bluuebunny/crossref_metadata_2025_split huggingface dataset:
For running or burying—The toe fringe ofPhrynocephalus mystaceusis important
Authors: Zheng Peng , Liang Tao , An Jing , Shi Lei 
Published: December 2019

AbstractToe fringe is the most typical morphological feature of lizards adapted to sandy environments, and toe fringe is suitable for testing the adaptive convergence suggested by form-environment correlations.Phrynocephalus mystaceusmainly lives in dune habitats, has a developed bilateral toe fringe, and exhibits fast sand-diving behavior for predator avoidance. We tested the effects of resecting the medial and bilateral toe fringes on the locomotor performance and sand-diving performance ofP. mystaceus.The results showed that the individuals that had their medial toe fringe removed exhibited significantly faster sprint speeds than the unresected and all resected individuals (P<0.05). The results of stepwise regression analysis show that the relative area of the toe fringe is an important morphological feature that affects locomotor performance. The sand-burial performance scores of the unresected individuals were significantly greater than those of the resected individuals (P<0.05). The results of stepwise regression analysis show that the relative area of toe fringe and the axilla-groin length are the main morphological features that affect the sand-diving performance ofP. mystaceus. After the bilateral toe fringe was removed, a significant negative correlation between locomotor and sand-diving performance was observed (P<0.05). Taken together, these results provide experimental evidence that toe fringe is positively associated with the locomotor and sand-diving performance ofP. mystaceus.
Antigen-driven PD-1+TOX+EOMES+and PD-1+TOX+BHLHE40+synovial T lymphocytes regulate chronic inflammationin situ
Authors: Maschmeyer Patrick , Anne Heinz Gitta , Skopnik Christopher Mark , Lutter Lisanne , Mazzoni Alessio , Heinrich Frederik , von Stuckrad Sae Lim , Wirth Lorenz Elias , Tran Cam Loan , Riedel René , Lehmann Katrin , Sakwa Imme , Cimaz Rolando , Giudici Francesco , Mall Marcus Alexander , Enghard Philipp , Vastert Bas , Chang Hyun-Dong , Durek Pawel , Annunziato Francesco , van Wijk Femke , Radbruch Andreas , Kallinich Tilmann , Mashreghi Mir-Farzin 
Published: December 2019

Introduction/AbstractT lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulationin vitro1–29. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA)30–33. However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the heterogeneity of synovial T lymphocytes in JIA patients by single cell RNA-sequencing. We identify subpopulations of T lymphocytes expressing genes reflecting recent activation by antigenin situ. A PD-1+TOX+EOMES+population of CD4+T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+TOX+BHLHE40+population of CD4+, and a mirror population of CD8+T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.
Nanopore sequencing of native adeno-associated virus (AAV) single-stranded DNA using a transposase-based rapid protocol
Authors: Radukic Marco T. , Brandt David , Haak Markus , Müller Kristian M. , Kalinowski Jörn 
Published: December 2019

ABSTRACTNext-generation sequencing of single-stranded DNA (ssDNA) enables transgene characterization of gene-therapy vectors such as adeno-associated virus (AAV), but current library generation uses complicated and potentially biased second-strand synthesis. We report that libraries for nanopore sequencing of ssDNA can be conveniently created without second-strand synthesis using a transposase-based protocol. We show for bacteriophage M13 ssDNA that the MuA transposase has unexpected residual activity on ssDNA, explained in part by transposase action on transient double-stranded hairpins. In case of AAV, library creation is additionally aided by genome hybridization. We demonstrate the power of direct sequencing combined with nanopore long reads by characterizing AAV vector transgenes. Sequencing yielded reads up to full genome length, including GC-rich inverted terminal repeats. Unlike short-read techniques, single reads covered genome-genome and genome-contaminant fusions and other recombination events, while additionally providing information on epigenetic methylation. Single-nucleotide variants across the transgene cassette were revealed and secondary genome packaging signals were readily identified. Moreover, comparison of sequence abundance with qPCR results demonstrated the technique’s future potential for quantification of DNA impurities in AAV vector stocks. The findings promote direct nanopore sequencing as a fast and versatile platform for ssDNA characterization, such as AAV ssDNA in research and clinical settings.
DNA methylation across the genome in aged human skeletal muscle tissue and stem cells: The role of HOX genes and physical activity
Authors: Turner DC , Gorski PP , Maasar MF , Seaborne RA , Baumert P , Brown AD , Kitchen MO , Erskine RM , Dos-Remedios I , Voisin S , Eynon N , Sultanov RI , Borisov OV , Larin AK , Semenova EA , Popov DV , Generozov EV , Stewart CE , Drust B , Owens DJ , Ahmetov II , Sharples AP 
Published: December 2019

AbstractSkeletal muscle tissue demonstrates global hypermethylation with aging. However, methylome changes across the time-course of differentiation in aged human muscle derived stem cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged muscle stem cells over several time points of differentiation (0, 72 hours, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; ‘pathways-in-cancer’ (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), ‘rap1-signaling’, ‘axon-guidance’ and ‘hippo-signalling’. Aged muscle stem cells also demonstrated a hypermethylated profile in pathways; ‘axon-guidance’, ‘adherens-junction’ and ‘calcium-signaling’, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alteration in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in the ‘focal adhesion’ and ‘PI3K-AKT signalling’ pathways. While the methylomes were vastly different between muscle tissue and isolated muscle stem cells, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle and tissue and stem cells (on genesKIF15, DYRK2, FHL2, MRPS33, ABCA17P). Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. WithHOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2andHOXC10all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionallyHOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, withHOXD8, HOXC9, HOXB1andHOXC-AS3hypermethylated andHOXC10andHOXC-AS2hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression forHOXB1, HOXA3andHOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulatingHOXB1andHOXA3methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and muscle stem cells and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.
Evidence for novel transient cell clusters in the neonatal mouse retina
Authors: de Montigny Jean , Krishnamoorthy Vidhyasankar , Rozenblit Fernando , Gollisch Tim , Sernagor Evelyne 
Published: December 2019

AbstractWaves of spontaneous activity sweep across the neonatal mouse retinal ganglion cell (RGC) layer, driven by directly interconnected cholinergic starburst amacrine cells from postnatal day (P) 0-10, followed by waves driven by glutamatergic bipolar cells. We found transient clusters of auto-fluorescent cells in the RGC layer during the period of cholinergic waves. They appear around the optic nerve head at P2 and become gradually displaced towards the periphery between P2-8 and then they disappear. Pan-retinal multielectrode array recordings reveal that cholinergic wave origins follow a similar, non-random developmental center-to-periphery pattern. Electrical imaging unmasks hotspots of dipole electrical activity occurring in the vicinity of wave origins. We propose that these activity hotspots are the sites for wave initiation and may originate from the transient cell clusters, reminiscent of activity in transient subplate neurons in the developing cortex, suggesting a universal hyper-excitability mechanism in developing CNS networks during the critical period for brain wiring.
Cerebellum-specific deletion of the GABAAreceptor δ subunit alters anxiety-like, social and maternal behaviors without affecting motor performance
Authors: Rudolph Stephanie , Guo Chong , Pashkovski Stan , Osorno Tomas , Gillis Winthrop , Krauss Jeremy , Nyitrai Hajnalka , Flaquer Isabella , El-Rifai Mahmoud , Datta Robert Sandeep , Regehr Wade 
Published: December 2019

AbstractGABAAreceptors containing the δGABAAsubunit (δGABAARs) are involved in many physiological and pathophysiological processes, such as sleep, pain, stress, anxiety-related behaviors, and postpartum depression. These extrasynaptically located, high affinity and slowly desensitizing receptors mediate tonic inhibition throughout the brain, including in granule cells (GCs) of the cerebellar input layer. However, the extent to which δGABAARs control the excitability of the cerebellar input layer and ultimately regulate behavior is unknown. We therefore deleted δGABAAsubunits specifically from GCs and determined the behavioral consequences in mice. Deletion reduced tonic inhibition and increased input layer excitability, but remarkably, did not affect either locomotion or motor learning. Unexpectedly, δGABAAdeletion heightened anxiety-like behaviors, and caused female-specific alterations in social and maternal behavior. Our findings establish that the cerebellar input layer is critical for regulating diverse behaviors that are relevant to psychiatric and neurodevelopmental disorders but were previously not associated with the cerebellum.
Trehalose Stabilizing Protein in a Water Replacement Scenario: Insights from Molecular Dynamics Simulation
Authors: Shao Qiang , Wang Jinan , Zhu Weiliang 
Published: December 2019

AbstractHow trehalose has exceptional property in helping biomolecules preserve their native structures remains a subject of active research. Running molecular dynamics simulations on a model protein in low-concentrated trehalose solution and pure water, respectively, the present study verifies the ability of trehalose in stabilizing protein native structure and provides a comprehensive atomic-level picture of the molecular interactions among protein, trehalose, and water in their mixed solution. Trehalose directly interacts to and meanwhile affects the interactions between the other speciesviahydrogen bonding: 1) trehalose molecules are clustered through inter-molecular hydrogen bonding interaction; 2) trehalose forms hydrogen bond with water which influences the strength of water-water hydrogen bonding network but does not impair protein-water hydrogen bonding; 3) trehalose is accessible to form hydrogen bonds towards protein and simultaneously replace water molecules around protein which reduces the hydrogen bonding possibility from water to protein, in accordance with “water replacement” scenario.
Principles for rational Cas13d guide design
Authors: Wessels Hans-Hermann , Méndez-Mancilla Alejandro , Guo Xinyi , Legut Mateusz , Daniloski Zharko , Sanjana Neville E. 
Published: December 2019

AbstractType VI CRISPR enzymes have recently been identified as programmable RNA-guided, RNA-targeting Cas proteins with nuclease activity that allow for specific and robust target gene knock-down without altering the genome. However, we currently lack information about optimal Cas13 guide RNA designs for high target RNA knock-down efficacy. To close this gap, we conducted four massively-parallel Cas13 screens targeting the mRNA of a destabilized green fluorescent protein (GFP) transgene and CD46, CD55 and CD71 cell surface proteins in human cells. In total, we measured the activity of 24,460 guide RNA including 6,469 perfect match guide RNAs and a diverse set of guide RNA variants and permutations with mismatches relative to the target sequences.We find that guide RNAs show high diversity in knock-down efficiency driven by crRNA-specific features as well as target site context. Moreover, while single mismatches generally reduce knock-down to a modest degree, we identify a critical region spanning spacer nucleotides 15 – 21 that is largely intolerant to target site mismatches. We developed a computational model to identify guide RNAs with high knock-down efficacy. We confirmed the model’s generalizability across a large number of endogenous target mRNAs and show that Cas13 can be used in forward genetic pooled CRISPR-screens to identify essential genes. Using this model, we provide a resource of optimized Cas13 guide RNAs to target all protein-coding transcripts in the human genome, enabling transcriptome-wide forward genetic screens.
microRNA profiling of mouse cortical progenitors and neurons reveals miR-486-5p as a novel regulator of neurogenesis
Authors: Dori Martina , Cavalli Daniel , Lesche Mathias , Massalini Simone , Haj Abdullah Alieh Leila , Cardoso de Toledo Beatriz , Khudayberdiev Sharof , Schratt Gerhard , Dahl Andreas , Calegari Federico 
Published: December 2019

ABSTRACTMicroRNAs (miRNAs) are short (∼22 nt) single-stranded non-coding RNAs that regulate gene expression at the post-transcriptional level. Over the past years, many studies have extensively characterized the involvement of miRNA-mediated regulation in neurogenesis and brain development. However, a comprehensive catalog of cortical miRNAs cell-specifically expressed in progenitor types of the developing mammalian cortex is still missing. Overcoming this limitation, here we exploited a double reporter mouse line previously validated by our group to allow the identification of the transcriptional signature to neurogenic commitment and provide the field with the complete atlas of miRNAs expression in proliferating neural stem cells, neurogenic progenitors and newborn neurons during corticogenesis. By extending the currently known list of miRNAs expressed in the mouse brain by over two fold, our study highlights the power of cell type-specific analyses for the detection of transcripts that would otherwise be diluted out when studying bulk tissues. We further exploited our data by predicting putative novel miRNAs and validated the power of our approach by providing novel evidence for the involvement of miR-486 as a novel player in brain development.
Time-ResNeXt for epilepsy recognition based on EEG signals
Authors: Wang shaoqiang , Wang Yifan , Wang Shudong 
Published: December 2019

AbstractObjectiveTo automatically detect dynamic EEG signals to reduce the time cost of epilepsy diagnosis. In the signal recognition of electroencephalogram (EEG) of epilepsy, traditional machine learning and statistical methods require manual feature labeling engineering in order to show excellent results on a single data set. And the artificially selected features may carry a bias, and cannot guarantee the validity and expansibility in real-world data. In practical applications, deep learning methods can release people from feature engineering to a certain extent. As long as the focus is on the expansion of data quality and quantity, the algorithm model can learn automatically to get better improvements. In addition, the deep learning method can also extract many features that are difficult for humans to perceive, thereby making the algorithm more robust.MethodBased on the design idea of ResNeXt deep neural network, this paper designs a Time-ResNeXt network structure suitable for time series EEG epilepsy detection to identify EEG signals.ResultsThe accuracy rate of Time-ResNeXt in the detection of EEG epilepsy can reach 90.50%.ConclusionThe Time-ResNeXt network structure produces extremely advanced performance on the benchmark dataset (Berne-Barcelona dataset), and has great potential for improving clinical practice.
Tackling misinformation in agriculture
Authors: Stroud Jacqueline L. 
Published: December 2019

AbstractFarmers are encouraged to embrace digital media to fill the voids caused by the privatisation of Agricultural Knowledge and Information Systems. Widespread sustainable agriculture misinformation undermines the role of science, participatory research, and evidence-based decision making. Simply providing information is insufficient, misinformation is tackled by creating a network that fosters accurate information exchange. Here I used Twitter and blended learning technologies to create a research partnership with farmers based on their beliefs that earthworms indicate good soils management. Through co-design, farmers transformed this symbol into a systematic field observation network, assessing earthworm populations to the ecological group level. Our community (#WorldWormWeek) revealed the falsehoods in misinformation such as: “Farmers around the world have been turning their fields into subterranean deserts”. This social learning network was resilient to further misinformation by the national press. Real data trends were fundamentally different to predictions made by science advancing models of global earthworm populations. Anecic earthworms (including middens) were absent in 1 in 5 fields, directly informing management practices to avoid soil biological pitfalls in no-tillage adoption. Simplistic earthworm counts to indicate soil health are rendered obsolete, a depth of information exchange can be achieved by building science-farmer partnerships using digital communications and co-designed frameworks. However, the scientific consensus, whilst generally positive about the research impact, revealed 42 % scientists rated this research as “not at all useful” or “slightly useful” to scientists. This reveals the hopeless situation where the co-production of knowledge and feedback loop linking farming-science is not broadly considered ‘science advancing’, and brought #Wormscience to an end. The next step would have been to optimizeLumbricus terrestrisbiocontrol actions targeting the soil-borne crop pathogenFusariumspp. and detoxification of its mycotoxins, to reduce fungicide dependency in staple crop production; aligned with societal sustainable agriculture aspirations.
Distance preserving dimension reduction with local-topology based scaling for improved classification of Biomedical data-sets
Authors: Khosla Karaj , Jha Indra Prakash , Kumar Vibhor 
Published: December 2019

AbstractDimension reduction is often used for several procedures of analysis of high dimensional biomedical data-sets such as classification or outlier detection. To improve performance of such data-mining steps, preserving both distance information and local topology among data-points could be more useful than giving priority to visualisation in low dimension. Therefore, we introduce topology preserving distance scaling (TPDS) to augment dimension reduction method meant to reproduce distance information in higher dimension. Our approach involves distance inflation to preserve local topology to avoid collapse during distance preservation based optimisation. Applying TPDS on diverse biomedical data-sets revealed that besides providing better visualisation than typical distance preserving methods, TPDS leads to better classification of data points in reduced dimension. For data-sets with outliers, the approach of TPDS also proves to be useful, even for purely distance-preserving method for achieving better convergence.
Validation of a Mathematical Model of Cancer Incorporating Spontaneous and Induced Evolution to Drug Resistance
Authors: Gevertz Jana L. , Greene James M. , Sontag Eduardo D. 
Published: December 2019

AbstractThis paper continues the study of a model which was introduced in earlier work by the authors to study spontaneous and induced evolution to drug resistance under chemotherapy. The model is fit to existing experimental data, and is then validated on additional data that had not been used when fitting. In addition, an optimal control problem is studied numerically.
Stimulus dependent relationships between behavioral choice and sensory neural responses
Authors: Chicharro Daniel , Panzeri Stefano , Haefner Ralf M. 
Published: December 2019

AbstractUnderstanding the relationship between trial-to-trial variability in neural responses of sensory areas and behavioral choices is fundamental to elucidate the mechanisms of perceptual decision-making. In two-choice tasks, activity-choice co-variations have traditionally been quantified with choice probabilities (CP). It has been so far commonly assumed that choice-related neural signals are separable from stimulus-driven responses, which has led to characterizing activity-choice covariations only with a single CP value estimated combining trials from all stimulus levels. In this work we provide theoretical and experimental evidence for the stimulus dependence of the relationship between neural responses and behavioral choices. We derived a general analytical CP expression for this dependency under the general assumption that a decision threshold converts an internal stimulus estimate into a binary choice. This expression predicts a stereotyped threshold-induced CP modulation by the stimulus information content. We reanalyzed data from Britten et al. (1996) and found evidence of this modulation in the responses of macaque MT cells during a random dot discrimination task. Moreover, we developed new methods of analysis that allowed us to further identify a richer structure of cell-specific CP stimulus dependencies. Finally, we capitalised on this progress to develop new generalized linear models (GLMs) with stimulus-choice interaction terms, which show a higher predictive power and lead to a more precise assessment of how much each neuron is stimulus- or choice-driven, hence allowing a more accurate comparison across areas or cell types. Our work suggests that characterizing the patterns of stimulus dependence of choice-related signals is essential to properly determine how neurons in different areas contribute to linking sensory representations to perceptual decisions.