bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust Small Molecule-Aided Cardiac Reprogramming Systems Selective to Cardiac Fibroblasts
Authors: Tao Yanmeng , Yang Yang , Yang Zhenghao , Wang Lipeng , Wang Shi-Qiang , Zhao Yang 
Published: September 2023

SUMMARYDirect cardiac reprogramming to induce cardiomyocyte-like cells, e.g. by GMT (Gata4, Mef2c and Tbx5), is a promising route for regenerating damaged heartin vivoand disease modellingin vitro. Supplementation with additional factors and chemical agents can enhance efficiency but raises concerns regarding selectivity to cardiac fibroblasts and complicates delivery for in situ cardiac reprogramming. Here, we screened 2000 chemicals with known biological activities and found that a combination of 2C (SB431542 and Baricitinib) significantly enhances cardiac reprogramming by GMT. Without Gata4, MT (Mef2c and Tbx5) plus 2C could selectively reprogram cardiac fibroblasts with enhanced efficiency, kinetics, and cardiomyocyte function. Moreover, 2C significantly enhanced cardiac reprogramming in human cardiac fibroblasts. 2C synergistically enhances cardiac reprogramming by inhibiting Alk5, Tyk2 and downregulating Oas2, Oas3, Serpina3n and Tgfbi. 2C enables selective and robust cardiac reprogramming that can greatly facilitate disease modellingin vitroand advance clinical therapeutic heart regenerationin vivo.
The Implant-Induced Foreign Body Response is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins
Authors: Ghosh Mallika , McGurk Fraser , Norris Rachael , Dong Andy , Nair Sreenidhi , Jellison Evan , Murphy Patrick , Verma RajKumar , Shapiro Linda H 
Published: September 2023

AbstractImplanted medical devices from artificial heart valves, arthroscopic joints to implantable sensors often induce a Foreign Body Response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the Foreign Body Giant cells (FBGCs), accompanied by inflammatory cytokines, matrix deposition and eventually, deleterious fibrotic implant encapsulation. Despite efforts to improve biocompatibility, implant-induced FBR persists, compromising the utility of devices and making efforts to control the FBR imperative for long-term function. Controlling macrophage fusion in FBGC formation presents a logical target to prevent implant failure, but the actual contribution of FBGCs to FBR-induced damage is controversial. CD13 is a molecular scaffold andin vitroinduction of CD13KObone-marrow progenitors generates many more MGCs than WT, suggesting CD13 regulates macrophage fusion. Moreover, in the mesh implant model of FBR, CD13KOmice produced significantly more peri-implant FBGCs with enhanced TGFβ expression and increased collagen deposition vs. WT. Pre-fusion, increased protrusion and microprojection formation accompanies hyperfusion in the absence of CD13. Expression of fusogenic proteins driving cell-cell fusion was aberrantly sustained at high levels in CD13KOMGCs, which we show is due to a novel CD13 function, regulating ubiquitin/proteasomal protein degradation. By controlling protein degradation, CD13 becomes a physiologic brake preventing aberrant macrophage fusion and may be a novel therapeutic target to improve success of implanted medical devices. Furthermore, our data directly implicates FBGCs in the detrimental fibrosis that characterizes the FBR.
Structure and dynamics of a pentameric KCTD5/Cullin3/Gβγ E3 ubiquitin ligase complex
Authors: Nguyen Duc Minh , Rath Deanna H. , Devost Dominic , Pétrin Darlaine , Rizk Robert , Ji Alan X. , Narayanan Naveen , Yong Darren , Zhai Andrew , Kuntz Douglas A. , Mian Maha U.Q. , Pomroy Neil C. , Keszei Alexander F.A. , Benlekbir Samir , Mazhab-Jafari Mohammad T. , Rubinstein John L. , Hébert Terence E. , Privé Gilbert G. 
Published: September 2023

AbstractHeterotrimeric G proteins can be regulated by post-translational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain (CTD), engages CUL3 to form the central scaffold of a cullin- RING E3 ligase complex (CRL3KCTD5) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3NTD/Gβ1γ2assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5BTB/CUL3NTDand KCTD5CTD/Gβγ moieties of the structure. CRL3KCTD5engages the E3 ligase ARIH1 to ubiquitylate Gβγ in an E3-E3 super-assembly, and extension of the structure to include full- length CUL3 with RBX1 and an ARIH1∼ubiquitin conjugate reveals that some conformational states position the ARIH1∼ubiquitin thioester bond to within 10 Å of lysine-23 of Gβ and likely represent priming complexes. Most previously described CRL/substrate structures have consisted of monovalent complexes and have involved flexible peptide substrates. The structure of the KCTD5/CUL3NTD/Gβγ complex shows that the oligomerization of a substrate receptor can generate a polyvalent E3 ligase complex and that the internal dynamics of the substrate receptor can position a structured target for ubiquitylation in a CRL3 complex.Significance StatementIn humans, ∼600 enzyme complexes can carry out protein ubiquitylation, and the most abundant class of these are the cullin3-RING-ligase complexes (CRL3s). CRL3s are multiprotein complexes built around a BTB/cullin3 core, and the incorporation of different BTB proteins into this scaffold results in distinct architectures that ubiquitylate a wide range of substrates. In most cases, it is not known how the complexes are tuned to their substrates. We show that the BTB protein KCTD5 is the central organizer in a CRL3KCTD5complex, and that the architecture and internal dynamics of KCTD5 are essential for positioning a Gβγ substrate protein near an activated ubiquitin for the transfer reaction. This explains how KCTD5 targets Gβγ for proteasomal degradation and regulates cellular activities.
Effect of alpha-tubulin acetylation on the doublet microtubule structure
Authors: Yang Shun Kai , Kubo Shintaroh , Black Corbin , Peri Katya , Dai Daniel , Valente Melissa , Gaertig Jacek , Bui Khanh Huy 
Published: September 2023

AbstractAcetylation of α-tubulin at the lysine 40 residue (αK40) by ATAT1/MEC-17 acetyltransferase modulates microtubule properties and occurs in most eukaryotic cells. Acetylated microtubules are more stable and damage resistant. αK40 acetylation is the only known microtubule luminal post-translational modification site. The luminal location suggests that the modification tunes the lateral interaction of protofilaments inside the microtubule. In this study, we examined the effect of tubulin acetylation on the doublet microtubule in the cilia ofTetrahymena thermophilausing a combination of cryo-electron microscopy, molecular dynamics, and mass spectrometry. We found that αK40 acetylation exerts a small-scale effect on the doublet microtubule structure and stability by influencing the lateral rotational angle. In addition, comparative mass spectrometry revealed a link between αK40 acetylation and phosphorylation in cilia.
Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis
Authors: Imoto Yuuta , Xue Jing , Luo Lin , Raychaudhuri Sumana , Itoh Kie , Ma Ye , Craft George E. , Kwan Ann H. , Mackay Joel P. , Ha Taekjip , Watanabe Shigeki , Robinson Phillip J. 
Published: September 2023

SummaryDynamin 1 (Dyn1) has two major splice variants, xA and xB, with unique C-terminal extensions of 20 and 7 amino acids, respectively. Of these, only Dyn1xA is enriched at endocytic zones and accelerates vesicle fission during ultrafast endocytosis. Here, we report that the long tail variant, Dyn1xA, achieves this localization by preferentially binding to Endophilin A through a newly defined Class II binding site overlapping with its extension, at a site spanning the splice boundary. Endophilin binds this site at higher affinity than the previously reported site, and this affinity is determined by amino acids outside the binding sites acting as long distance elements within the xA tail. Their interaction is regulated by the phosphorylation state of two serine residues specific to the xA variant. Dyn1xA and Endophilin colocalize in patches near the active zone of synapses. Mutations selectively disrupting Endophilin binding to the long extension cause Dyn1xA mislocalization along axons. In these mutants, endocytic pits are stalled on the plasma membrane during ultrafast endocytosis. These data suggest that the specificity for ultrafast endocytosis is defined by the phospho-regulated interaction of Endophilin A through a newly identified site of Dyn1xA’s long tail.
Grounding, framing, and problematising research in online, distance and digital education
Authors: Lim David C.L. , Zawacki-Richter Olaf , Jung Insung 
Published: September 2023

PurposeThis paper engages Olaf Zawacki-Richter and Insung Jung in a frank and penetrating conversation that seeks to ground, frame, and problematise research in the field conceptualised as “open, distance and digital education” (ODDE). Taking as starting point the recent publication of the landmark Handbook of Open, Distance, and Digital Education (2022), it segues into a broad critique of the shortcomings of ODDE research, the importance of knowledge production on the meso- and macro-levels, the autonomy of ODDE as a field coming into its own, the place of postfoundationalism in ODDE discourse, and related topics that are pivotal in ODDE today.Design/methodology/approachThe semi-structured interview was employed as the primary qualitative research method.FindingsThe research imperative of the relatively young but complex field of ODDE today is not the incessant reiteration of the same but rather a strategic reorientation that, first, circumvents the well-documented yet too-often-overlooked shortcomings of ODDE research and, second, promotes transboundary collaborations with the potential for system-wide impact.Originality/valueThis novel interview-based critique of ODDE research demonstrates that extending the scholarly discourse beyond the conventional report format is a productive method for enriching conversations on ODDE and vitalising the field itself.
The impact of integrating a compulsory community-oriented research program within undergraduate medical curriculum on graduates' scientific publications: perspectives from Arabian Gulf University
Authors: Alzayani Salman , Al-Roomi Khaldoon , Jaradat Ahmed , Hamdi Ali M. , Shehata Mohamed H. 
Published: September 2023

PurposeMedical schools aspire to graduate doctors who are competent in interpreting, conducting and publishing scientific research. Hence, the purpose of the paper is explore the impact of a structured compulsory community-oriented, project-based research program in the undergraduate medical curriculum on medical graduates’ future careers, publications and motivation for scientific research.Design/methodology/approachAn online questionnaire was sent through the Alumni Association of the Arabian Gulf University (AGU) to medical graduates who have valid email addresses, seeking information on their scientific productivity along with demographic and current employment data. Responses were collated and analyzed using a standard statistical software package. The chi-square test and p-value were calculated. P-value <0.05 was considered statistically significant.FindingsCompleted forms were received from 91 medical graduates. In this sample, almost a quarter of the respondents have published a research paper out of their undergraduate research project, and about 50% have published at least one paper (as main or co-author) after graduation. Both demographic and medical specialty was not related to the doctor's perception of the benefits they have attained from the compulsory undergraduate research program. However, medical graduates who are at senior levels in their medical careers and those who are employed in secondary healthcare are significantly more likely to publish research papers.Originality/valueThe compulsory community-oriented, project-based research program in AGU has positively contributed to the research productivity of graduates, and it would be worthwhile to include such programs as an integral part of the undergraduate medical curriculum.
Explore, eat and revisit: does local food consumption value influence the destination’s food image?
Authors: Gupta Vikas , Galati Antonino , Sharma Savita 
Published: September 2023

PurposeThis research investigates how foreign tourists' revisit intentions are influenced by their local food consumption (LFC) value by emphasizing their attitude towards the local food and the corresponding destination food image. It will also reveal the foreign tourists' food consumption value and explore its influences on the destination's food image.Design/methodology/approachThe data collection was performed from 433 foreign tourists who visited Delhi, India, using a structured survey instrument and chief constructs were measured as the first-order reflective variables. The 39 items associated with the LFC value underwent both exploratory and confirmatory evaluations. The authors employed partial least square structural equation modeling (PLS-SEM). The model's discriminant and convergent validity, consistency and overall fit were evaluated using confirmatory factor analysis (CFA).FindingsThe findings revealed that “tourists' attitudes and behaviors toward the local cuisine” had a significant and positive influence on their “intention to visit/revisit” and “intention to recommend”. Also, “destination food image” significantly and positively influenced the “intention of tourist to visit/revisit”; however, it negatively and insignificantly influenced the “intention of tourists to recommend”.Research limitations/implicationsThis research used five variables related to LFC—quality, health/nutrition, emotion, prestige and price—that impact tourists' attitudes and behaviors toward local foods in Delhi. However, in addition to these constructs, other factors or constructs may be involved that could affect the tourists' attitudes and behaviors. Future studies might explore and include these constructs to provide a more comprehensive image of Delhi's LFC value.Originality/valueUnderstanding tourists' food-linked behaviors is critical for effective market conduct. However, the interrelations between travelers' destination food image, LFC value, their perceptions of the local cuisine and behavioral intentions are still unknown, and this will be one of the first attempts to discuss these behaviors.
Factors influencing the individual investors of Bangladesh to opt for investment in ṣukūk
Authors: Chowdhury Tasruma Sharmeen , Salema S.M. Kalbin 
Published: September 2023

PurposeThis study aims to identify the factors that influence the willingness of Bangladeshi retail investors to invest in ṣukūk.Design/methodology/approachThe authors surveyed Bangladeshi retail investors using a structured questionnaire to understand their perspectives on potential investment in ṣukūk. The authors considered the behavioral aspects of retail investors and the desired ṣukūk features to analyze the demand side. Factors and regression analyses were performed to identify the persuading factors.FindingsThe results indicate that investor awareness is a fundamental factor in potential investments in ṣukūk. Investors perceive the security represented by government and third-party guarantees as a persuasive feature of ṣukūk. The tradability and tenor of ṣukūk also affect the investment intention. Sharīʿah consciousness of the investors also plays a significant role in their investment decisions.Research limitations/implicationsOne limitation of this study is that it incorporates potential individual investors only, and precludes institutional investors. In the future, there is scope for research to explore the demand factors impacting institutional investors of ṣukūk in Bangladesh.Practical implicationsThe authors expect that the study will aid policymakers and ṣukūk issuers in crafting strategies to cater to the needs of Bangladeshi retail investors.Originality/valueThis study is the earliest research conducted in Bangladesh to determine the factors impacting the willingness of individual investors to make their potential investments in ṣukūk. To the best of the authors' knowledge, no study has analyzed the desired ṣukūk features from the perspective of Bangladeshi retail investors.
A four-node rectangular plate finite element using Airy functions with transverse shear
Authors: Abderrahmani Sifeddine 
Published: September 2023

PurposeAmong different types of engineering structures, plates play a significant role. Their analysis necessitates numerical modeling with finite elements, such as triangular, quadrangular or sector plate elements, owing to the intricate geometrical shapes and applied loads. The scope of this study is the development of a new rectangular finite element for thin plate bending based on the strain approach using Airy's function. It is called a rectangular plate finite element using Airy function (RPFEUAF) and has four nodes. Each node had three degrees of freedom: one transverse displacement (w) and two normal rotations (x, y).Design/methodology/approachEquilibrium conditions are used to generate the interpolation functions for the fields of strain, displacements and stresses. The evolution of the Airy function solutions yielded the selection of these polynomial bi-harmonic functions. The variational principle and the analytical integration approach are used to evaluate the basic stiffness matrix.FindingsThe numerical findings for thin plates quickly approach the Kirchhoff solution. The results obtained are compared to the analytical solution based on Kirchhoff theory.Originality/valueThe efficiency of the strain based approach using Airy's function is confirmed, and the robustness of the presented element RPFEUAF is demonstrated. Because of this, the current element is more reliable, better suited for computations and especially intriguing for modeling this kind of structure.
Employee silence as a response to cronyism in the workplace: the roles of felt violation and continuance commitment
Authors: Islam Talat , Rizvi Farheen , Farooq Waqas , Ahmed Ishfaq 
Published: September 2023

PurposeThe practice of cronyism is a pervasive problem for most businesses and a great hindrance for employees, but empirical literature on its outcomes is scant. In light of such gaps, the objective of this study is to examine the relationship between organizational cronyism and employees' silence behavior through the mediating role of felt violation and the moderating role of continuance commitment.Design/methodology/approachA time-lagged cross-sectional survey comprising 226 respondents is carried out in a metropolitan city of a developing country (Lahore, Pakistan). The respondents were selected using the convenience sampling technique.FindingsThe findings reveal that organizational cronyism influences employees' silence (acquiescent and quiescent) both directly and indirectly (via felt violation). However, continuance commitment was noted to work as a boundary condition only between felt violation and quiescent silence.Research limitations/implicationsAlthough the study deals with common method bias by collecting data in two waves, it may restrict causality. The findings not only have implications for the academicians, but also contribute to the conservation of resources theory. This study suggests organizations develop and implement a comprehensive intervention strategy that focuses on both prevention and damage control as a result of organizational cronyism.Originality/valueDrawing upon the conservation of resources theory, this study adds value to the literature by empirically investigating the outcomes of cronyism at work. Moreover, the outcomes and mechanisms under consideration have largely been ignored in the literature.
Amaro's business model innovation: DNVB or platform?
Authors: da Silva Wellington José , Araújo Giselle da Costa , Rehder Adriano , Pedroso Marcelo Caldeira 
Published: September 2023

PurposeThis teaching case aims to analyze the business model of Amaro, a company that directly sells lifestyle goods to end consumers (B2C), focused on the women's market. Amaro's original business model is introduced and a challenging dilemma is proposed: could Amaro innovate its business model, moving from a digitally native vertical brand (DNVB)-type company to a platform, specifically a vertical marketplace focused on the female audience? Would Amaro be prepared for this evolution or would it be more appropriate to focus on or strengthen the DNVB model?Design/methodology/approachThis teaching case was developed based on in-depth interviews with Amaro's leadership. The teaching notes were proposed based on business model innovation, competitive positioning and market trends concepts. The teaching case considers a new type of business model called DNVB. Students can review the concepts, create analyses and recommend which strategic options can leverage the company for a new growing cycle.FindingsUsing the case study in the classroom should promote the discussion and reflections on business model innovation and the future of retail in omnichannel contexts - Amaro offers products online (on an e-commerce platform and native mobile applications) and physically in locations called guide shops. The authors suggested the adoption of frameworks and tools (e.g. the competitive positioning map to allow students to visualize ways to compare strategies and make decisions).Research limitations/implicationsThe case introduces a fictional dilemma related to the decision to maximize offline or online investments or completely change the company's business model by adding a new vertical marketplace approach.Practical implicationsThis teaching case contributes to the student's learning about business model innovation and evolution. Case discussions could explore contemporary concepts such as value proposition, disintermediation and omnichannel commerce.Originality/valueOffering goods directly to the consumers by using modern technological architecture through vertical integration within the supply chain makes the DNVB business model an original topic in the start-up segment.