bluuebunny/crossref_metadata_2025_split huggingface dataset:
A deficiency screen of theXchromosome for Rap1 GTPase dominant interacting genes inDrosophilaborder cell migration
Authors: Messer C. Luke , Burghardt Emily , McDonald Jocelyn A. 
Published: January 2025

AbstractCollective cell migration is critical to embryonic development, wound healing, and the immune response, but also drives tumor dissemination. Understanding how cell collectives coordinate migration in vivo has been a challenge, with potential therapeutic benefits that range from addressing developmental defects to designing targeted cancer treatments. The small GTPase Rap1 has emerged as a regulator of both embryogenesis and cancer cell migration. How active Rap1 coordinates downstream signaling functions required for coordinated collective migration is poorly understood.Drosophilaborder cells undergo a stereotyped and genetically tractable in vivo migration within the developing egg chamber of the ovary. This group of 6-8 cells migrates through a densely packed tissue microenvironment and serves as an excellent model for collective cell migration during development and disease. Rap1, like all small GTPases, has distinct activity state switches that link extracellular signals to organized cell behaviors. Proper regulation of Rap1 activity is essential for successful border cell migration yet the signaling partners and other downstream effectors are poorly characterized. Using the known requirement for Rap1 in border cell migration, we conducted a dominant suppressor screen for genes whose heterozygous loss modifies the migration defects observed upon constitutively activeRap1V12expression. Here we identified seven genomic regions on theXchromosome that interact withRap1V12. We mapped three genomic regions to single Rap1-interacting genes,frizzled 4,Ubiquitin specific protease 16/45, andstrawberry notch. Thus, this unbiased screening approach identified multiple new candidate regulators of Rap1 activity with roles in collective border cell migration.
Norditerpene natural products from subterranean fungi with anti-parasitic activity
Authors: Kolas Alexandra , Rusman Yudi , Maia Ana C.G. , Williams Jessica , Fumuso Fernanda G. , Cotto-Rosario Alexis , Onoh Chidiebere , Baggar Hanen , Piaskowski Mary L. , Baigorria Christian , Paes Raphaella , Chakrabarti Debopam , Weible Lyssa , Ojo Kayode K. , O’Connor Roberta M. , Salomon Christine E. 
Published: January 2025

AbstractCryptosporidiumis a common, waterborne gastrointestinal parasite that causes diarrheal disease worldwide. Currently there are no effective therapeutics to treat cryptosporidiosis in at-risk populations. Since natural products are a known source of anti-parasitic compounds, we screened a library of extracts and pure natural product compounds isolated from bacteria and fungi collected from subterranean environments for activity againstCryptosporidium parvum. Eight structurally related norditerpene lactones isolated from the fungusOidiodendron truncatumcollected from the Soudan Iron mine in Minnesota showed potent activity and were further tested to identify the most active compounds. The availability of a diverse suite of natural structural analogs with varying activities allowed us to determine some structure activity relationships for both anti-parasitic activity as well as cytotoxicity. The two most potent compounds, oidiolactones A and B, had EC50s against intracellularCryptosporidium parvumof 530 and 240 nM respectively without cytotoxicity to confluent HCT-8 host cells. Both compounds also inhibited the related parasiteToxoplasma gondii. Oidiolactone A was active against asexual, but not sexual, stages ofC. parvum, and killed 80% of the parasites within 8 hours of treatment. This compound reducedC. parvuminfection by 70% in IFNγ−/− mice, with no signs of toxicity. The high potency, low cytotoxicity, andin vivoactivity combined with high production, easy isolation from fungi, and synthetic accessibility make oidiolactones A and B attractive scaffolds for the development of new anti-Cryptosporidiumtherapeutics.
Polarization light-sheet microscopy and tomography (PLµTo) for flow-based imaging of 3D microcarrier mesenchymal stem cell culture
Authors: Benavides Oscar R. , White Berkley P. , Kaunas Roland , Gregory Carl A. , Walsh Alex J. 
Published: January 2025

AbstractLight-sheet microscopy is an increasingly popular imaging tool for studying biological processes, however, it generally requires the use of exogenous fluorescent contrast agents which can be toxic to live cells. Light-sheet tomography is the label-free analog of light-sheet microscopy, utilizing elastic scattering contrast to visualize the structure of the biological sample. Here, we present a multi-modal polarization light-sheet microscopy and tomography (PLµTo) system for on-line, non-destructive, and non-invasive volumetric imaging of human mesenchymal stem cells, also referred to as mesenchymal stromal cells, attached to spherical gelatin methacryloyl microcarriers for image analysis-based quantitative monitoring of adherent stem cell culture expansion. The PLµTo system, which is built on an inverted selective plane illumination configuration, is compatible with standard horizontal sample mounting and microfluidics for multimodal volumetric data acquisition. This work is the first demonstration of scattering-based volume optical imaging flow cytometry.
FGF12A Regulates Nav1.5 via CaM-regulated and CaM-independent Mechanisms
Authors: Woodbury Lucy , Angsutararux Paweorn , Marras Martina , Wagner Emily , Abella Carlota , Li Anna , Silva Jonathan R. 
Published: January 2025

AbstractOpening of the cardiac voltage-gated Na+ channel (Nav1.5) is responsible for robust depolarization of the cardiac action potential, while inactivation, which rapidly follows, allows for repolarization. Regulation of both the voltage- and time-dependent kinetics of Nav1.5 inactivation can alter the ability of the heart to initiate and sustain a re-entrant arrhythmia. The C-terminal domain (CTD) of Nav1.5 has been shown to modulate fast inactivation of the channel, and multiple auxiliary proteins bind to the CTD, including calmodulin (CaM) and intracellular fibroblast growth factor 12A (FGF12A). Recently, a non-canonical CaM-binding site was also discovered on the N-terminal of A-splice variants of iFGFs. We performed cut-open Vaseline gap (COVG) voltage-clamp to test whether FGF12A with and without CaM regulates Nav1.5 gating. In WT Nav1.5 channels, FGF12A with and without CaM present had a minimal effect on the voltage dependence of both activation and inactivation. Conversely, when CaM is absent on the Nav1.5 CTD (IQ/AA), a dramatic shift in steady-state inactivation (SSI) occurred, regardless of whether CaM was present on FGF12A. These two distinct mechanisms are operative in Nav1.5 LQT3 mutations where FGF12A requires CaM to shift in the voltage-dependence of inactivation, but not to inhibit the persistent late current. We conclude that there are two distinct mechanisms by which FGF12A modulates the Nav1.5 channel: CaM-regulated alteration of the voltage dependence of inactivation and CaM-independent inhibition of persistent late current.
Dissecting the Role of Flagellar Subunits inC. difficileMucosal Colonization
Authors: Biwas Baishakhi , Do Thi Van Thanh , Auchtung Jennifer , Piepenbrink Kurt H. 
Published: January 2025

AbstractClostridioides difficileis a common cause of acute gastrointestinal (GI) inflammation in mammals, which can have detrimental effects on host health.C. difficileassociated disease (CDAD) requires the secretion of high-molecular weight toxins after colonization of the GI tract. The molecular mechanisms of GI colonization byC. difficile, include potential interactions with host cells and the mucus layer formed from secreted mucin glycoproteins.C. difficileassociates with the mucus layerin vivoand will associate with both epithelial cells and mucosal surfacesin vitro. Previously, we found a substantial defect in binding to mucosal surfaces for mutants of the major flagellar subunit,fliC, while mutation of the major subunit of type IV pili,pilA1, showed increased adhesion. To elucidate the mechanisms by whichC. difficileinteracts withex vivomucosal surfaces, we have measured swimming motility, mucosal adhesion and levels of flagellation by transmission electron microscopy for mutants of flagellar and T4P genes inC. difficileR20291. We discovered that thepilA1mutant showed increased flagellation, while decreases in flagellation were found forfliC, fliD,andflg-OFF (a phase-locked mutant with low transcription of the F3 flagellar operon) which were associated with both low swimming motility and low adhesion to mucosal surfaces. However, the reversedflg-ON mutant showed increased flagellation without a significant increase in adhesion. We also found that thefliCmutant was defective in binding to mucus-secreting HT-29 MTX cells, but not HT-29 cells. These results imply that at least two molecular pathways contribute toC. difficilemucosal adhesion. In addition to their direct roles encoding T4P and flagellar subunits,pilA1andfliCmay contribute to regulating other factors relevant to mucosal adhesion.
Cross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles
Authors: Fan Chengcheng , Keeffe Jennifer R. , Malecek Kathryn E. , Cohen Alexander A. , West Anthony P. , Baharani Viren A. , Rorick Annie V. , Gao Han , Gnanapragasam Priyanthi N.P. , Rho Semi , Alvarez Jaasiel , Segovia Luisa N. , Hatziioannou Theodora , Bieniasz Paul D. , Bjorkman Pamela J. 
Published: January 2025

AbstractTherapeutic monoclonal antibodies (mAbs) against SARS-CoV-2 become obsolete as spike substitutions reduce antibody binding. To induce antibodies against conserved receptor-binding domain (RBD) regions for protection against SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD-nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles. Here, we describe neutralizing mAbs from mosaic-8b–immunized rabbits, some on par with Pemgarda (the only currently FDA-approved therapeutic mAb). Deep mutational scanning,in vitroselection of spike resistance mutations, and cryo-EM structures of spike-antibody complexes demonstrated targeting of conserved epitopes. Rabbit mAbs included critical D-gene segment features in common with human anti-RBD mAbs, despite rabbit genomes lacking an equivalent human D-gene segment. Thus, mosaic RBD-nanoparticle immunization coupled with multiplexed screening represent an efficient way to generate and select therapeutic pan-sarbecovirus and pan-SARS-2 variant mAbs.
Enhancing Breast Cancer Classification with Stacked Convolutional Neural Networks for Whole-Slide Image Analysis
Authors: Mujawar Tasmiya 
Published: January 2025

AbstractThis study explores an advanced approach to automatic breast cancer characterization by leveraging convolutional neural networks (CNNs) trained on 224×224 pixel patches from whole-slide images (WSIs). I compared two architectures, VGG-16 and WRN-4-2, across two classification problems: benign versus cancer, and benign, DCIS, versus IDC. Results indicated that WRN-4-2 slightly outperformed VGG-16 on the two-class problem but underperformed on the three-class problem. Stacking CNNs with increased input sizes (512×512, 768×768, and 1024×1024 pixels) significantly improved accuracy, with the 1024×1024 network achieving the highest performance but at a higher computational cost. Dense prediction maps were generated from these stacked networks, enabling effective whole-slide image classification with approximately 90% accuracy for detecting cancer. However, performance for distinguishing between benign, DCIS, and IDC lesions was lower at 76.6%. Future improvements could involve stain standardization, enhanced resolution of prediction maps using architectures like U-net, and comparative studies of multi-resolution approaches to further refine cancer detection and classification accuracy.
Loss of DHX36/G4R1, a G4 resolvase, drives genome instability and regulates innate immune gene expression in cancer cells
Authors: Bartosik Anna R. , Hou Pei-Chi , Vaughn James P. , Smaldino Philip J. , Ratan Aakrosh , Mayo Marty W. , Yuh-Hwa Wang 
Published: January 2025

SUMMARYG-quadruplexes (G4s) are four-stranded alternative secondary structures formed by guanine-rich nucleic acids and are prevalent across the human genome. G4s are enzymatically resolved using specialized helicases. Previousin vitrostudies showed that DEAH-box Helicase 36 (DHX36/G4R1/RHAU), has the highest specificity and affinity for G4 structures. Here, by mapping genome-wide DNA double-strand breaks (DSBs), we demonstrate that knockout (KO) of DHX36 helicase increases DSB enrichment at G4 sites and that the presence of the G4 motif is a significant mediator of genome instability at regulatory regions. The loss of DHX36 corresponds with the significant upregulation of NF-κB transcriptional programs, culminating in the production and secretion of proinflammatory cytokines. Loss of DHX36 expression results in an increase in the innate immune signaling stimulator of interferon response cGAMP interactor 1 (STING1) expression and activation of genes involved in immune response pathways. Importantly, higher levels ofDHX36mRNA expression in human B-cell acute lymphoblastic leukemia correlate with improved overall survival relative to lower expression ofDHX36, highlighting its critical role in preserving genome integrity at a cellular level and in the context of cancer.
Mutant p53R175H-Associated Protection of Ovarian Cancer Precursor Cells from Cisplatin Requires Expression of SLC6A6 Taurine Transporter
Authors: Polotaye Teagan , Centeno Daniel , Iwanicki Marcin 
Published: January 2025

ABSTRACTTumor suppressor gene TP53 is ubiquitously mutated in ovarian cancer precursor lesions that undergo pervasive accumulation of DNA damage. Prior literature provides evidence that the expression of mutant p53 protein in epithelial cells is associated with increased survival in response to DNA-damaging treatments. Hence, identification and understanding of the mechanisms that, in response to DNA damage accumulation, support survival of ovarian cancer precursor cells carrying p53 mutations might provide important information about the evolution of the disease. Here we used a combination of OC precursor cell models, biochemistry, microscopy, and flow cytometry to provide evidence that the taurine transporter, the SLC6A6 molecule, contributes to cell protection from DNA-damaging (cisplatin) treatment. We found that expression of mutant p53R175Hin OC precursor cells, the fallopian tube non-ciliated epithelial (FNE) cells, induced resistance to the DNA-damaging agent cisplatin. Most importantly, shRNA-mediated targeting of SLC6A6 transcript re-sensitized FNE cells expressing mutant p53R175Hto cisplatin treatment. Our studies are consistent with the model that the loss of SLC6A6 alters mechanisms involved in the regulation of cell survival in response to DNA damage.
Corporate culture and discontinued operations
Authors: Sun Li 
Published: January 2025

PurposeWe investigate the relation between corporate culture and the likelihood of discontinuing business operations.Design/methodology/approachWe rely on regression analysis in our study.FindingsWe find a significant negative relation, suggesting that firms with strong corporate culture are less likely to discontinue business operations. To enhance the incremental contributions of our study, we delve into the moderating role of corporate culture on the aforementioned relation and identify several factors that, when coupled with corporate culture, could indirectly impact the decision-making process regarding discontinuing operations. We also find that the negative relation between corporate culture and discontinued operations is mainly driven by firms with lower earnings performance, and this relation becomes stronger for high-tech firms. Lastly, we find that stronger culture is associated with a larger magnitude of discontinued operations for firms reporting discontinued operations, and this positive association is largely driven by firms reporting income-decreasing discontinued operations.Originality/valueOur analysis adds to two independent streams of research: corporate culture in management literature and discontinued operations in accounting literature. Prior research, in particular, focuses on examining if and how managers exploit discontinued operations to manipulate earnings. By showing a significant negative impact of corporate culture on the likelihood of discontinuing business operations, our research undoubtedly adds to the body of understanding regarding the factors that lead managers to discontinue certain operations.
Innovation management and nanotechnology: a PRISMA-based analysis and research implications
Authors: Rajapaksha Sisitha , Yapa Piumika , Munaweera Imalka 
Published: January 2025

Purpose
Innovation management in nanotechnology entails the strategic supervision of the entire process of creating and executing novel concepts, technologies and products at the nanoscale. By efficiently overseeing innovation in nanotechnology, organizations can leverage the revolutionary capabilities of nanomaterials and nanodevices to develop state-of-the-art solutions, improve their competitive edge and tackle global issues. Bibliometric studies are scarce related to the field of innovation management and nanotechnology. The purpose of this study is to assess the existing knowledge pertaining to the keywords, innovation management and nanotechnology and identify potential research implications for the future.

Design/methodology/approach
This study has been conducted systematically using the revolutionary PRISMA methodology. Research articles (46) were retrieved from Scopus and Web of Science databases using the keywords “Nanotechnology” and “Innovation Management” and 22 articles were systematically selected. VOSviewer software was used to conduct keyword co-occurrence analysis to identify under explored research areas.

Findings
By integrating the principles of lean production into innovation management practices in nanotechnologies, organizations can enhance their processes, promote continuous improvement, create value for customers and enhance their ability to innovate effectively in a competitive and dynamic environment. Examining the management of innovation in nanotechnology has revealed the potential to alter the future trajectory of technological advancement worldwide.

Originality/value
This research provides a new perspective on the combination of innovation management and nanotechnology, integrating lean production principles. This study uses a systematic bibliometric analysis to discover underexplored research areas and highlights the potential for transformation.
An exploratory study on the practice of operational excellence in the automotive industry in Morocco
Authors: Kazancoglu Yigit , Garza-Reyes Jose Arturo , Elgharbaoui Mohammed , Abbana Bennani Chaymae 
Published: January 2025

Purpose
This study aims to explore the implementation of operational excellence (OpEx) within the Moroccan automotive industry, focusing on its perception, adoption and integration into organizational structures.

Design/methodology/approach
This research uses a qualitative, exploratory design, using semi-structured interviews with eight key experts from various ecosystems within the Moroccan automotive industry. A purposive expert sampling method was used to select participants with significant experience in OpEx, ensuring a deep, context-specific understanding of its implementation.

Findings
This study reveals that Moroccan automotive firms adopt OpEx practices in a phased, structured manner, beginning with foundational methodologies such as Lean manufacturing, 5S and Kaizen, before progressing to advanced tools like Six Sigma. The integration of these practices is typically supported by dedicated teams within engineering and production departments, with some firms establishing specialized OpEx departments reporting directly to plant directors. While notable progress has been made in the adoption of OpEx, significant challenges remain, particularly regarding the technical expertise required for advanced methodologies like Six Sigma. Nevertheless, strong support from international parent companies and Morocco’s highly integrated automotive ecosystem has been identified as key enablers in accelerating the adoption of OpEx best practices.

Research limitations/implications
The generalizability of this study is constrained by its focus on a specific industry and region. While the qualitative findings provide valuable insights into the Moroccan automotive sector, further research is needed to broaden the scope across different industries and geographical contexts. Future studies could explore the application of OpEx practices in other developing economies or investigate the role of Industry 4.0 technologies in enhancing OpEx outcomes.

Originality/value
This study contributes to the limited body of research on OpEx implementation in developing economies, offering empirical insights from the Moroccan automotive industry. The findings provide practical insights for industry practitioners and theoretical contributions toward understanding how OpEx practices can be adapted and scaled within the unique context of emerging economies.
Sustaining continuous improvement programs proposition of influential elements and a maturity-benchmark model
Authors: Chirinos Orlando , Habchi Georges , Pralus Magali , Magnani Florian , Messaoudene Zahir 
Published: January 2025

Purpose
The purpose of this paper is to shed light on the studies regarding the influential elements that contribute to the sustainability of continuous improvement (CI) programs. It aims to define the notion of sustainability and to identify and explore the influential elements that could encompass such a definition.

Design/methodology/approach
A comprehensive literature review was conducted to categorise various interpretations of sustainability into distinct dimensions. This approach also identified 16 influential elements that have the potential to sustain CI programs. A self-assessment survey involving 80 French companies was used to evaluate these elements through the Plan, Do, Check, Act framework. In addition, a maturity-benchmark model is introduced to help evaluate the degree of maturity of the most influential elements of CI programs.

Findings
The results highlight the inherent paradox in sustaining CI programs, where robustness and adaptability must coexist. The study identifies a relationship between influential elements and organisational maturity levels, offering actionable insights to help companies advance through these stages. Human-centered elements, such as leadership and employee engagement, have the greatest impact on CI sustainability, emphasizing the importance of fostering a people-centric culture. Conversely, operational elements are less influential, suggesting a need for balanced strategies.

Originality/value
This paper discusses a topic that is rarely addressed, namely, how to sustain CI programs within a CI framework. This paper provides a novel synthesis of influential elements and their relationships to organisational maturity within a CI framework, challenging traditional static views of sustainability. By emphasizing the dynamic and evolving nature of CI programs, it bridges theory and practice, offering organisations a practical model for continuous reassessment and adaptation.