bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structural dynamics of macropinosome formation and PI3-kinase-mediated sealing revealed by lattice light sheet microscopy
Authors: Quinn Shayne E. , Huang Lu , Kerkvliet Jason G. , Swanson Joel A. , Smith Steve , Hoppe Adam D. , Anderson Robert B. , Thiex Natalie W. , Scott Brandon L. 
Published: December 2020

AbstractMacropinosomes are formed by shaping actin-rich plasma membrane ruffles into large intracellular organelles in a phosphatidylinositol 3-kinase (PI3K)-coordinated manner. Here, we utilize lattice lightsheet microscopy and image visualization methods to map the three-dimensional structure and dynamics of macropinosome formation relative to PI3K activity. We show that multiple ruffling morphologies produce macropinosomes and that the majority form through collisions of adjacent PI3K-rich ruffles. By combining multiple volumetric representations of the plasma membrane structure and PI3K products, we show that PI3K activity begins early throughout the entire ruffle volume and continues to increase until peak activity concentrates at the base of the ruffle after the macropinosome closes. Additionally, areas of the plasma membrane rich in ruffling had increased PI3K activity and produced many macropinosomes of various sizes. Pharmacologic inhibition of PI3K activity had little effect on the rate and morphology of membrane ruffling, demonstrating that early production of 3’-phosphoinositides within ruffles plays a minor role in regulating their morphology. However, 3’-phosphoinositides are critical for the fusogenic activity that seals ruffles into macropinosomes. Taken together, these data indicate that local PI3K activity is amplified in ruffles and serves as a priming mechanism for closure and sealing of ruffles into macropinosomes.
Host-pathogen genetic interactions underlie tuberculosis susceptibility
Authors: Smith Clare M. , Baker Richard E. , Proulx Megan K. , Mishra Bibhuti B. , Long Jarukit E. , Park Sae Woong , Lee Ha-Na , Kiritsy Michael C. , Bellerose Michelle M. , Olive Andrew J. , Murphy Kenan C. , Papavinasasundaram Kadamba , Boehm Frederick J. , Reames Charlotte J. , Meade Rachel K. , Hampton Brea K. , Linnertz Colton L. , Shaw Ginger D. , Hock Pablo , Bell Timothy A. , Ehrt Sabine , Schnappinger Dirk , de Villena Fernando Pardo-Manuel , Ferris Martin T. , Ioerger Thomas R. , Sassetti Christopher M. 
Published: December 2020

AbstractThe outcome of an encounter withMycobacterium tuberculosisdepends on the pathogen’s ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate the heterogeneity of tuberculosis disease. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library ofMtbmutants to associate bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and produce qualitatively distinct immune states. Global analysis ofMtbmutant fitness across the CC panel revealed that many virulence pathways are only in specific host microenvironments, identifying the large fraction of the pathogen’s genome that has been maintained to ensure fitness in a diverse population. Both immunological and bacterial traits were associated with genetic variants distributed across the mouse genome, identifying the specific host-pathogen genetic interactions that influence pathogenesis.
Inhibition of lysyl oxidase-like 2 ameliorates folic acid-induced renal tubulointerstitial fibrosis
Authors: Choi Sung-Eun , Jeon Nara , Choi Hoon Young , Jeong Hyeon Joo , Lim Beom Jin 
Published: December 2020

AbstractTubulointerstitial fibrosis is characterized by accumulation of the extracellular matrix in the interstitium. Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, is known for promoting cancer metastasis, invasion, and stromal fibrosis in various organs. Our previous study demonstrated expression of LOXL2 in kidney podocytes and tubular epithelial cells, and the association between elevated LOXL2 and tubulointerstitial fibrosis. The present study evaluated the effect of LOXL2 inhibition using an inhibitory monoclonal antibody (AB0023) on tubulointerstitial fibrosis in a folic acid-induced tubulointerstitial fibrosis mouse model. We also evaluated the association of LOXL2 with epithelial-mesenchymal transformation related moleculesin vitrousing HK-2 cells. Our data demonstrate that AB0023 prevented the progression of tubulointerstitial fibrosis significantly, as determined by trichrome and picro-sirius red staining, as well as the total collagen assay. The mean expression of phosphorylated Smad2 and Smad4 was lower in the AB0023-treated group although it was not statistically significant. Following transforming growth factor-β (TGF-β) challenge, LOXL2-deficient HK-2 cells exhibited significantly lower expression of the mesenchymal markers vimentin and fibronectin than control HK-2 cells. In conclusion, LOXL2 inhibition ameliorates renal fibrosis through the TGF-β/Smad signalling pathway.
Oct1 cooperates with Smad transcription factors to promote mesodermal lineage specification
Authors: Perovanovic Jelena , Wu Yifan , Abewe Hosiana , Shen Zuolian , Hughes Erik P. , Gertz Jason , Chandrasekharan Mahesh B. , Tantin Dean 
Published: December 2020

ABSTRACTThe transition between pluripotent and tissue-specific states is a key aspect of development. Understanding the pathways driving these transitions will facilitate the engineering of properly differentiated cells for experimental and therapeutic uses. Here, we showed that during mesoderm differentiation, the transcription factor Oct1 activated developmental lineage-appropriate genes that were silent in pluripotent cells. Using mouse embryonic stem cells (ESCs) with an inducible knockout of Oct1, we showed that Oct1 deficiency resulted in poor induction of mesoderm-specific genes, leading to impaired mesodermal and terminal muscle differentiation. Oct1-deficient cells exhibited poor temporal coordination of the induction of lineage-specific genes and showed inappropriate developmental lineage branching, resulting in poorly differentiated cell states retaining epithelial characteristics. In ESCs, Oct1 localized with the pluripotency factor Oct4 at mesoderm-associated genes and remained bound to those loci during differentiation after the dissociation of Oct4. Binding events for Oct1 overlapped with those for the histone lysine demethylase Utx, and an interaction between Oct1 and Utx suggested that these two proteins cooperate to activate gene expression. The specificity of the ubiquitous Oct1 for the induction of mesodermal genes could be partially explained by the frequent coexistence of Smad and Oct binding sites at mesoderm-specific genes and the cooperative stimulation of mesodermal gene transcription by Oct1 and Smad3. Together, these results identify Oct1 as a key mediator of mesoderm lineage–specific gene induction.
Non-homologous end joining factors XLF, PAXX and DNA-PKcs support neural stem and progenitor cells development
Authors: Gago-Fuentes Raquel , Oksenych Valentyn 
Published: December 2020

AbstractNon-homologous end-joining (NHEJ) is a major DNA repair pathway in mammalian cells that recognizes, processes and fixes DNA damages throughout the cell cycle, and is specifically important for homeostasis of post-mitotic neurons and developing lymphocytes. Neuronal apoptosis increases in the mice lacking core NHEJ factors Ku70 and Ku80. Inactivation of other core NHEJ genes, either Xrcc4 or Lig4, leads to massive neuronal apoptosis in the central nervous system (CNS) that correlates with embryonic lethality in mice. Inactivation of one accessory NHEJ gene,e.g. Paxx, Mri and Dna-pkcs, results in normal CNS development due to compensatory effects of Xlf. Combined inactivation of Xlf/Paxx, Xlf/Mri and Xlf/Dna-pkcs, however, results in late embryonic lethality and high levels of apoptosis in CNS. To determine the impact of accessory NHEJ on early stages of neurodevelopment, we isolated neural stem and progenitors cells from mouse embryos and investigated proliferation, self-renewal and differentiation capacity of these cells lacking either Xlf,Paxx, Dna-pkcs, Xlf/Paxx or Xlf/Dna-pkcs. We found that accessory NHEJ factors are important for maintaining the neural stem and progenitor cell populations and neurodevelopment in mammals, which is particularly evident in the double knockout models.
Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first six months of the COVID-19 pandemic
Authors: Lubin Joseph H. , Zardecki Christine , Dolan Elliott M. , Lu Changpeng , Shen Zhuofan , Dutta Shuchismita , Westbrook John D. , Hudson Brian P. , Goodsell David S. , Williams Jonathan K. , Voigt Maria , Sarma Vidur , Xie Lingjun , Venkatachalam Thejasvi , Arnold Steven , Alvarado Luz Helena Alfaro , Catalfano Kevin , Khan Aaliyah , McCarthy Erika , Staggers Sophia , Tinsley Brea , Trudeau Alan , Singh Jitendra , Whitmore Lindsey , Zheng Helen , Benedek Matthew , Currier Jenna , Dresel Mark , Duvvuru Ashish , Dyszel Britney , Fingar Emily , Hennen Elizabeth M. , Kirsch Michael , Khan Ali A. , Labrie-Cleary Charlotte , Laporte Stephanie , Lenkeit Evan , Martin Kailey , Orellana Marilyn , de la Campa Melanie Ortiz-Alvarez , Paredes Isaac , Wheeler Baleigh , Rupert Allison , Sam Andrew , See Katherine , Zapata Santiago Soto , Craig Paul A. , Hall Bonnie L. , Jiang Jennifer , Koeppe Julia R. , Mills Stephen A. , Pikaart Michael J. , Roberts Rebecca , Bromberg Yana , Hoyer J. Steen , Duffy Siobain , Tischfield Jay , Ruiz Francesc X. , Arnold Eddy , Baum Jean , Sandberg Jesse , Brannigan Grace , Khare Sagar D. , Burley Stephen K. 
Published: December 2020

AbstractThree-dimensional structures of SARS-CoV-2 and other coronaviral proteins archived in the Protein Data Bank were used to analyze viral proteome evolution during the first six months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48,000 viral proteome sequences showed how each one of the 29 viral study proteins have undergone amino acid changes. Structural models computed for every unique sequence variant revealed that most substitutions map to protein surfaces and boundary layers with a minority affecting hydrophobic cores. Conservative changes were observed more frequently in coresversusboundary layers/surfaces. Active sites and protein-protein interfaces showed modest numbers of substitutions. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for six drug discovery targets and four structural proteins comprising the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and functional interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.
Mapping the human auditory cortex using spectrotemporal receptive fields generated with magnetoencephalography
Authors: Falet Jean-Pierre R. , Côté Jonathan , Tarka Veronica , Martinez-Moreno Zaida-Escila , Voss Patrice , de Villers-Sidani Etienne 
Published: December 2020

AbstractWe present a novel method to map the functional organization of the human auditory cortex noninvasively using magnetoencephalography (MEG). More specifically, this method estimates via reverse correlation the spectrotemporal receptive fields (STRF) in response to a dense pure tone stimulus, from which important spectrotemporal characteristics of neuronal processing can be extracted and mapped back onto the cortex surface. We show that several neuronal populations can be found examining the spectrotemporal characteristics of their STRFs, and demonstrate how these can be used to generate tonotopic gradient maps. In doing so, we show that the spatial resolution of MEG is sufficient to reliably extract important information about the spatial organization of the auditory cortex, while enabling the analysis of complex temporal dynamics of auditory processing such as best temporal modulation rate and response latency given its excellent temporal resolution. Furthermore, because spectrotemporally dense auditory stimuli can be used with MEG, the time required to acquire the necessary data to generate tonotopic maps is significantly less for MEG than for other neuroimaging tools that acquire BOLD-like signals.
Influence of fast-food restaurant service quality and its dimensions on customer perceived value, satisfaction and behavioural intentions
Authors: Slack Neale J. , Singh Gurmeet , Ali Jazbeen , Lata Reshma , Mudaliar Karishma , Swamy Yogita 
Published: December 2020

PurposeThe purpose of this study is to investigate the effect of fast-food restaurant service quality (compound effect of food quality, physical environment quality and employee service quality) and its dimensions (when acting independently) on customer perceived value, satisfaction and behavioural intentions.Design/methodology/approachData was collected from 400 fast-food restaurant customers in Fiji using a public-intercept survey. The study used descriptive and inferential analysis. This research also used backward elimination multiple regressions to test the hypotheses of this study.FindingsThe compound effect of fast-food restaurant service quality dimensions on customer perceived value revealed food quality and physical environment quality are significant determinants of customer perceived value, however employee service quality is not. In contrast, the effect of the fast-food service quality dimensions acting independently on customer perceived value revealed the three dimensions are significant determinants of customer perceived value. Results also confirmed that customer perceived value is a significant determinant of customer satisfaction and customer satisfaction is a significant determinant of behavioural intentions.Research limitations/implicationsThis study highlights to fast-food restaurateurs and marketers the importance of determining the compound effect of fast-food restaurant service quality dimensions, delivering the right combination of fast-food restaurant service quality dimensions to customers and not singling out dimensions in an attempt to enhance restaurant service quality.Originality/valueThis study makes important contributions towards understanding the compound effect of fast-food restaurant service quality dimensions and the independent effect of these dimensions on the formation of customer perceived value, customer satisfaction and behavioural intentions.
Exploring types, drivers and outcomes of social e-HRM
Authors: Martini Mattia , Cavenago Dario , Marafioti Elisabetta 
Published: December 2020

PurposeThis paper explores the use of social media (SM) in Human Resource Management (HRM). Building on the configurational approach, the study investigates the existence of different configurations of social e-HRM, their consequences for the organizations and their predictors.Design/methodology/approachThis empirical study draws on a survey administered to HR directors of 176 companies operating in Italy. Two-step cluster analysis, test for variance and logistic regressions were employed for data analysis.FindingsThree social e-HRM configurations emerged – non-use, relational use and extended relational use – which distinguish different goals for using SM in HRM. The three configurations lead to similar outcomes for organizations, even if SM users, in general, enjoy greater success than non-users. Certain structural, strategic and HRM factors are systematically and variously associated with each configuration.Research limitations/implicationsThe study is based on cross-sectional research, and thus it is difficult to identify causal links between the variables. The study also relies on data collected in a specific national context, which limits the generalizability of the results.Practical implicationsThe study suggests that different and equally effective social e-HRM configurations exist and that their presence is predicted by specific structural, strategic and HRM factors.Originality/valueThe study contributes to an emerging and still scarce literature on types, drivers and outcomes of SM use in HRM.
Effects of managers' environmental attitudes on waste management practices in small hotels in Accra
Authors: Mensah Ishmael , Ampofo Emmanuel Twumasi 
Published: December 2020

PurposeDrawing on the upper echelons theory, the study examines the effects of environmental attitudes of hotel managers on the waste management practices of small hotels in the context of a developing country.Design/methodology/approachA survey involving 246 managers of small hotels in the Accra Metropolitan Area was undertaken using a questionnaire that was based on the Waste Management Hierarchy and the revised New Ecological Paradigm (NEP) scales.FindingsResults of the study showed that environmental attitudes of managers significantly influence the waste management practices of hotels, specifically, the anti-anthropocentricism, anti-exceptionalism, eco-crisis and balance-of-nature dimensions of the NEP scale. The study also found that all the environmental attitude dimensions had more significant effects on the waste disposal option because usually in developing countries, small hotels by their nature are more predisposed to undertaking this option.Research limitations/implicationsFuture studies should use longitudinal data to make causal inferences and consider the use of a rigorous statistical test such as common latent factor analysis.Practical implicationsWaste management problems in small hotels require softer sustainability strategies geared towards creating environmental awareness and inculcating the right environmental values in hotel managers in order to change the way managers view the environment.Originality/valueResults of the study indicate that in the context of small hotels in developing countries, managers with eco-centric attitudes are more likely to engage in less expensive waste management practices rather than the most environmentally-friendly options.
A design science-based case study of retail chain delivery operations and its implications
Authors: Su Shong-lee Ivan , Fan Xuemei , Shou Yongyi 
Published: December 2020

PurposeThe study aims to explore and develop a smart route planning system for the cross-docking delivery operations of a large supermarket chain using an action research (AR) approach and assessing through a design science research (DSR) lens.Design/methodology/approachThis study took a problem-solving AR (PAR) approach toward the delivery operational issue of the case firm. The research process has accorded with the solution incubation and the refinement phases defined by a DSR framework. An intervention-based research framework for DSR is developed to assess the validity of this study as a DSR research and derive mid-range theories.FindingsDramatic operational and financial improvements were achieved for the case firm. Significant and unintended environmental and social benefits were also found. A design proposition (DP) and several mid-range theories are proposed as an extension of AR research to DSR research.Research limitations/implicationsA problem-solving DSR research can be better assessed by the intervention-based DSR framework developed in this study. DSR studies should be encouraged for both practical and theoretical advancement purposes.Practical implicationsA challenging business problem-solving study can be tackled effectively through an industry/academic collaboration taking a PAR approach to deliver substantial values and organization transformational results.Social implicationsDrivers and store associates are safer with smart delivery operations in the case firm.Originality/valueThere are still limited PAR design science case studies in the supply chain/logistics research literature. The research experience and findings gained from this study provide more insights toward how this type of research can be conducted and assessed.
Investigating the positive role of urban tourism in creating sustainable revenue opportunities in the municipalities of large-scale cities: the case of Iran
Authors: Faraji Amin , Khodadadi Masood , Nematpour Mohammad , Abidizadegan Shirin , Yazdani Hamid Reza 
Published: December 2020

Purpose
The purpose of this study is to demonstrate that unsustainable revenues in municipalities are short term and may have an adverse effect on urban systems. Focusing on stable financial resources can reduce such adverse effects. According to the legal obligations of municipalities in the creation of sustainable revenue, developing tourism-based activities in municipalities can play a significant role in providing a sustainable income.

Design/methodology/approach
This study aims to assess the positive effects of economic opportunities related to tourism for the municipalities in Iran’s large-scale cities and to identify the hidden opportunities of tourism. Also, from interviews and analysis of themes based on the situation, task, action, result model, tourism opportunities have been extracted and classified.

Findings
As a result of this research, hidden income-generating opportunities of urban tourism have been identified for municipalities, including those depending on situation, tasks, actions and results. For each of these categories, strategies for the realization of tourism opportunities are presented. Tourism’s hidden opportunities include those relating to organizational aspects, tourism planning, tourism diplomacy, handicrafts, health tourism, event tourism and urban tourism marketing.

Originality/value
By taking advantage of these opportunities, income generation, employment and urban management will be improved in the municipalities.