bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide profiling of druggable active tumor defense mechanisms to enhance cancer immunotherapy
Authors: Kishton Rigel J. , Patel Shashank J. , Vodnala Suman K. , Decker Amy E. , Patel Yogin , Sukumar Madhusudhanan , Yamamoto Tori N. , Yu Zhiya , Ji Michelle , Henning Amanda N. , Gurusamy Devikala , Palmer Douglas C. , Lo Winifred , Pasetto Anna , Malekzadeh Parisa , Deniger Drew C. , Wood Kris C. , Sanjana Neville E. , Restifo Nicholas P. 
Published: November 2019

SummaryAll current highly effective anti-tumor immunotherapeutics depend on the activity of T cells, but tumor cells can escape immune recognition by several mechanisms including loss of function in antigen presentation and inflammatory response genes, expression of immunomodulatory proteins and an immunosuppressive tumor microenvironment. In contrast, the comprehensive identification of strategies that sensitize tumor cells to immunotherapy in vivo has remained challenging. Here, we combine a two-cell type (2CT) whole-genome CRISPR-Cas9 screen with dynamic transcriptional analysis (DTA) of tumor upon T cell encounter to identify a set of genes that tumor cells express as an active defense against T cell-mediated killing. We then employed small molecule and biologic screens designed to antagonize gene products employed by tumor cells to actively defend against T cell-mediated tumor destruction and found that the inhibition of BIRC2, ITGAV or DNPEP enhanced tumor cell destruction by T cells. Mechanistically, we found that BIRC2 promoted immunotherapy resistance through inhibiting non-canonical NF-κB signaling and limiting inflammatory chemokine production. These findings show the path forward to improving T cell-mediated tumor destruction in the clinic.
XenoCP: Cloud-based BAM cleansing tool for RNA and DNA from Xenograft
Authors: Rusch Michael , Ding Liang , Arunachalam Sasi , Thrasher Andrew , Jin Hongjian , Macias Michael , Kasper Lawryn , Silveira Andre , Dyer Michael A. , Baker Suzanne J. , Zhang Jinghui 
Published: November 2019

ABSTRACTSummaryXenografts are important models for cancer research and the presence of mouse reads in xenograft next generation sequencing data can potentially confound interpretation of experimental results. We present an efficient, cloud-based BAM-to-BAM cleaning tool called XenoCP to remove mouse reads from xenograft BAM files. We show application of XenoCP in obtaining accurate gene expression quantification in RNA-seq and tumor heterogeneity in WGS of xenografts derived from brain and solid tumors.Availability and ImplementationSt. Jude Cloud (https://pecan.stjude.cloud/permalink/xenocp) and St. Jude Github (https://github.com/stjude/XenoCP)
Cerebrovascular reactivity assessment with O2-CO2 exchange ratio under brief breath hold challenge
Authors: Chan Suk Tak , Evans Karleyton C. , Song Tian Yue , Selb Juliett , van der Kouwe Andre , Rosen Bruce R. , Zheng Yong Ping , Ahn Andrew , Kwong Kenneth K. 
Published: November 2019

AbstractHypercapnia during breath holding is believed to be the dominant driver behind the modulation of cerebral blood flow (CBF). Here we showed that the cerebrovascular responses to brief breath hold epochs were coupled not only with increased partial pressure of carbon dioxide (PCO2), but also with a decrease in partial pressure of oxygen (PO2). We used transcranial Doppler ultrasound to evaluate the CBF changes during breath holding by measuring the cerebral blood flow velocity (CBFv) in the middle cerebral arteries, a pair of cerebral arteries that supply most parts of the brain. The regional CBF changes during breath hold epochs were mapped with blood oxygenation level dependent (BOLD) signal changes as surrogate of CBF changes using functional magnetic resonance imaging (fMRI) technique. Given the interdependence of the dynamic changes between PCO2 and PO2, we found that the breath-by-breath O2-CO2 exchange ratio (bER), namely the ratio of changes in PO2 (ΔPO2) to changes in PCO2 (ΔPCO2) between end inspiration and end expiration, was superior to either ΔPO2 or ΔPCO2 alone in coupling with the changes of CBFv and BOLD signals under breath hold challenge. The regional cerebrovascular reactivity (CVR) results derived by regressing BOLD signal changes on bER under breath hold challenge resembled those derived by regressing BOLD signal changes on end-tidal partial pressure of CO2 (PETCO2) under exogenous CO2 challenge. Our findings provide a novel insight on the potential of using bER to better quantify CVR changes under breath hold challenge, although the physiological mechanisms of cerebrovascular changes underlying breath hold and exogenous CO2 challenges are potentially different.
Multiple routes to interspecific territoriality in sister species of North American perching birds
Authors: Cowen Madeline C. , Drury Jonathan P. , Grether Gregory F. 
Published: November 2019

ABSTRACTBehavioral interference between species can influence a wide range of ecological and evolutionary processes. Here we test foundational hypotheses regarding the origins and maintenance of interspecific territoriality, and evaluate the role of interspecific territoriality and hybridization in shaping species distributions and transitions from parapatry to sympatry in sister species of North American perching birds (Passeriformes). We found that interspecific territoriality is pervasive among sympatric sister species pairs, and that interspecifically territorial species pairs have diverged more recently than sympatric non-interspecifically territorial pairs. None of the foundational hypotheses alone explain the observed patterns of interspecific territoriality, but our results support the idea that some cases of interspecific territoriality arise from misdirected intraspecific aggression while others are evolved responses to resource competition. The combination of interspecific territoriality and hybridization appears to be an unstable state associated with parapatry, while species that are interspecifically territorial and do not hybridize are able to achieve extensive fine- and coarse-scale breeding range overlap. In sum, these results suggest that interspecific territoriality has multiple origins and that interspecific territoriality and hybridization together can have striking impacts on species ranges.
Integrating multi-OMICS data through sparse Canonical Correlation Analysis for predicting complex traits: A comparative study
Authors: Rodosthenous Theodoulos , Shahrezaei Vahid , Evangelou Marina 
Published: November 2019

AbstractMotivationRecent developments in technology have enabled researchers to collect multiple OMICS datasets for the same individuals. The conventional approach for understanding the relationships between the collected datasets and the complex trait of interest would be through the analysis of each OMIC dataset separately from the rest, or to test for associations between the OMICS datasets. In this work we show that by integrating multiple OMICS datasets together, instead of analysing them separately, improves our understanding of their in-between relationships as well as the predictive accuracy for the tested trait. As OMICS datasets are heterogeneous and high-dimensional (p >> n) integrating them can be done through Sparse Canonical Correlation Analysis (sCCA) that penalises the canonical variables for producing sparse latent variables while achieving maximal correlation between the datasets. Over the last years, a number of approaches for implementing sCCA have been proposed, where they differ on their objective functions, iterative algorithm for obtaining the sparse latent variables and make different assumptions about the original datasets.ResultsThrough a comparative study we have explored the performance of the conventional CCA proposed by Parkhomenko et al. [2009], penalised matrix decomposition CCA proposed by Witten and Tibshirani [2009] and its extension proposed by Suo et al. [2017]. The aferomentioned methods were modified to allow for different penalty functions. Although sCCA is an unsupervised learning approach for understanding of the in-between relationships, we have twisted the problem as a supervised learning one and investigated how the computed latent variables can be used for predicting complex traits. The approaches were extended to allow for multiple (more than two) datasets where the trait was included as one of the input datasets. Both ways have shown improvement over conventional predictive models that include one or multiple datasets.Contacttr1915@ic.ac.uk
Natural diversity in the predatory behavior facilitates the establishment of a new robust model strain for nematode-trapping fungi
Authors: Yang Ching-Ting , de Ulzurrun Guillermo Vidal-Diez , Pedro Gonçalves A. , Lin Hung-Che , Chang Ching-Wen , Huang Tsung-Yu , Chen Sheng-An , Lai Cheng-Kuo , Tsai Isheng J. , Schroeder Frank C. , Stajich Jason E. , Hsueh Yen-Ping 
Published: November 2019

AbstractNematode-trapping fungi (NTF) are a group of specialized microbial predators that consume nematodes when food sources are limited. Predation is initiated when conserved nematode ascaroside pheromones are sensed, followed by the development of complex trapping devices. To gain insights into the co-evolution of this inter-kingdom predator-prey relationship, we investigated natural populations of nematodes and NTF, that we found to be ubiquitous in soils.Arthrobotrysspecies were sympatric with various nematode species and behaved as generalist predators. The ability to sense prey amongst wild isolates ofA. oligosporavaried greatly, as determined by the number of traps after exposure toCaenorhabditis elegans. While some strains were highly sensitive toC. elegansand the nematode pheromone ascarosides, others responded only weakly. Furthermore, strains that were highly sensitive to the nematode prey also developed traps faster. The polymorphic nature of trap formation correlated with competency in prey killing, as well as with the phylogeny ofA. oligosporanatural strains, calculated after assembly and annotation of the genomes of twenty isolates. A chromosome level genome assembly and annotation was established for one of the most sensitive wild isolate, and deletion of the only G proteinβsubunit-encoding gene ofA. oligosporanearly abolished trap formation, implicating G protein signaling in predation. In summary, our study establishes a highly responsiveA. oligosporawild isolate as a novel model strain for the study of fungal-nematode interactions and demonstrates that trap formation is a fitness character in generalist predators of the NTF family.Significance statementNematode-trapping fungi (NTF) are carnivorous microbes that hold potential to be used as biological control agents due to their ability to consume nematodes. In this work we show that NTF are ubiquitous generalist predators found in sympatry with their prey in soil samples. Wild isolates of NTF displayed a naturally diverse ability to execute their predatory lifestyle. We generated a large whole genome sequencing dataset for many of the fungal isolates that will serve as the basis of future projects isolates. In particular, we establish TWF154, a highly responsive strain ofArthrobotrys oligospora, as a model strain to study the genetics of NTF. Lastly, we provide evidence that G-protein signaling is necessary for trap induction in NTF.
Pericyte-Like Cells Undergo Transcriptional Reprogramming and Distinct Functional Adaptations in Acute Lung Injury
Authors: Hung CF , Holton S , Chow YH , Liles WC , Gharib SA , Altemeier WA 
Published: November 2019

AbstractBackgroundWe previously reported on the role of pericyte-like cells as functional sentinel immune cells in lung injury. However, much about the biological role of pericytes in lung injury remains unknown. Lung pericyte-like cells are well-positioned to sense disruption to the epithelial barrier and coordinate local inflammatory responses due to their anatomic niche within the alveoli. In this report, we characterized transcriptional responses and functional changes in pericyte-like cells following activation by alveolar components from injured and uninjured lungs in a mouse model of acute lung injury (ALI).MethodsWe purified pericyte-like cells from lung digests using PDGFRβ as a selection marker and expanded them in culture as previously described (1). We induced sterile acute lung injury in mice with recombinant human Fas ligand (rhFasL) instillation followed by mechanical ventilation (1). We then collected bronchoalveolar lavage fluid (BALF) from injured and uninjured mice. Purified pericyte-like cells in culture were exposed to growth media only (control), BALF from uninjured mice, and BALF from injured mice for 6 and 24 h. RNA collected from these treatment conditions were processed for RNAseq. Targets of interest identified by pathway analysis were validated using in vitro and in vivo assays.ResultsWe observed robust global transcriptional changes in pericyte-like cells following treatment with uninjured and injured BALF at 6 h, but this response persisted for 24 h only after exposure to injured BALF. Functional enrichment analysis of pericytes treated with injured BALF revealed activation of immuno-inflammatory, cell migration and angiogenesis-related pathways, whereas processes associated with tissue development and remodeling were down-regulated. We validated select targets in the inflammatory, angiogenesis-related, and cell migratory pathways using functional biological assays in vitro and in vivo.ConclusionLung pericyte-like cells are highly responsive to alveolar compartment content from both uninjured and injured lungs, but injured BALF elicits a more sustained response. The inflammatory, angiogenic, and migratory changes exhibited by activated pericyte-like cells underscore the phenotypic plasticity of these specialized stromal cells in the setting of acute lung injury.
Mechanistic origin of drug interactions between translation-inhibiting antibiotics
Authors: Kavčič Bor , Tkačik Gašper , Bollenbach Tobias 
Published: November 2019

SummaryAntibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we demonstrate that these interactions can be accounted for by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generated translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimicked antibiotic action and their interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further showed that the kinetics of drug uptake and binding together with growth laws allows direct prediction of a large fraction of observed interactions, yet fails for suppression. Simultaneously varying two translation bottlenecks in the same cell revealed how the dense traffic of ribosomes and competition for translation factors results in previously unexplained suppression. This result highlights the importance of “continuous epistasis” in bacterial physiology.
Single-Cell Virtual Cytometer allows user-friendly and versatile analysis and visualization of multimodal single cell RNAseq datasets
Authors: Pont Frédéric , Tosolini Marie , Gao Qing , Perrier Marion , Madrid-Mencía Miguel , Huang Tse Shun , Neuvial Pierre , Ayyoub Maha , Nazor Kristopher , Fournié Jean Jacques 
Published: November 2019

ABSTRACTThe development of single cell transcriptomic technologies yields large datasets comprising multimodal informations such as transcriptomes and immunophenotypes. Currently however, there is no software to easily and simultaneously analyze both types of data. Here, we introduce Single-Cell Virtual Cytometer, an open-source software for flow cytometry-like visualization and exploration of multi-omics single cell datasets. Using an original CITE-seq dataset of PBMC from an healthy donor, we illustrate its use for the integrated analysis of transcriptomes and phenotypes of functional maturation in peripheral T lymphocytes from healthy donors. So this free and open-source algorithm constitutes a unique resource for biologists seeking for a user-friendly analytic tool for multimodal single cell datasets.
In situ cryo-electron tomography reveals filamentous actin within the microtubule lumen
Authors: Paul Danielle M , Mantell Judith , Borucu Ufuk , Coombs Jennifer , Surridge Katherine J , Squire John , Verkade Paul , Dodding Mark P 
Published: November 2019

AbstractMicrotubules and filamentous (F-) actin engage in complex interactions to drive many cellular processes from subcellular organisation to cell division and migration. This is thought to be largely controlled by proteins that interface between the two structurally distinct cytoskeletal components. Here, we use cryo-electron tomography to demonstrate that the microtubule lumen can be occupied by extended segments of F-actin in small-molecule induced, microtubule-based cellular projections. We uncover an unexpected versatility in cytoskeletal form that may prompt a significant development of our current models of cellular architecture and offer a new experimental approach for the in-situ study of microtubule structure and contents.
Magnetic-Alignment of Polymer Nanodiscs Probed by Solid-State NMR Spectroscopy
Authors: Ravula Thirupathi , Kim JaeWoong , Lee Dong-Kuk , Ramamoorthy Ayyalusamy 
Published: November 2019

AbstractThe ability of amphipathic polymers to self-assemble with lipids and form nanodiscs has been a boon for the field of functional reconstitution of membrane proteins. In a field dominated by detergent micelles, a unique feature of polymer nanodiscs is their much-desired ability to align in the presence of an external magnetic field. Magnetic alignment facilitates the application of solid-state NMR spectroscopy and aids in the measurement of residual dipolar couplings (RDCs) via well-established solution NMR spectroscopy. In this study, we comprehensively investigate the magnetic-alignment properties of SMA-QA polymer based nanodiscs by using 31P and 14N solid-state NMR experiments under static conditions. The results reported herein demonstrate the spontaneous magnetic-alignment of large-size (≥ 20 nm diameter) SMA-QA nanodiscs (also called as macro-nanodiscs) with the lipid-bilayer-normal perpendicular to the magnetic field direction. Consequently, the orientation of macro-nanodiscs are further shown to flip their alignment axis parallel to the magnetic field direction upon the addition of a paramagnetic lanthanide salt. These results demonstrate the use of SMA-QA polymer nanodiscs for solid-state NMR applications including structural studies on membrane proteins.
Dual oxidase geneDuoxand Toll-like receptor 3 geneTLR3in the Toll pathway suppress zoonotic pathogens through regulating the intestinal bacterial community homeostasis inHermetia illucensL.
Authors: Huang Yaqing , Yu Yongqiang , Zhan Shuai , Tomberlin Jeffery K. , Huang Dian , Cai Minmin , Zheng Longyu , Yu Ziniu , Zhang Jibin 
Published: November 2019

AbstractBlack soldier fly (BSF;Hermetia illucensL.) larvae can convert fresh pig manure into protein and fat-rich biomass, which can then be used as livestock feed. Currently, it is the only insect approved for such purposes in Europe, Canada, and the USA. Pig manure is rich in zoonotic pathogens (e.g.,Staphylococcus aureusandSalmonellaspp.). BSF larvae inhibit these zoonotic pathogens; however, the mechanism is unclear. We employed RNAi, qRT-PCR, and Illumina MiSeq bacterial 16S rDNA high-throughput sequencing molecular techniques to study the interaction between the two immune genes (Duoxin Duox-reactive oxygen species [ROS] immune system andTLR3in the Toll signaling pathway) and zoonotic pathogens to determine the mechanisms resulting in pathogen suppression.Results indicated thatBsf Duox-TLR3RNAi increased bacterial load but decreased the relative abundance ofProvidenciaandDysgonomonasintestinal symbionts. Concurrently,Bsf Duox-TLR3RNAi inactivated the NF-κ B signaling pathway, downregulated the expression of antimicrobial peptides, and diminished inhibitory effects on zoonotic pathogen. The resulting dysbiosis stimulated an immune response by activatingBsfDuoxand promoting ROS, which regulated the composition and structure of the gut bacterial community.Thus,BsfDuoxandBsfTLR3are important factors in regulating the gut key bacteriaProvidenciaandDysgonomonashomeostasis while inhibiting target zoonotic pathogens.
BlobToolKit – Interactive quality assessment of genome assemblies
Authors: Challis Richard , Richards Edward , Rajan Jeena , Cochrane Guy , Blaxter Mark 
Published: November 2019

AbstractReconstruction of target genomes from sequence data produced by instruments that are agnostic as to the species-of-origin may be confounded by contaminant DNA. Whether introduced during sample processing or through co-extraction alongside the target DNA, if insufficient care is taken during the assembly process, the final assembled genome may be a mixture of data from several species. Such assemblies can confound sequence-based biological inference and, when deposited in public databases, may be included in downstream analyses by users unaware of underlying problems.We present BlobToolKit, a software suite to aid researchers in identifying and isolating non-target data in draft and publicly available genome assemblies. BlobToolKit can be used to process assembly, read and analysis files for fully reproducible interactive exploration in the browser-based Viewer. BlobToolKit can be used during assembly to filter non-target DNA, helping researchers produce assemblies with high biological credibility.We have been running an automated BlobToolKit pipeline on eukaryotic assemblies publicly available in the International Nucleotide Sequence Data Collaboration and are making the results available through a public instance of the Viewer at https://blobtoolkit.genomehubs.org/view. We aim to complete analysis of all publicly available genomes and then maintain currency with the flow of new genomes. We have worked to embed these views into the presentation of genome assemblies at the European Nucleotide Archive, providing an indication of assembly quality alongside the public record with links out to allow full exploration in the Viewer.
Including Data Analytical Stability in Cluster-based Inference
Authors: Roels Sanne P. , Loeys Tom , Moerkerke Beatrijs 
Published: November 2019

AbstractIn the statistical analysis of functional Magnetic Resonance Imaging (fMRI) brain data it remains a challenge to account for simultaneously testing activation in over 100.000 volume units or voxels. A popular method that reduces the dimensionality of this test problem is cluster-based inference. We propose a new testing procedure that allows to control the family-wise error (FWE) rate at the cluster level but improves cluster-based test decisions in two ways by (1) taking into account a measure for data analytical stability and (2) allowing a more voxel-based interpretation of the results. For each voxel, we define the re-selection rate conditional on a given FWE-corrected threshold and use this rate, which is a measure of stability, into the selection process. In our procedure, we set a more liberal and a more conservative FWE controlling threshold. Clusters that survive the liberal but not the conservative threshold are retained if sufficient evidence for voxelwise stability is available. Cluster that survive the conservative threshold are retained anyhow, and clusters that do not survive the liberal threshold are not further considered. Using the Human Connectome Project Data (Van Essen et al., 2012), we demonstrate how in a group analysis our method results not only in a higher number of selected voxels but also in a larger overlap between different test images. Additionally, we demonstrate the ability of our procedure to control the FWE, also in relatively small sample sizes.