bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of transplantable and biologically responsive colonic tissue from human induced pluripotent stem cells using a rapid co-differentiation platform
Authors: Dalleywater William , Predeus Alexander V. , Cakir Batuhan , Mazin Pavel , Vadakekolathu Jayakumar , Rutella Sergio , Meakin Marian L. , Ritchie Alison A. , Montazid Shamir , Cuevas Ocaña Sara , Holmes Nadine , Wright Victoria , Sang Fei , Bills Adam , Sculthorpe Declan , Elmentaite Rasa , Teichmann Sarah A. , Irshad Shazia , Tomlinson Ian , Silver Andrew , Wildman Ricky D. , Hannan Nicholas R.F , Rose Felicity R.A.J. , Ilyas Mohammad 
Published: December 2023

BackgroundThe colonic mucosa consists of cell populations derived from multiple lineages. Induced pluripotent stem cells (iPSCs) are capable of generating large numbers of differentiated cells from any lineage. Thus, iPSCs are highly versatile for derivation of intestinal cells for generation of colonic mucosal tissue for clinical and biological applications.ObjectiveWe set out to create a human iPSC (hiPSC) multi-lineage co-differentiation platform capable of generating colonic mucosal tissue in vitro.DesignWe used hiPSCs and designed a differentiation protocol consisting of small molecules and recombinant growth factors to generate multiple cell lineages. Cells were seeded onto collagen hydrogels (forming colonic patches - CoPs) and modulated with multiple growth factors important in intestinal biology. CoPs were transplanted into immunosuppressed mice. Generated cells and tissues were profiled with transcriptomic analysis.ResultshiPSC co-differentiation led to multiple intestinal epithelial, mesenchymal and endothelial cell populations. Seeded onto collagen scaffolds these cells created CoPs, which were transplanted into mouse subcutis. Engrafted CoPs developed into normal-looking colonic mucosa containing epithelial crypts (with enterocytes, goblet cells and neuroendocrine cells), multiple lamina propria-resident stromal populations and muscularis mucosae smooth muscle. They anastomosed to murine vasculature and maintained in-vitro for several weeks. We demonstrated that CoPs respond to known signalling pathways important in colonic mucosal biology and fibrogenesis, showing potential to provide a complex model of colonic pathobiology.ConclusionThis platform could offer an accurate model of intestinal pathobiology, supply cells for regenerative cell therapies to treat intestinal disease, and provide therapeutic autologous grafts to repair damaged colon.
Cooperative Gsx2-DNA Binding Requires DNA Bending and a Novel Gsx2 Homeodomain Interface
Authors: Webb Jordan A. , Farrow Edward , Cain Brittany , Yuan Zhenyu , Yarawsky Alexander E. , Schoch Emma , Gagliani Ellen K. , Herr Andrew B. , Gebelein Brian , Kovall Rhett A. 
Published: December 2023

ABSTRACTThe conserved Gsx homeodomain (HD) transcription factors specify neural cell fates in animals from flies to mammals. Like many HD proteins, Gsx factors bind A/T-rich DNA sequences prompting the question — how do HD factors that bind similar DNA sequencesin vitroregulate specific target genesin vivo? Prior studies revealed that Gsx factors bind DNA both as a monomer on individual A/T-rich sites and as a cooperative homodimer to two sites spaced precisely seven base pairs apart. However, the mechanistic basis for Gsx DNA binding and cooperativity are poorly understood. Here, we used biochemical, biophysical, structural, and modeling approaches to (1) show that Gsx factors are monomers in solution and require DNA for cooperative complex formation; (2) define the affinity and thermodynamic binding parameters of Gsx2/DNA interactions; (3) solve a high-resolution monomer/DNA structure that reveals Gsx2 induces a 20° bend in DNA; (4) identify a Gsx2 protein-protein interface required for cooperative DNA binding; and (5) determine that flexible spacer DNA sequences enhance Gsx2 cooperativity on dimer sites. Altogether, our results provide a mechanistic basis for understanding the protein and DNA structural determinants that underlie cooperative DNA binding by Gsx factors, thereby providing a deeper understanding of HD specificity.
Two distinct modes of hemodynamic responses across the human cortex
Authors: Epp Samira M. , Castrillón Gabriel , Yuan Beijia , Andrews-Hanna Jessica , Preibisch Christine , Riedl Valentin 
Published: December 2023

ABSTRACTFunctional magnetic resonance imaging (fMRI) detects changes in brain activity by measuring fluctuations in blood oxygenation. This interpretation relies on the mechanism of neurovascular coupling, which closely links changes in neuronal activity to changes in cerebral blood flow (CBF). Whether uniform neurovascular coupling applies to the entire human cortex is yet to be proven. We used blood-oxygenation-level-dependent (BOLD) fMRI along with quantitative fMRI to assess the cerebral metabolic rate of oxygen (CMRO2) associated with both positive and negative BOLD signal changes (ΔBOLD). In contradiction to the canonical hemodynamic model of BOLD signal responses, we found discordant CMRO2 in 12-36% of voxels with significant positive and in 52-66% of voxels with significant negative ΔBOLD. This implies that a considerable number of voxels with negative ΔBOLD exhibit increased metabolic activity and vice versa. During the baseline state, we found a lower oxygen extraction fraction (OEF) and oxygen metabolism in discordant compared to concordant voxels. During task states, ΔOEF replaces ΔCBF as the primary mechanism of oxygen supply in discordant voxels. Thus, we propose OEF as a complementary hemodynamic response type to CBF in regulating oxygen demand in the human brain. In such conditions, the traditional interpretation of positive and negative BOLD signal changes in terms of increased or decreased neural activity will be misleading, and we recommend quantitative fMRI or additional CBF measurements for a more valid interpretation of regional BOLD signal changes in relation to neuronal activity.
TheCryptococcusextracellular vesicle transcriptome
Authors: Taheraly Adam , Maufrais Corinne , Moyrand Frédérique , Colin Jessie , Coppee Jean-Yves , Janbon Guilhem 
Published: December 2023

AbstractExtracellular vesicles (EVs) are now recognized as key players in the biology of numerous organisms, including pathogenic fungi. However, studying EVs in these organisms remains challenging. The recent implementation of new protocols to purify EVs in the pathogenic yeastCryptococcus neoformanshas resulted in a more detailed description of their structure and protein composition. Although a few publications describing RNA molecules associated with EVs have already been published, we reasoned that these new protocols would be beneficial for gaining a deeper understanding of the EV transcriptome. We thus purified EVs and confirmed that some RNAs were associated with these EV extracts. Iodixanol gradient analyses also revealed that these RNAs co-sedimented with EVs. We then sequenced these RNAs in parallel with RNAs extracted from the very cells producing these EVs using different types of sequencing libraries. Our data confirm the presence of siRNAs and tRFs associated with EVs, some of which are enriched. We also identified some snoRNAs, which inCryptococcus are mostly borne by coding gene or lncRNA introns.
Replication-attenuated r3LCMV vectors potentiate tumor control via IFN-I
Authors: Chung Young Rock , Awakoaiye Bakare , Dangi Tanushree , Fourati Slim , Penaloza-MacMaster Pablo 
Published: December 2023

SummaryViral vectors are being used for the treatment of cancer. Yet their efficacy varies among tumors and their use poses challenges in immunosuppressed patients, underscoring the need for alternatives. We report striking antitumoral effects by a nonlytic viral vector based on attenuated lymphocytic choriomeningitis virus (r3LCMV). We show in multiple tumor models that injection of tumor-bearing mice with this novel vector results in improved tumor control and survival. Importantly, r3LCMV also improved tumor control in immunodeficient Rag1-/- mice. Single cell RNA-Seq analyses, antibody blockade experiments, and KO models revealed a critical role for host IFN-I in the antitumoral efficacy of r3LCMV vectors. Collectively, these data demonstrate potent antitumoral effects by a replication-attenuated LCMV vector and unveil mechanisms underlying its antitumoral efficacy.
Targeting F-actin stress fibers to suppress the dedifferentiated phenotype in chondrocytes
Authors: Schofield Mandy M. , Rzepski Alissa , Hammerstedt Jonah , Shah Sohan , Mirack Chloe , Parreno Justin 
Published: December 2023

AbstractActin is a central mediator of the chondrocyte phenotype. Monolayer expansion of articular chondrocytes on tissue culture polystyrene, for cell-based repair therapies, leads to chondrocyte dedifferentiation. During dedifferentiation, chondrocytes spread and filamentous (F-)actin reorganizes from a cortical to a stress fiber arrangement causing a reduction in cartilage matrix expression and an increase in fibroblastic matrix and contractile molecule expression. While the downstream mechanisms regulating chondrocyte molecular expression by alterations in F-actin organization have become elucidated, the critical upstream regulators of F-actin networks in chondrocytes are not completely known. Tropomyosin (TPM) and the RhoGTPases are known regulators of F-actin networks. The purpose of this study is to elucidate the regulation of passaged chondrocyte F-actin stress fiber networks and cell phenotype by the specific TPM, TPM3.1, and the RhoGTPase, CDC42. Our results demonstrated that TPM3.1 associates with cortical F-actin and stress fiber F-actin in primary and passaged chondrocytes, respectively. In passaged cells, we found that TPM3.1 inhibition causes F-actin reorganization from stress fibers back to cortical F-actin and also causes an increase in G/F-actin. CDC42 inhibition also causes formation of cortical F-actin. However, CDC42 inhibition, but not TPM3.1 inhibition, leads to the re-association of TPM3.1 with cortical F-actin. Both TPM3.1 and CDC42 inhibition reduces nuclear localization of myocardin related transcription factor, which is known to suppress dedifferentiated molecule expression. We confirmed that TPM3.1 or CDC42 inhibition partially redifferentiates passaged cells by reducing fibroblast matrix and contractile expression, and increasing chondrogenic SOX9 expression. A further understanding on the regulation of F-actin in passaged cells may lead into new insights to stimulate cartilage matrix expression in cells for regenerative therapies.
Early stage of life is characterized by increased excitability of the auditory cortex in both humans and rats
Authors: Lehtomäki Krista , Keinänen Jari , Parkkonen Lauri , Mondal Riaz Uddin , Penttonen Markku , Parviainen Tiina 
Published: December 2023

ABSTRACTAuditory evoked response (ER) undergoes notable changes during childhood and likely reflects changes in synaptic signaling in the auditory cortex. Establishing the interspecies generalizability of electrophysiological indicators of cortical maturation would offer a means to better understand the neurodevelopment of the human brain. We measured cortical ERs to simple auditory probes in three age groups of human subjects and juvenile rats. These two species exhibited a remarkably similar long-latency (150–350 ms poststimulus) response in the auditory cortex, specifically pronounced in the younger individuals in both species. An age-dependent pattern of activity was evident at the level of single trials, and the late response showed stronger trial-by-trial stability in children than the early, adult-like 100-ms response, especially in humans. This robust development-related pattern of sensory cortex excitability is likely to represent a distinct synaptic event and may be a marker of the maturational stage, especially in GABAergic cortical circuits.
Two transcriptional cascades orchestrate cockroach leg regeneration
Authors: Ren Chonghua , Wen Yejie , Zheng Shaojuan , Zhao Zheng , Li Ethan Yihao , Zhao Chenjing , Liao Mingtao , Li Liang , Zhang Xiaoshuai , Liu Suning , Yuan Dongwei , Wang Wei , Fei Jifeng , Li Sheng 
Published: December 2023

SummaryThe mystery of appendage regeneration has fascinated humans for centuries, while the regulatory mechanisms remain unclear. In this study, a transcriptional landscape of regenerating leg was established in the American cockroach,Periplaneta americana, an ideal model for appendage regeneration with remarkable regeneration capacity. Through a large-scalein vivoscreening, we identified multiple signaling pathways and transcription factors (TFs) controlling leg regeneration. Specifically,zfh-2andbowl,which have not been previously implicated in appendage regeneration, contributes to blastema proliferation and morphogenesis in two novel transcriptional cascades BMP/JAK-STAT-zfh-2-bab1/B-H2/Lim1and Notch-drm/bowl-bab1. Notably,zfh-2was found working as a direct target of BMP signaling to promote cell proliferation in the blastema. These mechanisms might be conserved in the appendage regeneration of vertebrates from an evolutionary perspective. Overall, our findings reveal that two crucial transcriptional cascades orchestrate distinct cockroach leg regeneration processes, significantly advancing the comprehension of molecular mechanism in appendage regeneration.
Anthropometric evaluation of side, sex and age by radiological examination of the normal ankle joint among adult Egyptian population
Authors: Nasr El-Din Wael Amin , Mohammed Ali Mona Hassan , Madani Gisma Ahmed , Abdel Fattah Islam Omar 
Published: December 2023

PurposeSex and age estimation is important, particularly when information about the deceased is unavailable. There are limited radiological studies investigating side, sex and age differences in normal ankle morphometric parameters. The authors’ goal was to evaluate different ankle joint morphometric measurements and document variations among Egyptians.Design/methodology/approachA prospective study was conducted throughout 23 months on 203 (100 males and 103 females) adult Egyptians, aged between 20-69 years old, who were referred for a plain x-ray of bilateral normal ankle joints.FindingsAnkle parameters showed no statistical difference between both sides, except for tarsal width (TaW) which was significantly higher on right than left side (26.92 ± 2.66 vs 26.18 ± 2.65 mm). Males showed significantly higher morphometric values except for anteroposterior gap (APG) and talus height (TaH) which were significantly higher in females (2.29 ± 0.80 vs 1.80 ± 0.61 mm and 13.01 ± 1.68 vs 11.87 ± 1.91 mm, respectively). There was significant increase in tibial arc length, APG, distance of level of MTiTh from anterior limit of mortise, distance of level of MTiTh from vertex of mortise, sagittal distance between tibial and talar vertices and sagittal radius of trochlea tali arc in old age group compared to young one. A significant decrease in tibial width, malleolar width, TaW and TaH was noted in old age group compared to young one.Originality/valueAnkle joints of both sides are mostly symmetrical; however, there are significant differences in most morphometric values due to sex and age factors. These findings may be essential during side, sex and age determination.
An integrated model of social media brand engagement: an empirical study of the Vietnamese luxury residential property market
Authors: Sinh My Nguyen , Nguyen Long T.V. , Pham Hiep Cong 
Published: December 2023

PurposeProperty developers identify the vital role of social media brand engagement (SMBE) in sustaining their businesses in competitive marketplaces, but it remains underexplored. This paper examines how SMBE mediates the effects of firm-generated content (FGC) and user-generated content (UGC) on brand trust, considering the moderating effects of social media influencer endorsement (SMIE) and self-image congruence (SIC) for luxury residential properties (LRPs).Design/methodology/approachAround 516 high-income homebuyers in Vietnam who shared information about LRP on social media were targeted to test the research model empirically. The primary data collected from paper-based surveys were analysed using SPSS 26 and AMOS 24.FindingsResults indicate that FGC and UGC positively impact SMBE and consequently significantly affect brand trust. Further, results confirm the moderating roles of SMIE and SIC in the effects of FGC and UGC on SMBE.Research limitations/implicationsData and sample size were limited to meet the generalisation from different nations and cross cultures.Practical implicationsThe authors' findings suggest that marketers should apply the authors' integrated SMBE model to strengthen brand–consumer interactions and increase their sales revenue.Originality/valueThis study is the first in its application of the uses and gratifications theory and self-congruence theory to investigate how SMBE mediates the relationship between FGC and brand trust as well as between UGC and brand trust. Noticeably, this study makes a novel contribution as the first to quantitatively explore the moderating effects of SMIE and SIC in the authors' research model.
Pricing strategy of first-enjoy-after-pay service offered by two-sided media platforms
Authors: Zhang Xiaojing , Zhang Yulin 
Published: December 2023

PurposeThis study highlights the impact of mental accounts on a user's decision-making regarding payment schemes and aims to determine the pricing strategy for the first-enjoy-after-pay service offered by the two-sided media platforms.Design/methodology/approachThis study establishes a game-theoretic model and utilizes backward induction to derive the equilibrium price by maximizing the monopolist's profit.FindingsThe findings indicate that the conditions for a two-sided media platform to offer the first-enjoy-after-pay service depend on the trade-off between pleasure attenuation and pain buffering and the effect of time discounts. Moreover, the authors found that the time discount is a critical factor in determining pricing strategies under various payment schemes offered by the platform.Research limitations/implicationsThis work adopts a uniform pricing strategy for users who opt for either immediate or post-payment schemes. Nevertheless, it is important to note that this approach has limitations in terms of offering discriminatory pricing for those who choose both payment schemes.Practical implicationsThis analytical work provides valuable insights for two-sided media platforms to optimize their payment scheme strategies and pricing considering the influence of a user's mental account.Originality/valueIn a two-sided media platform, the authors provide applicable conditions for the platform to offer first-enjoy-after-pay service considering the effect of mental accounts. Further, the authors show the optimal pricing strategy under different payment schemes provided by the platform.
Process model for international building permit benchmarking and a validation example using the Israeli building permit process
Authors: Fauth Judith , Bloch Tanya , Soibelman Lucio 
Published: December 2023

PurposeBuilding permitting is mostly a manual, labor intensive and time-consuming process. Initiatives for streamlining the process are not always helpful since they often fail to address the core problems within the process. A framework for modeling the permitting process can be useful to identify bottlenecks, core challenges and best practices. Hence, the authors aim to demonstrate and validate a previously suggested workflow for permit process modeling using the permitting process in Israel as a test case.Design/methodology/approachThe authors implement qualitative expert interviews for data acquisition. The collected data are then processed for a qualitative data analysis. The results of the analysis are then validated using a focus group workshop in the field of building permits. In the test case the focus group consisted of Israeli experts.FindingsThe authors present a detailed overview of the as-is building permit process in Israel and the existing challenges. Through this test case, the authors found that the framework is applicable in different countries and that it can provide valuable insights into the core problems within the process. In addition, application of the same framework in different countries can provide comparable results that would allow the authors to identify best practices.Originality/valueThe major contribution of this work is the development and validation of a framework for building permitting process modeling which can be used to identify existing challenges and bottlenecks in the process. Implementing a structured and unified approach provides an opportunity to easily compare processes in different countries to identify best practices.
Enhancing risk assessment: an improved Bayesian network approach for analyzing interactions among risks
Authors: Madihi Mohammad Hosein , Shirzadi Javid Ali Akbar , Nasirzadeh Farnad 
Published: December 2023

PurposeIn traditional Bayesian belief networks (BBNs), a large amount of data are required to complete network parameters, which makes it impractical. In addition, no systematic method has been used to create the structure of the BBN. The aims of this study are to: (1) decrease the number of questions and time and effort required for completing the parameters of the BBN and (2) present a simple and apprehensible method for creating the BBN structure based on the expert knowledge.Design/methodology/approachIn this study, by combining the decision-making trial and evaluation laboratory (DEMATEL), interpretive structural modeling (ISM) and BBN, a model is introduced that can form the project risk network and analyze the impact of risk factors on project cost quantitatively based on the expert knowledge. The ranked node method (RNM) is then used to complete the parametric part of the BBN using the same data obtained from the experts to analyze DEMATEL.FindingsCompared to the traditional BBN, the proposed method will significantly reduce the time and effort required to elicit network parameters and makes it easy to create a BBN structure. The results obtained from the implementation of the model on a mass housing project showed that considering the identified risk factors, the cost overruns relating to material, equipment, workforce and overhead cost were 37.6, 39.5, 42 and 40.1%, respectively.Research limitations/implicationsCompared to the traditional BBN, the proposed method will significantly reduce the time and effort required to elicit network parameters and makes it easy to create a BBN structure. The results obtained from the implementation of the model on a mass housing project showed that considering the identified risk factors, the cost overruns relating to material, equipment, workforce and overhead cost were 37.6, 39.5, 42 and 40.1%, respectively. The obtained results are based on a single case study project and may not be readily generalizable.Originality/valueThe presented framework makes the BBN more practical for quantitatively assessing the impact of risk on project costs. This helps to manage financial issues, which is one of the main reasons for project bankruptcy.