Puech 
Published: June 2020

AbstractArbuscular mycorrhizal symbiosis is a mutualistic interaction between most land plants and fungi of the glomeromycotina subphylum. The initiation, development and regulation of this symbiosis involve numerous signalling events between and within the symbiotic partners. Among other signals, phytohormones are known to play important roles at various stages of the interaction. During presymbiotic steps, plant roots exude strigolactones which stimulate the fungus, and favour the initiation of symbiosis. At later stages, different plant hormone classes can act as positive or negative regulators of the interaction. Although the fungus is known to reciprocally emit regulatory signals, its potential contribution to the phytohormonal pool has received little attention, and has so far only been addressed by indirect assays. In this study, using mass spectrometry, we analyzed phytohormones released into the medium by germinated spores of the arbuscular mycorrhizal fungusRhizophagus irregularis. We detected the presence of a cytokinin (isopentenyl-adenosine) and an auxin (indole-acetic acid). In addition, we identified a gibberellin (gibberellic acid 4) in spore extracts. We also used gas chromatography to show thatR. irregularisproduces ethylene from methionine and the α-keto γ-methylthiobutyric acid pathway. These results highlight the possibility for AM fungi to use phytohormones to interact with their host plants, or to regulate their own development.
A split methyl halide transferase AND gate that reports by synthesizing an indicator gas
Authors: Fulk Emily M. , Huh Dongkuk , Atkinson Joshua T. , Lie Margaret , Masiello Caroline A. , Silberg Jonathan J. 
Published: June 2020

AbstractIt is challenging to detect microbial reactions in highly opaque or autofluorescent environments like soils, seawater, and wastewater. To develop a simple approach for monitoring post-translational reactions within microbes situated in environmental matrices, we designed a methyl halide transferase (MHT) fragment complementation assay that reports by synthesizing an indicator gas. We show that backbone fission within regions of high sequence variability in the Rossmann-fold domain yields split MHT (sMHT) AND gates whose fragments cooperatively associate to synthesize CH3Br. Additionally, we identify a sMHT whose fragments require fusion to pairs of interacting partner proteins for maximal activity. We also show that sMHT fragments fused to FKBP12 and the FKBP-rapamycin binding domain of mTOR display significantly enhanced CH3Br production in the presence of rapamycin. This gas production is reversed in the presence of the competitive inhibitor of FKBP12/FKPB dimerization, indicating that sMHT is a reversible reporter of post-translational reactions. This sMHT represents the first genetic AND gate that can report on protein-protein interactions via an indicator gas. Because indicator gases can be measured in the headspaces of complex environmental samples, this protein fragment complementation assay should be useful for monitoring the dynamics of diverse molecular interactions within microbes situated in hard-to-image marine and terrestrial matrices.
Campaign-Based Citizen Science for Environmental Mycology: the “Science Solstice” and “Summer Soil-stice” Projects to Assess Drug Resistance in Air and SoilborneAspergillus fumigatus
Authors: Shelton Jennifer M. G. , Fisher Matthew C. , Singer Andrew C. 
Published: June 2020

AbstractCitizen science projects are often undertaken for ecological and environmental research purposes but also have great potential for use in microbiology research to track the emergence and spread of pathogens in the environment. ‘Science Solstice’ and ‘Summer Soil-stice’ are mycology citizen science projects aimed at assessing drug resistance inAspergillus fumigatusfungal spores found in air and soil, respectively, in the United Kingdom (UK).A. fumigatusplays an important role in the environment as a decomposer of plant material, but is also an opportunistic human lung pathogen. Infection with drug-resistant spores can lead to a worse clinical outcome for the patient.On the first four solstice and equinox days between June 2018 and June 2019, volunteers were asked to collect air samples from their homes and workplaces and return them to our lab in Freepost envelopes. An additional round of samples was requested from volunteer’s gardens and/or compost on the June 2019 solstice. In total, 787 volunteers returned 2,132 air samples and 509 soil samples, which grew a total of 7,991A. fumigatuscolonies. The estimated total cost of the study was £2,650; the equivalent of 33 pence perA. fumigatuscolony grown.Incorporating citizen science into the environmental surveillance of drug-resistantA. fumigatusallowed for the simultaneous collection of hundreds of environmental samples across the entire UK on the same day. The insights generated from this study would not be practical in the absence of public participation and offers opportunities to ask scientific questions that were previously unaskable.
Task Related Neural Activity Following Primary Motor Cortical Ischemic Injury in Rats
Authors: Pack Andrea R. , Murphy Max D. , Barbay Scott , Nudo Randolph J. , Guggenmos David J. 
Published: June 2020

ABSTRACTAcquired injuries to primary motor cortex (M1) contribute to motor impairment and disability. Functional recovery is predicated on the reorganization of spared areas, which has been demonstrated through cortical motor map representations and neuroanatomical projection and termination patterns. The purpose of this study was to understand how neurophysiological outputs of spared motor areas relate to motor recovery of a skilled reach task following an ischemic infarct to M1. We examined changes in single unit activity within ipsilesional pre-motor (PM) and contralesional M1 cortices of rats during a behavioral task after a unilateral ischemic injury to ipsilesional M1. The data show a shift in neuronal firing patterns in the contralateral PM and ipsilateral M1 during behavioral recovery in lesion rats compared to a non-lesion control group, suggesting that spike-timing properties are altered in specific phases of the task, and that this altered activity may support spontaneous restoration of motor behavior.SIGNIFICANCE STATEMENTFollowing ischemic stroke to primary motor cortex (M1), motor recovery is associated with reorganization of spared cortical motor areas in injured and spared hemispheres. Currently, it is unclear how cortical plasticity within spared motor areas relates to motor recovery. This study examines how task-related neural activity within spared motor areas in rats correlates with motor restoration of a skilled reach task following an ischemic infarct to M1. The data suggest contralateral pre-motor and ipsilateral M1 alter their neural response profiles with respect to the timing of a motor task during recovery. To our knowledge, this is the first demonstration of a compensatory single-spike neurophysiological mechanism that may explain how remote, spared cortical areas contribute to functional recovery after M1 injury.
The impact of interactions on invasion and colonization resistance in microbial communities
Authors: Kurkjian Helen , Akbari M. Javad , Momeni Babak 
Published: June 2020

AbstractIn human microbiota, the prevention or promotion of invasions can be crucial to human health. Invasion outcomes, in turn, are impacted by the composition of resident communities and interactions among resident microbes. Microbial communities differ from communities composed of other types of organisms in that many microbial interactions are mediated by chemicals that are released into or consumed from the environment. We ask what determines invasion outcomes in such microbial communities. Here, we use a model based on chemical-mediated interactions among microbial species to assess the impact of positive and negative interactions on invasion outcomes. We classified invasion outcomes as resistance, augmentation, displacement, or disruption depending on whether the richness of the resident community was maintained or dropped and whether the invader was maintained in the community or went extinct. We found that as the number of invaders increased relative to size of the resident community, resident communities were increasingly disrupted. As facilitation of the invader by the resident community increased, resistance outcomes were replaced by displacement and augmentation. By contrast, as facilitation increased among residents, displacement outcomes shifted to resistance. When facilitation of the resident community by the invader was eliminated, augmentation outcomes were replaced by displacement outcomes, while when inhibition of residents by invaders was eliminated, there was little change in the frequency of invasion outcomes. These results suggest that a better understanding of the chemical-mediated interactions within resident communities and between residents and invaders is crucial to predicting the success of invasions into microbial communities.
Effects of a Contusive Spinal Cord Injury on Spinal Motor Neuron Activity and Conduction Time in Rats
Authors: Borrell Jordan A. , Krizsan-Agbas Dora , Nudo Randolph J. , Frost Shawn B. 
Published: June 2020

AbstractObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation.ApproachAdult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At four weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles.Main resultsIn healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10-12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ~20-60 ms, generally following a Gaussian distribution, rising above baseline at time LON, followed by a peak response (Lp), and then falling below baseline at time LOFF. EMG responses occurred between LONand Lp(25-27 ms). In SCI rats, short-latency responses were still present, long-latency responses were disrupted or eliminated, and EMG responses were never evoked. The retention of the short-latency responses indicates that spared descending spinal fibers, most likely via the cortico-reticulospinal pathway, can still depolarize spinal cord motor neurons after a dorsal midline contusion injury.SignificanceThis study provides novel insights into the role of alternate pathways for voluntary control of hindlimb movements after SCI that disrupts the corticospinal tract in the rat.