bluuebunny/crossref_metadata_2025_split huggingface dataset:
IPEV: Identification of Prokaryotic and Eukaryotic Virus-derived sequences in virome using deep learning
Authors: Yin Hengchuang , Wu Shufang , Tan Jie , Guo Qian , Li Mo , Jiang Xiaoqing , Zhu Huaiqiu 
Published: May 2023

AbstractBackgroundThe virome obtained through virus-like particle enrichment contain a mixture of prokaryotic and eukaryotic virus-derived fragments. Accurate identification and classification of these elements are crucial for understanding their roles and functions in microbial communities. However, the rapid mutation rates of viral genomes pose challenges in developing high-performance tools for classification, potentially limiting downstream analyses.FindingsWe present IPEV, a novel method that combines trinucleotide pair relative distance and frequency with a 2D convolutional neural network for distinguishing prokaryotic and eukaryotic viruses in viromes. Cross-validation assessments of IPEV demonstrate its state-of-the-art precision, significantly improving the F1-score by approximately 22% on an independent test set compared to existing methods when query viruses share less than 30% sequence similarity with known viruses. Furthermore, IPEV outperforms other methods in terms of accuracy on most real virome samples when using sequence alignments as annotations. Notably, IPEV reduces runtime by 50 times compared to existing methods under the same computing configuration. We utilized IPEV to reanalyze longitudinal samples and found that the gut virome exhibits a higher degree of temporal stability than previously observed in persistent personal viromes, providing novel insights into the resilience of the gut virome in individuals.ConclusionsIPEV is a high-performance, user-friendly tool that assists biologists in identifying and classifying prokaryotic and eukaryotic viruses within viromes. The tool is available athttps://github.com/basehc/IPEV.
Large differences in collateral blood vessel abundance among individuals arise from multiple genetic variants
Authors: Faber James E , Zhang Hua , Xenakis James G , Bell Timothy A , Hock Pablo , de Villena Fernando Pardo-Manuel , Ferris Martin T , Rzechorzek Wojciech 
Published: May 2023

AbstractCollateral blood flow varies greatly among humans for reasons that remain unclear, resulting in significant differences in ischemic tissue damage. A similarly large variation has also been found in mice that is caused by genetic background-dependent differences in the extent of collateral formation, termed collaterogenesis—a unique angiogenic process that occurs during development and determines collateral number and diameter in the adult. Previous studies have identified several quantitative trait loci (QTL) linked to this variation. However, understanding has been hampered by the use of closely related inbred strains that do not model the wide genetic variation present in the “outbred” human population. The Collaborative Cross (CC) multiparent mouse genetic reference panel was developed to address this limitation. Herein we measured the number and average diameter of cerebral collaterals in 60 CC strains, their 8 founder strains, 8 F1 crosses of CC strains selected for abundant versus sparse collaterals, and 2 intercross populations created from the latter. Collateral number evidenced 47-fold variation among the 60 CC strains, with 14% having poor, 25% poor-to-intermediate, 47% intermediate-to-good, and 13% good collateral abundance, that was associated with large differences in post-stroke infarct volume. Genome-wide mapping demonstrated that collateral abundance is a highly polymorphic trait. Subsequent analysis identified: 6 novel QTL circumscribing 28 high-priority candidate genes harboring putative loss-of-function polymorphisms (SNPs) associated with low collateral number; 335 predicted-deleterious SNPs present in their human orthologs; and 32 genes associated with vascular development but lacking protein coding variants. This study provides a comprehensive set of candidate genes for future investigations aimed at identifying signaling proteins within the collaterogenesis pathway whose variants potentially underlie genetic-dependent collateral insufficiency in brain and other tissues.
PXPermute: Unveiling staining importance in multichannel fluorescence microscopy
Authors: Boushehri Sayedali Shetab , Kornivetc Aleksandra , Waibel Domink J. E. , Kazeminia Salome , Schmich Fabian , Marr Carsten 
Published: May 2023

AbstractImaging Flow Cytometry (IFC) enables rapid acquisition of thousands of single-cell images per second, capturing information from multiple fluorescent channels. However, the conventional process of staining cells with fluorescently labeled conjugated antibodies for IFC analysis is labor-intensive, costly, and potentially detrimental to cell viability. To streamline experimental workflows and reduce expenses, it is imperative to identify the most relevant channels for downstream analysis. In this study, we present PXPermute, a user-friendly and powerful method that assesses the significance of IFC channels for a given task, such as cell profiling. Our approach evaluates channel importance by permuting pixel values within each channel and analyzing the resulting impact on the performance of machine learning or deep learning models. Through rigorous evaluation on three multi-channel IFC image datasets, we demonstrate the superiority of PXPermute in accurately identifying the most informative channels, aligning with established biological knowledge. To facilitate systematic investigations of channel importance and aid biologists in optimizing their experimental designs, we have released PXPermute as an easy-to-use open-source Python package.
Mechanisms underlying the therapeutic effects of Semen Cuscutae in treating Recurrent Spontaneous Abortion based on Network Pharmacology and Molecular Docking
Authors: Zheng Wenfei , Lei Manshu , Yao Yao , Zhan Jingqiong , Zhang Yiming , Huang Feng 
Published: May 2023

AbstractBackgroundThis paper aims to analyze the active components of SC by network pharmacology and screen the most stable compounds with TNF-a by molecular docking, to explore the mechanism of SC treatment of RSA and provide theoretical basis for drug development.MethodsActive compounds ofSCand the potential inflammatory targets of RSA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database and GeneCard, respectively. The interaction network of RSA–SC-target gene was accomplished and Visualizing by STRING database and Cytoscape software.GO and KEGG pathway enrichment analyses were obtained from DAVID to further explore the RSA mechanism and therapeutic effects ofSC. Interactions between TNF-α and active compounds were analyzed by molecular docking.Results10 active ingredients and 128 target genes were screened fromSC, and 79 of them intersected with RSA target inflammatory genes,which were considered to be potential therapeutic targets. Network pharmacological analysis showed that Sesamin, matrine, matrol and other SC active components had good correlation with the inflammatory target genes of RSA.Related genes include PGR, PTGS1, PTGS2, TGFB1 and CHRNA7. Multiple signaling pathways are involved in RSA pathogenesis,sunh as TNF-α signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway, proteoglycans in cancer, FoxO signaling pathway, etc. Molecular docking results suggested that sesamin was the most appropriate natural TNFis.ConclusionOur findings provide an important role and basis for further research on the molecular mechanism of SC treatment of RSA and drug development of TNFis.
Enhanced late blight resistance by engineering an EpiC2B-insensitive immune protease
Authors: Schuster Mariana , Eisele Sophie , Armas-Egas Liz , Kessenbrock Till , Kourelis Jiorgos , Kaiser Markus , van der Hoorn Renier A. L. 
Published: May 2023

AbstractCrop protection strategies relying on the improvement of the natural plant immune system via genetic engineering are sustainable solutions against the pathogen thread on food security. Here we describe a novel way to improve the plant immune system by immune protease engineering. As proof of concept, we increased resistance against the late blight pathogenPhytopththora infestansby rendering the tomato secreted immune protease Pip1 insensitive to theP. infestans-secreted inhibitor Epic2B. This concept can be applied to secreted immune proteases in crops by precision breeding.
BCL6 is a context-dependent mediator of the glioblastoma response to irradiation therapy
Authors: Tribe Anna K.W. , Peng Lifeng , Teesdale-Spittle Paul H. , McConnell Melanie J. 
Published: May 2023

AbstractGlioblastoma is a rapidly fatal brain cancer with no cure. The resistance of glioblastoma tumours to available therapies means that more effective treatments are desperately needed. Previous research showed that the transcriptional repressor protein BCL6 is upregulated by chemo– and radiotherapy in glioblastoma and that inhibition of BCL6 enhances the effectiveness of these therapies. Therefore, BCL6 is a promising target to improve the efficacy of available treatments for glioblastoma. BCL6 is known as a transcriptional repressor in germinal centre B cells and is an oncogene in lymphoma, as well as in other cancers. However, previous research indicated that BCL6 induced by chemotherapy or irradiation in glioblastoma may not act as a transcriptional repressor. This study aimed to clarify the role of BCL6 in the response of glioblastoma to irradiation. The effect of BCL6 inhibition on the whole proteome response of glioblastoma cells to fractionated and acute irradiation treatment was investigated. Acute irradiation appeared to cause BCL6 to switch from a repressor of the DNA damage response to a promoter of stress response signalling. Rapid immunoprecipitation mass spectrometry of endogenous proteins enabled identification of proteins associated with BCL6 in untreated and irradiated glioblastoma cells. BCL6 associated with transcriptional coregulators in untreated glioblastoma and its association with the corepressor NCOR2 was validated using proximity ligation assays. However, the association of BCL6 with transcriptional regulatory proteins was lost in response to acute irradiation. This was accompanied by the irradiation-induced association of BCL6 with synaptic and plasma membrane proteins. Overall, these results reveal that the activity of BCL6 in glioblastoma therapy responses is context-dependent and may be mediated by the intensity of cellular stress.
Red blood cell-derived extracellular vesicles with miR-204 mimic loading for pediatric neuroblastoma treatment
Authors: Chiangjong Wararat , Panachan Jirawan , Keadsanti Sujitra , Newburg David S. , Morrow Ardythe L. , Hongeng Suradej , Chutipongtanate Somchai 
Published: May 2023

AbstractNeuroblastoma (NB) is the most common extracranial solid tumor in pediatric population with a high degree of heterogeneity in clinical outcomes, ranging from spontaneous remission to rapid progression and death. Upregulation of a tumor suppressor miR-204 in patient-derived neuroblastoma tumors was associated with good prognosis independent of known risk factors. While miR-204 is recognized as a therapeutic candidate, its delivery was unavailable. This study aimed to develop red blood cell-derived extracellular vesicles (RBC-EVs) as the miR-204 carrier and evaluate the inhibitory activity against neuroblastoma cell lines and spheroids. MiR-204 mimics were loaded into RBC-EVs (RBC-EVmiR-204) by electroporation with the optimized parameters of 250 V, 20 ms, 10 pulsing times. RBC-EVmiR-204, but not the native RBC-EVs, could inhibit cell viability, migration and spheroid formation and growth of MYCN-amp and MYCN non-amplification (MYCN-NA) NB cells, even though the suppressive effects were more preferable in MYCN-amp NB. For the mechanistic insight, SWATH-proteomics suggested that RBC-EVmiR-204induced dysregulation of ribosomal proteins and alterations in RNA metabolism, leading to inhibiting neuroblastoma progression. This study developed RBC-EVmiR-204as an alternative/adjunct therapy of pediatric neuroblastoma. The therapeutic efficacy of RBC-EVmiR-204should be further investigated in preclinical models and clinical studies.
Chikungunya virus glycoproteins transform macrophages into productive viral dissemination vessels
Authors: Yao Zhenlan , Ramachandran Sangeetha , Huang Serina , Jami-Alahmadi Yasaman , Wohlschlegel James A. , Li Melody M.H. 
Published: May 2023

AbstractDespite their role as innate sentinels, macrophages are cellular reservoirs for chikungunya virus (CHIKV), a highly pathogenic arthropod-borne alphavirus that has caused unprecedented epidemics worldwide. Here, we took interdisciplinary approaches to elucidate the CHIKV determinants that subvert macrophages into virion dissemination vessels. Through comparative infection using chimeric alphaviruses and evolutionary selection analyses, we discovered for the first time that CHIKV glycoproteins E2 and E1 coordinate efficient virion production in macrophages with the domains involved under positive selection. We performed proteomics on CHIKV-infected macrophages to identify cellular proteins interacting with the precursor and/or mature forms of viral glycoproteins. We uncovered two E1-binding proteins, signal peptidase complex subunit 3 (SPCS3) and eukaryotic translation initiation factor 3 (eIF3k), with novel inhibitory activities against CHIKV production. These results highlight how CHIKV E2 and E1 have been evolutionarily selected for viral dissemination likely through counteracting host restriction factors, making them attractive targets for therapeutic intervention.
Reconstitution ofC9orf72(GGGGCC) repeat-associated non-AUG translation with purified components
Authors: Ito Hayato , Machida Kodai , Ueyama Morio , Nagai Yoshitaka , Imataka Hiroaki , Taguchi Hideki 
Published: May 2023

AbstractNucleotide repeat expansion of GGGGCC (G4C2) in the non-coding region ofC9orf72is the most common genetic cause underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Transcripts harboring this repeat expansion undergo the translation of dipeptide repeats via a non-canonical process known as repeat-associated non-AUG (RAN) translation. In order to ascertain the essential components required for RAN translation, we successfully recapitulated G4C2-RAN translation using an in vitro reconstituted translation system comprising human factors, namely the human PURE system. Our findings conclusively demonstrate that the presence of fundamental translation factors is sufficient to mediate the elongation from the G4C2repeat. Additionally, we observed ribosomal frameshifting from the poly Gly-Ala dipeptide frame to other frames during the elongation process. Furthermore, the initiation mechanism proceeded in a 5’ cap-dependent manner, independent of eIF2A or eIF2D. In contrast to cell lysate-mediated RAN translation, where longer G4C2repeats enhanced translation, we discovered that the expansion of the G4C2repeats inhibited translation elongation using the human PURE system. These results suggest that the repeat RNA itself functions as a repressor of RAN translation. Taken together, our utilization of a reconstituted RAN translation system employing minimal factors represents a distinctive and potent approach for elucidating the intricacies underlying RAN translation mechanism.Significance statementEvery cellular protein undergoes synthesis through a process known as translation. While the fundamental aspects of translation have been established, recent advancements have unveiled various noncanonical translation pathways, including the translation originating from “noncoding” RNAs. Within this context, certain neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), are linked to the translation of noncoding RNAs, referred to as repeat-associated non-AUG (RAN) translation, the underlying mechanism of which remains controversial. To dissect the complicated nature of RAN translation, this study employs a reconstituted cell-free translation system comprised of human translation factors. By reconstituting RAN translation utilizing a minimal set of factors, this bottom-up approach not only facilitates the elucidation of its mechanism but also offers a distinctive avenue for pharmaceutical development.
Development of a SARS-CoV-2 monoclonal antibody panel and its applicability as a reagent in high-throughput fluorescence reduction neutralization and immunohistochemistry assays
Authors: Coelho Gabriela Mattoso , Cataneo Allan Henrique Depieri , Raboni Sonia Mara , Nogueira Meri Bordignon , Vaz de Paula Caroline Busatta , Simões Flórido Almeida Ana Clara , Rogerio Vanessa Zulkievicz , Zanchin Nilson T. , de Noronha Lucia , Zanluca Camila , Duarte dos Santos Claudia Nunes 
Published: May 2023

AbstractSince its emergence in late 2019, infection by SARS-CoV-2 (COVID-19 disease) has quickly spread worldwide, leading to a pandemic that has caused millions of deaths and huge socio-economic losses. Although vaccination against COVID-19 has significantly reduced disease mortality, it has been shown that protection wanes over time, and that circulating SARS-CoV-2 variants may escape vaccine-derived immunity. Therefore, serological studies are still necessary to assess protection in the population and better guide vaccine booster programs. A common measure of protective immunity is the presence of neutralizing antibodies (nAbs). However, the gold standard method for measuring nAbs (plaque reduction neutralization test, or PRNT) is laborious and time-consuming, limiting its large-scale applicability. In this study, we developed a high-throughput fluorescence reduction neutralization assay (FRNA) to detect SARS-CoV-2 nAbs. Because the assay relies on immunostaining, we also developed and characterized in-house monoclonal antibodies (mAbs) to lower assay costs and reduce the vulnerability of the test to reagent shortages. Using samples collected before the pandemic and from individuals vaccinated against COVID-19, we showed that the results of the FRNA we developed using commercial and in-house mAbs strongly correlated with those of the standard PRNT method while providing results in 70% less time. In addition to providing a fast, reliable, and high-throughput alternative for measuring nAbs, the FRNA can be easily customized to assess other SARS-CoV-2 variants of concern (VOCs).
Study design features increase replicability in cross-sectional and longitudinal brain-wide association studies
Authors: Kang Kaidi , Seidlitz Jakob , Bethlehem Richard A.I. , Xiong Jiangmei , Jones Megan T. , Mehta Kahini , Keller Arielle S. , Tao Ran , Randolph Anita , Larsen Bart , Tervo-Clemmens Brenden , Feczko Eric , Dominguez Oscar Miranda , Nelson Steve ,   Lifespan Brain Chart Consortium,   3R-BRAIN,   AIBL,   Alzheimer’s Disease Neuroimaging Initiative,   Alzheimer’s Disease Repository Without Borders Investigators,   CALM Team,   CCNP,   COBRE,   cVEDA,   Harvard Aging Brain Study,   IMAGEN,   POND,   The PREVENT-AD Research Group, Schildcrout Jonathan , Fair Damien , Satterthwaite Theodore D. , Alexander-Bloch Aaron , Vandekar Simon 
Published: May 2023

AbstractBrain-wide association studies (BWAS) are a fundamental tool in discovering brain-behavior associations. Several recent studies showed that thousands of study participants are required for good replicability of BWAS because the standardized effect sizes (ESs) are much smaller than the reported standardized ESs in smaller studies. Here, we perform analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional magnetic resonance imaging studies from the Lifespan Brain Chart Consortium (77,695 total scans) to demonstrate that optimizing study design is critical for increasing standardized ESs and replicability in BWAS. A meta-analysis of brain volume associations with age indicates that BWAS with larger variability in covariate have larger reported standardized ES. In addition, the longitudinal studies we examined reported systematically larger standardized ES than cross-sectional studies. Analyzing age effects on global and regional brain measures from the United Kingdom Biobank and the Alzheimer’s Disease Neuroimaging Initiative, we show that modifying longitudinal study design through sampling schemes improves the standardized ESs and replicability. Sampling schemes that improve standardized ESs and replicability include increasing between-subject age variability in the sample and adding a single additional longitudinal measurement per subject. To ensure that our results are generalizable, we further evaluate these longitudinal sampling schemes on cognitive, psychopathology, and demographic associations with structural and functional brain outcome measures in the Adolescent Brain and Cognitive Development dataset. We demonstrate that commonly used longitudinal models can, counterintuitively, reduce standardized ESs and replicability. The benefit of conducting longitudinal studies depends on the strengths of the between-versus within-subject associations of the brain and non-brain measures. Explicitly modeling between-versus within-subject effects avoids averaging the effects and allows optimizing the standardized ESs for each separately. Together, these results provide guidance for study designs that improve the replicability of BWAS.
Robotic process automation deployments: a step-by-step method to investment appraisal
Authors: Ylä-Kujala Antti , Kedziora Damian , Metso Lasse , Kärri Timo , Happonen Ari , Piotrowicz Wojciech 
Published: May 2023

PurposeRobotic process automation (RPA) has recently emerged as a technology focusing on the automation of repetitive, frequent, voluminous and rule-based tasks. Despite a few practical examples that document successful RPA deployments in organizations, evidence of its economic benefits has been mostly anecdotal. The purpose of this paper is to present a step-by-step method to RPA investment appraisal and a business case demonstrating how the steps can be applied to practice.Design/methodology/approachThe methodology relies on design science research (DSR). The step-by-step method is a design artefact that builds on the mapping of processes and modelling of the associated costs. Due to the longitudinal nature of capital investments, modelling uses discounted cashflow and present value methods. Empirical grounding characteristic to DSR is achieved by field testing the artefact.FindingsThe step-by-step method is comprised of a preparatory step, three modelling steps and a concluding step. The modelling consists of compounding the interest rate, discounting the investment costs and establishing measures for comparison. These steps were applied to seven business processes to be automated by the case company, Estate Blend. The decision to deploy RPA was found to be trivial, not only based on the initial case data, but also based on multiple sensitivity analyses that showed how resistant RPA investments are to changing circumstances.Practical implicationsBy following the provided step-by-step method, executives and managers can quantify the costs and benefits of RPA. The developed method enables any organization to directly compare investment alternatives against each other and against the probable status quo where many tasks in organizations are still carried out manually with little to no automation.Originality/valueThe paper addresses a growing new domain in the field of business process management by capitalizing on DSR and modelling-based approaches to RPA investment appraisal.