bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular signalling modulates Scar/WAVE complex activity through Abi phosphorylation
Authors: Singh Shashi Prakash , Thomason Peter A. , Insall Robert H. 
Published: October 2021

AbstractThe lamellipodia and pseudopodia of migrating cells are produced and maintained by the Scar/WAVE complex. Thus, actin-based cell migration is largely controlled through regulation of Scar/WAVE. Here we report that the Abi subunit - not Scar/WAVE – is phosphorylated in response to extracellular signalling. Like Scar, Abi is phosphorylated after the complex has been activated, implying that Abi phosphorylation modulates pseudopodia, rather than causing new ones to be made. Consistent with this, Scar/WAVE complex mutants that cannot bind Rac are also not phosphorylated. Several environmental cues also affect Abi phosphorylation - cell-substrate adhesion promotes it and increased extracellular osmolarity diminishes it. Both unphosphorylatable and phosphomimetic Abi efficiently rescue the chemotaxis of Abi KO cells and pseudopodia formation, confirming that Abi phosphorylation is not required for activation or inactivation of the Scar/WAVE complex. However, pseudopodia and Scar/WAVE patches in the cells with unphosphorylatable Abi protrude for longer, altering pseudopod dynamics and cell speed. Cells in which Scar and Abi are both unphosphorylatable can still form pseudopods, but migrate substantially faster. We conclude that extracellular signals and environmental responses modulate cell migration by tuning the behaviour of the Scar/WAVE complex after it has been activated.
Deep learning-based tumor microenvironment segmentation is predictive of tumor mutations and patient survival in non-small-cell lung cancer
Authors: Rączkowski Łukasz , Paśnik Iwona , Kukiełka Michał , Nicoś Marcin , Budzinska Magdalena A. , Kucharczyk Tomasz , Szumiło Justyna , Krawczyk Paweł , Crosetto Nicola , Szczurek Ewa 
Published: October 2021

AbstractDespite the fact that tumor microenvironment (TME) and gene mutations are the main determinants of progression of the deadliest cancer in the world – lung cancer – their interrelations are not well understood. Digital pathology data provide a unique insight into the spatial composition of the TME. Various spatial metrics and machine learning approaches were proposed for prediction of either patient survival or gene mutations from these data. Still, these approaches are limited in the scope of analyzed features and in their explainability and as such fail to transfer to clinical practice. Here, we generated 23,199 image patches from 55 hematoxylin-and-eosin (H&E)-stained lung cancer tissue sections and annotated them into 9 different tissue classes. Using this dataset, we trained a deep neural network ARA-CNN, achieving per-class AUC ranging from 0.72 to 0.99. We applied the trained network to segment 467 lung cancer H&E images downloaded from The Cancer Genome Atlas (TCGA) database. We used the segmented images to compute human interpretable features reflecting the heterogeneous composition of the TME, and successfully utilized them to predict patient survival (c-index 0.723) and cancer gene mutations (largest AUC 73.5% for PDGFRB). Our approach can be generalized to different cancer types to inform precision medicine strategies.
Can single-component protein condensates form multiphase architectures?
Authors: Garaizar Adiran , Espinosa Jorge R. , Joseph Jerelle A. , Krainer Georg , Shen Yi , Knowles Tuomas P.J. , Collepardo-Guevara Rosana 
Published: October 2021

AbstractPhase-separated biomolecular condensates that contain multiple coexisting phases are widespread in vitro and in cells. Multiphase condensates emerge readily within multi-component mixtures of biomolecules (e.g. proteins and nucleic acids) when the different components present sufficient physicochemical diversity (e.g. in inter-molecular forces, structure, and chemical composition) to sustain separate coexisting phases. Because such diversity is highly coupled to the solution conditions (e.g. temperature, pH, salt, composition), it can manifest itself immediately from the nucleation and growth stages of condensate formation, develop spontaneously due to external stimuli, or progressively as the condensates age. Here, we investigate thermodynamic factors that can explain the intrinsic transformation of single-component condensates into multiphase architectures during the nonequilibrium process of ageing. We develop a multiscale model that integrates atomistic simulations of proteins, sequence-dependent coarse-grained simulations of condensates, and a minimal model of dynamically ageing condensates with non-conservative inter-molecular forces. Our nonequilibrium simulations of condensate ageing predict that single-component condensates that are initially homogeneous and liquid-like can transform into gel-core/liquid-shell or liquid-core/gel-shell multiphase condensates as they age, due to gradual and irreversible enhancement of inter-protein interactions. The type of multiphase architecture is determined by the ageing mechanism, the molecular organization of the gel and liquid phases, and the chemical make up of the protein. Notably, we predict that inter-protein disorder-to-order transitions within the prion-like domains of intracellular proteins could lead to the required non-conservative enhancement of inter-molecular interactions. Our study, therefore, predicts a potential mechanismSignificance StatementBiomolecular condensates are highly diverse systems spanning not only homogeneous liquid droplets, but also gels, glasses, and even multiphase architectures that contain various coexisting liquid-like and/or gel-like inner phases. Multiphase architectures form when the different biomolecular components in a multi-component condensate establish sufficiently imbalanced inter-molecular forces to sustain different coexisting phases. While such a requirement seems, at first glance, impossible to fulfil for a condensate formed exclusively of chemically-identical proteins (i.e., single-component), our simulations predict conditions under which this may be possible. During condensate ageing, a sufficiently large imbalance in inter-molecular interactions can emerge intrinsically from the accumulation of protein structural transitions—driving even single-component condensates into nonequilibrium liquid-core/gel-shell or gel-core/liquid-shell multiphase architectures.
SBMate: A Framework for Evaluating Quality of Annotations in Systems Biology Models
Authors: Shin Woosub , Hellerstein Joseph L. , Munarko Yuda , Neal Maxwell L. , Nickerson David P. , Rampadarath Anand K. , Sauro Herbert M. , Gennari John H. 
Published: October 2021

AbstractThe interests in repurposing and reusing systems biology models have been growing in recent years. Semantic annotations play an important role for this, as they provide crucial information on the meanings and functions of models. However, there are a limited number of tools that evaluate the existence or quality of such annotations. In this paper, we introduce SBMate, a python package that would serve as a framework for evaluating the quality of annotations in systems biology models. Three default metrics are provided: coverage, consistency, and specificity. Coverage checks whether annotations exist in a model. Consistency tests if the annotations are appropriate for the given model element. Finally, specificity represents how detailed the annotations are. We analyzed 1,000 curated models from the BioModels repository using the three metrics and discussed the results. Additional metrics can be easily added to extend the current version of SBMate.
Threshold Selection for Brain Connectomes
Authors: Theis Nicholas , Rubin Jonathan , Cape Joshua , Iyengar Satish , Prasad Konasale M. 
Published: October 2021

AbstractIntroductionStructural and functional brain connectomes built using macroscale data collected through magnetic resonance imaging (MRI) may contain noise that contributes to false-positive edges, which can obscure structure-function relationships with implications for data interpretation. Thresholding procedures are routinely applied in practice to optimize network density by removing low-signal edges, but there is limited consensus regarding the appropriate selection of thresholds. We compare existing methods and propose a novel alternative objective function thresholding (OFT) method.MethodsThe performance of thresholding approaches, including a percolation-based approach and an objective function-based approach, is assessed by (a) computing the normalized mutual information (NMI) of community structure between a known network and a simulated, perturbed networks to which various forms of thresholding have been applied, and (b) comparing the density and the clustering coefficient (CC) between the baseline and thresholded networks.ResultsIn our analysis, the proposed objective function-based threshold exhibits the best performance in terms of high similarity between the underlying networks and their perturbed, thresholded counterparts, as quantified by NMI and CC analysis on the simulated functional networks.DiscussionExisting network thresholding methods yield widely different results when graph metrics are computed. Thresholding based on the objective function appears to maintain a set of edges such that the resulting network shares the community structure and clustering features present in the original network. This outcome provides proof-of-principle evidence that thresholding based on the objective function could offer a useful approach to reducing the network density of functional connectivity data.Impact StatementNetwork thresholding refers to removing edges between node pairs in a functional network that have weak edge-weights that may arise from unwanted variability or noise. Since edge-weight cutoffs used to generate a binary network can be sensitive to thresholding, we introduce a novel thresholding algorithm. We find that when applied to networks derived via perturbations, namely through simulated functional connectivity of a known network, this approach yields a binary network that is more similar to the known network compared to using existing thresholding approaches. Thus, our algorithm is a competitive candidate for use in thresholding of brain connectome.
Annotation of Putative Circadian Rhythm-Associated Genes in Diaphorina citri (Hemiptera : Liviidae)
Authors: Reynolds Max , de Oliveira Lucas , Vosburg Chad , Paris Thomson , Massimino Crissy , Norus Jordan , Ortiz Yasmin , Espino Michelle , Davis Nina , Masse Ron , Neiman Alan , Holcomb Rachel , Gervais Kylie , Kemp Melissa , Hoang Maria , Shippy Teresa D. , Hosmani Prashant S. , Flores-Gonzalez Mirella , Mueller Lukas A. , Hunter Wayne B. , Benoit Joshua B. , Brown Susan J. , D’Elia Tom , Saha Surya 
Published: October 2021

AbstractThe circadian rhythm is a process involving multiple genes that generates an internal molecular clock, allowing organisms to anticipate environmental conditions produced by the earth’s rotation on its axis. This report presents the results of the manual curation of twenty-seven genes likely associated with circadian rhythm in the genome of Diaphorina citri, the Asian citrus psyllid. This insect acts as the vector of the bacterial pathogen Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening disease (Huanglongbing). This disease is the most severe detriment to citrus industries and has drastically decreased crop yields worldwide. Based on the genes identified in the psyllid genome, namely cry1 and cry2, D. citri likely possesses a circadian model similar to that of the lepidopteran butterfly, Danaus plexippus. Manual annotation of these genes will allow future molecular therapeutics to be developed that can disrupt the psyllid biology.
Endoglin deficiency elicits hypoxia-driven congestive heart failure in zebrafish
Authors: Lelièvre Etienne , Bureau Charlotte , Bordat Yann , Frétaud Maxence , Langevin Christelle , Jopling Chris , Kissa Karima 
Published: October 2021

AbstractHereditary hemorrhagic Telangiectasia (HHT) is a rare genetic disease relying on mutations affecting components of Bone Morphogenetic Protein and Transforming Growth Factor-β (BMP/TGF-β) signaling pathway in endothelial cells. This disorder is characterized by arterio-venous malformations prone to rupture. and ensuing hemorrhages are responsible for iron deficiency anemia. Along with Activin receptor-like kinase ALK1, Endoglin is involved in the vast majority of HHT cases. In this report, we characterized zebrafish endoglin locus and demonstrated that it produces two phylogenetically conserved protein isoforms using a distinctive alternative splicing mechanism. Functional analysis of a Crispr/Cas9 zebrafish Endoglin mutant revealed that Endoglin deficiency results in massive death during the course from juvenile stage to adulthood. Endoglin deficient fish develop a cardiomegaly resulting in heart failure and hypochromic anemia which both stem from chronic hypoxia. Histological analysis and confocal imaging evidenced structural alterations of the developing gill and its underlying vascular network that tally with hypoxia. Finally, phenylhydrazine treatment demonstrated that lowering hematocrit/blood viscosity alleviates heart failure and enhances survival of Endoglin deficient fish. Altogether, our data indicate that Endoglin is crucial for gill vascular development and that further studies using zebrafish in general and this endoglin mutant in particular will provide crucial hints regarding the molecular and cellular events altered in HHT for the development of new therapeutic strategies.Summary StatementEndoglin deficiency in zebrafish recapitulates critical aspects of Hereditary Hemorrhagic Telangiectasia (HHT) and will thus constitute a valuable model in large scale screens for HHT-active drugs.
Neural mechanisms underlying anxiety-related deficits of attentional inhibition: direct ERP evidence from the Pd component
Authors: Liping Hu , Zhang Huikang , Hongsi Tang , Shen Lin , Wu Rui , Yan Huang 
Published: October 2021

AbstractBehavioral evidence shows that anxious individuals tend to be distracted by irrelevant stimulation not only for threat-related stimuli but also for non-emotional neutral stimuli. These findings suggest that anxious individuals may have a general impairment of attentional control, especially inhibition function. However, the neural mechanism underlying the anxiety-related impairment in attentional control is unclear. Here, in a visual search task with geometric stimuli, we examined attentional processing of the non-emotional neutral distractor on participants with different levels of anxiety, using the event-related-potential (ERP) indices of attentional selection (N2 posterior contralateral [N2pc]) and top-down inhibition (distractor positivity [Pd]). We found that distractor-evoked Pd amplitudes were negatively correlated with trait-anxiety scores, i.e., the higher the level of anxiety, the worse the ability of attentional inhibition. In contrast, the amplitudes of distractor-evoked N2pc did not vary with anxiety levels, suggesting that trait-anxiety level does not affect stimulus-driven attentional capture. We also observed attentional processing of target stimuli and found that the peak latency of target-evoked N2pc was delayed as anxiety levels rise, suggesting that anxiety impairs the efficiency of top-down attentional selection of the target. The present study provides direct neurophysiological evidence for general anxiety-related impairment of attentional control.
Development of risk factors taxonomy in ramp operations for corporate sustainability
Authors: Yazgan Ebru , Durmaz Vildan , Yilmaz Ayse Kucuk 
Published: October 2021

Purpose
This research has the potential to contribute to the understanding of the sustainable ground handling operations framework. Ramp operations as the main system of ground handling include critical services for aircraft/airlines. The purpose of this study is to identify the risk factors in ramp operations for all related stakeholders’ awareness to enhance flight safety. Classifying risk factors, the four main performance fields under risk taxonomy is determined. Thus, managers may allocate resources effectively to handle related threats for corporate sustainability.

Design/methodology/approach
New taxonomy with human performance value indicators, which sources from the environment is developed. New developed taxonomy is entitled as “environmental value approach,” which represents environmental value-based approach. The developed new risk factors taxonomy is divided into groups such as ramp personnel, organizational, sustainability-based risk factors: triple view and ergonomics obtained from an extensive literature review and experts’ opinions in the field of human performance.

Findings
The findings of this research show that managers need a risk management-oriented approach to manage the human factor affecting performance and sustainability. The newly developed taxonomy offers not only identifying the sources of unsafe operational risk factors but also using as a decision-support tool to manage risks for achieving their sustainability goals. When managerial decisions are made according to risk taxonomy and managing these risks, then corporate performance and individual performance may improve.

Originality/value
The new taxonomy presents the performance-based management of the human factor with a holistic and systematic risk management-based approach. There is no risk taxonomy study designed considering ramp operations and sustainability-based human factor performance.
“Actions speak louder than words”: an impact of service recovery antecedents on customer delight in quick-service restaurants
Authors: Agnihotri Durgesh , Kulshreshtha Kushagra , Tripathi Vikas , Chaturvedi Pallavi 
Published: October 2021

PurposeThe purpose of this study is to conceptualize and analyze a framework that provides greater understanding toward the impact of service recovery antecedents such as role clarity, customer service orientation, employee empowerment and employee relational behavior on customer satisfaction and customer delight in the context of quick-service restaurants (QSRs).Design/methodology/approachA self-administered questionnaire was distributed to 408 participants who had experienced service recovery efforts by leading QSRs on social media. The current paper draws upon the prevailing literature to test a series of research hypotheses through structural equation modeling.FindingsThe findings of the study have confirmed that antecedents of service recovery are good to describe customer satisfaction and customer delight in the setting of QSRs. Besides, the study provides an understanding on how monetary compensation moderates the relationship between customer delight and customer satisfaction.Practical implicationsThis study carries an understanding on how frontline employees must operate in a non-conventional and innovative way to resolve customers' issues and show commitment with truthfulness to provide excellent services to make customers feel delightful.Originality/valueThis is a unique study to understand the role of service recovery antecedents to describe customer satisfaction and customer delight in the social media environment. In addition, the results support the possibilities of implementing prompt service recovery efforts using social media.
Impact of audit committee characteristics and external audit quality on firm performance: evidence from India
Authors: Al-ahdal Waleed M. , Hashim Hafiza Aishah 
Published: October 2021

Purpose
The purpose of this paper is to analyse the influence of audit committee characteristics and external audit quality on the performance of non-financial public limited companies listed on the National Stock Exchange 100.

Design/methodology/approach
One-way random effect panel data regression was applied to 74 non-financial firms in the Nifty 100 from 2014 until 2019. The overall audit committee index and external audit index were built based on the new Indian Companies Act, 2013 and on a review of the literature to capture the impact of the new Act on firm financial performance.

Findings
The outcome of the study revealed that there is lack of evidence to show that audit committee characteristics improve the performance of top Indian non-financial listed firms. However, external audit quality was found to have a significant positive impact on the financial performance of firms as measured by Tobin’s Q, while firm size and leverage were found to have a significant impact on the financial performance of firms as measured by return on assets and return on equity.

Practical implications
This paper will be greatly beneficial for financial practitioners and policymakers because it provides practical suggestions and recommendations about the types of external audit that are indispensable for the overall effectiveness and performance of firms. The study findings may also aid strategic policy formulation and execution for better corporate governance practices for the purpose of profit and wealth maximisation.

Originality/value
To the best of the authors’ knowledge, to date, no previous research has evaluated the effects of audit committee features and external audit quality on the financial performance of firms in India after the implementation of the new Companies Act, 2013. Hence, this study fills this void in the present literature by examining the overall features of the audit committee and external audit and their impact on firm performance in the setting of India.
Sustainable relevancy in the changing library job market in Kuwait
Authors: Buarki Hanadi Jumah , Alomar Mashael , Abdulhadi Munirah 
Published: October 2021

PurposeThe Library and Information Science (LIS) discipline face challenges such as technology applications and information overload in its effort to remain relevant in the challenging job market. This study aims to determine the skills and knowledge needed for LIS professionals in the job market to rethink the current syllabus and offer better future employability.Design/methodology/approachThe research used a survey method to collect data concerning personal information, LIS employment opportunities, job titles and skills needed. Content analysis followed to determine librarianship job listings and the need for LIS graduate jobs in Kuwait.FindingsThe findings suggested difficulties and challenges; they also compiled a comprehensive list of skills needed and recommended courses and institutions hiring LIS graduates. The research improves decision-making in syllabus development and experiences recommended by employers.Practical implicationsAcademic departments can follow this research to develop and update their syllabuses according to the requirements of the job market, thus offering better future job opportunities.Social implicationsAs LIS graduates are provided with better education, the updating of their employability skills will help them socially by recognising their employment status and economically by raising their pay.Originality/valueThe research is the first in Kuwait to collect LIS job titles and analyse employability needs.