bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep mutational scanning identifies variants of Cas1 and Cas2 that increase spacer acquisition in type II-A CRISPR-Cas systems
Authors: Hofmann Raphael , Herman Calvin , Mo Charlie Y. , Mathai Jacob , Marraffini Luciano A. 
Published: October 2024

ABSTRACTA remarkable feature of CRISPR-Cas systems is their ability to acquire short sequences from invading viruses to create a molecular record of infection. These sequences, known as spacers, are inserted into the CRISPR locus by the Cas1-Cas2 integrase complex and mediate sequence- specific immunity in prokaryotes. Spacer acquisition has been used to develop unique biotechnological applications such as the immunization of industrially relevant bacteria against bacteriophage infection and the recording of biological signals into stable genetic information. These technologies, however, are constrained by the low efficiency of the spacer acquisition process. To overcome this limitation, we developed a genetic system that combined deep mutational scanning (DMS) ofcasgenes from theStreptococcus pyogenestype II-A CRISPR- Cas system with a method that selects bacteria that acquire new spacers. This procedure enabled the identification ofcasmutations that support up to a sevenfold increase in the levels of spacer acquisition and a significant enhancement of immunity against phage infection. In addition, our analysis revealed key interactions at the Cas1-Cas2 interface critical for spacer integration. Our findings provide insights into the molecular determinants of spacer acquisition and offer a platform to improve CRISPR-Cas-based applications.
Biosynthesis of glucosaminyl phosphatidylglycerol inPseudomonas aeruginosa
Authors: Khan Fabiha Zaheen , Palmer Kelli L. , Guan Ziqiang 
Published: October 2024

AbstractGlucosaminyl phosphatidylglycerol (GlcN-PG) was first identified in bacteria in the 1960s and was recently reported inPseudomonas aeruginosa. Despite the important implications in altering membrane charge (by the modification of anionic PG with cationic glucosamine), the biosynthesis and functions of GlcN-PG have remained uncharacterized. Using bioinformatic and lipidomic analysis, we identified a 3-gene operon, renamed asgpgSDF, that is responsible for the biosynthesis and potential transport of GlcN-PG inP. aeruginosa:gpgSencodes a novel glycotransferase that is responsible for the modification of phosphatidylglycerol (PG) withN-acetylglucosamine (GlcNAc) to produce GlcNAc-PG, andgpgDencodes a novel deacetylase that removes the acetyl group from GlcNAc-PG to produce GlcN-PG. The third gene in the operon,gpgF, is predicated to encode a flippase whose activity remains to be experimentally verified. As expected, the heterologous expression of thegpgSDFoperon inEscherichia coliresulted in production of both GlcNAc-PG and GlcN-PG. The identification of the biosynthetic genes of GlcN-PG paves the way for the investigation of its biological and pathological functions, which has significant implications in our understanding of the unique membrane physiology, pathogenesis and antimicrobial resistance ofP. aeruginosa.
Plexin/Semaphorin Antagonism Orchestrates Collective Cell Migration, Gap Closure and Organ sculpting by Contact-Mesenchymalization
Authors: Bischoff Maik C. , Norton Jenevieve E. , Peifer Mark 
Published: October 2024

AbstractCell behavior emerges from the intracellular distribution of properties like protrusion, contractility and adhesion. Thus, characteristic emergent rules of collective migration can arise from cell-cell contacts locally tweaking architecture – orchestrating self-regulation during development, wound healing, and cancer progression. The newDrosophilatestis-nascent-myotube-system allows dissection of contact-dependent migration in vivo at high resolution. Here, we describe a process driving gap-closure during migration: Contact-mesenchymalization via the axon guidance factor Plexin A. This is crucial for testis myotubes to migrate as a continuous sheet, allowing normal sculpting-morphogenesis. Cells must stay filopodial and dynamically ECM-tethered near cell-cell contacts to spread while collectively moving. Our data suggest Semaphorin 1B acts as a Plexin A antagonist, fine-tuning activation. Our data reveal a contact-dependent mechanism to maintain sheet-integrity during migration, driving organ-morphogenesis using a highly conserved pathway. This is relevant for understanding mesenchymal organ-sculpting and gap-closure in migratory contexts like angiogenesis.
A large reverse-genetic screen identifies numerous regulators of testis nascent myotube collective cell migration and collective organ sculpting
Authors: Bischoff Maik C. , Norton Jenevieve E. , Munguia Erika A. , Gurley Noah J. , Clark Sarah E. , Korankye Rebecca , Gyabaah Emmanuel Addai , Encarnacion Taino , Serody Christopher J. , Jones Corbin D. , Peifer Mark 
Published: October 2024

AbstractCollective cell migration is critical for morphogenesis, homeostasis, and wound healing. During development migrating mesenchymal cells form tissues that shape some of the body’s organs. We have developed a powerful model for examining this, exploring how Drosophila testis nascent myotubes migrate onto the testis during pupal development, forming the muscles that ensheath it and also creating its characteristic spiral shape. To define genes that regulate this process, we have carried out RNAseq to define the genes expressed in myotubes during migration. Using this dataset, we curated a list of 131 ligands, receptors and cytoskeletal regulators, including all Rho-family GTPase GAPs and GEFs, as candidates. We then used the GAL4/UAS system to express 279 shRNAs targeting these genes, using the muscle specific driver dMef2>GAL4, and examined the adult testis. We identified 29 genes with diverse roles in testis morphogenesis. Some have phenotypes consistent with defects in collective cell migration, while others alter testis shape in different ways, revealing some of the underlying logic of testis morphogenesis. We followed up one of these genes in more detail—that encoding the Rho-family GEF dPix. dPix knockdown leads to a drastic reduction in migration and a substantial loss of muscle coverage. Our data suggest different isoforms of dPix play distinct roles in this process, reveal a role for its protein partner Git. We also explore whether cdc42 activity regulation or cell adhesion are among the dPix mechanisms of action. Together, our RNAseq dataset and genetic analysis will provide an important resource for the community to explore cell migration and organ morphogenesis.
Catabolism of extracellular glutathione supplies amino acids to support tumor growth
Authors: Hecht Fabio , Zocchi Marco , Tuttle Emily T. , Ward Nathan P. , Smith Bradley , Kang Yun Pyo , Cazarin Juliana , Soares Zamira G. , Ozgurses Mete Emir , Zhao Huiping , Sheehan Colin , Alimohammadi Fatemeh , Munger Lila D. , Trivedi Dhvani , Asantewaa Gloria , Blick-Nitko Sara K. , Zoeller Jason J. , Chen Ying , Vasiliou Vasilis , Turner Bradley M. , Muir Alexander , Coloff Jonathan L. , Munger Joshua , DeNicola Gina M. , Harris Isaac S. 
Published: October 2024

AbstractRestricting amino acids from tumors is an emerging therapeutic strategy with significant promise. While typically considered an intracellular antioxidant with tumor-promoting capabilities, glutathione (GSH) is a tripeptide of cysteine, glutamate, and glycine that can be catabolized, yielding amino acids. The extent to which GSH-derived amino acids are essential to cancers is unclear. Here, we find that GSH catabolism promotes tumor growth. We show that depletion of intracellular GSH does not perturb tumor growth, and extracellular GSH is highly abundant in the tumor microenvironment, highlighting the potential importance of GSH outside of tumors. We find supplementation with GSH can rescue cancer cell survival and growth in cystine-deficient conditions, and this rescue is dependent on the catabolic activity of γ-glutamyltransferases (GGTs). Finally, pharmacologic targeting of GGTs’ activity prevents the breakdown of circulating GSH, lowers tumor cysteine levels, and slows tumor growth. Our findings indicate a non-canonical role for GSH in supporting tumors by acting as a reservoir of amino acids. Depriving tumors of extracellular GSH or inhibiting its breakdown is potentially a therapeutically tractable approach for patients with cancer. Further, these findings change our view of GSH and how amino acids, including cysteine, are supplied to cells.
Targetable treatment resistance in thyroid cancer with clonal hematopoiesis
Authors: Tiedje Vera , Vela Pablo Sánchez , Yang Julie L. , Untch Brian R. , Boucai Laura , Stonestrom Aaron J. , Costa Alberto Bueno , Expósito Sebastià Franch , Srivastava Avi , Kerpelev Marina , Greenberg Jillian , Wereski Mathew , Kulick Amanda , Chen Kevin , Qin Tianyue , Im Soo-Yeon , Krishnan Aishwarya , Martinez Benitez Anthony R. , Pluvinet Raquel , Sahin Merve , Menghrajani Kamal , Krishnamoorthy Gnana P. , de Stanchina Elisa , Zehir Ahmet , Satija Rahul , Knauf Jeffrey , Bowman Robert L , Esteller Manel , Devlin Sean , Berger Michael F. , Koche Richard P. , Fagin James A. , Levine Ross L 
Published: October 2024

AbstractAnaplastic thyroid cancer (ATC) is a clinically aggressive malignancy with a dismal prognosis. Combined BRAF/MEK inhibition offers significant therapeutic benefit in patients withBRAFV600E-mutant ATCs. However, relapses are common and overall survival remains poor. Compared with differentiated thyroid cancer, a hallmark of ATCs is significant infiltration with myeloid cells, particularly macrophages. ATCs are most common in the aging population, which also has an increased incidence ofTET2-mutant clonal hematopoiesis (CH). CH-mutant macrophages have been shown to accelerate CH-associated pathophysiology including atherosclerosis. However, the clinical and mechanistic contribution of CH-mutant clones to solid tumour biology, prognosis and therapeutic response has not been elucidated. Here we show thatTET2-mutant CH is enriched in the tumour microenvironment of patients with solid tumours and associated with adverse prognosis in ATC patients. We find thatTet2-mutant macrophages selectively infiltrate mouseBrafV600E-mutant ATC and that their overexpression of Tgfβ-family ligands mediates resistance to BRAF/MEK inhibition. Importantly, inhibition of Tgfβ signaling restores sensitivity to MAPK pathway inhibition, opening a path for synergistic strategies to improve outcomes of patients with ATCs and concurrent CH.
An abstract relational map emerges in the human medial prefrontal cortex with consolidation
Authors: Baram Alon , Nili Hamed , Barreiros Ines , Samborska Veronika , Behrens Timothy E. J. , Garvert Mona M. 
Published: October 2024

AbstractUnderstanding the structure of a problem, such as the relationships between stimuli, supports fast learning and flexible reasoning. Recent theoretical suggestions have highlighted the usefulness of explicit structural representations that are fully divorced from sensory details for generalisation. Rodent work has suggested that abstraction of structure occurs gradually, over time, in cortex. However, direct evidence of such explicit relational representations in humans is scarce, and its relationship to consolidation mechanisms is underexplored. Here, we use a graph-learning paradigm to find such a relational map in the human medial prefrontal cortex. Importantly, this representation was absent early after learning but emerged on the time scale of days. These results shed new light on neural representations underlying the remarkable human ability to draw accurate inferences from little data.
Determinants of ChatGPT adoption among students in higher education: the moderating effect of trust
Authors: Foroughi Behzad , Iranmanesh Mohammad , Ghobakhloo Morteza , Senali Madugoda Gunaratnege , Annamalai Nagaletchimee , Naghmeh-Abbaspour Bita , Rejeb Abderahman 
Published: October 2024

Purpose
ChatGPT is a cutting-edge chatbot powered by artificial intelligence that could revolutionise and advance the teaching and learning process. Drawing on the technology acceptance model (TAM) and information system (IS) success model, this study aims to investigate determinants of students’ intention to use ChatGPT for education purposes.

Design/methodology/approach
The partial least squares technique was used to analyse 406 usable data collected from university students in Malaysia.

Findings
The results confirmed the relationships between perceived usefulness (PU), perceived ease of use (PEU), attitude and intention to use proposed by TAM. PU and PEU are influenced by system quality. Surprisingly, trust in information moderates negatively the influences of PEU and PU on attitude.

Practical implications
The findings provide insight for higher education institutions, unit instructors and ChatGPT developers on what may promote the use of ChatGPT in higher education.

Originality/value
The study contributes to the literature by exploring the determinants of ChatGPT adoption, extending the TAM model by incorporating IS success factors and assessing the moderating effect of trust in information.
A bibliometric analysis of smallholder farmers’ climate change adaptation challenges: a SADC region outlook
Authors: Shoko Kori Dumisani , Musakwa Walter , Kelso Clare 
Published: October 2024

Purpose
This paper aims to explore pathways in which adaptation challenges may occur. Focus is on the barriers to adaptation, challenges to adaptation and maladaptation with reference to smallholder farmers in the Southern African Development Community region.

Design/methodology/approach
Bibliometric analysis techniques were used to track the literature on smallholder farmers’ adaptation challenges. Web of Science was the main data source. A total of 41 articles were retained for analysis and exported into Visualization of Similarities Viewer Software where the development of research on the subject, co-occurrence of keywords analysis, top publishers, citations and total link strength was done.

Findings
Results indicate that research on smallholder farmers’ adaptation challenges is not new but has gained more consideration post-2020. The main adaptation challenges emanate from perception barriers and constraints based on determinants of adoption, limitations for resilience building and achieving sustainable adaptation as well as contestations around Climate Smart Agriculture technologies.

Practical implications
Effective design of adaptation policies should center on prioritizing the needs of the local people. This would reduce the occurrences of smallholder farmers’ adaptation challenges, promote resilience building and contribute toward achieving sustainable adaptation.

Originality/value
It is equally important to document adaptation challenges. However, adaptation challenges are rarely shared with the same enthusiasm as its successes. This work focuses on the matter with the intention of conscientizing smallholder farmers to reduce the risk of repeating the same adaptation mistakes.
Lean logistics and corporate green practices: messianic methodologies for achieving business excellence in the logistics industry via green stakeholder satisfaction
Authors: Afum Ebenezer , Agyabeng-Mensah Yaw , Baah Charles 
Published: October 2024

Purpose
This study aims to explore how logistics firms exploit lean logistics and corporate green practices as significant catalysts for achieving business excellence via the mediation roles of green internal stakeholder satisfaction and green external stakeholder satisfaction.

Design/methodology/approach
Questionnaire is used in garnering data from 137 Ghanaian logistics firms. Structural equation modeling, particularly partial least squares, was applied to test all hypotheses.

Findings
The results confirm the notion that although lean logistics has positive effect on business performance, the effect is insignificant; hence, it is the concurrent implementation of lean logistics and corporate green practices that leads to superior business performance. The mediation analysis further confirms that both green internal stakeholder satisfaction and green external stakeholder satisfaction are significant precursors through which logistics firms can achieve superior business performance when lean logistics and corporate green practices can influence business performance.

Research limitations/implications
Data is collected from logistics firms from a single country. Hence, the results obtained cannot be imported to reflect the general occurrence in other geographical settings.

Practical implications
This study informs managers of logistics firms that lean and green strategies are compatible when implemented together; hence, it should not be treated in isolation. Managers are further enlightened that in their pursuit of business excellence, there is a need to prioritize green internal stakeholder satisfaction and green external stakeholder satisfaction via prudent investment in lean and green practices.

Originality/value
The research model proposed in this study magnifies the literature on lean and environmental management via bridging the literature gap concerning the interrelationship between lean logistics, corporate green practices, green internal stakeholder satisfaction, green external stakeholder satisfaction and business performance.
Game-based learning about the circular economy in building sustainable communities: a case of international and interdisciplinary university collaboration
Authors: Waite Imge Akcakaya , Akcay Kavakoglu Aysegul , Robescu Lacramioara Diana , Cocarta Diana Mariana , Vuta Liana Ioana 
Published: October 2024

Purpose
This study aims to enhance integration of game-based learning (GBL) as a tool for conveying intricate circular economy (CE) concepts effectively into international and interdisciplinary higher education collaborations for the development of sustainable communities.

Design/methodology/approach
A series of game-based workshops by the Circular EELISA Community of the EELISA European University program were examined in terms of their compliance with literature-based GBL characteristics and their international, interdisciplinary and online conduct. An online survey conducted with 17 workshop and/or challenge organizers from four participating universities in different countries revealed expert experiences and perceptions on these points.

Findings
It was found that sensory elements, rewards and game choice enhanced engagement and motivation in all gamification, serious game and storytelling experiences, and that a combination of multiple GBL approaches was more effective than a single-method challenge design. Diversity-friendly collaboration, cooperation and immersion were particularly important when involving culturally and disciplinarily diverse participants.

Practical implications
This study offers practical recommendations to improve both the performance of GBL-based learning environments in current and future education alliances and collaborations and the potential of GBL approaches to motivate youth to contribute to more sustainable communities across and beyond Europe.

Originality/value
The findings underscore the value of innovative pedagogical methods in shaping environmentally conscious mindsets and practices across institutions of higher education. To that end, this is the first study that investigates GBL in CE education with implications for international university cooperation.
ESG performance variability: profitability and market implications for real estate entities in a worldwide context
Authors: Morri Giacomo , Colantoni Federico , De Paolis Antonio Maria 
Published: October 2024

PurposeThe central aim of this study is to examine the relationship between ESG metrics and financial outcomes in the real estate industry, honing in on particular sectors and geographical areas. Utilizing ESG ratings and pillar scores as indicators of sustainability performance, this research endeavors to discern their effects on measures of profitability and market performance.Design/methodology/approachDrawing on a dataset encompassing more than 200 publicly listed companies in the real estate sector, this research utilizes a fixed effects regression model and instrumental variables to scrutinize the data. This approach enables a thorough evaluation of how governance, environmental and social dimensions influence the financial and market outcomes of these entities.FindingsThe research reveals a complex relationship between ESG factors and financial performance, defying any simplistic, universal application. The connection is marked by diversity, deeply influenced by the unique aspects of each real estate industry segment and the particularities of regional markets. Specifically, the environmental aspect often corresponds with an increase in ROA, yet this pattern is not consistent throughout all cases. On the other hand, the social aspect is frequently associated with diminished performance indicators, while the influence of governance factors varies, affecting financial outcomes less predictably.Originality/valueWith its pioneering methodology, the research delves into the granular impacts of ESG factors within individual real estate sectors and specific countries. Insights into the Real Estate Rental, Development and Operations sector as well as firms operating in Oceania, extend the conversation in an area of ESG literature that has been relatively uncharted. Moreover, the study’s illumination of how environmental, social and governance elements distinctly influence financial results injects fresh viewpoints into the ongoing dialogue on sustainable business practices.
New approaches to improving the student experience at Aberystwyth University libraries: from library surveys to cognitive mapping
Authors: Kensler Elizabeth 
Published: October 2024

PurposeThe findings are based on experience at Aberystwyth Universities libraries using surveys and user experience (UX) activities to identify and understand user requirements.Design/methodology/approachThis paper was initially conceived and developed as a presentation for the LibPMC Conference in July 2023. It is included in this special conference issue for this conference.FindingsThere are challenges to successful integration of UX into user engagement processes across the library and IT services. To improve shared analysis and collaborative ideas generation we developed an interactive data dashboard.Originality/valueThe research is based on practical approaches to improving our understanding of student use and requirements at Aberystwyth University libraries. It explores mechanisms used to collect findings from all areas of UX, including library surveys, focus groups and UX activities to be able to analyse and share all student experience data – to be able to analyse themes and generate ideas and actions for development.