bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of novel bat coronaviruses in Spain
Authors: Soriano-Tordera Clàudia , Buigues Jaime , Viñals Adrià , Muscolino Elena , Martínez-Recio Raquel , Díez Juana , Monrós Juan S , Cuevas José M. , Dufloo Jérémy , Sanjuán Rafael
Published: January 2025

The zoonotic transmission of bat coronaviruses poses a threat to human health. However, the diversity of bat-borne coronaviruses remains poorly characterized in many geographical areas. Here, we recovered six complete coronavirus genomes by performing a metagenomic analysis of fecal samples from hundreds of individual bats captured in Spain, a country with high bat species diversity. Three of these genomes corresponded to potentially novel coronavirus species belonging to the alphacoronavirus genus. Phylogenetic analyses revealed that some of these viruses are closely related to coronaviruses previously described in bats from other countries, suggesting the existence of a shared viral reservoir worldwide. Using viral pseudotypes, we investigated the receptor usage of the identified viruses and found that one of them can use human and bat ACE2, highlighting its zoonotic potential. However, the receptor usage of the other viruses remains unknown. This study broadens our understanding of coronavirus diversity and identifies research priorities for the prevention of zoonotic viral outbreaks.

Author summary

Bats carry many viruses, some of which can cross the species barrier and infect humans, a process known as zoonosis. In particular, bat-borne coronaviruses pose a significant threat to human health. To improve our pandemic preparedness, it is essential to characterize the diversity and zoonotic potential of bat coronaviruses. However, such research efforts have historically suffered from a strong geographical bias. For example, despite the rich bat diversity in Spain, few studies have searched for coronaviruses in Iberian bats. Here, we used viral metagenomics to test for the presence of coronaviruses in more than 200 bat samples collected across Spain. We detected six complete coronaviruses, three of which were proposed to be new viral species. We characterized their relationship to previously identified viruses and their ability to use known coronavirus receptors to enter cells, demonstrating that one virus could use human ACE2 as a receptor. Our results highlight the diversity of bat-borne coronaviruses in Spain, their zoonotic potential, and the need to better characterize coronavirus diversity worldwide.
TRIM21-NUP98 interface accommodates structurally diverse molecular glue degraders
Authors: Cheng Yalong , Cao Longzhi , Lu Panrui , Xue Lei , Li Xiaomei , Wang Qingyang , Dou Dengfeng , Li Jin , Han Ting
Published: January 2025

Molecular glue degraders enable targeted protein degradation by bridging interactions between target proteins and E3 ubiquitin ligases. Whereas some protein-protein interfaces exhibit the capacity to accommodate structurally diverse degraders, the extent of this adaptability across molecular glue targets remains unclear. We recently identified (S)-ACE-OH as a molecular glue degrader that recruits the E3 ubiquitin ligase TRIM21 to the nuclear pore complex by recognizing NUP98, thereby inducing the degradation of nuclear pore proteins. Here, we analyzed public compound toxicity data across a large collection of cell lines and identified two additional molecular glue degraders, PRLX 93936 and BMS-214662, that engage the TRIM21-NUP98 interface to induce the degradation of nucleopore proteins. Additionally, we confirmed that HGC652, another TRIM21-dependent molecular glue degrader, also binds at this interface. Together with our previously characterized degrader (S)-ACE-OH, these findings demonstrate that the TRIM21-NUP98 interface can accommodate structurally diverse molecular glue degraders, expanding the potential for its therapeutic exploitation.
PyPE_RESP: A tool to facilitate and standardize derivation of RESP charges
Authors: Lapsien Marco , Bonus Michele , Gahan Lianne , Raguin Adélaïde , Gohlke Holger
Published: January 2025

We introduce PyPE_RESP, a tool to facilitate and standardize partial atomic charge derivation using the RESP approach. PyPE_RESP builds upon the open-source Python package RDKit for chemoinformatics and the AMBER suite for molecular simulations. PyPE_RESP provides an easy setup of multi-conformer and multi-molecule Restrained Electrostatic Potential (RESP) fitting while allowing a comprehensive definition of charge constraint groups through multiple methods. As a command line tool, PyPE_RESP can be integrated into batch processes. The software enables the derivation of partial atomic charges for additive and polarizable force fields. It outputs constraint group and non-constraint group charges to give an immediate overview of the fit result. PyPE_RESP will be distributed with AmberTools and compatible with most computing platforms.

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Redox homeostasis in ferroptosis and aging: a causal role forfard-1anddhs-25inCaenorhabditis elegans
Authors: Pensotti Roberta , Sciandrone Barbara , Bovio Federica , Schröter Laura , Maglioni Silvia , Thewes Leonie , Forcella Matilde Emma , Fusi Paola Alessandra , Rossi Andrea , Berndt Carsten , Ventura Natascia , Regonesi Maria Elena
Published: January 2025

Aging is a natural process characterized by a progressive physiological decline that undermines health and well-being in the elderly population. It is widely accepted that an unbalanced redox state belongs to the hallmarks of aging, but its role as one of the main drivers of ferroptosis is quite recent. Ferroptosis is a form of iron-dependent cell death caused by massive phospholipid peroxidation. The excessive accumulation of intracellular reactive oxygen species and iron, as well as the failure of the main cellular antioxidant systems, cause ferroptotic cell death. While clear roles for ferroptosis in pathological conditions such as cancer or neurodegeneration have been described, its physiological roles and regulators are less clearly understood.

Here, usingCaenorhabditis elegansas a powerful model organism for aging studies, we uncover a role for ferroptosis in physiological aging mediated by disturbed redox homeostasis. We evaluated healthspan parameters in aC. eleganswild-type strain highlighting how several age-related features differentially decline during aging. A progressive loss of the capability to contrast external stressors, with an increase in hydroxyl radicals and a failure of the glutathione antioxidant system demonstrated the progressive disruption of redox homeostasis in older age. Moreover, we showed that selected genes involved in redox metabolism are downregulated with aging. Among them, mutant strains of the fatty acyl-CoA reductase,fard-1, and of the dehydrogenase,dhs-25, displayed higher sensitivity to a ferroptosis inducer, increased lipid peroxidation, anticipated drop in total glutathione and reduced lifespan. Accordingly, the expression of one of the closest mammaliansdhs-25homolog, the hydroxysteroid 17-Beta Dehydrogenase 8, was downregulated in cells which are more sensitive to ferroptosis.

Our results clearly prove a causal role for ferroptosis inC. elegansaging driven by oxidative stress, unveiling novel genes involved in this connection that may constitute targets for possible interventions to improve healthy aging.
Improving functional protein generation via foundation model-derived latent space likelihood optimization
Authors: Guan Changge , Wan Fangping , Torres Marcelo D. T. , de la Fuente-Nunez Cesar
Published: January 2025

A variety of deep generative models have been adopted to performde novofunctional protein generation. Compared to 3D protein design, sequence-based generation methods, which aim to generate amino acid sequences with desired functions, remain a major approach for functional protein generation due to the abundance and quality of protein sequence data, as well as the relatively low modeling complexity for training. Although these models are typically trained to match protein sequences from the training data, exact matching of every amino acid is not always essential. Certain amino acid changes (e.g., mismatches, insertions, and deletions) may not necessarily lead to functional changes. This suggests that maximizing the training data likelihood beyond the amino acid sequence space could yield better generative models. Pre-trained protein large language models (PLMs) like ESM2 can encode protein sequences into a latent space, potentially serving as functional validators. We propose training functional protein sequence generative models by simultaneously optimizing the likelihood of training data in both the amino acid sequence space and the latent space derived from a PLM. This training scheme can also be viewed as a knowledge distillation approach that dynamically re-weights samples during training. We applied our method to train GPT- like models (i.e., autoregressive transformers) for antimicrobial peptide (AMP) and malate dehydrogenase (MDH) generation tasks. Computational experiments confirmed that our method outperformed various deep generative models (e.g., generative adversarial net, variational autoencoder, and GPT model without the proposed training strategy) on these tasks, demonstrating the effectiveness of our multi-likelihood optimization strategy.
Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC)
Authors: Monsen Paige J. , Bommi Prashant V. , Grigorescu Arabela A. , Lauing Kristen L. , Mao Yingyu , Berardi Payton , Zhai Lijie , Ojo Oluwatomilayo , Penco-Campillo Manon , Koch Taylor , Egozi Michael , Jha Sonam V. , Dunne Sara F. , Jiang Hong , Song Guiqin , Zhang Fang , Kregel Steven , Vaziri-Gohar Ali , Fanning Sean , Sanchez-Gomez Pilar , Allen Jacob M. , Yamini Bakhtiar , Lukas Rimas V. , Wainwright Derek A. , Schiltz Gary E.
Published: January 2025

Indoleamine 2,3-dioxygenase 1 (IDO1) is a potently immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and non-enzymatic functions. Pharmacological therapies targeting IDO1 enzyme activity have generally failed to improve the overall survival of patients with cancer. Developing new therapeutic agents that are capable of neutralizing both enzyme-and non-enzyme-derived immunosuppressive IDO1 effects is therefore of high interest. We previously described the development of a novel Proteolysis Targeting Chimera (PROTAC), NU223612, that degrades IDO1 in cultured human glioblastoma (GBM) cells, as well as in well-established brain tumors,in vivo. In this study, we rationally optimized the composition, rigidity, and linker orientation of the PROTAC structure to create NU227326, which degrades IDO1 with a DC50of 5 nM in human GBM cells. Mechanistic studies showed that IDO1 degradation occurred through the ubiquitin-proteasome system and was sustained for at least 2 days, supporting NU227326 as a highly potent IDO1 PROTAC suitable for further studies in GBM and other human cancers.
Morphological responses of a temperate salt marsh foraminifer,Haynesinasp., to coastal acidification
Authors: Powers Chris , Paz Alberto , Zyck Amaelia , Harri Kaylee , Geraci Madison , Bernhard Joan M. , Zhang Ying
Published: January 2025

Coastal acidification leads to widespread impacts on calcifying organisms across the world’s oceans, which could result in decreased calcium carbonate deposition and the dissolution of calcium carbonate. As an abundant group of calcifying organisms, some protists within the phylum Foraminifera demonstrate potential success under elevated partial pressure of carbon dioxide (pCO2) due to their ability to modulate intracellular pH. However, little is known about their responses under more extreme acidification conditions that are already seen in certain coastal environments. Here we exposedHaynesina, a foraminiferal genus that is prevalent in temperate coastal salt marshes, to moderate (pCO2= 2386.05+/-97.14 μatm) and high acidification (pCO2= 4797.64+/-157.82 μatm) conditions through the duration of 28 days. We demonstrate that although this species is capable of withstanding moderate levels of coastal acidification with little impact on their overall test thickness, they could experience deposition deficiency and even dissolution of the calcareous test under highly elevatedpCO2. Interestingly, such a deficit was primarily seen among live foraminifera, as compared to dead specimens, throughout the four-week experiment. We propose that a combination of environmental stress and the physiological process of test formation (i.e., calcite precipitation) could induce thinning of the test surface. Therefore, with the acceleration of coastal acidification due to anthropogenic production of CO2, benthic foraminifera amongst coastal ecosystems could reach a tipping point that leads to thinning and dissolution of their calcareous tests, which in turn, will impair their ecological function as a carbon sink.

Importance

The calcareous foraminifera protists are responsible for large proportions of calcium carbonate production across the global ocean. Their responses to ocean and coastal acidification are essential for understanding carbon and mineral cycling in diverse marine ecosystems. However, relatively few studies have examined more extreme conditions related to what is seen in coastal habitats (e.g.pCO2> 2,500 μatm), and the response of individual test chambers have never been inspected. Here, we consider the response ofHaynesinasp., a benthic foraminifera obtained from temperate coastal sediments to moderate and high acidification regimes. Comparison of test thicknesses across treatment conditions and among individual chambers ofHaynesinasp. revealed potential tolerance under moderate acidification but demonstrated impaired new chamber formation and test dissolution under high acidification. Our results suggest that with growing anthropogenic CO2production, foraminifera could reach a tipping point that leaves their ecological function as a carbon sink at greater risk.
TGFBR2Highmesenchymal glioma stem cells phenocopy regulatory T cells to suppress CD4+ and CD8+ T cell function
Authors: Johnson Amanda L , Khela Harmon S. , Korleski Jack , Sall Sophie , Li Yunqing , Zhou Weiqiang , Smith-Connor Karen , Lopez-Bertoni Hernando , Laterra John
Published: January 2025

Attempts to activate an anti-tumor immune response in glioblastoma (GBM) have been met with many challenges due to its inherently immunosuppressive tumor microenvironment. The degree and mechanisms by which molecularly and phenotypically diverse tumor-propagating glioma stem cells (GSCs) contribute to this state are poorly defined. In this study, our multifaceted approach combining bioinformatics analyses of clinical and experimental datasets, single-cell sequencing, and molecular and pharmacologic manipulation of patient-derived cells identified GSCs expressing immunosuppressive effectors mimicking regulatory T cells (Tregs). We show that thisImmunosuppressiveTreg-Like (ITL) GSC state is specific to the mesenchymal GSC subset and is associated with and driven specifically by TGF-β type II receptor (TGFBR2) in contrast to TGFBR1. Transgenic TGFBR2 expression in patient-derived GBM neurospheres promoted a mesenchymal transition and induced a 6-gene ITL signature consisting of CD274 (PD-L1), NT5E (CD73), ENTPD1 (CD39), LGALS1 (galectin-1), PDCD1LG2 (PD-L2), and TGFB1. This TGFBR2-driven ITL signature was identified in clinical GBM specimens, patient-derived GSCs and systemic mesenchymal malignancies. TGFBR2HighGSCs inhibited CD4+ and CD8+ T cell viability and their capacity to kill GBM cells, effects reversed by pharmacologic and shRNA-based TGFBR2 inhibition. Collectively, our data identify an immunosuppressive GSC state that is TGFBR2-dependent and susceptible to TGFBR2-targeted therapeutics.
Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome
Authors: Merino-Cacho Laura , Barroso-Gomila Orhi , Pozo-Rodríguez Mónica , Muratore Veronica , Guinea-Pérez Claudia , Serrano Álvaro , Pérez Coralia , Cano-López Sandra , Urcullu Ainhoa , Azkargorta Mikel , Iloro Ibon , Galdeano Carles , Juárez-Jiménez Jordi , Mayor Ugo , Elortza Felix , Barrio Rosa , Sutherland James D.
Published: January 2025

Background

The specificity of the ubiquitination process is mediated by the E3 ligases. Discriminating genuine substrates of E3s from mere interacting proteins is one of the major challenges in the field. We previously developed BioE3, a biotin-based approach that uses BirA-E3 fusions together with ubiquitin fused to a low-affinity AviTag to obtain a site-specific and proximity-dependent biotinylation of the substrates. We proved the suitability of BioE3 to identify targets of RING and HECT-type E3 ligases.

Methods

BioE3 experiments were performed in HEK293FT and U2OS stable cell lines expressing TRIPZ-bioGEFUb transiently transfected with BirA-cereblon (CRBN). Cells were seeded using biotin-free media, adding a short-biotin pulse. We evaluated the applicability of the BioE3 system to CRBN and molecular glues by western blot and confocal microscopy, blocking the proteasome with bortezomib, inhibiting NEDDylation with MLN4924 and treating the cells with pomalidomide. For the identification of endogenous substrates and neosubstrates we analyzed the eluates of streptavidin pull-downs of BioE3 experiments by LC-MS/MS. Analysis of targets which ubiquitination changes significantly upon treatment was done using two-sided Student’s t-test. Orthogonal validations were performed by histidine pull-down, GFP-trap and computational modelling.

Results

Here we demonstrate that BioE3 is suitable for the multi-protein complex Cullin-RING E3s ligases (CRLs), the most utilized by targeted protein degradation strategies. Choosing CRBN as proof of concept, one of the substrate receptors of CRL4 E3 ligase, we identified both endogenous substrates and novel neosubstrates upon pomalidomide treatment, including CSDE1 which contains a G-loop motif potentially involved in the binding to CRBN in presence of pomalidomide. Importantly, we observed a major rearrangement of the endogenous ubiquitination landscape upon treatment with this molecular glue.

Conclusions

The ability of BioE3 to detect and compare both substrates and neosubstrates, as well as how substrates change in response to treatments, will facilitate both target and off-target identifications and offer a broader characterization and validation of targeted protein degradation degraders, like molecular glues and PROTACs.
KilR ofE. coliRac prophage is a dual morphogenetic inhibitor of bacterial cell shape
Authors: Marepalli Anusha , Nandhakumar Muruganandam , Govindarajan Sutharsan
Published: January 2025

Bacterial cryptic prophages encode genes that reduce the viability of the host, upon induction, but also contribute to host survival during stress conditions. Rac is a cryptic prophage ofEscherichia coliand it encodes a toxic protein KilR which causes morphological defects to the host. But the mechanistic basis of its action is not well understood. In this study, we provide evidence that KilR is a dual morphogenetic inhibitor that affects cell division and cytoskeletal organization. We show that KilR expression is highly toxic, as demonstrated previously, and its predicted C-terminal unstructured region plays a crucial role in its function via a length-dependent manner. Low levels of KilR expression lead to cell filamentation and disruption of Z-rings, while high levels result in rod-shaped defects and mislocalization of the MreB cytoskeletal protein. Using fluorescent fusions, we observed that KilR is diffusively localized in the cytoplasm. When MreBCD proteins are overexpressed, KilR co-localizes with them, forming membrane-associated filaments, indicating a physical association. However, overexpressed MreBCD proteins does not alleviate the KilR-associated growth defect, unlike FtsZ. Finally, we present evidence that chromosomal KilR contributes to the co-inhibition of FtsZ and MreB localization in response to oxidative stress. Our data indicate that KilR inhibits MreB-associated cytoskeletal system, in addition to its effect on FtsZ-associated cell division system. We propose that dual inhibition activity of KilR contributes to its high level of toxicity and to its function in SOS-independent DNA damage tolerance during oxidative stress.

IMPORTANCE

KilR is a Rac cryptic prophage encoded toxic protein which contributes to host survival during oxidative stress conditions. It is known to inhibit cell division by targeting the tubulin homolog, FtsZ. In this study, we show that KilR is a dual morphogenetic inhibitor that affects FtsZ-mediated cell division and MreB-mediated cell elongation. Simultaneous inhibition of cell division and cell elongation are known to be crucial for bacterial survival during stress conditions like oxidative stress. Our study identifies KilR as a dual morphogenetic inhibitor, offering insights into how bacterial-phage coevolution drives the emergence of cryptic prophage elements, with specific genes enhancing bacterial fitness.
CSDE1 regulates miR-20a-5p/ TMBIM6 axis in melanoma
Authors: Ramakrishna Sushmitha , Guitart Tanit , Gebauer Fatima , Kakumani Pavan Kumar
Published: January 2025

RNA-binding proteins (RBPs) and microRNAs (miRNAs) play crucial roles in regulating gene expression at the post-transcriptional level in tumorigenesis. They primarily target the 3′UTRs of mRNAs to control their translation and stability. However, their co-regulatory effects on specific mRNAs in the pathogenesis of particular cancers are yet to be fully explored. CSDE1 is an RBP that promotes melanoma metastasis, and the mechanisms underlying its function in melanoma development are yet to be fully understood. In the current study, we report that CSDE1 enhances TMBIM6 protein expression without altering its mRNA levels in melanoma cells, indicating post-transcriptional regulation. CSDE1 and AGO2 competitively bind to TMBIM6 mRNA, and we identify miR-20-5p, which represses TMBIM6 expression, regulates the binding of CSDE1 to TMBIM6 mRNA. Further, the RNA-binding mutant of CSDE1 foregoes its competitive binding to the mRNA, allowing AGO2-mediated silencing of TMBIM6 expression. Our study highlights the pivotal role of CSDE1 in regulating miR-20a-5p function and the expression of TMBIM6 in melanoma cells, thus unveiling the potential of therapeutic strategies targeting this regulatory pathway in treating malignant skin cancers.
Probabilities of finding trace profile donors and their paternal relatives in Y-STR reference databases
Authors: Olsen Tóra Oluffa Stenberg , Morling Niels , Eriksen Poul Svante , Kampmann Marie-Louise , Mogensen Helle Smidt , Andersen Mikkel Meyer
Published: January 2025

Forensic investigative genetic genealogy using Y-chromosome short tandem repeat (Y-STR) DNA profiles can give investigative leads in criminal cases by searching for the Y-STR trace profile or similar but not identical Y-STR profiles in relevant Y-STR databases. We conducted a simulation study with Yfiler™Plus and PowerPlex®Y23 Y-STR profiles to estimate the probabilities of finding matches and near-matches in Y-STR databases. The success rate of finding the trace profile donors or their close relatives was quantified. We used the malan R software package to simulate the populations based on the Wright-Fisher model with the YHRD Y-STR mutation rates where uncertainties were incorporated in a Bayesian manner, a variance in reproductive success of 0.2, and a constant size for 100 generations followed by a 2% growth for 150 generations. Y-STR databases were generated by randomly drawing Y-STR profiles from a Yfiler™Plus and PowerPlex®Y23 Y-STR population data set, respectively.

In a population of 500,066 individuals, a database size of 0.5% of the population resulted in a Y-STR database match probability of ca. 6% and 10% for Yfiler™Plus and PowerPlex®Y23, respectively. Increasing the database size to 5% of the population resulted in a Y-STR match probability of ca. 41% and 54% for Yfiler™Plus and PowerPlex®Y23, respectively. When a Y-STR match was found in the database, the probability of one of the individuals with the matching profiles being related within five meioses to the trace donor was ca. 64% and 56% for Yfiler™Plus and PowerPlex®Y23, respectively, including the cases where the Y-STR profile originated from the donor. In this case, the closest relative in the database was found among the matching individuals with a probability of ca. 91%.
Completeness estimation of large-scale single-cell sequencing projects
Authors: Miihkinen Mitro , Vakkilainen Sara , Aittokallio Tero
Published: January 2025

During embryonic development, cells undergo differentiation into highly specialized cell types. Taking advantage of single-cell RNA sequencing, substantial resources have been invested towards cataloguing these differentiated cell types by their transcriptomic profiles. Despite the extensive efforts to profile different organs and their cellular compositions, metrics to assess the completeness of such datasets have been lacking. In this cellular biodiversity analysis, we used the increasingly available single-cell data together with statistical methods, originally developed for assessing the species richness of ecological communities, to provide cellular diversity estimates for any organ based on single-cell RNA sequencing data, as well as estimating how cell types are distributed along different organ systems. Deriving from such cellular richness estimates, we establish a statistical framework that allows estimation of the completeness of any large-scale single-cell profiling projects, after which additional sequencing efforts do not anymore reveal new insights into an organ’s cellular composition. Such estimates can serve as stoppage-points for the ongoing sequencing projects for more cost-efficient completion of the remaining profiling on various human tissues.
Assessing the inference of single-cell phylogenies and population dynamics from genetic lineage tracing data
Authors: Pilarski Julia , Stadler Tanja , Seidel Sophie
Published: January 2025

Background

Multicellular organisms develop from a single cell by repeated rounds of cell division, differentiation and apoptosis, which can be displayed in a single-cell phylogenetic tree. Genetic lineage tracing allows us to investigate this development by tracking the ancestry of individual cells as populations grow and change over time. However, accurate reconstruction of the cell phylogeny and quantification of the corresponding phylodynamic parameters - division, differentiation and apoptosis rate - from this tracking data remains challenging and needs to be systematically evaluated.

Results

We perform simulations and assess, using the Bayesian framework, the joint inference of time-scaled cell phylogenies and phylodynamic parameters from CRISPR lineage recordings with random or sequential edits. Principally, we characterize the inference improvement as the recorder capacity increases. Further, we characterize the increase of accuracy of phylogenetic reconstruction when using sequential compared to random recordings, i.e. when using the additional information contained in the order of edits. Moreover, we find that CRISPR lineage recordings carry a strong signal on the rates of cell division. When the phylodynamic parameters are inferred under models that match the true dynamics and when sufficiently many cells of each type are sampled, also cell death and differentiation rates can be estimated from the data.

Conclusion

In this study, we evaluate how much information on cellular development can be extracted from genetic lineage tracing data using phylogenetic and phylodynamic methodology. We identify important experimental, conceptual, and computational limitations for the inference which can guide future advancements in the field.
Single-cell sequencing reveals psilocybin induces sustained cell-type specific plasticity in mouse medial prefrontal cortex
Authors: Zhou Delong , Schuler Heike , Cvetkovska Vedrana , Meccia Juliet , Harutyunyan Ashot S. , Ragoussis Jiannis , Bagot Rosemary C.
Published: January 2025

The ever-increasing burden of psychiatric disorders and limitations of current treatments have fueled enormous interest in the therapeutic potential of psychedelics. Yet how psychedelics, such as psilocybin, produce lasting therapeutic effects is unclear. Using scRNA-sequencing we identify a type of deep layer near projecting neuron that is most robustly regulated in the medial prefrontal cortex of female mice 24h after psilocybin. We show that this cell-type specificity does not align with 5-HT2Areceptor expression but is consistent with the integrated signaling via cell-type specific 5-HT receptor co-expression patterns. Cell-cell communication reveals that psilocybin also broadly suppresses GABAergic inhibition. Ultimately, psilocybin induces plasticity-related genes in subsets of excitatory neurons suggesting that psilocybin induces sustained increases in neuroplasticity in the mouse mPFC. Our findings point to L5/6NP neurons as a key mediator of psilocybin’s neuroplastic effects.
Exploring Abelian–non-Abelian kinetic mixing in SMEFT and beyond
Authors: Tran Van Que , Yuan Tzu-Chiang
Published: January 2025

We explore a novel scenario involving Abelian–non-Abelian kinetic mixing within the framework of the Standard Model effective field theory (SMEFT) and its extension with a real triplet scalar field. In SMEFT, this mixing arises exclusively from a dimension-6 operator involving the Standard Model Higgs doublet, while the real triplet scalar field introduces an additional dimension-5 operator. We derive the modifications to electroweak gauge boson properties and impose constraints using electroweak precision data. In SMEFT, we find that Z-pole data at the Large Electron–Positron Collider imposes a stringent constraint on the kinetic mixing parameter, requiring it to be less than O(10−4), which corresponds to a new physics scale of about 10 TeV. In the SMEFT+triplet scenario, the constraint can be significantly relaxed with a sizeable triplet vacuum expectation value while preserving custodial symmetry in a finely tuned parameter space. Future measurements from the Circular Electron Positron Collider could probe the kinetic mixing parameter down to an order of magnitude smaller. Constraints from the Higgs signal strength data, Bs→μ+μ−, and muon (g−2) are also discussed.

Published by the American Physical Society
2025
Frugal business model innovation in an Indian emerging market: a multiple case study
Authors: Natasha Saqib
Published: January 2025

Purpose

This multiple case study aims to investigate the frugal business model innovation exemplified by three pioneering organisations in India: Aravind Eye Care System (AECS), ChotuKool and SELCO India. This study elucidates the key factors contributing to their success and explores the broader implications for frugal innovation in addressing societal challenges in emerging markets.

Design/methodology/approach

The authors use a qualitative case study methodology to analyse the approaches of AECS, ChotuKool and SELCO India towards product development, distribution strategies and financing mechanisms and their impact on underserved communities. Data is collected through archival research and analysis of secondary sources.

Findings

The findings of the study reveal common themes and unique characteristics of frugal business model innovation across the three organisations. Key findings include innovative approaches to product/service design, distribution channels tailored to reach underserved populations and the implementation of flexible financing mechanisms to make products/services accessible to low-income consumers.

Research limitations/implications

This study enhances the understanding of frugal innovation in emerging markets and highlights the importance of affordability, accessibility and sustainability in driving positive social impact. Limitations include focus on only three case studies and the qualitative nature of the research, which may limit generalisability.

Practical implications

This study offers insights for managers and decisionmakers on implementing frugal innovation strategies to address societal challenges and promote inclusive growth in emerging markets. Key managerial implications include the importance of understanding local contexts, building partnerships and leveraging innovative financing mechanisms. The study provides guidance for practitioners and social entrepreneurs in developing scalable and sustainable solutions for underserved communities. Practical implications include the adoption of decentralised distribution models, customisation of products/services and investment in capacity-building and training programmes.

Social implications

The study highlights the significant impact of frugal business model innovation on underserved communities, including improved access to essential services, enhanced quality of life and socioeconomic empowerment. Implications for society include the potential for frugal innovation to address pressing societal challenges and promote inclusive growth.

Originality/value

The originality and value of this study lie in its comprehensive analysis of frugal business model innovation across multiple sectors in the Indian context. By examining the experiences of AECS, ChotuKool and SELCO India, the study contributes to the literature on frugal innovation and provides actionable insights for businesses, policymakers and development practitioners seeking to create positive social impact in emerging countries.
How do digital ­oriented firms perform superior environmental performance? A natural resource ­based view
Authors: Zhang Qianjun , Ouyang You , Li Lixu
Published: January 2025

Purpose

A global industrial revolution driven by carbon neutrality and digital technologies (DTs) is fast gaining momentum. However, the present understanding of how firms should leverage digitalization for sustainability is underdeveloped. This paper aims to explore how digital orientation can improve environmental performance from the natural resource-based view.

Design/methodology/approach

Using a sample set of 132 Chinese firms, the authors adopt the hierarchical regression analysis and bootstrap approach to examine the hypotheses.

Findings

The empirical results show that green DT usage, green DT disposal and green practices-DT fit are three factors that mediate the positive relationship between digital orientation and environmental performance. In addition, of the five possible mediational paths, only the serial mediation of green DT usage and green practices-DT fit, as well as the serial mediation of green DT disposal and green practices-DT fit, show significant effects.

Originality/value

The authors contribute to the current digitalization and sustainability literature by demonstrating the processes through which digital orientation influences environmental performance. The study also provides managerial implications for firms to adjust their operations.
Metaverse marketing: a review and future research agenda
Authors: Kumar Rajeev , Aneja Preeti , Jadaun Ranjana , Kiran P. B. Narendra , Saxena Neha , Saxena Shubham , Singh Priyank Kumar , Painoli Arun Kant
Published: January 2025

Purpose

The metaverse represents a rapidly evolving digital environment that blurs the lines between physical and virtual reality, and it offers unique opportunities and challenges for businesses and marketers. The purpose of this study is to provide a comprehensive review of metaverse marketing research. The present study reviews the literature on metaverse to identify theories, contexts, gaps and methodologies using TCCM framework (Theories, Contexts, Characteristics and Methodology) to set a future research agenda.

Design/methodology/approach

A review was conducted of 179 English papers related to metaverse marketing from 2010 to 2023 from the Scopus and Web of Science core collection after applying relevant filters using the TCCM framework.

Findings

The findings suggest that the studies have inadequately distinguished metaverse as something that only builds interactive experiences that combine the virtual environment and the real world, whereas the theoretical domain of metaverse is dominated by studies in various domains. The applicability of metaverse marketing research is pertinent in various domains of the management field. The study explores various facets of metaverse marketing to capture its dynamic nature.

Research limitations/implications

By presenting a comprehensive review, themes and knowledge gaps of the research on metaverse marketing, this study will enhance research output and provide valuable tools for future research on metaverse.

Practical implications

By analyzing metaverse in marketing, the companies will be able to use this concept effectively to formulate innovative marketing strategies and personalized consumer experiences and understand consumer behavior. Furthermore, research into metaverse marketing will be helpful in offering predictions about future trends in consumer behavior, technology adoption and virtual world development.

Originality/value

This study provides a thorough analysis of the current state of research on metaverse in marketing and provides a road map for further research in this area.
Gamers’ gratifications and continuous intention to play eSports: the mediating role of gamers’ satisfaction-a PLS-SEM and NCA study
Authors: Fayyaz Muhammad Shahzeb , Abbasi Amir Zaib , Ahmad Rehan , Qummar Muhammad Hamza , Tsiotsou Rodoula H. , Mahmood Saqib
Published: January 2025

Purpose

This study aims to investigate the relationship between different hedonic (e.g. enjoyment and escapism) and utilitarian (e.g. achievement and challenge) gratifications and continuous intention to play eSports, considering the mediating role of gamer’s satisfaction. Uses and Gratification theory (U&G) has been employed as the study’s theoretical framework.

Design/methodology/approach

The present study used a survey research method and a self-administered questionnaire to collect the data. The data was gathered on-site from students of three universities in Pakistan’s Islamabad and Rawalpindi regions. Study respondents involved people from Gen Z and Gen Y aged between 18 to 25 and 26 to 40. A total of 401 responses were evaluated using the partial least squares structural equation modeling (PLS-SEM) and necessary condition analysis (NCA).

Findings

The PLS-SEM findings evidence that eSports players’ hedonic (e.g. enjoyment and escapism) and utilitarian (e.g. challenge) gratification positively impact gamers’ satisfaction, which subsequently drives eSports gamers’ continuance intention behavior. Furthermore, gamers’ satisfaction positively mediated the relationship between gratifications (e.g. enjoyment and escapism refer to hedonic, whereas achievement and challenge represent utilitarian) and continuance intentions. NCA on eSports gamers’ satisfaction and continuance intention identified critical predictive factors. The analysis revealed that only enjoyment is necessary for predicting satisfaction. Interestingly, NCA results also indicated that enjoyment, achievement, escapism, challenge and satisfaction are all necessary for predicting eSports gamers’ continuance intention.

Originality/value

This study investigates the mediating role of eSports gamers’ satisfaction between gamers’ perceived gratifications (i.e. enjoyment, escapism, achievement, challenge) and their continuous intention to play in the Pakistani context. More importantly, we employ a multi-method approach (e.g. a combined approach of PLS-SEM with NCA) to determine the sufficient and necessary conditions of the outcome variable comprising satisfaction and continuous intention.
Green entrepreneurial leadership as a catalyst of green service innovative behaviour: a serial mediation model with a dual theoretical lens
Authors: Ahmed Zeeshan , Khosa Mishal , Nguyen Nhat Tan , Kayode Ibikunle Afeez , Abbas Javaria , Akhtar Adeel
Published: January 2025

Purpose

Recent literature in environmental management suggests that fostering employees’ innovative behaviour in green service is vital for enhancing the environmental sustainability of hospitality organizations. Despite this, few efforts have been made to understand how green entrepreneurial leadership (GEL) relates to green service innovative behaviour (GSIB). This study aims to examine whether GEL can promote GSIB among hospitality employees through the serial mediation of green learning orientation (GLO) and green knowledge acquisition (GKA) using the conservation of resources theory. The authors expect environmental dynamism to strengthen the relationship between GEL and employees’ GSIB, leveraging the resource-based view theory.

Design/methodology/approach

This study collected data through a multi-wave survey (four waves, two weeks apart) from 341 employees working in three-to-five-star hotels in Pakistan’s major cities. The authors used partial least squares structural equation modelling to evaluate the hypotheses proposed in the theoretical model.

Findings

The study revealed a significant relationship between GEL and employee GSIB, mediated by GLO and GKA. In addition, environmental dynamism strengthened the relationship of GEL with employee GSIB.

Originality/value

The research advances the literature on GEL in the hospitality sector by providing insights into the mediating and moderating processes that translate GEL into GSIB among hospitality employees. Moreover, the research provides important implications for hotels investing in green initiatives and looking for ways to foster employees’ GSIB.
Unraveling digital nomadism: a comprehensive bibliometric review of emerging research and trends
Authors: de Sousa Bárbara Viana , Bastida Maria , Vieira Elvira
Published: January 2025

Purpose

This study aims to examine the phenomenon of digital nomadism within the broader context of digital global mobility, namely through the identification and analysis of existing investigations, shedding light on the social implications and growing impacts of digital nomadism on society.

Design/methodology/approach

A systematic review was conducted on publications available in Scopus and Web of Science databases from 2001 to 2023, covering various disciplines such as computer science, business and economics, social sciences and more. Following defined guidelines, 1047 papers were selected for analysis.

Findings

The review reveals insights into the social implications and impacts of DN, proposing a framework based on a Bibliographic mapping, including four clusters: DN dimensions, digital nomads context, balance work–life leisure and impacts. With these findings, the paper highlights research gaps and guides future investigations at the intersection of new work models, business and society.

Research limitations/implications

Limitations include the specific scope of the review and consequently limited the selection of papers. The results provide directions for a future conceptualization and investigation of several shades of DN, helping scholars improve their understanding of this field progress and reflect on it from multiple perspectives.

Practical implications

This study is beneficial for policymakers to prepare or adapt changes in labor or tax law as well as employers managing digital nomads and co-working spaces.

Social implications

DN has significant social implications, influencing work practices, societal norms and community dynamics. Understanding these implications is crucial for addressing the evolving nature of work and society.

Originality/value

This research contributes to a better understanding of DN and provides valuable insights for future studies and interventions aimed at addressing the impacts of this transformative social phenomenon. Additionally, using bibliometric analysis and science mapping tools adds originality to the study, offering a visual representation of the DN research landscape, culminating in a complete DN framework.
Contagious viruses’ corollaries and deterioration of quality education in developing countries: an integrated model of artificial intelligence (AI) awareness and remote working
Authors: Zaheer Muhammad Asif , Anwar Tanveer Muhammad , Albeshr Mohamed , Manzoor Maryam , Khan Zoia
Published: January 2025

Purpose

This paper aims to provide the integrated model with artificial intelligence (AI) awareness for the betterment of the higher education system in crisis i.e. fear of contagious viruses (different kinds of flu, monkeypox, chickenpox, COVID-19, etc.) corollaries in developing nations where the quality of education depends on teachers’ commitment, stress and the turnover intention.

Design/methodology/approach

This empirical investigation employs a self-administered survey distributed among the faculty members within higher education institutions (HEIs) of the Punjab province and the Federal Capital Territory (FCT) Islamabad, Pakistan. The final sample of 622 faculty members was collected through convenience sampling, and structural equation modeling was performed with SmartPLS to assess the proposed model.

Findings

The study reveals that remote work significantly enhances organizational commitment while concurrently lowering the turnover intention. Conversely, perceived work stress negatively impacts organizational commitment but positively influences turnover intention. Organizational commitment partially mediates between perceived work stress and turnover intention but exhibited no mediation between remote work and turnover intention. Notably, fear of contagious viruses and AI awareness positively moderate and amplify both the perceived work stress with turnover intention and remote working with organizational commitment, respectively.

Research limitations/implications

The current study extends the AI-mediated social exchange theory (MET) by observing faculty members of HEIs in the context of remote working, perceived work stress, commitment, turnover intention, fear of contagious viruses and AI awareness. Moreover, the successful application of AI-MET extended the researcher’s understanding of quality education in crisis.

Practical implications

The study offers several contributions including applications of technical skills with AI awareness among faculty members to provide quality education for society’s welfare. Moreover, HEIs should arrange training programs for performance enhancement.

Originality/value

This research provided a quality-based model for HEIs for developing nations to deal with forthcoming calamities of contagious viruses and deliver quality education through remote working during lockdown. Nowadays, off-campus education during calamity situations has been an alternative to on-campus education. Therefore, HEIs must introduce AI awareness to increase the dedication of faculty members toward society’s welfare with the utilization of full effort.
Fluctuating asymmetry in ecological and environmental research: Quo vadis?
Authors: Kozlov Mikhail V.
Published: January 2025

Májeková et al. (2024) demonstrated that leaf fluctuating asymmetry (FA) is not a reliable indicator of stress. I broaden the perspective on the findings by these authors.

High prevalence of confirmation bias could explain why as much as 39% of 131 unique entries (plant species × stress type) in the database of published studies compiled by these authors showed the significant increase in FA with stress.

The use of blind methods should be considered obligatory for any study addressing environmental or genetic impacts on FA.

Both data and conclusions from FA‐related studies that did not report blinding should only be used when proof of negligible impact from confirmation bias can be provided.

It is essential that all measures taken against biases are described in each submitted manuscript, and that the need to check for these requirements is included in instructions for reviewers.

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