bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural neurodevelopment at the individual level - a life-course investigation using ABCD, IMAGEN and UK Biobank data
Authors: Shi Runye , Xiang Shitong , Jia Tianye , Robbins Trevor W. , Kang Jujiao , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L.W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Poustka Luise , Hohmann Sarah , Millenet Sabina , Fröhner Juliane H. , Smolka Michael N. , Vaidya Nilakshi , Walter Henrik , Whelan Robert , Schumann Gunter , Lin Xiaolei , Sahakian Barbara J. , Feng Jianfeng ,   IMAGEN Consortium
Published: September 2023

Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to the lack of large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages and the neurobiological basis underlying individual heterogeneity remains poorly understood. Using structural magnetic resonance imaging from the IMAGEN cohort (n=1,543), we show that adolescents can be clustered into three groups defined by distinct developmental patterns of whole-brain gray matter volume (GMV). Genetic and epigenetic determinants of group clustering and long-term impacts of neurodevelopment in mid-to-late adulthood were investigated using data from the ABCD, IMAGEN and UK Biobank cohorts. Group 1, characterized by continuously decreasing GMV, showed generally the best neurocognitive performances during adolescence. Compared to Group 1, Group 2 exhibited a slower rate of GMV decrease and worsened neurocognitive development, which was associated with epigenetic changes and greater environmental burden. Further, Group 3 showed increasing GMV and delayed neurocognitive development during adolescence due to a genetic variation, while these disadvantages were attenuated in mid-to-late adulthood. In summary, our study revealed novel clusters of adolescent structural neurodevelopment and suggested that genetically-predicted delayed neurodevelopment has limited long-term effects on mental well-being and socio-economic outcomes later in life. Our results could inform future research on policy interventions aimed at reducing the financial and emotional burden of mental illness.
Mechanisms of type I interferon production by chicken TLR21
Authors: Guabiraba Rodrigo , Rodrigues Damaris Ribeiro , Manna Paul T. , Chollot Mélanie , Saint-Martin Vincent , Trapp Sascha , Oliveira Marisa , Bryant Clare E , Ferguson Brian J
Published: September 2023

The innate immune response relies on the ability of host cells to rapidly detect and respond to microbial nucleic acids. Toll-like receptors (TLRs), a class of pattern recognition receptors (PRRs), play a fundamental role in distinguishing self from non-self at the molecular level. In this study, we focused on TLR21, an avian TLR that recognizes DNA motifs commonly found in bacterial genomic DNA, specifically unmethylated CpG motifs. TLR21 is believed to act as a functional homologue to mammalian TLR9. By analysing TLR21 signalling in chickens, we sought to elucidate avian TLR21 activation outputs in parallel to that of other nucleic acid species. Our analyses revealed that chicken TLR21 (chTLR21) triggers the activation of NF-κB and induces a potent type-I interferon response in chicken macrophages, similar to the signalling cascades observed in mammalian TLR9 activation. Notably, the transcription of interferon beta (IFNB) by chTLR21 was found to be dependent on both NF-κB and IRF7 signalling, but independent of the TBK1 kinase, a distinctive feature of mammalian TLR9 signalling. These findings highlight the conservation of critical signalling components and downstream responses between avian TLR21 and mammalian TLR9, despite their divergent evolutionary origins. These insights into the evolutionarily conserved mechanisms of nucleic acid sensing contribute to the broader understanding of host-pathogen interactions across species.
When the heart meets the mind Exploring the brain-heart interaction during time perception
Authors: Khoshnoud Shiva , Leitritz David , Bozdağ Meltem Çinar , Igarzábal Federico Alvarez , Noreika Valdas , Wittmann Marc
Published: September 2023

It has been hypothesized that time estimation relies on bodily rhythms and interoceptive signals, such as heartbeats. Extending previous research demonstrating this connection, we provided further electrophysiological evidence that the brain registers heartbeats while tracking time intervals. We evaluated the heartbeat-evoked potential (HEP) and the contingent negative variation (CNV) during an auditory duration-reproduction task with intervals lasting 4, 8, and 12 seconds and a control reaction-time task employing the exact durations. The (interoceptive) Self-Awareness Questionnaire (SAQ) and the heartbeat-counting task (HCT) were administered. The SAQ, but not the HCT scores, correlated with the mean reproduced durations for 4s, 8s, and 12s intervals: the higher the SAQ score (a stronger awareness of bodily signals), the longer the duration reproductions and the more accurate the timing behavior. The HEP amplitude within 130-270 ms (HEP1) and 470-520 ms (HEP2) after the R peak was smaller for the 4s interval than for the 8s and 12s intervals. This is a timing-specific effect, as the HEP amplitude did not differ for intervals in the reaction-time task. A ramp-like increase in HEP2 amplitudes was significant for the duration-encoding phase of the timing task, but not for the control reaction-time task. The HEP2 increase within the reproduction phase of the timing task correlated significantly with the reproduced durations for the 8s and the 12s intervals. The larger the registered increase in the HEP2, the greater the under-reproduction of the estimated duration. The initial and late CNV components were significantly more negative during the encoding phase than during the reaction-time task. Given the link between these components with attention modulation and temporal memory, we interpret the CNV findings as indicating greater executive resources oriented towards time. We conclude that interoceptive awareness (SAQ) and state-like cortical responses to the heartbeat (HEP) predict duration reproductions, emphasizing the notion of the embodiment of time.
An analytical derivation of the distribution of distances between heterozygous sites in diploid species to efficiently infer demographic history
Authors: Arndt Peter F. , Massip Florian , Sheinman Michael
Published: September 2023

Heterozygous sites are not uniformly distributed along a diploid genome. Rather, their density varies as a result of recombination events, and their local density reflects the time to the last common ancestor of the maternal and paternal copies of a genomic region. The distribution of the density of heterozygous sites therefore carries information about the history of the population size. Despite previous efforts, an exact derivation of the distribution of heterozygous sites is still lacking. As a consequence, the estimation of population size variation is difficult and requires several simplifying assumptions. Using a novel theoretical framework, we are able to derive an analytical formula for the distribution of distances between heterozygous sites. Our theory can account for arbitrary demographic histories, including bottlenecks. In the case of a constant population size the distribution follows a simple function and exhibits a power-law tail proportional torαwithα=−3, whereris the distance between heterozygous sites. This prediction is accurately validated when considering heterozygous sites in individuals of African descent. Other populations migrated out of Africa and underwent at least one bottleneck which left a distinct mark on their interval distribution between heterozygous sites, i.e., an overrepresentation of intervals between 10 and 100 kbp in length. Our analytical theory for non-constant population sizes reproduces this behavior and can be used to study historical changes in population size with high accuracy. The simplicity of our approach facilitates the analysis of demographic histories for diploid species, requiring only a single unphased genome.
COVID-19 ORF3a Viroporin Influenced Common and Unique Cellular Signalling Cascades in Lung, Heart and Brain Choroid Plexus Organoids with Additional Enriched MicroRNA Network Analyses for Lung and Brain Tissues
Authors: Chakraborty Soura , Chatterjee Shrabonti , Mardi Subhashree , Mahata Joydeep , Kateriya Suneel , Punnakkal Pradeep , Anirudhan Gireesh
Published: September 2023

Tissue specific implications of SARS-CoV-2 encoded accessory proteins are not fully understood. SARS-CoV-2 infection can severely affect three major organs – the heart, lung, and brain. We analysed SARS-CoV-2 ORF3a interacting host proteins in these three major organs. Further we identified common and unique interacting host proteins, their targeting miRNAs (lung and brain), and delineated associated biological processes reanalysing RNA-seq data from the brain (COVID-19 infected/uninfected Choroid Plexus Organoids study), lung tissue from COVID-19 patients/healthy subjects, and cardiomyocyte cells based transcriptomics analyses. Ourin silicostudies showed ORF3a interacting proteins could vary depending upon tissues. Number of unique ORF3a interacting proteins in brain, lung and heart were 10, 7 and 1 respectively. Though common pathways influenced by SARS-CoV-2 infection were more, unique 21 brain and 7 heart pathways were found. One unique pathway for heart was negative regulation of calcium ion transport. Reported observations of COVID-19 patients with the history of hypertension taking calcium channel blockers (CCBs) or dihydorpyridine CCBs had elevated rate of intubation or increased rate of intubation/death respectively. Also likelihood of hospitalization of chronic CCB users with COVID-19 was more in comparison to long term Angiotensin Converting Enzyme inhibitors/Angiotensin Receptor Blockers users. Further studies are necessary to confirm this. miRNA analysis of ORF3a interacting proteins in brain and lung revealed, 2 of 37 brain miRNAs and 1 of 25 lung miRNAs with high degree and betweenness indicating their significance as hubs in the interaction network. Our study could help in identifying potential tissue specific COVID-19 drug/drug repurposing targets.
Longitudinal Deep Multi-Omics Profiling in aCLN3Δex7/8Minipig Model Reveals Novel Biomarker Signatures for Batten Disease
Authors: Rechtzigel Mitchell J , Lee Brittany , Neville Christine , Huang Ting , Campos Alex Rosa , Motamedchaboki Khatereh , Hornburg Daniel , Johnson Tyler B , Swier Vicki J , Weimer Jill M , Brudvig Jon J
Published: September 2023

Development of therapies for CLN3 Batten disease, a rare pediatric lysosomal storage disorder, has been hindered by the lack of etiological insights and translatable biomarkers to clinics. Here, we used a deep multi-omics approach to discover new biomarkers using longitudinal serum samples from a porcine model of CLN3 disease. Comprehensive metabolomics was combined with a nanoparticle-based LC-MS-based proteomic profiling coupled with TMTpro 18-plex to generate quantitative data on 769 metabolites and 2,634 proteins, collectively the most exhaustive multi-omics profile conducted on serum from a porcine model, which was previously impossible due a to lack of efficient deep serum proteome profiling technologies compatible with model organisms. The presymptomatic disease state was characterized by elevations in glycerophosphodiester species and lysosomal proteases, while later timepoints were enriched with species involved in immune cell activation and sphingolipid metabolism. Cathepsin S, Cathepsin B, glycerophosphoinositol, and glycerophosphoethanolamine captured a large portion of the genotype-correlated variation between healthy and diseased animals, suggesting that an index score based on these analytes could have great utility in the clinic.
Dietary Restriction Fails to Extend Lifespan ofDrosophilaModel of Werner Syndrome
Authors: Sember Eileen , Chennakesavula Ranga , Beard Breanna , Opoola Mubaraq , Hwangbo Dae-Sung
Published: September 2023

Werner syndrome (WS) is a rare genetic disease in humans, caused by mutations in theWRNgene that encodes a protein containing helicase and exonuclease domains. WS is characterized by symptoms of accelerated aging in multiple tissues and organs, involving increased risk of cancer, heart failure, and metabolic dysfunction. These conditions ultimately lead to the premature mortality of patients with WS. In this study, using the null mutant flies (WRNexoΔ) for the gene WRNexo (CG7670), homologous to the exonuclease domain of WRN in humans, we examined how diets affect the lifespan, stress resistance, and sleep/wake patterns of aDrosophilamodel of WS. We observed that dietary restriction (DR), one of the most robust non-genetic interventions to extend lifespan in animal models, failed to extend the lifespan ofWRNexoΔmutant flies and even had a detrimental effect in females. Interestingly, the mean lifespan ofWRNexoΔmutant flies was not reduced on a protein-rich diet compared to that of wild-type flies. Compared to wild type control flies, the mutant flies also exhibited altered responses to DR in their resistance to starvation and oxidative stress, as well as changes in sleep/wake patterns. These findings show that the WRN protein is necessary for mediating the effects of DR and suggest that the exonuclease domain of WRN plays an important role in metabolism in addition to its primary role in DNA repair and genome stability. Our results also raise the possibility that diet-mediated interventions could ameliorate the symptoms of WS.
Exploiting Charge State Distribution to Probe Intramolecular Interactions in Gas-Phase Phosphopeptides and Enhance Proteomics Analyses
Authors: Gorshkov Vladimir , Kjeldsen Frank
Published: September 2023

Charging of analytes is a prerequisite for performing mass spectrometry analysis. In proteomics, electrospray ionization stands as the dominant technique for this process. Although the observation of differences in the peptide charge state distribution (CSD) is well-known among experimentalists, its analytical value remains underexplored. To investigate the utility of this dimension, we analyzed several public datasets, comprising over 250,000 peptide CSD profiles from the human proteome. We found that the dimension of the CSD demonstrates high reproducibility across multiple laboratories, mass analyzers, and extensive time intervals. The general observation was that the CSD enabled effective partitioning of the peptide property space, resulting in enhanced discrimination between sequence or constitutional peptide isomers. Next, by evaluating the CSD values of phosphorylated peptides, we were able to differentiate between phosphopeptides that indicate the formation of intramolecular structures in the gas phase and those that do not. The reproducibility of the CSD values (mean cosine similarity above 0.97 for most of the experiments), qualified CSD data suitable to train a deep learning model capable of accurately predicting CSD values (mean cosine similarity – 0.98). When we applied the CSD dimension to MS1- and MS2-based proteomics experiments, we consistently observed around a 5% increase in protein and peptide identification rate. Even though the CSD dimension is not as effective a discriminator as the widely-used retention time dimension, it still holds potential for application in direct infusion proteomics.
Engram cell connectivity as a mechanism for information encoding and memory function
Authors: Ortega-de San Luis Clara , Pezzoli Maurizio , Urrieta Esteban , Ryan Tomás J.
Published: September 2023

Information derived from experiences is incorporated into the brain as changes to ensembles of cells, termed engram cells, that allow memory storage and recall. The mechanism by which those changes hold specific information is unclear. Here we test the hypothesis that the specific synaptic wiring between engram cells is the substrate of information storage. First, we monitor how learning modifies the connectivity pattern between engram cells at a monosynaptic connection involving the hippocampal vCA1 region and the amygdala. Then, we assess the functional significance of these connectivity changes by artificially activating or inhibiting its presynaptic and postsynaptic components respectively. Finally, we identify a synaptic plasticity mechanism mediated by PSD-95, which impacts the connectivity pattern among engram cells and contributes to the long-term stability of the memory. These findings impact our theory of learning and memory by helping us explain the translation of specific information into engram cells and how these connections shape brain function.
Anti-S-layer monoclonal antibodies impactC. difficilephysiology
Authors: Hunault Lise , Auria Emile , England Patrick , Deschamps Julien , Briandet Romain , Kremer Vanessa , Iannascoli Bruno , Vidal-Maison Léo , Guo Chunguang , Macdonald Lynn , Péchiné Séverine , Denève-Larrazet Cécile , Dupuy Bruno , Gorochov Guy , Bruhns Pierre , Sterlin Delphine
Published: September 2023

Clostridioides difficile(C. difficile), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults and is characterized by high levels of recurrence and mortality. Surface-layer Protein A (SlpA), the most expressed protein on bacterial surface, plays a crucial role in the early stages of infection although its role inC. difficilephysiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and correlate with improved outcome ofC. difficileinfection (CDI). However, the precise mechanisms of how anti-S-layer antibodies can confer protection to the host remain unknown. In this study, we report the first monoclonal antibodies (mAbs) targeting S-layer of the reference strain 630. Characterization of these mAbs unravels important roles for S-layer protein in growth, toxin secretion, and biofilm formation with, surprisingly, opposite effects of different anti-SlpA mAbs on these functions. One anti-SlpA mAb impairedC. difficilegrowth and restored sensitivity to lysozyme-induced lysis. These findings suggest that anti-S-layer antibody responses may include protective and detrimental effects for the host and provide important insights for designing adequate S-layer-targeting therapeutics.
The Role of Vitamin D inEmiliania huxleyi: A Microalgal Perspective on UV Exposure
Authors: Eliason Or , Malitsky Sergey , Panizel Irina , Feldmesser Ester , Porat Ziv , Sperfeld Martin , Segev Einat
Published: September 2023

An essential interaction between sunlight and eukaryotes involves the production of vitamin D through exposure to ultraviolet (UV) radiation. While extensively studied in vertebrates, the role of vitamin D in non-animal eukaryotes like microalgae remains unclear. To investigate the potential involvement of vitamin D in the response of microalgae to UV, we focus onEmiliania huxleyi, a microalga found in shallow ocean depths that are exposed to UV radiation. Our results show thatE. huxleyialgae produce vitamin D2and D3in response to UV irradiation. We further demonstrate thatE. huxleyialgae respond to external administration of vitamin D at the transcriptional level, regulating the expression of protective mechanisms that are also regulated in response to UV. Our data reveal that addition of vitamin D enhances the algal photosynthetic performance while reducing harmful reactive oxygen species buildup. This study contributes to understanding the function of vitamin D inE. huxleyiand sheds light on its role in non-animal eukaryotes, as well as its potential importance in marine ecosystems.
Generation and characterisation of anArabidopsis thaliana f3h/fls1/anstriple mutant that accumulates eriodictyol derivatives
Authors: Schilbert Hanna Marie , Busche Mareike , Sáez Vania , Angeli Andrea , Weisshaar Bernd , Martens Stefan , Stracke Ralf
Published: September 2023

Background

Flavonoids are plant specialised metabolites, which derive from phenylalanine and acetate metabolism. They possess a variety of beneficial characteristics for plants and humans. Several modification steps in the synthesis of tricyclic flavonoids cause for the amazing diversity of flavonoids in plants. The 2-oxoglutarate-dependent dioxygenases (2-ODDs) flavanone 3-hydroxylase (F3H, synonym FHT), flavonol synthase (FLS) and anthocyanidin synthase (ANS, synonym leucoanthocyanidin dioxigenase (LDOX)), catalyse oxidative modifications to the central C ring. They are highly similar and have been shown to catalyse, at least in part, each other’s reactions. FLS and ANS have been identified as bifunctional enzymes in many species, includingArabidopsis thaliana, stressing the capability of plants to bypass missing or mutated reaction steps on the way to flavonoid production. However, little is known about such bypass reactions and the flavonoid composition of plants lacking all three central flavonoid 2-ODDs.

Results

To address this issue, we generated af3h/fls1/ansmutant, as well as the corresponding double mutants and investigated the flavonoid composition of this mutant collection. Thef3h/fls1/ansmutant was further characterised at the genomic level by analysis of a nanopore DNA sequencing generated genome sequence assembly and at the transcriptomic level by RNA-Seq analysis. The mutant collection established, including the novel double mutantsf3h/fls1andf3h/ans, was used to validate and analyse the multifunctionalities of F3H, FLS1, and ANSin planta. Metabolite analyses revealed the accumulation of eriodictyol and additional glycosylated derivatives in mutants carrying thef3hmutant allele, resulting from the conversion of naringenin to eriodictyol by flavonoid 3’-hydroxylase (F3’H) activity.

Conclusions

We describe thein plantamultifunctionality of the three central flavonoid 2-ODDs fromA. thalianaand identify a bypass in thef3h/fls1/anstriple mutant that leads to the formation of eriodictyol derivatives. As (homo-)eriodictyols are known as bitter taste maskers, the annotated eriodictyol (derivatives) and in particular the observations made on theirin plantaproduction, could provide valuable insights for creating of novel food supplements.
Human hippocampus and dorsomedial prefrontal cortex infer and update latent causes during social interaction
Authors: Mahmoodi Ali , Luo Shuyi , Harbison Caroline , Piray Payam , Rushworth Matthew
Published: September 2023

When an important event occurs, the observer should identify which features of the environment might have caused it. This is the latent cause inference problem, and it must be solved if observers are to understand their environments. The problem is acute in social settings where individuals may not make equal contributions to the outcomes they achieve together. Here, we designed a novel task in which participants inferred which of two characters was the more likely to have been responsible for outcomes achieved by working together. Using computational modelling, univariate and multivariate analysis of human fMRI, and continuous theta burst stimulation we identified two brain regions that solved the task. Notably, as each outcome occurred, it was possible to decode inference of its cause (the responsible character) from activity in hippocampus. Activity in dorsomedial prefrontal cortex updated estimates of association between cause -- the responsible character – and the outcome.
Metabotropic signaling within somatostatin interneurons controls transient thalamocortical inputs during development
Authors: Dwivedi Deepanjali , Dumontier Dimitri , Sherer Mia , Lin Sherry , Mirow Andrea MC , Qiu Yanjie , Xu Qing , Liebman Samuel A , Joseph Djeckby , Datta Sandeep R , Fishell Gord , Pouchelon Gabrielle
Published: September 2023

During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian “fire together, wire together” precept. However, select connections, essential for circuit development, are transient. They are effectively connected early in development, but strongly diminish during maturation. The mechanisms by which transient connectivity recedes are unknown. To investigate this process, we characterize transient thalamocortical inputs, which depress onto somatostatin inhibitory interneurons during development, by employing optogenetics, chemogenetics, transcriptomics and CRISPR-based strategies. We demonstrate that in contrast to typical activity-dependent mechanisms, transient thalamocortical connectivity onto somatostatin interneurons is non-canonical and involves metabotropic signaling. Specifically, metabotropic-mediated transcription, of guidance molecules in particular, supports the elimination of this connectivity. Remarkably, we found that this developmental process impacts the development of normal exploratory behaviors of adult mice.
The apoptotic splicing regulators RBM5 and RBM10 are subunits of the U2 snRNP engaged with intron branch sites on chromatin
Authors: Damianov Andrey , Lin Chia-Ho , Huang Jeffrey , Zhou Lin , Jami-Alahmadi Yasaman , Wohlschlegel James , Black Douglas L.
Published: September 2023

Understanding the mechanisms of pre-mRNA splicing and spliceosome assembly is limited by technical challenges to examining spliceosomes in vivo. Here we report the isolation of RNP complexes derived from precatalytic A or B-like spliceosomes solubilized from the chromatin pellet of lysed nuclei. We found that these complexes contain U2 snRNP proteins and a portion of the U2 snRNA, bound with intronic branch sites prior to the first catalytic step of splicing. Sequencing these pre-mRNA fragments allowed the transcriptome-wide mapping of branch sites with high sensitivity. In addition to known U2 snRNP proteins, these complexes contained the proteins RBM5 and RBM10. RBM5 and RBM10 are alternative splicing regulators that control exons affecting apoptosis and cell proliferation in cancer, but were not previously shown to associate with the U2 snRNP or to play roles in branch site selection. We delineate a common segment of RBM5 and RBM10, separate from their known functional domains, that is required for their interaction with the U2 snRNP. We identify a large set of splicing events regulated by RBM5 and RBM10 and find that they predominantly act as splicing silencers. Disruption of their U2 interaction renders the proteins inactive for repression of many alternative exons. We further find that these proteins assemble on branch sites of nearly all exons across the transcriptome, including those whose splicing is not altered by them. We propose a model where RBM5 and RBM10 act as components of the U2 snRNP complex. From within this complex, they sense structural features of branchpoint recognition to either allow progression to functional spliceosome or rejection of the complex to inhibit splicing.
Inverse and ProportionaltransModulation of Gene Expression in Human Aneuploidies
Authors: Zhang Shuai , Wang Ruixue , Zhang Ludan , Birchler James A. , Sun Lin
Published: September 2023

Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried chromosomes are inversely or proportionallytrans-modulated, while a subset of genes on the varied chromosomes are compensated. Less genome-wide modulation is found for sex chromosome aneuploidy compared with autosomal aneuploidy due to X inactivation and the retention of dosage sensitive regulators on both sex chromosomes to limit the effective dosage change. We also found that lncRNA and mRNA can have different responses to aneuploidy. Furthermore, we analyzed the relationship between dosage-sensitive transcription factors and their targets, which illustrated the modulations and indicates genomic imbalance is related to stoichiometric changes of components of gene regulatory complexes.
Dominant CIZ1 fragments drive epigenetic instability and are expressed in early stage cancers
Authors: Turvey Gabrielle L. , de Alba Ernesto López , Stewart Emma , Byrom Lewis , Cook Heather , Sofi Sajad , Alalti Ahmad , Ainscough Justin F-X , Mason Andrew , Antson Alfred A , Coverley Dawn
Published: September 2023

CIZ1 is a nuclear matrix protein that is part of the large RNA-dependent supramolecular assembly complexes (SMACs) that form at the inactive X chromosome (Xi) in female cells, and smaller assemblies throughout the nucleus in males and females. It plays a role in maintenance of epigenetic state and gene expression in differentiated cells, via stabilisation of histone post-translational modifications H2AK119ub1 and H3K27me3, added by polycomb repressive complexes (PRC) 1 and 2.

Here, we show that expression of the N-terminal replication domain (RD) and C-terminal anchor domain (AD) of human CIZ1 transcript is uncoupled, with consistently elevated AD in early stage breast cancers, and sporadically elevated AD in other common solid tumours. At the protein level CIZ1-Xi SMACs are corrupted in female breast cancers cells, and this is accompanied by elevated AD-encoding transcripts.

We modelled the effect of AD fragments in primary murine embryonic fibroblasts and observed dominant-negative interference with CIZ1 SMACs during their assembly in early G1 phase. Mutagenesis identified the matrin 3 homology domain as essential for self-interaction to form stable homodimersin vitro, and as a determinant of its dominant-negative effect in cells, implicating the dimerization interface in CIZ1 SMAC integrity.

SMAC disruption was coincident with depletion of PRC1-dependent H2AK119ub1 from Xi chromatin, in a manner abrogated by the PR-deubiquitinase inhibitor PR619, suggesting that CIZ1 SMACs normally stabilise H2AK119ub1 by shielding Xi chromatin from attack by deubiquitinases. Moreover, SMAC disruption was accompanied by changes in gene expression within days.

Together, the data suggest that inappropriate expression of CIZ1 AD fragments could drive epigenetic instability in early stage breast cancers by destabilizing the CIZ1 SMACs that normally protect repressed chromatin.

Abstract Figure
Corporate sustainability performance and firm performance: the state-of-the-art and future research agenda
Authors: Kumari Garima , Joshi Yatish
Published: September 2023

Purpose

The past years have seen more studies exploring corporate sustainability performance (CSP) and firm performance nexus, but there has been a lack of analysis using bibliometric studies. This study aims to provide a structure for the CSP-firm performance relationship to gain valuable insights for further research.

Design/methodology/approach

Bibliometric analysis was carried on 462 articles from the Scopus database spanning 1987–2022 using VOSviewer and R software Bibliometrix.

Findings

The study overviews the most notable articles, authors, journals, countries and institutions. Four main clusters are identified to determine research themes using bibliographic coupling (documents). Additionally, co-occurrence analysis (keywords) reveals three themes indicating current and future research trends.

Originality/value

The study presents an overview of the evolution of research on CSP-firm performance nexus. This work consolidates bibliometric analysis and systematic literature review on CSP and firm performance, covering all significant work on the topic and presenting the field's knowledge map and future research directions.
Impact of digital capability on firm resilience: the moderating role of coopetition behavior
Authors: Chen Congjun , Pan Jieyi , Liu Shasha , Feng Taiwen
Published: September 2023

Purpose

In the digital economy, digital capability has become an important dynamic capability of enterprises and plays an essential role in enhancing firm resilience. This study aims to investigate the relationships among digital capability, knowledge search, coopetition behavior and firm resilience based on knowledge-based view and resource-based view.

Design/methodology/approach

This study uses the hierarchical regression and bootstrapping methods to test the theoretical framework and research hypotheses. The survey data were collected from 241 Chinese enterprises.

Findings

Digital capability has significantly positive effects on knowledge search and firm resilience. Knowledge search positively affects firm resilience and partially mediates the relationship between digital capability and firm resilience. Coopetition behavior weakens the relationship between digital capability and knowledge search, and the mediating effect of knowledge search in the relationship between digital capability and firm resilience. The moderating effect of coopetition behavior on the relationship between digital capability and firm resilience is insignificant.

Originality/value

This study clarifies the effect of digital capability on firm resilience and uncovers the “black box” from digital capability to firm resilience. In addition, this research enriches the literature on digital capability and firm resilience and expands the application of knowledge-based view and resource-based view in the digital context.
Quantum accountability: when does enough become too much in top pay decision-making?
Authors: Shortland Susan , Perkins Stephen J.
Published: September 2023

Purpose

The purpose of this paper is to examine how and why individuals involved in executive remuneration (top pay) decision-making consider quantum as being appropriate rather than excessive, theorised under the rubric of accountability.

Design/methodology/approach

In-depth interviews were conducted with non-executive directors (NEDs) serving on remuneration committees (Remcos), institutional investors, their external advisers and internal HR reward experts. Transcripts were analysed using NVivo and the Gioia qualitative methodology.

Findings

Defining, measuring and applying performance conditionality in the determination of top pay quantum such that it aligns with company strategy/culture and values, as well as individual recipient motivations, is difficult. While creative approaches to setting top pay so as to attract, retain and motivate key personnel are welcomed, these risk Remco members' personal/organisational reputations. Members recognise disconnection between top pay quantum and general pay levels and how the media highlights social inequality leading to public distrust. They believe they can contribute to more socially acceptable quantum by applying their own values in top pay decision-making.

Originality/value

Sanctions-based, trust-based and selection/peer networks/felt-based accountability theory is used to explain decision-makers’ actions when determining top pay quantum. This paper extends felt accountability theory to encompass public/societal accountability in the context of the appropriateness of top pay quantum decisions.
Executive perceptions of course and educator performance on flipped classroom
Authors: Pereira Bueno Ricardo Luiz , Ribeiro Serra Fernando Antonio , Scafuto Isabel Cristina
Published: September 2023

Purpose

This article aims to examine the related effects between out-of-class activities, mediated by in-class activities, on the perception of course and teacher performance in a flipped classroom institutionalized setting.

Design/methodology/approach

The authors argue that institutionalized out-of-class (content) and in-class (learning) activities positively impact course and teaching quality perception. This study used a sample of 978 responses from MBA students to conduct a path model analysis to test four hypotheses developed from literature from flipped classroom proposing the positive relationship of out-of-class activities in in-class activities and its influence on the course and teaching performance.

Findings

The findings reported that out-class and in-class activities and educator performance influenced course performance perception. In-class activities mediated the out-of-class activities’ impact and directly impacted educator’s and course performance. Educator performance is positively correlated with course performance. Overall, executives have a positive perception on institutionalized flipped classroom for MBA courses as an effective provision form. The flipped classroom is able to mobilize their experiences and enrich learners’ educational experience.

Research limitations/implications

Only one unit of the higher education organization was studied, and the authors do not consider indirect effects of the environment on variable’s relationships nor the indirect effects whose would be a suggested for future studies.

Originality/value

The present study provides new insights on flipped classroom. This study evidenced that flipped classroom planned and standardized in an institutional level positively impacts the outcome within the context of executive education.
A 30-year journey of hospitality and tourism research: a comprehensive topic modeling analysis
Authors: Kurt Senol , Assefa Feven Zewdie , Tuzlukaya Sule Erdem , Karatepe Osman M.
Published: September 2023

Purpose

The purpose of this study is to provide an overview of the research conducted on hospitality and tourism articles published in Q1 category journals from 1990 to 2023. This study also aims to measure the topic prevalence in selected journals throughout the years, their change over time and similarities of journals.

Design/methodology/approach

Latent dirichlet allocation algorithm is used as a topic modeling method to identify and analyze topics in hospitality and tourism research over the past 30 years.

Findings

The results of the study indicate that hospitality and tourism research has recently focused on topics such as employee behavior, customer satisfaction, online reviews, medical tourism and tourist experience. However, the results also indicate a negative trend in topics such as hotel management, sustainability, profession, economic growth and tourist destination.

Practical implications

This study can be used to examine the evolution of research patterns over time, find hot and cold themes and uncover untapped or understudied areas. This can aid academics in their investigations and practitioners in making sound strategic decisions.

Originality/value

This study contributes to the existing literature by providing a new approach and comprehensive analysis of hospitality and tourism research topics. It delineates an overview of the progression of hospitality and tourism research over the past 30 years, identifies the trending topics and explores the potential impacts that these identified topics may have on future studies.
Understanding coordination in humanitarian action: insights from the activities–resources–actors model
Authors: Tosi Laetitia , Marty Justine
Published: September 2023

Purpose

This study aims to propose an analytical tool based on the activities–resources–actors (ARA) model to understand the coordination mechanisms in humanitarian action. The tool identifies the phases of humanitarian action and analyzes the underlying mechanisms that facilitate coordination among organizations.

Design/methodology/approach

This study uses a literature review to develop analytical grids and theoretical propositions based on the ARA model.

Findings

The ARA model is a useful tool for understanding coordination mechanisms in humanitarian action. The study identifies key elements of interaction systems and characterizes the phases of humanitarian action. Effective coordination among organizations is essential for successful aid delivery. The study provides four theoretical propositions.

Research limitations/implications

Future research could validate the propositions formulated in this study through case studies.

Practical implications

The analytical grids proposed in this study can be used by humanitarian organizations to improve their coordination mechanisms and aid delivery processes.

Social implications

Effective humanitarian action can help alleviate the suffering of individuals affected by crises and contribute to the overall well-being of communities. The analytical tool proposed in this study can improve the effectiveness of humanitarian action and ultimately benefit society.

Originality/value

This paper presents an original approach by leveraging the ARA model to develop an analytical tool for humanitarian action, which is useful for both practitioners and researchers. In addition, the paper attempts to overcome the siloed vision of humanitarian action by highlighting “emergency-development” aspect.
Role of job satisfaction in microfinance institutions' performance: considering performance appraisal, training and development
Authors: Ohene Afriyie Emelia , Jin Yan , Yakubu Mariama , Awudu Iddrisu
Published: September 2023

Purpose

This study aims to examine the influence of training and development (TAD), including performance appraisal (PFA), on the performance of microfinance institutions in a developing economy.

Design/methodology/approach

A random sampling drew 100 microfinance institutions in Ghana's Greater Accra Region. Then, a purposive sampling approach selected a cross-section of employees in these institutions. Finally, the data were collected from a sample of 367 respondents, such as managers, utilizing a survey questionnaire. Structural equation modeling (SEM) was used to test hypothesized relationships.

Findings

The study results indicate that PFA has a statistically significant positive relationship with organizational performance, and this relationship is partially mediated by job satisfaction (JBS). Interestingly, the TAD process does not have a statistically significant positive relationship with organizational performance when JBS is present in the model. In fact, JBS fully mediates the relationship between TAD and organizational performance.

Research limitations/implications

The study is limited to microfinance in tiers two and three in Greater Accra city of Ghana and did not include the entire country. Although the city of Accra provides a generalized representation of the research, which can be replicated, some variables and results may be impacted if other tiers of microfinance organizations are incorporated.

Practical implications

TAD, as well as PFA, enhance the performance of microfinance and can be utilized as tools for competitive advantage in small and medium-sized enterprises (SMEs) (e.g. microfinance institutions). The study accentuates the value of TAD, PFA and JBS in microfinance in a developing country like Ghana.

Originality/value

This is an original study investigating the effect of TAD and PFA practices on the performance of SMEs in a developing country like Ghana. Also, the study analyses JBS as a mediation variable to performance using SEM, which advances the research methodology in this research field.
Does practicing healthy lifestyles improve the technical efficiency of farms?
Authors: Adebisi Oluwaremilekun Ayobami , Muhammad-Lawal Abdulazeez , Adebisi Luke Oloruntoba
Published: September 2023

Purpose

The purpose of this paper is to ascertain if practising healthy lifestyles improves the technical efficiency of farms in Kwara state, Nigeria. In theory, all deviations from the optimum level of output are due to random effects and inefficiency of producers in which their health plays a key part and is dependent on the kind of lifestyle practiced whether healthy or unhealthy.

Design/methodology/approach

Cross-sectional data were employed through a three-staged sampling technique to pick 320 arable crop farmers across the state using a well-defined questionnaire. Data analysis was carried out using descriptive statistics, healthy lifestyles index (HLI), stochastic production frontier (SPF) and propensity score matching (PSM).

Findings

First, the analysis showed that about one-third of the sampled arable crop farmers practised healthy lifestyles. Second, the average technical efficiency of arable crop production for farmers who practised a healthy lifestyle was 0.893, and the level of technical inefficiency of the farms was determined by health-related lifestyle status, number of day's illness and educational level. Third, technical efficiency was improved by 0.00431067 for farms whose farmers practised a healthy lifestyle.

Originality/value

Rather than seeing that technical efficiencies of farms are attributed to farm characteristics, inputs used and socioeconomic characteristics alone, the findings suggest that technical inefficiencies of arable crop farmers were also due to the kind of lifestyle practised, which was evidenced in the increased efficiency for farmers who practised healthy lifestyle.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-05-2023-0353
A replication and extension of wine retail consumer purchase patterns: double jeopardy and duplication of purchase laws
Authors: Wilson Damien , Winchester Maxwell , Visser Michael S.
Published: September 2023

Purpose

This study aims to understand the degree of predictability and value in analyzing consumer purchase patterns in the US wine retail market. The study considers whether brands in US wine retailing follow the well-established Duplication of Purchase Law and Double Jeopardy Law.

Design/methodology/approach

Over 20,000 customer panel wine purchases were analyzed from a number of locations within a supermarket chain based on the West Coast of the USA. Cross-purchasing behavior for the top 20 wine brands by market penetration was analyzed to assess whether the well-established Duplication of Purchase Law and Double Jeopardy Law hold up in this wine retail setting in the USA. The degree of predictability and the existence of anomalies in expected cross-purchasing behavior were identified in the analysis.

Findings

Results confirmed a Double Jeopardy pattern and that wine cross-purchasing patterns for the most part followed the Duplication of Purchase Law. However, exceptions to these patterns were found, which indicated areas in need of managerial attention due to the potential to remedy, develop or monitor the most prominent variations between predicted and realized cross-purchasing behavior. Repeated identification of variations has been identified in other product categories, known as market partitions.

Originality/value

Although it is commonly believed that wine is a unique product category, the results of this study demonstrate that consumer behavior toward wine is similar to other fast-moving consumer goods. The exceptions suggest that while similar consumer purchase patterns are evident, consumers are more likely to cross purchase wine brands and grape types more than would be expected given Duplication of Purchase Law benchmarks.