bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-organ structural homogeneity of amyloid fibrils in ATTRv-T60A amyloidosis patients, revealed by Cryo-EM
Authors: Fernandez-Ramirez Maria del Carmen , Nguyen Binh A. , Singh Preeti , Afrin Shumaila , Evers Bret , Basset Parker , Wang Lanie , Pękała Maja , Ahmed Yasmin , Singh Virender , Canepa Jacob , Wosztyl Aleksandra , Li Yang , Saelices Lorena 
Published: May 2024

AbstractATTR amyloidosis is a degenerative disorder characterized by the systemic deposition of the protein transthyretin. These amyloid aggregates of transthyretin (ATTR) can deposit in different parts of the body causing diverse clinical manifestations. Our laboratory aims to investigate a potential relationship between the different genotypes, organ of deposition, clinical phenotypes, and the structure of ATTR fibrils. Using cryo-electron microscopy, we have recently described how the neuropathic related mutations ATTRv-I84S and ATTRv-V122Δ can drive structural polymorphism inex vivofibrils. Here we question whether the mutation ATTRv-T60A, that commonly triggers cardiac and neuropathic symptoms, has a similar effect. To address this question, we extracted and determined the structure of ATTR-T60A fibrils from multiple organs (heart, thyroid, kidney, and liver) from the same patient and from the heart of two additional patients. We have found a consistent conformation among all the fibril structures, acquiring the “closed-gate morphology” previously found in ATTRwt and others ATTRv related to cardiac or mixed manifestations. The closed-gate morphology is composed by two segments of the protein that interact together forming a polar channel, where the residues glycine 57 to isoleucine 68 act as a gate of the polar cavity. Our study indicates that ATTR-T60A fibrils present in peripheral organs adopt the same structural conformation in all patients, regardless of the organ of deposition.
A red algal polysaccharide influences the multicellular development of the choanoflagellateSalpingoeca rosetta
Authors: Perotti Olivia , Esparza Gabriel Viramontes , Booth David S. 
Published: May 2024

AbstractWe uncovered an interaction between a choanoflagellate and alga, in which porphyran, a polysaccharide produced by the red algaPorphyra umbilicalis, induces multicellular development in the choanoflagellateSalpingoeca rosetta. We first noticed this possible interaction when we tested the growth ofS. rosettain media that was steeped withP. umbilicalisas a nutritional source. Under those conditions,S. rosettaformed multicellular rosette colonies even in the absence of any bacterial species that can induce rosette development. In biochemical purifications, we identified porphyran, a extracellular polysaccharide produced by red algae, as the rosette inducing factor The response ofS. rosettato porphyran provides a biochemical insight for associations between choanoflagellates and algae that have been observed since the earliest descriptions of choanoflagellates. Moreover, this work provides complementary evidence to ecological and geochemical studies that show the profound impact algae have exerted on eukaryotes and their evolution, including a rise in algal productivity that coincided with the origin of animals, the closest living relatives of choanoflagellates.
Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARγ
Authors: Shang Jinsai , Kojetin Douglas J. 
Published: May 2024

ABSTRACTPeroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor transcription factor that regulates gene expression programs in response to ligand binding. Endogenous lipids and synthetic ligands, including covalent antagonist inhibitors such as GW9662 and T0070907, are thought to compete for the orthosteric pocket in the ligand-binding domain (LBD). However, we previously showed that synthetic PPARγ ligands can cooperatively cobind with and reposition a bound endogenous orthosteric ligand to an alternate site, synergistically regulating PPARγ structure and function (Shang et al., 2018). Here, we reveal the structural mechanism of cobinding between a synthetic covalent antagonist inhibitor with other synthetic ligands. Biochemical and NMR data show that covalent antagonist inhibitors weaken—but do not prevent—the binding of other synthetic ligands via an allosteric mechanism rather than direct ligand clashing. The covalent ligands shift the LBD ensemble toward a transcriptionally repressive conformation, which structurally clashes with and reduces the orthosteric binding affinity of non-covalent synthetic ligands. Crystal structures reveal different non-covalent synthetic ligand-specific cobinding mechanisms ranging from alternate site binding to unexpectedly adopting an orthosteric binding mode by altering the covalent ligand binding pose. Our findings not only highlight the significant flexibility of the PPARγ orthosteric pocket and its ability to accommodate multiple ligands simultaneously, but also demonstrate that GW9662 and T0070907 should not be used as reliable chemical tools to inhibit the binding of other ligands to PPARγ.
Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation
Authors: Stadnicki Emily J , Ludewig Hannes , Kumar Ramasamy P , Wang Xicong , Qiao Youwei , Kern Dorothee , Bradshaw Niels 
Published: May 2024

AbstractReversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives diverse diseases, kinases and phosphatases have been targets for drug discovery, with some achieving remarkable clinical success. Most protein kinases are activated by phosphorylation of their activation loops, which shifts the conformational equilibrium of the kinase towards the active state. To turn off the kinase, protein phosphatases dephosphorylate these sites, but how the conformation of the dynamic activation loop contributes to dephosphorylation was not known. To answer this, we modulated the activation loop conformational equilibrium of human p38α MAP kinase with existing kinase inhibitors that bind and stabilize specific inactive activation loop conformations. From this, we discovered three inhibitors that increase the rate of dephosphorylation of the activation loop phospho-threonine by the PPM serine/threonine phosphatase WIP1. Hence, these compounds are “dual-action” inhibitors that simultaneously block the active site and stimulate p38α dephosphorylation. Our X-ray crystal structures of phosphorylated p38α bound to the dual-action inhibitors reveal a shared flipped conformation of the activation loop with a fully accessible phospho-threonine. In contrast, our X-ray crystal structure of phosphorylated apo human p38α reveals a different activation loop conformation with an inaccessible phospho-threonine, thereby explaining the increased rate of dephosphorylation upon inhibitor binding. These findings reveal a conformational preference of phosphatases for their targets and suggest a new approach to achieving improved potency and specificity for therapeutic kinase inhibitors.
Knowledge management–performance nexus: Mediating effect of motivation and innovation
Authors: Ştefan Simona Cătălina , Popa Ion , Olariu Ana Alexandra , Popa Ştefan Cătălin , Popa Cătălina-Florentina 
Published: May 2024

PurposeThe current study has a two-fold purpose. Firstly, it aims to analyze the extent to which knowledge management (KM) affects the performance of individuals (task and contextual) on the one hand and that of organizations (product or service, perceived and financial) on the other hand. Secondly, it proposes to investigate the mediating effect of motivation and innovation in the relationship between KM and individual and organizational performance.Design/methodology/approachPartial least squares structural equation modeling (PLS-SEM) was employed in this study, with mediation analysis performed using advanced PLS-SEM techniques. A total of 1,284 respondents from organizations in both the public and private sectors were included in the sample.FindingsThe findings emphasize that KM has a more significant direct effect on individual performance compared to organizational performance. Concurrently, in terms of indirect influence, it is found that KM, through motivation and innovation, has a positive and significant effect on both individual and organizational performances, with a higher influence on the organizational one.Originality/valueThe originality of the work can be noted in designing two different structural models to represent the proposed relationships at the individual and organizational levels. These findings could provide organizational decision makers with empirical evidence, helping them (1) internalize the significance of the KM process in organizations as well as its subsequent effects on individual and organizational performance and (2) identify factors that mediate variable relationships.
Have we reached a technological plateau? A situational awareness approach to overcome the barriers limiting the development of BIM-based plugins
Authors: Saad Ali M. , Badran Hasan D. , Ajayi Saheed , Sarhan Saad 
Published: May 2024

Purpose
The construction industry has embraced building information modelling (BIM) as a practical methodology towards digitalisation. However, critics believe BIM has reached a plateau in addressing distinctive construction challenges. As a result, literature has seen an increase in the development and use of BIM-based plugins. Overall, the plugins have been critical in delivering custom-built solutions to longstanding construction challenges. The purpose of this study is to empirically investigate this trend and the potential barriers undermining the wider development of BIM plugins, by that contributing to a stimulating research topic and a growing knowledge gap.

Design/methodology/approach
Methodologically, this study used a quantitative approach to collect data through a carefully designed questionnaire. This study achieved a sample size of 39 experts who have been involved in developing, experimenting and publishing BIM-based plugins for specific construction activities.

Findings
The findings led to the identification of the key barriers to using BIM-based plugins and the identification of the key strategies to overcome them across the three situational awareness (SA) phases. Results also suggest that the development and use of plugins are destined to increase, and the research community can now rely on the insights of this paper as a departure point to address the technological plateau in BIM-related research.

Originality/value
To the best of the authors’ knowledge, this is the first study to empirically identify and assess the barriers undermining the wider development of BIM-based plugins. This study contributes to theory by building on SA, by challenging existing wisdom and fostering new knowledge around strategies to overcome the evaluated barriers.
Interactive and educational simulation tool for permanent magnet synchronous machines
Authors: Schugardt Alexander , Kaiser Louis , Avcilar Fatih , Schäfer Uwe 
Published: May 2024

Purpose
This paper aims to present an interactive design and simulation tool for permanent magnet synchronous machines based on the finite-element-method. The tool is intended for education and research on electrical machines.

Design/methodology/approach
A coupling between the software MATLAB and finite element method magnetics is used. Several functionalities are included as modular scripts and represented in the form of a graphical user interface. Included are fully parametrized motor models, automatic winding generations and the evaluation of torque waveforms, core losses and speed-torque-diagrams. A survey was conducted to determine how the motivation of students concerning the covered topics is influenced by using the tool.

Findings
Due to its simplicity and the intuitive visualization of the results, the tool provides direct access to the topic of electrical machines without having to deal with separate scripts. The modular structure of the software allows simple extensions with new functions. Because students can directly contribute to the tool with their own work, their motivation for using and extending it increases.

Originality/value
The presented tool offers more functionalities compared to similar free software packages, e.g. the calculation of core losses and speed-torque diagrams. Also, it is designed in such a way that it can be easily understood and extended by students.
Digital economy and regional innovation: unveiling the spatial dynamics and human capital influence in China
Authors: Bu Ya , Yu Xinghui , Li Hui 
Published: May 2024

Purpose
The paper aims to examine the digital economy's influence on China's regional innovation and development. It focuses on direct effects and spatial spillover across regions, and the mediating role of human capital. This analysis is vital for policy and strategic planning in the digital era.

Design/methodology/approach
This study uses panel data from 30 Chinese provinces (2004–2019) and uses the entropy method to quantify the digital economy's development. It investigates its impact on regional innovation using a dynamic spatial Durbin model (SDM) and mediation effect model, assessing direct effects, spatial spillover and human capital's mediating role. Various control variables are included for comprehensive analysis.

Findings
Findings show the digital economy significantly boosts regional innovation, acting as a growth driver. However, impacts vary regionally, with the central region gaining more than the eastern and western areas. Spatial spillover effects are mixed, showing negative short-term and positive long-term impacts under different weight matrices. Human capital is crucial for fostering innovation through the digital economy.

Originality/value
The paper offers unique insights into the spatial dynamics of the digital economy's impact on regional innovation in China. It advances understanding of the digital economy's role in regional development using innovative methods like the entropy method and dynamic SDM. Highlighting human capital as a key mediating factor enriches discussions on digital economy strategies for regional innovation.
Optimization design of custom pattern based on microclimate heat transfer
Authors: Zhang Yijie , Guo Ziyi , Wei Jiangang , Li Yijun 
Published: May 2024

PurposeThe aim of this paper is to achieve a reasonable microclimate between clothing and the human body and optimize the custom dress pattern.Design/methodology/approachAn interactive design method of 3D modeling, virtual try-on and heat transfer simulation are used. First, a 3D dress is designed with nonuniform rational B-splines curves and tried on virtually. After that, the heat transfer in the body-air-clothing microclimate and temperature distributions on the clothing surface are obtained. Based on the heat transfer in the body-air-clothing system, we design a method to improve the thermal comfort by optimizing the garment pattern digitally. Then, this paper utilized two heat transfer validating indexes to quantify the improvement of thermal comfort, and evaluate the modified model of dress.FindingsThe microclimate under the clothing is varied with the air gap distance, and the heat transfer on the area of the clavicle, bust point and front abandon are higher than other parts due to the narrow air gaps. In view of thermal comfort, the pattern optimization changes the distance ease and reforms the air circulating efficiency. The mean heat transfer and its standard variance are changing by about 10% and more than 20%. Thus, the heat transfer evaluation indexes are suitable to represent the heat transfer and thermal comfort in the microclimate system.Research limitations/implicationsIt can be concluded that the methodology proposed in this paper has the advantage of interactive design, 3D visualization and local heat transfer simulation. This technology meets the need of personalized customization and well-considered garment and has broad application prospects.Originality/valueThis study demonstrates that modifying the distance ease on body key girths based on heat transfer is a reliable way to improve thermal comfort. This method meets the consumers’ demand of the comfort of body-fit clothing under the condition of daily activities.
The effect of retail shelf position on private-label brand evaluations
Authors: Tofighi Maryam , Grohmann Bianca 
Published: May 2024

PurposeThis research examines the effects of physical proximity (close vs distant) of retailers’ private label brands (PLBs) relative to national brands (NBs) and brand display orientation (horizontal [brands occupy the same shelf] vs vertical [brands occupy different shelves]) on consumers’ PLB quality perceptions and PLB evaluations.Design/methodology/approachTwo experiments involving real brands in different product categories tested the hypotheses.FindingsA PLB positioned close (vs distant) to a NB is evaluated more favorably and this effect is mediated by increased PLB quality perceptions, but only in a horizontal brand display. In a vertical brand display, a PLB positioned close (vs distant) to a NB is evaluated less favorably and this effect is mediated by decreased PLB quality perceptions.Research limitations/implicationsThe findings suggest that to enhance consumers’ PLB quality perceptions and evaluations, PLBs be positioned next to (rather than on separate shelves) and close to (rather than distant from) NBs in the same product category.Originality/valueAlthough the literature suggests that the best shelf position for PLBs is close to NBs, there is a lack of empirical research on the effects of relative shelf positioning on consumers’ quality perceptions and subsequent PLB evaluations. This research finds that both physical proximity and brand display orientation play an important role.
Value implications of followers in social marketplaces: insights into ego network structures
Authors: Wang Shan , Wang Fang 
Published: May 2024

PurposeIn social marketplaces, follower ego networks are integral social capital assets for online sellers. While previous research has underscored the positive impact of the follower number on seller performance, little attention has been given to the structure of follower networks and their value implications. This research investigates two structural properties of follower networks—network centralization and density—and examines their main and contingent effects on sellers’ sales performance.Design/methodology/approachA 13-month panel dataset of 1,150 sellers in Etsy, a social marketplace for handmade and vintage products, was collected and analyzed. A fixed effects model was adopted to validate the hypotheses on the main effect of centralization and density, as well as the moderating effects of two store attributes: store age and product diversification.FindingsWe find that both network centralization and density negatively impact sellers’ sales performance, and these effects vary across store age and product diversification levels. Specifically, the negative effect of network centralization is less pronounced for older stores than young ones, whereas the negative effect of density is more severe for stores with high product diversification.Originality/valueThis research contributes to social commerce research by highlighting the significance of network structure, alongside network size, in assessing the value of followers and offers practical guidance for sellers in social marketplaces seeking to optimize their follower networks.
Investigating the relationship between brand logo, customer satisfaction, attitude and repurchase intention of online services
Authors: Akbari Mohammad , Nazarzad Shadi , Ghasemi Namaghi Mohamad 
Published: May 2024

PurposeIn this paper, the relationship of brand logo and purchase intention is investigated along with the mediating role of customer satisfaction, brand preference and brand attitude. The research is conducted on an online passenger transport company called Tapsi.Design/methodology/approachIn this study, we examine the positive effect of brand logo on brand attitude, consumer satisfaction and strengthening the intention to buy and brand preference by customer satisfaction. The statistical population was randomly selected. We design a conceptual model and then prepare a standard online questionnaire and send it to the target groups. Among this, the participants, 59% are women and 41% are men. After collecting the data through the software Smart-PLS3, we start the analysis. According to Cronbach's alpha and AVE, the validity and reliability of the model are confirmed.FindingsThe study shows that the brand logo has a positive and direct influence on customer attitude and satisfaction, and customer satisfaction mediates the purchase intention and brand preference. Given that the brand logo describes the company, managers must be very sensitive to design of a proper logo and spend enough time and money on it.Originality/valueFew studies have examined the effectiveness of the brand logo the present study and the results show that the brand logo and its structures are directly related to brand attitude as a result of consumer satisfaction in all services even transportation services. The first thing consumers see when they first use a company’s services is the company logo. The brand and its logo can change the attitude and decision of the customer. Past studies have also shown that the brand logo can have a direct impact on customer satisfaction and customer preference for the brand. Therefore a model was prepared and the mentioned variables were selected. Brand preference as a mediating variable has a positive role on buying intention. However all relationships and their predictive power have been confirmed.