bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer blues? A validated judgment bias task suggests pessimism in nude mice with tumors
Authors: Resasco A. , MacLellan A. , Ayala M. A. , Kitchenham L. , Edwards A. M. , Lam S. , Dejardin S. , Mason G.
Published: February 2021

In humans, affective states can bias responses to ambiguous information: a phenomenon termed judgment bias (JB). Judgment biases have great potential for assessing affective states in animals, in both animal welfare and biomedical research. New animal JB tasks require construct validation, but for laboratory mice (Mus musculus), the most common research vertebrate, a valid JB task has proved elusive. Here (Experiment 1), we demonstrate construct validity for a novel mouse JB test: an olfactory Go/Go task in which subjects dig for high- or low-value food rewards. In C57BL/6 and Balb/c mice faced with ambiguous cues, latencies to dig were sensitive to high/low welfare housing, environmentally-enriched animals responding with relative ‘optimism’ through shorter latencies. Illustrating the versatility of a validated JB task across fields of research, it further allowed us to test hypotheses about the mood-altering effects of cancer (Experiment 2). Male nude mice bearing subcutaneous lung adenocarcinomas responded more pessimistically than healthy controls to ambiguous cues. Similar effects were not seen in females, however. To our knowledge, this is the first validation of a mouse JB task and the first demonstration of pessimism in tumor-bearing animals. This task, especially if refined to improve its sensitivity, thus has great potential for investigating mouse welfare, the links between affective state and disease, depression-like states in animals, and hypotheses regarding the neurobiological mechanisms that underlie affect-mediated biases in judgment.
On the evolution of host specificity: a case study of helminths
Authors: Pfenning-Butterworth Alaina C. , Botero-Cañola Sebastian , Cressler Clayton E.
Published: February 2021

The significant variation in host specificity exhibited by parasites has been separately linked to evolutionary history and ecological factors in specific host-parasite associations. Yet, whether there are any general patterns in the factors that shape host specificity across parasites more broadly is unknown. Here we constructed a molecular phylogeny for 249 helminth species infecting free-range mammals and find that the influence of ecological factors and evolutionary history varies across different measures of host specificity. Whereas the phylogenetic range of hosts a parasite can infect shows a strong signal of evolutionary constraint, the number of hosts a parasite infects does not. Our results shed new light on the evolution of host specificity in parasites, suggesting that phylogenetic breadth may capture the evolutionary potential of a parasite to jump between hosts, whereas the number of hosts may reflect ecological opportunity. Finally, we show parasite phylogenies can also provide an alternative perspective on zoonosis by identifying which hosts are infected by a broad phylogenetic range of parasites.
The Future is Less Concrete than the Present: A Neural Signature of the Concreteness of Prospective Thought Is Modulated by Temporal Proximity during Intertemporal Decision-Making
Authors: Lee Sangil , Parthasarathi Trishala , Cooper Nicole , Zauberman Gal , Lerman Caryn , Kable Joseph W.
Published: February 2021

Why do people discount future rewards? Multiple theories in psychology argue that future events are imagined less concretely than immediate events, thereby diminishing their perceived value. Here we provide neuroscientific evidence for this proposal. First, we construct a neural signature of the concreteness of prospective thought, using an fMRI dataset where the concreteness of imagined future events is orthogonal to their valence by design. Then, we apply this neural signature in two additional fMRI datasets, each using a different delay discounting task, to show that neural measures of concreteness decline as rewards are delayed farther into the future.

Significance Statement

People tend to devalue, or discount, outcomes in the future relative to those that are more immediate. This tendency is evident in people’s difficulty in making healthy food choices or saving money for retirement. Several psychological theories propose that discounting occurs because delayed outcomes are perceived less concretely that more immediate ones. Here we build a brain decoder for the concreteness of future thought and use this unobtrusive measure to show that outcomes are processed less concretely as they occur farther into the future.
GABA plays a key role in plant acclimation to a combination of high light and heat stress
Authors: Balfagón Damián , Gómez-Cadenas Aurelio , Rambla José L. , Granell Antonio , Ollas Carlos de , Mittler Ron , Zandalinas Sara I
Published: February 2021

Plants are frequently subjected to different combinations of abiotic stresses, such as high light intensity and elevated temperatures. These environmental conditions pose an important threat to agriculture production, affecting photosynthesis and decreasing yield. Metabolic responses of plants, such as alterations in carbohydrates and amino acid fluxes, play a key role in the successful acclimation of plants to different abiotic stresses, directing resources towards stress responses and suppressing growth. Here we show that the primary metabolic response ofArabidopsis thalianaplants to high light or heat stress is different than that of plants subjected to a combination of high light and heat stress. We further demonstrate that a combination of high light and heat stress results in a unique metabolic response that includes increased accumulation of sugars and amino acids, coupled with decreased levels of metabolites participating in the tricarboxylic acid (TCA) cycle. Among the amino acids exclusively accumulated during a combination of high light and heat stress, we identified the non-proteinogenic amino acid γ-aminobutyric acid (GABA). Analysis of different mutants deficient in GABA biosynthesis, in particular two independent alleles of glutamate decarboxylase 3 (gad3), reveal that GABA plays a key role in the acclimation of plants to a combination of high light and heat stress. Taken together, our findings identify a new role for GABA in regulating plant responses to stress combination.

One sentence summary

The non-proteinogenic amino acid γ-aminobutyric acid (GABA) is required for plant acclimation to a combination of high light and heat stress in Arabidopsis.
Medicago SativaDefensin 1 (MsDef1), A Natural Tumor Targeted Sensitizer for Improving Chemotherapy: Translation from Anti-Fungal Agent to Potential Anti-Cancer Agent
Authors: Pandurangi Raghu S. , Karwa Amol , Sagaram Uma Shankar , Shah Dilip
Published: February 2021

Introduction

MsDef1, a 45-amino acid cysteine-rich peptide from the seed ofMedicago sativais an antifungal defensin small protein. It exhibits broad-spectrum antifungal activity against fungal pathogens of plants at low micromolar concentrations. The common vulnerability of fungal and cancer cells determines the utility of MsDef1 as a potential anti-tumor agent.

Results

The solution dynamics of15N-labeled MsDef1,15N longitudinal relaxation (T1) and15N-1H Nuclear Overhauser Effect (NOE) shows that GlcCer binds at two sites on the peptide molecule, i.e., Asp36-Cys39 and amino acids between 12-20 and 33-40. MsDef1 interacts with drug resistant breast cancer MCF-7R cells, permeates GlcCer-rich plasma membrane and releases apoptotic ceramide. This results in the activation of ceramide pathway involving interaction of the peptide with intracellular thioredoxin (Trx), another tumor specific biomarker. MsDef1 oxidizes Trx through four S-S bonds and in the process, gets reduced to thiols. Oxidation of Trx is correlated with the activation of Apoptosis Stimulating Kinase 1 (ASK1) which is known to sensitize cancer cells to chemotherapeutics including front-line drug Doxorubicin. A combination of MsDef1 and Doxorubicin exhibits 5-10-fold greater apoptosisin vitroin MDR triple negative breast cancer (TNBC) cells compared to either MsDef1 or Doxorubicin alone.

Conclusion

An antifungal plant defensin MsDef1 is shown to be a cell permeating peptide (CPP) for MDR cancer cells targeted to two tumor specific targets activating two cell death pathways. That makes MsDef1, potentially a tumor targeted sensitizer neoadjuvant to cancer therapy.
Domain adaptive neural networks improve cross-species prediction of transcription factor binding
Authors: Cochran Kelly , Srivastava Divyanshi , Shrikumar Avanti , Balsubramani Akshay , Hardison Ross C. , Kundaje Anshul , Mahony Shaun
Published: February 2021

The intrinsic DNA sequence preferences and cell-type specific cooperative partners of transcription factors (TFs) are typically highly conserved. Hence, despite the rapid evolutionary turnover of individual TF binding sites, predictive sequence models of cell-type specific genomic occupancy of a TF in one species should generalize to closely matched cell types in a related species. To assess the viability of cross-species TF binding prediction, we train neural networks to discriminate ChIP-seq peak locations from genomic background and evaluate their performance within and across species. Cross-species predictive performance is consistently worse than within-species performance, which we show is caused in part by species-specific repeats. To account for this domain shift, we use an augmented network architecture to automatically discourage learning of training species-specific sequence features. This domain adaptation approach corrects for prediction errors on species-specific repeats and improves overall cross-species model performance. Our results demonstrate that cross-species TF binding prediction is feasible when models account for domain shifts driven by species-specific repeats.
Fast, efficient and virus-free generation ofTRAC-replaced CAR T cells
Authors: Kath Jonas , Du Weijie , Thommandru Bernice , Turk Rolf , Amini Leila , Stein Maik , Zittel Tatiana , Martini Stefania , Ostendorf Lennard , Wilhelm Andreas , Akyüz Levent , Rehm Armin , Höpken Uta E. , Pruß Axel , Künkele Annette , Jacobi Ashley M. , Volk Hans-Dieter , Schmueck-Henneresse Michael , Reinke Petra , Wagner Dimitrios L.
Published: February 2021

Chimeric Antigen Receptor (CAR) redirected T cells are a potent treatment option for certain hematological malignancies. Recently, site-specific insertion of CARs into the T cell receptor (TCR) alpha constant (TRAC) locus using gene editing and adeno-associated viruses was shown to generate CAR T cells with improved functionality over their retrovirally transduced counterparts. However, the development of viruses for gene transfer is complex and associated with extensive costs at early clinical stages. Here, we provide an economical and virus-free method for efficient CAR insertion into theTRAClocus of primary human T cellsviaCRISPR-Cas mediated homology-directed repair (HDR). While the toxicity induced by transfected double-stranded template (donor) DNA was not fully prevented by pharmacological means, the combination of DNA-sensor inhibitors and HDR enhancers resulted in highly efficient gene editing with TCR-to-CAR replacement rates reaching up to 68%. The resulting TCR-deficient CAR T cells show antigen-specific cytotoxicity and cytokine productionin vitro. Our GMP-compatible non-viral platform technology lays the foundation for clinical trials and fast-track generation of novel CAR T cells applicable for autologous or allogeneic off-the-shelf use.
PDBrenum: a webserver and program providing Protein Data Bank files renumbered according to their UniProt sequences
Authors: Faezov Bulat , Dunbrack Roland L.
Published: February 2021

The Protein Data Bank (PDB) was established at Brookhaven National Laboratories in 1971 as an archive for biological macromolecular crystal structures. In early 2021, the database has more than 175,000 structures solved by X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy, and other methods. Many proteins have been studied under different conditions, including binding partners such as ligands, nucleic acids, or other proteins; mutations, and post-translational modifications, thus enabling extensive comparative structure-function studies. However, these studies are made more difficult because authors are allowed by the PDB to number the amino acids in each protein sequence in any manner they wish. This results in the same protein being numbered differently in the available PDB entries. For instance, some authors may include N-terminal signal peptides or the N-terminal methionine in the sequence numbering and others may not. In addition to the coordinates, there are many fields that contain information regarding specific residues in the sequence of each protein in the entry. Here we provide a webserver and Python3 application that fixes the PDB sequence numbering problem by replacing the author numbering with numbering derived from the corresponding UniProt sequences. We obtain this correspondence from the SIFTS database from PDBe. The server and program can take a list of PDB entries or a list of UniProt identifiers (e.g., “P04637” or “P53_HUMAN”) and provide renumbered files in mmCIF format and the legacy PDB format for both asymmetric unit files and biological assembly files provided by PDBe.

Availability

Source code is freely available athttps://github.com/Faezov/PDBrenum. The webserver is located at:http://dunbrack3.fccc.edu/PDBrenum.

Contact

bulat.faezov@fccc.eduorroland.dunbrack@fccc.edu.
Metabolomics, Transcriptomics and Functional Glycomics Reveals Bladder Cancer Cells Plasticity and Enhanced Aggressiveness Facing Hypoxia and Glucose Deprivation
Authors: Peixoto Andreia , Freitas Rui , Ferreira Dylan , Relvas-Santos Marta , Paulo Paula , Cardoso Marta , Soares Janine , Gaiteiro Cristiana , Palmeira Carlos , Teixeira Filipe , Ferreira Rita , José Oliveira Maria , Silva André M. N. , Lara Santos Lúcio , Ferreira José Alexandre
Published: February 2021

Bladder cancer constitutes one of the deadliest genitourinary diseases, especially when diagnosed at late stages. These tumours harbour microenvironmental niches characterized by low levels of oxygen (hypoxia) and limited glucose supply due to poor vascularization. However, the synergic contribution of these features to disease development is poorly understood. Here, we demonstrated that cells with distinct histopathological and molecular backgrounds responded similarly to such stimuli. Cancer cells arrested proliferation, significantly increased invasive capacityin vitroand enhanced tolerance to cisplatin-based chemotherapy. Reoxygenation and access to glucose restored basal proliferation and invasion levels without triggering stress-induced apoptosis, denoting significant cellular plasticity in adapting to microenvironmental cues. Whole transcriptomics showed major molecular reprogramming, supporting main functional alterations. Metabolomics evidenced fatty acidsβ-oxidation as main bioenergetic pathway rather than anaerobic glycolysis generally adopted by hypoxic cells. Joint pathway analysis also suggested relevant alterations in mucin-typeO-glycan biosynthesis. Glycomics confirmed a major antagonization ofO-glycosylation pathways, leading to simple cell glycophenotypes characterized by the accumulation of immature short-chainO-glycans such as Tn and STn antigens at the cell surface. Glycoengineered models reflecting simple cell glycophenotypes were developed and functional studiesin vitroandin vivoshowed that Tn and STn overexpression decreased proliferation and promoted chemoresistance, reinforcing their close link with tumour aggressiveness. Collectively, we have demonstrated that hypoxia and glucose deprivation trigger more aggressive cell behaviours, in what appears to be an escape mechanism from microenvironmental stress. We propose that, altered glycosylation may be used to target these subpopulations, paving the way for precision oncology.
Probing Patterning in Microbial Consortia with picCASO: a Cellular Automaton for Spatial Organisation
Authors: Venkatraghavan Sankalpa , Anantakrishnan Sathvik , Raman Karthik
Published: February 2021

Microbial consortia exhibit spatial patterning across diverse environments. Since probing the self-organization of natural microbial communities is limited by their inherent complexity, synthetic models have emerged as attractive alternatives. In this study, we develop novel frameworks of bacterial communication and explore the emergent spatiotemporal organization of microbes. Specifically, we build quorum sensing-mediated models of microbial growth that are utilized to characterize the dynamics of communities from arbitrary initial configurations and establish the effectiveness of our communication strategies in coupling the growth rates of microbes. Our simulations indicate that the behavior of quorum sensing-coupled consortia can be most effectively modulated by the rates of secretion of AHLs. Such a mechanism of control enables the construction of desired relative populations of constituent species in spatially organized populations. Our models accurately recapitulate previous experiments that have investigated pattern formation in synthetic multi-cellular systems. Additionally, our software tool enables the easy implementation and analysis of our frameworks for a variety of initial configurations and simplifies the development of sophisticated gene circuits facilitating distributed computing. Overall, we demonstrate the potential of spatial organization as a tunable parameter in synthetic biology by introducing a communication paradigm based on the location and strength of coupling of microbial strains.

Author Summary

Interacting microorganisms that coexist in a given environment tend to have well-defined spatial arrangements. While the emergence of such organization is seen across different microbiomes in nature, it is hitherto not well understood. Decoding the inherent spatial patterning of microbes is constrained by the complexity of their natural habitats. Here, we take advantage of synthetic models of microbial communities to study the dynamics of emergent spatial organization. Our framework of bacterial communication utilizes modular synthetic devices to couple growth rates. In addition to uncovering potential principles of spatial organization, this work enables the construction of complex genetic circuits distributed across communicating strains. Additionally, we have developed a software tool, picCASO, that streamlines the investigation of microbial systems communicating through such frameworks.
The APOBEC3A deaminase drives episodic mutagenesis in cancer cells
Authors: Petljak Mia , Chu Kevan , Dananberg Alexandra , Bergstrom Erik N. , Morgen Patrick von , Alexandrov Ludmil B. , Stratton Michael R. , Maciejowski John
Published: February 2021

The APOBEC3 family of cytidine deaminases is widely speculated to be a major source of somatic mutations in cancer1–3. However, causal links between APOBEC3 enzymes and mutations in human cancer cells have not been established. The identity of the APOBEC3 paralog(s) that may act as prime drivers of mutagenesis and the mechanisms underlying different APOBEC3-associated mutational signatures are unknown. To directly investigate the roles of APOBEC3 enzymes in cancer mutagenesis, candidateAPOBEC3genes were deleted from cancer cell lines recently found to naturally generate APOBEC3-associated mutations in episodic bursts4. Deletion of theAPOBEC3Aparalog severely diminished the acquisition of mutations of speculative APOBEC3 origins in breast cancer and lymphoma cell lines. APOBEC3 mutational burdens were undiminished inAPOBEC3Bknockout cell lines.APOBEC3Adeletion reduced the appearance of the clustered mutation typeskataegisandomikli, which are frequently found in cancer genomes. The uracil glycosylase UNG and the translesion polymerase REV1 were found to play critical roles in the generation of mutations induced by APOBEC3A. These data represent the first evidence for a long-postulated hypothesis that APOBEC3 deaminases generate prevalent clustered and non-clustered mutational signatures in human cancer cells, identify APOBEC3A as a driver of episodic mutational bursts, and dissect the roles of the relevant enzymes in generating the associated mutations in breast cancer and B cell lymphoma cell lines.
A phosphorylation of RIPK3 kinase initiates an intracellular apoptotic pathway that promotes corpus luteum regression
Authors: Li Dianrong , Chen Jie , Guo Jia , Li Lin , Cai Gaihong , Chen She , Huang Jia , Yang Hui , Zhuang Yinhua , Wang Fengchao , Wang Xiaodong
Published: February 2021

Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) normally signals to necroptosis by phosphorylating MLKL. We report here that when the cellular RIPK3 chaperone Hsp90/CDC37 level is low, RIPK3 also signals to apoptosis. The apoptotic function of RIPK3 requires phosphorylation of the serine 165/threonine 166 sites on its kinase activation loop, resulting in inactivation of RIPK3 kinase activity while gaining the ability to recruit RIPK1, FADD, and caspase-8 to form a cytosolic caspase-activating complex, thereby triggering apoptosis. We found that PGF2αinduces RIPK3 expression in luteal granulosa cells in the ovary to cause luteal regression through this RIPK3-mediated apoptosis pathway. Mice carrying homozygous phosphorylation-resistant RIPK3 S165A/T166A knockin mutations failed to respond to PGF2αbut retained pro-necroptotic function, whereas mice with phospho-mimicking S165D/T166E homozygous knockin mutation underwent spontaneous apoptosis in multiple RIPK3-expressing tissues and died shortly after birth. Thus, RIPK3 signals to either necroptosis or apoptosis depending on its serine 165/threonine 166 phosphorylation status.
Thalamocortical axons control the cytoarchitecture of neocortical layers by area-specific supply of secretory proteins
Authors: Sato Haruka , Hatakeyama Jun , Iwasato Takuji , Araki Kimi , Yamamoto Nobuhiko , Shimamura Kenji
Published: February 2021

Neuronal abundance and thickness of each cortical layer is specific to each area, but how this fundamental feature arises during development remains poorly understood. While some of area-specific features are controlled by intrinsic cues such as morphogens and transcription factors, the exact influence and mechanisms of action by extrinsic cues, in particular the thalamic axons, have not been fully established. Here we identify a thalamus-derived factor, VGF, which is indispensable for thalamocortical axons to maintain the proper amount of layer 4 neurons in the mouse sensory cortices. This process is prerequisite for further maturation of the primary somatosensory area, such as barrel field formation instructed by a neuronal activity-dependent mechanism. Our results also provide an insight into regionalization of brain in that highly site-specific axon projection anterogradely confers further regional complexity upon the target field through locally secreting signaling molecules from axon terminals.
Direct activation of endothelial cells by SARS-CoV-2 nucleocapsid protein is blocked by Simvastatin
Authors: Qian Yisong , Lei Tianhua , Patel Parth S. , Lee Chi H , Monaghan-Nichols Paula , Xin Hong-Bo , Qiu Jianming , Fu Mingui
Published: February 2021

Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the SARS-CoV-2 viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved with endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through TLR2/NF-κB and MAPK signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkablely, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, MERS-CoV, HUB1-CoV and influenza virus H1N1 did not affect endothelial activation. These findings are well consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy, and suggests that simvastatin, an FDA-approved lipid-lowering drug, may benefit to prevent the pathogenesis and improve the outcome of COVID-19 patients.
The Progenetix oncogenomic resource in 2021
Authors: Huang Qingyao , Carrio-Cordo Paula , Gao Bo , Paloots Rahel , Baudis Michael
Published: February 2021

In cancer, copy number aberrations (CNA) represent a type of nearly ubiquitous and frequently extensive structural genome variations. To disentangle the molecular mechanisms underlying tumorigenesis as well as identify and characterize molecular subtypes, the comparative and meta-analysis of large genomic variant collections can be of immense importance. Over the last decades, cancer genomic profiling projects have resulted in a large amount of somatic genome variation profiles, however segregated in a multitude of individual studies and datasets. The Progenetix project, initiated in 2001, curates individual cancer CNA profiles and associated metadata from published oncogenomic studies and data repositories with the aim to empower integrative analyses spanning all different cancer biologies.

During the last few years, the fields of genomics and cancer research have seen significant advancement in terms of molecular genetics technology, disease concepts, data standard harmonization as well as data availability, in an increasingly structured and systematic manner. For the Progenetix resource, continuous data integration, curation and maintenance have resulted in the most comprehensive representation of cancer genome CNA profiling data with 138’663 (including 115’357 tumor) CNV profiles. In this article, we report a 4.5-fold increase in sample number since 2013, improvements in data quality, ontology representation with a CNV landscape summary over 51 distinctive NCIt cancer terms as well as updates in database schemas, and data access including new web front-end and programmatic data access. Database URL:progenetix.org
BET Inhibition Enhances TNF Mediated Anti-Tumor Immunity
Authors: Wellinger Lisa C. , Hogg Simon J. , Newman Dane M. , Friess Thomas , Geiss Daniela , Michie Jessica , Ramsbottom Kelly M. , Bacac Marina , Fauti Tanja , Marbach Daniel , Jarassier Laura , Thienger Phillip , Paehler Axel , Cluse Leonie A. , Kearney Conor J. , Vervoort Stephin J. , Oliaro Jane , Shortt Jake , Ruefli-Brasse Astrid , Rohle Daniel , Johnstone Ricky W.
Published: February 2021

Targeting chromatin binding proteins and modifying enzymes can concomitantly affect tumor cell proliferation and survival, as well as enhance anti-tumor immunity and augment cancer immunotherapies. By screening a small molecule library of epigenetics-based therapeutics, BET bromodomain inhibitors (BETi) were identified as agents that promote the anti-tumor activity of CD8+T-cells. BETi sensitized diverse tumor types to the cytotoxic effects of the pro-inflammatory cytokine TNF. By preventing the recruitment of BRD4 to p65-boundcis-regulatory elements, BETi suppressed the induction of inflammatory gene expression, including the key NF-κB target genesBIRC2(cIAP1)andBIRC3(cIAP2). Disruption of pro-survival NF-κB signaling by BETi led to unrestrained TNF-mediated activation of the extrinsic apoptotic cascade and tumor cell death. Administration of BETi in combination with T-cell bispecific (TCB) antibodies increased bystander killing of tumor cells and enhanced tumor growth inhibitionin vivoin a TNF-dependent manner. This novel epigenetic mechanism of immunomodulation may guide future use of BETi as adjuvants for immune oncology agents.

STATEMENT OF SIGNIFICANCE

Manipulating the epigenome is an evolving strategy to enhance anti-tumor immunity. We demonstrate that BET bromodomain inhibitors potently sensitize solid tumors to CD8+T-cell killing in a TNF-dependent manner. This immunomodulatory mechanism can be therapeutically leveraged to augment immuno-oncology therapies, including TCB antibodies and immune checkpoint blockade.
The internet of things in the food supply chain: adoption challenges
Authors: Aamer Ammar Mohamed , Al-Awlaqi Mohammed Ali , Affia Ifadhila , Arumsari Silvia , Mandahawi Nabeel
Published: February 2021

Purpose

The food supply chain (FSC) challenges coupled with global disruptions, such as the recent coronavirus disease 2019 (COVID-19) pandemic outbreak, exacerbate its vulnerability. The Internet of things (IoT) is one of the disruptive technologies being adopted in food supply chain management (FSCM). This study aims to address the challenges of IoT adoption in the FSC by systematically analyzing the prior pertinent literature.

Design/methodology/approach

A structured literature review was used to collate a list of peer-reviewed and relevant publications. A total of 72 out of 210 articles were selected for the final evaluation.

Findings

The literature review findings suggest five themes: technical, financial, social, operational, educational and governmental related challenges. A total of 15 challenges were devised from the review related literature of IoT adoption. The study concludes with future research recommendations for scholars and practical implications for practitioners.

Research limitations/implications

While this study focuses on the overall FSC, further research should address other domains in the FSC such as cold supply chain, agriculture and perishable food to gain a better contextual understanding of the specific case.

Originality/value

The topic of IoT adoption in the FSCM is still considered emerging. Therefore, the present work contributes to the limited studies and documentation on the level of IoT implementation in the FSCM. This study should help organizations to assimilate how to adopt and manage the IoT application by addressing the factors and challenges presented in this research.
Systematic literature review of sentiment analysis in the Spanish language
Authors: Osorio Angel Sonia , Peña Pérez Negrón Adriana , Espinoza-Valdez Aurora
Published: February 2021

Purpose

Most studies on Sentiment Analysis are performed in English. However, as the third most spoken language on the Internet, Sentiment Analysis for Spanish presents its challenges from a semantic and syntactic point of view. This review presents a scope of the recent advances in this area.

Design/methodology/approach

A systematic literature review on Sentiment Analysis for the Spanish language was conducted on recognized databases by the research community.

Findings

Results show classification systems through three different approaches: Lexicon based, Machine Learning based and hybrid approaches. Additionally, different linguistic resources as Lexicon or corpus explicitly developed for the Spanish language were found.

Originality/value

This study provides academics and professionals, a review of advances in Sentiment Analysis for the Spanish language. Most reviews on Sentiment Analysis are for English, and other languages such as Chinese or Arabic, but no updated reviews were found for Spanish.
Consequences of managerial indecisiveness
Authors: Caemmerer Barbara , Goerne Jobst , Mulki Jay P.
Published: February 2021

Purpose

In a banking context, this study applies uncertainty management theory (UMT) to test the impact of managerial indecisiveness on salespersons' trust in their manager, perceived role ambiguity and turnover intentions. In addition, the moderating role of managers' leadership style on the link between indecisiveness perceptions and role ambiguity is tested.

Design/methodology/approach

A questionnaire was distributed among customer facing employees from a multinational bank in one of the large metropolitan cities in India. In total, out of 360 questionnaires distributed, 255 responses were coded for analysis resulting in a response rate of 71%. Structural equation modeling, mediation and moderation analyses were applied.

Findings

Perceptions of managerial indecisiveness strengthen role ambiguity, which negatively impacts trust in the manager, which in turn increases turnover intentions. The level of participative leadership moderates the link between indecisiveness and role ambiguity.

Originality/value

This is one of the first studies in the sales literature that examines how managerial indecisiveness, role ambiguity and trust in the supervisor can impact salespersons' turnover intentions. Thus, this research makes a useful contribution by examining how managers' decision-making style can shape employee cognition and behavior at the workplace.
Hospitality managers in turbulent times: the COVID-19 crisis
Authors: Giousmpasoglou Charalampos , Marinakou Evangelia , Zopiatis Anastasios
Published: February 2021

Purpose

This study aims to explore the role General Managers (GMs) play in mitigating the effects of the unprecedented COVID-19 pandemic.

Design/methodology/approach

Qualitative structured interviews conducted online with 50 hospitality GMs from 45 countries are used to explore the impact of the pandemic on the industry’s operational norms and the role of managers in both managing the crisis and planning contingencies for recovery.

Findings

The findings enhance the conceptual capital in this emerging field and provide insights on how GMs behave during crises. Four related sub-themes emerged from the data analysis, namely, contingency planning and crisis management, resilience and impact on GM roles, the impact on hotels’ key functional areas and some GMs’ suggestions for the future of luxury hospitality.

Research limitations/implications

This study generates empirical data that inform contemporary debates about crisis management and resilience in hospitality organizations at a micro-level operational perspective.

Practical implications

Findings suggest that, in times of uncertainty and crisis, luxury hotel GMs are vital in coping with changes and leading their organizations to recovery. GMs’ resilience and renewed role and abilities enable them to adapt rapidly to external changes on their business environment.

Originality/value

This study is unique in terms of scale and depth, as it provides useful insights regarding the GM’s role during an unprecedented crisis such as COVID-19.
Long-term focus and attitude toward entrepreneurial behaviors: the moderating effect of industry-clockspeed
Authors: Thapa Nischal , Shah Puspa
Published: February 2021

Purpose

This study aims to identify and examine the antecedents of attitude toward entrepreneurial behaviors (ATEB) of firms. Additionally, this study also identifies and examines the antecedents of innovativeness and proactiveness. Furthermore, this study explains how factors within and outside the organization affect ATEB, innovativeness and proactiveness.

Design/methodology/approach

This study uses the attention-based view (ABV) and examines the effects of long-term focus and industry clockspeed on attitude toward firms’ entrepreneurial behaviors (EB). This study measures ATEB by analyzing the top management team’s words in the earnings conference calls. It applies the two-stage least squares regression with fixed effects and instrumental variables to conduct the empirical analysis.

Findings

The results indicate that the direct effects of long-term focus and industry clockspeed on ATEB are not significant. However, the moderating effect of industry clockspeed on the relationship between long-term focus and EB is significant and positive. The results indicate that firms that are operating in fast clockspeed industries exhibiting long-term focus exhibit EB. Furthermore, the results also indicate that long-term focus and industry clockspeed collectively affect innovativeness and proactiveness.

Practical implications

This research helps firms to develop entrepreneurial behavior operating under various task environment conditions.

Originality/value

This study applies the ABV of the firm and contributes to the area of firm-level EB, while prior studies have not implemented this perspective in investigating firm-level EB. Past studies have not applied the ABV of the firm to study EB, innovativeness and proactiveness either independently or collectively.
The effect of supply chain responsiveness on customer development
Authors: Asamoah David , Nuertey Dorcas , Agyei-Owusu Benjamin , Akyeh Joseph
Published: February 2021

Purpose

The study examines how supply chain responsiveness (logistics process responsiveness, operations systems responsiveness and supplier network responsiveness) impacts the ability of firms to attract, satisfy and retain customers.

Design/methodology/approach

Using a quantitative approach, a total of 250 questionnaires were distributed to firms in the Kumasi metropolis in the Ashanti Region of Ghana, with 100 useable responses retrieved. The effect of supply chain responsiveness on customer development was analysed using partial least squares structural equation modelling.

Findings

The findings showed that operations systems responsiveness and supplier network responsiveness drive the logistics systems responsiveness of firms as hypothesized. It was also revealed that operations systems responsiveness and logistics process responsiveness enhanced customer development, but supplier network responsiveness did not. Logistics process responsiveness additionally partially mediated the effect of operations systems responsiveness on customer development.

Originality/value

To the best of the researchers' knowledge, no previous studies have empirically examined interrelationships between the dimensions of supply chain responsiveness. Additionally, no previous study has examined the effect of supply chain responsiveness on customer development.
Correlates of burnout among Indian primary school teachers
Authors: Chakravorty Arjun , Singh Pankaj
Published: February 2021

Purpose

This study aims to examine the correlates of burnout among primary school teachers working with public schools in Chhattisgarh-India.

Design/methodology/approach

Data were collected from 713 teachers using a questionnaire survey. Using partial least square path modeling, this study tests the proposed measurement and structural model.

Findings

The study confirmed that general job demands and emotional job demands in a school environment significantly correlated with burnout, which, in turn, has increased somatic symptoms and decreased pro-social behavior among teachers. However, the association of burnout with absenteeism was insignificant. Emotional intelligence (EI) was found to buffer the adverse associations of general job demands and emotional job demands on burnout.

Practical implications

The findings of this study demonstrate that EI has buffering effects on high job demands that consequently reduce burnout. This will help educators and policymakers in shaping and formulating effective policies and practices to deal with burnout.

Originality/value

Earlier studies exploring burnout of primary school teachers, especially in the Indian context, had focused exclusively on demographic factors. This study is an early attempt to understand the impact of contextual factors on burnout thereby helping in designing appropriate interventions thereof. This study additionally rationalizes the unexplored association of burnout with pro-social behavior among educators.
A deplorable community in Bangladesh: tea garden workers
Authors: Rahaman Md. Saidur , Reza Syed Muhammod Ali , Rahman Md. Mizanur , Solaiman Chowdhury Md.
Published: February 2021

Purpose

Throughout history, tea garden workers are treated as slaves of employers and live an inhuman life in modern society. This paper aims to provide an account of the deplorable community (workers) of the tea garden in Bangladesh.

Design/methodology/approach

The authors used a mixed-method research approach to conduct this study. In the first stage, using a semi-structured questionnaire, Focus group discussions (FGDs) were done by forming two groups from two districts to get a clear picture of the tea garden workers’ living standards in Bangladesh. Based on the findings of the FGD, the researchers prepared a structured questionnaire containing the basic elements of their quality of work life. In this stage, the authors collected the information from 200 tea workers about their quality of work life.

Findings

The major finding showed that the overall country’s economy is booming because of tea workers’ contributions, but their economic conditions gradually become impoverished. The workers’ are living with colossal poverty and vulnerability. Besides, the workers are supposed to get fundamental rights, including food, clothing, shelter, education and health, but the higher authorities were found indifferent to take the necessary initiative to implement these rights.

Research limitations/implications

The data was collected only from the tea garden workers. This study excluded any other parties (trade union leaders, panchayats, garden managers and owners). Thus, it is suggested that the researchers should conduct a similar study covering the opinion, including all the parties.

Practical implications

Both the workers and the higher authorities of the tea garden might benefit from this study’s findings. Workers will be more aware of their basic rights. The authorities can also prepare some effective policies to improve the overall quality of life of the tea workers.

Originality/value

To the best knowledge of the authors, this is the first study on tea garden workers’ inhuman life in Bangladesh in the entire emerald insight publishers.
The wage premium and market structure: theory and empirical evidence from Chilean manufacturers
Authors: Wu Ruohan , Miranda Mario Javier , Yen Meng-Fen
Published: February 2021

Purpose

This paper aims to examine how the “wage premium,” the percentage by which wages earned by skilled workers exceed those of unskilled workers, varies across industries characterized by different levels of competitiveness.

Design/methodology/approach

A theoretical model employing constant elasticity of substitution (CES) utility function and constant returns to scale production function is developed and analyzed to derive the effects of industry competitiveness on the wage premium. Econometric methods are applied to Chilean manufacturing data to test implications of theoretical model.

Findings

Once the relative factor endowment is being controlled, market competition significantly reduces the wage premium. More specifically, given with the same relative factor endowment, the wage premium is significantly higher under oligopolistic competition than under monopolistic competition. Empirical evidence from Chilean manufacturers supports our theoretical conclusions.

Practical implications

During economic development, the reallocation of production factors from unskilled labor-intensive to skilled labor-intensive industries raises the wage premiums received by skilled workers. Besides, skilled workers will earn higher wages by working in more highly concentrated industries instead of more competitive industries. This needs to be considered by government policymakers who must balance promotion of technical change with prevention of extreme the income inequality.

Originality/value

This paper examines how market structure affects wage premiums, providing new insights into a well-established literature that largely maintains that wage premiums are primarily a function of relative factor endowments or international trade.
Effect of corporate social responsibility on eco-citizenship behaviour in luxury hotels: eco-lifestyle as a moderator
Authors: Mensah Henry Kofi , Agyapong Ahmed , Osei Benjamin Appiah
Published: February 2021

Purpose

The issues regarding environmental behaviour in the hospitality sector are relatively underexplored, particularly in developing economies. To date, studies on corporate social responsibility (CSR) have reported a positive effect on the behaviour of employees generally. Inspite of the heightened interest in CSR and environmental behaviour, inquiry on this relationship is still deficient in a rigorous examination of potential boundary conditions. Therefore, this study examined the moderating influence of eco-lifestyle on the association between CSR and eco-citizenship behaviour (ECB) as well as its dimensions.

Design/methodology/approach

This study adopted a cross-sectional technique with a sample of 812 employees selected from luxury hotels via simple random sampling. A self-reported questionnaire was used to collect data from the hotel employees Descriptive statistics, Pearson’s correlation test and structural equation modelling were used to present findings.

Findings

The results of this study confirmed that CSR positively influences ECB upon controlling for education, job tenure, income and employee rank. Moreover, eco-lifestyle positively moderates the influence of CSR on ECB and each of its three domains. This study concluded that eco-lifestyle increases the positive impact of CSR on ECB.

Originality/value

Apparently, previous studies in this research area have often proffered an insufficient explanation on the conditions by which CSR positively influence employees’ environmental behaviour. This study considered this condition and examined the extent to which the association between CSR and ECB is moderated by the eco-lifestyle of employees in luxury hotels.
The experience – economy revisited: an interdisciplinary perspective and research agenda
Authors: Chevtchouk Yanina , Veloutsou Cleopatra , Paton Robert A.
Published: February 2021

Purpose

The marketing literature uses five different experience terms that are supposed to represent different streams of research. Many papers do not provide a definition, most of the used definitions are unclear, the different experience terms have similar dimensionality and are regularly used interchangeably or have the same meaning. In addition, the existing definitions are not adequately informed from other disciplines that have engaged with experience. This paper aims to build a comprehensive conceptual framework of experience in marketing informed by related disciplines aiming to provide a more holistic definition of the term.

Design/methodology/approach

This research follows previously established procedures by conducting a systematic literature review of experience. From the approximately 5,000 sources identified in three disciplines, 267 sources were selected, marketing (148), philosophy (90) and psychology (29). To address definitional issues the analysis focused on enlightening four premises.

Findings

This paper posits that the term brand experience can be used in all marketing-related experiences and proposes four premises that may resolve the vagaries associated with the term’s conceptualization. The four premises address the what, who, how and when of brand experience and aim to rectify conceptual issues. Brand experience is introduced as a multi-level phenomenon.

Research limitations/implications

The suggested singular term, brand experience, captures all experiences in marketing. The identified additional elements of brand experience, such as the levels of experience and the revision of emotions within brand experience as a continuum, tempered by repetition, should be considered in future research.

Practical implications

The multi-level conceptualization may provide a greater scope for dynamic approaches to brand experience design thus providing greater opportunities for managers to create sustainable competitive advantages and differentiation from competitors.

Originality/value

This paper completes a systematic literature review of brand experience across marketing, philosophy and psychology which delineates and enlightens the conceptualization of brand experience and presents brand experience in a multi-level conceptualization, opening the possibility for further theoretical, methodological and interdisciplinary promise.