bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid invisible frequency tagging reveals nonlinear integration of auditory and visual information
Authors: Drijvers Linda , Jensen Ole , Spaak Eelke 
Published: May 2020

AbstractDuring communication in real-life settings, the brain integrates information from auditory and visual modalities to form a unified percept of our environment. In the current magnetoencephalography (MEG) study, we used rapid invisible frequency tagging (RIFT) to generate steady-state evoked fields and investigated the integration of audiovisual information in a semantic context. We presented participants with videos of an actress uttering action verbs (auditory; tagged at 61 Hz) accompanied by a gesture (visual; tagged at 68 Hz, using a projector with a 1440 Hz refresh rate). Integration difficulty was manipulated by lower-order auditory factors (clear/degraded speech) and higher-order visual factors (congruent/incongruent gesture). We identified MEG spectral peaks at the individual (61/68 Hz) tagging frequencies. We furthermore observed a peak at the intermodulation frequency of the auditory and visually tagged signals (fvisual- fauditory= 7 Hz), specifically when lower-order integration was easiest because signal quality was optimal. This intermodulation peak is a signature of nonlinear audiovisual integration, and was strongest in left inferior frontal gyrus and left temporal regions; areas known to be involved in speech-gesture integration. The enhanced power at the intermodulation frequency thus reflects the ease of lower-order audiovisual integration and demonstrates that speech-gesture information interacts in higher-order language areas. Furthermore, we provide a proof-of-principle of the use of RIFT to study the integration of audiovisual stimuli, in relation to, for instance, semantic context.
Maintenance of species differences in closely related tetraploid parasiticEuphrasia(Orobanchaceae) on an isolated island
Authors: Becher Hannes , Brown Max R. , Powell Gavin , Metherell Chris , Riddiford Nick J. , Twyford Alex D. 
Published: May 2020

AbstractPolyploidy is pervasive in angiosperm evolution and plays important roles in adaptation and speciation. However, polyploid groups are understudied due to complex sequence homology, challenging genome assembly, and taxonomic complexity. Here we study adaptive divergence in taxonomically complex eyebrights (Euphrasia), where recent divergence, phenotypic plasticity and hybridisation blur species boundaries. We focus on three closely-related tetraploid species with contrasting ecological preferences, and which are sympatric on Fair Isle, a small isolated island in the British Isles. Using a common garden experiment, we show a genetic component to the morphological differences present between these species. Using whole genome sequencing and a novelk-mer approach, we demonstrate an allopolyploid origin, with sub-genome divergence of approximately 5%. Using ~2 million SNPs we show sub-genome homology across species consistent with a common origin, with very low sequence divergence characteristic of recent speciation. This genetic variation is broadly structured by species, with clear divergence of Fair Isle heathlandE. micrantha,while grasslandE. arcticaand coastalE. foulaensisare more closely related. Overall, we show tetraploidEuphrasiais an allopolyploid system characterised by postglacial species divergence, where adaptation to novel environments may be conferred by old variants rearranged into new genetic lineages.
DietaryS. maltophiliapromotes fat storage by enhancing lipogenesis and ER-LD contacts inC. elegans
Authors: Xie Kang , Liu Yangli , Li Xixia , Zhang Hong , Zhang Shuyan , Mak Ho Yi , Liu Pingsheng 
Published: May 2020

AbstractDietary and symbiotic bacteria can exert powerful influence on metazoan lipid metabolism. Here, we demonstrate that feedingCaenorhabditis elegans (C. elegans)with the opportunistic pathogenic bacteriaStenotrophomonas maltophilia (S. maltophilia)retards growth and promotes excessive fat storage. Gene expression analysis reveals that dietaryS. maltophiliainduces a lipogenic transcriptional response that includes the SREBP ortholog SBP-1, and fatty acid desaturases FAT-6 and FAT-7. Live imaging and ultrastructural analysis suggest that excess fat is stored in greatly expanded lipid droplets (LDs), as a result of enhanced endoplasmic reticulum-LD interaction. We also report that loss of function mutations incyp-35B1ordpy-9inC. elegansconfers resistance toS. maltophilia.Our work delineates a new model for understanding microbial regulation of metazoan physiology.
Proteomic and functional mapping of cardiac NaV1.5 channel phosphorylation reveals multisite regulation of surface expression and gating
Authors: Lorenzini Maxime , Burel Sophie , Lesage Adrien , Wagner Emily , Charrière Camille , Chevillard Pierre-Marie , Evrard Bérangère , Maloney Dan , Ruff Kiersten M. , Pappu Rohit V. , Wagner Stefan , Nerbonne Jeanne M. , Silva Jonathan R. , Townsend R. Reid , Maier Lars S. , Marionneau Céline 
Published: May 2020

AbstractPhosphorylation of NaV1.5 channels regulates cardiac excitability, yet the phosphorylation sites regulating channel function and the underlying mechanisms remain largely unknown. Using a systematic quantitative phosphoproteomic approach, we analyzed NaV1.5 channel complexes purified from non-failing and failing mouse left ventricles, and we identified 42 phosphorylation sites on NaV1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic NaV1.5 mutants revealed the roles of three phosphosites in regulating NaV1.5 channel expression and gating. The phosphorylated serines-664 and -667 regulate the voltage-dependence of channel activation in a cumulative manner, whereas phosphorylation of the nearby serine-671, which is increased in failing hearts, decreases cell surface NaV1.5 expression and peak Na+current. No additional roles could be assigned to the other clusters of phosphosites. Taken together, the results demonstrate that ventricular NaV1.5 is highly phosphorylated, and that the phosphorylation-dependent regulation of NaV1.5-encoded channels is highly complex, site-specific and dynamic.AbbreviationsA, alanine; E, glutamate; HEK-293, Human Embryonic Kidney 293 cells; INa, peak Na+current; INaL, late Na+current; IP, immunoprecipitation; mαNaVPAN, anti-NaVchannel subunit mouse monoclonal antibody; MS, Mass Spectrometry; MS1, mass spectrum of peptide precursors; MS2 or MS/MS, fragmentation mass spectrum of peptides selected in narrow mass range (2 Da) from MS1 scan; NaV, voltage-gated Na+channel; pS, phosphoserine; pT, phosphothreonine; S, serine; T, threonine; TAC, Transverse Aortic Constriction; TMT, Tandem Mass Tag.
Hypoxia Depletes Contaminating CD45+Hematopoietic Cells from Bone Marrow Stromal Cell (BMSC) Cultures: Methods for BMSC Culture Purification
Authors: Guo Wendi , Spiller Kassandra V. , Tang Jackie , Karner Courtney M. , Hilton Matthew J. , Wu Colleen 
Published: May 2020

SUMMARYCulture expanded bone marrow stromal cells (BMSCs) are easily isolated, can be grown rapidlyen masse,and contain both skeletal stem cells (SSCs) and multipotent mesenchymal progenitors (MMPs). Despite this functional heterogeneity, BMSC cultures continue to be utilized for many applications due to the lack of definitive and universally accepted markers to prospectively identify and purify SSCs. Isolation of BMSCs is widely based on their adherence to tissue culture plastic; however, this method poses unique challenges when working with murine models. In particular, hematopoietic cell contamination is a significant impediment during the isolation or murine BMSCs. Several strategies to reduce hematopoietic contamination have been developed with varying levels of success. In this study, we found that up to 60% of cells isolated in standard BMSC cultures expressed the hematopoietic marker CD45. Remarkably, when cultured at a physiological oxygen tension of 1% O2, there was a 10-fold reduction in hematopoietic cells associated with a concomitant increase in PDGFRα+expressing stromal cells. This finding was due, in part, to a differential response of the two populations to low oxygen tension, or hypoxia. Specifically, in standard tissue culture conditions of 21% O2, CD45+hematopoietic cells showed increased proliferation coupled with no observable changes in cell death when compared to their counterparts grown at 1% O2. In contrast, PDGFRα+stromal cells responded to hypoxia by increasing proliferation and exhibiting a 10-fold decrease in cell death. In summary, we describe a simple and reliable method exploiting the divergent biological response of hematopoietic and stromal cells to hypoxia to significantly increase the PDGFRα+stromal cell population in murine BMSC cultures.
Roosting ecology of the southernmost bats,Myotis chiloensisandHistiotus magellanicus, in southern Tierra del Fuego, Chile
Authors: Ossa Gonzalo , Lilley Thomas M. , Waag Austin G. , Meierhofer Melissa B. , Johnson Joseph S. 
Published: May 2020

ABSTRACTThere are few studies of day-roosting ecology of bats inhabiting the southernmost forests of South America, where cool summer temperatures and land management practices pose several challenges. The goal of the present study was to describe day-roosting habitats and patterns of thermoregulation in two bat species occurring on Tierra del Fuego,Myotis chiloensis(Chilean myotis) andHistiotus magellanicus(southern big-eared brown bat), during late spring. To do so, we tagged 17 bats with temperature-sensitive radio-transmitters, located 17 day-roosts, and collected 81 days of skin temperature data. We concurrently recorded ambient air temperature to determine its effect on torpor use. Both species were found roosting in large diameter (77.8 ± 6 cm), typically live,Nothofagus pumiliotrees (lenga) located on the edges of forest gaps or within stands primarily composed of smaller, younger trees. Bats of both species frequently used torpor, with skin temperatures dropping below a torpor threshold on 89% of days (n= 72) and daily minimum skin temperatures averaging 16.5 °C over the course of our study. Average daily air temperature was a significant predictor of torpor use, with lower skin temperatures and more time spent in torpor observed on colder days. Minimum skin temperature and time spent torpid did not vary between bat species, nor did the characteristics of day-roosts. These data show that spring temperatures in Tierra del Fuego pose an energetic challenge that bats meet through frequent use of torpor, and likely, habitat selection. We recommend local conservation efforts keep these thermal challenges in mind by retaining large trees, which may provide warmer microclimates or room for social groups.
Calcium ions promote membrane fusion by forming negative-curvature inducing clusters on specific anionic lipids
Authors: Allolio Christoph , Harries Daniel 
Published: May 2020

ABSTRACTVesicles enriched in certain negatively charged lipids, such as phosphatidylserine and PIP2, are known to undergo fusion in the presence of calcium ions without assistance from protein assemblies. Other lipids do not exhibit this propensity, even if they are negatively charged. Using our recently developed methodology, we extract elastic properties of a representative set of lipids. This allows us to trace the origin of lipid-calcium selectivity in membrane fusion to the formation of lipid clusters with long-range correlations that induce negative curvature on the membrane surface. Furthermore, the clusters generate lateral tension in the headgroup region at the membrane surface, concomitantly increasing its Gaussian bending modulus. Finally, calcium binding also reduces the orientational polarization of water around the membrane headgroups, potentially reducing the hydration force acting between membranes. Binding calcium only weakly increases membrane bending rigidity and tilt moduli, in agreement with experiments. We show how the combined effects of calcium binding to membranes lower the barriers along the fusion pathway that lead to the formation of the fusion stalk as well as the fusion pore.
Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT
Authors: Jia Wen , Tripathi Shubham , Chakraborty Priyanka , Chedere Adithya , Rangarajan Annapoorni , Levine Herbert , Jolly Mohit Kumar 
Published: May 2020

AbstractEpithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are central to metastatic aggressiveness and therapy resistance in solid tumors. While molecular determinants of both processes have been extensively characterized, the heterogeneity in the response of tumor cells to EMT and MET inducers has come into focus recently, and has been implicated in the failure of anti-cancer therapies. Recent experimental studies have shown that some cells can undergo an irreversible EMT depending on the duration of exposure to EMT-inducing signals. While the irreversibility of MET, or equivalently, resistance to EMT, has not been studied in as much detail, evidence supporting such behavior is slowly emerging. Here, we identify two possible mechanisms that can underlie resistance of cells to undergo EMT: epigenetic feedback in ZEB1/GRHL2 feedback loop and stochastic partitioning of biomolecules during cell division. Identifying the ZEB1/GRHL2 axis as a key determinant of epithelial-mesenchymal plasticity across many cancer types, we use mechanistic mathematical models to show how GRHL2 can be involved in both the abovementioned processes, thus driving an irreversible MET. Our study highlights how an isogenic population may contain subpopulation with varying degrees of susceptibility or resistance to EMT, and proposes a next set of questions for detailed experimental studies characterizing the irreversibility of MET/resistance to EMT.
Bacterial diets differentially alter lifespan and healthspan trajectories inC. elegans
Authors: Stuhr Nicole L. , Curran Sean P. 
Published: May 2020

ABSTRACTDiet is one of the more variable aspects in life due to the variety of options that organisms are exposed to in their natural habitats. In the laboratory,C. elegansare raised on bacterial monocultures, traditionally theE. coli Bstrain OP50, and spontaneously occurring microbial contaminants are removed to limit experimental variability because diet - including the presence of contaminants, can exert a potent influence over animal physiology. In order to diversify the menu available to cultureC. elegansin the lab, we have isolated and cultured three such microbes:Methylobacterium, Xanthomonas, andSphingomonas.The nutritional composition of these bacterial foods is unique, and when fed toC. elegans, can differentially alter multiple life history traits including development, reproduction, and metabolism. In light of the influence each food source has on specific physiological attributes, we comprehensively assessed the impact of these bacteria on animal health and devised a blueprint for utilizing different food combinations over the lifespan, in order to promote longevity. The expansion of the bacterial food options to use in the laboratory will provide a critical tool to better understand the complexities of bacterial diets and subsequent changes in physiology and gene expression.
Molecular basis for the ATPase-powered substrate translocation by the Lon AAA+ protease
Authors: Li Shanshan , Hsieh Kan-Yen , Su Shih-Chieh , Pintilie Grigore D. , Zhang Kaiming , Chang Chung-I 
Published: May 2020

AbstractThe Lon AAA+ (adenosine triphosphatases associated with diverse cellular activities) protease (LonA) converts ATP-fuelled conformational changes into sufficient mechanical force to drive translocation of the substrate into a hexameric proteolytic chamber. To understand the structural basis for the substrate translocation process, we have determined the cryo-electron microscopy (cryo-EM) structure ofMeiothermus taiwanensisLonA (MtaLonA) at 3.6 Å resolution in a substrate-engaged state. Substrate interactions are mediated by the dual pore-loops of the ATPase domains, organized in spiral staircase arrangement from four consecutive protomers in different ATP-binding and hydrolysis states; a closed AAA+ ring is nevertheless maintained by two disengaged ADP-bound protomers transiting between the lowest and highest position. The structure reveals a processive rotary translocation mechanism mediated by LonA-specific nucleotide-dependent allosteric coordination among the ATPase domains, which is induced by substrate binding.
Prediction and characterization of transcription factors involved in drought stress response
Authors: Gupta Chirag , Ramegowda Venkategowda , Basu Supratim , Pereira Andy 
Published: May 2020

AbstractTranscription factors (TFs) play a central role in regulating molecular level responses of plants to external stresses such as water limiting conditions, but identification of such TFs in the genome remains a challenge. Here, we describe a network-based supervised machine learning framework that accurately predicts and ranks all TFs in the genome according to their potential association with drought tolerance. We show that top ranked regulators fall mainly into two ‘age’ groups; genes that appeared first in land plants and genes that emerged later in theOryzaclade. TFs predicted to be high in the ranking belong to specific gene families, have relatively simple intron/exon and protein structures, and functionally converge to regulate primary and secondary metabolism pathways. Repeated trials of nested cross-validation tests showed that models trained only on regulatory network patterns, inferred from large transcriptome datasets, outperform models trained on heterogenous genomic features in the prediction of known drought response regulators. A new R/Shiny based web application, called the DroughtApp, provides a primer for generation of new testable hypotheses related to regulation of drought stress response. Furthermore, to test the system we experimentally validated predictions on the functional role of the rice transcription factorOsbHLH148, using RNA sequencing of knockout mutants in response to drought stress and protein-DNA interaction assays. Our study exemplifies the integration of domain knowledge for prioritization of regulatory genes in biological pathways of well-studied agricultural traits.One Sentence SummaryNetwork-based supervised machine learning accurately predicts transcription factors involved in drought tolerance.
Determinants of Adenine-mutagenesis in Diversity-Generating Retroelements
Authors: Handa Sumit , Reyna Andres , Wiryaman Timothy , Ghosh Partho 
Published: May 2020

ABSTRACTDiversity-generating retroelements (DGRs) vary protein sequences to the greatest extent known in the natural world. These elements are encoded by constituents of the human microbiome and the microbial ‘dark matter’. Variation occurs through adenine-mutagenesis, in which genetic information in RNA is reverse transcribed faithfully to cDNA for all template bases but adenine. We investigated the determinants of adenine-mutagenesis in the prototypicalBordetellabacteriophage DGR through anin vitrosystem composed of the reverse transcriptase bRT, Avd protein, and a specific RNA. We found that the catalytic efficiency for correct incorporation during reverse transcription by the bRT-Avd complex was strikingly low for all template bases, with the lowest occurring for adenine. Misincorporation across a template adenine was only somewhat lower in efficiency than correct incorporation. We found that the C6, but not the N1 or C2, purine substituent was a key determinant of adenine-mutagenesis. bRT-Avd was insensitive to the C6 amine of adenine but recognized the C6 carbonyl of guanine. We also identified two bRT amino acids predicted to nonspecifically contact incoming dNTPs, R74 and I181, as promoters of adenine-mutagenesis. Our results suggest that the overall low catalytic efficiency of bRT-Avd is intimately tied to its ability to carry out adenine-mutagenesis.
Optoacoustic imaging of GLP-1 Receptor with a near-infrared exendin-4 analog
Authors: Roberts Sheryl , Khera Eshita , Choi Crystal , Navaratna Tejas , Grimm Jan , Thurber Greg M. , Reiner Thomas 
Published: May 2020

AbstractLimitations in current imaging tools have long challenged the imaging of small pancreatic islets in animal models. Here, we report the first development and in vivo validation testing of a broad spectrum and high absorbance near infrared optoacoustic contrast agent, E4x12-Cy7. Our near infrared tracer (E4x12-Cy7) is based on the amino acid sequence of exendin-4 and targets the glucagon-like peptide-1 receptor (GLP-1R). Cell assays confirmed that E4x12-Cy7 has a high binding affinity (IC50= 4.6 ± 0.8 nM). Using the multi-spectral optoacoustic tomography (MSOT), we imaged E4x12-Cy7 and optoacoustically visualized ß-cell insulinoma xenograftsin vivofor the first time. In the future, similar optoacoustic tracers that are specific for ß-cells and combines optoacoustic and fluorescence imaging modalities could prove to be important tools for monitoring the pancreas for the progression of diabetes.
Suicidal Thoughts, Behaviors, and Event-Related Potentials: A Systematic Review and Meta-Analysis
Authors: Gallyer Austin J. , Dougherty Sean P. , Burani Kreshnik , Albanese Brian J. , Joiner Thomas E. , Hajcak Greg 
Published: May 2020

AbstractBackgroundSuicidal thoughts and behaviors (STBs) are thought to result from, at least in part, abnormalities in various neural systems. Event-related potentials (ERPs) are a useful method for studying neural activity and can be leveraged to study neural deficits related to STBs; however, it is unknown how effective ERPs are at differentiating various STB groups. The present meta-analysis examined how well ERPs can differentiate (a) those with and without suicidal ideation, (b) those with and without suicide attempts, (c) those with different levels of suicide risk, and (d) differences between those with suicide attempts versus those with suicidal ideation only.MethodThis meta-analysis included 208 effect sizes from 2,517 participants from 27 studies. We used a random-effects meta-analysis using a restricted maximum likelihood estimator with robust variance estimation. We meta-analyzed ERP-STB combinations that had at least three effect sizes across two or more studies.ResultsA qualitative review found that for each ERP and STB combination, the literature is highly mixed. Our meta-analyses largely did not find significant relationships between STBs and ERPs. We also found that the literature is likely severely underpowered, with most studies only being sufficiently powered to detect unrealistically large effect sizes.ConclusionsOur results provided little-to-no support for a reliable relationship between the ERPs assessed and STBs. However, the current literature is severely underpowered, and there are many methodological weaknesses that must be resolved before making this determination. We recommend large-scale collaboration and improvements in measurement practices to combat the issues in this literature.