bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring genomic data coupled with 3D chromatin structures using the WashU Epigenome Browser
Authors: Li Daofeng , Purushotham Deepak , Harrison Jessica K. , Wang Ting 
Published: January 2022

AbstractBiological functions are not only encoded by the genome’s sequence but also regulated by its three-dimensional (3D) structure. More and more studies have revealed the importance of 3D chromatin structures in development and diseases; therefore, visualizing the connections between genome sequence, epigenomic dynamics (1D) and the 3D genome becomes a pressing need. The WashU Epigenome Browser introduces a new 3D visualization module to integrate visualization of 1D (such as sequence features, epigenomic data) and 2D data (such as chromosome conformation capture data) with 3D genome structure. Genomic coordinates are encoded in 3D models of the chromosomes; thus, all genomic information displayed on a 1D genome browser can be visualized on a 3D model, supported by genome browser utilities and facilitating interpretation of genomic data. Biological information that is difficult to illustrate in 1D becomes more intuitive when displayed in 3D, providing novel and powerful tools for investigators to hypothesize and understand the connections between biological functions and 3D genome structures.
A systematic review of the factors associated with suicide attempts among sexual-minority adolescents
Authors: Wang Xavier , Gan Quan , Zhou Junwen , Cosquer Mireille , Falissard Bruno , Corruble Emmanuelle , Jousselme Catherine , Gressier Florence 
Published: January 2022

AbstractIntroductionSuicide attempt is a worldwide major public health problem, that accounts for 1.4% of all deaths worldwide Recent literature reported higher risk of suicide attempt among adolescents associated with sexual minority status but few systematic reviews focused on the risk and protective factors. For that reason, it seems necessary to examine risk and protective factors of attempted suicide in sexual minority adolescents.MethodsWe conducted a systematic review of published studies on factors associated with suicide attempts in LGBT adolescents. 4 databases up to December 2020 were searched to find relevant studies.ResultsIn addition to the factors usually found in general population (gender, ethnic minorities, childhood trauma, psychiatric symptoms, addictive behaviors), some factors have been independently associated with suicide attempt in LGBT population: early coming out, not acceptable by families, not satisfied with LGBT friendship, too few number of friends, physical abuse, sexual abuse and bullying. The protective factors of suicide attempt reported in LGBT population were feeling safety at school, teacher support, anti-bullying policy, and other adult’s support.ConclusionEffective preventive measures for suicide attempt among LGBT youth need to be developed and implemented. The impact of interventions targeting teacher responses to LGBT stigma, discussion of LGBT issues in class and reactions of family and friends to the coming out of LGBT youth should be further investigated.
Developing all-in-one virus-like particles for Cas9 mRNA/single guide RNA co-delivery and aptamer-containing lentiviral vectors for improved gene expression
Authors: Yadav Manish , Atala Anthony , Lu Baisong 
Published: January 2022

AbstractLentiviral vectors (LVs) are widely used for delivering foreign genes for long-term expression. Normal LVs contain the RNA genome, which is reverse transcribed into DNA and integrates into the host genome to mediate long-term gene expression. Recently, virus-like particles (VLPs) were developed for mRNA delivery. In these VLPs, packaging mRNA into the particles is achieved via interactions between the aptamer and aptamer-binding protein (ABP), and mRNA is not reverse transcribed or integrated. These VLPs are useful for delivering Cas9 mRNA for short-term endonuclease expression. Generating high-titer normal integrating LVs is challenging. Until recently, VLPs were not efficient for co-delivering Cas9 mRNA and single guide RNA (sgRNA). By fusing ABP to the N-terminus of HIV Gag protein, hybrid particles were developed to co-deliver Cas9 mRNA and sgRNA. But the method for modifying Gag impaired particle assembly. Previously we found that adding an ABP after the second zinc finger domain of nucleocapsid (NC) protein had minimal effects on particle assembly. Based on this observation, we developed hybrid particles to co-deliver Cas9 mRNA and sgRNA. We further improved LVs for integrated gene expression by including an aptamer sequence in lentiviral transfer plasmids, which improved lentiviral particle production and enhanced LV genomic RNA packaging. In summary, we describe development of new all-in-one VLPs for co-delivery of Cas9 mRNA and sgRNA and new LVs for enhanced vector production and gene expression.
Pathogen Detection in RNA-Seq Data with Pathonoia
Authors: Liebhoff Anna-Maria , Menden Kevin , Laschtowitz Alena , Franke Andre , Schramm Christoph , Bonn Stefan 
Published: January 2022

AbstractMotivationRecent evidence suggests that bacterial and viral infections may cause or exacerbate many human diseases. One method of choice to detect microbes in tissue is RNA sequencing. While the detection of specific microbes using RNA sequencing offers good sensitivity and specificity, untargeted approaches suffer from very high false positive rates and a lack of sensitivity for lowly abundant organisms.ResultsWe introduce Pathonoia, an algorithm that detects viruses and bacteria in RNA sequencing data with high precision and recall. Pathonoia first applies an established k-mer based method for species identification and then aggregates this evidence over all reads in a sample. In addition, we provide an easy-to-use analysis framework that highlights potential microbe-host cell interactions by correlating the microbial to host gene expression. Pathonoia outperforms competing algorithms in microbial detection specificity, both on in silico and real datasets. Lastly, we present two case studies in human liver and brain in which microbial infection might exacerbate disease.AvailabilityA Python package for Pathonoia sample analysis and a guided analysis Jupyter notebook for bulk RNAseq datasets are available on GitHub https://github.com/kepsi/Pathonoia.Contactaliebho1@jhu.edu and s.bonn@uke.deGraphical Abstract
Adipose tissue dysfunction and visceral fat are associated to hepatic insulin resistance and severity of NASH even in lean individuals
Authors: Saponaro Chiara , Sabatini Silvia , Gaggini Melania , Carli Fabrizia , Rosso Chiara , Positano Vincenzo , Armandi Angelo , Caviglia Gian Paolo , Faletti Riccardo , Bugianesi Elisabetta , Gastaldelli Amalia 
Published: January 2022

AbstractBackground & AimsNonalcoholic fatty liver disease (NAFLD) is a heterogeneous disorder, but the factors that determine this heterogeneity remain poorly understood. Adipose tissue (AT) dysfunction is causally linked to NAFLD since it causes intrahepatic triglyceride (IHTG) accumulation through increased hepatic lipid flow, due to insulin resistance (IR) and pro-inflammatory adipokines release. While many studies in NAFLD have looked at total adiposity (that is mainly subcutaneous fat, SC-AT), it is still unclear the impact of visceral fat (VF). Thus, we investigated how VF vs. SC-AT were related to NAFLD in lean, overweight, and obese individuals compared to lean controls.MethodsThirty-four non-diabetic NAFLD with liver biopsy and eight lean control individuals (CT) were enrolled in this study. We measured fat distribution (VF, SC-AT and IHTG) by magnetic resonance imaging (MRI), adiponectin concentration, free fatty acids (FFAs) and triglyceride (TAG) concentration and composition by mass spectrometry (MS), lipolysis and IR by tracer infusion.ResultsIHTG was positively associated with lipolysis, adipose tissue IR, TG concentrations, and increased ratio of saturated/unsaturated fatty acids. VF was higher in NAFLD (including lean individuals) compared to controls, was increased with fibrosis stage and was associated with IR in liver, muscle and adipose tissue, increased lipolysis, and decreased adiponectin levels. Collectively, our results suggest that VF accumulation, given its location close to the liver, is one of the major risk factors for NAFLD.ConclusionsThese findings propose VF as an early indicator of NAFLD independently of BMI, which may allow for evidence-based prevention and intervention strategies.
A GSVA based gene set synergizing with CD4+T cell bearing harmful factors yield risk signals in HBV related diseases via amalgamation of artificial intelligence
Authors: Huang Jun , Zhao Chunbei , Zhang Xinhe , Zhao Qiaohui , Zhang Yanting , Chen Liping , Dai Guifu 
Published: January 2022

AbstractGenes encoding chemokines and extracellular matrix (ECM) play pivotal roles in chronic HBV infection (CHB), HBV related fibrosis (HBV-LF) and hepatocellular carcinoma (HBV-HCC). The landscape and potential of these genes in prognosis across diseases stages have not been fully and systemically understood. In this study, we defined an HBV-LF associated gene set comprised of chemokines and ECM related genes directly induced by initial HBV infection through GSVA algorithm that named as CLST (C stands for CXCL9, CXCL10, CCL19 and CCL20; L for LUM; S for SOX9 and SPP1; T for THBS1, THBS2) and evaluated its biomarker values in CHB and HBV-LF. Enrichment scores (ES) of CLST was subsequently observed synergized with activated CD4+T cells (aCD4) highly related to T helper cell 17 (TH17) associated genes and immune checkpoints and addressed as risk signals due to bearing harmful prognosis factors in tumor tissues of patients with HBV-HCC. Dual higher enrichment score (ES) of CLST and aCD4 in HBV-HCC patients exhibited worse overall survival (OS). Feature genes specific to these two gene sets showed promising clinical relevance in early-stage of HBV-HCC definition and OS prediction incorporating laboratory parameters via artificial intelligence (AI) systems. Finally, a novel mechanistic insight into the issue was proposed that PEG IFN-α as an immunotherapy through modulating CLST signal in treatment responders and these immune signals down-regulation could be beneficial for HBV related diseases control and prevention. Together, our study provides GSVA and AI derived immunogenomic prognosis signatures and clinical utility of these signals will be benefit for HBV related diseases cure.
Behavioral and neurochemical effects of novel N-Benzyl-2-phenylethylamine derivatives in adult zebrafish
Authors: Demin Konstantin A. , Kupriyanova Olga V. , Shevyrin Vadim A. , Derzhavina Ksenia A. , Krotova Nataliya A. , Ilyin Nikita P. , Kolesnikova Tatiana O. , Galstyan David S. , Kositsyn Iurii M. , Khaybaev Abubakar-Askhab S. , Seredinskaya Maria V. , Dubrovskii Yaroslav , Sadykova Raziya G. , Nerush Maria O. , Mor Mikael S. , Petersen Elena V. , Strekalova Tatyana , Efimova Evgeniya V. , Bozhko Dmitrii V. , Myrov Vladislav O. , Kolchanova Sofia M. , Polovian Aleksander I. , Galumov Georgii K. , Kalueff Allan V. 
Published: January 2022

AbstractSerotonergic hallucinogenic drugs potently affect human brain and behavior, and have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing rodent studies, zebrafish (Danio rerio) is a powerful animal model for screening neuroactive drugs, including serotonergic agents. Here, we test ten different N-Benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the - OCH3, -OCF3, -F, -Cl and -Br substitutions in theorthoposition of phenyl ring ofN-benzyl fragment, assessing their behavioral and neurochemical effects in adult zebrafish. Overall, substitutions inN-benzyl fragment primarily affected zebrafish locomotion, and in phenethylamine moiety - anxiety-like behavior, also modulating brain serotonin and/or dopamine turnover. We also identified several behavioral clusters, including anxiogenic/hypolocomotor (24H-NBF, 24H-NBOMe and 34H-NBF), behaviorally inert (34H-NBBr, 34H-NBCl and 34H- NBOMe), anxiogenic/hallucinogenic-like (24H-NBBr, 24H-NBCl and 24H-NBOMe(F)), and anxiolytic/hallucinogenic-like (34H-NBOMe(F)) agents. The 24H-NBOMe(F) and 34H-NBOMe(F) also reduced despair-like behavior in zebrafish. The artificial intelligence-driven phenotyping supports association of multiple compounds with NMDA antagonists and/or MDMA, supporting their potential hallucinogenic-like properties, as well as other valuable psychoactive effects.In silicofunctional molecular activity modelling also supports existing of similarities between studied NBPEAs drugs, MDMA, and ketamine. Functional analysis implicates potential involvement of serotonin release stimulating activity, calcium channel (voltage-sensitive) activity, some serotonin receptors activity and variety of psychiatric and neurologic disorders treatments activities. Overall, we report potent neuroactive properties of several novel syntheticN-benzylphenylethylamines in anin vivovertebrate model system (zebrafish), raising the possibility of their potential use in clinical practice.
Phenotypic dissection of epithelial lineages and therapeutic manipulation of differentiation programs in human Adenoid Cystic Carcinomas (ACCs)
Authors: Viragova Sara , Aparicio Luis , Zhao Junfei , Valencia Salazar Luis E. , Schurer Alexandra , Dhuri Anika , Sahoo Debashis , Moskaluk Christopher A. , Rabadan Raul , Dalerba Piero 
Published: January 2022

ABSTRACTAdenoid Cystic Carcinoma (ACC) is a rare and aggressive form of salivary gland cancer, characterized by the co-existence within tumor tissues of two distinct populations of malignant cells, phenotypically similar to the myoepithelial and ductal lineages of normal salivary glands. Using a novel computational approach for single-cell RNA-seq analysis, we identified two cell-surface markers (CD49f, KIT) that enable the differential purification of myoepithelial-like (CD49fhigh/KITneg) and ductal-like (CD49flow/KIT+) cells from ACC patient derived xenografts (PDX). Using prospective xeno-transplantation experiments, we demonstrate that myoepithelial-like cells act as progenitors of ductal-like cells. Using three-dimensional (3D) organoid cultures, we demonstrate that agonists of retinoic acid (RA) signaling promote differentiation of myoepithelial-like cells into ductal-like cells, while inhibitors of RA signaling selectively kill ductal-like cells. Finally, we demonstrate that BMS493, an inverse agonist of RA signaling, can be successfully leveraged for the in vivo treatment of human ACCs.
Splicing factor BUD31 promotes ovarian cancer progression through sustaining the expression of anti-apoptotic BCL2L12
Authors: Wang Zixiang , Wang Shourong , Qin Junchao , Zhang Xiyu , Lu Gang , Liu Hongbin , Guo Haiyang , Wu Ligang , Shao Changshun , Kong Beihua , Liu Zhaojian 
Published: January 2022

SUMMARYDysregulated expression of splicing factors has important roles in cancer development and progression. However, it remains a challenge to identify the cancer-specific splicing variants. Here we demonstrated that spliceosome component BUD31 is increased in ovarian cancer, and its higher expression predicts worse prognosis. We characterized the BUD31 binding motif and found that BUD31 preferentially binds exon-intron regions near splicing sites by CLIP-seq. Further analysis revealed that BUD31 inhibition results in extensive exon skipping and decreased abundance of long CDS isoforms. In particular, we identified BCL2L12, an anti-apoptotic BCL2 family member, as a functional splicing target of BUD31. BUD31 stimulates the inclusion of exon 3 to generate full-length BCL2L12 and promotes ovarian cancer progression. Knockdown of BUD31 or splice-switching antisense oligonucleotide treatment promotes exon 3 skipping and results in a truncated isoform of BCL2L12 that undergoes nonsense-mediated mRNA decay, and the cells subsequently undergo apoptosis. Our findings reveal BUD31-regulated exon inclusion as a critical factor in ovarian cancer cell survival and progression.
MOJITOO: a fast and universal method for integration of multimodal single cell data
Authors: Cheng Mingbo , Li Zhijian , Costa Ivan G. 
Published: January 2022

ABSTRACTThe advent of multi-modal single cell sequencing techniques have shed new light on molecular mechanisms by simultaneously inspecting transcriptomes, epigenomes and proteomes of the same cell. However, to date, the existing computational approaches for integration of multimodal single cell data are either computationally expensive, require the delineation of parameters or can only be applied to particular modalities.We present a single cell multi-modal integration method, named MOJITOO (Multi-mOdal Joint IntegraTion of cOmpOnents). MOJITOO uses canonical correlation analysis for a fast and parameter free detection of a shared representation of cells from multimodal single cell data. Moreover, estimated canonical components can be used for interpretation, i.e. association of modality specific molecular features with the latent space. We evaluate MOJITOO using bi- and tri-modal single cell data sets and show that MOJITOO outperforms existing methods regarding computational requirements, preservation of original latent spaces and clustering.
Implicit adaptation is modulated by the relevance of feedback
Authors: Parvin Darius E. , Tsay Jonathan , Dang Kristy V. , Stover Alissa R. , Ivry Richard B. , Morehead J. Ryan 
Published: January 2022

ABSTRACTGiven that informative and relevant feedback in the real world is often intertwined with distracting and irrelevant feedback, we asked how the relevancy of visual feedback impacts implicit sensorimotor adaptation. To tackle this question, we presented multiple cursors as visual feedback in a center-out reaching task and varied the task relevance of these cursors. In other words, participants were instructed to hit a target with a specific task-relevant cursor, while ignoring the other cursors. In Experiment 1, we found that reach aftereffects were attenuated by the mere presence of distracting cursors, compared to reach aftereffects in response to a single task-relevant cursor. The degree of attenuation did not depend on the position of the distracting cursors. In Experiment 2, we examined the interaction between task relevance and attention. Participants were asked to adapt to a task-relevant cursor/target pair, while ignoring the task-irrelevant cursor/target pair. Critically, we jittered the location of the relevant and irrelevant target in an uncorrelated manner, allowing us to index attention via how well participants tracked the position of target. We found that participants who were better at tracking the task-relevant target/cursor pair showed greater aftereffects, and interestingly, the same correlation applied to the task-irrelevant target/cursor pair. Together, these results highlight a novel role of task relevancy on modulating implicit adaptation, perhaps by giving greater attention to informative sources of feedback, increasing the saliency of the sensory prediction error.
Ultra-flexible and Stretchable Intrafascicular Peripheral Nerve Recording Device with Axon-dimension, Cuff-less Microneedle Electrode Array
Authors: Yan Dongxiao , Jiman Ahmad A. , Bottorff Elizabeth C. , Patel Paras R. , Meli Dilara , Welle Elissa J. , Ratze David C. , Havton Leif A. , Chestek Cynthia A. , Kemp Stephen W.P. , Bruns Tim M. , Yoon Euisik , Seymour John 
Published: January 2022

AbstractPeripheral nerve mapping tools with higher spatial resolution are needed to advance systems neuroscience, and potentially provide a closed-loop biomarker in neuromodulation applications. Two critical challenges of microscale neural interfaces are (i) how to apply them to small peripheral nerves, and (ii) how to minimize chronic reactivity. We developed a flexible microneedle nerve array (MINA), which is the first high-density penetrating electrode array made with axon-sized silicon microneedles embedded in low-modulus thin silicone. We present the design, fabrication, acute recording, and chronic reactivity to an implanted MINA. Distinctive units were identified in the rat peroneal nerve. We also demonstrate a long-term, cuff-free, and suture-free fixation manner using rose bengal as a light-activated adhesive for two timepoints. The tissue response at 1-week included a sham (N=5) and MINA-implanted (N=5) group, and the response at 6-week also included a sham (N=3) and MINA-implanted (N=4) group. These conditions were quantified in the left vagus nerve of rats using histomorphometry. Micro-CT was added to visualize and quantify tissue encapsulation around the implant. MINA demonstrated a reduction in encapsulation thickness over previously quantified interfascicular methods. Future challenges include techniques for precise insertion of the microneedle electrodes and demonstrating long-term recording.
Experimental Design and Power Calculation in Omics Circadian Rhythmicity Detection
Authors: Zong Wei , Seney Marianne L. , Ketchesin Kyle D. , Gorczyca Michael T. , Liu Andrew C. , Esser Karyn A. , Tseng George C. , McClung Colleen A. , Huo Zhiguang 
Published: January 2022

AbstractCircadian clocks are 24-hour endogenous oscillators in physiological and behavioral processes. Though recent transcriptomic studies have been successful in revealing the circadian rhythmicity in gene expression, the power calculation for omics circadian analysis have not been fully explored. In this paper, we develop a statistical method, namely CircaPower, to perform power calculation for circadian pattern detection. Our theoretical framework is determined by three key factors in circadian gene detection: sample size, intrinsic effect size and sampling design. Via simulations, we systematically investigate the impact of these key factors on circadian power calculation. We not only demonstrate that CircaPower is fast and accurate, but also show its underlying cosinor model is robust against variety of violations of model assumptions. In real applications, we demonstrate the performance of CircaPower using mouse pan-tissue data and human post-mortem brain data, and illustrate how to perform circadian power calculation using mouse skeleton muscle RNA-Seq pilot as case study. Our method CircaPower has been implemented in an R package, which is made publicly available on GitHub (https://github.com/circaPower/circaPower).