bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of novel Actinobacteriophage Giantsbane reveals unexpected cluster AU relationships
Authors: Chen Pei Ying , Liu Christopher , Dang Preston , Zhang Michael , Kapinos Andrew , Ngo Ryan , Reddi Krisanavane , Parker Jordan Moberg , Freise Amanda C. 
Published: January 2020

ABSTRACTBacteriophages that infectArthrobacter, a genus of bacteria which play key ecological roles in soil, warrant further study. Giantsbane, a novel Actinobacteriophage, was isolated usingArthrobacter globiformisas a host. Transmission electron microscopy and whole-genome sequencing revealed aSiphoviridaemorphology and a genome length of 56,734 bp. Genome annotation identified 94 putative genes, such as a duplicated major tail protein and a major capsid and protease fusion protein. No genes were associated with lysogeny, indicating a lytic phage. Giantsbane was assigned to the phage cluster AU. Batch average nucleotide identity analysis and phylogenetic networks constructed from shared genes revealed unexpected nucleotide and gene content similarities within cluster AU. These findings have resulted in the creation of two new AU subclusters and the resubclustering of three AU bacteriophages. Analysis using Phamerator and MEME identified repeated motifs and a gene cassette present in all evaluated cluster AU phages which may promote recombination. These findings offer the first intra-cluster analysis of cluster AU phages and further our understanding of the relationships between closely related bacteriophages.
Geometric Analysis of Regime Shifts in Coral Reef Communities
Authors: Tekwa Edward W. , McManus Lisa C. , Greiner Ariel , Colton Madhavi A. , Webster Michael S. , Pinsky Malin L. 
Published: January 2020

AbstractCoral reefs are among the many communities believed to exhibit regime shifts between alternative stable states, single-species dominance, and coexistence. Proposed drivers of regime shifts include changes in grazing, spatial clustering, and ocean temperature. Here we distill the dynamic regimes of coral-macroalgal interaction into a three-dimensional geometry, akin to thermodynamic phase diagrams of state transitions, to facilitate analysis. Specific regime-shifting forces can be understood as bifurcation vectors through the cubic regime geometry. This geometric perspective allows us to understand multiple forces simultaneously in terms of the stability and persistence of interacting species. For example, in a coral-macroalgae community, grazing on macroalgae can lead to alternative stable states when there is no spatial clustering (e.g., high habitat connectivity). However, with spatial clustering, grazing can lead to coexistence because of elevated local intraspecific competition. The geometrical analysis of regime shifts is applicable to any two-species communities and can help conservation efforts navigate complexity and abrupt changes.
Presynaptic PTPσ organizes neurotransmitter release machinery at excitatory synapses
Authors: Han Kyung Ah , Lee Hee-Yoon , Lim Dongseok , Shin Jungsu , Yoon Taek Han , Lee Chooungku , Rhee Jeong-Seop , Liu Xinran , Um Ji Won , Choi Se-Young , Ko Jaewon 
Published: January 2020

AbstractLeukocyte common antigen-related receptor tyrosine phosphatases (LAR-RPTPs) are evolutionarily conserved presynaptic organizers. The synaptic role of vertebrate LAR-RPTPsin vivo, however, remains unclear. This study systematically analyzed the effects of genetic deletions of LAR-RPTP genes by generating single conditional knockout (cKO) mice targeting PTPσ and PTPδ. Although the numbers of synapses were reduced in cultured neurons deficient in individual PTPs, abnormalities in synaptic transmission, synaptic ultrastructures, and vesicle localization were observed only in PTPσ-deficient neurons. Strikingly, loss of presynaptic PTPσ reduced neurotransmitter release prominently at excitatory synapses, concomitant with drastic reductions in excitatory innervations onto postsynaptic target areasin vivo. However, postsynaptic PTPσ deletion had no effect on excitatory synaptic strength. Furthermore, conditional deletion of PTPσ in ventral CA1 specifically altered anxiety-like behaviors. Taken together, these results demonstrate that PTPσ is abona fidepresynaptic adhesion molecule that controls neurotransmitter release and excitatory inputs.
Mitogen-activated protein kinase activity drives cell trajectories in colorectal cancer
Authors: Uhlitz Florian , Bischoff Philip , Peidli Stefan , Sieber Anja , Obermayer Benedikt , Blanc Eric , Trinks Alexandra , Lüthen Mareen , Ruchiy Yana , Sell Thomas , Mamlouk Soulafa , Arsie Roberto , Wei Tzu-Ting , Klotz-Noack Kathleen , Schwarz Roland F , Sawitzki Birgit , Kamphues Carsten , Beule Dieter , Landthaler Markus , Sers Christine , Horst David , Blüthgen Nils , Morkel Markus 
Published: January 2020

AbstractIn colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define colorectal cancer cell types and signals controlling their development. More than 30,000 epithelial single cell transcriptomes of tumors and matched non-cancerous tissues of twelve colorectal cancer patients were clustered into six patient-overarching groups defined by differential activities of oncogenic signaling pathways such as mitogen-activated protein kinase and oncogenic traits such as replication stress. RNA metabolic labeling and assessment of RNA velocity in patient-derived organoids revealed developmental trajectories of colorectal cancer cells organized along a mitogen-activated protein kinase activity gradient. This was in contrast to normal colon organoid cells developing along graded Wnt activity. Experimental targeting of EGFR-BRAF-MEK in cancer organoids affected signaling and gene expression contingent on predictive KRAS/BRAF mutations and induced cell plasticity overriding default developmental trajectories, providing a basis for non-genetic resistance to targeted therapies.
ideal: an R/Bioconductor package for Interactive Differential Expression Analysis
Authors: Marini Federico , Linke Jan , Binder Harald 
Published: January 2020

AbstractBackgroundRNA sequencing (RNA-seq) is an ever increasingly popular tool for transcriptome profiling. A key point to make the best use of the available data is to provide software tools that are easy to use but still provide flexibility and transparency in the adopted methods. Despite the availability of many packages focused on detecting differential expression, a method to streamline this type of bioinformatics analysis in a comprehensive, accessible, and reproducible way is lacking.ResultsWe developed theidealsoftware package, which serves as a web application for interactive and reproducible RNA-seq analysis, while producing a wealth of visualizations to facilitate data interpretation. ideal is implemented in R using the Shiny framework, and is fully integrated with the existing core structures of the Bioconductor project. Users can perform the essential steps of the differential expression analysis work-flow in an assisted way, and generate a broad spectrum of publication-ready outputs, including diagnostic and summary visualizations in each module, all the way down to functional analysis. ideal also offers the possibility to seamlessly generate a full HTML report for storing and sharing results together with code for reproducibility.Conclusionideal is distributed as an R package in the Bioconductor project (http://bioconductor.org/packages/ideal/), and provides a solution for performing interactive and reproducible analyses of summarized RNA-seq expression data, empowering researchers with many different profiles (life scientists, clinicians, but also experienced bioinformaticians) to make theidealuse of the data at hand.
A Learning-Based Formulation of Parametric Curve Fitting for Bioimage Analysis
Authors: Mandal Soham , Uhlmann Virginie 
Published: January 2020

AbstractParametric curve models are convenient to describe and quantitatively characterize the contour of objects in bioimages. Unfortunately, designing algorithms to fit smoothly such models onto image data classically requires significant domain expertise. Here, we propose a convolutional neural network-based approach to predict a continuous parametric representation of the outline of biological objects. We successfully apply our method on the Kaggle 2018 Data Science Bowl dataset composed of a varied collection of images of cell nuclei. This work is a first step towards user-friendly bioimage analysis tools that extract continuously-defined representations of objects.
Concepts and Software Package for Efficient Quality Control in Targeted Metabolomics Studies – MeTaQuaC
Authors: Kuhring Mathias , Eisenberger Alina , Schmidt Vanessa , Kränkel Nicolle , Leistner David M. , Kirwan Jennifer , Beule Dieter 
Published: January 2020

ABSTRACTTargeted quantitative mass spectrometry metabolite profiling is the workhorse of metabolomics research. Robust and reproducible data is essential for confidence in analytical results and is particularly important with large-scale studies. Commercial kits are now available which use carefully calibrated and validated internal and external standards to provide such reliability. However, they are still subject to processing and technical errors in their use and should be subject to a laboratory’s routine quality assurance and quality control measures to maintain confidence in the results. We discuss important systematic and random measurement errors when using these kits and suggest measures to detect and quantify them. We demonstrate how wider analysis of the entire dataset, alongside standard analyses of quality control samples can be used to identify outliers and quantify systematic trends in order to improve downstream analysis. Finally we present the MeTaQuaC software which implements the above concepts and methods for Biocrates kits and creates a comprehensive quality control report containing rich visualization and informative scores and summary statistics. Preliminary unsupervised multivariate analysis methods are also included to provide rapid insight into study variables and groups. MeTaQuaC is provided as an open source R package under a permissive MIT license and includes detailed user documentation.
TALC: Transcript-level Aware Long Read Correction
Authors: Broseus Lucile , Thomas Aubin , Oldfield Andrew J. , Severac Dany , Dubois Emeric , Ritchie William 
Published: January 2020

ABSTRACTMotivationLong-read sequencing technologies are invaluable for determining complex RNA transcript architectures but are error-prone. Numerous “hybrid correction” algorithms have been developed for genomic data that correct long reads by exploiting the accuracy and depth of short reads sequenced from the same sample. These algorithms are not suited for correcting more complex transcriptome sequencing data.ResultsWe have created a novel reference-free algorithm called TALC (Transcription Aware Long Read Correction) which models changes in RNA expression and isoform representation in a weighted De-Bruijn graph to correct long reads from transcriptome studies. We show that transcription aware correction by TALC improves the accuracy of the whole spectrum of downstream RNA-seq applications and is thus necessary for transcriptome analyses that use long read technology.Availability and ImplementationTALC is implemented in C++ and available athttps://gitlab.igh.cnrs.fr/lbroseus/TALC.Contactwilliam.ritchie@igh.cnrs.fr
The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats
Authors: Makhijani Viren H. , Franklin Janay P. , Voorhies Kalynn Van , Fortino Brayden , Besheer Joyce 
Published: January 2020

AbstractPost-traumatic stress disorder (PTSD) is a psychiatric illness that can increase the risk for developing an alcohol use disorder (AUD). While clinical data has been useful in identifying similarities in the neurobiological bases of these disorders, preclinical models are essential for understanding the mechanism(s) by which PTSD increases the risk of developing AUD. The purpose of these studies was to examine if exposure of male Long-Evans rats to the synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) would increase alcohol self-administration, potentially by facilitating transfer of salience towards cues, and alter neuronal response to alcohol as measured by the immediate early gene c-Fos. In Experiment 1 rats exposed to repeated (4x) TMT showed reductions in goal-tracking behavior in Pavlovian conditioned approach, and increases in alcohol self-administration. In Experiment 2 rats exposed to repeated TMT showed blunted basolateral amygdala c-Fos response to alcohol, and increased correlation between medial prefrontal cortex and amygdala subregions. In Experiment 3 rats exposed to single, but not repeated TMT showed increases in alcohol self-administration, and no change in anxiety-like behavior or hyperarousal. In Experiment 4, rats showed no habituation of corticosterone response after 4 TMT exposures. In summary, exposure of male rats to TMT can cause escalations in alcohol self-administration, reductions in goal-tracking behavior, and reduction in BLA response to alcohol. These studies outline and utilize a novel preclinical model that can be used to further neurobiological understanding of the relationship between PTSD and AUD.
Development of Systemic Immune Dysregulation in a Rat Trauma Model with Biomaterial-Associated Infection
Authors: Vantucci Casey E. , Ahn Hyunhee , Schenker Mara L. , Pradhan Pallab , Wood Levi B. , Guldberg Robert E. , Roy Krishnendu , Willett Nick J. 
Published: January 2020

ABSTRACTOrthopedic biomaterial-associated infections remain a large clinical challenge, particularly with open fractures and segmental bone loss. Invasion and colonization of bacteria within immune-privileged canalicular networks of the bone can lead to local, indolent infections that can persist for years without symptoms before eventual catastrophic hardware failure. Host immunity is essential for bacterial clearance and an appropriate healing response, and recent evidence has suggested an association between orthopedic trauma and systemic immune dysregulation and immunosuppression. However, the impact of a local infection on this systemic immune response and subsequent effects on the local response is poorly understood and has not been a major focus for addressing orthopedic injuries and infections. Therefore, this study utilized a model of orthopedic biomaterial-associated infection to investigate the effects of infection on the long-term immune response. Here, despite persistence of a local, indolent infection lacking outward symptoms, there was still evidence of long-term immune dysregulation with systemic increases in MDSCs and decreases in T cells compared to non-infected trauma. Further, the trauma only group exhibited a regulated and coordinated systemic cytokine response, which was not present in the infected trauma group. Locally, the infection group had attenuated macrophage infiltration in the local soft tissue compared to the non-infected group. Our results demonstrate widespread impacts of a localized orthopedic infection on the systemic and local immune responses. Characterization of the immune response to orthopedic biomaterial-associated infection may identify key targets for immunotherapies that could optimize both regenerative and antibiotic interventions, ultimately improving outcomes for these patients.
The RNA pseudoknots in foot-and-mouth disease virus are dispensable for genome replication but essential for the production of infectious virus
Authors: Ward Joseph C. , Lasecka-Dykes Lidia , Neil Chris , Adeyemi Oluwapelumi , Gold Sarah , McLean Niall , Wright Caroline , Herod Morgan R. , Kealy David , Warner Emma , King Donald P. , Tuthill Tobias J. , Rowlands David J. , Stonehouse Nicola J. 
Published: January 2020

AbstractThe positive stranded RNA genomes of picornaviruses comprise a single large open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). Foot-and-mouth disease virus (FMDV) has an unusually large 5′ UTR (1.3 kb) containing five structural domains. These include the internal ribosome entry site (IRES), which facilitates initiation of translation, and the cis-acting replication element (cre). Less well characterised structures are a 5′ terminal 360 nucleotide stem-loop, a variable length poly-C-tract of approximately 100-200 nucleotides and a series of two to four tandemly repeated pseudoknots (PKs). We investigated the structures of the PKs by selective 2′ hydroxyl acetylation analysed by primer extension (SHAPE) analysis and determined their contribution to genome replication by mutation and deletion experiments. SHAPE and mutation experiments confirmed the importance of the previously predicted PK structures for their function. Deletion experiments showed that although PKs are not essential for replication, they provide genomes with a competitive advantage. However, although replicons and full-length genomes lacking all PKs were replication competent, no infectious virus was rescued from genomes containing less than one PK copy. This is consistent with our earlier report describing the presence of putative packaging signals in the PK region.
Open syntaxin overcomes synaptic transmission defects in diverseC. elegansexocytosis mutants
Authors: Tien Chi-Wei , Yu Bin , Huang Mengjia , Stepien Karolina P. , Sugita Kyoko , Xie Xiaoyu , Han Liping , Monnier Philippe P. , Zhen Mei , Rizo Josep , Gao Shangbang , Sugita Shuzo 
Published: January 2020

SummaryAssembly of SNARE complexes that mediate neurotransmitter release requires opening of a ‘closed’ conformation of UNC-64/syntaxin. Rescue ofunc-13/Munc13phenotypes by overexpressed open UNC-64/syntaxin suggested a specific function of UNC-13/Munc13 in opening UNC-64/ syntaxin. Here, we revisit the effects of openunc-64/syntaxin by generating knockin (KI) worms. The KI animals exhibited enhanced spontaneous and evoked exocytosis compared to wild-type animals. Unexpectedly, the open syntaxin KI partially suppressed exocytosis defects of various mutants, includingsnt-1/synaptotagmin,unc-2/P/Q/N-type Ca2+channel alpha-subunit, andunc-31/CAPS in addition tounc-13/Munc13 andunc-10/RIM, and enhanced exocytosis intom-1/Tomosyn mutants. However, open syntaxin aggravated the defects ofunc-18/Munc18 mutants. Correspondingly, open syntaxin partially bypasses the requirement of Munc13 but not Munc18 for liposome fusion. Our results show that facilitating opening of syntaxin enhances exocytosis in a wide range of genetic backgrounds, and may provide a general means to enhance synaptic transmission in normal and disease states.
A Physiological Characterization in Controlled Bioreactors Reveals a Novel Survival Strategy forDebaryomyces hanseniiat High Salinity and Confirms its Halophilic Behavior
Authors: Navarrete Clara , Frost August T. , Ramos-Moreno Laura , Krum Mette R. , Martínez José L. 
Published: January 2020

AbstractDebaryomyces hanseniiis traditionally described as a halotolerant non-conventional yeast, being the model organism for the study of osmo- and salt tolerance mechanisms in eukaryotic systems for the past 30 years.However, unravelling ofD. hansenii’sbiotechnological potential has always been difficult due to the persistent limitations in the availability of efficient molecular tools described for this yeast. Additionally, there is a lack of consensus and contradictory information along the recent years that limits a comprehensive understanding of its central carbon metabolism, mainly due to a lack of physiological studies in controlled and monitored environments. Moreover, there is controversy about the diversity in the culture conditions (media composition, temperature and pH among others) used by different groups, which makes it complicated when trying to get significant conclusions and behavioural patterns.In this work, we present for the first time a physiological characterization ofD. hanseniiin batch cultivations using highly instrumented and controlled lab-scale bioreactors. Our findings contribute to a more complete picture of the central carbon metabolism and the external pH influence on the yeast ability to tolerate high Na+and K+concentrations. Finally, the controversial halophilic/halotolerant character of this yeast is further clarified.
Topologically associating domain (TAD) boundaries stable across diverse cell types are evolutionarily constrained and enriched for heritability
Authors: McArthur Evonne , Capra John A. 
Published: January 2020

ABSTRACTTopologically associating domains (TADs) are fundamental units of three-dimensional (3D) nuclear organization. The regions bordering TADs—TAD boundaries—contribute to the regulation of gene expression by restricting interactions of cis-regulatory sequences to their target genes. TAD and TAD boundary disruption have been implicated in rare disease pathogenesis; however, we have a limited framework for integrating TADs and their variation across cell types into the interpretation of common trait-associated variants. Here, we investigate an attribute of 3D genome architecture—the stability of TAD boundaries across cell types—and demonstrate its relevance to understanding how genetic variation in TADs contribute to complex disease. By synthesizing TAD maps across 37 diverse cell types with 41 genome-wide association studies (GWAS), we investigate the differences in functionality and evolutionary pressure on variation in TADs versus TAD boundaries. We quantify their contribution to trait heritability and sequence-level evolutionary constraint and demonstrate that genetic variation in TAD boundaries contributes more to complex trait heritability, especially for immunologic, hematologic, and metabolic traits. We also show that TAD boundaries are more evolutionarily constrained than TADs. Next, stratifying boundaries by their stability across cell types, we find substantial differences. Boundaries stable across cell types are further enriched for complex trait heritability, evolutionary constraint, CTCF binding, and housekeeping genes compared to boundaries unique to a specific cell type. This suggests greater functional importance for stable boundaries. Thus, considering TAD boundary stability across cell types provides valuable context for understanding the genome’s functional landscape and enabling 3D-structure aware variant interpretation.