bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matrisome gene expression is altered during non-allometric heart growth in genetically enlargedDrosophila
Authors: Andrews Rachel M. , Jacobs J. Roger 
Published: March 2024

AbstractThe cardiac extracellular matrix (ECM) is critical to defining the biophysical properties of the heart that adapt to changing stresses with growth or disease. The ECM is commonly dysregulated in chronic disease such as hypertension, diabetes, and cardiomyopathies, often leading to the development of fibrosis. There are no treatment options to address most ECM cardiomyopathies, but developing therapeutic targets necessitates an understanding of the regulation of ECM remodelling. Here, we employ a larvalDrosophilaovergrowth model (“giant larvae”) to overload the heart and alter ECM remodellingin vivo. These larvae grow to immense sizes without exhibiting hallmarks of obesity. Remarkably, cardiac ECM organization scales allometrically despite overload. The main effect observed is a change in Collagen fibril thickness, possibly reflecting changes to tension in the system. Overgrowth-induced changes in gene expression similarly suggest changes in Collagen assembly, such as a dramatic increase in LOXL2, the main Collagen crosslinking enzyme. This could indicate that larvae may compensate for the stress of overgrowth by stabilizing the Collagen network. The enlarged hearts of giant larvae cannot contract fully at systole. Taken together, this reveals non-allometric changes to cardiac form and output with increasing body size. Overall, our overgrowth model presents an intriguing opportunity to examine the ability of a system to tolerate overgrowth without the metabolic inputs of obesity.
Stochastic variation in the FOXM1 transcription program mediates replication stress tolerance
Authors: Segeren Hendrika A. , Wierenga Kathryn A. , Riemers Frank M. , van Liere Elsbeth A. , Westendorp Bart 
Published: March 2024

AbstractOncogene-induced replication stress (RS) is a vulnerability of cancer cells that forces reliance on the intra-S-phase checkpoint to ensure faithful genome duplication. Inhibitors of the crucial intra-S-phase checkpoint kinases ATR and CHK1 have been developed, but persistent proliferation and resistance to these drugs remain problematic. Understanding drug tolerance mechanisms is impeded by analysis of bulk samples, which neglect tumor heterogeneity and often fail to accurately interpret cell cycle-mediated resistance. Here, by combining intracellular immunostaining and RNA-sequencing of single cells, we characterized the transcriptomes of oncogenic RAS-expressing cells that exhibit variable levels of RS when challenged with a CHK1 inhibitor in combination with the chemotherapeutic drug gemcitabine. We identified 40 genes differentially expressed between tolerant and sensitive cells, including several FOXM1 target genes. While complete knockdown ofFOXM1impeded cell proliferation, a partial knockdown protected cells against DNA damage, and improved recovery from drug-induced RS. Our results suggest that low levels of FOXM1 expression protects subsets of oncogenic RAS-expressing cells against DNA damage during drug-induced replication stress.
Linked emergence of racial disparities in mental health and epigenetic biological aging across childhood and adolescence
Authors: Aikins Muna , Willems Yayouk , Mitchell Colter , Goosby Bridget , Raffington Laurel 
Published: March 2024

AbstractMarginalization due to structural racism may confer an increased risk for aging-related diseases – in part – via effects on people’s mental health. Here we leverage a prospective birth cohort study to examine whether the emergence of racial disparities in mental health and DNA-methylation measures of biological aging (i.e., DunedinPACE, GrimAge Acceleration, PhenoAge Acceleration) are linked across childhood and adolescence. We further consider to what extent racial disparities are statistically accounted for by perinatal and postnatal factors in preregistered analyses of N=4,898 participants from the Future of Families & Child Wellbeing Study, of which N=2,039 had repeated saliva DNA methylation at ages 9 and 15 years. We find that racially marginalized children had higher levels of externalizing and internalizing behaviors and diverging longitudinal internalizing slopes. Black compared to White identifying children, children living in more racially segregated neighborhoods, and racially marginalized children more affected by colorism tended to have higher age-9 levels of biological aging and more biological age acceleration over adolescence. Notably, longitudinal increases in internalizing and externalizing behavior were correlated with longitudinal increases in biological aging. While racial and ethnic disparities in mental health were largely statistically accounted for by socioeconomic variables, racial differences in biological aging were often still visible beyond covariate controls. Our findings indicate that racial disparities in mental health and biological aging are linked and emerge early in life. Programs promoting racial health equity must address the psychological and physical impacts of structural racism in children. Comprehensive measures of racism are lacking in current population cohorts.
Repetitive head impacts induce neuronal loss and neuroinflammation in young athletes
Authors: Butler Morgane L.M.D. , Pervaiz Nida , Breen Kerry , Calderazzo Samantha , Ypsilantis Petra , Wang Yichen , Breda Julia Cammasola , Mazzilli Sarah , Nicks Raymond , Spurlock Elizabeth , Hefti Marco M. , Fiock Kimberly L. , Huber Bertrand R. , Alvarez Victor E. , Stein Thor D. , Campbell Joshua D. , McKee Ann C. , Cherry Jonathan D. 
Published: March 2024

AbstractRepetitive head impacts (RHI) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE). Currently, CTE can only be diagnosed after death and the multicellular cascade of events that trigger initial hyperphosphorylated tau (p-tau) deposition remain unclear. Further, the symptoms endorsed by young individuals with early disease are not fully explained by the extent of p-tau deposition, severely hampering development of therapeutic interventions. Here, we show that RHI exposure associates with a multicellular response in young individuals (<51 years old) prior to the onset of CTE p-tau pathology that correlates with number of years of RHI exposure. Leveraging single nucleus RNA sequencing of tissue from 8 control, 9 RHI-exposed, and 11 low stage CTE individuals, we identify SPP1+ inflammatory microglia, angiogenic and inflamed endothelial cell profiles, reactive astrocytes, and altered synaptic gene expression in excitatory and inhibitory neurons in all individuals with exposure to RHI. Surprisingly, we also observe a significant loss of cortical sulcus layer 2/3 neurons in contact sport athletes compared to controls independent of p-tau pathology. Finally, we identify TGFB1 as a potential signal mediating microglia-endothelial cell cross talk through ligand-receptor analysis. These results provide robust evidence that multiple years of RHI exposure is sufficient to induce lasting cellular alterations that may underlie p-tau deposition and help explain the early pathogenesis in young former contact sport athletes. Furthermore, these data identify specific cellular responses to repetitive head impacts that may direct future identification of diagnostic and therapeutic strategies for CTE.
The plant specific cohesin subunit SYN4 contributes to 3D genome organization
Authors: Paajanen Pirita , Proksch Carsten , Krüger Sylvia , Gorzolka Karin , Ziegler Jörg , Romeis Tina , Dodd Antony N. , Bomblies Kirsten , Handrick Vinzenz 
Published: March 2024

SummaryChromatin architecture in the cells of animals and fungi influences gene expression. The molecular factors that influence higher genome architecture in plants and their effects on gene expression remain unknown. Cohesin complexes, conserved in eukaryotes, are essential factors in genome structuring. Here, we investigated the relevance of the plant-specific somatic cohesin subunit SYN4 for chromatin organisation inArabidopsis thaliana.Plants mutated inSYN4were studied using HRM, Hi-C, RNA sequencing, untargeted and targeted metabolomics and physiological assays to understand the role of this plant-specific cohesin.We show thatsyn4mutants exhibit altered intra- and interchromosomal interactions, expressed as sharply reduced contacts between telomeres and chromosome arms but not between centromeres, and differences in the placement and number of topologically associated domains (TADs)-like structures. By transcriptome sequencing, we also show thatsyn4mutants have altered gene expression, including numerous genes that control abiotic stress responses.The response to drought stress inArabidopsisis strongly influenced by the genome structure insyn4mutants, potentially due to altered expression ofCYP707A3, an ABA 8’-hydroxylase.In briefThe 3D architecture of the genome extensively influences gene expression in animals and fungi. We show that the plant-specific cohesin subunit SYN4 affects intra- and interchromosomal interactions including telomere clustering, with consequences for the expression of genes of transient and induced biological pathways and the biosynthesis of bioactive compounds. Highly condensed genome structures at theCYP707A3locus positively affects the stress response to water deprivation regulated by abscisic acid.
Type 1 diabetes and parasite infection: an exploratory study in the NOD mouse
Authors: Giraud Emilie , Fiette Laurence , Melanitou Evie 
Published: March 2024

AbstractMicroorganisms have long been suspected to influence the outcome of immune-related syndromes, particularly autoimmune diseases. Type 1 diabetes (T1D) results from the autoimmune destruction of the pancreatic islets’ insulin-producing beta cells, causing high glycemia levels. Genetics is part of its etiology, but environmental factors, particularly infectious microorganisms, also play a role.It was shown that bacteria, viruses, and parasites, influence the outcome of T1D in mice and humans. We have used the Non-Obese Diabetic (NOD) mouse that spontaneously develops T1D to address the influence of a parasitic infection, leishmaniasis.Leishmania amazonensisare intracellular eukaryotic parasites replicating predominantly in macrophages and are responsible for cutaneous leishmaniasis. The implication of Th1 immune responses in T1D and leishmaniasis led us to study this parasite in the NOD mouse model. We have previously constructed osteopontin knockout mice in an NOD genetic background and demonstrated that this protein plays a role in the T1D phenotype. In addition, osteopontin (OPN) has been found i) to play a role in the immune response to various infectious microorganisms and ii) to be implicated in other autoimmune conditions, such as multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in mice.We present herein data demonstrating the implication of OPN in the response toLeishmaniain the NOD mouse and the influence of this parasitic infection on T1D. This exploratory study aims to investigate the environmental infectious component of the autoimmune response, including through Th1 immunity, common to both T1D and leishmaniasis.
Developing a multidimensional risk assessment model for sustainable construction projects
Authors: Wuni Ibrahim Yahaya 
Published: March 2024

PurposeSustainable construction re-engineers the conventional project lifecycle to integrate sustainability solutions. The additional sustainability requirements introduce new layers of complexity, challenges and risks that if unaddressed, can derail the gains in sustainable construction projects. This study developed a multidimensional risk assessment model for sustainable construction projects in the United Arab Emirates (UAE).Design/methodology/approachThe research activities a comprised comprehensive literature review to shortlist relevant risks, an analysis of the probability – impact rating of the shortlisted risks – and the development of a risk assessment model for SC projects in the UAE. The model is developed based on the multicriteria framework and mathematical formulation of the fuzzy synthetic evaluation approach.FindingsThe developed model quantified the overall risk level in sustainable construction projects to be 3.71 on a 5-point Likert scale, indicating that investment in SC projects in the UAE is risky and should be carefully managed. The developed model further revealed that each of the risk groups, comprising management (3.82), technical (3.78), stakeholder (3.68), regulatory (3.66), material (3.53) and economic risks (3.502), presents a significant threat to realizing outcomes typical of SC projects.Originality/valueThis study developed a multidimensional risk assessment model capable of objectively quantifying the overall risk level and provides decision support to project teams to improve risk management in sustainable construction projects.
Hybrid entrepreneurship, job satisfaction and the spillover effect of creativity
Authors: Crider Cole J. , Aghaey Alireza , Lortie Jason , Peake Whitney O. , Digan Shaun 
Published: March 2024

PurposeThe purpose of this study is to empirically examine how individuals’ hybrid entrepreneurial venturing activities (HEVA) influence key characteristics associated with one’s wage work, namely creativity and job satisfaction.Design/methodology/approachThrough a cross-sectional self-administered survey design, data were gathered from 465 US-based useable responses via Amazon Mechanical Turk and analyzed using structural equation modeling (SEM).FindingsFindings show individuals reporting higher levels of HEVA – such as creating, founding, starting or running – tend to also exhibit higher levels of creativity and job satisfaction in their workplaces. Findings further reveal that income negatively moderates the relationship between creativity and wage work job satisfaction.Practical implicationsBy providing a better understanding of how engaging in HEVA can impact creativity and job satisfaction, this study has important implications for (1) managers seeking to influence key employee outcomes and (2) employees considering such entrepreneurial activities.Originality/valueThis paper adds to the growing scholarly and practitioner interest in hybrid entrepreneurship and its outcomes. Specifically, the paper adds new insights regarding how engaging in HEVA can influence individual skills (i.e. creativity) or organizational goals (i.e. employee job satisfaction). In doing so, the paper also uses insights from the intrinsic/extrinsic motivation literature to suggest how extrinsic motivators (such as income) can interact with intrinsically motivated behaviors (such as creativity) in influencing employee outcomes in wage work. Finally, the paper contributes to the growing interest in applying the empowerment perspective within entrepreneurship research by exploring where and how empowerment may occur.
Labour mobility, short-time work and working from home: establishments' behaviour during the COVID-19 crisis
Authors: Bellmann Lisa , Bellmann Lutz , Hübler Olaf 
Published: March 2024

PurposeWe enquire whether short-time work (STW) avoids firings as intended by policymakers and is associated with unintended side effects by subsidising some establishments and locking in some employees. Additionally, where it was feasible, establishments used working from home (WFH) to continue working without risking an increase in COVID-19 infections and allowing employed parents to care for children attending closed schools.Design/methodology/approachUsing 21 waves of German high-frequency establishment panel data collected during the COVID-19 crisis, we investigate how STW and WFH are associated with hirings, firings, resignations and excess labour turnover (or churning).FindingsOur results show the important influences of STW and working from home on employment dynamics during the pandemic. By means of STW, establishments are able to avoid an increase in involuntary layoffs and hiring decreases significantly. In contrast, WFH is associated with a rise in resignations, as can be expected from a theoretical perspective.Originality/valueWhile most of the literature on STW and WFH is unrelated and remains descriptive, we consider them in conjunction and conduct panel data analyses. We apply data and methods that allow for the dynamic pattern of STW and working from home during the pandemic. Furthermore, our data include relevant establishment-level variables, such as the existence of a works council, employee qualifications, establishment size, the degree to which the establishment was affected by the COVID-19 crisis, industry affiliation and a wave indicator for the period the survey was conducted.
From virtual reality to cultural reality: integration of virtual reality into teaching culture in foreign language education
Authors: Tafazoli Dara 
Published: March 2024

Purpose
This research paper aimed to investigate the affordances of using virtual reality (VR) in teaching culture among in-service teachers of teaching Persian to speakers of other languages (TPSOL) in Iran.

Design/methodology/approach
This qualitative case study, conducted at two Iranian universities, used purposeful sampling to select 34 eligible in-service Persian teachers from a pool of 73. Data collection used an open-ended questionnaire and interviews.

Findings
Before the TPSOL in-service training workshop, teachers expressed their reservations regarding the use of VR to teach culture in TPSOL courses. The emerged themes were “skepticism toward effectiveness,” “practicality concerns,” “limited awareness of VR applications,” “technological apprehension” and “prevalence of traditional teaching paradigms.” During the post-workshop interview, it was discovered that the teachers’ perceptions of VR in teaching culture had undergone a positive shift. The workshop generated emergent themes that reflected positive perceptions and affordances for using VR to teach culture in TPSOL, including “enhanced cultural immersion,” “increased student engagement,” “simulation of authentic cultural experiences,” and “facilitation of interactive learning environments.”

Research limitations/implications
One primary limitation is the lack of prior experience with VR for teaching practices in real-world classrooms among the participants. While the study aimed to explore the potential of VR in enhancing pedagogical approaches, the absence of participants with prior exposure to VR in educational contexts may impact the generalizability of the findings to a broader population. Additionally, the study faced practical constraints, such as the unavailability of sufficient facilities in the workshop. As a result, the instructor had to project the VR cont7ent on a monitor, potentially diverging from the immersive nature of true VR experiences. These limitations offer opportunities for future research to refine methodologies and gain a more comprehensive understanding of the implications of integrating VR into teaching practices.

Originality/value
Extensive research has been conducted on the effectiveness of VR in language education. However, there is a significant gap in research on TPSOL, which is considered a less commonly taught language. This study aims to address this gap by exploring the use of VR in the TPSOL through the lenses of in-service teachers. As part of a larger investigation, this qualitative inquiry focuses on the perceptions of in-service teachers about VR, with a particular emphasis on the cultural understanding of the Persian language.
Analyzing the drivers of blockchain adoption for supply chain in Pakistan
Authors: Khalil Muhammad Mohsin , Ahmed Waqar 
Published: March 2024

Purpose
In recent years, technological advancement has played a crucial role in the growth of emerging economies. However, as with any novel technological development, there are often concerns and hesitations surrounding its implementation. This study aims to investigate the factors influencing blockchain adoption and usage. Thereby evaluating its impact on supply chain performance.

Design/methodology/approach
This is a deductive research based on the modified form unified theory of acceptance and use of technology, which is a persuasive model that has been used in numerous studies on the acceptance and usage of information technology systems. For this study, valid data was collected from 129 management-level supply chain professionals and policymakers working in diverse manufacturing industries. The collected data was used for testing hypotheses by deploying the structural equation modeling technique.

Findings
The findings of this study reveal that facilitating conditions and technology readiness highly are key influencers for organizations to implement this disruptive technology. Moreover, blockchain adoption and usage can significantly enhance supply chain performance.

Originality/value
Blockchain technology is a novel and promising disruptive technology that industries are looking forward to adopting and using. For the policymakers and supply chain strategists working in a developing country, this study offers a comprehensive viewpoint on the swift acceptance and usage of blockchain technology to facilitate supply chain operations.
The Historic, Present and Future Role of Regulation in Securing the Standards of ‘Public Value’ Media
Authors: Hughes Jacquie 
Published: March 2024

AbstractThis article examines the evolution of public service broadcasting (PSB) regulation in the UK, contrasting two opposing perspectives on its role and addressing its contemporary challenges. Analysing the historical context and recent regulatory changes, the article argues that PSB remains vital to the UK's media landscape, providing high quality content and serving the public good. However, it identifies technological advancements and political interference as significant threats to its continued success. The article critically evaluates the draft Media Bill's potential to address these challenges and enhance PSB's competitiveness. Additionally, it raises concerns about potential bias within the regulatory body, Ofcom, urging greater transparency and fairness in its oversight of the media market. The article emphasises the need for a robust regulatory framework to ensure the continued viability of PSB and foster a vibrant and diverse media ecosystem.
BBC Funding: Much Ado about the Cost of a Coffee a Week
Authors: Barwise Patrick 
Published: March 2024

AbstractBBC funding (the licence fee model and the funding level) has been turned into a big issue out of all proportion to the low financial stakes—equivalent to the cost of one takeaway coffee a week for the whole household, excluding those with free TV licences. This article first proposes and explores three possible reasons for all the fuss: that licence payers take the BBC for granted, underestimating the value they get from it; that the attacks on BBC funding are part of a wider ‘war’ against it, driven by commercial or political vested interests; and that at least some of the criticisms of the licence fee reflect genuine, although much exaggerated, disadvantages. The article then evaluates four alternative funding models: advertising, subscriptions, general taxation and a universal household levy. It argues that the best long‐term model would be a flat, universal household levy, with exemptions for those least able to pay, as in Germany, with the funding level set by an independent body organised by Ofcom; and that, because the licence fee is becoming harder to sustain, this new funding model should be introduced at the start of the next BBC Charter in January 2028.