bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLASP2 facilitates dynamic actin filament organization along the microtubule lattice
Authors: Rodgers NC , Lawrence EJ , Sawant AV , Efimova N , Gonzalez-Vasquez G , Hickman TT , Kaverina I , Zanic M 
Published: September 2022

ABSTRACTCoordination between the microtubule and actin networks is essential for cell motility, neuronal growth cone guidance, and wound healing. Members of the CLASP (Cytoplasmic Linker-Associated Protein) family of proteins have been implicated in the cytoskeletal crosstalk between microtubules and actin networks, however, the molecular mechanisms underlying CLASPs role in cytoskeletal coordination are unclear. Here, we investigate CLASP2α’s crosslinking function with microtubules and F-actin. Our results demonstrate that CLASP2α crosslinks F-actin to the microtubule lattice in vitro. We find that the crosslinking ability is retained by L-TOG2-S, a minimal construct containing the TOG2 domain and serine-arginine rich region of CLASP2α. Furthermore, CLASP2α promotes the accumulation of multiple actin filaments along the microtubule, supporting up to 11 F-actin landing events on a single microtubule lattice region. CLASP2α also facilitates dynamic organization of polymerizing actin filaments templated by the microtubule network, with F-actin forming bridges between individual microtubules. Finally, we find that depletion of CLASPs in vascular smooth muscle cells results in disorganized actin fibers and reduced co-alignment of actin fibers with microtubules, suggesting that CLASP and microtubules contribute to higher-order actin structures. Taken together, our results indicate that CLASP2α can directly crosslink F-actin to microtubules, and that this microtubule-CLASP-actin interaction may influence overall cytoskeletal organization in cells.
Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection
Authors: Zhou Terry , Gilliam Nora J. , Li Sizhen , Spaudau Simone , Osborn Raven M. , Anderson Christopher S. , Mariani Thomas J. , Thakar Juilee , Dewhurst Stephen , Mathews David H. , Huang Liang , Sun Yan 
Published: September 2022

AbstractDefective viral genomes (DVGs) have been identified in many RNA viruses as a major factor influencing antiviral immune response and viral pathogenesis. However, the generation and function of DVGs in SARS-CoV-2 infection are less known. In this study, we elucidated DVG generation in SARS-CoV-2 and its relationship with host antiviral immune response. We observed DVGs ubiquitously from RNA-seq datasets ofin vitroinfections and autopsy lung tissues of COVID-19 patients. Four genomic hotspots were identified for DVG recombination and RNA secondary structures were suggested to mediate DVG formation. Functionally, bulk and single cell RNA-seq analysis indicated the IFN stimulation of SARS-CoV-2 DVGs. We further applied our criteria to the NGS dataset from a published cohort study and observed significantly higher DVG amount and frequency in symptomatic patients than that in asymptomatic patients. Finally, we observed unusually high DVG frequency in one immunosuppressive patient up to 140 days after admitted to hospital due to COVID-19, first-time suggesting an association between DVGs and persistent viral infections in SARS-CoV-2. Together, our findings strongly suggest a critical role of DVGs in modulating host IFN responses and symptom development, calling for further inquiry into the mechanisms of DVG generation and how DVGs modulate host responses and infection outcome during SARS-CoV-2 infection.ImportanceDefective viral genomes (DVGs) are ubiquitously generated in many RNA viruses, including SARS-CoV-2. Their interference activity to full-length viruses and IFN stimulation provide them the potential for novel antiviral therapies and vaccine development. SARS-CoV-2 DVGs are generated through the recombination of two discontinuous genomic fragments by viral polymerase complex and the recombination is also one of the major mechanisms for the emergence of new coronaviruses. Focusing on the generation and function of SARS-CoV-2 DVGs, these studies identify new hotspots for non-homologous recombination and strongly suggest that the secondary structures within viral genomes mediate the recombination. Furthermore, these studies provide the first evidence for IFN stimulation activity ofde novoDVGs during natural SARS-CoV-2 infection. These findings set up the foundation for further mechanism studies of SARS-CoV-2 recombination and provide the evidence to harness DVGs’ immunostimulatory potential in the development of vaccine and antivirals for SARS-CoV-2.
Cohesin mediates DNA loop extrusion and sister chromatid cohesion by distinct mechanisms
Authors: Nagasaka Kota , Davidson Iain F. , Stocsits Roman R. , Tang Wen , Wutz Gordana , Betty Paul , Panarotto Melanie , Litos Gabriele , Schleiffer Alexander , Gerlich Daniel Wolfram , Peters Jan-Michael 
Published: September 2022

SummaryCohesin connects CTCF binding sites and other genomic loci in cis to form chromatin loops, and replicated DNA molecules in trans to mediate sister chromatid cohesion. Whether cohesin uses distinct or related mechanisms to perform these functions is unknown. Here we describe a cohesin hinge mutant, which can extrude DNA into loops but is unable to mediate cohesion. Our results suggest that the latter defect arises during cohesion establishment. The observation that cohesin’s cohesion and loop extrusion activities can be separated indicates that cohesin uses distinct mechanisms to perform these two functions. Unexpectedly, the same hinge mutant can also not be stopped by CTCF boundaries as well as wildtype cohesin. This suggests that cohesion establishment and cohesin’s interaction with CTCF boundaries depend on related mechanisms and raises the possibility that both require transient hinge opening to entrap DNA inside the cohesin ring.
Drug repurposing for Cystic Fibrosis: identification of drugs that induce CFTR-independent fluid secretion in nasal organoids
Authors: Rodenburg Lisa W. , Delpiano Livia , Railean Violeta , Centeio Raquel , Pinto Madalena C. , Smits Shannon M.A. , van der Windt Isabelle S. , van Hugten Casper F.J. , van Beuningen Sam F.B. , Rodenburg Remco N.P. , van der Ent Cornelis K. , Amaral Margarida D. , Kunzelmann Karl , Gray Michael A. , Beekman Jeffrey M. , Amatngalim Gimano D. 
Published: September 2022

AbstractIndividuals with Cystic Fibrosis (CF) suffer from severe respiratory disease due to a genetic defect in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene, which impairs airway epithelial ion and fluid secretion. New CFTR modulators that restore mutant CFTR function have been recently approved for a large group of people with CF (pwCF), but ∼19% of pwCF cannot benefit from CFTR modulators [1]. Restoration of epithelial fluid secretion through non-CFTR pathways might be an effective treatment for all pwCF. Here we developed a medium-throughput 384-wells screening assay using nasal CF airway epithelial organoids, with the aim to repurpose FDA-approved drugs as modulators of non-CFTR dependent epithelial fluid secretion. From a ∼1400 FDA-approved drug library, we identified and validated 12 FDA-approved drugs that induced CFTR-independent fluid secretion. Among the hits were several cAMP-mediating drugs, including β2-adrenergic agonists. The hits displayed no effects on chloride conductance measured in Ussing chamber, and fluid secretion was not affected by TMEM16A as demonstrated by knockout (KO) experiments in primary nasal epithelial cells. Altogether, our results demonstrate the use of primary nasal airway cells for mediumscale drug screening, target validation with a highly efficient protocol for generating CRISPR-Cas9 KO cells and identification of compounds which induce fluid secretion in a CFTR- and TMEM16A-indepent manner.
Multifaceted modes of γ-tubulin complex recruitment and microtubule nucleation at mitotic centrosomes
Authors: Zhu Zihan , Becam Isabelle , Tovey Corinne A. , Yen Eugenie C. , Bernard Fred , Guichet Antoine , Conduit Paul T. 
Published: September 2022

SummaryMicrotubule nucleation is mediated by γ-tubulin ring complexes (γ-TuRCs). In most eukaryotes, a GCP4/5/4/6 “core” complex promotes γ-tubulin small complex (γ-TuSC) association to generate cytosolic γ-TuRCs. Unlike γ-TuSCs, however, this core complex is non-essential in various species and absent from budding yeasts. InDrosophila, Spindle defective-2 (Spd-2) and Centrosomin (Cnn) redundantly recruit γ-tubulin complexes to mitotic centrosomes. Here we show that Spd-2 recruits γ-TuRCs formed via the GCP4/5/4/6 core, but that Cnn can recruit γ-TuSCs directly via its well-conserved CM1 domain, similar to its homologues in budding yeast. When centrosomes fail to recruit γ-tubulin complexes, they still nucleate microtubules via the TOG domain protein Mini-spindles (Msps), but these microtubules have different dynamic properties. Our data therefore help explain the dispensability of the GCP4/5/4/6 core and highlight the robustness of centrosomes as microtubule organising centres. They also suggest that the dynamic properties of microtubules are influenced by how they were nucleated.
IRF7 impacts on prostate cancer cell survival in response to radiation
Authors: Pickard Adam , Amoroso Francesca , McCulloch Kelsey , Erickson Andrew , Sachdeva Ashwin , Steele Rebecca , Mukherjee Debayan , Dellett Margaret , McComb Jonathan , McCaffery Laura , Hart Claire A. , Brown Michael D. , McDade Simon , Waugh David , Clarke Noel , Butterworth Karl , Illidge Tim , Mirtti Tuomas , Overton Ian M. , Mills Ian G. 
Published: September 2022

AbstractUnderstanding the impact of radiotherapy on the evolution of treatment resistant prostate cancer is critical for selecting effective treatment combinations. Whilst activation of Type 1 interferon signalling is a hallmark of how cells respond to viral infection, in cancer cells, multiple stresses are known to activate this same response. In this study we have evaluated for the first time the changes in the interferon response induced by culturing prostate cancer cells under sphere- forming conditions and following irradiation. We report a conserved upregulated transcript profile for both conditions that is strongly associated with therapeutic resistance and cell survival in vitro and in vivo. The profile includes and is regulated by the Type 1 interferon master regulator IRF7 which, when depleted, delays tumour re-growth following irradiation. We immuno-stained two independent prostate cohorts for IRF7 and found that increased expression, particularly in cases with low PTEN expression, correlated with poor prognosis. To more comprehensively characterise the impact of IRF7 and radiation on cells, RNA-Seq was performed on IRF7 knockdown cells at different radiation doses. We identified a number of biological processes that were IRF7-dependent, including the formation of stem-like cell populations and also therapeutic vulnerabilities. For example, irradiation sensitised surviving cells to either a combination of an IKKε/TBK1 and a MEK inhibitor or treatment with an inhibitor of IDO1, an IRF7- dependent gene. Translationally our work suggests that IRF7 expression can be used to stratify patients who may not benefit from receiving radiotherapy alone but rather may benefit from treatment combinations. In two cohorts treated with radical intent, strong IRF7 staining was associated with disease-specific death implicating this pathway as a convergence point for therapeutic resistance in prostate and potentially other cancer types.
Board characteristics and demand for audit quality: a meta-analysis
Authors: Kalia Deepali , Basu Debarati , Kundu Sayantan 
Published: September 2022

PurposeThe study explores extant knowledge on the nature of the relationship between internal and external corporate governance mechanisms, particularly board characteristics and audit quality, respectively, while also investigating how the relationship varies across geographies.Design/methodology/approachThe extant knowledge is synthesized using a meta-analysis, which is conducted using a sample of 56 empirical studies from publications of varying grades. The studies span over 25 years (1996–2021) and cover 147 empirical samples (343,787 firm-year observations) across more than 20 countries. The dependent variable is audit fees, and the independent variable captures 12 different measures of board characteristics.FindingsOverall, the results reveal a positive association between board characteristics and audit fees, indicating complementarity between governance mechanisms. Effect size analysis shows board characteristics, like size and independence, are positively associated with audit fees. However, heterogeneity is noted for some characteristics, and further analysis by geography (developed vs emerging countries) explains the heterogeneity.Practical implicationsThis study helps multiple stakeholders like firms, shareholders, boards, regulators and policymakers in designing and strengthening governance frameworks.Social implicationsBoth governance and auditing literature benefit from identifying specific board characteristics that drive audit quality consistently across different institutional settings and samples. Heterogeneity analysis helps improve the understanding of contradictions documented in prior literature.Originality/valueThis meta-analysis is the first to explore the interplay between internal and external corporate governance mechanisms, with a focus on board characteristics and audit quality. The study provides valuable insights on how different governance mechanisms influence each other while highlighting, for the first time, how the interaction between governance mechanisms varies by a country's level of development.
The innovation potential of Islamic crowdfunding platforms in contributing to sustainable development
Authors: Testa Stefania , Atawna Thaer , Baldi Gino , Cincotti Silvano 
Published: September 2022

PurposeThis paper aims at explaining variances in the contribution of Islamic crowdfunding platforms (ICFPs) to sustainable development (SD), by adopting an institutional logic perspective (ILP). ICFPs represent a dual institutional overlap between two logics (the Western-mainstream and the Islamic logic) which have an impact on corporate social responsibility (CSR) interpretations, practices, and decisions and whose conflicts are mitigated by choosing different resolution strategies. The authors aim at showing that this choice affects SD differently.Design/methodology/approachThe authors develop a conceptual typology through the following steps: (1) choice of variables and identification of corresponding variable domains, through literature review. Variables chosen are the elemental CSR dimensions related to various social and environmental corporate responsibilities to whom diverse meaning and emphasis are given under the Western-mainstream and Islamic logics. (2) Identification of three distinct ideal types of ICFPs, building on different resolution strategies to mitigate conflicts between logics; (3) development, for each ideal type, of a set of implications related to SD; (4) implementation of a first test aiming at assigning real cases to each ideal type.FindingsThe authors identify Western-mimicking (platforms adopting as resolution strategy decoupling or compartmentalizing strategies), Islamic-driven (platforms focusing on one prevailing logic) and Syncretism-inspired (platforms adopting hybridizing practices) ideal-types.Originality/valueIt is the first paper suggesting ILP to explain variances in crowdfunding platforms' role in addressing SD. It focuses on a specific type of CF platforms till now neglected.
Enhancement of turbulent thermal convection in a circular tube with a slotted twisted tape
Authors: Perng Shiang-Wuu , Wu Horng Wen , Kelana Nugroho Putra , Guo Yi-Ling , Yang Chen-Jui 
Published: September 2022

Purpose
The purpose of this paper, computational fluid dynamics (CFD) work, is to promote turbulent thermal convection in a heated circular tube using a passive scheme of a slotted twisted sheet.

Design/methodology/approach
The inventive design uses square-cut and conjugate triangular perforations to diversify the twisted tape for better thermal convection. The current novel passive scheme methodology is accomplished by carving the same square cuts and slitting various sizes of equilateral triangle perforations (side length varies between 8 and 16 mm). The re-normalisation group turbulence model and the semi-implicit method for pressure-linked equation method examine the turbulent thermal convection aspects of all simulations at different Reynolds numbers (6,000, 10,000 and 14,000).

Findings
The analyses of simulations exhibit that the placement of a twisted tape with triangle perforations and equidistant square cuts can effectually promote thermal convection in a circular tube. A larger-sized triangle perforation can increase the thermal convection enhancement and thermal performance factor, but an enlarged perforation may decrease the thermal convection enhancement and thermal performance factor. As a result, compared with the smooth circular tube, the circular tube with the slotted twisted sheet slit by a 10 mm equilateral triangle brings about the maximum improvement ratio of the mean Nusselt number of about 2.8 at Re = 6,000. Under weighing the friction through the circular tube, the tube with the slotted twisted sheet slit by a 10 mm equilateral triangle gains the best thermal performance factor of about 1.36 at Re = 6,000.

Research limitations/implications
The working fluid is water and its physical features are assumed to be constant. In addition, the fluid is considered a steady flow in this CFD work.

Practical implications
These CFD predictions will benefit the development of heat exchanger tubes equipped with a slotted twisted sheet to acquire preferable thermal convection enhancement.

Social implications
Higher thermal performance achieved by placing a slotted twisted tape in a heated tube will benefit society in lower energy consumption, machinery maintenance costs and impact on the environment.

Originality/value
This study combined triangle perforations and square cuts on the twisted sheet. This combination can induce the fluid flow across the sheet to disturb the swirling flow and then promote the fluid mixing to increase thermal convection. Therefore, this modified tape can be a profitable passive device for designing a heat exchanger.
Perceived workplace incivility and psychological well-being in higher education teachers: a multigroup analysis
Authors: Sood Sarita , Kour Dhanvir 
Published: September 2022

PurposeThe purpose of this study was to investigate the impact of perceived workplace incivility (WPI) on psychological well-being (PWB) in teachers of higher education and to test for the moderating role of gender and organizational tenure on the relationship between perceived WPI and PWB.Design/methodology/approachData were collected from teachers (N = 341) employed in government and private colleges through convenience sampling. A structural equation modeling technique was used for model testing.FindingsResults showed a moderate level of perceived WPI by teachers from their colleagues or supervisors. Perceived WPI had a negative impact on PWB. Sixteen percent of the variance in PWB was explained by perceived WPI. Further, the multigroup analysis showed gender to moderate the relationship between perceived WPI and PWB, and this relationship was stronger for males than females. Organizational tenure was not a significant moderator.Research limitations/implicationsThese findings expand the literature on perceived WPI and suggest that stringent policies are essential in academia to minimize the incidence of WPI. Additionally, interventions are to be introduced to mitigate the negative outcomes of WPI both at the individual and organizational levels.Originality/valueThe study explores the role of demographic variables (gender and organizational tenure) in the relationship between perceived WPI and PWB in teachers. The empirical evidence suggests higher perceived WPI in male teachers leading to lower PWB. The organizational tenure of an employee shows no influence on the assessment of the stressor.
Influence of algorithmic management practices on workplace well-being – evidence from European organisations
Authors: Kinowska Hanna , Sienkiewicz Łukasz Jakub 
Published: September 2022

PurposeExisting literature on algorithmic management practices – defined as autonomous data-driven decision making in people's management by adoption of self-learning algorithms and artificial intelligence – suggests complex relationships with employees' well-being in the workplace. While the use of algorithms can have positive impacts on people-related decisions, they may also adversely influence job autonomy, perceived justice and – as a result – workplace well-being. Literature review revealed a significant gap in empirical research on the nature and direction of these relationships. Therefore the purpose of this paper is to analyse how algorithmic management practices directly influence workplace well-being, as well as investigating its relationships with job autonomy and total rewards practices.Design/methodology/approachConceptual model of relationships between algorithmic management practices, job autonomy, total rewards and workplace well-being has been formulated on the basis of literature review. Proposed model has been empirically verified through confirmatory analysis by means of structural equation modelling (SEM CFA) on a sample of 21,869 European organisations, using data collected by Eurofound and Cedefop in 2019, with the focus of investigating the direct and indirect influence of algorithmic management practices on workplace well-being.FindingsThis research confirmed a moderate, direct impact of application of algorithmic management practices on workplace well-being. More importantly the authors found out that this approach has an indirect influence, through negative impact on job autonomy and total rewards practices. The authors observed significant variation in the level of influence depending on the size of the organisation, with the decreasing impacts of algorithmic management on well-being and job autonomy for larger entities.Originality/valueWhile the influence of algorithmic management on various workplace practices and effects is now widely discussed, the empirical evidence – especially for traditional work contexts, not only gig economy – is highly limited. The study fills this gap and suggests that algorithmic management – understood as an automated decision-making vehicle – might not always lead to better, well-being focused, people management in organisations. Academic studies and practical applications need to account for possible negative consequences of algorithmic management for the workplace well-being, by better reflecting complex nature of relationships between these variables.