bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic basis of choline import involved in teichoic acids and lipopolysaccharide modification
Authors: Bärland Natalie , Rueff Anne-Stéphanie , Cebrero Gonzalo , Hutter Cedric A.J. , Seeger Markus A. , Veening Jan-Willem , Perez Camilo
Published: September 2021

Phosphocholine molecules decorating bacterial cell wall teichoic acids and outer-membrane lipopolysaccharide have significant roles in adhesion to host cells, immune evasion, and persistence. Bacteria carrying the operon that performs phosphocholine decoration, synthesize phosphocholine after uptake of the choline precursor by LicB, a conserved transporter among divergent species. Streptococcus pneumoniae is a prominent pathogen where phosphocholine decoration plays a fundamental role in virulence. Here we present cryo-electron microscopy and crystal structures of S. pneumoniae LicB, revealing distinct conformational states and describing architectural and mechanistic elements essential to choline import. Together with in vitro and in vivo functional characterization, we found that LicB displays proton-coupled import activity and promiscuous selectivity involved in adaptation to choline deprivation conditions, and describe LicB inhibition by synthetic nanobodies (sybodies) and hemicholinium-3. Our results provide novel insights into the molecular mechanism of a key transporter involved in bacterial pathogenesis and establish a basis for inhibition of the phosphocholine modification pathway across bacterial phyla.
Single Nucleotide Substitutions Effectively Block Cas9 and Allow for Scarless Genome Editing inCaenorhabditis elegans
Authors: Medley Jeffrey C. , Hebbar Shilpa , Sydzyik Joel T. , Zinovyeva Anna Y.
Published: September 2021

InCaenorhabditis elegans, germline injection of Cas9 complexes is reliably used to achieve genome editing through homology-directed repair of Cas9-generated DNA breaks. To prevent Cas9 from targeting repaired DNA, additional blocking mutations are often incorporated into homologous repair templates. Cas9 can be blocked either by mutating the PAM sequence that is essential for Cas9 activity or by mutating the guide sequence that targets Cas9 to a specific genomic location. However, it is unclear how many nucleotides within the guide sequence should be mutated, since Cas9 can recognize “off-target” sequences that are imperfectly paired to its guide. In this study, we examined whether single-nucleotide substitutions within the guide sequence are sufficient to block Cas9 and allow for efficient genome editing. We show that a single mismatch within the guide sequence effectively blocks Cas9 and allows for recovery of edited animals. Surprisingly, we found that a low rate of edited animals can be recovered without introducing any blocking mutations, suggesting a temporal block to Cas9 activity inC. elegans. Furthermore, we show that the maternal genome of hermaphrodite animals is preferentially edited over the paternal genome. We demonstrate that maternally provided haplotypes can be selected using balancer chromosomes and propose a method of mutant isolation that greatly reduces screening efforts post-injection. Collectively, our findings expand the repertoire of genome editing strategies inC. elegansand demonstrate that extraneous blocking mutations are not required to recover edited animals when the desired mutation is located within the guide sequence.
Hidden conformations differentiate day and night in a circadian pacemaker
Authors: Swan Jeffrey A. , Sandate Colby R. , Chavan Archana G. , Freeberg Alfred M. , Etwaru Diana , Ernst Dustin C. , Palacios Joseph G. , Golden Susan S. , LiWang Andy , Lander Gabriel C. , Partch Carrie L.
Published: September 2021

The AAA+ protein KaiC is the central pacemaker for cyanobacterial circadian rhythms. Composed of two hexameric rings with tightly coupled activities, KaiC undergoes changes in autophosphorylation on its C-terminal (CII) domain that restrict binding of of clock proteins on its N-terminal (CI) domain to the evening. Here, we use cryo-electron microscopy to investigate how daytime and nighttime states of CII regulate KaiB binding to CI. We find that the CII hexamer is destabilized during the day but takes on a rigidified C2-symmetric state at night,concomitant with ring-ring compression. Residues at the CI-CII interface are required for phospho-dependent KaiB association, coupling ATPase activity on CI to cooperative KaiB recruitment. Together these studies reveal how daily changes in KaiC phosphorylation regulate cyanobacterial circadian rhythms.

One-Sentence Summary

Cryo-EM structures of KaiC in its day and night states reveal the structural basis for assembly of clock regulatory complexes.
The morning burst: Shifting daily patterns of ATP production in Drosophila and temporal windows for their improvement in ageing
Authors: Shinhmar Harpreet , Kam Jaimie Hoh , Mitrofanis John , Hogg Chris , Jeffery Glen
Published: September 2021

Mitochondria produce energy for cell function via adenosine triphosphate (ATP) and are regulated by a molecular 24h clock. Here we use Drosophila melanogaster to reveal shifts in whole animal ATP production over 24h, showing a marked peak in the morning that declines around midday and remains low from then through to the following morning. Mitochondrial membrane potential and ATP production has been shown previously to improve after long wavelength exposure, but apparently not at all times. Hence, to explore this further we exposed flies to 670nm at different times. Exposures between 08.00 and 11.00 resulted in a significant increase in ATP, while exposures at other times had no effect. Within the morning window, not all times were equally effective, however, 670nm exposure mid-morning when ATP production was maximal did not increase ATP, possibly because mitochondria lacked spare capacity at this time. Hence, in the morning there is a complex dynamic relationship between long wavelength light and mitochondria. Mitochondrial function and the influence of long wavelengths are conserved across species from fly to human, and determining the time points for light administration to improve function in ageing and disease is of key importance. Our data progress this search and reveal the outline of these times.
Effects ofCatha Edulis Forskon Spatial Cognition and correlation with serum electrolytes in Wild- type Male White Albino Rats
Authors: Limenie Abebaye Aragaw , Dugul Tesfaye Tolessa , Eshetu Eyasu Mekonnen
Published: September 2021

Background

The burdens of psychostimulant use disorders are becoming a worldwide problem. One of the psychostimulants widely consumed in Ethiopia and East African countries isCatha edulis Forsk(khat). However, no studies have been conducted on the cognitive effects of khat and its correlation with serum electrolytes. The present study was aimed to evaluate the effects of khat on cognitive functions and its correlation with serum electrolytes.

Materials and Methods

A total of 36 adult (7-8 weeks) wild-type male Swiss albino rats weighing between 213 and 229g were used in this study. The rats were received crude khat extract subchronically (kesc) (100 mg/kg, 200 mg/kg and 300 mg/kg b.w), khat juice (khJ 2.5 mL/kg) and 2% tween 80 in distilled water (T80W- v/v, vehicle) and khat extract subacutely (kesa) (300 mg/kg). Spatial learning and memory were measured using Morris water maze model and serum electrolytes were measured using Cobas 6000. The data were analyzed using SPSS version 21.0 and Microsoft Excel.

Results

Spatial learning was improved with trials across the groups, while average escape latency (s) and swim path-length (cm) of rats that received kesc 200 mg/kg (p<0.001 and p<0.001) and kesc 300 mg/kg (p<0.01 and p<0.001) was significantly greater than rats that received the vehicle. However, there was no significant difference in the latency between rats that received kesa 300mg/kg and vehicle (p>0.05). Thigmotaxis was significantly higher in rats that received all doses of khat extract (p<0.001). The time spent in the target quadrant in rats that received kesc 300 mg/kg was significantly reduced (p<0.05). Serum calcium level was inversely correlated with the escape latency (R=−0.417, p<0.05) in rats that received khat.

Conclusions

khat extract and juice administered subchronically, but not subacute administration, impaired learning and memory in rats and was associated with serum calcium reduction. The neuronal basis for such alteration should be investigated.
SDR enzymes oxidize specific lipidic alkynylcarbinols into cytotoxic protein-reactive species
Authors: Demange Pascal , Joly Etienne , Marcoux Julien , Zanon Patrick R. A. , Listunov Dymytrii , Rullière Pauline , Barthes Cécile , Noirot Céline , Izquierdo Jean-Baptiste , Pradines Karen , Hee Romain , de Brito Maria Vieira , Marcellin Marlène , Serre Rémi-Félix , Bouchez Olivier , Burlet-Schiltz Odile , Oliveira Maria Conceição Ferreira , Ballereau Stéphanie , Bernardes-Génisson Vania , Maraval Valérie , Calsou Patrick , Hacker Stephan M. , Génisson Yves , Chauvin Remi , Britton Sébastien
Published: September 2021

Hundreds of cytotoxic natural or synthetic lipidic compounds contain chiral alkynylcarbinol motifs, but the mechanism of action of those potential therapeutic agents remains unknown. Using a genetic screen in haploid human cells, we discovered that the enantiospecific cytotoxicity of numerous terminal alkynylcarbinols, including the highly cytotoxic dialkynylcarbinols, involves a bioactivation by HSD17B11, a short-chain dehydrogenase/reductase (SDR) known to oxidize the C-17 carbinol center of androstan-3-alpha,17-beta-diol to the corresponding ketone. A similar oxidation of dialkynylcarbinols generates dialkynylketones, that we characterize as highly protein-reactive electrophiles. We established that, once bioactivated in cells, the dialkynylcarbinols covalently modify several proteins involved in protein-quality control mechanisms, resulting in their lipoxidation on cysteines and lysines through Michael addition. For some proteins, this triggers their association to cellular membranes and results in endoplasmic reticulum stress, unfolded protein response activation, ubiquitin-proteasome system inhibition and cell death by apoptosis. Finally, as a proof-of-concept, we show that generic lipidic alkynylcarbinols can be devised to be bioactivated by other SDRs, including human RDH11 and HPGD/15-PGDH. Given that the SDR superfamily is one of the largest and most ubiquitous, this unique cytotoxic mechanism-of-action could be widely exploited to treat diseases, in particular cancer, through the design of tailored prodrugs.

Graphical abstract
Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates
Authors: Chiuppesi Flavia , Nguyen Vu H. , Park Yoonsuh , Contreras Heidi , Karpinski Veronica , Faircloth Katelyn , Nguyen Jenny , Kha Mindy , Johnson Daisy , Martinez Joy , Iniguez Angelina , Zhou Qiao , Kaltcheva Teodora , Frankel Paul , Kar Swagata , Sharma Ankur , Andersen Hanne , Lewis Mark G. , Shostak Yuriy , Wussow Felix , Diamond Don J.
Published: September 2021

Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen Modified Vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.
Exploring accountability of Australia and New Zealand's temporary labour mobility programmes in Samoa using a talanoa approach
Authors: Perkiss Stephanie , Taule’alo Tautalaaso , Dun Olivia , Klocker Natascha , Liki Asenati , Tanima Farzana
Published: September 2021

Purpose

Temporary labour mobility programmes (TLMPs) are initiated by high-income nations to fill their labour demands by offering temporary work opportunities to migrants from low-income nations. TLMPs also seek to contribute to economic development in workers' home countries. This paper aims to assess the accountability of New Zealand's Recognised Seasonal Employer (RSE) Scheme and Australia's Seasonal Worker Programme (SWP) in reaching their economic development objectives in one sending nation, Samoa.

Design/methodology/approach

A qualitative study with RSE and SWP workers and key informants (collectively stakeholders) in Samoa was undertaken to assess the contributions of these schemes to economic development. An interdisciplinary research approach was taken using the Pacific methodology of talanoa. Talanoa was used to “operationalise engagement” and empower local stakeholder accounts.

Findings

Talanoa supported the elicitation of accounts that contributed nuanced insights into the accountability of TLMPs. Specifically, stakeholder accounts revealed limitations in the ability of the RSE Scheme and SWP to meet their economic development objectives for Samoan communities and workers. Adjustments are necessary to meet Pacific nations' economic development objectives.

Practical implications

This study responds to calls for on-the-ground accounts of stakeholders involved in TLMPs. It provides insights that may contribute to the development of more effective TLMPs, particularly regarding economic development in workers' home countries.

Originality/value

Drawing on dialogic accounting literature, which calls for engagement with the marginalised, a talanoa approach has been engaged to assess TLMPs via on-the-ground participant accounts in a specific context. This paper introduces talanoa to the critical and social accounting literature, to move beyond a typical accounting qualitative interview process and encourage greater engagement and collaboration with Pacific scholars and partners.
Deterrents to the adoption of green walls: a hybrid fuzzy-based approach
Authors: Tabatabaee Sanaz , Ashour Mojtaba , Mohandes Saeed Reza , Sadeghi Haleh , Mahdiyar Amir , Hosseini M. Reza , Ismail Syuhaida
Published: September 2021

Purpose

Green walls (GWs), comprising living walls and green facades, have been touted as environmentally friendly products in architectural design. GWs can be viable in every aspect of sustainability; they provide residents of buildings with a wide range of economic, social and environmental benefits. Despite this, the adoption rate of GW is still in its infancy stage, and the existing literature concerning the hindrances inhibiting GW adoption is very limited. To address these gaps, the aim of this paper is to identify and prioritize the hindrances to GW adoption in Hong Kong.

Design/methodology/approach

After identifying 17 hindrances through an in-depth review of literature, the fuzzy Delphi method (FDM) is employed to refine the hindrances based on the local context with the help of 21 qualified experts in the field. Subsequently, Fuzzy Parsimonious Analytic Hierarchy Process (FPAHP) is exploited as a recently developed technique to prioritize the identified hindrances.

Findings

Results reveal that the most significant hindrances to the adoption of GW are maintenance cost, high installation cost, difficulties in maintenance, sophisticated implementation and inducement to fire. Findings call for scholars to address ways to improve GW installation practices and methods in order to eradicate the hindrances and provide lessons for policymakers, assisting them in facilitating the larger-scale adoption of GW.

Originality/value

Considering the dearth of studies on hindrances to the adoption of GWs, this paper provides a comprehensive outlook of the issue, providing knowledge that can be used as a building block for future scholars within the field. It also provides valuable insights for stakeholders within the construction industry about the hindrances to the adoption of GWs which could direct their efforts toward better implementation of it.
Non-financial reporting and company financial performance: a systematic literature review and integrated framework
Authors: Crous Cornelie , Battisti Enrico , Leonidou Erasmia
Published: September 2021

Purpose

The purpose of this paper is to examine the different aspects of non-financial reporting that may influence company financial performance. In particular, the authors present an integrated framework of these features that have a direct impact on the financial sustainability of firms for future researchers to further explore and expand the boundaries of the domain.

Design/methodology/approach

A systematic literature review of peer-reviewed papers, covering the period 2015–2020, was done, and 41 paper were identified and analysed via a thematic review, to identify variables that either positively or negatively impact on the financial performance of listed companies. The literature focuses on disclosures related to integrated reporting disclosures, sustainability disclosures (also called corporate social responsibility (CSR) disclosures) and corporate governance disclosures. A synthesised inter-textual coherence strategy has been followed during the interpretation of the findings.

Findings

The results of the synthesised inter-textual coherence strategy were the development of an integrated framework, which indicates that the inclusion of control variables in regression analysis has no impact on the direction of the relationship between quality reporting and financial reporting.

Originality/value

To the best of the authors’ knowledge, this paper is the first to provide a comparison between the impact of the different types of reporting and financial sustainability.
Proximal and distal antecedents of problematic information technology use in organizations
Authors: Pirkkalainen Henri , Tarafdar Monideepa , Salo Markus , Makkonen Markus
Published: September 2021

Purpose

Excessive use of work-related information technology (IT) devices can lead to major performance and well-being concerns for organizations. Extant research has provided evidence of the incidence of such problematic IT use in organizations. We extend the understanding of problematic IT use by examining its individual (proximal) and organizational (distal) antecedents.

Design/methodology/approach

Drawing from the self-worth theory and the concept of fear of being left behind, we address proximal antecedents that lead to problematic IT use. Drawing from the concept of autonomy paradox, we address distal antecedents of problematic IT use through a positive association with the two proximal antecedents. We report the results of a field study involving 846 individuals who use IT for work. Structural equation modeling was employed to analyze the data.

Findings

The results indicate that the proximal antecedents (IT insecurity and fear of missing out) are positively associated with problematic IT use. The distal antecedents (IT use autonomy and involvement facilitation) are positively associated with the proximal antecedents except for the relationship between IT use autonomy and IT insecurity, which was found statistically non-significant. Furthermore, fear of missing out fully mediates the effect of IT use autonomy on problematic IT use, whereas IT insecurity and fear of missing out fully mediate the effects of involvement facilitation on problematic IT use.

Originality/value

The paper theoretically extends the understanding of problematic IT use and identifies novel its proximal and distal antecedents.
Exploring the effects of team coordination and power distance on effective software process tailoring: a theoretical perspective
Authors: Lee Jung-Chieh , Chen Chung-Yang
Published: September 2021

Purpose

Software process tailoring (SPT) plays a critical role in contemporary software development. Because SPT determines how a software project proceeds, its effectiveness should be investigated. Specifically, SPT is a collaborative yet highly conflictual process, and the existing literature has paid little or no attention to how team members coordinate and to how power distance (PD) influences coordination under this conflictual situation for the purpose of fostering SPT effectiveness.

Design/methodology/approach

A propositional research method is utilized by reviewing the extant literature regarding SPT, team coordination and PD. Accordingly, several propositions are developed to theorize the contributive and moderating effects of team coordinative capabilities and PD on SPT effectiveness.

Findings

This study advances the understanding of the underlying mechanisms of the four distinct coordination capabilities in performing SPT, which will help software firms comprehend the moderating effects of PD on the relationships among coordinative capabilities and SPT effectiveness.

Originality/value

This study extends coordination theory and reveals four coordination capabilities that nurture SPT effectiveness. Moreover, this study demonstrates how power plays a role in the coordination of a team through the collaborative yet divergent SPT decision process to yield an integrative tailoring solution. In particular, we take a fresh viewpoint of PD considering the member-member relationship in exploring its moderating effects in the SPT context.
Sustainability through the lens of the professional adviser: the case for brand trust
Authors: Stoica Michael , Hickman Thomas M.
Published: September 2021

Purpose

This investigation builds on two domains. First, professional service providers, such as dentists and veterinarians, represent an understudied link in the distribution channel. Their recommendation of products, such as toothpaste and pet food, are impactful to their clientele. Second, for consumers, sustainability is growing as a motivating factor in product consideration. Consequently, brands committed to sustainability want to promote their products accordingly to connect with the consumer. The purpose of this study is to determine how to trust in sustainable brands is built in the mind of professional service providers, as they are influential in their clients’ decision process.

Design/methodology/approach

Structural equation modeling was used to test the conceptual model that predicted how brand trust of sustainable products is built in the mind of the professional service provider using a sample of 457 veterinarians.

Findings

Results revealed that trust in sustainable brands is built via professionals’ expertise in sustainability and their perception of the importance of sustainability. Additionally, the perception of altruistic motivations had a positive impact on brand trust while the perception of strategic motivations had no influence on trust in sustainable brands.

Originality/value

Previous studies typically examine sustainability in an organizational context or as a brand consideration factor for consumers. This research focuses on professional service providers, who operate independently of the organization, alongside the formal distribution channel. The study examines how their perception of sustainability importance and their perceived motives of brands engaging in sustainability activities impacts their trust in sustainable brands.
Non-fungible tokens and libraries
Authors: Fernandez Peter
Published: September 2021

Purpose

This paper aims to help information professionals understand the foundational concepts of this technology and how these are related to libraries so that they can evolve services alongside it.

Design/methodology/approach

This column will define what a non-fungible tokens (NFT) is, explore the relevant trends impacting its development and examine how it intersects with the traditional roles of the library.

Findings

NFTs represent a new and growing technology that intersections with many of the same concepts that are core to librarianship. Libraries are community institutions that engender widespread trust, whereas NFTs are built atop cryptocurrency that seeks to enable anonymous peer-to-peer interactions.

Originality/value

Summary.
Cold spray micro-defects and post-treatment technologies: a review
Authors: Zhizhong Wang , Chao Han , Huang Guosheng , Bin Han , Bin Han
Published: September 2021

Purpose

The deposition of particles onto a substrate during the cold spraying (CS) process relies on severe plastic deformation, so there are various micro-defects induced by insufficient deformation and severe crushing. To solve the problems, many post-treat techniques have been used to improving the quality by eliminating the micro-defects. This paper aims to help scholars and engineers in this field a better and systematic understand of CS technology by summarizing the post-treatment technologies that have been investigated recently years.

Design/methodology/approach

This review summarizes the types of micro-defects and introduces the effect of micro-defects on the properties of CS coating/additive manufactured, illustrates the post-treatment technologies and its effect on the microstructure and performances, and finally outlooks the future development trends of post-treatments for CS.

Findings

There are significant discoveries in post-treatment technology to change the performance of cold spray deposits. There are also many limitations for post-treatment methods, including improved performance and limitations of use. Thus, there is still a strong requirement for further improvement. Hybrid post-treatment may be a more ideal method, as it can eliminate more defects than a single method. The proposed ultrasonic impact treatment could be an alternative method, as it can densify and flatten the CS deposits.

Originality/value

It is the first time to reveal the influence factors on the performances of CS deposits from the perspective of microdefects, and proposed corresponding well targeted post-treatment methods, which is more instructive for improving the performances of CS deposits.
Tree phyllospheres are a habitat for diverse populations of CO‐oxidizing bacteria
Authors: Palmer Jess L. , Hilton Sally , Picot Emma , Bending Gary D. , Schäfer Hendrik
Published: September 2021

Carbon monoxide (CO) is both a ubiquitous atmospheric trace gas and an air pollutant. While aerobic CO‐degrading microorganisms in soils and oceans are estimated to remove ~370 Tg of CO per year, the presence of CO‐degrading microorganisms in above‐ground habitats, such as the phyllosphere, and their potential role in CO cycling remains unknown. CO‐degradation by leaf washes of two common British trees, Ilex aquifolium and Crataegus monogyna, demonstrated CO uptake in all samples investigated. Based on the analyses of taxonomic and functional genes, diverse communities of candidate CO‐oxidizing taxa were identified, including members of Rhizobiales and Burkholderiales which were abundant in the phyllosphere at the time of sampling. Based on predicted genomes of phyllosphere community members, an estimated 21% of phyllosphere bacteria contained CoxL, the large subunit of CO‐dehydrogenase. In support of this, data mining of publicly available phyllosphere metagenomes for genes encoding CO‐dehydrogenase subunits demonstrated that, on average, 25% of phyllosphere bacteria contained CO‐dehydrogenase gene homologues. A CO‐oxidizing Phyllobacteriaceae strain was also isolated from phyllosphere samples which contains genes encoding both CO‐dehydrogenase as well as a ribulose‐1,5‐bisphosphate carboxylase‐oxygenase. These results suggest that the phyllosphere supports diverse and potentially abundant CO‐oxidizing bacteria, which are a potential sink for atmospheric CO.
Impact of a mid‐urethral synthetic mesh sling on long‐term risk of systemic conditions in women with stress urinary incontinence: a national cohort study
Authors: Muller P , Gurol‐Urganci I , Thakar R , Ehrenstein MR , Van Der Meulen J , Jha S
Published: September 2021

Objective

To compare the incidence of systemic conditions between women who had surgical treatment for stress incontinence with mesh and without mesh.

Design

National cohort study.

Setting

English National Health Service.

Population

Women with no previous record of systemic disease who had first‐time urinary incontinence surgery between 1 January 2006 and 31 December 2013, followed up to the earliest of 10 years or 31 March 2019.

Methods

Competing‐risks regression was used to estimate hazard ratios (HR), adjusted for patient characteristics, with HR > 1 indicating increased incidence following mesh surgery.

Main outcome measures

First postoperative admission with a record of autoimmune disease, fibromyalgia or myalgic encephalomyelitis up to 10 years following the first incontinence procedure.

Results

The cohort included 88 947 women who had mesh surgery and 3389 women who had non‐mesh surgery. Both treatment groups were similar with respect to age, socio‐economic deprivation, comorbidity and ethnicity. The 10‐year cumulative incidence of autoimmune disease, fibromyalgia or myalgic encephalomyelitis was 8.1% (95% CI 7.9–8.3%) in the mesh group and 9.0% (95% CI 8.0–10.1%) in the non‐mesh group (adjusted HR 0.89, 95% CI 0.79–1.01; P = 0.07). A sensitivity analysis including only autoimmune diseases as an outcome returned a similar result.

Conclusions

These findings do not support claims that synthetic mesh slings cause systemic disease.

Tweetable abstract

No evidence of increased risk of systemic conditions after stress incontinence treatment with a mesh sling.
Does Progress on Universal Health Coverage Explain COVID Cases and Deaths?
Authors: Thapa Bishnu , Ossimetha Angelina , Rahman Momotazur , Galarraga Omar
Published: September 2021

Research Objective

The trajectory of COVID‐19 pandemic has been different across different countries and regions, with varying number of per‐population cases and deaths. Such variation may be a function of a number of country‐specific factors such as population distribution, disease profile, non‐pharmaceutical interventions (e.g., lockdowns) undertaken at the wake of the pandemic, political leadership, and others.

Our objective is to examine the extent to which a country's progress towards universal health coverage (UHC) explains COVID outcomes. We also measure how the effect of UHC varies across different levels of social capital. We proxy the UHC progress using service coverage index (SCI). The SCI is a broad‐based measure of UHC, and is tracked at the country level by the World Health Organization (WHO) and its collaborating partners.

Our overall hypothesis is that the UHC‐SCI has a protective effect on health, and therefore, is negatively associated with the COVID outcomes (COVID cases and deaths per 100 k population).

Study Design

We use longitudinal data‐based generalized linear models (GLMs) to investigate the relationship between the outcome variable (COVID cases and deaths) and the key explanatory variables. We run cross‐country linear regressions, with month fixed effects and country‐level clustering. We run two sets of linear regressions. First, we regress each COVID outcome on the SCI. Second, we regress each COVID outcome on the SCI and the interaction term between SCI and social capital. Both sets of regressions include controls for GDP per capita, share of population above 65, stringency measures, and COVID testing rates.

Our data for the SCI comes from the WHO while the longitudinal (monthly) data on COVID outcomes and other key variables come from “ourworldindata.org” (University of Oxford). The data on government trust is obtained from the social capital component of the Legatum Prosperity Index (LPI), 2019.

Population Studied

173 countries.

Principal Findings

Our findings show that there is a positive and strong association between UHC‐SCI and COVID outcomes. This is counterintuitive, and we suspect it is likely due to the dependency of testing for the actual ascertainment of cases and deaths. The coefficient on the interaction term (between SCI and social capital), however, is negative and statistically significant.

Conclusions

The effect of UHC seems to be protective among countries that are characterized by high level of social capital.

Implications for Policy or Practice

The effect of UHC seems to be protective among countries that are characterized by high level of social capital.
Overcrowded Housing Increases Risk for COVID‐19 Mortality: An Ecological Study
Authors: Varshney Karan , Adalbert Jenna
Published: September 2021

Research Objective

COVID‐19 has devastated the United States (US) population and exacerbated existing health inequalities. Those residing in areas of high population density are at an elevated risk, suggesting that residence in an overcrowded household may result in heightened vulnerability. However, as the association between residing in an overcrowded household and risk of mortality from COVID‐19 is unknown, the purpose of this study was to analyze this relationship.

Study Design

COVID‐19 data for Los Angeles County was acquired, along with data on housing and demographics. Overcrowded households were defined as having 1.0+ persons per room. Bivariate regression was then performed, followed by backwards stepwise linear regression. This included overcrowded housing as a predictor variable and COVID‐19 death totals as an outcome variable. Collinearity was assessed via the variance inflation factors (VIF); variables were removed if they had a VIF >8.

Population Studied

Population‐level data was retrieved for each of the 85 cities in Los Angeles county, the region with the highest number of COVID‐19 cases in the US. Data for this population came from the Los Angeles County Government, as well as the US Census Bureau.

Principal Findings

Bivariate regression indicated that the number of overcrowded households was positively associated with total COVID‐19 deaths (standardized β = 0.844, p < 0.001). COVID‐19 case totals, number of individuals aged 60 or above, and number of overcrowded households met conditions for inclusion in the backwards stepwise linear regression model. This analysis revealed all independent variables were positively associated with number of deaths, with the largest effect being seen with overcrowded housing (standardized β1 = 0.386, p = 0.001), followed by number of cases (standardized β2 = 0.307, p = 0.014), and number of individuals aged 60+ (standardized β3 = 0.282, p < 0.001).

Conclusions

Overcrowded housing was found to be a major risk factor for COVID‐19 mortality and served as a better predictor of number of deaths in a city than the number of people 60+, and even the total number of COVID‐19 cases.

Implications for Policy or Practice

These findings have important implications for addressing the COVID‐19 pandemic. While age and comorbidities have frequently been described as risk factors for poor outcomes, these findings indicate a critical need for COVID‐19 control efforts to more thoroughly assess for overcrowded housing. The striking absence of research and data collection on overcrowded housing indicates a clear direction for future studies.
Multimarket Contact and Mutual Forbearance in Audit Markets
Authors: DEKEYSER SIMON , GAEREMYNCK ANN , KNECHEL W. ROBERT , WILLEKENS MARLEEN
Published: September 2021

Competition in audit markets is an important topic but direct tests of market competition have been limited. In this paper, we examine how audit firms behave when they are confronted with competition from another firm in a wide range of industry segments in a local market. Sharing a large number of market segments can lead to mutual forbearance among audit rivals. Such mutual forbearance is likely to manifest as higher audit fees in a market because rivals are hesitant to aggressively compete in the face of potential competitive retaliation. Using a sample of 25,662 observations from 2004 to 2015, we find evidence that supports this argument as proxied by the extent that audit firms compete in the same industries in the same locations. This result persists after controlling for several tight fixed‐effects specifications based on time, location, industry, and market segments. In supplementary tests, we also find that the likelihood of client switching is negatively associated with the multi‐industry contact of the incumbent, but clients that do switch are more likely to choose an alternative audit firm that confronts the predecessor auditor in fewer market segments. Our evidence is consistent with mutual forbearance among rival audit firms when confronted with the same competitor in different market segments.
Absence of complementary sex determination in twoLeptopilinaspecies (Figitidae, Hymenoptera) and a reconsideration of its incompatibility with endosymbiont‐induced thelytoky
Authors: Chen Fangying , Schenkel Martijn , Geuverink Elzemiek , van de Zande Louis , Beukeboom Leo W.
Published: September 2021

Complementary sex determination (CSD) is a widespread sex determination mechanism in haplodiploid Hymenoptera. Under CSD, sex is determined by the allelic state of one or multiple CSD loci. Heterozygosity at one or more loci leads to female development, whereas hemizygosity of haploid eggs and homozygosity of diploid eggs results in male development. Sexual (arrhenotokous) reproduction normally yields haploid male and diploid female offspring. Under asexual reproduction (thelytoky), diploidized unfertilized eggs develop into females. Thelytoky is often induced by bacterial endosymbionts that achieve egg diploidization by gamete duplication. As gamete duplication leads to complete homozygosity, endosymbiont‐induced thelytokous reproduction is presumed to be incompatible with CSD, which relies on heterozygosity for female development. Previously, we excluded CSD in fourAsobara(Braconidae) species and proposed a two‐step mechanism forWolbachia‐induced thelytoky inAsobara japonica. Here, we conclusively reject CSD in two cynipid wasp species,Leptopilina heterotomaandLeptopilina clavipes. We further show that thelytoky inL. clavipesdepends onWolbachiatiter but that diploidization and feminization steps cannot be separated, unlike inA. japonica. We discuss what these results reveal about the sex determination mechanism ofL. clavipesand the presumed incompatibility between CSD and endosymbiont‐induced thelytoky in the Hymenoptera.
Identification of circ_0058357 as a regulator in non‐small cell lung cancer cells resistant to cisplatin by miR‐361‐3p/ABCC1 axis
Authors: Chu Dan , Li Pengpeng , Li Yameng , Shi Jiang , Huang Siyuan , Jiao Pengfei
Published: September 2021

Background

Drug resistance is a major clinical drawback behind the failure of chemotherapy in non‐small cell lung cancer (NSCLC). In this study, we undertook to identify the precise role of circular RNA (circRNA) circ_0058357 in the functional properties of DDP‐resistant NSCLC cells.

Methods

Circ_0058357, miR‐361‐3p and ATP‐binding cassette (ABC) subfamily C member 1 (ABCC1) were quantified by qRT‐PCR and western blot. Cell survival and viability were gauged by MTT assay. Cell proliferation, apoptosis, invasion and migration were measured by EdU, flow cytometry, transwell and wound‐healing assays, respectively. The direct relationship between miR‐361‐3p and circ_0058357 or ABCC1 was validated by dual‐luciferase reporter assay.

Results

Our data showed that circ_0058357 was highly expressed in DDP‐resistant NSCLC tissues and cells. Inhibition of circ_0058357 repressed cell growth, invasion, migration, and promoted DDP sensitivity and cell apoptosis of H1299/DDP and A549/DDP cells in vitro. Moreover, inhibition of circ_0058357 diminished the growth of A549/DDP cells and sensitized them to the cytotoxic effect of DDP in vivo. Mechanistically, circ_0058357 contained a miR‐361‐3p binding site and miR‐361‐3p was identified as a molecular mediator of circ_0058357 regulation. MiR‐361‐3p suppressed ABCC1 expression by binding to ABCC1 3′UTR, and miR‐361‐3p‐mediated inhibition of ABCC1 affected the growth, invasion, migration, apoptosis and DDP sensitivity of H1299/DDP and A549/DDP cells. Furthermore, circ_0058357 regulated ABCC1 expression by competitively binding to shared miR‐361‐3p.

Conclusions

Our findings identified that inhibition of circ_0058357 suppresses the growth and metastasis of H1299/DDP and A549/DDP cells and sensitizes them to DDP therapy partially by targeting the miR‐361‐3p/ABCC1 axis.
Prenatal alcohol and cannabis exposure can have opposing and region‐specific effects on parvalbumin interneuron numbers in the hippocampus
Authors: Reid Hannah M. O. , Snowden Taylor M. , Shkolnikov Irene , Breit Kristen R. , Rodriguez Cristina , Thomas Jennifer D. , Christie Brian R.
Published: September 2021

Background

We recently showed that alcohol and cannabis can interact prenatally, and in a recent review paper, we identified parvalbumin‐positive (PV) interneurons in the hippocampus as a potential point of convergence for these teratogens.

Methods

A 2 (Ethanol [EtOH], Air) × 2 (tetrahydrocannabinol [THC], Vehicle) design was used to expose pregnant Sprague‐Dawley rats to either EtOH or air, in addition to either THC or the inhalant vehicle solution, during gestational days 5–20. Immunohistochemistry was performed to detect PV interneurons in 1 male and 1 female pup from each litter at postnatal day 70.

Results

Significant between‐group and subregion‐specific effects were found in the dorsal cornu ammonis 1 (CA1) subfield and the ventral dentate gyrus (DG). In the dorsal CA1 subfield, there was an increase in the number of PV interneurons in both the EtOH and EtOH +THC groups, but a decrease with THC alone. There were fewer changes in interneuron numbers overall in the DG, though there was a sex difference, with a decrease in the number of PV interneurons in the THC‐exposed group in males. There was also a greater cell layer volume in the DG in the EtOH +THC group than the control group, and in the CA1 region in the EtOH group compared to the control and THC groups.

Conclusions

Prenatal exposure to alcohol and THC differentially affects parvalbumin‐positive interneuron numbers in the hippocampus, indicating that both individual and combined exposure can impact the balance of excitation and inhibition in a structure critically involved in learning and memory processes.
Hydrokinetic pancreatic function and insulin secretion are moduled by Cl− uniporter Slc26a9 in mice
Authors: Li T. , di Stefano G. , Raza G. S. , Sommerer I. , Riederer B. , Römermann D. , Tan X. , Tan Q. , Pallagi P. , Hollenbach M. , Herzig K.‐H. , Seidler U.
Published: September 2021

Aim

Slc26a9 is a member of the Slc26 multifunctional anion transporter family. Polymorphisms in Slc26a9 are associated with an increased incidence of meconium ileus and diabetes in cystic fibrosis patients. We investigated the expression of Slc26a9 in the murine pancreatic ducts, islets and parenchyma, and elucidated its role in pancreatic ductal electrolyte and fluid secretion and endocrine function.

Methods

Pancreatic Slc26a9 and CFTR mRNA expression, fluid and bicarbonate secretion were assessed in slc26a9−/− mice and their age‐ and sex‐matched wild‐type (wt) littermates. Glucose and insulin tolerance tests were performed.

Results

Compared with stomach, the mRNA expression of Slc26a9 was low in pancreatic parenchyma, 20‐fold higher in microdissected pancreatic ducts than parenchyma, and very low in islets. CFTR mRNA was ~10 fold higher than Slc26a9 mRNA expression in each pancreatic cell type. Significantly reduced pancreatic fluid secretory rates and impaired glucose tolerance were observed in female slc26a9−/− mice, whereas alterations in male mice did not reach statistical significance. No significant difference was observed in peripheral insulin resistance in slc26a9−/− compared to sex‐ and aged‐matched wt controls. In contrast, isolated slc26a9−/− islets in short term culture displayed no difference in insulin content, but a significantly reduced glucose‐stimulated insulin secretion compared to age‐ and sex‐matched wt islets, suggesting that the impaired glucose tolerance in the absence of Slc26a9 expression these is a pancreatic defect.

Conclusions

Deletion of Slc26a9 is associated with a reduction in pancreatic fluid secretion and impaired glucose tolerance in female mice. The results underline the importance of Slc26a9 in pancreatic physiology.
Exploring men’s vulnerability in the global South: Methodological reflections
Authors: Zweig Patricia
Published: September 2021

In South Africa, young men are generally considered to generate many of the risks associated with informal settlement life, yet their own vulnerability in these environments is seldom considered. Seeking insights into male susceptibility in these impoverished urban spaces is methodologically challenging. How does one encourage poor marginalised young men to speak with candour about their insecurities and challenges? The research methods used, while facilitating openness, should also build their confidence as they reflect on the challenges of everyday life. This paper describes the methodological journey undertaken in a study of young Black men living in informal settlements in Cape Town, South Africa, revealing how they perceive their vulnerability in these environments. It demonstrates how a suite of methods gradually developed through trial and error, with the young men themselves assisting in the adaptation of tools, ranging from interviews using adapted participatory methods to non‐prescriptive diary‐writing. Together they delivered deep and penetrating insights into the lives of the young men, and the nature of their vulnerability.