bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similarities and distinctions in the activation of theCandida glabrataPdr1 regulatory pathway by azole and non-azole drugs
Authors: Conway Thomas P. , Vu Bao Gia , Beattie Sarah R. , Krysan Damian J. , Moye-Rowley W. Scott 
Published: September 2024

AbstractIncidences of fluconazole (FLC) resistance amongCandida glabrataclinical isolates is a growing issue in clinics. The pleiotropic drug response (PDR) network inC.glabrataconfers azole resistance and is defined primarily by the Zn2Cys6zinc cluster-containing transcription factor Pdr1 and target genes such asCDR1, that encodes an ATP-binding cassette transporter protein thought to act as a FLC efflux pump. Mutations in thePDR1gene that render the transcription factor hyperactive are the most common cause of fluconazole resistance among clinical isolates. The phenothiazine class drug fluphenazine and a molecular derivative, CWHM-974, which both exhibit antifungal properties, have been shown to induce the expression of Cdr1 inCandidaspp. We have used a firefly luciferase reporter gene driven by theCDR1promoter to demonstrate two distinct patterns ofCDR1promoter activation kinetics: gradual promoter activation kinetics that occur in response to ergosterol limitations imposed by exposure to azole and polyene class antifungals and a robust and rapidCDR1induction occurring in response to the stress imposed by fluphenazines. We can attribute these different patterns ofCDR1induction as proceeding through the promoter region of this gene since this is the only segment of the gene included in the luciferase reporter construct. Genetic analysis indicates that the signaling pathways responsible for phenothiazine and azole induction ofCDR1overlap but are not identical. The short time course of phenothiazine induction suggests that these compounds may act more directly on the Pdr1 protein to stimulate its activity.ImportanceCandida glabratahas emerged as the second-leading cause of candidiasis due in part to its ability to acquire high level resistance to azole drugs, a major class of antifungal, that acts to block the biosynthesis of the fungal sterol ergosterol. The presence of azole drugs causes the induction of a variety of genes involved in controlling susceptibility to this drug class including drug transporters and ergosterol biosynthetic genes such asERG11. We found that the presence of azole drugs leads to an induction of genes encoding drug transporters andERG11, while exposure ofC. glabratacells to antifungals of the phenothiazine class of drugs caused a much faster and larger induction of drug transporters but notERG11. Coupled with further genetic analyses of the effects of azole and phenothiazine drugs, our data indicate that these compounds are sensed and responded to differentially in the yeast cell.
Altered development and network connectivity in a human neuronal model of 15q11.2 deletion-related neurodevelopmental disorders
Authors: Habela Christa W. , Liu Shiyu , Taga Arens , Dastgheyb Raha , Haughey Norman , Bergles Dwight , Song Hongjun , Ming Guo-Li , Maragakis Nicholas J. 
Published: September 2024

AbstractThe chromosome 15q11.2 locus is deleted in 1.5% of patients with genetic epilepsy and confers a risk for intellectual disability and schizophrenia. Individuals with this deletion demonstrate increased cortical thickness, decreased cortical surface area and white matter abnormalities. Human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPC) from 15q11.2 deletion individuals exhibit early adhesion junction and migration abnormalities, but later neuronal development and function have not been fully assessed. Imaging studies indicating altered structure and network connectivity in the anterior brain regions and the cingulum suggest that in addition to alterations in progenitor dynamics, there may also be structural and functional changes within discrete networks of mature neurons. To explore this, we generated human forebrain cortical neurons from iPSCs derived from individuals with or without 15q11.2 deletion and used longitudinal imaging and multielectrode array analysis to evaluate neuronal development over time. 15q11.2 deleted neurons exhibited fewer connections and an increase in inhibitory neurons. Individual neurons had decreased neurite complexity and overall decreased neurite length. These structural changes were associated with a reduction in multiunit action potential generation, bursting and synchronization. The 15q11.2 deleted neurons also demonstrated specific functional deficits in glutamate and GABA mediated network activity and synchronization with a delay in the maturation of the inhibitory response to GABA. These data indicate that deletion of the 15q11.2 region is sufficient to impair the structural and functional maturation of cortical neuron networks which likely underlies the pathologic changes in humans with the 15q11.2 deletion.
Clustered macrophages cooperate to eliminate tumors via coordinated intrudopodia
Authors: Dooling Lawrence J. , Anlaş Alişya A. , Tobin Michael P. , Ontko Nicholas M. , Marchena Tristan , Wang Maximilian , Andrechak Jason C. , Discher Dennis E. 
Published: September 2024

AbstractMacrophages often pervade solid tumors, but their nearest neighbor organization is understudied and potentially enables key functions such as phagocytosis. Here, we observe dynamic macrophage clusters in tumors under conditions that maximize cancer cell phagocytosis and use reductionist approaches to uncover pathways to cluster formation and roles for tumor-intrusive pseudopodia, which we term ‘intrudopodia’. Macrophage clusters form over hours on low- adhesion substrates after M1 polarization with interferons, including T cell-derived cytokines, and yet clusters prove fluid on timescales of minutes. Clusters also sort from M2 macrophages that disperse on the same substrates. M1 macrophages upregulate specific cell-cell adhesion receptors but suppress actomyosin contractility, and while both pathways contribute to cluster formation, decreased cortical tension was predicted to unleash pseudopodia. Macrophage neighbors in tumor spheroids indeed extend intrudopodia between adjacent cancer cell junctions – at least when phagocytosis conditions are maximized, and coordinated intrudopodia help detach and individualize cancer cells for rapid engulfment. Macrophage clusters thereby provide a cooperative advantage for phagocytosis to overcome solid tumor cohesion.
Structure-guided engineering of type I-F CASTs for targeted gene insertion in human cells
Authors: Lampe George D. , Liang Ashley R. , Zhang Dennis J. , Fernández Israel S. , Sternberg Samuel H. 
Published: September 2024

ABSTRACTConventional genome editing tools rely on DNA double-strand breaks (DSBs) and host recombination proteins to achieve large insertions, resulting in a heterogeneous mixture of undesirable editing outcomes. We recently leveraged a type I-F CRISPR-associated transposase (CAST) from thePseudoalteromonasTn7016transposon (PseCAST) for DSB-free, RNA-guided DNA integration in human cells, taking advantage of its programmability and large payload capacity.PseCAST is the only characterized CAST system that has achieved human genomic DNA insertions, but multiple lines of evidence suggest that DNA binding may be a critical bottleneck that limits high-efficiency activity. Here we report structural determinants of target DNA recognition by thePseCAST QCascade complex using single-particle cryogenic electron microscopy (cryoEM), which revealed novel subtype-specific interactions and RNA-DNA heteroduplex features. By combining our structural data with target DNA library screens and rationally engineered protein mutations, we uncovered CAST variants that exhibit increased integration efficiency and modified PAM stringency. Structure predictions of key interfaces in the transpososome holoenzyme also revealed opportunities for the design of hybrid CASTs, which we leveraged to build chimeric systems that combine high-activity DNA binding and DNA integration modules. Collectively, our work provides unique structural insights into type I-F CAST systems while showcasing multiple diverse strategies to investigate and engineer new RNA-guided transposase architectures for human genome editing applications.
Higher resolution pooled genome-wide CRISPR knockout screening in Drosophila cells using Integration and Anti-CRISPR (IntAC)
Authors: Viswanatha Raghuvir , Entwisle Samuel , Hu Claire , Reap Kelly , Butnaru Matthew , Mohr Stephanie E. , Perrimon Norbert 
Published: September 2024

AbstractCRISPR screens enable systematic, scalable genotype-to-phenotype mapping. We previously developed a pooled CRISPR screening method forDrosophila melanogasterand mosquito cell lines using plasmid transfection and site-specific integration to introduce single guide (sgRNA) libraries, followed by PCR and sequencing of integrated sgRNAs. While effective, the method relies on early constitutive Cas9 activity that potentially can lead to discrepancies between genome edits and sgRNAs detected by PCR, reducing screen accuracy. To address this issue, we introduce a new method to co-transfect a plasmid expressing the anti-CRISPR protein AcrIIa4 to suppress Cas9 activity during early sgRNA expression, which we term “IntAC” (integrase with anti-CRISPR). IntAC allowed us to construct a new CRISPR screening approach driven by the high strengthdU6:3promoter. This new library dramatically improved precision-recall of fitness genes across the genome, retrieving 90-95% of essential gene groups within 5% error, allowing us to generate the most comprehensive list of cell fitness genes yet assembled forDrosophila. Our analysis determined that elevated sgRNA levels, made permissible by the IntAC approach, drove much of the improvement. TheDrosophilafitness genes show strong correlation with human fitness genes and underscore the effects of paralogs on gene essentiality. We further demonstrate that IntAC combined with a targeted sgRNA sub-library enabled precise positive selection of a transporter under solute overload. IntAC represents a straightforward enhancement to existingDrosophilaCRISPR screening methods, dramatically increasing accuracy, and might also be broadly applicable to virus-free CRISPR screens in other cell types, including mosquito, lepidopteran, tick, and mammalian cells.
The Penrose effect in the internationalization of professional service firms: an analysis of Japanese patent firms
Authors: Nakamoto Ryuichi , Chen Hao-Cheng , Noguchi Hiroki , Funatsu Shohei 
Published: September 2024

PurposeThe Penrose effect, or the limitation of the growth rate during expansion due to managerial constraints, has been examined in the context of business diversification, withdrawal and MNE’s foreign direct investment, primarily in the for-profit sector. However, insufficient attention has been paid to its impact on professional service firms, particularly in the context of their expansion through service exports. The main purpose of this study is to examine the Penrose effect in the internationalization of professional service firms through service exports.Design/methodology/approachThis study focuses on large Japanese patent firms as traditional professional service firms and constructs panel data for 48 large patent firms over the observation period from 2002 to 2010 to test our hypotheses.FindingsOur results demonstrate a negative relationship between degree of internationalization and international business growth, thus confirming the Penrose effect. Furthermore, we found that the degree of internationalization has a curvilinear relationship with international business growth and that institutional distance does not have a negatively moderating effect on the relationship between the degree of internationalization and international business growth.Originality/valueThis study made a theoretical contribution to Penrose's growth theory and previous studies on international management and professional service firms and international management by showing that the Penrose effect can be observed in the international expansion of professional service firms through service exports. Moreover, this study identifies the factors that modify the Penrose effect, thereby making a significant theoretical contribution.
Circular economy strategies for minimising construction waste in Sri Lanka: focus on the preconstruction stage
Authors: Victar Hasith Chathuranga , Waidyasekara K.G.A.S. 
Published: September 2024

Purpose
The concept of Circular Economy (CE) has gained significant traction in addressing the issue of Construction and Demolition (C&D) waste, which is generated because of global urbanisation and urban renewal. Therefore, this research aims to explore the applicability of CE strategies to minimise the C&D Waste Management (WM) issues in Sri Lanka considering the preconstruction stage of the building project.

Design/methodology/approach
The research adopted a qualitative approach, using three expert interview rounds with the Delphi technique. In each round, 17, 15 and 12 experts were involved. A manual content analysis method was used to analyse the collected data.

Findings
Findings uncovered effective strategies in CE to address the 14 issues within C&D WM and its effects on the project management iron triangle in Sri Lanka. Integrating CE strategies within the construction sector to tackle C&D WM issues can significantly contribute to establishing a more sustainable, robust and resource-conscious built environment. By adopting CE strategies such as design for adaptability of existing buildings and design for disassembly, construction projects can optimise the project's timeline, cost and quality factors.

Originality/value
This will help to minimise the demand for virgin materials and reduce the volume of waste generated. Using recycled materials also helps close the loop of the materials cycle, thereby contributing to the CE. Also, this research contributes uniquely by offering practical, context-driven solutions that align with Sri Lanka’s construction sector.
The risk transmission from the COVID-19 to MENA stock markets: what is the best safe haven asset during the pandemic?
Authors: Chkili Walid 
Published: September 2024

PurposeThis paper investigates potential safe haven assets for Middle East and North Africa (MENA) stock markets during the uncertainty period of the COVID-19 pandemic.Design/methodology/approachThis study applies the dynamic conditional correlation–generalized autoregressive conditionally heteroskedastic (DCC-GARCH) model and the Diebold–Yilmaz spillover index for ten MENA stock markets, three precious metals and Bitcoin for the period 2013–2021.FindingsEmpirical results show, on the one hand, that the COVID-19 crisis risk has been transmitted to MENA stock markets through volatility spillover across markets. This has increased the conditional volatility for all markets. On the other hand, findings point out that the dynamic correlation between the precious metals/Bitcoin and stock markets is not stable and switches between low positive and negative values during the period under studies. Extending analysis to portfolio management, results reveal that investors should include precious metals/Bitcoin in their portfolio of stocks in order to reduce the risk of the portfolio. Finally, for the period of COVID-19, the analysis concludes that gold preserves its traditional role as a safe haven for MENA stock markets during the pandemic, while Bitcoin fails to provide this property.Practical implicationsThese results have several implications for international investors, risk managers and financial analysts in terms of portfolio diversifications and hedging strategies. Indeed, the exploration of the volatility connectedness between financial, commodity and cryptocurrency markets becomes an essential task for all market participants during the COVID-19 outbreak. Such analysis can help investors and portfolio managers to evaluate the risk of investments in the MENA stock markets during the crisis period and to achieve the optimal diversification strategy and hedging instruments.Originality/valueThe paper interests MENA stock markets that experienced the last decade a substantial development in terms of market capitalization and number of listed firms. To the author’s knowledge, this is the first study that investigates the dynamic correlation between MENA stock markets and four potential safe haven assets, including three precious metals and Bitcoin. In addition, the paper employs two types of models, namely the DCC-GARCH model and the Diebold-Yilmaz spillover index.
Thermally radiative nanofluid heat transfer analysis inside a closed chamber with gyrotactic microorganisms
Authors: Sreedevi Paluru , Reddy P. Sudarsana 
Published: September 2024

Purpose
This paper aims to numerically examine the impact of gyrotactic microorganisms and radiation on heat transport features of magnetic nanoliquid within a closed cavity. Thermophoresis, chemical reaction and Brownian motion are also considered in flow geometry for the moment of nanoparticles.

Design/methodology/approach
Finite element method (FEM) was depleted to numerically approximate the temperature, momentum, concentration and microorganisms concentration of the nanoliquid. The present simulation was unsteady state, and the resulting transformed equations are simulated by FEM-based Mathematica algorithm.

Findings
It has been found that isotherm patterns get larger with increasing values of the magnetic field parameter. Additionally, numerical codes for rate of heat transport impedance inside the cavity with an increasing Brownian motion parameter values.

Originality/value
To the best of the authors’ knowledge, the research work carried out in this paper is new, and no part is copied from others’ works.
Effects of strategic value orientation on personal data privacy, value in use and organizational reputation
Authors: Durans Amilson de Araujo , Mainardes Emerson Wagner 
Published: September 2024

PurposeThis study assesses whether the strategic orientation of financial institutions to provide value to customers influences the dimensions of personal data privacy perceived by consumers of banking services. We also analysed whether these dimensions directly influence the value in use and, indirectly, the reputation of financial institutions.Design/methodology/approachBased on the literature, a model was developed to verify the proposed relationships. To test the model, we collected data via an online questionnaire from 2,422 banking customers, with analysis using structural equation modelling with partial least squares estimation.FindingsThe results suggest that strategic value orientation tends to have a direct positive influence on the constructs knowledge, control, willingness to value privacy and trust in sharing personal information and a direct negative influence on the personal data privacy experience. Three dimensions of personal data privacy (knowledge, willingness to value privacy and trust in sharing personal information) tend to have a direct positive influence on value in use. The results showed that the dimensions of personal data privacy experience and control had a significant and negative impact on the value in use construct. Another finding is the positive influence of value in use on organizational reputation. Investing in strategic value orientation can generate consumer perceptions of personal data privacy, which is reflected in the value in use and reputation of banks.Originality/valueThis study is theoretically original because it brings up the organizational reputation of financial institutions based on the strategic orientation to offer value to customers, personal data privacy and the value in use of banking services. The study of these relationships is unprecedented in the literature.
A mixed design study on challenges and experiences with gender diversity management in Ethiopian public higher education institutions
Authors: Assefa Easaw Alemayehu 
Published: September 2024

PurposeThis study explores the challenges and experiences associated with managing gender diversity in Ethiopian public higher education institutions (HEIs) to inform policies and practices for promoting gender equality and inclusivity. Therefore, examining and shedding light on the challenges and experiences of GDM in Ethiopian public HEIs is the main goal of the research, which also aims to make suggested improvements. It focuses on the perspectives of vice presidents, student deans, instructors, gender office deans and students from HEIs.Design/methodology/approachA mixed methods approach was used, with 395 respondents providing quantitative data and 34 respondents contributing qualitative data. Data collection involved four instruments: a survey questionnaire, interviews, observation and document analysis.FindingsThe study reveals diverse challenges and experiences related to gender diversity at the selected five Ethiopian public HEIs. Positive and negative instances of gender diversity management (GDM) were documented, highlighting the complexity of the issue. Despite the challenges, the study identified insightful scenarios that offer potential solutions.Originality/valueThis study is pioneering in its examination of the challenges and experiences of GDM in Ethiopian public HEIs. It provides a comprehensive understanding of gender diversity within the unique context of the Ethiopian HEIs.
Entrepreneurial actions under uncertainty: the role of psychological variables and decision logics
Authors: Ratinho Tiago , Sarasvathy Saras D. 
Published: September 2024

PurposeEntrepreneurial action under uncertainty has captured the interest of scholars and practitioners alike. However, this growing body of research has yet to connect entrepreneurial action with actual actions of entrepreneurs. We combine insights from effectuation theory and the psychology of entrepreneurship to investigate drivers of entrepreneurial actions involved in starting and running ventures, particularly optimism, self-efficacy and the use of causal and effectual logics.Design/methodology/approachThe study employs a unique mixed-method approach combining a survey with experience sampling data. After measuring demographics, preference for effectual or causal logics and psychological variables, the 197 US entrepreneurs sampled entrepreneurs logged their daily actions in the form of asks during 60 consecutive days.FindingsResults suggest that self-efficacy and causal logics are key drivers of entrepreneurial actions, while optimism serves as a deterrent. Interestingly, the impact of self-efficacy on actions is moderated by the entrepreneur’s experience level, measured both in years and past asking experience.Originality/valueThe potential of the ask as the basic mechanism for entrepreneurial actions is explored. Based on the findings, the authors offer new and fertile insights by linking psychological traits to entrepreneurial actions, causal and effectual logics and entrepreneurial expertise development.