bluuebunny/crossref_metadata_2025 huggingface dataset:
NMR analysis of the homodimeric structure of a D-Ala-D-Ala metallopeptidase, VanX, from vancomycin-resistant bacteria
Authors: Konuma Tsuyoshi , Takai Tomoyo , Tsuchiya Chieko , Nishida Masayuki , Hashiba Miyu , Yamada Yudai , Oe Ayaka , Shirai Haruka , Nagadoi Aritaka , Chikaishi Eriko , Akagi Ken-ichi , Akashi Satoko , Yamazaki Toshio , Akutsu Hideo , Ikegami Takahisa
Published: October 2023

Bacteria that have acquired resistance to most antibiotics, particularly those causing nosocomial infections, create serious problems. Among these, the emergence of vancomycin-resistant enterococci was a tremendous shock considering that vancomycin is the last resort for controlling methicillin-resistantStaphylococcus aureus. Therefore, there is an urgent need to develop an inhibitor of VanX, a protein involved in vancomycin resistance. Although the crystal structure of VanX has been resolved, its asymmetric unit contains six molecules aligned in a row. We have developed a structural model of VanX as a stable dimer in solution, primarily utilizing nuclear magnetic resonance (NMR) residual dipolar coupling. Despite the 46 kDa molecular mass of the dimer, which is typically considered too large for NMR studies, we successfully assigned the main chain using an amino acid-selective unlabeling method. Because we found that the Zn2+-coordinating active sites in the dimer structure were situated in the opposite direction to the dimer interface, we generated an active monomer by mutating the dimer interface. The monomer consists of only 202 amino acids and is expected to be used in future studies to screen and improve inhibitors using NMR.
Refining the transcriptional landscapes for distinct clades of virulent phages infectingpseudomonas aeruginosa
Authors: Putzeys Leena , Wicke Laura , Boon Maarten , Noort Vera van , Vogel Jörg , Lavigne Rob
Published: October 2023

The introduction of high-throughput sequencing has resulted in a surge of available bacteriophage genomes, unveiling their tremendous genomic diversity. However, our current understanding of the complex transcriptional mechanisms that dictate their gene expression during infection is limited to a handful of model phages. Here, we applied ONT-cappable-seq to reveal the transcriptional architecture of six different clades of virulent phages infectingPseudomonas aeruginosa. This long-read microbial transcriptomics approach is tailored to globally map transcription start and termination sites, transcription units and putative RNA-based regulators on dense phage genomes. Specifically, the full-length transcriptomes of LUZ19, LUZ24, 14-1, YuA, PAK_P3 and giant phage phiKZ during early, middle and late infection were collectively charted. Beyond pinpointing traditional promoter and terminator elements and transcription units, these transcriptional profiles provide insights in transcriptional attenuation and splicing events and allow straightforward validation of Group I intron activity. In addition, ONT-cappable-seq data can guide genome-wide discovery of novel regulatory element candidates, including non-coding RNAs and riboswitches. This work substantially expands the number of annotated phage-encoded transcriptional elements identified to date, shedding light on the intricate and diverse gene expression regulation mechanisms inPseudomonasphages, which can ultimately be sourced as tools for biotechnological applications in phage and bacterial engineering.
The V-ATPase-ATG16L1 axis recruits LRRK2 to facilitate lysosomal stress responses
Authors: Eguchi Tomoya , Sakurai Maria , Wang Yingxue , Saito Chieko , Yoshii Gen , Wileman Thomas , Mizushima Noboru , Kuwahara Tomoki , Iwatsubo Takeshi
Published: October 2023

Leucine-rich repeat kinase 2 (LRRK2), a Rab kinase associated with Parkinson’s disease and several inflammatory diseases, has been shown to localize to stressed lysosomes and get activated to regulate lysosomal homeostasis. However, the mechanisms of LRRK2 recruitment and activation have not been well understood. Here we found that the ATG8 conjugation system regulates the recruitment of LRRK2 as well as LC3 onto single membranes of stressed lysosomes/phagosomes. This recruitment did not require FIP200-containing autophagy initiation complex, nor did it occur on double-membrane autophagosomes, suggesting independence from canonical autophagy. Consistently, LRRK2 recruitment was regulated by the V-ATPase-ATG16L1 axis, which requires the WD40 domain of ATG16L1 and specifically mediates ATG8 lipidation on single membranes. This mechanism was also responsible for the lysosomal stress-induced activation of LRRK2 and the resultant regulation of lysosomal secretion and enlargement. These results indicate that the V-ATPase-ATG16L1 axis serves a novel non-autophagic role in the maintenance of lysosomal homeostasis by recruiting LRRK2.
High-speed imaging of giant unilamellar vesicle formation in cDICE
Authors: Van de Cauter Lori , Jawale Yash K. , Tam Daniel , Baldauf Lucia , van Buren Lennard , Koenderink Gijsje H. , Dogterom Marileen , Ganzinger Kristina A.
Published: October 2023

Giant unilamellar vesicles (GUVs) are widely used asin vitromodel membranes in biophysics and as cell-sized containers in synthetic biology. Despite their ubiquitous use, there is no one-size-fits-all method for their production. Numerous methods have been developed to meet the demanding requirements of reproducibility, reliability, and high yield, while simultaneously achieving robust encapsulation. Emulsion-based methods are often praised for their apparent simplicity and good yields; hence, methods like continuous droplet interface crossing encapsulation (cDICE) that make use of this principle, have gained popularity. However, the underlying physical principles governing the formation of GUVs in cDICE and related methods remain poorly understood. To this end, we have developed a high-speed microscopy setup that allows us to visualize GUV formation in real-time. Our experiments reveal a complex droplet formation process occurring at the capillary orifice, generating both larger droplets and, likely, GUV-sized satellite droplets. According to existing theoretical models, the oil-water interface should allow for crossing of all droplets, but based on our observations and theoretical modelling of the fluid dynamics within the system, we find a size-selective crossing of GUV-sized droplets only. Finally, we demonstrate that proteins in the inner solution affect GUV formation by increasing the viscosity and altering lipid adsorption kinetics. These results will not only contribute to a better understanding of GUV formation processes in cDICE, but ultimately also aid the development of more reliable and efficient methods for GUV production.

Graphical abstract

We developed a high-speed microscopy setup to study giant unilamellar vesicle formation in cDICE, revealing a complex droplet formation process occurring at the capillary orifice and size-selectivity at the oil-water interface.
Unlocking the Mycorrhizal Nitrogen Pathway Puzzle: Metabolic Modelling and multi-omics unveil Pyrimidines’ Role in Maize Nutrition via Arbuscular Mycorrhizal Fungi Amidst Nitrogen Scarcity
Authors: Decouard Bérengère , Chowdhury Niaz Bahar , Saou Aurélien , Rigault Martine , Quilleré Isabelle , Sapir Thomas , Marmagne Anne , le Roux Christine Paysant , Launay-Avon Alexandra , Guerard Florence , Mauve Caroline , Gakière Bertrand , Lévy-Leduc Céline , Barbillon Pierre , Courty Pierre-Emmanuel , Wipf Daniel , Hirel Bertrand , Saha Rajib , Dellagi Alia
Published: October 2023

Maize is currently the most productive cereal crop in the world (www.faostat.org). Maize can form a symbiotic relationship with the Arbuscular Mycorrhizal Fungus (AMF),Rhizophagus irregularis. In this relationship, the fungus provides the plant with additional water and mineral nutrients, while the plant supplies carbon compounds to the fungus. Little is known about the N metabolism disruption during symbiosis in both partners. To address this issue, two genetically distant maize lines were studied in terms of physiological and molecular responses to AMF inoculation by dual RNA-seq, metabolomics and phenotyping. Interestingly, the beneficial effects of the AMF were observed mainly under conditions of limited N fertilization. Under such conditions, the AMF helped maintain plant biomass production. The availability of nitrogen was found to be a crucial factor influencing all the traits studied showing that the level of N supply plays a pivotal role in determining how maize plants interact with the AMF. Despite the two maize lines showing different transcriptomic and metabolomic responses toR. irregularis, their agro-physiological traits remained similar. Both the plant and fungal transcriptomes were more significantly influenced by the level of N nutrition rather than the specific maize genotype. This suggests that N availability has a more profound impact on gene expression in both organisms than the genetic makeup of the maize plant. To understand the metabolic implications of this symbiotic relationship, we integrated transcriptomic data into our recently built multi-organ Genome-scale metabolic model (GSM) called iZMA6517. Remarkably, this modelling approach was supported by metabolomics profiling, in particular increased leaf pyrimidine levels in response to AMF inoculation under limiting N supply. Consistently, fungal genes involved in pyrimidine de novo synthesis and salvage were found to be expressed in symbiotic roots. Our work highlights nucleotide and ureides metabolism as previously unrecognized factors contributing to the symbiotic N nutrition facilitated byR. irregularis, thereby enhancing maize growth. This study demonstrates the effectiveness of integrating multi-omics approaches with mathematical modelling to uncover novel metabolic mechanisms associated with AM symbiosis, without a priori.
A singleMicrocoleusspecies causes benthic cyanotoxic blooms worldwide
Authors: Junier Pilar , Cailleau Guillaume , Fatton Mathilda , Udriet Pauline , Hashmi Isha , Bregnard Danae , Corona-Ramirez Andrea , di Francesco Eva , Kuhn Thierry , Mangia Naïma , Zhioua Sami , Hunkeler Daniel , Bindschedler Saskia , Sieber Simon , Gonzalez Diego
Published: October 2023

Recently, proliferations of benthic cyanobacteria producing derivatives of anatoxin-a have been reported in rivers all over the world. In three river systems, in New Zealand, the USA, and Canada, a cohesive cluster ofMicrocoleusstrains was responsible for toxin production. Here, we document a similar toxigenic event that occurred at the mouth of the river Areuse in lake Neuchâtel (Switzerland) and caused the death of several dogs. Using 16S RNA-based community analysis, we show that riverine benthic communities are dominated by Oscillatoriales and especially byMicrocoleusstrains. We correlate the detection of one sequence variant with the presence of anatoxin-a derivatives and use metagenomics to assemble a complete circular genome of the strain. The strain is distinct from the ones isolated in New Zealand, the USA, and Canada, but belongs to the same species; it shares significant traits with them, in particular a relatively small genome and incomplete vitamin biosynthetic pathways. Overall, our results suggest that the major anatoxin-a-associated benthic proliferations worldwide can be traced back to a single ubiquitous species,Microcoleus anatoxicus,rather than to a diversity of cyanobacterial lineages. We recommend that this species be monitored internationally in order to help predict and mitigate similar cyanotoxic events.
PARP10 is Critical for Stress Granule Initiation
Authors: Jayabalan Aravinth Kumar , Bhambhani Krishna , L Leung Anthony K
Published: October 2023

Stress granules (SGs) are cytoplasmic biomolecular condensates enriched with RNA, translation factors, and other proteins. They form in response to stress and are implicated in various diseased states including viral infection, tumorigenesis, and neurodegeneration. Understanding the mechanism of SG assembly, particularly its initiation, offers potential therapeutic avenues. Although ADP-ribosylation plays a key role in SG assembly, and one of its key forms—poly(ADP-ribose) or PAR—is critical for recruiting proteins to SGs, the specific enzyme responsible remains unidentified. Here, we systematically knock down the human ADP-ribosyltransferase family and identify PARP10 as pivotal for SG assembly. Live-cell imaging reveals PARP10’s crucial role in regulating initial assembly kinetics. Further, we pinpoint the core SG component, G3BP1, as a PARP10 substrate and find that PARP10 regulates SG assembly driven by both G3BP1 and its modeled mechanism. Intriguingly, while PARP10 only adds a single ADP-ribose unit to proteins, G3BP1 is PARylated, suggesting its potential role as a scaffold for protein recruitment. PARP10 knockdown alters the SG core composition, notably decreasing translation factor presence. Based on our findings, we propose a model in which ADP-ribosylation acts as a rate-limiting step, initiating the formation of this RNA-enriched condensate.

HIGHLIGHTS

PARP10 plays a crucial role in the initial SG assembly kinetics.

The core SG component G3BP1 is a substrate of PARP10.

PARP10 is required for SG assembly mediated by G3BP1 or its synthetic mimic.

PARP10 knockdown reduces the levels of translation factors within the SG core.
Structure of the endosomal CORVET tethering complex
Authors: Shvarev Dmitry , König Caroline , Susan Nicole , Langemeyer Lars , Walter Stefan , Perz Angela , Fröhlich Florian , Ungermann Christian , Moeller Arne
Published: October 2023

Cells depend on their endolysosomal system for nutrient uptake and downregulation of plasma membrane proteins. These processes rely on endosomal maturation, which requires multiple membrane fusion steps. Early endosome fusion is promoted by the Rab5 GTPase and its effector, the hexameric CORVET tethering complex, which is homologous to the lysosomal HOPS. How these related complexes recognize their specific target membranes remains entirely elusive. Here, we solved the structure of CORVET by cryo-electron microscopy and revealed its minimal requirements for membrane tethering. As expected, the core of CORVET and HOPS resembles each other. However, the function-defining subunits show marked structural differences. Notably, we discovered that unlike HOPS, CORVET depends not only on Rab5 but also on phosphatidylinositol-3-phosphate (PI3P) and membrane packaging defects for tethering, implying that an organelle-specific membrane code enables fusion. Our data suggest that both shape and membrane interactions of CORVET and HOPS are conserved in metazoans, thus providing a paradigm how tethering complexes function.

One-Sentence Summary

Using cryo-EM, we solved the structure of the CORVET tethering complex and explained how it promotes endosome fusion.
Cnot3is required for male germ cell development and spermatogonial stem cell maintenance
Authors: Chen Qing , Malki Safia , Xu Xiaojiang , Bennett Brian , Lackford Brad L. , Kirsanov Oleksandr , Geyer Christopher B. , Hu Guang
Published: October 2023

The foundation of spermatogenesis and lifelong fertility is provided by spermatogonial stem cells (SSCs). SSCs divide asymmetrically to either replenish their numbers (self-renewal) or produce undifferentiated progenitors that proliferate before committing to differentiation. However, regulatory mechanisms governing SSC maintenance are poorly understood. Here, we show that the CCR4-NOT mRNA deadenylase complex subunit CNOT3 plays a critical role in maintaining spermatogonial populations in mice.Cnot3is highly expressed in undifferentiated spermatogonia, and its deletion in spermatogonia resulted in germ cell loss and infertility. Single cell analyses revealed thatCnot3deletion led to the de-repression of transcripts encoding factors involved in spermatogonial differentiation, including those in the glutathione redox pathway that are critical for SSC maintenance. Together, our study reveals that CNOT3 – likely via the CCR4-NOT complex – actively degrades transcripts encoding differentiation factors to sustain the spermatogonial pool and ensure the progression of spermatogenesis, highlighting the importance of CCR4-NOT-mediated post-transcriptional gene regulation during male germ cell development.

Highlights

Cnot3is predominantly expressed in undifferentiated spermatogonia, and its expression decreases in later stages.

Conditional deletion ofCnot3leads to total germ cell loss and male infertility.

CNOT3 represses transcripts encoding factors involved in spermatogonial differentiation.

CNOT3 protects spermatogonial stem cells maintenance via GSH/redox pathway.

Graphical Abstract

Cnot3 promotes SSC self-renewal by balancing ROS production via the regulation of GSH production
Cytotoxic rhamnolipid micelles drive acute virulence inPseudomonas aeruginosa
Authors: Xu Qi , Kang Donghoon , Meyer Matthew D. , Pennington Christopher L. , Gopal Citrupa , Schertzer Jeffrey W. , Kirienko Natalia V.
Published: October 2023

Pseudomonas aeruginosais an opportunistic human pathogen that has developed multi- or even pan-drug resistance towards most frontline and last resort antibiotics, leading to increasing infections and deaths among hospitalized patients, especially those with compromised immune systems. Further complicating treatment,P. aeruginosaproduces numerous virulence factors that contribute to host tissue damage and immune evasion, promoting bacterial colonization and pathogenesis. In this study, we demonstrate the importance of rhamnolipid production in host-pathogen interactions. Secreted rhamnolipids form micelles that exhibited highly acute toxicity towards murine macrophages, rupturing the plasma membrane and causing organellar membrane damage within minutes of exposure. While rhamnolipid micelles (RMs) were particularly toxic to macrophages, they also caused membrane damage in human lung epithelial cells, red blood cells, Gram-positive bacteria, and even non-cellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated toP. aeruginosavirulence against murine macrophages in various panels of clinical isolates. Altogether, our findings suggest that rhamnolipid micelles are highly cytotoxic virulence factors that drive acute cellular damage and immune evasion duringP. aeruginosainfections.
The ribonucleoprotein-mediated CRISPR–Cas9 system induces recurrent Aire gene mutations in contrast to the nickase expression vector in murinein vitroorin vivomodels
Authors: Tanaka Pedro P. , Monteiro Cíntia J. , Duarte Max J. , Oliveira Ernna D. , Monteleone-Cassiano Ana C. , Mascarenhas Romário S. , Machado Mayara C. Vieira , Matos Adriana A. , Brito Letícia A. , Oliveira Alina O. , Cunha Thiago M. , Donadi Eduardo A. , Passos Geraldo A.
Published: October 2023

Althoughin vitromTEC cultures can help determine the role of the autoimmune regulator (Aire) gene, the mechanisms of Aire mutations were identified using Aire mutant mice. Nevertheless, long-term cultures of mTECs from mice are difficult to establish. To overcome this, we used a CRISPR–Cas9 system to edit Aire in a murine mTEC linein vitroand mouse embryos. Two ribonucleoprotein (RNP) complexes were designed to separately target Aire exons 6 and 8. NHEJ-derived indels or HDR-derived mutations were obtained. Recurrent NHEJ-derived mutations were observed among editions, one in exon 6 (del 3554G) and the other in exon 8 (del 5676_5677TG), i.e., the exon 6 mutation was kept in an mTEC clone editedin vitroandin vivoin a mouse, and the exon 8 mutation was kept in mTECsin vitro. None of the mutations obtained with the nickase system were recurrent, indicating the participation of the RNP complex.
Redox Activated Substrates for Enhancing Activatable Cyclopropene Bioorthogonal Reactions
Authors: Kao Wei-Siang , Huang Wei , Zhang Yunlei , Meyer Andrea , Laughlin Scott T.
Published: October 2023

Bioorthogonal chemistry has become a mainstay in chemical biology and is making inroads in the clinic with recent advances in protein targeting and drug release. Since the field’s beginning, a major focus has been on designing bioorthogonal reagents with good selectivity, reactivity, and stability in complex biological environments. More recently, chemists have imbued reagents with new functionalities like click-and-release or light/enzyme-controllable reactivity. We have previously developed a controllable cyclopropene-based bioorthogonal ligation, which has excellent stability in physiological conditions and can be triggered to react with tetrazines by exposure to enzymes, biologically significant small molecules, or light spanning the visual spectrum. Here, to improve reactivity and gain a better understanding of this system, we screened diene reaction partners for the cyclopropene. We found that a cyclopropene–quinone pair is 26 times faster than reactions with 1,2,4,5-tetrazines. Additionally, we showed that the reaction of the cyclopropene–quinone pair can be activated by two orthogonal mechanisms, caging group removal on the cyclopropene and oxidation/reduction of the quinone. Finally, we demonstrated that this caged cyclopropene–quinone can be used as a bioorthogonal imaging tool to label the membranes of cultured cells.
Reassessing the substrate specificities of the majorStaphylococcus aureuspeptidoglycan hydrolases lysostaphin and LytM
Authors: Antenucci Lina , Virtanen Salla , Thapa Chandan , Jartti Minne , Pitkänen Ilona , Tossavainen Helena , Permi Perttu
Published: October 2023

Orchestrated action of peptidoglycan (PG) synthetases and hydrolases is vital for bacterial growth and viability. Although the function of several PG synthetases and hydrolases is well-understood, the function, regulation, and mechanism of action of PG hydrolases characterized as lysostaphin-like endopeptidases have remained elusive. Many of these M23 family members can hydrolyse glycyl-glycine peptide bonds and show lytic activity againstStaphylococcus aureuswhose PG contains a pentaglycine bridge, but their exact substrate specificity and hydrolysed bonds are still vaguely determined.

In this work, we have employed NMR spectroscopy to study both the substrate specificity and the bond cleavage of the bactericide lysostaphin and theS. aureusPG hydrolase LytM. Yet, we provide substrate-level evidence for the functional role of these enzymes. Indeed, our results show that the substrate specificities of these structurally highly homologous enzymes are similar, but unlike observed earlier both LytM and lysostaphin prefer the D-Ala-Gly cross-linked part of mature peptidoglycan. However, we show that while lysostaphin is genuinely a glycyl-glycine hydrolase, LytM can also act as a D-alanyl-glycine endopeptidase.
Cleave and Rescue gamete killers create conditions for gene drive in plants
Authors: Oberhofer Georg , Johnson Michelle L. , Ivy Tobin , Antoshechkin Igor , Hay Bruce A.
Published: October 2023

Gene drive elements promote the spread of linked traits, even when their presence confers a fitness cost to carriers, and can be used to change the composition or fate of wild populations. Cleave and Rescue (ClvR) drive elements sit at a fixed chromosomal position and include a DNA sequence-modifying enzyme such as Cas9/gRNAs (the Cleaver/Toxin) that disrupts endogenous versions of an essential gene, and a recoded version of the essential gene resistant to cleavage (the Rescue/Antidote).ClvRspreads by creating conditions in which those lackingClvRdie because they lack functional versions of the essential gene. We demonstrate the essential features ofClvRgene drive in the plantArabidopsis thalianathrough killing of gametes that fail to inherit aClvRthat targets the essential gene YKT61, whose expression is required in male and female gametes for their survival. Resistant (uncleavable but functional) alleles, which can slow or prevent drive, were not observed. Modeling shows plantClvRs are likely to be robust to certain failure modes and can be used to rapidly drive population modification or suppression. Possible applications in plant breeding, weed control, and conservation are discussed.
FluxNorm: Toolbox for metabolic flux assay normalization byin situcell counting
Authors: Djaja Nathalie A. , Bracha Teva , Yu Seungyoon B. , Wang Haoming , Carlson Natasha M. , Pekkurnaz Gulcin
Published: October 2023

Plate-based quantitative metabolic flux analysis has emerged as the central technology to examine cellular metabolism and mitochondrial bioenergetics. However, accurate interpretation of metabolic activity between different experimental conditions in multi-well microplates requires data normalization based onin situcell counts. Here, we describe FluxNorm, a platform-independent semi-automated computational workflow, validated for three different cell types, to normalize cell density for accurate assessment of cellular bioenergetics.
Threat awareness and counter-terrorism preparedness of Dutch hospitals: a cross-sectional survey
Authors: Barten Dennis G. , Janssen Maud , De Cauwer Harald , Keereweer Dennis , Tan Edward , van Osch Frits , Mortelmans Luc
Published: October 2023

Background

Workplace violence, including violent extremism, is a growing concern in the healthcare environment. Furthermore, there has been a disproportionate rise in the rate of terrorist attacks on hospitals during the past two decades. Hospitals are vulnerable targets due to their easy accessibility and their high density of patients, staff and visitors. Nonetheless, little is known about the hospitals’ awareness of these risks, and to which extent these facilities protect themselves from violent extremism and terrorist attacks.

Methods

This was a cross-sectional survey study among emergency managers of acute care hospitals in the Netherlands. The questionnaire included 42 items across six themes: demographic (hospital) data; general and emergency department (ED) access control; ED security and preparedness; online security and offline transparency; violence, terrorism and warfare; and impact of the COVID-19 pandemic. Responses were collected and stored in a secured online database, and subsequently exported to an Excel spreadsheet for descriptive analysis. Continuous data were reported as means or as medians with interquartile ranges (IQR), using SPSS. Categorical data were reported as absolute numbers and as valid percentages.

Results

The questionnaire was completed on behalf of 33 out of 71 hospital organizations (46%), representing 38 out of 82 EDs (46%). Hospitals had broadly different policies with regards to patient and visitor registration, and the presence of security guards. Most hospitals had controlled vehicle access for the parking lot and ambulance bay, but this was not 24/7 in all hospitals. A paragraph on terrorist attacks was included in 34% of hospital disaster plans. Eighteen percent of hospitals had previous experience with acts of violent extremism and 55% of hospitals had sustained (attempted) cyberattacks. Whilst the likelihood of a physical terrorist attack was deemed low at 3.6 (median 4, IQR 2.6) on a 10-point Likert scale, the likelihood of a cyberattack was considered high at 7.3 (median 8, IQR 2.3). A significant proportion of emergency managers reported to experience an increased risk of violence since the onset of the COVID-19 pandemic.

Conclusion

Practice variation with regards to counter-terrorism defence measures in Dutch hospitals is high. The preparedness of hospitals for terrorist attacks or acts of violent extremism could be improved and may benefit from uniform, evidence based hospital security policies.
Marketplace accessibility: a service-provider perspective
Authors: Husemann Katharina C. , Zeyen Anica , Higgins Leighanne
Published: October 2023

Purpose

This study aims to explore the strategies that service providers use to facilitate marketplace accessibility, and identify the key challenges in that process. The authors do so to develop a roadmap towards improved accessibility and disability inclusion in the marketplace.

Design/methodology/approach

The authors conducted eight semi-structured interviews with service providers (curators, visitor service coordinators and access managers) at museums who run access programmes for customers with visual impairment (VI), along with an embodied duo-ethnography of those programmes.

Findings

Service providers foster autonomous, embodied and social access. Resource constraints, safety concerns and exposed differences between customers compromise access. To overcome these challenges, service providers engage in three inclusionary strategies – informing, extending and sensitizing.

Research limitations/implications

This service provider- and VI-focus present limitations. Future research should consider a poly-vocal approach that includes the experiences of numerous stakeholders to holistically advance marketplace accessibility; and apply the marketplace accessibility findings upon different disabilities in other marketplace contexts.

Practical implications

This study offers a roadmap for policymakers and service providers on: which types of access should and can be created; what challenges may be encountered; how to manage these challenges; and, thus, how to advance accessibility beyond regulations.

Originality/value

This study contributes a service provider perspective on marketplace accessibility that goes beyond removing “disabling” barriers towards creating opportunities for co-creation; an approach towards marketplace accessibility that fosters inclusiveness while considering the inherent challenges of that process; and an illustration of posthumanism’s empirical value in addressing issues of accessibility in the marketplace.
The determinants of abusive supervision
Authors: Moin Muhammad Farrukh , Khan Ali Nawaz
Published: October 2023

Purpose

On the basis of affective events theory, this study aims to examine the connection between work-related events (i.e. supervisor role ambiguity and role conflicts) and abusive supervision via emotion (i.e. supervisor frustration). This study also examines the moderating role of supervisor personality traits (i.e. neuroticism and conscientiousness).

Design/methodology/approach

This study collected lagged and multisource field data (472 subordinates and supervisors dyads) from the service organizations.

Findings

The data collected supported majority of this study’s hypothesized relationships regarding determinants of abusive supervision.

Practical implications

This study underlines what triggers supervisor abuse. This study also enables organizations with the intervention opportunity to reduce the effects of supervisor role ambiguity, role conflict, negative emotions and personality on triggering abusive supervision.

Originality/value

Prior research on abusive supervision has extensively focused on its outcomes, leaving a noteworthy research gap about what triggers abusive supervision. To fill this important gap in leadership literature, this study proposed and tested a research model of determinants of supervisor abuse. Thus, this study contributes to leadership and abusive supervision research. Implications and future research directions are discussed.
Shareholder activism and accounting reporting complexity
Authors: Dao Mai , Xu Hongkang
Published: October 2023

Purpose

In this paper the authors aim to examine whether shareholder activism is associated with accounting reporting complexity (ARC).

Design/methodology/approach

The authors employ ordinary least squares (OLS) and a sample of 19,530 firm-year observations (representing 3,377 unique firms) over the 2010–2019 period to test the prediction.

Findings

The authors find that firms with shareholder activism provide more complex accounting reporting. Further, both types of activism (including Concern & Dispute and Control & Discussion) are positively associated with ARC. The authors also find that the association between shareholder activism and ARC is more pronounced when the firms have a higher level of litigation risk and a higher proportion of institutional ownership. Collectively, the findings suggest that firms with shareholder activism may be under more pressure to disclose more accounting items, leading to more complex accounting reporting.

Originality/value

The study may be informative to regulators considering the costs and benefits of shareholder activism in financial reporting.
Green entrepreneurship in Saudi Arabia: shaping the landscape of the greener economy
Authors: Abdelwahed Nadia A. Abdelmegeed , Al Doghan Mohammed A. , Saraih Ummi Naiemah , Soomro Bahadur Ali
Published: October 2023

Purpose

Entrepreneurship is one of the pillars of economic development and helps to green the economy. This study investigates the factors that affect green entrepreneurship (GE) in small- and medium-sized enterprises (SMEs) in Saudi Arabia.

Design/methodology/approach

Using quantitative modes, this study's findings are based on 334 valid cases from Saudi Arabian SME employees.

Findings

Using path analysis, this study’s findings reveal that green entrepreneurial skills (GES), green opportunities (GOs), entrepreneurial motivation (EM), green incentives (GIs), availability of capital (AoC) and green entrepreneurial self-efficacy (GESE) have positive and significant effects on GE. Moreover, GESE mediates GE's relationships with GES, GOs, EM, GIs and AoC.

Practical implications

This study's findings support the development of green business practices in terms of green business planning, training and skills. The research provides opportunities for green businesses. Policymakers and SME authorities would benefit from this study's findings in producing green goods and services.

Originality/value

This study empirically confirms the role of various factors such as GESE and GE among Saudi Arabian SMEs.
Impact of social media influencers' credibility
on millennial consumers' green purchasing behavior: a concept paper on
personal and social identities
Authors: Rodrigo Arani , Mendis Trevor
Published: October 2023

Purpose

The purpose of this paper is to provide the theoretical insights with regard
to the green purchasing intention–behavior gap and the role played by
social media influences in abating this gap. This paper takes into
consideration a wider aspect with regard to the antecedents of behavioral
intention through personal and social identities in place of the antecedents
presented in the theory of planned behavior and social-identity theory.
Furthermore, as the theories lack an explanation of how to reduce the
intention–behavior gap, this paper also argues the source credibility
model (SCM) in explaining the impact that social media influences can have
on the behavioral gap.

Design/methodology/approach

Hypothetical deductive method is proposed for this concept paper under the
positivism research paradigm.

Findings

Not applicable as this is a concept paper. However, the paper discusses the
theoretical and managerial implications.

Research
limitations/implications

This is a concept paper. Yes this paper discusses the theoretical,
managerial, and social/ecological implications.

Practical implications

This paper highlights the relevance of consumers' personal and social
identities when consumers make purchasing decisions regarding green
products. How managers can make marketing strategies, based on credibility
model, involving social media influences as product endorsers and
ambassadors, as well as the policy makers to design products, earmark
consumer behavior and to conduct marketing campaigns in time to come.

Social implications

As to how policies can be designed and adopted for bio-based economies where
sustainability and circularity are given priority and to increase the
attention of businesses moving toward sustainable practices.

Originality/value

Original thought developed based on research, theoretical and market
gaps.
Variation in local population size predicts social network structure in wild songbirds
Authors: Beck Kristina B. , Farine Damien R. , Firth Josh A. , Sheldon Ben C.
Published: October 2023

The structure of animal societies is a key determinant of many ecological and evolutionary processes. Yet, we know relatively little about the factors and mechanisms that underpin detailed social structure.

Among other factors, social structure can be influenced by habitat configuration. By shaping animal movement decisions, heterogeneity in habitat features, such as vegetation and the availability of resources, can influence the spatiotemporal distribution of individuals and subsequently key socioecological properties such as the local population size and density. Differences in local population size and density can impact opportunities for social associations and may thus drive substantial variation in local social structure.

Here, we investigated spatiotemporal variation in population size at 65 distinct locations in a small songbird, the great tit (Parus major) and its effect on social network structure. We first explored the within‐location consistency of population size from weekly samples and whether the observed variation in local population size was predicted by the underlying habitat configuration. Next, we created social networks from the birds' foraging associations at each location for each week and examined if local population size affected social structure.

We show that population size is highly repeatable within locations across weeks and years and that some of the observed variation in local population size was predicted by the underlying habitat, with locations closer to the forest edge having on average larger population sizes. Furthermore, we show that local population size affected social structure inferred by four global network metrics. Using simple simulations, we then reveal that much of the observed social structure is shaped by social processes. Across different population sizes, the birds' social structure was largely explained by their preference to forage in flocks. In addition, over and above effects of social foraging, social preferences between birds (i.e. social relationships) shaped certain network features such as the extent of realized social connections.

Our findings thus suggest that individual social decisions substantially contribute to shaping certain social network features over and above effects of population size alone.
Transmisogyny in later (1588–1623) hagiography on Mother Juana de la Cruz (1481–1534)
Authors: Becker Claire
Published: October 2023

In this article, I contextualise and explain the restriction of what I term ‘trans potential’ in later hagiography on the Spanish visionary abbess Mother Juana de la Cruz (1481–1534). The first written work on Juana included a functionally transmasculine narrative (Juana passed briefly as a man) and a functionally transfeminine narrative (God miraculously feminised the previously male Juana prior to her birth, leaving her with an Adam's apple). In later works, the transmasculine narrative appears significantly modified, and the transfeminine narrative does not appear at all. These textual reformulations, I conclude, are most legible within the framework of transmisogyny.
Monocyte‐to‐lymphocyte ratio and gastrointestinal disorder‐related hospitalization in patients on maintenance hemodialysis
Authors: Tian Maolu , Yuan Jing , He Pinghong , Yu Fangfang , Long Changzhu , Zha Yan
Published: October 2023

Introduction

To explore the association between monocyte‐to‐lymphocyte ratio (MLR) and the risk of hospitalization due to gastrointestinal (GI) disorder in hemodialysis (HD) patients.

Methods

In this multicenter, observational cohort study, 1626 patients were enrolled in 2019 and followed up to 2 years. Cox regression models were performed to estimate the association of MLR with GI disorder‐related hospitalization risk. Receiver‐operating characteristic (ROC) analyses were conducted to evaluate the cutoff value of MLR in identifying GI disorder‐related hospitalization.

Results

During a median follow‐up of 24 months, GI disorder‐related hospitalization occurred in 107 patients. Higher MLR was independently associated with greater risks of GI disorder‐related hospitalization. Furthermore, a cut‐off value of 0.42 differentiated patients with GI disorder‐related hospitalization from those without GI involvement.

Conclusion

MLR was associated with the occurrence of GI disorder‐related hospitalization in HD patients. The blood MLR could be monitored as a useful marker to predict GI disorder‐related hospitalization.
Senolytics prevent caveolar CaV3.2‐RyR axis malfunction in old vascular smooth muscle
Authors: Lin Jie , Guo Weiming , Luo Qingtian , Zhang Qingping , Wan Teng , Jiang Changyu , Ye Yuanchun , Lin Haihuan , Fan Gang
Published: October 2023

Aging is a major risk factor for cardiovascular diseases. Our previous studies demonstrate that aging impairs the caveolar T‐type CaV3.2‐RyR axis for extracellular Ca2+ influx to trigger Ca2+ sparks in vascular smooth muscle cells (VSMCs). We hypothesize that the administration of senolytics, which can selectively clear senescent cells, could preserve the caveolar CaV3.2‐RyR axis in aging VSMCs. In this study, 10‐month‐old mice were administered the senolytics cocktail consisting of dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi‐weekly for 4 months. Using VSMCs from mouse mesenteric arteries, we found that Ca2+ sparks were diminished after caveolae disruption by methyl‐β‐cyclodextrin (10 mM) in cells from D + Q treated but not vehicle‐treated 14‐month‐old mice. D + Q treatment promoted the expression of CaV3.2 in 14‐month‐old mesenteric arteries. Structural analysis using electron tomography and immunofluorescence staining revealed the remodeling of caveolae and co‐localization of CaV3.2‐Cav‐1 in D + Q treatment aged mesenteric arteries. In keeping with theoretical observations, Cav3.2 channel inhibition by Ni2+ (50 μM) suppressed Ca2+ in VSMCs from the D + Q group, with no effect observed in vehicle‐treated arteries. Our study provides evidence that age‐related caveolar CaV3.2‐RyR axis malfunction can be alleviated by pharmaceutical intervention targeting cellular senescence. Our findings support the potential of senolytics for ameliorating age‐associated cardiovascular disease.
Mixed ownership reform, political connections, and overinvestment
Authors: Wang Jizhou , He Jin’an , Cebula Richard , Foley Maggie , Peng Fangping
Published: October 2023

The study discovers that mixed ownership reform aimed at enhancing the performance and resource allocation efficiency of state‐owned enterprises may have unintended consequences in China. When the nature of state‐owned control remains unchanged, there is a risk of increased overinvestment due to misaligned interests between state‐owned equity representatives and companies. This incentive can be mitigated by introducing nonstate shareholders with political connections. The study employs a double machine learning method to analyze data from state‐owned listed companies that introduced nonstate shareholders through stock issuance between 2008 and 2019. The research underscores that modern corporate governance mechanisms are crucial for successful mixed ownership reform.
Opioid prescribing, pain, and hospital stay of general surgery patients with oxycodone allergies in South Australia
Authors: Kovoor Joshua G. , Bacchi Stephen , Gupta Aashray K. , Vo Tammy , Lam Cindy , Lam Lydia , Jiang Melinda , Stretton Brandon , To Minh‐Son , Nann Silas , Ovenden Christopher D. , Hewitt Joseph N. , Goh Rudy , Reid Jessica L. , Hugh Thomas J. , Dobbins Christopher , Hewett Peter J. , Trochsler Markus I. , Kette Frank E. , Maddern Guy J.
Published: October 2023

Background

The frequency of oxycodone adverse reactions, subsequent opioid prescription, effect on pain and patient care in general surgery patients are not well known. This study aimed to determine prevalence of documented oxycodone allergy and intolerances (independent variables) in a general surgical cohort, and association with prescribing other analgesics (particularly opioids), subjective pain scores, and length of hospital stay (dependent variables).

Methods

This retrospective cohort study included general surgery patients from two South Australian hospitals between April 2020 and March 2022. Multivariable logistic regression evaluated associations between previous oxycodone allergies and intolerances, prescription records, subjective pain scores, and length of hospital stay.

Results

Of 12 846 patients, 216 (1.7%) had oxycodone allergies, and 84 (0.7%) oxycodone intolerances. The 216 oxycodone allergy patients had lower odds of receiving oxycodone (OR 0.17, P < 0.001), higher odds of tramadol (OR 3.01, P < 0.001) and tapentadol (OR 2.87, P = 0.001), but 91 (42.3%) still received oxycodone and 19 (8.8%) morphine. The 84 with oxycodone intolerance patients had lower odds of receiving oxycodone (OR 0.23, P < 0.001), higher odds of fentanyl (OR 3.6, P < 0.001) and tramadol (OR 3.35, P < 0.001), but 42 (50%) still received oxycodone. Patients with oxycodone allergies and intolerances had higher odds of elevated subjective pain (OR 1.60, P = 0.013; OR 2.36, P = 0.002, respectively) and longer length of stay (OR 1.36, P = 0.038; OR 2.24, P = 0.002, respectively) than patients without these.

Conclusions

General surgery patients with oxycodone allergies and intolerances are at greater risk of worse postoperative pain and longer length of stay, compared to patients without. Many still receive oxycodone, and other opioids that could cause cross‐reactivity.
Tear film proteome changes following Tobradex® therapy in anterior blepharitis
Authors: Muttuvelu Danson Vasanthan , Cehofski Lasse Jørgensen , Utheim Tor Paaske , Chen Xiangjun , Vorum Henrik , Rasmussen Marie Louise Roed , Heegaard Steffen , Khan Asif Manzoor , Abduljabar Ahmed Basim , Honoré Bent
Published: October 2023

Purpose

The management of blepharitis continues to challenge clinicians due to the poorly understood aetiology of the condition. We recently identified the family of intracellular plakin proteins as essential driving forces underlying anterior blepharitis. A large‐scale protein analysis was used to study if a topical dexamethasone/tobramycin solution could be used to reverse the expression of plakin proteins.

Methods

Tear film samples from treatment naïve patients with anterior blepharitis (n = 15) were collected with Schirmer filtration paper. A subgroup of the patients (n = 10) received treatment with a dexamethasone/tobramycin 1 + 3 mg/mL ophthalmic suspension (Tobradex®) for 3 weeks and collection of tear film samples was repeated. The samples were analysed with label‐free quantification nano liquid chromatography–tandem mass spectrometry requiring quantification in at least 70% of the samples in each group. Proteins were considered differentially expressed if p < 0.05.

Results

Following Tobradex® intervention, 27 proteins were upregulated while 61 proteins were downregulated. Regulated proteins after Tobradex® treatment were involved in intermediate filament cytoskeleton organization including downregulation of the plakin proteins envoplakin, epiplakin and periplakin. Plectin, a protein of the plakin family, remained unchanged after Tobradex® therapy. Tobradex® treatment resulted in the regulation of proteins involved in translation including a cluster of downregulated ribosomal proteins. Tobradex® intervention was associated with the regulation of proteins involved in fructose metabolism and glycolytic processes including fructose‐1.6‐bisphosphatase 1, fructose‐bisphosphate aldolases A and B, pyruvate kinase PKM and transketolase. Ig lambda chain V‐I region, prominin‐1, and protein Niban were upregulated after Tobradex® treatment.

Conclusions

Tobradex treatment reversed the expression of plakin proteins in anterior blepharitis. Topical solutions which inhibit the expression of plakin proteins may have the potential to restore the ocular surface integrity in anterior blepharitis and should be explored further.