bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome instability drives epistatic adaptation in the human pathogen Leishmania
Authors: Bussotti Giovanni , Piel Laura , Pescher Pascale , Domagalska Malgorzata A. , Shanmugha Rajan K. , Cohen-Chalamish Smadar , Doniger Tirza , Hiregange Disha-Gajanan , Myler Peter J , Unger Ron , Michaeli Shulamit , Späth Gerald F.
Published: June 2021

How genome instability is harnessed for fitness gain despite its potential deleterious effects is largely elusive. An ideal system to address this important open question is provided by the protozoan pathogen Leishmania, which exploits frequent variations in chromosome and gene copy number to regulate expression levels. Using ecological genomics and experimental evolution approaches we provide first evidence that Leishmania adaptation relies on epistatic interactions between functionally associated gene copy number variations in pathways driving fitness gain in a given environment. We further uncover post-transcriptional regulation as a key mechanism that compensates for deleterious gene dosage effects and provides phenotypic robustness to genetically heterogenous parasite populations. Finally, we correlate dynamic variations in snoRNA gene dosage with changes in rRNA 2’-O-methylation and pseudouridylation, suggesting translational control is an additional layer of parasite adaptation. Leishmania genome instability is thus harnessed for fitness gain by genome-dependent variations in gene expression, and genome-independent, compensatory mechanisms. This allows for polyclonal adaptation and maintenance of genetic heterogeneity despite strong selective pressure. The epistatic adaptation described here needs to be considered in Leishmania epidemiology and biomarker discovery, and may be relevant to other fast evolving, eukaryotic cells that exploit genome instability for adaptation, such as fungal pathogens or cancer.

One Sentence Summary

Epistatic interactions harness genome instability for Leishmania fitness gain.
Freely-moving mice visually pursue prey using a retinal area with least optic flow
Authors: Holmgren Carl D. , Stahr Paul , Wallace Damian J. , Voit Kay-Michael , Matheson Emily J. , Sawinski Juergen , Bassetto Giacomo , Kerr Jason N. D.
Published: June 2021

Mice have a large visual field that is constantly stabilized by vestibular ocular reflex driven eye rotations that counter head-rotations. While maintaining their extensive visual coverage is advantageous for predator detection, mice also track and capture prey using vision. However, in the freely moving animal quantifying object location in the field of view is challenging. Here, we developed a method to digitally reconstruct and quantify the visual scene of freely moving mice performing a visually based prey capture task. By isolating the visual sense and combining amouse eye optic model with the head and eye rotations, the detailed reconstruction of the digital environment and retinal features were projected onto the corneal surface for comparison, and updated throughout the behavior. By quantifying the spatial location of objects in the visual scene and their motion throughout the behavior, we show that the image of the prey is maintained within a small area, the functional focus, in the upper-temporal part of the retina. This functional focus coincides with a region of minimal optic flow in the visual field and consequently minimal motion-induced image blur during pursuit, as well as the reported high density-region of Alpha-ON sustained retinal ganglion cells.
Carbonyl Post-Translational Modification Associated with Early Onset Type 1 Diabetes Autoimmunity
Authors: Yang Mei-Ling , Connolly Sean E. , Gee Renelle , Lam TuKiet , Kanyo Jean , Clarke Steven G. , Clarke Catherine F. , James Eddie A. , Speake Cate , Evans-Molina Carmella , Wen Li , Herold Kevan C. , Mamula Mark J.
Published: June 2021

Inflammation and oxidative stress in pancreatic islets amplify the appearance of various post-translational modifications (PTMs) to self-proteins. Herein, we identified a select group of carbonylated islet proteins arising before the onset of hyperglycemia in non-obese diabetic (NOD) mice. Of particular interest, we identified carbonyl modification of the prolyl-4-hydroxylase beta subunit (P4Hb) that is responsible for proinsulin folding and trafficking as an autoantigen in both human and murine type 1 diabetes. We found the carbonylated-P4Hb is amplified in stressed islets coincident with decreased glucose-stimulated insulin secretion and altered proinsulin to insulin ratios. Moreover, circulating autoantibodies against P4Hb were detected in prediabetic NOD mice and in early human type 1 diabetes prior to the onset of anti-insulin autoimmunity. Our studies provide mechanistic insight into the pathways of proinsulin metabolism and those creating autoantigenic forms of insulin in type 1 diabetes.
Frequency chasing of individual megadalton ions in an Orbitrap analyzer improves precision of analysis in single molecule mass spectrometry
Authors: Wörner Tobias P. , Aizikov Konstantin , Snijder Joost , Fort Kyle L. , Makarov Alexander A. , Heck Albert J.R.
Published: June 2021

To enhance the performance of charge detection mass spectrometry, we investigated the behavior of macromolecular single ions on their paths towards and within the Orbitrap analyzer. We discovered that ions in mass beyond one megadalton reach a plateau of stability and can be successfully trapped for seconds, travelling a path length of multiple kilometers, thereby enabling precise mass analysis with an effective resolution of greater than 100,000 at m/z 35,000. Through monitoring the frequency of individual ions, we show that these high mass ions, rather than being lost from the trap, can gradually lose residual solvent molecules and, in rare cases, a single elementary charge. Our observations highlight the importance of efficient desolvation for optimal charge detection mass spectrometry and inspired us to implement multiple improved data acquisition strategies. We demonstrate that the frequency drift of single ions due to desolvation and charge stripping can be corrected, which improves the effective ion sampling 23-fold and gives a two-fold improvement in mass precision and resolution, as demonstrated in the analysis of various viral particles.
Targeting Gi/o protein-coupled receptor signaling blocks HER2-induced breast cancer development and enhances HER2-targeted therapy
Authors: Lyu Cancan , Ye Yuanchao , Lensing Maddison M , Wagner Kay-Uwe , Weigel Ronald J. , Chen Songhai
Published: June 2021

G protein coupled receptors (GPCRs) are among the most desirable drug targets for human disease. Although GPCR dysfunction drives the development and progression of many tumors including breast cancer (BC), targeting individual GPCRs has limited efficacy as a cancer therapy because numerous GPCRs are activated. In this study, we sought a new way of blocking GPCR activation in HER2+-BC by targeting a subgroup of GPCRs that couple to Gi/o proteins (Gi/o-GPCRs). Using cell lines and transgenic mouse models, we showed in mammary epithelial cells, HER2 hyperactivation altered GPCR expression, particularly, Gi/o-GPCRs. Gi/o-GPCR stimulation transactivated EGFR and HER2, which in turn activated the PI3K/AKT and Src pathways. Uncoupling Gi/o-GPCRs from cognate Gi/o proteins by pertussis toxin (PTx) inhibited BC cell proliferation and migration in vitro and suppressed HER2-driven tumor formation and metastasis in vivo. Moreover, targeting Gi/o-GPCR signaling via PTx, PI3K, or Src inhibitors enhanced HER2-targeted therapy. These results indicate that HER2 hyperactivation in BC cells drives aberrant Gi/o-GPCR signaling, and Gi/o-GPCR signals converge on PI3K/AKT and Src signaling pathways to promote cancer progression and the development of resistance to HER2-targeted therapy. Our findings suggest a new way to pharmacologically deactivate GPCR signaling to block tumor growth and enhance therapeutic efficacy.
Novel Role of UHRF1 in DNA methylation-mediated repression of latent HIV-1
Authors: Verdikt Roxane , Bouchat Sophie , Pasternak Alexander O. , Nestola Lorena , Darcis Gilles , Avettand-Fenoel Véronique , Vanhulle Caroline , Aït-Ammar Amina , Bendoumou Maryam , Plant Estelle , Douce Valentin Le , Delacourt Nadège , Cicilionytė Aurelija , Necsoi Coca , Corazza Francis , Bittencourt Passaes Caroline Pereira , Schwartz Christian , Bizet Martin , Fuks François , Sáez-Cirión Asier , Rouzioux Christine , Wit Stéphane De , Berkhout Ben , Gautier Virginie , Rohr Olivier , Lint Carine Van
Published: June 2021

The multiplicity, heterogeneity and dynamic nature of HIV-1 latency mechanisms are reflected in the current lack of functional cure for HIV-1 and in the various reported ex vivo potencies of latency- reversing agents. Here, we investigated the molecular mechanisms underlying the potency of the DNA methylation inhibitor 5-aza-2’-deoxycytidine (5-AzadC) in HIV-1 latency reversal. Doing so, we uncovered specific demethylation CpG signatures induced by 5-AzadC in the HIV-1 promoter. By analyzing the binding modalities to these CpG, we revealed the recruitment of the epigenetic integrator UHRF1 to the HIV-1 promoter. We further demonstrated the role of UHRF1 in DNA methylation- mediated silencing of the latent HIV-1 promoter. As a proof-of-concept to this molecular characterization, we showed that pharmacological downregulation of UHRF1 in ex vivo HIV+ patient cell cultures resulted in potent reactivation of latent HIV-1. Together, we identify UHRF1 as a novel actor in HIV-1 gene silencing and highlight that it constitutes a new molecular target for HIV-1 curative strategies.
Mechanistic Insights Revealed by YbtPQ in the Occluded State
Authors: Hu Wenxin , Parkinson Chance , Zheng Hongjin
Published: June 2021

Recently, several ATP-binding cassette (ABC) importers have been found to adopt the typical fold of type IV ABC exporters. Presumably, these importers would function under the transport scheme of “alternating access” like those exporters: cycling through conformations of inward-open, occluded, and outward-open. Understanding how the exporter-like importers move substrates in the opposite direction requires structural studies in all the major conformations. To shed light on that, here we report the structure of yersiniabactin importer YbtPQ from uropathogenic Escherichia coli in the occluded conformation trapped by ADP-vanadate (ADP.Vi) at 3.1Å resolution determined by cryo electron microscopy. The structure shows unusual local rearrangements in multiple helices and loops in its transmembrane domains (TMDs). In addition, the dimerization of nucleotide-binding domains (NBDs) promoted by the vanadate trapping is highlighted by the “screwdriver” action happening at one of the two hinge points. These structural observations are rare and thus provide valuable information to understand the structural plasticity of the exporter-like ABC importers.
Mapping Activity-Dependent Quasi-Stationary States of Mitochondrial Membranes with Graphene-Induced Energy Transfer Imaging
Authors: Raja Sufi Oasim , Chizhik Alexey I. , Schmidt Christoph F. , Enderlein Jörg , Ghosh Arindam
Published: June 2021

Graphene-induced energy transfer (GIET) was recently introduced for the precise localization of fluorescent molecules along the optical axis of a microscope. GIET is based on near-field energy transfer from an optically excited fluorophore to a single sheet of graphene. As a proof-of-concept, we demonstrated its potential by determining the distance between the two leaflets of supported lipid bilayers (SLBs) with sub-nanometer accuracy. Here, we use GIET imaging for three-dimensional reconstruction of the mitochondrial membrane architecture. We map two quasi-stationary states of the inner and outer mitochondrial membranes before and during adenosine tri-phosphate (ATP) synthesis. We trigger the ATP synthesis state in vitro by activating mitochondria with precursor molecules. Our results demonstrate that the inner membrane (IM) approaches the outer membrane (OM) while the outer membrane (OM) does not show a measurable change in average axial position upon activation. As a result, the inter-membrane space (IM-OM distance) is reduced by ∼2 nm upon activation of the mitochondria. This direct experimental observation of the subtle dynamics of mitochondrial membranes and the change in inter-membrane distance induced by ATP synthesis is relevant for our understanding of the physical functioning of mitochondria.
Skeletal dysplasia-causing TRPV4 mutations suppress the hypertrophic differentiation of human iPSC-derived chondrocytes
Authors: Dicks Amanda R. , Maksaev Grigory I. , Harissa Zainab , Savadipour Alireza , Tang Ruhang , Steward Nancy , Liedtke Wolfgang , Nichols Colin G. , Wu Chia-Lung , Guilak Farshid
Published: June 2021

Mutations in the TRPV4 ion channel can lead to a range of skeletal dysplasias. However, the mechanisms by which TRPV4 mutations lead to distinct disease severity remain unknown. Here, we use CRISPR-Cas9-edited human induced pluripotent stem cells (hiPSCs) harboring either the mild V620I or lethal T89I mutations to elucidate the differential effects on channel function and chondrogenic differentiation. We found that hiPSC-derived chondrocytes with the V620I mutation exhibited increased basal currents through TRPV4. However, both mutations showed more rapid calcium signaling with a reduced overall magnitude in response to TRPV4 agonist GSK1016790A compared to wildtype. There were no differences in overall cartilaginous matrix production, but the V620I mutation resulted in reduced mechanical properties of cartilage matrix later in chondrogenesis. mRNA sequencing revealed that both mutations upregulated several anterior HOX genes and downregulated antioxidant genes CAT and GSTA1 throughout chondrogenesis. BMP4 treatment upregulated several essential hypertrophic genes in WT chondrocytes; however, this hypertrophic maturation response was inhibited in mutant chondrocytes. These results indicate that the TRPV4 mutations alter BMP signaling in chondrocytes and prevent proper chondrocyte hypertrophy, as a potential mechanism for dysfunctional skeletal development. Our findings provide potential therapeutic targets for developing treatments for TRPV4-mediated skeletal dysplasias.
Evolving small-molecule biosensors with improved performance and reprogrammed ligand specificity using OrthoRep
Authors: Javanpour Alex A. , Liu Chang C.
Published: June 2021

Genetically-encoded biosensors are valuable for the optimization of small-molecule biosynthesis pathways, because they transduce the production of small-molecule ligands into a readout compatible with high-throughput screening or selection in vivo. However, engineering biosensors with appropriate response functions and ligand specificities remains challenging. Here, we show that the continuous hypermutation system, OrthoRep, can be effectively applied to evolve biosensors with high dynamic range, reprogrammed activity towards desired non-cognate ligands, and proper operational range for coupling to biosynthetic pathways. In particular, we encoded the allosteric transcriptional factor, BenM, on OrthoRep such that propagation of host yeast cells resulted in BenM’s rapid and continuous diversification. When these cells were subjected to cycles of culturing and sorting on BenM activity in the presence and absence of its cognate ligand, muconic acid, or the non-cognate ligand, adipic acid, we obtained multiple BenM variants that respond to their corresponding ligands. These biosensors outperform previously-engineered BenM-based biosensors by achieving substantially greater dynamic range (up to ~180-fold-induction) and broadened operational range. Expression of select BenM variants in the presence of a muconic acid biosynthetic pathway demonstrated sensitive biosensor activation without saturating response, which should enable pathway and host engineering for higher production of muconic and adipic acids. Given the streamlined manner in which high-performance and versatile biosensors were evolved using OrthoRep, this study provides a template for generating custom biosensors for metabolic pathway engineering and other biotechnology goals.
Macrophages stimulate epicardial VEGFaa expression to trigger cardiomyocyte proliferation in larval zebrafish heart regeneration
Authors: Bruton Finnius A. , Kaveh Aryan , Ross-Stewart Katherine M. , Matrone Gianfranco , Oremek Magdalena E.M. , Solomonidis Emmanouil G. , Tucker Carl S. , Mullins John J. , Brittan Mairi , Taylor Jonathan M. , Rossi Adriano G. , Denvir Martin A.
Published: June 2021

Cardiac injury induces a sustained macrophage response in both zebrafish and mammals. Macrophages perform a range of both beneficial and detrimental functions during mammalian cardiac repair, yet their precise roles in zebrafish cardiac regeneration are not fully understood. Here we characterise cardiac regeneration in the rapidly regenerating larval zebrafish laser injury model and use macrophage ablation and macrophage-null irf8 mutants to define the role of macrophages in key stages of regeneration. Live heartbeat-synchronised imaging and RNA sequencing revealed an early proinflammatory phase, marked by tnfa+ macrophages, which then resolved to an anti-inflammatory, profibrotic phase. Macrophages were required for cardiomyocyte proliferation but not for functional or structural recovery following injury. Importantly, we found that macrophages are specifically recruited to the epicardial-myocardial niche, triggering the expansion of the epicardium which upregulates VEGFaa expression to induce cardiomyocyte proliferation. Hence, revealing a novel mechanism by which macrophages facilitate cardiac regeneration.
Transcriptional reprogramming and constitutive PD-L1 expression in melanoma are associated with dedifferentiation and activation of interferon and tumor necrosis factor signaling pathways
Authors: Ahn Antonio , Rodger Euan J. , Gimenez Gregory , Stockwell Peter A. , Parry Matthew , Hersey Peter , Chatterjee Aniruddha , Eccles Michael R.
Published: June 2021

Melanoma is the most aggressive type of skin cancer, with increasing incidence worldwide. Advances in targeted therapy and immunotherapy have improved the survival of melanoma patients experiencing recurrent disease, but unfortunately treatment resistance frequently reduces patient survival. Resistance to targeted therapy is associated with transcriptomic changes, and has also been shown to be accompanied by increased expression of programmed death ligand 1 (PD-L1), a potent inhibitor of immune response. Intrinsic upregulation of PD-L1 is associated with genome-wide DNA hypomethylation and widespread alterations in gene expression in melanoma cell lines. However, an in-depth analysis of the transcriptomic landscape of melanoma cells with intrinsically upregulated PD-L1 expression is lacking. To determine the transcriptomic landscape of intrinsically upregulated PD-L1 expression in melanoma, we investigated transcriptomes in melanomas with constitutive versus inducible PD-L1 expression (referred to as PD-L1CON and PD-L1IND). RNA-Seq analysis was performed on seven PD-L1CON melanoma cell lines and ten melanoma cell lines with low inducible PD-L1IND expression. We observed that PD-L1CON melanoma cells had a reprogrammed transcriptome with a characteristic pattern of dedifferentiated gene expression, together with active interferon (IFN) and tumor necrosis factor (TNF) signalling pathways. Furthermore, we identified key transcription factors that were also differentially expressed in PD-L1CON versus PD-L1IND melanoma cell lines. Overall, our studies describe transcriptomic reprogramming of melanomas with PD-L1CON expression.

Simple Summary

Melanoma, an aggressive form of skin cancer, is frequently associated with drug resistance in the advanced stages. For instance, frequently resistance is observed to sequential treatment of melanoma with targeted therapy and immunotherapy. In this research, the authors investigated whether potential transcriptional mechanisms and pathways associated with PD-L1 protein expression could underlie targeted therapy drug resistance in melanoma. The authors found a PD-L1 expression transcriptional pattern underlies resistance to targeted therapy in a subgroup of melanomas. These melanomas were markedly dedifferentiated, as compared to melanomas that were not drug resistant. Understanding changes in transcription and molecular pathways that lead to drug resistance could allow researchers to develop interventions to prevent drug resistance from occurring in melanoma, which could also be relevant to other cancer types.
In vivo augmentation of a complex gut bacterial community
Authors: Cheng Alice G. , Ho Po-Yi , Jain Sunit , Meng Xiandong , Wang Min , Yu Feiqiao Brian , Iakiviak Mikhail , Brumbaugh Ariel R. , Nagashima Kazuki , Zhao Aishan , Patil Advait , Atabakhsh Katayoon , Weakley Allison , Yan Jia , Higginbottom Steven , Neff Norma , Sonnenburg Justin L. , Huang Kerwyn Casey , Fischbach Michael A.
Published: June 2021

Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex but not both, limiting their utility. In accompanying work, we constructed a complex synthetic community (104 strains, hCom1) containing the most common taxa in the human gut microbiome. Here, we used an iterative experimental process to improve hCom1 by filling open metabolic and/or anatomical niches. When we colonized germ-free mice with hCom1 and then challenged it with a human fecal sample, the consortium exhibited surprising stability; 89% of the cells and 58% of the taxa derive from the original community, and the pre- and post-challenge communities share a similar overall structure. We used these data to construct a second version of the community, adding 22 strains that engrafted following fecal challenge and omitting 7 that dropped out (119 strains, hCom2). In gnotobiotic mice, hCom2 exhibited increased stability to fecal challenge and robust colonization resistance against pathogenic Escherichia coli. Mice colonized by hCom2 versus human feces are similar in terms of microbiota-derived metabolites, immune cell profile, and bacterial density in the gut, suggesting that this consortium is a prototype of a model system for the human gut microbiome.
The respiratory supercomplex from C. glutamicum
Authors: Moe Agnes , Kovalova Terezia , Król Sylwia , Yanofsky David J. , Bott Michael , Sjöstrand Dan , Rubinstein John L. , Högbom Martin , Brzezinski Peter
Published: June 2021

Corynebacterium glutamicum is a preferentially aerobic Gram-positive bacterium belonging to the Actinobacteria phylum, which also includes the pathogen Mycobacterium tuberculosis. In the respiratory chain of these bacteria, complexes III (CIII) and IV (CIV) form a CIII2CIV2 supercomplex that catalyzes oxidation of menaquinol and reduction of dioxygen to water. Electron transfer within the CIII2CIV2 supercomplex is linked to transmembrane proton translocation, which maintains an electrochemical proton gradient that drives ATP synthesis and transport processes. We isolated the C. glutamicum supercomplex and used cryo-EM to determine its structure at 2.9 Å resolution. The structure shows a central CIII2 dimer flanked by a CIV on each side. One menaquinone is bound in each of the QN and QP sites in each CIII, near the cytoplasmic and periplasmic sides, respectively. In addition, we identified a menaquinone positioned ~14 Å from heme bL on the periplasmic side. A di-heme cyt. cc subunit provides an electronic connection between each CIII monomer and the adjacent CIV. In CIII2, the Rieske iron-sulfur (FeS) proteins are positioned with the iron near heme bL. Multiple subunits interact to form a convoluted sub-structure at the cytoplasmic side of the supercomplex, which defines a novel path that conducts protons into CIV.
Nafamostat-interferon-alpha combination suppresses SARS-CoV-2 infection by targeting cooperatively host TMPRSS2 in vitro and in vivo
Authors: Ianevski Aleksandr , Yao Rouan , Lysvand Hilde , Grødeland Gunnveig , Legrand Nicolas , Oksenych Valentin , Zusinaite Eva , Tenson Tanel , Bjørås Magnar , Kainov Denis E.
Published: June 2021

SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here, we address these challenges by combining Pegasys (IFNa) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results indicate that Serpin E1 is an important mediator of the antiviral activity of IFNa and that both Serpin E1 and camostat can target the same cellular factor TMPRSS2, which plays a critical role in viral replication. The low doses of the drugs in combination may have several clinical advantages, including fewer adverse events and improved patient outcome. Thus, our study may provide a proactive solution for the ongoing pandemic and potential future coronavirus outbreaks, which is still urgently required in many parts of the world.
Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types
Authors: Rhodes Katherine , Barr Kenneth A , Popp Joshua M , Strober Benjamin J , Battle Alexis , Gilad Yoav
Published: June 2021

Most disease-associated loci, though located in putatively regulatory regions, have not yet been confirmed to affect gene expression. One reason for this could be that we have not examined gene expression in the most relevant cell types or conditions. Indeed, even large-scale efforts to study gene expression broadly across tissues are limited by the necessity of obtaining human samples post-mortem, and almost exclusively from adults. Thus, there is an acute need to expand gene regulatory studies in humans to the most relevant cell types, tissues, and states. We propose that embryoid bodies (EBs), which are organoids that contain a multitude of cell types in dynamic states, can provide an answer. Single cell RNA-sequencing now provides a way to interrogate developmental trajectories in EBs and enhance the potential to uncover dynamic regulatory processes that would be missed in studies of static adult tissue. Here, we examined the properties of the EB model for the purpose mapping inter-individual regulatory differences in a large variety of cell types.
The Catholic Church abuse scandal in Ireland: two steps forward, one step back by Pope Francis?
Authors: Pang Augustine , Hogan Eada , Andrasevic Igor
Published: June 2021

Purpose

Ireland is viewed as the shining base for Catholicism. That image is shattered as survivors revealed the abuse in the Magdalene Laundries and Mother and Baby Homes, and sexual abuse by priests. This study aims to examine image repair efforts by the Pope during his August 2018 visit.

Design/methodology/approach

Examined against the Letter of His Holiness released days earlier, this study evaluates all the Pope's speeches during his visit to Ireland using the image repair theory (Benoit and Pang, 2008) as its theoretical lens.

Findings

Pope Francis used the evasion of responsibility strategy to address the Magdalene Laundries and Mother and Baby Homes scandal and denial, corrective action and mortification for sex abuse crisis.

Research limitations/implications

Addresses call by Ferguson et al. (2018) to examine the consistency and effectiveness of strategies.

Practical implications

Beyond rhetoric, stakeholders would be looking to organizational leaders to provide relief and concrete steps to recover from their pain.

Originality/value

A leader's narratives represent the organization's narratives; thus, insights from this study can help leaders plan what they should say when conducting image repair. It is not just their own reputations that are on the line but, in this case, it is also the reputations of the people they represent
Bridging the gender digital divide: an analysis of existing guidance for gender digital inclusion programmes’ evaluations
Authors: Pawluczuk Alicja , Lee JeongHyun , Gamundani Attlee Munyaradzi
Published: June 2021

Purpose

This aim of this paper is to examine the existing gender digital inclusion evaluation guidance and proposes future research recommendations for their evaluation. Despite modern progress in towards gender equality and women’s empowerment movements, women’s access to, use of and benefits from digital technologies remain limited owing to economic, social and cultural obstacles. Addressing the existing gender digital divide is critical in the global efforts towards the United Nations’ Sustainable Development Goals (SDGs). In recent years, there has been a global increase of gender digital inclusion programmes for girls and women; these programmes serve as a mechanism to learn about gender-specific digital needs and inform future digital inclusion efforts. Evaluation reports of gender digital inclusion programmes can produce critical insights into girls’ and women’s learning needs and aspirations, including what works and what does not when engaging girls and women in information and communications technologies. While there are many accounts highlighting the importance of why gender digital inclusion programmes are important, there is limited knowledge on how to evaluate their impact.

Design/methodology/approach

The thematic analysis suggests three points to consider for the gender digital inclusion programmes evaluation: context-specific understanding of gender digital inclusion programmes; transparency and accountability of the evaluation process and its results; and tensions between evaluation targets and empowerment of evaluation participants.

Findings

The thematic analysis suggests three points of future focus for this evaluation process: context-specific understanding of gender digital inclusion programmes; transparency and accountability of the evaluation process and its results; and tensions between evaluation targets and empowerment of evaluation participants.

Originality/value

The authors propose recommendations for gender digital inclusion evaluation practice and areas for future research.
Well-being and career change intention: COVID-19’s impact on unemployed and furloughed hospitality workers
Authors: Chen Chun-Chu (Bamboo) , Chen Ming-Hsiang
Published: June 2021

Purpose

This study aims to examine the psychological distress experienced by unemployed and furloughed hospitality workers during the COVID-19 crisis and further investigate how this distress affects their career change intentions.

Design/methodology/approach

Derived from a sample of 607 unemployed and furloughed hospitality workers during the COVID-19 pandemic, the data for this research are analyzed using structural equation modeling.

Findings

This study reveals that unemployed and furloughed hospitality workers are financially strained, depressed, socially isolated and panic-stricken due to the pandemic’s effects. These effects lead to impaired well-being and an increased intention to leave the hospitality industry. Female and younger employees are impacted to a greater extent, while furloughed workers received fewer impacts compared to their laid-off compatriots.

Research limitations/implications

This study suggests that lockdown restrictions need to be implemented more deliberately, and the psychological well-being of the hospitality workforce deserves more immediate and continuing attention. It advises that hospitality businesses consider furloughs over layoffs when workforce reduction measures are necessary to combat the financial crisis.

Originality/value

This study adds to the current literature by examining the impact of the COVID-19 pandemic from the employee perspective. New insights are offered on the psychological toll of workforce reduction strategies during the financial fallout and how these distressing experiences affect career change intention.
Forging a collective entrepreneurial identity within existing organizations through corporate venturing
Authors: Zhang Ying , Biniari Marina G.
Published: June 2021

Purpose

This study unpacks how organizational members construct a collective entrepreneurial identity within an organization and attempt to instill entrepreneurial features in the organization's existing identity.

Design/methodology/approach

The study draws on the cases of two venturing units, perceived as entrepreneurial groups within their respective parent companies. Semi-structured interviews and secondary data were collected and analyzed inductively and abductively.

Findings

The data revealed that organizational members co-constructed a “corporate entrepreneur” role identity to form a collective shared belief and communities of practice around what it meant to act as an entrepreneurial group within their local corporate context and how it differentiated them from others. Members also clustered around the emergent collective entrepreneurial identity through sensegiving efforts to instill entrepreneurial features in the organization's identity, despite the tensions this caused.

Originality/value

Previous studies in corporate entrepreneurship have theorized on the top-down dynamics instilling entrepreneurial features in an organization's identity, but have neglected the role of bottom-up dynamics. This study reveals two bottom-up dynamics that involve organizational members' agentic role in co-constructing and clustering around a collective entrepreneurial identity. This study contributes to the middle-management literature, uncovering champions' identity work in constructing a “corporate entrepreneur” role identity, with implications for followers' engagement in constructing a collective entrepreneurial identity. This study also contributes to the organizational identity literature, showing how tensions around the entrepreneurial group's distinctiveness may hinder the process of instilling entrepreneurial features in an organization's identity.
Coaching to develop teacher professional noticing: planning with students and mathematics in mind
Authors: Jakopovic Paula M.
Published: June 2021

Purpose

This paper examines how intentional mathematics coaching practices can develop teacher professional noticing of “ambitious teaching practices” (NCTM, 2020) through connected, collaborative coaching cycles.

Design/methodology/approach

Narrative analysis is used to examine observations of a mathematics coach and novice teacher to better understand the role of the coach in helping teachers attend to ambitious mathematics teaching (AMT) practices.

Findings

The initial findings of this study suggest that intentional use of focused goals, iterative coaching cycles and a gradual release model of coaching can support shifts in noticing of AMT from being led by the coach to being facilitated by the teacher.

Originality/value

This study offers new insights into the functions of mathematics coaching that can foster shifts in teacher noticing and practice toward AMT. It contributes to the literature on what mathematics coaching looks and sounds like in the context of conversations with teachers, as well as the potential influence that structured, intentional, ongoing coaching supports can have on teacher noticing.
From paradoxes to trade-offs: metaroutine enabled multi level ambidexterity at Tata Motors, India
Authors: Dutta Swarup Kumar , Snehvrat Saurav
Published: June 2021

Purpose

The purpose of this paper is to explore the multi-level ambidexterity challenges through the metaroutine lens. Further, while confronting the ambidexterity challenges, it is found that what is paradox at one level can be understood as tradeoffs at another level. This study uses an in-depth multi-level case study of Tata Motors, an Indian automotive giant highlighting the ambidexterity dynamics across strategic, business unit and functional levels to demonstrate that paradoxes at the strategic level are converted to manageable tradeoffs at the business unit/ operational level. Also, metaroutine-enabled ambidexterity explains a possible way through which multi-level ambidexterity can be promoted and managed within organizations.

Design/methodology/approach

This study uses a case-based methodology (Eisenhardt, 1989) similar to the approach of Adler et al. (1999). The field research consisted of in-depth interviews, which focus on gathering information from the key involved members in the field, thus enabling us to understand how multi-level ambidexterity is promoted within Tata Motors. A semi-structured interview guide was used to collect data for this study.

Findings

The metaroutine lens offers an alternative route to explain the multi-level ambidexterity dynamics at Tata Motors. The ambidexterity questions at different levels in Tata Motors seem to be a mixture of paradoxes and tradeoffs. However, a key trend emerges. At the strategic and business unit level, the firm wanted to exploit their existing products and explore new customer segments. At the product level, the strategic and NPI core team wanted to best combine the customer centric explorations with exploitations resulting in cost savings. The ambidexterity questions at these two levels seem to be paradoxes. However, as the authors analyze the functional domains, it appears that each individual domain was working under increased constraints. Hence, the ambidexterity questions at the domain level seem to be a tradeoff based on the constraints faced by individual functional domains.

Originality/value

This study presents an in-depth multi-level case study of an Indian automotive giant, Tata Motors. The authors present the role of metaroutines in shaping the ambidexterity issues during the development of passenger vehicles. This study builds on the seminal work of Adler et al., 1999, and extends the discussion to the framing of the ambidexterity question as a paradox and/or a tradeoff. The core argument of this paper is that balancing opposite polarities in business models is basically a paradoxical issue in the exploitation/ exploration relationship.
Antecedents and consequences of the perceived usefulness of smoking cessation online health communities
Authors: Li Chenglong , Li Hongxiu , Suomi Reima
Published: June 2021

Purpose

An empirical study investigated the antecedents to perceived usefulness (PU) and its consequences in the context of smoking cessation online health communities (OHCs).

Design/methodology/approach

To validate a research model for perceived informational support, perceived emotional support and perceived esteem support, the authors conducted a partial-least-squares analysis of empirical data from an online survey (N = 173) of users of two smoking cessation OHCs. The proposed model articulates these as antecedents to PU from a social support perspective, and knowledge sharing and continuance intention are expressed as consequences of PU.

Findings

The empirical study identified that the PU of smoking cessation OHCs is influenced by perceived emotional support and perceived esteem support, and perceived informational support indirectly affects PU via these factors. In turn, PU exerts a positive influence on both knowledge sharing and continuance intention. Also, knowledge sharing positively affects continuance intention.

Originality/value

The study contributes to scholarship on users' postadoption behavior in the context of smoking cessation OHCs by disentangling the antecedents to PU from a social support perspective and pinpointing some important consequences of PU. The research also has practical implications for managing smoking cessation OHCs.
How does the yield variability in rainfed crops respond to climate variables? Evidence from pulses yields in Telangana, India
Authors: Guntukula Raju , Goyari Phanindra
Published: June 2021

Purpose

This paper aims to evaluate the effects of climate variables on the mean yield and yield variability of major pulse crops in the Telangana state of India.

Design/methodology/approach

Authors have estimated the Just and Pope (1978, 1979) production function using panel data at the district level of four major pulses in nine former districts of Telangana for 36 years during 1980–2015. A three-stage feasible generalized least squares estimation procedure has been followed. The mean yield and yield variance functions have been estimated individually for each of these study crops, namely, Bengal gram, green gram, red gram and horse gram.

Findings

Results have shown that changes in climatic factors such as rainfall and temperature have significant influences on the mean yield levels and yield variance of pulses. The maximum temperature is observed to have a significant adverse impact on the mean yield of a majority of pulses, and it is also a risk-enhancing factor for a majority of pulses except horse gram. However, the minimum temperature is positively related to the mean yields of the study crops except for Bengal gram, and it is having a risk-reducing impact for a majority of study crops. Rainfall is observed to have a negative impact on the mean yields of all pulses, but it is a risk-enhancing factor for only one crop, i.e. Bengal gram. Thus, rising temperatures and excess rainfall are not favorable to the productivity of pulses in study districts.

Research limitations/implications

The present study is based on the secondary data at the district level and is considering only one state. Season-wise primary data, including farm-specific characteristics, could have been better. The projected climate change and its impact on the mean yields and yield variance of pulses need to be considered in a future study.

Originality/value

According to the best of our knowledge, this is the first study to empirically evaluate the impact of climatic variables on the mean yields and yield variability of major pulses in Telangana using a panel data for major pulses and nine districts of 36 years time-series during 1980–2015. The study has given useful policy recommendations.
Sustainable facility relocation in agriculture systems using the GIS and best–worst method
Authors: Yousefi-Babadi Abolghasem , Bozorgi-Amiri Ali , Tavakkoli-Moghaddam Reza
Published: June 2021

Purpose

To avoid sub-optimization in wheat storage centers, one of the most strategic facilities, it is necessary to review and relocate them to be optimized regularly. The present study aims to propose an integrated method using geographic information systems (GISs) and an appropriate weighting algorithm for the relocation of wheat storage facilities.

Design/methodology/approach

To achieve the goal mentioned above, sustainability pillars in facility location and relocation are initially developed; afterward, a set of suitable criteria are obtained from various scientific resources. Then, the weight of each sustainable development pillar and its corresponding sub-criteria were identified through utilizing the best–worst method (BWM). By applying the obtained weights in the ArcGIS software package, various geographical layers were designed, and land-use planning, logistics planning and sustainable logistics planning are carried out in the regions. The regions are ranked based on the scores obtained in the processes, and the best regions are selected for sustainable relocation problem.

Findings

A case study including 430 regions (counties) in Iran is conducted to evaluate the efficiency of the suggested approach. The study results indicate that Iran possesses a superior state for establishing wheat storage centers in terms of infrastructural and social aspects. Also, it is established that 16% of counties are recognized as sustainable locations for relocating the wheat storage facilities.

Research limitations/implications

There is no most suitable analysis of the wheat storage facilities, as well as their strategic position in the supply chain, and there is a lack of considering sustainability in wheat storage facility location, despite the particular importance of it to the supply chain.

Practical implications

This framework is applied in an Iranian wheat-bread supply chain to find the best sustainable facilities. It is noted that this algorithm can be applied in other strategic facilities by minor and some major changes.

Originality/value

Decision-makers can apply the proposed methodology to find the best relocation sites for wheat storage facilities as the main part of wheat-bread supply chain in order to prevent sub-optimization and improve the efficiency of their supply chain.
How nostalgia forges place attachment and revisit intention: a moderated mediation model
Authors: Cho Heetae
Published: June 2021

Purpose

Analyzing sport fans' emotions has attracted much attention and offered important implications for research on sport consumer behavior. As such, diverse emotional factors have been considered to understand their behavioral responses. However, the concept of nostalgia has been examined to a lesser extent in the context of sport. Thus, this study investigated the role of nostalgia and its relationships with place attachment and revisit intention. The frequency of past experience was used as a moderator in this study.

Design/methodology/approach

Data collection was performed during six professional baseball games in South Korea, and 461 responses were collected from sport tourists. This study tested the reliability and validity of the measurement model and examined the relationships between constructs.

Findings

Results showed that nostalgia positively affected place attachment and revisit intention; place attachment played a mediating role between nostalgia and revisit intention. In addition, this study found that the relationship between nostalgia and place attachment was moderated by past experience.

Originality/value

This study identified how nostalgia can drive the development of a bond between place and sport fans, encouraging them to keep returning to the place where they are attached.