bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid motor adaptation to bounce perturbations in online Pong game is independent from the visual tilt of the bouncing surface
Authors: Mikula Laura , ’t Hart Bernard Marius , Henriques Denise Y. P. 
Published: February 2022

AbstractMotor adaptation describes the ability of the motor system to counteract repeated perturbations in order to reduce movement errors. Most research in the field investigated adaptation in response to perturbations affecting the moving hand. Fewer studies looked at the effect of a perturbation applied to the movement target, however they used simplistic visual stimuli. In this study, we examined motor adaptation to perturbations affecting the motion of dynamic targets. In addition, we asked whether external visual cues in the environment could facilitate this process. To do so, participants were asked to play an online version of the Pong game in which they intercepted a ball bouncing off a wall using a paddle. A perturbation was applied to alter the post-bounce trajectory of the ball and the wall orientation was manipulated to be consistent or not with the ball trajectory. The “trained tilt” group (n = 34) adapted to the consistent condition and the “trained horizontal” group (n = 36) adapted to the inconsistent condition. In case participants optimally integrate external visual cues, the “trained tilt” group is expected to exhibit faster and/or more complete adaptation than the “trained horizontal” group. We found that the perturbation reduced interception accuracy. Participants showed large interception errors when the perturbation was introduced, followed by rapid error decrease and aftereffects (errors in the opposite direction) once the perturbation was removed. Although both experimental groups showed these typical markers of motor adaptation, we did not find differences in interception success rates or errors between the “trained tilt” and “trained horizontal” groups. Our results demonstrate that participants quickly adapted to the dynamics of the pong ball. However, the visual tilt of the bouncing surface did not enhance their performance. The present study highlights the ability of the motor system to adapt to external perturbations applied to a moving target in a more dynamical environment and in online settings. These findings underline the prospects of further research on sensorimotor adaptation to unexpected changes in the environment using more naturalistic and complex real-world or virtual reality tasks as well as gamified paradigms.
C. difficilemay be overdiagnosed in adults and is a prevalent commensal in infants
Authors: Ferretti Pamela , Wirbel Jakob , Maistrenko Oleksandr M , Van Rossum Thea , Alves Renato , Fullam Anthony , Akanni Wasiu , Schudoma Christian , Schwarz Anna , Thielemann Roman , Thomas Leonie , Kandels Stefanie , Hercog Rajna , Telzerow Anja , Letunic Ivica , Kuhn Michael , Zeller Georg , Schmidt Thomas SB , Bork Peer 
Published: February 2022

AbstractClostridioides difficileis an urgent threat in hospital-acquired infections world-wide, yet the microbial composition associated withC. difficile, in particular inC. difficileinfection (CDI) cases, remains poorly characterised. To investigate the gut microbiome composition in CDI patients, we analysed 534 metagenomes from 10 publicly available CDI study populations. We then trackedC. difficileon a global scale, screening 42,900 metagenomes from 253 public studies. Among the CDI cohorts, we detectedC. difficilein only 30% of the stool samples from CDI patients. However, we found that multiple other toxigenic species capable of inducing CDI-like symptomatology were prevalent. In addition, the majority of the investigated studies did not adhere to the recommended guidelines for a correct CDI diagnosis.In the global survey, we found thatC. difficileprevalence, abundance and biotic context were age-dependent.C. difficileis a rare taxon associated with reduced diversity in healthy adults, but common and associated with increased diversity in infants. We identified a group of species co-occurring withC. difficileexclusively in healthy infants, enriched in obligate anaerobes and in species typical of the healthy adult gut microbiome.C. difficilein healthy infants was therefore associated with multiple indicators of healthy gut microbiome maturation.Our analysis raises concerns about potential CDI overdiagnosis and suggests thatC. difficileis an important commensal in infants and that its asymptomatic carriage in adults depends on microbial context.
Identification of Mebendazole as an ethylene signaling activator reveals a role of ethylene signaling in the regulation of lateral root angles
Authors: He Wenrong , Truong Hai An , Zhang Ling , Cao Min , Arakawa Neal , Xiao Yao , Zhong Kaizhen , Hou Yingnan , Busch Wolfgang 
Published: February 2022

SUMMARYThe lateral root angle or gravitropic set-point angle (GSA) is an important trait for root system architecture (RSA) that determines the radial expansion of the root system. The GSA therefore plays a crucial role for the ability of plants to access nutrients and water in the soil. Despite its importance, only few regulatory pathways and mechanisms that determine GSA are known, and these mostly relate to auxin and cytokinin pathways. Here, we report the identification of a small molecule, Mebendazole (MBZ) that modulates GSA inArabidopsis thalianaroots and acts via the activation of ethylene signaling. We uncover that MBZ directly acts on the serine/threonine protein kinase CTR1, which is a negative regulator of ethylene signaling. Our study not only reveals that the ethylene signaling pathway is essential for GSA regulation, but it also identifies a small molecular modulator of RSA and the first small molecule that acts downstream of ethylene receptors and that directly activates ethylene signaling.In briefHeet al. identify a small molecule that regulates lateral root angle. They show that the compound increases lateral root angle by inhibiting CTR1 kinase activity, which in turn activates ethylene signaling. Therefore, they uncover that the ethylene pathway is involved in lateral root angle regulation.HighlightsMBZ increases lateral root angleMBZ regulates lateral root angle by activating ethylene signalingMBZ inhibits CTR1 kinase activityThe ethylene pathway is involved in lateral root angle regulation
cLD: Rare-variant disequilibrium between genomic regions identifies novel genomic interactions
Authors: Wang Dinghao , He Jingni , Perera Deshan , Cao Chen , Kossinna Pathum , Li Qing , Zhang William , Guo Xingyi , Platt Alexander , Wu Jingjing , Zhang Qingrun 
Published: February 2022

ABSTRACTLinkage disequilibrium (LD) is a fundamental concept in genetics; critical for studying genetic associations and molecular evolution. However, LD measurements are only reliable for common genetic variants, leaving low-frequency variants unanalyzed. In this work, we introduce cumulative LD (cLD), a stable statistic that captures the rare-variant LD between genetic regions, which reflects more biological interactions between variants, in addition to lack of recombination. We derived the theoretical variance of cLD using delta methods to demonstrate its higher stability than LD for rare variants. This property is also verified by bootstrapped simulations using real data. In application, we find cLD reveals an increased genetic association between genes in 3D chromatin interactions, a phenomenon recently reported negatively by calculating standard LD between common variants. Additionally, we show that cLD is higher between gene pairs reported in interaction databases, identifies unreported protein-protein interactions, and reveals interacting genes distinguishing case/control samples in association studies.
Brain signatures for neuropsychological and everyday memory achieve high replicability and explanatory power in two data cohorts
Authors: Fletcher Evan , Farias Sarah , DeCarli Charles , Gavett Brandon , Widaman Keith , De Leon Fransia , Mungas Dan 
Published: February 2022

AbstractBackgroundThe “brain signature of cognition” concept has garnered interest as a data-driven, exploratory approach to better understand key brain regions involved in specific cognitive functions, with the potential to maximally characterize brain substrates of clinical outcomes. However, to be a robust brain phenotype, the signature approach requires a statistical foundation showing that model performance replicates across a variety of cohorts. Here, we outline a procedure that provides this foundation for a signature models of two memory-related behavioral domains.MethodIn each of two independent data cohorts, we derived regional brain gray matter thickness associations for neuropsychological and everyday cognition memory, testing for replicability. In each cohort we computed regional association to outcome in 40 randomly selected “discovery subsets” of size N = 400; we generated spatial overlap frequency maps and selected high-frequency regions as “consensus” signature masks for each cohort. We tested replicability by comparing cohort-based consensus model fits in all discovery sets. We tested explanatory power in each full cohort, compare signature model fits with competing “standard” models of each outcome.ResultSpatial replications produced strongly convergent consensus signature regions derived from UCD and ADNI. Consensus model fits were highly correlated in 40 random subsets of each cohort indicating high replicability. In comparisons over each full cohort, signature models outperformed other models with one exception.ConclusionMultiple random model generations, followed by consensus selection of regional brain substrates, produced signature models that replicated model fits to outcome and outperformed other commonly used measures. Robust biomarkers of cognition and everyday function may be achievable by this method.FundingThis project was funded by R01 AG052132 (NIH/NIA)
Bioframe: Operations on Genomic Intervals in Pandas Dataframes
Authors:   Open2C, Abdennur Nezar , Fudenberg Geoffrey , Flyamer Ilya , Galitsyna Aleksandra A. , Goloborodko Anton , Imakaev Maxim , Venev Sergey V. 
Published: February 2022

AbstractMotivationGenomic intervals are one of the most prevalent data structures in computational genome biology, and used to represent features ranging from genes, to DNA binding sites, to disease variants. Operations on genomic intervals provide a language for asking questions about relationships between features. While there are excellent interval arithmetic tools for the command line, they are not smoothly integrated into Python, one of the most popular general-purpose computational and visualization environments.ResultsBioframeis a library to enable flexible and performant operations on genomic interval dataframes in Python.Bioframeextends the Python data science stack to use cases for computational genome biology by building directly on top of two of the most commonly-used Python libraries,numpyandpandas. ThebioframeAPI enables flexible name and column orders, and decouples operations from data formats to avoid unnecessary conversions, a common scourge for bioinformaticians. Bioframe achieves these goals while maintaining high performance and a rich set of features.Availability and implementationBioframeis open-source under MIT license, cross-platform, and can be installed from the Python package index. The source code is maintained by Open2C on Github athttps://github.com/open2c/bioframe.
A Model-Based Clustering via Mixture of Bayesian Hierarchical Models with Covariate Adjustment for Detecting Differentially Expressed Genes from Paired Design
Authors: Zhang Yixin , Liu Wei , Qiu Weiliang 
Published: February 2022

ABSTRACTThe causes of many complex human diseases are still largely unknown. Genetics plays an important role in uncovering the molecular mechanisms of complex human diseases. A key step to characterize the genetics of a complex human disease is to unbiasedly identify disease-associated gene transcripts in whole-genome scale. Confounding factors could cause false positives. Paired design, such as measuring gene expression before and after treatment for the same subject, can reduce the effect of known confounding factors. Model-based clustering, such as mixtures of Bayesian hierarchical models, has been proposed to detect gene transcripts differentially expressed between paired samples. However, not all known confounding factors can be controlled in a paired/match design. To the best of our knowledge, no clustering methods have the capacity to adjust for the effects of covariates yet. In this article, we proposed a novel mixture of Bayesian hierarchical models with covariate adjustment in identifying differentially expressed transcripts using high-throughput whole-genome data from paired design. Both simulation study and real data analysis show the good performance of the proposed method
Notch signaling in tumor vasculature programs cancer-associated fibroblasts to suppress anti-tumor immunity
Authors: Zhu Yu , Xiang Menglan , Brulois Kevin F. , Lazarus Nicole H. , Pan Junliang , Butcher Eugene C. 
Published: February 2022

SummaryScarcity of tumor-infiltrating T cells poses significant challenges to cancer treatment, but mechanisms that regulate T cell recruitment into the tumor microenvironment are unclear. Here we ask if the endothelial lining of tumor vasculature suppresses T cell infiltration. Using mouse pancreatic ductal adenocarcinoma models, we found that Notch signaling in endothelial cells (ECs) inhibits the pro-inflammatory functions of cancer-associated fibroblasts (CAFs) and prevents CAFs from secreting CXCL10, a chemokine that recruits anti-tumor T cells via its receptor CXCR3. Abrogation of canonical Notch signaling in ECs reprogrammed the phenotype of CAFs from myofibroblasts into pro-inflammatory fibroblasts, unleashed interferon gamma (IFNγ) responses in the tumor, and stimulated CXCL10/CXCR3-mediated recruitment of T cells to inhibit tumor growth. Collectively, these data uncover an important role of endothelial Notch signaling in shaping the tumor immune microenvironment, and suggest the potential of targeting EC-CAF crosstalk as an approach to enhance anti-tumor immunity in immunologically cold tumors.In briefHow blood vasculature shapes the tumor immune microenvironment is poorly defined. This study demonstrates that tumor endothelial cells reprogram cancer-associated fibroblasts to limit anti-tumor T cell recruitment, and suggests the potential of targeting endothelium-fibroblast crosstalk to overcome T cell scarcity in “cold” tumors and enhance anti-tumor immunity.
Identification of biological processes and signaling pathways in lactate-treated cancer cells
Authors: Qian Zhiwen , Gu Hanming , Chang Tingxiang 
Published: February 2022

AbstractCancer is a complex disease that involves the alterations of metabolic pathways and tumor microenvironment. Lactate in the tumor microenvironment leads to cancer proliferation, metastasis, and angiogenesis. However, the effect of lactate on prostate cancer cells is still unclear. Here, our objective is to identify the significant molecules and biological processes by analyzing the RNA-seq data. The GSE195639 was produced by the Illumina NextSeq 500 (Homo sapiens). The KEGG and GO analyses show that Herpes simplex virus 1 infection and Rap1 signaling pathway are considered major pathways during the lactate-treated cancer cells. Furthermore, we identified the top ten essential molecules including IL6, CASP3, JUN, MAPK3, BRCA1, PIK3R1, CCNA2, TPI1, APOE, and EXO1. Therefore, our study may provide novel insights into the mechanism of prostate cancers.
Read depth correction for somatic mutations
Authors: Anaya Jordan , Baras Alexander S. 
Published: February 2022

ABSTRACTThe ability to accurately detect mutations is a function of read depth and variant allele frequency (VAF). While the read depth distribution of a sample is observable, the true VAF distribution of all mutations in a sample is uncertain when there is low coverage depth. We propose to estimate the VAF distributions that would be observed with high-depth sequencing for samples with low sequencing depth by grouping samples with similar clonality and purity and using the VAF distributions observed with the high-depth mutations that are available. With these estimated high-depth VAF distributions we then calculate what the expected VAF distributions would be at a given depth and compare against the observed VAF distributions at that depth. Using this procedure we estimate that The Cancer Genome Atlas (TCGA) MC3 dataset only reports on average 83% of the mutations in a sample which would have been detected with high-depth sequencing. These results have important implications for comparing tumor mutational burden (TMB) estimates when samples are sequenced at different depths and for modeling high-depth, gene panel-based sequencing from the TCGA MC3 dataset.
Comprehensive dissection of immune microenvironment in the progression of early gastric cancer at spatial and single-cell resolution
Authors: Du Tiantian , Gao Huiru , Wu Honglei , Li Juan , Li Peilong , Gao Jie , Qi Qiuchen , Liu Xiaoyan , Du Lutao , Wang Yunshan , Wang Chuanxin 
Published: February 2022

AbstractWhile the changes of tumor immune microenvironment (TME) have critical implications for most tumor progression, works that could reveal the compositions and immunity features of TME are needed. Profiling gastric malignant cells at single-cells resolution has shown the transcriptional heterogeneity is represented at different states of gastric cancer, implying that diverse cell states may exist, including immune cells, and all components in TME make some balances in early gastric cancer (EGC) progression. However, it remains unclear how immune cells contributing malignancy of gastritis, constituting general characteristics of gastric TME. Furthermore, the role of specific interactions among cells in gastric TME remains to be illustrated. Here, we performed spatial transcriptomes and single-cell RNA-seq analysis across 18 gastric samples, identifying 17 celltypes and reconstructing their location information. We found that immune cells represented different degree of dysregulations during the progression from non-atrophic gastritis (NAG), atrophic gastritis (AG) to EGC, including imbalance of cytotoxic and inhibitory effects in T cells, maturation inhibition in B cells and malignant genes up-regulated obviously in myeloid cells. Besides, pathway activities showed that hypoxia, reactive oxygen species and fatty metabolism signaling were activated from AG stage, which may accelerate progression of EGC. Moreover, cellular interactions further identified the roles of hypoxia in gastric TME. Overall, the multi-omics data presented in this study offer a comprehensive view of immune cell types, states changes and locations within the gastric tissues during the progression from NAG, AG to EGC, advancing our understanding of the composition and immunity of different gastric states, offering diagnostic and preventive thoughts for EGC.
Inhibition of the tuft cell/ILC2 axis reduces gastric tumor development in mice
Authors: O’Keefe Ryan N , Carli Annalisa LE , Baloyan David , Afshar-Sterle Shoukat , Eissmann Moritz F , Poh Ashleigh R , Seillet Cyril , Locksley Richard M , Ernst Matthias , Buchert Michael 
Published: February 2022

AbstractAlthough gastric cancer is a leading cause of cancer-related deaths, systemic treatment strategies remain scarce. Here we explore a metabolite-triggered circuit between epithelial tuft cells and innate lymphoid type 2 cells (ILC2) that is evolutionarily optimized for intestinal remodeling in response to helminth infection. We demonstrate that tuft cell-derived interleukin 25 (IL25) acts as an alarmin on ILC2s to induce the release of IL13 as a growth factor for tuft cells, and propose that this model drives early metaplastic remodeling and gastric tumor formation. Genetic ablation of tuft cells, ILC2s or antibody-mediated neutralization of IL13 or IL25 reduces the growth of established tumors. Thus, the tuft cell/ILC2 axis provides an opportunity to therapeutically inhibit preneoplastic lesions and early-stage gastric cancer through repurposing of antibody-mediated therapies.One-Sentence SummaryTuft cells and type 2 innate lymphoid cells offer a new therapeutic target in gastric disease.
CRISPR-Detector: Fast and Accurate Detection, Visualization, and Annotation of Genome-Wide Mutations Induced by Gene Editing Events
Authors: Huang Lei , Wang Dan , Chen Haodong , Hu Jinnan , Dai Xuechen , Liu Chuan , Li Anduo , Shen Xuechun , Qi Chen , Sun Haixi , Zhang Dengwei , Chen Tong , Jiang Yuan 
Published: February 2022

AbstractThe leading edge of genome editing, driven by CRISPR/Cas technology, is revolutionizing biotechnologies. In pace with the burst of novel genome editing methods, bioinformatic tools to monitor the on/off-target events need to be more evolved as well. Existing tools suffer from limitations in speed and scalability, and they especially struggle with whole genome sequencing (WGS) data analysis which has the potential to detect off-target mutations at a genome-wide level via an unbiased manner. Here, we introduce our CRISPR-detector tool, which is a web-hosted or locally deployable pipeline with five key innovations: 1) optimized scalability allowing for WGS data analysis beyond BED (Browser Extensible Data) file-defined regions; 2) improved accuracy benefiting from haplotype-based variant calling to handle sequencing errors; 3) treated and control sample co-analysis to remove background variants existing prior to genome editing; 4) integrated structural variation (SV) calling; and 5) functional and clinical annotation of editing-induced mutations.
Prey size spectra and predator to prey size ratios of southern ocean salps
Authors: Fender Christian K. , Décima Moira , Gutiérrez-Rodríguez Andres , Selph Karen E. , Yingling Natalia , Stukel Michael R. 
Published: February 2022

AbstractSalp grazing is important in shaping planktonic food-web structure. However, little is known about the size ranges of their prey in the field or how grazing impacts size structure. This study investigated the feeding habits of 7 different species of salps, representing a variety of sizes and life stages across subtropical and subantarctic waters east of New Zealand. Scanning electron microscopy was used to examine the gut contents of 58 salps, which were then compared to water column plankton communities characterized via epifluorescence microscopy, FlowCam, and flow cytometry. While most of the gut contents resembled ambient waters, substantial differences were found amongst some co-occurring species, such as increased retention of submicron bacteria amongst smaller salps likeThalia democratica. We found that even for those salps capable of feeding on bacteria efficiently, nanoplankton and small microplankton still made up the majority of gut biomass. Larger microplankton were rarer in the guts than in the water column, potentially suggesting an upper size-threshold in addition to the lower size-threshold that has been the focus of most previous work. Salp carbon-weighted predator to prey size ratios were variable, with the majority falling between 1,000:1 and 10,000:1 depending largely on the size of the salp. Taken together our results indicate that despite being able to feed on submicron particles, picoplankton make up at most 26.4% (mean = 6.4%) of salp gut carbon and are relatively unimportant to the energetics of most salps in this region compared to nanoplankton such as small dinoflagellates and diatoms.