bluuebunny/crossref_metadata_2025_split huggingface dataset:
Joint phylogenetic estimation of geographic movements and biome shifts during the global diversification ofViburnum
Authors: Landis Michael J. , Eaton Deren A. R. , Clement Wendy L. , Park Brian , Spriggs Elizabeth L. , Sweeney Patrick W. , Edwards Erika J. , Donoghue Michael J. 
Published: October 2019

AbstractPhylogeny, fossils, biogeography, and biome occupancy provide evidence that reflects the singular evolutionary history of a clade. Despite the connections that bind them together, these lines of evidence are most often studied separately, by first inferring a fossil-dated molecular phylogeny, then mapping on ancestral ranges and biomes inferred from extant species. Here we jointly model the evolution of biogeographic ranges, biome affinities, and molecular sequences, incorporating fossils to estimate a dated phylogeny for all of the 163 extant species of the woody plant cladeViburnum(Adoxaceae) that we currently recognize. Our analyses indicate that while the majorViburnumlineages evolved in the Eocene, the majority of extant species originated since the Miocene.Viburnumradiated first in Asia, in warm, broad-leaved evergreen (lucidophyllous) forests. Within Asia we infer several early shifts into more tropical forests, and multiple shifts into forests that experience prolonged freezing. From Asia we infer two early movements into the New World. These two lineages probably first occupied warm temperate forests and adapted later to spreading cold climates. One of these lineages (Porphyrotinus) occupied cloud forests and moved south through the mountains of the Neotropics. Several other movements into North America took place more recently, facilitated by prior adaptations to freezing in the Old World. We also infer four disjunctions between Asia and Europe: theTinuslineage is the oldest and probably occupied warm forests when it spread, while the other three were more recent and in cold-adapted lineages. These results variously contradict published accounts, especially the view thatViburnumradiated initially in cold forests and, accordingly, maintained vessel elements with scalariform perforations. We explored how the location and biome assignments of fossils affected our inference of ancestral areas and biome states. Our results are sensitive to, but not entirely dependent upon, the inclusion of fossil biome data. We argue that it will be critical to take advantage of all available lines of evidence to decipher events in the distant past, and the joint estimation approach developed here provides cautious hope even when fossil evidence is limited.
In vitro Efficacy of Novel Glucan Synthase Inhibitor, Ibrexafungerp (SCY-078), Against Multidrug- and Pan-resistant Candida auris Isolates from the Outbreak in New York
Authors: Zhu Yan Chun , Barat Stephen A. , Borroto-Esoda Katyna , Angulo David , Chaturvedi Sudha , Chaturvedi Vishnu 
Published: October 2019

AbstractWe report low MIC50 of Ibrexafungerp (SCY-078) for 102 Candida auris clinical and surveillance isolates from outbreak in New York. The group included C. auris with a variable resistance to antifungal drugs. Five pan-resistant C. auris isolates were susceptible to Ibrexafungerp with low MIC50 range of 0.12-1 µg/ml.
Lost in Translation: population genomics and long-read sequencing reveals relaxation of concerted evolution of the ribosomal DNA cistron
Authors: Tremble Keaton , Suz Laura M. , Dentinger Bryn T.M. 
Published: October 2019

AbstractConcerted evolution of the ribosomal DNA array has been studied in numerous eukaryotic taxa, yet is still poorly understood. rDNA genes are repeated dozens to hundreds of times in the eukaryotic genome [1] and it is believed that these arrays are homogenized through concerted evolution [2, 3] preventing the accumulation of intragenomic, and intraspecific, variation. However, numerous studies have reported rampant intragenomic and intraspecific variation in the rDNA array [4–10], contradicting our current understanding of concerted evolution. The internal transcribed spacers (ITS) of the rDNA cistron are the most commonly used DNA barcoding region inFungi[11], and rely on concerted evolution to homogenize the rDNA array leading to a “barcode gap” [12]. Here we show that inBoletus edulisBull., ITS intragenomic variation persists at low allele frequencies throughout the rDNA array, this variation does not correlate with genomic relatedness between populations, and rDNA genes may not evolve in a strictly concerted fashion despite the presence of unequal recombination and gene conversion. Under normal assumptions, heterozygous positions found in ITS sequences represent hybridization between populations, yet through allelic mapping of the rDNA array we found numerous heterozygous alleles to be stochastically introgressed throughout, presenting a dishonest signal of gene flow. Moreover, despite the signal of gene flow in ITS, our organisms were highly inbred, indicating a disconnect between true gene flow and barcoding signals. In addition, we show that while the mechanisms of concerted evolution are ongoing in pseudo-heterozygous individuals, they are not fully homogenizing the ITS array. Concerted evolution of the rDNA array may insufficiently homogenize the ITS gene, allowing for misleading signals of gene flow to persist, vastly complicating the use of the ITS locus for DNA barcoding inFungi.
Identifying density-dependent interactions in collective cell behaviour
Authors: Browning Alexander P , Jin Wang , Plank Michael J , Simpson Matthew J 
Published: October 2019

AbstractScratch assays are routinely used to study collective cell behaviour in vitro. Typical experimental protocols do not vary the initial density of cells, and typical mathematical modelling approaches describe cell motility and proliferation based on assumptions of linear diffusion and logistic growth. Jin et al. (2016) find that the behaviour of cells in scratch assays is density-dependent, and show that standard modelling approaches cannot simultaneously describe data initiated across a range of initial densities. To address this limitation, we calibrate an individual based model to scratch assay data across a large range of initial densities. Our model allows proliferation, motility, and a direction bias to depend on interactions between neighbouring cells. By considering a hierarchy of models where we systematically and sequentially remove interactions, we perform model selection analysis to identify the minimum interactions required for the model to simultaneously describe data across all initial densities. The calibrated model is able to match the experimental data across all densities using a single parameter distribution, and captures details about the spatial structure of cells. Our results provide strong evidence to suggest that motility is density-dependent in these experiments. On the other hand, we do not see the effect of crowding on proliferation in these experiments. These results are significant as they are precisely the opposite of the assumptions in standard continuum models, such as the Fisher-Kolmogorov equation and its generalisations.
Heterogeneous synaptic weighting improves neural coding in the presence of common noise
Authors: Sachdeva Pratik S. , Livezey Jesse A. , DeWeese Michael R. 
Published: October 2019

AbstractSimultaneous recordings from the cortex have revealed that neural activity is highly variable, and that some variability is shared across neurons in a population. Further experimental work has demonstrated that the shared component of a neuronal population’s variability is typically comparable to or larger than its private component. Meanwhile, an abundance of theoretical work has assessed the impact shared variability has upon a population code. For example, shared input noise is understood to have a detrimental impact on a neural population’s coding fidelity. However, other contributions to variability, such as common noise, can also play a role in shaping correlated variability. We present a network of linear-nonlinear neurons in which we introduce a common noise input to model, for instance, variability resulting from upstream action potentials that are irrelevant for the task at hand. We show that by applying a heterogeneous set of synaptic weights to the neural inputs carrying the common noise, the network can improve its coding ability as measured by both Fisher information and Shannon mutual information, even in cases where this results in amplification of the common noise. With a broad and heterogeneous distribution of synaptic weights, a population of neurons can remove the harmful effects imposed by afferents that are uninformative about a stimulus. We demonstrate that some nonlinear networks benefit from weight diversification up to a certain population size, above which the drawbacks from amplified noise dominate over the benefits of diversification. We further characterize these benefits in terms of the relative strength of shared and private variability sources. Finally, we studied the asymptotic behavior of the mutual information and Fisher information analytically in our various networks as a function of population size. We find some surprising qualitative changes in the asymptotic behavior as we make seemingly minor changes in the synaptic weight distributions.
Dynamic encoding of social threat and spatial context in the hypothalamus
Authors: Krzywkowski Piotr , Penna Beatrice , Gross Cornelius T. 
Published: October 2019

AbstractTerritorial animals must be able to express social aggression or avoidance in a manner appropriate to spatial context and dominance status. Recent studies indicate that the ventromedial hypothalamus controls both innate aggression and avoidance, suggesting that it may encode an internal state of threat common to both behaviors. Here we used single unit in vivo calcium microendoscopy to identify neurons in the mouse ventromedial hypothalamus encoding social threat. Threat neurons were activated during social defeat as well as when the animal performed risk assessment. Unexpectedly, threat neurons were also activate in the chamber where the animal had been previously defeated and a distinct set of neurons emerged that were active in its home chamber, demonstrating the dynamic encoding of spatial context in the hypothalamus. Ensemble analysis of neural activity showed that social defeat induced a change in the encoding of social information and optogenetic activation of ventromedial hypothalamus neurons was able to elicit avoidance after, but not before social defeat, demonstrating a functional reorganization of the pathway by social experience. These findings reveal how instinctive behavior circuits in the hypothalamus dynamically encode spatial and sensory cues to drive adaptive social behaviors.
Directed evolution improves the catalytic efficiency of TEV protease
Authors: Sanchez Mateo I , Ting Alice Y 
Published: October 2019

AbstractTobacco etch virus protease (TEV) is one of the most widely-used proteases in biotechnology because of its exquisite sequence-specificity. A limitation, however, is its slow catalytic rate. We developed a generalizable yeast-based platform for directed evolution of protease catalytic properties. Protease activity is read out via proteolytic release of a membrane-anchored transcription factor, and we temporally regulate access to TEV’s cleavage substrate using a photosensory LOV domain. By gradually decreasing light exposure time, we enriched faster variants of TEV over multiple rounds of selection. Our S153N mutant (uTEV1Δ), when incorporated into the calcium integrator FLARE, improved the signal/background ratio by 27-fold, and enabled recording of neuronal activity in culture with 60-second temporal resolution. Given the widespread use of TEV in biotechnology, both our evolved TEV mutants and the directed evolution platform used to generate them, could be beneficial across a wide range of applications.
The genetic architecture of human brainstem structures and their involvement in common brain disorders
Authors: Elvsåshagen Torbjørn , Bahrami Shahram , van der Meer Dennis , Agartz Ingrid , Alnæs Dag , Barch Deanna M. , Baur-Streubel Ramona , Bertolino Alessandro , Beyer Mona K. , Blasi Giuseppe , Borgwardt Stefan , Boye Birgitte , Buitelaar Jan , Bøen Erlend , Celius Elisabeth Gulowsen , Cervenka Simon , Conzelmann Annette , Coynel David , Carlo Pasquale Di , Djurovic Srdjan , Eisenacher Sarah , Espeseth Thomas , Fatouros-Bergman Helena , Flyckt Lena , Franke Barbara , Frei Oleksandr , Gelao Barbara , Harbo Hanne Flinstad , Hartman Catharina A. , Håberg Asta , Heslenfeld Dirk , Hoekstra Pieter , Høgestøl Einar A. , Jonassen Rune , Jönsson Erik G. ,   Karolinska Schizophrenia Project (KaSP) consortium, Kirsch Peter , Kłoszewska Iwona , Lagerberg Trine Vik , Landrø Nils Inge , Hellard Stephanie Le , Lesch Klaus-Peter , Maglanoc Luigi A. , Malt Ulrik F. , Mecocci Patrizia , Melle Ingrid , Meyer-Lindenberg Andreas , Moberget Torgeir , Nordvik Jan Egil , Nyberg Lars , O’Connell Kevin S. , Oosterlaan Jaap , Papalino Marco , Papassotiropoulos Andreas , Pauli Paul , Pergola Giulio , Persson Karin , de Quervain Dominique , Reif Andreas , Rokicki Jarek , van Rooij Daan , Shadrin Alexey A. , Schmidt André , Schwarz Emanuel , Selbæk Geir , Soininen Hilkka , Sowa Piotr , Steen Vidar M. , Tsolaki Magda , Vellas Bruno , Wang Lei , Westman Eric , Ziegler Georg , Zink Mathias , Andreassen Ole A. , Westlye Lars T. , Kaufmann Tobias 
Published: October 2019

ABSTRACTBrainstem regions support critical bodily functions, yet their genetic architectures and involvement in brain disorders remain understudied. Here, we examined volumes of brainstem structures using magnetic resonance imaging in 43,353 individuals. In 27,034 genotyped healthy participants, we identified 16 genetic loci associated with whole brainstem volume and 10, 23, 3, and 9 loci associated with volumes of the midbrain, pons, superior cerebellar peduncle, and medulla oblongata, respectively. These loci were mapped to 305 genes, including genes linked to brainstem development and common brain disorders. We detected genetic overlap between the brainstem volumes and eight psychiatric and neurological disorders. Using imaging data from 16,319 additional individuals, we observed differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease. Together, our results provide new insights into the genetic underpinnings of brainstem structures and support their involvement in common brain disorders.
Genome Report: De novo assembly of a high-quality reference genome for the Horned Lark (Eremophila alpestris)
Authors: Mason Nicholas A. , Pulgarin Paulo , Cadena Carlos Daniel , Lovette Irby J. 
Published: October 2019

AbstractThe Horned Lark (Eremophila alpestris) is a species of small songbird that exhibits remarkable geographic variation in appearance and habitat across an expansive distribution. While E. alpestris and related species have been the focus of many ecological and evolutionary studies, we still lack a highly contiguous genome assembly for horned larks and related taxa (Alaudidae). Here, we present CLO_EAlp_1.0, a highly contiguous assembly for horned larks generated from blood samples of a wild, male bird captured in the Altiplano Cundiboyacense of Colombia. By combining short-insert and mate-pair libraries with the ALLPATHS-LG genome assembly pipeline, we generated a 1.04 Gb assembly comprised of 2708 contigs with an N50 of 10.58 Mb and a L50 of 29. After polishing the genome, we were able to identify 94.5% of single-copy gene orthologs from an Aves data set and 97.7% of single-copy gene orthologs from a vertebrata data set, indicating that our de novo assembly is near complete. We anticipate that this genomic resource will be useful to the broader ornithological community and those interested in studying the evolutionary history and ecological interactions of a widespread, yet understudied lineage of songbirds.
Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data
Authors: Ianevski Aleksandr , Giri Anil K , Aittokallio Tero 
Published: October 2019

AbstractSingle-cell transcriptomics enables systematic charting of cellular composition of complex tissues. Identification of cell populations often relies on unsupervised clustering of cells based on the similarity of their scRNA-seq profiles, followed by manual annotation of cell clusters using established marker genes. However, manual selection of marker genes is a time-consuming process that may lead to sub-optimal annotation results as the selected markers must be informative of both the individual cell clusters and various cell types present in the complex samples. Here, we developed a computational platform, termed ScType, which enables data-driven, fully-automated and ultra-fast cell-type identification based solely on given scRNA-seq data, combined with our comprehensive cell marker database as background information. Using a compendium of six scRNA-seq datasets from various human and mouse tissues, we show how ScType provides an unbiased and accurate cell-type annotation by guaranteeing the specificity of positive and negative marker genes both across cell clusters and cell types. We also demonstrate how ScType enables distinguishing between healthy and malignant cell populations, based on single-cell calling of single-nucleotide variants, making it a versatile tool for exploration and use of single-cell transcriptomic data for anticancer applications. The widely-applicable method is deployed both as an interactive web-tool (https://sctype.app), and as an open-source R-package, connected with a comprehensive ScType database of specific markers.
Lineage-Specific Epigenomic and Genomic Activation of the Oncogene HNF4A Promotes Gastrointestinal Adenocarcinomas
Authors: Pan Jian , Silva Tiago C. , Gull Nicole , Yang Qian , Plummer Jasmine , Chen Stephanie , Daigo Kenji , Hamakubo Takao , Gery Sigal , Ding Ling-Wen , Jiang Yan-Yi , Hu Shao-Yan , Xu Li-Yan , Li En-Min , Ding Yanbing , Klempner Samuel J. , Berman Benjamin P. , Phillip Koeffler H. , Lin De-Chen 
Published: October 2019

AbstractBackgroundsGastrointestinal adenocarcinomas (GIACs) of the tubular GI tract including esophagus, stomach, colon and rectum comprise most GI cancers and share a spectrum of genomic features. However, the unified epigenomic changes specific to GIACs are less well-characterized.We applied mathematical algorithms to large-scale DNA methylome and transcriptome profiles to reconstruct transcription factor (TF) networks using 907 GIAC samples from The Cancer Genome Atlas (TCGA). Complementary epigenomic technologies were performed to investigate HNF4A activation, including Circularized Chromosome Conformation Capture (4C), Chromatin immunoprecipitation (ChIP) sequencing, Whole Genome Bisulfite Sequencing (WGBS), and Assay for Transposase-Accessible Chromatin (ATAC) sequencing. In vitro and in vivo cellular phenotypical assays were conducted to study HNF4A functions.ResultsWe identified a list of functionally hyperactive master regulator (MR)TFs shared across different GIACs. As the top candidate, HNF4A exhibited prominent genomic and epigenomic activation in a GIAC-specific manner. We further characterized a complex interplay between HNF4A promoter and three distal enhancer elements, which was coordinated by GIAC-specific MRTFs including ELF3, GATA4, GATA6 and KLF5. HNF4A also self-regulated its own promoter and enhancers. Functionally, HNF4A promoted cancer proliferation and survival by transcriptionally activating many downstream targets including HNF1A and factors of Interleukin signaling in a lineage-specific manner.ConclusionWe use a large cohort of patient samples and an unbiased mathematical approach to highlight lineage-specific oncogenic MRTFs, which provide new insights into the GIAC-specific gene regulatory networks, and identify potential therapeutic strategies against these common cancers.
Juvenile rank acquisition influences fitness independent of adult rank
Authors: Strauss Eli D , Shizuka Daizaburo , Holekamp Kay E 
Published: October 2019

AbstractSocial rank has been identified as a significant determinant of fitness in a variety of species. The importance of social rank suggests that the process by which juveniles come to establish their position in the social hierarchy is a critical component of social development. Here, we use the highly predictable process of rank acquisition in spotted hyenas to study the consequences of variation in rank acquisition in early life. In spotted hyenas, rank is ‘inherited’ through a learning process called ‘maternal rank inheritance.’ This pattern is highly predictable: ~80% of juveniles acquire the exact rank predicted by the rules of maternal rank inheritance. This predictable nature of rank acquisition in these societies allows the process of rank acquisition to be studied independently from the ultimate rank that each juvenile attains. In this study, we use a novel application of the Elo-rating method to calculate each juvenile’s deviation from expected pattern of maternal rank inheritance during development. Despite variability in rank acquisition in juveniles, most of these juveniles come to attain the exact rank expected of them according to the rules of maternal rank inheritance. Nevertheless, we find that transient variation in rank acquisition in early life predicts long term fitness consequences for these individuals: juveniles ‘underperforming’ their expected ranks show reduced survival and lower lifetime reproductive success than better-performing peers. Finally, we present evidence that this variability in rank acquisition in early life represents a source of early life adversity, and that multiple sources of early life adversity have cumulative, but not compounding, effects on fitness.
Mechanotransduction activity facilitates hair cell toxicity caused by the heavy metal cadmium
Authors: Schmid Caleigh , Alampi Isabella , Briggs Jay , Tarcza Kelly , Stawicki Tamara M 
Published: October 2019

AbstractHair cells are sensitive to many insults including environmental toxins such as heavy metals. We show here that cadmium can consistently kill hair cells of the zebrafish lateral line. Disrupting hair cell mechanotransduction genetically or pharmacologically significantly reduces the amount of hair cell death seen in response to cadmium, suggesting a role for mechanotransduction in this cell death process, possibly as a means for cadmium uptake into the cells. Likewise, when looking at multiple cilia-associated gene mutants that have previously been shown to be resistant to aminoglycoside-induced hair cell death, resistance to cadmium-induced hair cell death is only seen in those with mechanotransduction defects. In contrast to what was seen with mechanotransduction, significant protection was not consistently seen from other ions previously shown to compete for cadmium uptake into cells or tissue including zinc and copper. These results show that functional mechanotransduction activity is playing a significant role in cadmium-induced hair cell death.