bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Assessment of Somatic Copy Number Variation Calling Using Next-Generation Sequencing Data
Authors: Chen Yun-Ching , Seifuddin Fayaz , Nguyen Cu , Yang Zhaowei , Chen Wanqiu , Yan Chunhua , Chen Qingrong , Wang Charles , Xiao Wenming , Pirooznia Mehdi , Meerzaman Daoud ,   The Somatic Mutation Working Group of the SEQC-II Consortium
Published: February 2021

AbstractCopy number variation (CNV) is a common type of mutation that often drives cancer progression. With advances in next-generation sequencing (NGS), CNVs can be detected in a detailed manner via newly developed computational tools but quality of such CNV calls has not been carefully evaluated. We analyzed CNV calls reported by 6 cutting-edge callers for 91 samples which were derived from the same cancer cell line, prepared and sequenced by varying the following factors: type of tissue sample (Fresh vs. Formalin Fixed Paraffin Embedded (FFPE)), library DNA amount, tumor purity, sequencing platform (Whole-Genome Sequencing (WGS) versus Whole-Exome Sequencing (WES)), and sequencing coverage. We found that callers greatly determined the pattern of CNV calls. Calling quality was drastically impaired by low purity (<50%) and became variable when WES, FFPE, and medium purity (50%-75%) were applied. Effects of low DNA amount and low coverage were relatively minor. Our analysis demonstrates the limitation of benchmarking somatic CNV callers when the real ground truth is not available. Our comprehensive analysis has further characterized each caller with respect to confounding factors and examined the consistency of CNV calls, thereby providing guidelines for conducting somatic CNV analysis.
Face-to-face interventions to encourage enrolment in cardiac rehabilitation; a scoping review protocol
Authors: Rasmussen Birgit , Håkonsen Sasja Jul , Toft Bente Skovsby 
Published: February 2021

ABSTRACTIntroductionCardiac rehabilitation has become an integral part of secondary treatment of cardiovascular heart disease. Despite evidence demonstrating that cardiac rehabilitation improves prognoses, reduces disease progression, and helps patients to find a new foothold in life, many patients do not enrol. Face-to-face interventions can encourage patients to enrol, however, it is unclear which strategies have been developed, how they are structured in a hospital context, and whether they target the life-world of the patients. The objective of this scoping review is to map and evaluate the nature and characteristics of studies that have reported on face-to-face interventions to encourage patients to enrol in cardiac rehabilitation.Methods and analysisThis review will be guided by the Joanna Briggs Institute Methodology for Scoping Reviews. A search strategy developed in cooperation with a research secretary will be applied in six databases including studies published from 2000 in English, Danish, Norwegian, Swedish, and German with no restriction on publication type or study design. Studies involving adult patients with ischemic heart disease or heart failure will be included. Studies providing the intervention after enrolment in cardiac rehabilitation will be excluded. Study selection will be performed independently by two reviewers. Data will be extracted by two reviewers using predefined data charting forms. The presentation of data will be a narrative summary of the characteristics and key findings to facilitate the integration of diverse evidence, and as we deem appropriate will be supported by a diagrammatic or tabular presentation.Ethics and disseminationThis scoping review will use data from existing publications and does not require ethical approval. Results will be reported through publication in a scientific journal and presented on relevant conferences and disseminated as part of future workshops with professionals involved in communication with patients about enrolment in cardiac rehabilitation.ARTICLE SUMMARYStrength and Limitations of this studyThis protocol outlines a rigorous design that includes the use of an established scoping review methodology and a search strategy developed in cooperation with a research librarianThe search strategy has no restrictions to study design, includes five different languages, and will cover six different databasesAs this review is inclusive to all study types and aims to provide an overview of the landscape of interventions to encourage enrolment in cardiac rehabilitation a quality assessment will not be performedWhile the review will be non-discriminant towards article study types and methodologies, a limitation of the study is that books and grey literature will not be included
The Antiviral Enzyme, Viperin, Activates Protein Ubiquitination by the E3 Ubiquitin Ligase, TRAF6
Authors: Patel Ayesha M. , Marsh E. Neil G. 
Published: February 2021

ABSTRACTViperin is a broadly conserved radical SAM enzyme that synthesizes the antiviral nucleotide ddhCTP. In higher animals viperin expression also accelerates the degradation of various cellular and viral proteins necessary for viral replication; however, the details of this process remain largely unknown. Here we show that viperin activates a component of the protein ubiquitination machinery, which plays an important role in both protein degradation and immune signaling pathways. We demonstrate that viperin binds the E3 ubiquitin ligase, TRAF6, which catalyzes K63-linked ubiquitination associated with immune signaling pathways. Viperin activates ubiquitin transfer by TRAF6 ~2.5-fold and causes a significant increase in polyubiquitinated forms of TRAF6 that are important for mediating signal transduction. Our observations both imply a role for viperin as an agonist of immune signaling and suggest that viperin may activate other K48-linked E3-ligases involved in targeting proteins for proteasomal degradation.
Environmental control of Pub1 (NEDD4 family E3 ligase) inS. pombeis regulated by TORC2 and Gsk3
Authors: Wang Tingting , Woodman Philip , Humphrey Sean J. , Petersen Janni 
Published: February 2021

AbstractCells respond to changing nutrient environments by adjusting the abundance of surface nutrient transporters and receptors. This can be achieved by modulating ubiquitin-dependent endocytosis, which in part is regulated by the NEDD4 family of E3 ligases. Here we report novel regulation of Pub1, a fission yeastSchizosaccharomyces pombemember of the NEDD4-family of E3 ligases. We show that nitrogen stress inhibits Pub1 function, thereby increasing the abundance of the amino acid transporter Aat1 at the plasma membrane and enhancing sensitivity to the toxic arginine analogue canavanine. We show that TOR complex 2 (TORC2) signalling negatively regulates Pub1, thus TORC2 mutants under nutrient stress have decreased Aat1 at the plasma membrane and are resistant to canavanine. Inhibition of TORC2 signalling increases Pub1 phosphorylation, and this is dependent on Gsk3 activity. Addition of the Tor inhibitor Torin1 increases phosphorylation of Pub1 at serine 199 (S199) by 2.5-fold, and Pub1 protein levels in S199A phospho-ablated mutants are reduced. S199 is conserved in NEDD4 and is located immediately upstream of a WW domain required for protein interaction. Together, we describe how the major TORC2 nutrient-sensing signalling network regulates environmental control of Pub1 to modulate the abundance of nutrient transporters.
GAT-FD: An Integrated MATLAB Toolbox for Graph Theoretical Analysis of Task-Related Functional Dynamics
Authors: Cao Meng , Wu Ziyan , Li Xiaobo 
Published: February 2021

ABSTRACTFunctional connectivity (FC) has been demonstrated to be varying over time during sensory and cognitive processes. Quantitative examinations of such variations can significantly advance our understanding on large-scale functional organizations and their topological dynamics that support normal brain functional connectome and can be altered in individuals with brain disorders. However, toolboxes that integrate the complete functions for analyzing task-related brain FC, functional network topological properties, and their dynamics, are still lacking. The current study has developed a MATLAB toolbox, the Graph Theoretical Analysis of Task-Related Functional Dynamics (GAT-FD), which consists of four modules for sliding-window analyses, temporal mask generation, estimations of network properties and dynamics, and result display, respectively. All the involved functions have been tested and validated using fMRI data collected from human subjects when performing a block-designed task. The results demonstrated that the GAT-FD allows for effective and quantitative evaluations of the functional network properties and their dynamics during the task period. As an open-source and user-friendly package, the GAT-FD and its detailed user manual are freely available athttps://www.nitrc.org/projects/gat_fdandhttps://centers.njit.edu/cnnl/gat_fd/.
De novo homology assessment from landmark data: A workflow to identify and track segmented structures in plant time series images
Authors: Hodge John G. , Li Qing , Doust Andrew N. 
Published: February 2021

AbstractAssessing the phenotypes underlying plant growth and development is integral to exploring the development, genetics, and evolution of morphology and plays an essential role in agronomic and basic research studies. Although various automated or semi-automated phenomic approaches have recently been developed, tools assessing differential growth of plant organs remains a key topic of interest, but one which is often difficult to analyze due to the requirements of segmenting and annotating specific structures or positions in the plant body in time-series data. To address this gap, we have developed a generalized workflow linking our previously published function,acute, with a companion function,homology, in the PlantCV environment. Thehomologyfunction uses a generalized strategy of dimensionality reduction viastarscapefollowed by hierarchical clustering throughconstellato identify ‘constellations’ of segments in eigenspace that represent the same landmark in consecutive images of a time-series. We devised a quality control function,constellaQC, that can test the accuracy of the clustering approach, and we use it to show that the approach accurately clustered the pseudo-landmarks derived fromacute, although with several sources of error. We discuss the reasons for and consequences of these errors in automated workflows, and suggest how to develop these functions so that they can easily be repurposed for other phenomics datasets that may vary in dimensional complexity.
Comparative Perturbation-Based Modeling of the SARS-CoV-2 Spike Protein Binding with Host Receptor and Neutralizing Antibodies : Structurally Adaptable Allosteric Communication Hotspots Define Spike Sites Targeted by Global Circulating Mutations
Authors: Verkhivker Gennady M. , Agajanian Steve , Oztas Deniz Yazar , Gupta Grace 
Published: February 2021

AbstractIn this study, we used an integrative computational approach focused on comparative perturbation-based modeling to examine molecular mechanisms and determine functional signatures underlying role of functional residues in the SARS-CoV-2 spike protein that are targeted by novel mutational variants and antibody-escaping mutations. Atomistic simulations and functional dynamics analysis are combined with alanine scanning and mutational sensitivity profiling for the SARS-CoV-2 spike protein complexes with the ACE2 host receptor are REGN-COV2 antibody cocktail (REG10987+REG10933). Using alanine scanning and mutational sensitivity analysis, we have shown that K417, E484 and N501 residues correspond to key interacting centers with a significant degree of structural and energetic plasticity that allow mutants in these positions to afford the improved binding affinity with ACE2. Through perturbation-based network modeling and community analysis of the SARS-CoV-2 spike protein complexes with ACE2 we demonstrate that E406, N439, K417 and N501 residues serve as effector centers of allosteric interactions and anchor major inter-molecular communities that mediate long-range communication in the complexes. The results provide support to a model according to which mutational variants and antibody-escaping mutations constrained by the requirements for host receptor binding and preservation of stability may preferentially select structurally plastic and energetically adaptable allosteric centers to differentially modulate collective motions and allosteric interactions in the complexes with the ACE2 enzyme and REGN-COV2 antibody combination. This study suggests that SARS-CoV-2 spike protein may function as a versatile and functionally adaptable allosteric machine that exploits plasticity of allosteric regulatory centers to fine-tune response to antibody binding without compromising activity of the spike protein.
Nano Pom-poms Prepared Highly Specific Extracellular Vesicles Expand the Detectable Cancer Biomarkers
Authors: He Nan , Thippabhotla Sirisha , Zhong Cuncong , Greenberg Zachary , Xu Liang , Pessetto Ziyan , Godwin Andrew K. , Zeng Yong , He Mei 
Published: February 2021

AbstractExtracellular vesicles (EVs), particularly exosomes, are emerging biomarker sources. However, due to heterogeneous populations secreted from diverse cell types, mapping EV multi-omic molecular information specifically to their pathogenesis origin for cancer biomarker identification is still extraordinary challenging. Herein, we introduced a novel 3D-structured nanographene immunomagnetic particles (NanoPoms) with unique flower pom-poms morphology and photo-click chemistry for specific marker-defined capture and release of intact small EVs. This specific EV isolation approach leads to the expanded identification of targetable cancer biomarkers with enhanced specificity and sensitivity, as demonstrated by multi-omic EV analysis of bladder cancer patient tissue fluids using the next generation sequencing of somatic DNA mutations, miRNAs, and the global proteome. The NanoPoms prepared sEVs also exhibit distinctive in vivo biodistribution patterns, highlighting the highly viable and integral quality. The developed method is simple and straightforward, and is applicable to nearly all types of biological fluids and amenable for scale up and high-throughput EV isolation.
Cardiac Atrial Compartmentalisation Proteomics: A Modified Density Gradient Method to Analyse Endo-lysosomal Proteins
Authors: Ayagama Thamali , Bose Samuel J , Capel Rebecca A , Priestman David A , Berridge Georgina , Fisher Roman , Galione Antony , Platt Frances M , Kramer Holger , Burton Rebecca A B 
Published: February 2021

SummaryThe importance of lysosomes in cardiac physiology and pathology are well established, and evidence for roles in calcium signalling are emerging. We describe a label-free proteomics method suitable for small cardiac tissue biopsies based on density-separated fractionation, which allows study of endo-lysosomal (EL) proteins.Density gradient fractions corresponding to tissue lysate; sarcoplasmic reticulum (SR), mitochondria (Mito) (1.3 g/ml); and EL with negligible contamination from SR or Mito (1.04 g/ml), were analysed using Western Blot, enzyme activity assay and LC-MS/MS analysis (adapted discontinuous Percoll, and sucrose differential density gradient).Kyoto Encyclopedia of Genes and Genomes, Reactome, Panther and Gene Ontology pathway analysis showed good coverage of RAB proteins and lysosomal cathepsins (including cardiac-specific cathepsin D) in the purified EL fraction. Significant EL proteins recovered included catalytic activity proteins. We thus present a comprehensive protocol and dataset of guinea-pig atrial EL organelle proteomics using techniques also applicable for non-cardiac tissue.
EPIGENETIC MODULATION VIA THE C-TERMINAL TAIL OF H2A.Z
Authors: Imre László , Nánási Péter , Benhamza Ibtissem , Enyedi Kata Nóra , Mocsár Gábor , Bosire Rosevalentine , Hegedüs Éva , Niaki Erfaneh Firouzi , Csóti Ágota , Darula Zsuzsanna , Csősz Éva , Póliska Szilárd , Scholtz Beáta , Mező Gábor , Bacsó Zsolt , Timmers H. T. Marc , Kusakabe Masayuki , Balázs Margit , Vámosi György , Ausio Juan , Cheung Peter , Tóth Katalin , Tremethick David , Harata Masahiko , Szabó Gábor 
Published: February 2021

ABSTRACTH2A.Z-nucleosomes are present in both euchromatin and heterochromatin and it has proven difficult to interpret their disparate roles in the context of their stability features. Using anin situassay of nucleosome stability and DT40 cells expressing engineered forms of the histone variant we show that native H2A.Z, but not C-terminally truncated H2A.Z (H2A.ZΔC), is released from nucleosomes of peripheral heterochromatin at unusually high salt concentrations. H2A.Z and H3K9me3 landscapes are reorganized in H2A.ZΔC-nuclei and overall sensitivity of chromatin to nucleases is increased. These tail-dependent differences are recapitulated upon treatment of HeLa nuclei with the H2A.Z-tail-peptide (C9), with MNase sensitivity being increased at specific regions including promoters. Introduced into live cells C9 elicits down-regulation of ∼560 genes with nonrandom chromosomal band-localization and pathway-spectrum. Thus, tail-dependent heterogeneity of H2A.Z-nucleosomes is revealed at all organization levels of chromatin and epigenetic modulation can be achieved by targeting molecular interactions involving its C-terminal tail.
Cooperative language learning elements to enhance social skills in English classrooms: a case study
Authors: Camacho-Minuche Gina , Espinoza-Celi Verónica , Ulehlova Eva 
Published: February 2021

PurposeThe aim was to prove the efficacy of the five cooperative learning elements applied in English classrooms and to demonstrate how effective they were to develop social skills in students.Design/methodology/approachThe qualitative approach allowed to analyse the data in order to determine the benefits of using these elements which help students to create a good rapport among them and do more productive activities to retain the knowledge. The instruments were Cooperative Learning Activity Planning Template that included 20 major steps in designing and assessing a cooperative learning activity designed by Susan Johnston. Additionally, rubrics that included the cooperative learning elements: face-to-face (promotive) interaction, positive interdependence, individual accountability, group processing and collaborative skills were necessary to assess students' accomplished tasks.FindingsFurthermore, when students played different roles, they attained their goal and did cooperative tasks more productively. All mentioned above enables Ecuadorian educational institutions to include better teaching methods and provokes consciousness of students' accomplishment towards their goals.Research limitations/implicationsIn the beginning, some constraints were presented; students did not have a clear idea about the main difference between group work and cooperative work. However, once they were aware of cooperative learning elements, they did incorporate them appropriately in each assigned activity which allowed them to obtain better results. Another limitation referred to master students who did not always provide learners with constant monitoring when they were working on cooperative activities; they simply believed that strong students could help the rest in the group if there was any inconvenience with the task, taking this situation for granted.Originality/valueThe originality of this study is reflected in the results obtained in the final product students presented since they used the elements in a more effective way to build social skills and achieve higher grades.
Are top executives important for earning management and firm risk? Empirical evidence from selected Chinese firms
Authors: Bhatti Khurram Iftikhar , Husnain Muhammad Iftikhar Ul , Saeed Abubakr , Naz Iram , Hashmi Syed Danial 
Published: February 2021

PurposeThis study examines the role of the observable and unobservable characteristics of top management on earning management and firm risk in China.Design/methodology/approachThe authors used manager-firm matched panel for 104 non-financial firms listed on the Shanghai Stock Exchange between 2010 and 2018. The authors also trace the persistence of managerial financial styles and their active role across two different firms between which managers switched during the sample period.FindingsThe results show that managers' financial styles indeed influence earning management and firm risk and that this influence differs across different managers. These findings are robust when tested for the persistence and active role of managers. Furthermore, individual characteristics such as age, gender, qualification and experience influence managers' financial styles.Practical implicationsGiven their findings, the authors propose that financial analysts and potential investors should not only depend on quantitative data but also consider the individual characteristics of managers when evaluating firms.Social implicationsThe findings of this study carry serious implications for managers, policymakers and potential investors. The findings assist the external auditors in measuring the risk of material misstatement, the various regulatory bodies to assess the quality of financial reporting and the users of financial statements to evaluate the earnings and make further investment decisions considering not only the quantitative data but also the individual characteristics of top managers.Originality/valueThe current study examines the observable and unobservable characteristics of top management on firm risk and earnings management in Chinese context.
Predicting consumers' digital piracy behaviour: does past experience matter?
Authors: Koay Kian Yeik , Tjiptono Fandy , Sandhu Manjit Singh 
Published: February 2021

PurposeDespite increasing anti-piracy legislation, digital piracy remains widespread and presents a huge barrier to the growth of creative industries globally. Hence, this study aims to examine predictors of digital piracy through the lens of an extended version of the theory of planned behaviour (TPB). Furthermore, the authors also examine the moderating effects of past experience (non-experienced versus experienced) on the relationships between the common four TPB dimensions on intention to engage in digital piracy.Design/methodology/approachUsing a survey method, the authors collected 832 student respondents in Semarang, Indonesia. Partial least squares structural equation modelling (PLS-SEM) was performed to analyse the proposed hypotheses.FindingsThe results showed that the influence of attitude, subjective norm and moral obligation on intention is significantly different between experienced and non-experienced consumers. The positive influence of attitude on intention to engage in digital piracy is stronger for non-experienced than experienced consumers. The influence of subjective norm on intention is significant and positive for non-experienced consumers but is not significant for experienced consumers. The influence of moral obligation on intention is significant and positive for non-experienced consumers but turns negative and significant for experienced consumers.Originality/valueThis research contributed to the body of knowledge by investigating the role of past experience as a moderator in the TPB model which renders the authors to have a better understanding of the differences in the thinking process between experienced and non-experienced consumers.