bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of signalling pathways involved in gill regeneration in zebrafish
Authors: Cadiz Laura , Reed Maddison , Monis Simon , Akimenko Marie-Andrée , Jonz Michael G.
Published: June 2023

The occurrence of regeneration of the organs involved in respiratory gas exchange amongst vertebrates is heterogeneous. In aquatic animals, such as amphibians and fishes, the gills regenerate completely following resection or amputation; whereas in mammals, only partial, facultative regeneration of lung tissue occurs following injury. Given the homology between gills and lungs, the capacity of gill regeneration in aquatic species is of major interest in determining the underlying molecular or signalling pathways involved in respiratory organ regeneration. In the present study, we used adult zebrafish (Danio rerio) to characterize signalling pathways involved in the early stages of gill regeneration. Regeneration of the gills, including the gas exchange surfaces, was induced by resection of the gill filaments and observed over a period of up to 10 days. We screened for the effects of the drugs, SU5402, dorsomorphin, and LY411575, which inhibit FGF, BMP or Notch signalling, respectively, on development of the blastema. Exposure to each drug for 5 days significantly reduced blastema formation in regenerates, compared to unresected controls. In separate experiments, and under normal conditions of regeneration, we used quantitative real-time PCR and observed an increased expression of genes encoding for the bone morphogenetic factor, Bmp2b, fibroblast growth factor, Fgf8a, a transcriptional regulator (Her6) involved in Notch signalling, and Sonic Hedgehog (Shha), in regenerating gills at 10 day post-resection, compared to unresected controls.In situhybridization confirmed that all four genes were expressed in regenerating gill tissue. This study implicates BMP, FGF, Notch and Shh signalling in gill regeneration in zebrafish.

SUMMARY STATEMENT

Gill regeneration in zebrafish is mediated by multiple signalling pathways, including BMP, FGF, Notch and Sonic Hedgehog.
Spatio-temporal mechanisms of consolidation, recall and reconsolidation in reward-related memory trace
Authors: Hamed Adam , Kursa Miron Bartosz , Karwicka Wiktoria , Piwoński Krzysztof Piotr , Falińska Monika , Danielewski Konrad , Rejmak-Kozicka Emilia , Włodkowska Urszula , Kubik Stepan , Czajkowski Rafał
Published: June 2023

The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in-situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.
Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase
Authors: Egbert Jeremy R. , Silbern Ivan , Uliasz Tracy F. , Lowther Katie M. , Yee Siu-Pok , Urlaub Henning , Jaffe Laurinda A.
Published: June 2023

In response to luteinizing hormone, multiple proteins in rat and mouse granulosa cells are rapidly dephosphorylated, but the responsible phosphatases remain to be identified. Because the phosphorylation state of phosphatases can regulate their interaction with substrates, we searched for phosphatases that might function in LH signaling by using quantitative mass spectrometry. We identified all proteins in rat ovarian follicles whose phosphorylation state changed detectably in response to a 30-minute exposure to LH, and within this list, identified protein phosphatases or phosphatase regulatory subunits that showed changes in phosphorylation. Phosphatases in the PPP family were of particular interest because of their requirement for dephosphorylating the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase in the granulosa cells, which triggers oocyte meiotic resumption. Among the PPP family regulatory subunits, PPP1R12A and PPP2R5D showed the largest increases in phosphorylation, with 4-10 fold increases in signal intensity on several sites. Although follicles from mice in which these phosphorylations were prevented by serine-to-alanine mutations in eitherPpp1r12aorPpp2r5dshowed normal LH-induced NPR2 dephosphorylation, these regulatory subunits and others could act redundantly to dephosphorylate NPR2. Our identification of phosphatases and other proteins whose phosphorylation state is rapidly modified by LH provides clues about multiple signaling pathways in ovarian follicles.

Graphical Abstract

Summary sentence

Quantitative mass spectrometric analysis of phosphatases whose phosphorylation state is rapidly modified by luteinizing hormone provides clues about how LH signaling dephosphorylates NPR2 as well as a resource for future studies.
Unsupervised Machine Learning for Species Delimitation, Integrative Taxonomy, and Biodiversity Conservation
Authors: Pyron R. Alexander
Published: June 2023

Integrative taxonomy combining data from multiple axes of biologically relevant variation is a major recent goal of systematics. Ideally, such taxonomies would be backed by similarly integrative species-delimitation analyses. Yet, most current methods rely solely or primarily on molecular data, with other layers often incorporated only in apost hocqualitative or comparative manner. A major limitation is the difficulty of deriving and implementing quantitative parametric models linking different datasets in a unified ecological and evolutionary framework. Machine Learning methods offer flexibility in this arena by learning high-dimensional associations between observations (e.g., individual specimens) across a wide array of input features (e.g., genetics, geography, environment, and phenotype) to delineate statistical clusters. Here, I implement an unsupervised method using Self-Organizing (or “Kohonen”) Maps (SOMs). Recent extensions called SuperSOMs can integrate an arbitrary number of layers, each of which exerts independent influence on the two-dimensional output clustering via empirically estimated weights. These output clusters can then be delimited intoKsignificant units that are interpreted as species or other entities. I show an empirical example inDesmognathussalamanders with layers representing alleles, space, climate, and traits. Simulations reveal that the SOM/SuperSOM approach can detectK=1, does not over-split, reflects contributions from all layers with signal, and does not allow layer size (e.g., large genetic matrices) to overwhelm other datasets, desirable properties addressing major concerns from previous methods. Finally, I suggest that these and similar methods could integrate conservation-relevant layers such as population trends and human encroachment to delimit management units from an explicitly quantitative framework grounded in the ecology and evolution of species limits and boundaries.
Competition for iron shapes metabolic antagonism betweenBacillus subtilisandPseudomonas
Authors: Lyng Mark , Jørgensen Johan P. B. , Schostag Morten D. , Jarmusch Scott A. , Aguilar Diana K. C. , Lozano-Andrade Carlos N. , Kovács Ákos T.
Published: June 2023

Siderophores have long been implicated in sociomicrobiology as determinants of bacterial interrelations. For plant-associated genera likeBacillusandPseudomonas, siderophores are well known for their biocontrol functions. Here, we explored the functional role of theBacillus subtilissiderophore bacillibactin in an antagonistic interaction withPseudomonas marginalis. The presence of bacillibactin strongly influenced the outcome of the interaction in an iron-dependent manner. The bacillibactin producerB. subtilisrestricts colony spreading ofP. marginalisby repressing the transcription of histidine kinase-encoding genegacS, thereby abolishing production of secondary metabolites such as pyoverdine and viscosin. By contrast, lack of bacillibactin restrictedB. subtiliscolony growth in a mechanism reminiscent of a siderophore tug-of-war for iron. Our analysis revealed that theBacillus-Pseudomonasinteraction is conserved across fluorescentPseudomonasspp., expanding our understanding of the interplay between two genera of the most well-studied soil microbes.
Dissociating the Contributions of Frontal Eye Field Activity to Spatial Working Memory and Motor Preparation
Authors: Jonikaitis Donatas , Noudoost Behrad , Moore Tirin
Published: June 2023

Neurons within dorsolateral prefrontal cortex of primates are characterized by robust persistent spiking activity exhibited during the delay period of working memory tasks. This includes the frontal eye field (FEF) where nearly half of the neurons are active when spatial locations are held in working memory. Past evidence has established the FEF’s contribution to the planning and triggering of saccadic eye movements as well as to the control of visual spatial attention. However, it remains unclear if persistent delay activity reflects a similar dual role in movement planning and visuospatial working memory. We trained monkeys to alternate between different forms of a spatial working memory task which could dissociate remembered stimulus locations from planned eye movements. We tested the effects of inactivation of FEF sites on behavioral performance in the different tasks. Consistent with previous studies, FEF inactivation impaired the execution of memory-guided saccades, and impaired performance when remembered locations matched the planned eye movement. In contrast, memory performance was largely unaffected when the remembered location was dissociated from the correct eye movement response. Overall, the inactivation effects demonstrated clear deficits on eye movements, regardless of task type, but little or no evidence of a deficit in spatial working memory. Thus, our results indicate that persistent delay activity in the FEF contributes primarily to the preparation of eye movements and not to spatial working memory.
Incomplete Reprogramming of DNA Replication Timing in Induced Pluripotent Stem Cells
Authors: Edwards Matthew M. , Wang Ning , Massey Dashiell J. , Egli Dieter , Koren Amnon
Published: June 2023

Induced pluripotent stem cells (iPSC) are a widely used cell system and a foundation for cell therapy. Differences in gene expression, DNA methylation, and chromatin conformation, which have the potential to affect differentiation capacity, have been identified between iPSCs and embryonic stem cells (ESCs). Less is known about whether DNA replication timing – a process linked to both genome regulation and genome stability – is efficiently reprogrammed to the embryonic state. To answer this, we profiled and compared genome-wide replication timing between ESCs, iPSCs, and cells reprogrammed by somatic cell nuclear transfer (NT-ESCs). While NT-ESCs replicated their DNA in a manner indistinguishable from ESCs, a subset of iPSCs exhibit delayed replication at heterochromatic regions containing genes downregulated in iPSC with incompletely reprogrammed DNA methylation. DNA replication delays were not the result of gene expression and DNA methylation aberrations and persisted after differentiating cells to neuronal precursors. Thus, DNA replication timing can be resistant to reprogramming and lead to undesirable phenotypes in iPSCs, establishing it as an important genomic feature to consider when evaluating iPSC lines.
CREATION AND CHARACTERIZATION OF A RECOMBINANT MAMMALIAN ORTHOREOVIRUS EXPRESSING HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 PEPTIDES
Authors: Jandick Nicole A. , Miller Cathy L.
Published: June 2023

Mammalian orthoreovirus (MRV) is an oncolytic virus that has been tested in over 30 clinical trials. Increased clinical success has been achieved when MRV is used in combination with other onco-immunotherapies. This has led the field to explore the creation of recombinant MRVs which incorporate immunotherapeutic sequences into the virus genome. This work focuses on creation and characterization of a recombinant MRV, S1/HER2nhd, which expresses three human epidermal growth factor receptor 2 (HER2) peptides (E75, AE36, and GP2) known to induce HER2 specific CD8+ and CD4+ T cells. We show S1/HER2nhd expresses HER2 peptides in infected cells and on the virion, and infects, replicates, and reduces HER2+ breast cancer cell survival. The oncolytic properties of MRV combined with HER2 peptide expression holds potential as a vaccine to prevent recurrences of HER2 expressing cancers.
Exploring the Interactive Effects of Seed and Site Limitation on Recruitment Dynamics inPanicum hallii
Authors: Razzaque Samsad , Juenger Thomas E
Published: June 2023

Seedling recruitment is a critical life history stage that is likely driven by the interplay of seed and microsite limitation and their interaction with seed traits. Here, we performed a factorial experiment involving seed addition and surface soil disturbance to explore the combined effects of seed and site availability using genotypes characterized by varying seed mass and dormancy traits. Additionally, we included hybrids that exhibited recombined seed trait relationships compared to natural genotypes, allowing us to assess the impact of specific seed traits on establishment across different sites. We detected a significant three-way interaction between seed addition, site conditions, and soil surface disturbance, influencing both seedling and adult recruitment inPanicum hallii, a perennial grass found in coastal mesic (lowland) and inland xeric (upland) habitats. This recruitment pattern suggests that lowland and upland establishment at foreign site is constrained by the interplay of seed and site limitations. Notably, soil surface disturbance facilitated recruitment of the upland genotype while constraining recruitment of the lowland genotype across all sites. Our results highlight the importance of seed size and dormancy as key factors impacting recruitment, suggesting a potential interactive relationship between these traits.
On the origin of F-wave: involvement of central synaptic mechanisms
Authors: Özyurt M. Görkem , Nascimento Filipe , Brownstone Robert M. , Beato Marco
Published: June 2023

Neurophysiological methods are used widely to gain information about motoneuron excitability and axon conduction in neurodegenerative diseases. The F-wave is a common biomarker used to test motoneuron properties in the diagnosis of neurological diseases. Although the origin of the F-wave is a subject of debate, the most widely accepted mechanism posits that the F-wave is generated by the backfiring of motoneurons stimulated antidromically from the periphery. In this study, we developed anex vivomouse sciatic nerve-attached spinal cord preparation with sensory axons severed in which stimulation of the whole sciatic nerve or its tibial branch evoked responses with the electrophysiological signatures of F-waves. Manipulations of synaptic transmission by either removal of extracellular calcium or block of post-synaptic glutamate receptors abolished these responses. These results suggest that F-waves are mediated by spinal microcircuits activated by recurrent motor axon collaterals via glutamatergic synapses.
In situ spatial reconstruction of distinct normal and pathological cell populations within the human adrenal gland
Authors: Fu Rui , Walters Kathryn , Koc Katrina , Baldwin Amber , Clay Michael , Kiseljak-Vassiliades Katja , Fishbein Lauren , Mukherjee Neelanjan
Published: June 2023

The human adrenal gland consists of concentrically organized functionally distinct regions responsible for hormone production. Dysregulation of adrenocortical cell differentiation alters the proportion and organization of the functional zones of the adrenal cortex leading to disease. Current models of adrenocortical cell differentiation are based on mouse studies, but there are known organizational and functional differences between human and mouse adrenal glands. This study aimed to investigate the centripetal differentiation model in the human adrenal cortex and characterize aldosterone-producing micronodules (APMs) to better understand adrenal diseases such as primary aldosteronism. We applied spatially resolvedin situtranscriptomics to human adrenal tissue sections from two individuals and identified distinct cell populations and their positional relationships. The results supported the centripetal differentiation model in humans, with cells progressing from the outer capsule to the zona glomerulosa, zona fasciculata, and zona reticularis. Additionally, we characterized two APMs in a 72-year-old female. Comparison with earlier APM transcriptomes indicated a subset of core genes, but also heterogeneity between APMs. The findings contribute to our understanding of normal and pathological cellular differentiation in the human adrenal cortex.
TRAIL agonists rescue mice from radiation-induced lung injury
Authors: Strandberg Jillian , Louie Anna , Lee Seulki , Hahn Marina , Srinivasan Praveen , George Andrew , De La Cruz Arielle , Zhang Leiqing , Borrero Liz Hernandez , Huntington Kelsey E. , De La Cruz Payton , Seyhan Attila A. , Koffer Paul P. , Wazer David E. , DiPetrillo Thomas A. , Azzoli Christopher G. , Rounds Sharon I. , Graff Stephanie L. , Abbas Abbas E. , Zhou Lanlan , El-Deiry Wafik S.
Published: June 2023

Cancer therapy is often limited by toxicity from pneumonitis. This often-lethal side effect is known to be impacted by innate immunity, and in particular the pathways regulated by the TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from the lethal effects of radiation. We found that two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound #10 (TIC10/ONC201), could achieve this goal. Both compounds could completely protect mice from lethality by reducing pneumonitis, alveolar-wall thickness, and oxygen desaturation. At the molecular level, this protection appeared to be due to the inhibition of CCl22, a macrophage-derived chemokine previously associated with radiation pneumonitis and pulmonary fibrosis. The discovery that short-term treatment with TRAIL pathway agonists effectively rescues animals from high doses of radiation exposure has important translational implications.

One Sentence Summary

Prevention of lethality, pneumonitis, lung fibrosis and skin dermatitis post-ψ-irradiation by short- term treatment with innate immune TRAIL pathway agonists
Enterovirus D68 capsid formation and stability requires acidic compartments
Authors: Galitska Ganna , Jassey Alagie , Wagner Michael A. , Pollack Noah , Jackson William T.
Published: June 2023

Enterovirus D68 (EV-D68), a picornavirus traditionally associated with respiratory infections, has recently been linked to a polio-like paralytic condition known as acute flaccid myelitis (AFM). EV-D68 is understudied, and much of the field’s understanding of this virus is based on studies of poliovirus. For poliovirus, we previously showed that low pH promotes virus capsid maturation, but here we show that, for EV-D68, inhibition of compartment acidification during a specific window of infection causes a defect in capsid formation and maintenance. These phenotypes are accompanied by radical changes in the infected cell, with viral replication organelles clustering in a tight juxtanuclear grouping. Organelle acidification is critical during a narrow window from 3-4hpi, which we have termed the “transition point,” separating translation and peak RNA replication from capsid formation, maturation and egress. Our findings highlight that acidification is crucial only when vesicles convert from RNA factories to virion crucibles.

Importance

The respiratory picornavirus enterovirus D68 is a causative agent of Acute Flaccid Myelitis, a childhood paralysis disease identified in the last decade. Poliovirus, another picornavirus associated with paralytic disease, is a fecal-oral virus which survives acidic environments when passing from host-to-host. Here we follow up on our previous work showing a requirement for acidic intracellular compartments for maturation cleavage of poliovirus particles. Enterovirus D68 requires acidic vesicles for an earlier step, assembly and maintenance of viral particles themselves. These data have strong implications for the use of acidification blocking treatments to combat enterovirus diseases.
Prevalence and distribution of non-typhoidalSalmonella entericaserogroups and serovars isolated from normally sterile sites: a global systematic review
Authors: Hagedoorn Nienke N. , Murthy Shruti , Birkhold Megan , Marchello Christian S. , Crump John A.
Published: June 2023

To inform vaccine development strategies, we aimed to systematically review evidence on the prevalence and distribution of non-typhoidalSalmonella entericaserogroups and serovars. We searched four databases from inception through 4 June 2021. We included articles that reported at least one non-typhoidalSalmonella entericastrain by serogroup or serovar isolated from a normally sterile site. Of serogrouped isolates, we pooled the prevalence of serogroup O:4, serogroup O:9, and other serogroups using random-effects meta-analyses. Of serotyped isolates, we pooled the prevalence ofSalmonellaTyphimurium (member of serogroup O:4),SalmonellaEnteritidis (member of serogroup O:9), and other serovars. Of 82 studies yielding 24,258 serogrouped isolates, pooled prevalence (95% CI) was 44.7% (36.3%-48.3%) for serogroup O:4, 45.4% (36.9%-49.0%) for serogroup O:9, and 9.9% (6.1%-13.3%) for other serogroups. Pooled prevalence (95%CI) was 36.8% (29.9%-44.0%) forSalmonellaTyphimurium, 37.8% (33.2%-42.4%) forSalmonellaEnteritidis, and 18.4% (11.4%-22.9%) for other serovars. Of global serogrouped non-typhoidalSalmonellaisolates from normally sterile sites, serogroup O:4 and O:9 together accounted for 90%. Of global serotyped isolates, serovars Typhimurium and Enteritidis together accounted for 75%. Vaccine development strategies covering serogroups O:4 and O:9, or serovars Typhimurium and Enteritidis, have the potential to prevent the majority of non-typhoidalSalmonellainvasive disease.

PROSPERO:CRD42022376658.

Key results

Invasive infections in normally sterile sites caused by non-typhoidalSalmonellahave a case fatality ratio of 15%.

Vaccine products for human non-typhoidalSalmonellaare in currently in development.

For future vaccine strategies, we provide global non-typhoidalSalmonellaserogroup and serovar coverage by region and by age groups.

Serogroups O:4 and O:9 account for 90% of isolates of non-typhoidalSalmonella entericafrom normally sterile sites.

Serovars Typhimurium and Enteritidis, members of serogroup O:4 and O:9, respectively, cover 75% of isolates of non-typhoidalSalmonella entericafrom normally sterile sites.
Modeling soybean growth: A mixed model approach
Authors: Delattre Maud , Toda Yusuke , Tressou Jessica , Iwata Hiroyoshi
Published: June 2023

The evaluation of plant and animal growth, separately for genetic and environmental effects, is necessary for genetic understanding and genetic improvement of environmental responses of plants and animals. We propose to extend an existing approach that combines nonlinear mixed-effects model (NLMEM) and the stochastic approximation of the Expectation-Maximization algorithm (SAEM) to analyze genetic and environmental effects on plant growth. These tools are widely used in many fields but very rarely in plant biology. During model formulation, a nonlinear function describes the shape of growth, and random effects describe genetic and environmental effects and their variability. Genetic relationships among the varieties were also integrated into the model using a genetic relationship matrix. The SAEM algorithm was chosen as an efficient alternative to MCMC methods, which are more commonly used in the domain. It was implemented to infer the expected growth patterns in the analyzed population and the expected curves for each variety through a maximum-likelihood and a maximum-a-posteriori approaches, respectively. The obtained estimates can be used to predict the growth curves for each variety. We illustrate the strengths of the proposed approach using simulated data and soybean plant growth data obtained from a soybean cultivation experiment conducted at the Arid Land Research Center, Tottori University. In this experiment, plant height was measured daily using drones, and the growth was monitored for approximately 200 soybean cultivars for which whole-genome sequence data were available. The NLMEM approach improved our understanding of the determinants of soybean growth and can be successfully used for the genomic prediction of growth pattern characteristics.

Author summary

Nonlinear models are useful for modeling animal and plant growth; however, their parameters are influenced by both genetic and environmental factors. If the same model can be applied to data with different genetic and environmental factors by allowing parameter variations, it can be used to understand, predict, and control the genetic and environmental influences of growth models based on parameter variation. In this study, we propose a statistical method based on nonlinear mixed-effects modeling. The simulation and real data analysis results show that the proposed method was effective in modeling the growth of genetically different soybean varieties under different drought conditions. The usefulness of the proposed method is expected to increase, as high-throughput measurements provide growth data for a large number of genotypes in various environments.
Novel joint enrichment test demonstrates high performance in simulations and identifies cell-types with enriched expression of inflammatory bowel disease risk loci
Authors: Voda Alexandru-Ioan , Jostins-Dean Luke
Published: June 2023

A number of methods have been developed to assess the enrichment of polygenic risk variants – from summary statistics of genome-wide association studies (GWAS) – within specific gene-sets, pathways, or cell-type signatures. The assumptions made by these methods vary, which leads to differences in results and performance across different genetic trait architectures and sample sizes. We devise a novel statistical test that combines independent signals from each of three commonly-used enrichment tests (LDSC, MAGMA & SNPsea) into a single P-value, called the block jackknife GWAS joint enrichment test (GWASJET). Through simulations, we show that this method has comparable or greater power than competing methods across a range of sample sizes and trait architectures. We use our new test in an extensive analysis of the cell-type specific enrichment of genetic risk for inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Counterintuitively, we find stronger enrichments of IBD risk genes in older gene expression data from bulk immune cell-types than in single-cell data from inflamed patient intestinal samples. We demonstrate that GWASJET removes many seemingly-spurious enriched cell-types identified by other methods, and identifies a core set of immune cells that express IBD risk genes, particularly myeloid cells that have been experimentally stimulated. We also demonstrate that many cell-types are differentially enriched for CD compared to UC risk genes, for example gamma-delta T cells show stronger enrichment for CD than UC risk genes.

Author summary

Genetic association studies have discovered a number of DNA variations that are associated with heritable human diseases and traits. One method of investigating the functions of these variants is to test whether they are enriched in parts of the genome associated with specific cell-types or cell conditions – defined by gene expression data or other similar data types. However, there are a number of published statistical methods to test such enrichments; these methdos make different assumptions and their results can vary, sometimes dramatically. We present a novel consensus method, called GWASJET, that combines the results of these different methods to produce a single result. We show that GWASJET can outperform individual methods in simulations. We apply this method to gene expression data from a number of tissues and conditions relevant to inflammatory bowel diseases (IBD). Our method removes potentially false results based ona prioribiological knowledge, and reveals that IBD genes are generally clustered in a large number of immune cell-types, especially myeloid cells treated with specific stimulatory molecules.
Pain hypersensitivity is dependent on autophagy protein Beclin 1 in males but not females
Authors: Tam Theresa H. , Zhang Wenbo , Tu YuShan , Hicks Janice L. , Farcas Sophia , Salter Michael W.
Published: June 2023

Chronic pain is a pervasive health, social, and economic problem affecting 1 in 5 individuals around the world. Increasingly, it is understood that alterations in fundamental cell biological processes are critical for chronic pain. A prominent cellular process is autophagy but whether it plays a role in pain is unknown. To investigate whether autophagy is involved in pain processing and is targetable for pain relief, we focused on Beclin 1, a component of the class III phosphatidylinositol 3-kinase (PI3K) complex necessary for initiating autophagy. Here, we found that inflammatory pain hypersensitivity in male mice lacking one allele ofBecn1is significantly greater than that in wild type mice. By contrast, in female mice, loss ofBecn1did not affect inflammation-induced pain hypersensitivity. Further, intrathecal delivery of an activator of Beclin 1, tat-beclin 1, reversed mechanical hypersensitivity induced by peripheral inflammation or peripheral nerve injury in males. Tat-beclin 1 also prevented mechanical hypersensitivity induced by exogenous brain-derived neurotrophic factor (BDNF), a core mediator of inflammatory and neuropathic pain in the spinal dorsal horn in males. Pain signaling pathways converge on enhancement ofN-methyl-D-aspartate receptors (NMDARs) in spinal dorsal horn neurons. We found that loss of Beclin 1 increases expression of the pain-critical NMDAR subunit, GluN2B, in the dorsal horn and upregulates synaptic NMDAR-mediated currents in dorsal horn neurons from males but not females. From our converging lines of evidence, we conclude that inhibition of Beclin 1 in the dorsal horn is critical in mediating inflammatory and neuropathic pain signaling pathways in males. Our findings provide the basis for sex-specific therapeutic approaches targeting pain with a new class of analgesics - activators of Beclin 1.
Does intellectual capital in Islamic banks outperform conventional banks? Evidence from GCC countries
Authors: Farooque Omar Al , AlObaid Rayed Obaid Hammoud , Khan Ashfaq Ahmad
Published: June 2023

Purpose

This study explores, first, the performance effect (accounting- and market-based performance) of intellectual capital (IC), measured using the value-added intellectual coefficient (VAIC) and its modified version (MVAIC), on Islamic and conventional listed banks in Gulf Cooperation Council (GCC) countries and, second, whether Islamic banks outperform conventional banks in utilising IC.

Design/methodology/approach

Using resource-based view theory and literature reviews, regression analyses are conducted on data for the period 2012–2019 on 26 Islamic and 42 conventional banks. For hypothesis testing, the generalised method of moments panel data regression analysis is applied after addressing endogeneity issues.

Findings

Results, after controlling for corporate governance, indicate that the performance effects of IC (VAIC and MVAIC) on both bank types largely converge and Islamic banks do not outperform conventional banks in IC use. IC has a stronger effect on accounting performance measures for conventional banks than for Islamic banks, but IC has some effect on market performance measures for Islamic banks alone. Corporate governance variables do not play a significant role in the presence of VAIC and MVAIC although there are differences in corporate governance between the two bank types.

Originality/value

This study bridges the gap in GCC banking sector literature on the association between IC efficiency and performance measures of Islamic and conventional banks, from a comparative perspective. It enhances understanding, about the IC–financial performance nexus, of policymakers, regulators, bank managers and other stakeholders interested in the influence of different business models, financing/investment methods and governance structure on the performance of both bank types.
Population modeling and housing demand prediction for the Saudi 2030 Vision: a case study of Riyadh City
Authors: Alhefnawi Mohammed A.M. , Lawal Dano Umar , Alshaikh Abdulrahman M. , Abd Elghany Gamal , Almusallam Abed A. , Paraman Sivakumar
Published: June 2023

Purpose

The Saudi 2030 Housing Program Vision aims to increase the population of Riyadh City, the capital of the Kingdom of Saudi Arabia, to between 15 and 20 million people. This paper aims to predict the demand for residential units in Riyadh City by 2030 in line with this vision.

Design/methodology/approach

This paper adopts a statistical modeling approach to estimate the residential demands for Riyadh City. Several population growth models, including the nonlinear quadratic polynomial spline regression model, the sigmoidal logistic power model and the exponential model, are tested and applied to Riyadh to estimate the expected population in 2030. The growth model closest to the Kingdom’s goal of reaching between 15 and 20 million people in 2030 is selected, and the paper predicts the required number of residential units for the population obtained from the selected model. Desktop database research is conducted to obtain the data required for the modeling and analytical stage.

Findings

The exponential model predicts a population of 16,476,470 in Riyadh City by 2030, and as a result, 2,636,235 household units are needed. This number of housing units required in Riyadh City exceeds the available residential units by almost 1,370,000, representing 108% of the available residential units in Riyadh in 2020.

Originality/value

This study provides valuable insights into the demand for residential units in Riyadh City by 2030 in line with the Saudi 2030 Housing Program Vision, filling the gap in prior research. The findings suggest that significant efforts are required to meet the housing demand in Riyadh City by 2030, and policymakers and stakeholders need to take appropriate measures to address this issue.
Business choice, location decision and success of small and medium enterprises in Uganda
Authors: Kakooza JohnBosco , Tusiime Immaculate , Namiyingo Sophia , Nabwami Ruth , Basemera Mellan
Published: June 2023

Purpose

This paper aims to report on the results of a study carried out to establish the contribution of business choice and location decision to the success of small and medium enterprises in an emerging economy like Uganda.

Design/methodology/approach

This study is cross-sectional and correlational. Data were collected through a questionnaire survey of 181 small and medium restaurants. The data were analyzed through correlation coefficients and hierarchical regression using statistical package for social sciences.

Findings

The findings reveal that both business choice and location decisions positively and significantly contribute to the success of small and medium enterprises. However, it was noted that more attention should be paid to location decision than business choice as determinants of SME success.

Originality/value

To the authors' knowledge, this is the first study to investigate the contribution of business choice and location decision to the success of SMEs using evidence from a developing African country like Uganda. Finally, this research offers practical contributions to managers and owners of SMEs who have to make strategic decisions for firm profitability, survival and growth in the competitive business arena.
Board informal hierarchy and audit quality: evidence from China
Authors: Zhang Yi , Wang Yang , Liao Jiaxin
Published: June 2023

Purpose

Improving audit quality is an important research area of managerial accounting. This study focuses on the informal institutions within organizations and their impact on audit quality. Specifically, this study aims to examine the impact of the informal hierarchy among directors on audit quality.

Design/methodology/approach

The authors examine Chinese companies with listed shares from 2008 to 2020. The authors proxy for audit quality using discretionary accruals and small profits, and use ordinary least squares regression to test their hypotheses.

Findings

The results demonstrate that the informal hierarchy of the board improves audit quality. The results are robust to a battery of sensitivity analyses. Additionally, there is weak evidence that the effect of the board’s informal hierarchy on audit quality is weaker in state-owned enterprises. Moreover, the mechanism tests indicate that the board’s informal hierarchy improves audit quality through the improvement of internal controls. In addition, the impact of the informal hierarchy among directors on audit quality further improves firm performance. However, audit fees are not reduced further because the board’s informal hierarchy demands higher audit quality by choosing industry audit experts.

Originality/value

This study not only enriches the research on the economic consequences of the board’s informal hierarchy but also expands on studies on antecedents of audit quality.
Implementation of augmented reality and mixed reality applications for smart facilities management: a systematic review
Authors: Salman Amna , Ahmad Wasiq
Published: June 2023

Purpose

The Operations and Maintenance (O&M) cost of a facility is typically 60–85% of the total life cycle cost of a building whereas its design and construction cost accounts for only 5–10%. Therefore, enhancing and optimizing the O&M of a facility is a crucial issue. In addition, with the increasing complexities in a building's operating systems, more technologically advanced solutions are required for proactively maintaining a facility. Thereby, a tool is needed which can optimize and reduce the cost of facility maintenance. One of the solutions is Augmented or Mixed Reality (AR/MR) technologies which can reduce repair time, training time and streamline inspections. Therefore, the purpose of this study is to establish contextual knowledge of AR/MR application in facilities operation and maintenance and present an implementation framework through the analysis and classification of articles published between 2015 and 2022.

Design/methodology/approach

To effectively understand all AR/MR applications in facilities management (FM), a systematic literature review is performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol was followed for searching and describing the search strategies. Keywords were identified through the concept mapping technique. The Scopus database and Google Scholar were employed to find relevant articles, books and conference papers. A thorough bibliometric analysis was conducted using VOS Viewer and subsequently, a thematic analysis was performed for the selected publications.

Findings

The use of AR/MR within facilities O&M could be categorized into five different application areas: (1) visualization; (2) maintenance; (3) indoor localization and positioning; (4) information management and (5) indoor environment. After a thematic analysis of the literature, it was found that maintenance and indoor localization were the most frequently used research application domains. The chronological evolution of AR/MR in FM is also presented along with the origin of publications, which showed that the technology is out of its infancy stage and is ready for implementation. However, literature showed many challenges hindering this goal, that is (1) reluctance of the organizational leadership to bear the cost of hardware and trainings for the employees, (2) Lack of BIM use in FM and (3) system lagging, crashing and unable to register the real environment. A preliminary framework is presented to overcome these challenges.

Originality/value

This study accommodates a variety of application domains within facilities O&M. The publications were systematically selected from the existing literature and then reviewed to exhibit various AR/MR applications to support FM. There have been no literature reviews that focus on AR and/or MR in the FM and this paper fills the gap by not only presenting its applications but also developing an implementation framework.
Managing crisis in the cruise industry: using internal communications to foster workforce resilience
Authors: Sharples Liz , Fletcher-Brown Judith , Nieto-García Marta , Sit Kokho , Viglia Giampaolo
Published: June 2023

Purpose

This paper aims to investigates the use of internal communications to foster workforce resilience in the cruise industry during a crisis. Drawing on the regulatory focus theory, this study explores how internal communication strategies can build employee resilience particularly at a time of difficulty. The regulatory focus theory explores the employee’s rationale for goal pursuit. Prevention-focused individuals are concerned with safety and responsibility while promotion-focused individuals focus on goal advancement. The authors seek to broaden the existing understanding of the application of the regulatory focus theory as a lens to inform internal communications crisis strategies.

Design/methodology/approach

Qualitative research using 15-semi structured interviews with cruise industry experts was undertaken during the pandemic. Applying a sensemaking and sense giving approach the researchers thematically analyzed the data in three stages, allowing for new theoretical insights to be uncovered.

Findings

The findings suggest that internal communication strategies should include prevention-focused messages emphasizing the cruise companies’ responsibility to employees, and promotion-focused communications, to include social interaction and individual growth opportunities.

Originality/value

This study’s contribution is three-fold. First, the authors extend the theoretical application of the regulatory focus theory to internal communication and identify a novel concurrent application of both prevention- and promotion-focused messages for developing a resilient workforce. Second, the authors introduce a preliminary conceptualization of an internal crisis communication strategy, emphasizing the concurrent application of prevention- and promotion-focused messages. Finally, the author offer practical suggestions for managing crisis communication strategies.
Geldanamycin ameliorates multiple organ dysfunction and microthrombosis in septic mice by inhibiting the formation of the neutrophil extracellular network by activating heat shock factor 1 HSF1
Authors: Li Jing , Xuan Ruijing , Wu Weidong , Zhang Hailong , Zhao Jie , Zhang Shan
Published: June 2023

Sepsis and septic shock are common critical illnesses in the intensive care unit with a high mortality rate. Geldanamycin (GA) has a broad spectrum of antibacterial and antiviral activity and has inhibitory effects on various viruses. However, whether GA affects sepsis due to infections remains unknown. In this study, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine in serum; neutrophil gelatinase‐associated lipocalin and kidney injury molecule‐1 in the urine, cytokines (tumour necrosis factor alpha, interleukin‐1β and interleukin‐6) in the bronchoalveolar lavage fluid and myeloperoxidase in the lung tissues were measured using enzyme‐linked immunosorbent assay kits. Pathological injury was measured by hematoxylin and eosin staining and neutrophils were measured by flow cytometry analysis; related expressions were analysed by qPCR, western blot and immunofluorescence assay. The results showed that GA significantly ameliorated cecum ligation and puncture (CLP)‐triggered liver, kidney and lung injury in septic mice. In addition, we found that GA dose‐dependently inhibited microthrombosis and alleviated coagulopathy in septic mice. Further molecular mechanism analysis suggests that GA may act through upregulation of heat shock factor 1 and tissue‐type plasminogen activator. In conclusion, our study elucidated the protective effects of GA in a mouse model established using CLP, and the results reveal that GA may be a promising agent for sepsis.
Classified out of society? How educational classification induces political alienation through feelings of misrecognition
Authors: van Noord Jochem , Spruyt Bram , Kuppens Toon , Spears Russell
Published: June 2023

Less educated citizens are both descriptively and substantively outnumbered by higher educated citizens in political and societal institutions. While social science has devoted much time to explain why such education effects exist, it has largely neglected the role of feelings of misrecognition in inducing political alienation among less educated citizens. We argue that education has become so central in processes of economic and social stratification that it is likely that less educated citizens feel misrecognized due to their marginal presence in societal and political institutions, which would then lead to their political alienation. This would in particular be the case in societies that are more ‘schooled’, that is, societies where schooling is a more dominant and steering institution. We analysed data from 49,261 individuals in 34 European countries and found that feelings of misrecognition were strongly related to political distrust, dissatisfaction with democracy, and vote abstention. These relations explained a significant part of the difference between higher and less educated citizens in political alienation. We also found that this mediation effect was larger in countries that are more schooled.