bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repression of lysosomal transcription factors Tfeb and Tfe3 is essential for the migration and function of microglia
Authors: Iyer Harini , Shen Kimberle , Meireles Ana M. , Talbot William S. 
Published: October 2020

AbstractAs the primary phagocytic cells of the central nervous system, microglia exquisitely regulate their lysosomal activity to facilitate brain development and homeostasis. However, mechanisms that coordinate lysosomal activity with microglia development, migration, and function remain unclear. Here we show that embryonic macrophages require the lysosomal GTPase RagA and the GTPase-activating protein Folliculin to colonize the brain in zebrafish. We demonstrate that embryonic macrophages inrragamutants show increased expression of lysosomal genes but display significant downregulation of immune and migration-related genes. Furthermore, we find that RagA and Folliculin repress the key lysosomal transcription factor Tfeb, and its homologs Tfe3a and Tfe3b, in the macrophage lineage. Using RNA-Sequencing, we establish that Tfeb and Tfe3 are required for activation of lysosomal target genes under conditions of stress but not for basal expression of lysosomal pathways. Collectively, our data define a lysosomal regulatory circuit essential for macrophage development and function in vivo.TeaserThe degradation machinery of the cell must be carefully controlled for the normal formation and function of key immune cells called microglia.
Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditiselegans
Authors: Charar Chayki , Metsuyanim-Cohen Sally , Gruenbaum Yosef , Bar Daniel Z 
Published: October 2020

AbstractAnimals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation oflmn-1, the singleCaenorhabditis eleganslamin gene, increased animal size and fat content, specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream to RAPTOR and S6K, key component and target of mTOR complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation oflmn-1restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.
Counterfactual Hypothesis Testing of Tumor Microenvironment Scenarios Through Semantic Image Synthesis
Authors: Li Daniel , Chen Jennifer , Ma Qiang , Xie Yubin , Liu Andrew , Cheung Justin , Gudjonson Herman , Nawy Tal , Pe’er Dana , Pe’er Itsik 
Published: October 2020

AbstractRecent multiplexed protein imaging technologies characterize cells, their spatial organization, and interactions within microenvironments at an unprecedented resolution. Although observational data can reveal spatial associations, it does not allow users to infer salient biological relationships and cellular interactions. To address this challenge, we develop a generative model that allows users to test hypotheses about the effect of cell-cell interactions on protein expression through in silico perturbation. Our Cell-Cell Interaction GAN (CCIGAN) model employs a generative adversarial network (GAN) architecture to generate high fidelity synthetic multiplexed images from semantic cell segmentations. Our approach is unique in that it learns relationships between all imaging channels simultaneously and yields biological insights from multiple imaging technologies in silico, capturing known tumor-immune cell interactions missed by other state-of-the-art GAN models.
Multiple Holins Contribute to Extracellular DNA Release inPseudomonas aeruginosaBiofilms
Authors: Hynen Amelia L. , Lazenby James J. , Savva George M. , McCaughey Laura C. , Turnbull Lynne , Nolan Laura M. , Whitchurch Cynthia B. 
Published: October 2020

AbstractBacterial biofilms are comprised of aggregates of cells encased within a matrix of extracellular polymeric substances (EPS). One key EPS component is extracellular DNA (eDNA), which acts as a ‘glue’, facilitating cell-cell and cell-substratum interactions. We have previously demonstrated that eDNA is produced inPseudomonas aeruginosabiofilms via explosive cell lysis. This phenomenon involves a subset of the bacterial population explosively lysing, due to peptidoglycan degradation by the endolysin Lys. Here we demonstrate that inP. aeruginosathree holins, AlpB, CidA and Hol, are involved in Lys-mediated eDNA release within both submerged (hydrated) and interstitial (actively expanding) biofilms, albeit to different extents, depending upon the type of biofilm and the stage of biofilm development. We also demonstrate that eDNA release events determine the sites at which cells begin to cluster to initiate microcolony formation during the early stages of submerged biofilm development. Furthermore, our results show that sustained release of eDNA is required for cell cluster consolidation and subsequent microcolony development in submerged biofilms. Overall, this study adds to our understanding of how eDNA release is controlled temporally and spatially withinP. aeruginosabiofilms.
GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells
Authors: Fernandez Rafael J , Gardner Zachary J G , Slovik Katherine J , Liberti Derek C , Estep Katrina N , Yang Wenli , Chen Qijun , Santini Garrett T , Perez Javier V , Root Sarah , Bhatia Ranvir , Tobias John W , Babu Apoorva , Morley Michael P , Frank David B , Morrisey Edward E , Lengner Christopher J , Johnson F. Brad 
Published: October 2020

SummaryDyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age-related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human iPSC-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Cultured DC mutant iAT2 cells accumulate shortened, uncapped telomeres and manifest defects in the growth of alveolospheres, hallmarks of senescence, and apparent defects in Wnt signaling. The GSK3 inhibitor, CHIR99021, which mimics the output of canonical Wnt signaling, enhances telomerase activity and rescues the defects. These findings support further investigation of Wnt agonists as potential therapies for DC related pathologies.
“Being on the wrong side of the digital divide”: seeking technological interventions for education in Northeast Nigeria
Authors: Martens Marianne , Hajibayova Lala , Campana Kathleen , Rinnert Gretchen Caldwell , Caniglia Joanne , Bakori Isa Garba , Kamiyama Tsukuru , Mohammed Liman Audu , Mupinga Davison M. , Oh Olivia Jeonghwa 
Published: October 2020

PurposeThis paper aims to report the initial findings of a project aiming to re-establish basic education in conflict-ravaged states in Northeastern Nigeria and to improve education providers' ability to plan and deliver basic educational services. The authors present a preliminary analysis of Nigerian teachers' access to information communication technology (ICT), their technology skills, as well associated national ICT policies.Design/methodology/approachThis case study uses results from two co-designed tools, administered using KoboToolbox to Education Managers in the first instance, and teachers in the second. The data from the tools form the basis for analysis.FindingsIn the first instance, educational managers reported a lack of access to technology, the internet and to training and professional development. In the second instance, teachers reported issues present in the classroom environment, including poor infrastructure, a lack of resources and over-crowded classrooms. Very few teachers had access to computers or to the internet.Research limitations/implicationsThe 33 educational managers represent a small sample size and may not be fully representative of the region covered. The ICT Capacity Audit tool listed Excel in two different areas – basic Excel skills and using Excel for data analysis – which could have caused confusion for participants. The data collection should be repeated, expanded and compared for consistency. For the team, changes to the proposed (SENSE) box content meant that we were not able to deliver low-tech tools, such as Boogie Boards, or high-tech tools, such as tablets, to schools.Originality/valueDespite seemingly insurmountable challenges, the research team identified low-tech tools as a feasible resource in the classroom. Existing tools, such as teachers' smartphones and use of the WhatsApp application, can be used for sharing educational resources and providing teacher training. This paper argues that Nigeria needs up-to-date national ICT policies to guide in-country efforts to develop implementation of information technology initiatives for education.
Safety plugins for risks prevention through design resourcing BIM
Authors: Rodrigues Fernanda , Antunes Flávio , Matos Raquel 
Published: October 2020

Purpose
The use of building information modelling (BIM) methodology has been increasing in the architecture, engineering, construction and operation sector, driven to a new paradigm of work with the use of three-dimensional (3D) parametric models. However, building information modelling (BIM) has been mostly used for as-built models of a building, not yet been widely used by designers during project and construction phases for occupational risks prevention and safety planning. This paper aims to show the capacity of developing tools that allow adding functionalities to Revit software to improve safety procedures and reduce the time spent on modelling them during the design phase.

Design/methodology/approach
To reach this objective, a structural 3D model of a building is used to validate the developed tools. A plugin prototype based on legal regulations was developed, allowing qualitative safety assessment through the application of job hazard analysis (JHA), SafeObject and checklists. These tools allow the automated detection of falls from height situations and the automated placement of the correspondent safety systems.

Findings
Revit application programming interface allowed the conception and addition of several functionalities that can be used in BIM methodology, and more specifically in the prevention of occupational risks in construction, contributing this paper to the application of a new approach to the prevention through design.

Originality/value
This paper is innovative and important because the developed plugins allowed: automated detection of potential falls from heights in the design stage; automated introduction of safety objects from a BIM Safety Objects Library; and the intercommunication between a BIM model and a safety database, bringing JHA integration directly on the project. The prototype of this work was validated for fall from height hazards but can be extended to other potentials hazards since the initial design stage.
Residents’ perception towards tourism impacts in Kashmir
Authors: Charag Asif Hamid , Fazili Asif Iqbal , Bashir Irfan 
Published: October 2020

PurposeThe purpose of this study is to understand the residents’ perception towards environmental, social, cultural and economic impacts of tourism development in Kashmir.Design/methodology/approachThe research instrument containing 27 items pertaining to six variables is adopted from the literature. A mix-method survey approach is used to solicit residents’ perceptions regarding environmental, social, cultural and economic impacts of the current level of tourism development. A total of 326 useful responses were subjected to descriptive statistics, analysis of variance (ANOVA) and post hoc analysis using SPSS (Version 22.0).FindingsIn general, the negative and positive impacts of tourism development are well perceived by the residents. The results indicate that the residents display positive perception regarding economic impacts, however, social and environmental impacts are negatively perceived. Furthermore, barring level of education, the study found no significant difference in the residents’ perception towards tourism impacts (environmental, social, cultural, economic, quality of life and cost of living).Research limitations/implicationsThe paper identifies perceived impacts and issues of tourism development thereby, proposing possible mitigating measures. Also, the study identifies the need to develop a comprehensive policy framework addressing the issues related to the resident’s negative feelings towards tourism impacts. Further, the study envisages the need for engaging residents in developing a progressive and participatory planning process for future tourism activities in the area.Social implicationsThe study offers critical social implications for city tourism development. It suggests a community-based approach should be adopted to sensitize residents about the positive benefits of tourism.Originality/valueThe study is a novel attempt concerning residents’ residents perceptual differences towards tourism impacts. Furthermore, this study investigated socio-cultural impacts of tourism under two separate categories for better understanding. in doing so, this study provides finer understanding of perception of residents towards tourism impacts in Indian context. The findings of the study will prove critical for different stakeholders in developing future tourism framework and policies in the region.
Sensitivity about inventory leanness
Authors: Chakrabarty Subrata , Wang Liang (Lucas) 
Published: October 2020

PurposeThis study aims to suggest that firms and stock market investors are more sensitive about inventory leanness when industry information technology (IT) usage is high. First, when industry IT usage is high, a firm's inventory leanness is more responsive to information inputs (cash holding and sales efficiency). Second, when industry IT usage is high, the price-to-earnings ratio (indicative of stock market investors' willingness to pay a premium) is more sensitive to the firm's inventory leanness.Design/methodology/approachThis study highlights the contextual role of industry IT usage during the 1998–2009 lost decade (wherein the steepest falls in manufacturing jobs happened in the USA).FindingsThe results highlight the significant contextual role of industry IT usage. In manufacturing industry sectors with high IT usage, (1) inventory levels of firms are more responsive to information inputs and (2) stock market investors have greater appreciation for inventory leanness.Originality/valueThe lost decade, 1998–2009, was a difficult period for the manufacturing industry. Nonetheless, there was variation in stock market valuations of manufacturing firms, with many firms outperforming others. Stock market investors were sensitive to inventory leanness. Firms that positively impressed stock market investors were strategically positioned in high IT usage industry sectors and prioritized inventory leanness. Further, their inventories were sensitive to information inputs – their inventories were leaner in response to improved sales-efficiency and/or shortage in cash.
Managing expectations with emotional accountability: making City Hospitals accountable during the COVID-19 pandemic in Turkey
Authors: Demirag Istemi , Fırtın Cemil Eren , Tekin Bilbil Ebru 
Published: October 2020

PurposeThis paper explores the role of the COVID-19 pandemic in the financial and parliamentary accountability mechanisms of public-private partnership (PPP) “City Hospitals” in Turkey. Diverse and changing accountability mechanisms are explored regarding budgetary, affordability and emotions during the COVID-19 pandemic.Design/methodology/approachThis is a case study of City Hospitals in Turkey. Empirical data are collected and analyzed qualitatively from publicly available government and related sources, Turkish National Audit reports (Sayistay), strategic healthcare investment plans, relevant laws, decrees and NGO reports and news articles.FindingsExisting accountability mechanisms for arranging and/or delivering value-for-money (VfM) in Turkish PPP hospitals are weak. This provided policy makers with more flexibility to manage expectations of its citizens in dealing with COVID-19 pandemic. Political decision makers, through PPPs, created political capital for themselves by engaging in emotional accountability at the expense of better financial and parliamentary accountability.Originality/valueThis article contributes to the literature by articulating how roles of accountability change in crisis and introduces the concept of emotional accountability during a period of heavy infrastructure investments in City Hospitals in Turkey.
Understanding managerial ambidexterity: a people–situation interaction approach
Authors: Wang Ruifang , Gibbons Patrick 
Published: October 2020

PurposeIt is increasingly recognised that managers play a central role in organisational ambidexterity. While some scholars have recently begun to explain the nature and antecedents of ambidextrous behaviour among managers, much remains to be learned about the micro-foundations of this behaviour. Adopting a people–situation interaction approach, this paper investigates the antecedents to managerial ambidexterity from both situational and individual difference considerations.Design/methodology/approachThis study adopts a quantitative approach using a combination of survey and archival data from 305 managers.FindingsThe results indicate that learning goal orientation is positively related with managerial ambidexterity, whereas there is no significant relationship between functional experience breadth and managerial ambidexterity. In testing moderation effects, discretionary slack is found to positively moderate the association between learning goal orientation and ambidexterity and between functional experiences and ambidexterity.Practical implicationsThis paper provides suggestions on employees selection and training, along with organisational support, in enacting managerial ambidexterity.Originality/valueGuided by individual difference theory, this paper adds value to one’s understanding of the antecedents to managerial ambidexterity. It contributes to the ambidexterity literature from the micro-foundation perspective.
Capability development in startup and mature enterprises
Authors: Ma Hongjia , Lang Chunting , Sun Qing , Singh Deeksha 
Published: October 2020

PurposeThe purpose of this study is to review the literature of enterprise capability, which comprises the three dimensions of operational, dynamic and improvisational capabilities, and analyze their differences. Through this review, the authors aim to enrich the enterprise capability theory and provide some directions for entrepreneurial practice in the face of volatility, uncertainty, complexity and ambiguity (VUCA).Design/methodology/approachThe study is based on a systematic review of the literature on enterprise capability as it relates to entrepreneurial firms, following the content analysis approach as described in Gaur and Kumar (2018).FindingsThe authors’ conceptual model compares the capability levels of startups and mature enterprises and presents a model for the dynamic evolution of the capability levels of enterprises. In doing so, this study enriches the enterprise capability theory and lays the theoretical foundation for the follow-up empirical research. The authors also provide guidance for entrepreneurial practice in the face of VUCA.Originality/valueIn recent years, scholars have begun to explore the issue of enterprise capability in the field of entrepreneurship. However, because of different research perspectives, one lacks clarity on the concept and dimensions of enterprise capability. The capability theory is relatively weak in guiding the practice of enterprises; enterprises lack effective response strategies in a changing environment, and the failure rate of startups is high. This study aims to develop a deeper understanding of enterprise capability.
The role of network structural properties in supply chain sustainability: a systematic literature review and agenda for future research
Authors: Alinaghian Leila , Qiu Jilin , Razmdoost Kamran 
Published: October 2020

Purpose
The purpose of this paper is to systematically review and assess the current status of research on supply chain sustainability from a network structural perspective and provide an organising framework for future scholarship in this area.

Design/methodology/approach
By adopting an evidence-based approach, this study conducts a systematic review of 73 articles from 18 peer-reviewed journals published between 2000 and 2020.

Findings
Adopting a social network analysis approach, the review identifies specific node-level (i.e. degree centrality, closeness centrality and betweenness centrality) and network-level (i.e. network density, network sub-groups and network diversity) structural properties that play a role in supply chain sustainability. The results reveal that structural properties determine the extent of perception of sustainability risks, the diffusion of sustainability targets, introduction of sustainable innovations, development of sustainability capabilities, adoption of sustainability initiatives and the monitoring of sustainability performance throughout the supply chain.

Originality/value
By distinguishing between supply network and sustainable supply network types, this study extends the existing understandings of the role of network connectivity patterns in supply chain sustainability through synthesising and evaluating the extant literature. This study further clarifies the role of these network structural properties in supply chain sustainability by describing their impact on a set of sustainable supply chain management practices through which firms achieve sustainability goals across their supply chains.
Theorising health professionals’ prevention and management practices with children and young people experiencing self‐harm: a qualitative hospital‐based case study
Authors: MacDonald Sarah , Sampson Catherine , Biddle Lucy , Kwak Sung Yeon , Scourfield Jonathan , Evans Rhiannon 
Published: October 2020

AbstractSelf‐harm in young people remains a significant concern. Studies of emergency departments have centred on negative professional attitudes. There has been limited interrogation and theorisation of what drives such attitudes, and the contexts that sustain them. Adopting a complex systems lens, this study aimed to explore how systems shape professional and patient interactions. It draws upon interviews with healthcare and affiliated professionals (n = 14) in a UK case study hospital, with primary focus on the emergency department. Data were analysed using a thematic approach and the principles of grounded theory. Four themes emerged, with the first three centralising how professionals’ practices operate within: (1) a framework of risk management; (2) expectations of progressing patients through the care pathway; and (3) a culture of specialist expertise, with resulting uncertainty about who is responsible for self‐harm. The fourth theme considers barriers to system change. A small number of participants described efforts to enact positive modifications to practices, but these were frustrated by entrenched system structures. The potential detrimental impacts for patient care and professional wellbeing are considered. Future practice needs systemic action to support professionals in treating patients experiencing self‐harm, while future research requires more ethnographic explorations of the complex system in situ.