bluuebunny/crossref_metadata_2025 huggingface dataset:
Applications of Boolean modeling to study the dynamics of a complex disease and therapeutics responses
Authors: Hemedan Ahmed Abdelmonem , Schneider Reinhard , Ostaszewski Marek
Published: April 2023

Computational modeling has emerged as a critical tool in investigating the complex molecular processes involved in biological systems and diseases. In this study, we apply Boolean modeling to uncover the molecular mechanisms underlying Parkinson’s disease (PD), one of the most prevalent neurodegenerative disorders. Our approach is based on the PD-map, a comprehensive molecular interaction diagram that captures the key mechanisms involved in the initiation and progression of PD. Using Boolean modeling, we aim to gain a deeper understanding of the disease dynamics, identify potential drug targets, and simulate the response to treatments. Our analysis demonstrates the effectiveness of this approach in uncovering the intricacies of PD. Our results confirm existing knowledge about the disease and provide valuable insights into the underlying mechanisms, ultimately suggesting potential targets for therapeutic intervention. Moreover, our approach allows us to parametrize the models based on omics data for further disease stratification. Our study highlight the value of computational modeling in advancing our understanding of complex biological systems and diseases, emphasizing the importance of continued research in this field. Furthermore, our findings have potential implications for the development of novel therapies for PD, which is a pressing public health concern. Overall, this study represents a significant step forward in the application of computational modeling to the investigation of neurodegenerative diseases, and underscores the power of interdisciplinary approaches in tackling challenging biomedical problems.
Development of subunit selective substrates forTrichomonas vaginalisproteasome
Authors: Fajtova Pavla , Hurysz Brianna M , Miyamoto Yukiko , Serafim Mateus , Jiang Zhenze , Trujillo Diego F. , Liu Lawrence , Somani Urvashi , Almaliti Jehad , Myers Samuel A. , Caffrey Conor R. , Gerwick William H. , Kirk Christopher J , Boura Evzen , Eckmann Lars , O’Donoghue Anthony J
Published: April 2023

The protozoan parasite,Trichomonas vaginalis(Tv) causes trichomoniasis, the most common, non-viral, sexually transmitted infection in the world. Only two closely related drugs are approved for its treatment. The accelerating emergence of resistance to these drugs and lack of alternative treatment options poses an increasing threat to public health. There is an urgent need for novel effective anti-parasitic compounds. The proteasome is a critical enzyme forT. vaginalissurvival and was validated as a drug target to treat trichomoniasis. However, to develop potent inhibitors of theT. vaginalisproteasome, it is essential that we understand which subunits should be targeted. Previously, we identified two fluorogenic substrates that were cleaved byT. vaginalisproteasome, however after isolating the enzyme complex and performing an in-depth substrate specificity study, we have now designed three fluorogenic reporter substrates that are each specific for one catalytic subunit. We screened a library of peptide epoxyketone inhibitors against the live parasite and evaluated which subunits are targeted by the top hits. Together we show that targeting of the β5 subunit ofT. vaginalisis sufficient to kill the parasite, however, targeting of β5 plus either β1 or β2 results in improved potency.
Methionine aminopeptidase 2 and its autoproteolysis product have different binding sites on the ribosome
Authors: Klein Marius A. , Wild Klemens , Kišonaitė Miglė , Sinning Irmgard
Published: April 2023

Excision of the initiator methionine is among the first co-translational processes that occur at the ribosome. While this crucial step in protein maturation is executed by two types of methionine aminopeptidases in eukaryotes (MAP1 and MAP2), additional roles in disease and translational regulation have drawn more attention to MAP2. Here, we report several cryo-EM structures of MAP2 at the 80S-ribosome. The MAP2 interaction is highly robust but can be perturbed by emerging nascent chains, which induce an adaptive tilting of the enzyme. In rotation, the MAP2-specific N-terminal extension engages in stabilizing interactions with the long rRNA expansion segment ES27L. Loss of this extension by autoproteolytic cleavage impedes the tunnel interaction, while promoting MAP2 to enter the ribosomal A-site, where it engages with crucial functional centers of translation. These findings reveal that proteolytic remodeling of MAP2 severely affects ribosome binding, and set the stage for targeted functional studies.
The bloodstream form ofTrypanosoma bruceidisplays non-canonical gluconeogenesis
Authors: Kovářová Julie , Moos Martin , Barrett Michael P. , Horn David , Zíková Alena
Published: April 2023

Trypanosoma bruceiis a causative agent of the Human and Animal African Trypanosomiases. The mammalian stage parasites infect various tissues and organs including the bloodstream, central nervous system, skin, adipose tissue and lungs. They rely on ATP produced in glycolysis, consuming large amounts of glucose, which is readily available in the mammalian host. In addition to glucose, glycerol can also be used as a source of carbon and ATP and as a substrate for gluconeogenesis. However, the physiological relevance of glycerol-fed gluconeogenesis for the mammalian-infective life cycle forms remains elusive. To demonstrate its (in)dispensability, first we must identify the enzyme(s) of the pathway. Loss of the canonical gluconeogenic enzyme, fructose-1,6-bisphosphatase, does not abolish the process hence at least one other enzyme must participate in gluconeogenesis in trypanosomes. Using a combination of CRISPR/Cas9 gene editing and RNA interference, we generated mutants for four enzymes potentially capable of contributing to gluconeogenesis: fructose-1,6-bisphoshatase, sedoheptulose-1,7-bisphosphatase, phosphofructokinase and transaldolase, alone or in various combinations. Metabolomic analyses revealed that flux through gluconeogenesis was maintained irrespective of which of these genes were lost. Our data render unlikely a previously hypothesised role of a reverse phosphofructokinase reaction in gluconeogenesis and preclude the participation of a novel biochemical pathway involving transaldolase in the process. The sustained metabolic flux in gluconeogenesis in our mutants, including a triple-null strain, indicates the presence of a unique enzyme participating in gluconeogenesis. Additionally, the data provide new insights into gluconeogenesis and the pentose phosphate pathway, and improve the current understanding of carbon metabolism of the mammalian-infective stages ofT. brucei.

Author Summary

Trypanosoma bruceiis a unicellular parasite causing sleeping sickness in humans and nagana disease in cattle. The parasite invades the bloodstream and cerebrospinal fluid and only recently, it has been shown to infect additional tissues such as skin, adipose tissue, or lungs. While the glucose-based metabolism of the bloodstream form is well understood, the parasite’s metabolism in these secondary tissues has not been sufficiently explored, despite its importance for drug development. One possibility is the use of gluconeogenesis since the mammalian-infective stages can use glycerol as a carbon and ATP source. First, enzymes involved in gluconeogenesis have to be identified, then it can be tested if the pathway is advantageous for the survival of the parasite. We generated mutants in four different enzymes potentially involved in this metabolic pathway. Surprisingly, the flux in gluconeogenesis was maintained in all cell lines tested, implying that another non-canonical enzyme participates in the production of glucose from glycerol in these parasites.
Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
Authors: Henrion Lucas , Martinez Juan Andres , Vandenbroucke Vincent , Delvenne Mathéo , Telek Samuel , Zicler Andrew , Grünberger Alexander , Delvigne Frank
Published: April 2023

Isogenic cell populations can cope with stress conditions by switching to alternative phenotypes. Even if it can lead to increased fitness in a natural context, this feature is typically unwanted for a range of applications (e.g., bioproduction, synthetic biology, biomedicine…) where it tends to decrease the controllability of the cellular response. However, little is known about the diversification profiles that can be adopted by a cell population. We characterized the diversification dynamics for various systems (bacteria and yeast) and for different phenotypes (utilization of alternative carbon sources, general stress response and more complex development patterns). Interestingly, our results suggest that the diversification dynamics and the fitness cost associated with cell switching are coupled. For quantifying the contribution of the switching cost on population dynamics, we built a stochastic model that allowed us to reproduce the dynamics observed experimentally and identified three diversification regimes, i.e., constrained (at low switching cost), dispersed (at medium and high switching cost), and bursty (for very high switching cost). Furthermore, we used a cell-machine interface that we call the Segregostat to demonstrate that different levels of control can be applied to these diversification regimes, enabling applications involving more precise cellular responses.
Differential Regulation of Retinoic Acid Metabolism in Fanconi Anemia
Authors: Blaize Justin L. , Noori Bahaa M. , Hunter Kelsey P. , Henrikson Kathryn A. , Atoyan Janet A. , Ardito Alan A. , Donovan Frank X. , Chandrasekharappa Settara C. , Schindler Detlev , Howlett Niall G.
Published: April 2023

Fanconi anemia (FA) is a rare genetic disease characterized by heterogeneous congenital abnormalities and increased risk for bone marrow failure and cancer. FA is caused by mutation of any one of 23 genes, the protein products of which function primarily in the maintenance of genome stability. An important role for the FA proteins in the repair of DNA interstrand crosslinks (ICLs) has been establishedin vitro. While the endogenous sources of ICLs relevant to the pathophysiology of FA have yet to be clearly determined, a role for the FA proteins in a two-tier system for the detoxification of reactive metabolic aldehydes has been established. To discover new metabolic pathways linked to FA, we performed RNA-seq analysis on non-transformed FA-D2 (FANCD2-/-) and FANCD2-complemented patient cells. Multiple genes associated with retinoic acid metabolism and signaling were differentially expressed in FA-D2 (FANCD2-/-) patient cells, includingALDH1A1andRDH10, which encode for retinaldehyde and retinol dehydrogenases, respectively. Increased levels of the ALDH1A1 and RDH10 proteins was confirmed by immunoblotting. FA-D2 (FANCD2-/-) patient cells displayed increased aldehyde dehydrogenase activity compared to the FANCD2-complemented cells. Upon exposure to retinaldehyde, FA-D2 (FANCD2-/-) cells exhibited increased DNA double-strand breaks and checkpoint activation indicative of a defect in the repair of retinaldehyde-induced DNA damage. Our findings describe a novel link between retinoic acid metabolism and FA and identify retinaldehyde as an additional reactive metabolic aldehyde relevant to the pathophysiology of FA.
Neural Geometry from Mixed Sensorimotor Selectivity for Predictive Sensorimotor Control
Authors: Zhang Yiheng , Chen Yun , Wang Tianwei , Cui He
Published: April 2023

Although recent studies suggest that activity in the motor cortex, in addition to generating motor outputs, receives substantial information regarding sensory inputs, it is still unclear how sensory context adjusts the motor commands. Here, we recorded population neural activity in the motor cortex via microelectrode arrays while monkeys performed flexible manual interceptions of moving targets. During this task, which requires predictive sensorimotor control, the activity of most neurons in the motor cortex encoding upcoming movements, was influenced by ongoing target motion. Single-trial neural states at the movement onset formed staggered orbital geometries, suggesting that target motion modulates peri-movement activity in an orthogonal manner. This neural geometry was further evaluated with a representational model and recurrent neural networks (RNNs) with task-specific input-output mapping. We propose that the sensorimotor dynamics can be derived from neuronal mixed sensorimotor selectivity and dynamic interaction between modulations.
An experimental comparison of the Digital Spatial Profiling and Visium spatial transcriptomics technologies for cancer research
Authors: Wang Taopeng , Harvey Kate , Reeves John , Roden Daniel L. , Bartonicek Nenad , Yang Jessica , Al-Eryani Ghamdan , Kaczorowski Dominik , Chan Chia-Ling , Powell Joseph , O’Toole Sandra , Lim Elgene , Swarbrick Alexander
Published: April 2023

Background

Spatial transcriptomic technologies are powerful tools for resolving the spatial heterogeneity of gene expression in tissue samples. However, little evidence exists on relative strengths and weaknesses of the various available technologies for profiling human tumour tissue. In this study, we aimed to provide an objective assessment of two common spatial transcriptomics platforms, 10X Genomics’ Visium and Nanostring’s GeoMx DSP.

Method

The abilities of the DSP and Visium platforms to profile transcriptomic features were compared using matching cell line and primary breast cancer tissue samples. A head-to-head comparison was conducted using data generated from matching samples and synthetic tissue references. Platform specific features were also assessed according to manufacturers’ recommendations to evaluate the optimal usage of the two technologies.

Results

We identified substantial variations in assay design between the DSP and Visium assays such as transcriptomic coverage and composition of the transcripts detected. When the data was standardised according to manufacturers’ recommendations, the DSP platform was more sensitive in gene expression detection. However, its specificity was diminished by the presence of non-specific detection. Our results also confirmed the strength and weakness of each platform in characterising spatial transcriptomic features of tissue samples, in particular their application to hypothesis generation versus hypothesis testing.

Conclusion

In this study, we share our experience on both DSP and Visium technologies as end users. We hope this can guide future users to choose the most suitable platform for their research. In addition, this dataset can be used as an important resource for the development of new analysis tools.
Heather pollen is not necessarily a healthy diet for bumble bees
Authors: Tourbez Clément , Semay Irène , Michel Apolline , Michez Denis , Gerbaux Pascal , Gekière Antoine , Vanderplanck Maryse
Published: April 2023

There is evidence that specialised metabolites of flowering plants occur in both vegetative parts and floral resources (i.e., pollen and nectar), exposing pollinators to their biological activities. While such metabolites may be toxic to bees, it may also help them to deal with environmental stressors. One example is heather nectar which has been shown to limit bumble bee infection by a trypanosomatid parasite,Crithidiasp., because of callunene activity. Besides in nectar, heather harbours high content of specialised metabolites in pollen such as flavonoids but they have been poorly investigated. In this study, we aimed to assess the impact ofCrithidiasp., heather pollen and its flavonoids on bumble bees using non-parasitised and parasitised microcolonies fed either control pollen diet (i.e., willow pollen), heather pollen diet, or flavonoid-supplemented pollen diet. We found that heather pollen and its flavonoids significantly affected microcolonies by decreasing pollen collection as well as offspring production, and by increasing male fat body content while parasite exposure had no significant effect except for an increase in male fat body. We did not highlight any medicinal effect of heather pollen or its flavonoids on parasitised bumble bees. Our results provide insight into the impact of pollen specialised metabolites in heather-bumble bee-parasite interactions. They underline the contrasting roles for bumble bees of the two floral resources and highlight the importance of considering both nectar and pollen when addressing medicinal effects of a plant towards pollinators.
An improved mouse model of sepsis based on intraperitoneal injections of the enriched culture of cecum slurry
Authors: Atre Rajat , Sharma Rahul , Obukhov Alexander G , Saqib Uzma , Umar Sadiq , Darwhekar Gajanan N , Baig Mirza S
Published: April 2023

Sepsis is a life-threatening clinical syndrome comprising multiorgan dysfunction caused by a disproportionate body immune response to infection that can lead to septic shock and death. The current sepsis model has certain limitations. The gold standard Cecal Ligation and Puncture (CLP) model is known for its high variability owing to the undefined extent of cecum ligation, unstandardized cecal content, and degree of puncture that may vary in different laboratories. Here, we present an improved, efficient intraperitoneal (i.p) injection-based cecal slurry culture method of sepsis. Using this novel approach, we determined the optimal polymicrobial concentration that is sufficient to cause sepsis in mice. We also proposed the enrichment of bacterial culture, allowing the development of either gram-negative or gram-positive bacteria-induced sepsis models. Since those enriched bacterial cultures can be stored in glycerol at −80°C, it gives the ethical advantage of avoiding animal sacrifice for each experiment and experimental reproducibility.
Therapeutic interventions on human xenografts promote systemic dissemination of oncogenes
Authors: Raghuram Gorantla V , Pal Kavita , Sriram Gaurav , Khan Afzal , Joshi Ruchi , Jadhav Vishalkumar , Shinde Sushma , Sheikh Alfina , Rane Bhagyeshri , Kangne Harshada , Mittra Indraneel
Published: April 2023

We generated xenografts of human cancer cells in mice, and using immuno-FISH analysis detected multiple co-localizing signals of human DNA and eight human oncoproteins in brain cells. Signals increased dramatically five days after treatment with chemotherapy, localized radiotherapy or surgery, which could be minimized by concurrent treatment with cell-free chromatin deactivating agents. These results suggest that therapeutic interventions may potentially encourage metastatic spread which is preventable by deactivating cell-free chromatin.
Early-life environmental effects on mitochondrial aerobic metabolism: an experimental brood size manipulation in wild great tits
Authors: Cossin-Sevrin Nina , Stier Antoine , Hukkanen Mikaela , Zahn Sandrine , Viblanc Vincent A. , Anttila Katja , Ruuskanen Suvi
Published: April 2023

Parental care (including postnatal provisioning) is a major component of the offspring’s early-life environment. In avian species, the number of chicks in the nest and subsequent sibling competition for food are known to affect chick’s growth, leading in some cases to long-lasting effects for the offspring. Because of its central role in converting energy, variation in the offspring’s mitochondrial metabolism could be an important pathway underlying variation in growth patterns. Here, we performed a brood size manipulation in great tits (Parus major) to unravel its impact on offspring’s mitochondrial metabolism and reactive oxygen species (ROS) production in red blood cells. We investigated the effects of brood size on chicks’ growth and survival, and tested for long-lasting effects on juvenile mitochondrial metabolism and phenotype. As expected, chicks raised in reduced broods had a higher body mass compared to enlarged and control groups. However, mitochondrial metabolism and ROS production were not significantly affected by the treatment either at chick or juvenile stages. Chicks in very small broods were smaller in size and had higher mitochondrial metabolic rates. The nest of rearing has a significant effect on nestling mitochondrial metabolism, yet variation in mitochondrial metabolism at the early-life stages are not associated with survival chances. The contribution of the rearing environment in determining offspring mitochondrial metabolism emphasizes the plasticity of mitochondrial metabolism in changing environments. Further studies would be needed to closely investigate what are the major environmental cues affecting the offspring mitochondrial metabolism during the growth period.
When is a slender not a slender? The cell-cycle arrest and scarcity of slender parasites challenges the role of bloodstream trypanosomes in infection maintenance
Authors: Larcombe Stephen D. , Briggs Emma M. , Savill Nick , Szoor Balazs , Matthews Keith R.
Published: April 2023

The development ofTrypanosoma bruceiin its mammalian host is marked by a distinct morphological change as replicative “slender” forms differentiate into cell-cycle arrested “stumpy” forms in a quorum-sensing dependent manner. Although stumpy forms dominate chronic infections at the population level, the proportion of replicative parasites at the individual cell level and the irreversibility of arrest in the bloodstream is unclear. Here, we experimentally demonstrate that developmental cell cycle arrest is definitively irreversible in acute and chronic infections in mice. Furthermore, analysis of replicative capacity and single-cell transcriptome profiling reveals a temporal hierarchy, whereby cell-cycle arrest and appearance of a stumpy-like transcriptome precedes irreversible commitment and morphological change. Unexpectedly, we show that proliferating parasites are exceptionally scarce in the blood after infections are established. This challenges the ability of bloodstream trypanosomes to sustain infection by proliferation or antigenic variation, these parasites instead being overwhelmingly adapted for transmission.
Foxp- and Skor-family proteins control differentiation of Purkinje cells from Ptf1a and Neurogenin1-expressing progenitors in zebrafish
Authors: Itoh Tsubasa , Uehara Mari , Yura Shinnosuke , Wang Jui Chun , Nakanishi Akiko , Shimizu Takashi , Hibi Masahiko
Published: April 2023

Cerebellar neurons such as Purkinje cells (PCs) and granule cells (GCs) are differentiated from neural progenitors expressing proneural genes. Zebrafish mutants of proneural genesptf1aandneurogenin1showed a reduction or loss of PCs, GABAergic interneurons (INs), and reduced expression of GC progenitor genesatoh1a/b/c. Lineage tracing revealed that theptf1a-expressing progenitors gave rise to PCs, INs, and a part of GCs in zebrafish. These data indicate that theptf1a/neurognin1-expressing neural progenitors can generate a variety of cerebellar neurons. In this study, we found that genes encoding transcriptional regulators Foxp1b and Foxp4, as well as Skor1b and Skor2, which are reportedly expressed in PCs, were not expressed inptf1a;neurogenin1mutants.foxp1b;foxp4mutants showed a strong reduction in PCs, whileskor1b;skor2mutants completely lacked PCs but instead displayed an increase in immature GCs. Misexpression ofskor2in GC progenitors expressingatoh1csuppressed GC fate. These data indicate that Foxp1b/4 and Skor1b/2 function as key transcriptional regulators in the initial step of PC differentiation fromptf1a/neurogenin1-expressing neural progenitors, while Skor1b and Skor2 control PC differentiation by suppressing their differentiation into GCs.
Enhanced performance of gene expression predictive models with protein-mediated spatial chromatin interactions
Authors: Chiliński Mateusz , Lipiński Jakub , Agarwal Abhishek , Ruan Yijun , Plewczynski Dariusz
Published: April 2023

There have been multiple attempts to predict the expression of the genes based on the sequence, epigenetics, and various other factors. To improve those predictions, we have decided to investigate adding protein-specific 3D interactions that play a major role in the compensation of the chromatin structure in the cell nucleus. To achieve this, we have used the architecture of one of the state-of-the-art algorithms, ExPecto (J. Zhou et al., 2018), and investigated the changes in the model metrics upon adding the spatially relevant data. We have used ChIA-PET interactions that are mediated by cohesin (24 cell lines), CTCF (4 cell lines), and RNAPOL2 (4 cell lines). As the output of the study, we have developed the Spatial Gene Expression (SpEx) algorithm that shows statistically significant improvements in most cell lines.
Xrp1 governs the stress response program to spliceosome dysfunction
Authors: Stanković Dimitrije , Tain Luke , Uhlirova Mirka
Published: April 2023

Co-transcriptional processing of nascent pre-mRNAs by the spliceosome is vital to regulating gene expression and maintaining genome integrity. Here, we show that the deficiency of functional U5 snRNPs inDrosophilaimaginal cells causes extensive transcriptome remodeling and accumulation of highly mutagenic R-loops, triggering a robust stress response and cell cycle arrest. Despite compromised proliferative capacity, the U5 snRNP deficient cells increased protein translation and cell size, causing intra-organ growth disbalance before being gradually eliminated via apoptosis. We identify the Xrp1-Irbp18 heterodimer as the primary driver of transcriptional and cellular stress program downstream of U5 snRNP malfunction. Knockdown ofXrp1orIrbp18in U5 snRNP deficient cells attenuated JNK and p53 activity, restored normal cell cycle progression and growth, and inhibited cell death. Reducing Xrp1-Irbp18, however, did not rescue the splicing defects and the organismal lethality, highlighting the requirement of accurate splicing for cellular and tissue homeostasis. Our work provides novel insights into the crosstalk between splicing and the DNA damage response and defines the Xrp1-Irbp18 heterodimer as a critical sensor of spliceosome malfunction.
The pitfalls of negative data bias for the T-cell epitope specificity challenge
Authors: Dens Ceder , Laukens Kris , Bittremieux Wout , Meysman Pieter
Published: April 2023

Summary / Abstract

Even high-performing machine learning models can have problems when deployed in a real-world setting if the data used to train and test the model contains biases. TCR–epitope binding prediction for novel epitopes is a very important but yet unsolved problem in immunology. In this article, we describe how the technique used to create negative data for the TCR–epitope interaction prediction task can lead to a strong bias and makes that the performance drops to random when tested in a more realistic scenario.
The hepatokine FGL1 regulates hepcidin and iron metabolism during the recovery from hemorrhage-induced anemia in mice
Authors: Sardo Ugo , Perrier Prunelle , Cormier Kevin , Sotin Manon , Desquesnes Aurore , Cannizzo Lisa , Ruiz-Martinez Marc , Thevenin Julie , Billoré Benjamin , Jung Grace , Abboud Elise , Peyssonnaux Carole , Nemeth Elizabeta , Ginzburg Yelena Z. , Ganz Tomas , Kautz Léon
Published: April 2023

As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure adequate supply of iron to the bone marrow for red blood cells production. However, mounting evidence suggested that another factor may exert a similar function. We identified the hepatokine FGL1 as a previously undescribed suppressor of hepcidin that is induced in the liver in response to hypoxia during the recovery from anemia and in thalassemic mice. We demonstrated that FGL1 is a potent suppressor of hepcidinin vitroandin vivo. Deletion ofFgl1in mice results in a blunted repression of hepcidin after bleeding. FGL1 exerts its activity by direct binding to BMP6, thereby inhibiting the canonical BMP-SMAD signaling cascade that controls hepcidin transcription.

Key points

1/ FGL1 regulates iron metabolism during the recovery from anemia.

2/ FGL1 is an antagonist of the BMP/SMAD signaling pathway.
Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma
Authors: Zacarías-Fluck Mariano F. , Massó-Vallés Daniel , Giuntini Fabio , González-Larreategui Íñigo , Kaur Jastrinjan , Casacuberta-Serra Sílvia , Jauset Toni , Martínez-Martín Sandra , Martín-Fernández Génesis , Serrano del Pozo Erika , Foradada Laia , Grueso Judit , Nonell Lara , Beaulieu Marie-Eve , Whitfield Jonathan R. , Soucek Laura
Published: April 2023

MYC's key role in oncogenesis and tumor progression has long been established for most human cancers. In melanoma, its deregulated activity by amplification of 8q24 chromosome or by upstream signaling coming from activating mutations in the RAS/RAF/MAPK pathway—the most predominantly mutated pathway in this disease—turns MYC into not only a driver but also a facilitator of melanoma progression, with documented effects leading to an aggressive clinical course and resistance to targeted therapy. Here, by making use of Omomyc, the most characterized MYC inhibitor to date that has just successfully completed a phase I clinical trial, we show for the first time that MYC inhibition in melanoma induces remarkable transcriptional modulation, resulting in severely compromised tumor growth and a clear abrogation of metastatic capacity independently of the driver mutation. By reducing MYC's transcriptional footprint in melanoma, Omomyc elicits gene expression profiles remarkably similar to those of patients with good prognosis, underlining the therapeutic potential that such an approach could eventually have in the clinic in this dismal disease.
Process management: systematic review of determining factors for automation
Authors: Arantes Mayara Cassiano , Santos Silvio Francisco dos , Simão Victor Gomes
Published: April 2023

Purpose

The objective of this article is to identify through a literature study which factors determine the success of process automation in management systems.

Design/methodology/approach

A systematic approach is applied to analyze the available literature on the topic. The first stage of the study consisted of analyzing publications aiming to identify aspects that may influence the implementation of automated process management tools in management systems. In the second stage, a synthesis of the information was performed, resulting in a set of representative factors of the aspects identified.

Findings

As a result of the literature review, determinant aspects were identified for the implementation of process automation in organizations in general. These elements are summarized in the following factors: Characterization and diversity of the context, Organizational Performance, People Engagement, Knowledge Management, Automated Process Management and Information Technology.

Originality/value

Prior knowledge of the determinants and associated aspects has the potential to optimize process automation, as it eliminates unnecessary steps and allows better application of the available resources.
Ripple effect of disruptions on performance in supply chains: an empirical study
Authors: Duong An Thi Binh , Pham Tho , Truong Quang Huy , Hoang Thinh Gia , McDonald Scott , Hoang Thu-Hang , Pham Hai Thanh
Published: April 2023

Purpose

The present study is performed to identify the propagation mechanism of the ripple effect as well as examine the simultaneous impact of risks on supply chain (SC) performance.

Design/methodology/approach

A theoretical framework with many hypotheses regarding the relationships between SC risk types and performance is established. The data are collected from a large-scale survey supported by a project of the Japanese government to promote sustainable socioeconomic development for the Association of Southeast Asian Nations (ASEAN) region, with the participation of 207 firms. Structural equation modeling (SEM) is used to test the hypotheses of the theoretical framework.

Findings

It is indicated that human-made risk causes operational risk, while natural risk causes both supply risk and operational risk. Furthermore, the impacts of human-made risk and natural risk on performance are amplified through operational risk.

Research limitations/implications

This study is one of the first attempts that identifies the propagation mechanism of the ripple effect and examines the simultaneous impact of risks on performance in construction SCs.

Originality/value

Although many studies on risk management in construction SCs have been carried out, they mainly focus on risk identification or quantification of risk impact. It is observed that research on the ripple effect of disruptions has been very scarce.
Digitalizing business models in hospitality ecosystems: toward data-driven innovation
Authors: Troisi Orlando , Visvizi Anna , Grimaldi Mara
Published: April 2023

Purpose

Digitalization accelerates the need of tourism and hospitality ecosystems to reframe business models in line with a data-driven orientation that can foster value creation and innovation. Since the question of data-driven business models (DDBMs) in hospitality remains underexplored, this paper aims at (1) revealing the key dimensions of the data-driven redefinition of business models in smart hospitality ecosystems and (2) conceptualizing the key drivers underlying the emergence of innovation in these ecosystems.

Design/methodology/approach

The empirical research is based on semi-structured interviews collected from a sample of hospitality managers, employed in three different accommodation services, i.e. hotels, bed and breakfast (B&Bs) and guesthouses, to explore data-driven strategies and practices employed on site.

Findings

The findings allow to devise a conceptual framework that classifies the enabling dimensions of DDBMs in smart hospitality ecosystems. Here, the centrality of strategy conducive to the development of data-driven innovation is stressed.

Research limitations/implications

The study thus developed a conceptual framework that will serve as a tool to examine the impact of digitalization in other service industries. This study will also be useful for small and medium-sized enterprises (SMEs) managers, who seek to understand the possibilities data-driven management strategies offer in view of stimulating innovation in the managers' companies.

Originality/value

The paper reinterprets value creation practices in business models through the lens of data-driven approaches. In this way, this paper offers a new (conceptual and empirical) perspective to investigate how the hospitality sector at large can use the massive amounts of data available to foster innovation in the sector.
The impact of personal reputation on leader emergence in autonomous work teams: theoretical considerations for future research
Authors: Horwitz Sujin K.
Published: April 2023

Purpose

Research has demonstrated that varying degrees and combinations of individual traits, behaviors and characteristics influence the emergence of leaders in teams. While existing models have shown that such variables affect leader choice independently and interactively, the overall findings suggest that there is still a lack of research on a potentially significant factor, the impact of personal reputation on leader selection in autonomous work teams (AWTs), an increasingly ubiquitous team practice in organizations. This preliminary review thus aims to offer a general overview of personal reputation and its effects on leader emergence in the context of AWTs.

Design/methodology/approach

By surveying extant literature on team leader emergence, this review has identified that the potential impact of personal reputation on leader selection in teams is significant yet largely ignored.

Findings

Models of leader emergence in teams should incorporate the realistic assumption that teams formed in organizations are often comprised of individuals who have information on others either directly or indirectly. Personal reputation based on an individual’s history thus moderates how one’s behaviors or traits exhibited become contextualized in the overall assessment of leader desirability and selection in teams.

Research limitations/implications

Based on a review of existing research on leadership emergence and personal reputation, this work contends that the external validity and predictive value of leader emergence models would greatly benefit from the inclusion of employee reputations as a moderating variable in the future assessment of the leader emergence process in AWTs.

Practical implications

By designing models that explain the potential effects of personal reputations on leader emergence in self-managed teams, team members and managers can be better elucidated and ultimately improve their understanding of the process of the evaluation and selection of team leaders.

Originality/value

Despite the prolific research on leader emergence, there is still a paucity of studies examining personal reputational effects on leader selection, especially in the context of AWTs. This work is the first review piece calling for the inclusion of personal reputation, a substantive factor overlooked and excluded in previous models, to enhance the current understanding of leader emergence in AWTs.
Perceived employability in a situation of crisis: the influence of the external context and perceived financial threat
Authors: Silva Ana Maria , Gomes Jorge F.S. , Monteiro Sílvia
Published: April 2023

Purpose

This study aims to analyse how people's perceived employability was affected during the coronavirus disease 2019 (COVID-19) pandemic. This study explores individuals' perceived financial threat, age and work situation as factors that shape perceived employability.

Design/methodology/approach

Data were collected via a survey at three different times between October 2020 and May 2021, which were chosen to reflect the evolution of the pandemic. The participants (n = 124) reported participants' perceived employability and financial threat during the pandemic in Portugal. Perceived employability is a multidimensional concept, as this includes the following scales: employment protective behaviour, employment risk, job-seeking behaviour, self-control and self-learning.

Findings

Participants' overall perceived employability failed to record significant variance over the period under analysis. Nevertheless, perceived employment protective behaviour decreased the most, especially in the case of young adults (aged 18 to 24). Individuals' perceived financial threat varied according to the external context, being lower during the last moment of data collection, which corresponded to the less-socially and economically restrictive period. Employees with the most stable work condition, i.e. with a permanent employment contract, were those who felt less financially threatened when compared to other respondents. A negative relationship between perceived employability and perceived financial threat was identified during the third moment of data collection.

Originality/value

The research informs about how individuals perceive themselves in a highly unpredictable and unstable context. The longitudinal approach shows how the external context affected people's perceived employability and financial threat throughout the pandemic.
Re-examining the roles of experience quality at festivals: a comparative analysis using SEM and fsQCA
Authors: Saha Parmita , Nath Atanu , Sit Kokho (Jason)
Published: April 2023

Purpose

The purpose of this study is to reexamine the dimensionality and role of experience quality (EQ) to explain other related factors, namely, perceived value, satisfaction and behavioral intention. Using dual methodological approaches of fuzzy set qualitative comparative analysis (fsQCA) and structural equations modeling (SEM), it seeks to establish the EQ’s construct and predictive validity.

Design/methodology/approach

Grounded in cross-sectional and online research design, the present study surveyed 881 attendees of an annual music festival (Malakoff) held in Norway and subjected the quantitative data to SEM and fsQCA.

Findings

Both SEM and fsQCA confirmed the socializing and enjoyment dimensions of EQ, with good validity and reliability, as well as the functional and emotional value dimensions explaining visitors’ perceived value of attending a festival. Both statistical analyses also showed that perceived value-derived satisfaction leads to behavioral intention regarding festival visits.

Practical implications

This study provides numerous valuable consequences for festival organizers, or marketers that can aid in developing effective strategies to measure visitors’ perceived quality of experience and numerous practical implications for festival organizers or marketers can help in developing effective strategies to measure visitors’ perceived quality of experience and then increase value perceptions, satisfaction and behavioral intentions toward attending festivals.

Originality/value

To the best of the authors’ knowledge, this study is among the first to adopt a dual-dimensional framework to measure EQ in festivals and establish its utility with two statistical approaches (SEM and fsQCA). It also shows the utility of perceived value, initially developed for adventure tourists, to study visitors’ experience with festivals.
Energy poverty and its impacts on health and education: a systematic review
Authors: Katoch Om Raj , Sharma Romesh , Parihar Sarita , Nawaz Ashraf
Published: April 2023

Purpose

People with energy poverty are denied the modern energy services such as cooking, lighting, heating, cooling and communication. These needs are all crucial to maintaining an acceptable level of living standards. This paper aims to examine the effects of energy poverty on health and education.

Design/methodology/approach

This systematic review was conducted using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The ScienceDirect, Scopus and Google Scholar databases were used to search the studies conducted between 2012 and 2022. Studies included in this review were searched with some combinations of keywords and saved in Mendeley Desktop for review and referencing. Of 1,745 articles retrieved after removing the duplicates from the databases, 22 met the inclusion criteria.

Findings

Out of the total 22 studies reviewed, six were conducted in Asia, six in Europe, four in Africa, three in developing countries and one each in North America, Australia and at global level. Results indicated that impacts of energy poverty on health and education were negative. Efforts should be made to improve the economic conditions of the population in order to allow them access to energy services to achieve higher levels of living.

Practical implications

As this systematic review excludes non-peer-reviewed literature, case studies, reports and theses, and only includes studies published between 2012 and 2022 in English language only, consequently, it may not provide an exhaustive overview of the literature on topic.

Originality/value

To the best of the authors’ knowledge, this is the first systematic review to investigate the relationship between energy poverty, health and education conducted here. The search methodologies involve systematic searches of databases and other manual searches. Considering the wide inclusion criteria, this review is useful as a general overview of the issues and identifies particular gaps in the existing evidence.
Green transformational leadership and pro-environmental behaviour: unravelling the underlying mechanism in the context of hotel industry
Authors: Sachdeva Chetna , Singh Tripti
Published: April 2023

Purpose

Despite the research conducted on transformational leadership has contributed to our understanding of its impact on non-green employee outcomes, there is still a lack of comprehension regarding the influence of environment-specific transformational leadership, also known as green transformational leadership (GTL), on employee green outcomes and the underlying mechanisms that drive this relationship. Thus, to address this gap, this study aims to examine the effects of GTL on pro-environmental behaviour (PEB) among employees working in three- to five-star hotels in India. The study also aims to investigate the potential mediating role of green human resource management (GHRM) and the moderating effect of environmental concern (EC) on the relationship between GHRM and PEB.

Design/methodology/approach

The study collected data from 181 employees working in various 3–5-star hotels operating in India. Structural equation modelling using Smart PLS-4 and SPSS PROCESS MACRO (Model 14) were used to test the hypotheses.

Findings

The results validated the significant positive impact of GTL on PEB. The findings suggest a significant mediating effect of GHRM in the GTL–PEB relationship, and EC negatively moderated the indirect effect of GTL on PEB through GHRM.

Practical implications

The findings suggest that GTL can have a positive impact on employee green outcomes in the hotel industry. The study provides useful insights for policymakers in the hospitality sector, specifically hotels.

Originality/value

To the best of the authors’ knowledge, this study is the first to examine the relationships between GTL, GHRM, EC and PEB using empirical data from hotels in India. The study contributes to the growing body of research on green leadership and employee green outcomes.
Role of perceived brand globalness and localness in developing consumer word-of-mouth in the hospitality industry
Authors: Safeer Asif Ali , Zhou Yewang
Published: April 2023

Purpose

The purpose of this study is to examine the role of perceived brand globalness (PBG) and perceived brand localness (PBL) in developing consumer word-of-mouth (CWOM) via brand attitude (BATT) by incorporating the moderating role of consumer ethnocentrism (CET) and perceived brand origin (PBO) as well as considering brand familiarity (BF) as a covariate in the context of global and local quick-service restaurant (QSR) brands in emerging markets.

Design/methodology/approach

This study obtained 764 responses from Chinese consumers through an online survey and analyzed the data using the maximum-likelihood estimation technique with structural equation modeling.

Findings

After controlling brand familiarity, this study revealed that PBG and PBL are critical components that drive brand attitude, which positively improves CWOM toward global and local QSR brands. Similarly, PBG and PBL are important brand attributes that directly influence CWOM. Importantly, this research found the significant role of PBO on brand attitude toward perceived local brands compared to global QSR brands. Although this study did not discover the influence of CET as expected. However, these insights may assist global and local managers to rethink their strategies in emerging markets.

Research limitations/implications

This study was conducted exclusively in China. However, additional studies may be considered in other countries, such as comparing Asian vs European consumers.

Practical implications

This study provides recommendations to global and local managers to support them in designing and executing several brand positioning strategies in the QSR industry.

Originality/value

This novel study contributes to the accessibility–diagnosticity theory and signaling theory by examining consumers' perceptions of global and local QSR brands.