bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photoswitchable binders enable temporal dissection of endogenous protein function
Authors: Westberg Michael , Song Daesun , Duong Vandon , Fernandez Daniel , Huang Po-Ssu , Lin Michael Z. 
Published: September 2023

AbstractGeneral methods for spatiotemporal control of specific endogenous proteins would be broadly useful for probing protein function in living cells. Synthetic protein binders that bind and inhibit endogenous protein targets can be obtained from nanobodies, designed ankyrin repeat proteins (DARPins), and other small protein scaffolds, but generalizable methods to control their binding activity are lacking. Here, we report robust single-chain photoswitchable DARPins (psDARPins) for bidirectional optical control of endogenous proteins. We created topological variants of the DARPin scaffold by computer-aided design so fusion of photodissociable dimeric Dronpa (pdDronpa) results in occlusion of target binding at baseline. Cyan light induces pdDronpa dissociation to expose the binding surface (paratope), while violet light restores pdDronpa dimerization and paratope caging. Since the DARPin redesign leaves the paratope intact, the approach was easily applied to existing DARPins for GFP, ERK, and Ras, as demonstrated by relocalizing GFP-family proteins and inhibiting endogenous ERK and Ras with optical control. Finally, a Ras-targeted psDARPin was used to determine that, following EGF-activation of EGFR, Ras is required for sustained EGFR to ERK signaling. In summary, psDARPins provide a generalizable strategy for precise spatiotemporal dissection of endogenous protein function.
Nature-Inspired Peptide of MtDef4 C-terminus Tail Enables Protein Delivery in Mammalian Cells
Authors: Lifshits Lucia Adriana , Breuer Yoav , Sova Marina , Gupta Sumit , Kadosh Dar , Weinberg Evgeny , Hayouka Zvi , Bar Daniel Z. , Gal Maayan 
Published: September 2023

AbstractCell-penetrating peptides hold great promise as versatile tools for the intracellular delivery of therapeutic agents. Various peptides have originated from natural proteins with antimicrobial activity. In this study, we investigated the mammalian cell-penetrating properties of a 16-residue peptide derived from the C-terminus tail of theMedicago truncatuladefensin protein, with the sequence GRCRHGFRRRCFCTTHC. We evaluated the ability of this peptide to penetrate multiple types of cells. Our results demonstrate that the peptide efficiently penetrates mammalian cells within minutes and at a sub-micromolar concentration. Moreover, upon N-terminal fusion to the fluorescent protein GFP, the peptide efficiently delivers the GFP into the cells. Despite its remarkable cellular penetration, the peptide has only a minor effect on cellular viability, making it a promising candidate for the development of a cell-penetrating peptide, with potential therapeutic applications.
PI3Kα inhibition blocks osteochondroprogenitor specification and the hyper-inflammatory response to prevent heterotopic ossification
Authors: Valer José Antonio , Deber Alexandre , Wits Marius , Pimenta-Lopes Carolina , Goumans Marie-José , Rosa José Luis , Sánchez-Duffhues Gonzalo , Ventura Francesc 
Published: September 2023

AbstractHeterotopic ossification (HO) occurs following mechanical trauma and burns, or congenitally in patients suffering from fibrodysplasia ossificans progressiva (FOP). Recently, we demonstrated that inhibitors of phosphatidyl-inositol 3-kinase alpha (PI3Kα) may be a useful therapy for patients undergoing HO. In this study, using the already marketed BYL719/Alpelisib/Piqray drug, we have further confirmed these results, detailed the underlying mechanisms of action, and optimized the timing of the administration of BYL719. We found that BYL719 effectively prevents HO even when administered up to three to seven days after injury. We demonstrate in cell cultures and in a mouse model of HO that the major actions of BYL719 are on-target effects through the inhibition of PI3Kα, without directly affecting ACVR1 or FOP-inducing ACVR1R206Hkinase activities.In vivo, we found that a lack of PI3Kα in progenitors at injury sites is sufficient to prevent HO. Moreover, time course assays in HO lesions demonstrate that BYL719 not only blocks osteochondroprogenitor specification, but also reduces the inflammatory response. BYL719 inhibits the migration, proliferation and expression of pro-inflammatory cytokines in monocytes and mast cells, suggesting that BYL719 hampers the hyper-inflammatory status of HO lesions. Altogether, these results highlight the potential of PI3Kα inhibition as a safe and effective therapeutic strategy for HO.
AntiviralWolbachiastrains associate withAedes aegyptiendoplasmic reticulum membranes and disturb host cell lipid distribution to restrict dengue virus replication
Authors: Loterio Robson K. , Monson Ebony A. , Templin Rachel , Bruyne Jyotika T. , Flores Heather A. , Mackenzie Jason M. , Ramm Georg , Helbig Karla J. , Simmons Cameron P. , Fraser Johanna E. 
Published: September 2023

AbstractThe insect endosymbiotic bacteriumWolbachia pipientisis being utilised as a biocontrol tool to reduce the incidence ofAedes aegypti-transmitted viral diseases like dengue. However, the precise mechanisms underpinningWolbachia’s antiviral activity are not well defined. Here we generated a panel ofAe. aegypti-derived cell lines infected with antiviral strainswMel andwAlbB or the non-antiviral strainwPip to understand host cell morphological changes specifically induced by antiviral strains. Antiviral strains were frequently found to be entirely wrapped by the host endoplasmic reticulum (ER) membrane, whilewPip bacteria clustered separately in the host cell cytoplasm. ER-derived lipid droplets (LDs) increased in volume inwMel-andwAlbB-infected cell lines and mosquito tissues compared to cells infected withwPip orWolbachia-free controls. Inhibition of fatty acid synthase (required for triacylglycerol biosynthesis) reduced LD formation and significantly restored ER-associated dengue virus replication in cells occupied bywMel. Together, this suggests that antiviralWolbachiastrains may specifically alter the lipid composition of the ER to preclude the establishment of DENV replication complexes. DefiningWolbachia’s antiviral mechanisms will support the application and longevity of this effective biocontrol tool that is already being used at scale.ImportanceAedes aegyptitransmits a range of important human pathogenic viruses like dengue. However, infection ofAe. aegyptiwith the insect endosymbiotic bacterium,Wolbachia, reduces the risk of mosquito to human viral transmission.Wolbachiais being utilized at field sites across more than 13 countries to reduce the incidence of viruses like dengue, but it is not well understood howWolbachiainduces its antiviral effects. To examine this at the subcellular level, we compared how different strains ofWolbachiawith varying antiviral strengths, associate with and modify host cell structures. Strongly antiviral strains were found to specifically associate with the host endoplasmic reticulum and induce striking impacts on host cell lipid distribution. InhibitingWolbachia-induced lipid redistribution partially restored dengue virus replication demonstrating this is a contributing role forWolbachia’s antiviral activity. These findings provide new insights into how antiviralWolbachiastrains associate with and modifyAe. aegyptihost cells.
The autonomic effects of transcutaneous auricular nerve stimulation at different sites on the external auricle of the ear
Authors: Bretherton Beatrice , Murray Aaron , Deuchars Susan , Deuchars Jim 
Published: September 2023

ABSTRACTTranscutaneous auricular nerve stimulation (tANS) applied to specific parts of the external ear has positive health effects in both healthy volunteers and patient groups. However, due to differences between studies in ear stimulation sites and extent of effect on autonomic variables, it is challenging to determine what part of the external ear is the optimum site for electrode placement. This study investigated the autonomic effects of bilateral tANS at four different sites on the external auricle of the ear: tragus, cymba concha, helix and earlobe. tANS was performed using modified surface electrodes connected to a transcutaneous electrical nerve stimulation (TENS) machine. Participants (n = 24) each underwent four sessions where a 15 minute period of stimulation (pulse width: 200 μs; pulse frequency: 30 Hz; current: adjusted to sensory threshold) was applied bilaterally to either the tragus, cymba concha, helix or earlobe. Heart rate and blood pressure were continuously recorded during 10-minute baseline, 15-minute stimulation and 10-minute recovery periods. Heart rate variability (HRV) was derived. Results showed that regardless of site, stimulation significantly influenced measures of HRV. Baseline LF/HF ratio predicted change in LF/HF ratio during stimulation for each site and for all sites combined. Response (i.e. change in LF/HF ratio between baseline and stimulation) was closely linked with measures reflecting starting autonomic function. This demonstrates the importance of evaluating how autonomic function is modulated by tANS in individual participants (as well as the whole group). These findings have key implications for adopting a tailored approach when considering the therapeutic/clinical applications of tANS.
Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism
Authors: Takahashi Hideyuki , Perez-Canamas Azucena , Ye Hongping , Han Xianlin , Strittmatter Stephen M. 
Published: September 2023

AbstractTMEM106B is an endolysosomal transmembrane protein not only associated with multiple neurological disorders including frontotemporal dementia, Alzheimer’s disease, and hypomyelinating leukodystrophy but also potentially involved in COVID-19. Additionally, recent studies have identified amyloid fibrils of C-terminal TMEM106B in both aged healthy and neurodegenerative brains. However, so far little is known about physiological functions of TMEM106B in the endolysosome and how TMEM106B is involved in a wide range of human conditions at molecular levels. Here, we performed lipidomic analysis of the brain of TMEM106B-deficient mice. We found that TMEM106B deficiency significantly decreases levels of two major classes of myelin lipids, galactosylceramide and its sulfated derivative sulfatide. Subsequent co-immunoprecipitation assay showed that TMEM106B physically interacts with galactosylceramidase. We also found that galactosyceramidase activity was significantly increased in TMEM106B-deficient brains. Thus, our results reveal a novel function of TMEM106B interacting with galactosyceramidase to regulate myelin lipid metabolism and have implications for TMEM106B-associated diseases.
Centrosome age breaks spindle size symmetry even in “symmetrically” dividing cells
Authors: Thomas Alexandre , Meraldi Patrick 
Published: September 2023

AbstractCentrosomes are the main microtubule organizing center in animal cells. Due to the semi-conservative nature of centrosome duplication, the two centrosomes differ in age. In asymmetric stem cell divisions, centrosome age can induce an asymmetry in half-spindle lengths. However, whether centrosome age affects the symmetry of the two half-spindles in tissue culture cells thought to divide symmetrically, is unknown. Here, we show that in human epithelial and fibroblastic cell lines centrosome age imposes a subtle spindle asymmetry that leads to asymmetric cell daughter sizes. At the mechanistic level, we show that this asymmetry depends on the preferential accumulation on old centrosomes of the microtubule nucleation-organizing proteins pericentrin, γ-tubulin, Cdk5Rap2, and TPX2, under the control of a cenexin-bound pool of the mitotic kinase Plk1. Moreover, we find that old centrosomes have a higher microtubule nucleation capacity. We therefore postulate that centrosome age breaks spindle size symmetry via microtubule nucleation even in cells thought to divide symmetrically.
A robust twin support vector machine based on fuzzy systems
Authors: Qiu Jianxiang , Xie Jialiang , Zhang Dongxiao , Zhang Ruping 
Published: September 2023

PurposeTwin support vector machine (TSVM) is an effective machine learning technique. However, the TSVM model does not consider the influence of different data samples on the optimal hyperplane, which results in its sensitivity to noise. To solve this problem, this study proposes a twin support vector machine model based on fuzzy systems (FSTSVM).Design/methodology/approachThis study designs an effective fuzzy membership assignment strategy based on fuzzy systems. It describes the relationship between the three inputs and the fuzzy membership of the sample by defining fuzzy inference rules and then exports the fuzzy membership of the sample. Combining this strategy with TSVM, the FSTSVM is proposed. Moreover, to speed up the model training, this study employs a coordinate descent strategy with shrinking by active set. To evaluate the performance of FSTSVM, this study conducts experiments designed on artificial data sets and UCI data sets.FindingsThe experimental results affirm the effectiveness of FSTSVM in addressing binary classification problems with noise, demonstrating its superior robustness and generalization performance compared to existing learning models. This can be attributed to the proposed fuzzy membership assignment strategy based on fuzzy systems, which effectively mitigates the adverse effects of noise.Originality/valueThis study designs a fuzzy membership assignment strategy based on fuzzy systems that effectively reduces the negative impact caused by noise and then proposes the noise-robust FSTSVM model. Moreover, the model employs a coordinate descent strategy with shrinking by active set to accelerate the training speed of the model.
Experimental study on the effect of solid lubricants on wheel rail contact wear and surface hardness evolution
Authors: Sun Peiwen , Yang Jianwei , Zhu AiHua , Hu Zhongshuo , Wang Jinhai , Liu Fu , Wang Xiaohui 
Published: September 2023

Purpose
The CL60 steel wheels of subway vehicles operating on specific lines require frequent refurbishment due to rapid wear and tear. Considering this issue, MoS2-based and graphite-based solid lubricants are used to reduce the wear rate of subway wheels and extend their service life.

Design/methodology/approach
Under laboratory conditions, the effect of MoS2-based and graphite-based solid lubricants on the friction and wear performance of subway wheels and rails was evaluated using a modified GPM-60 wear testing machine.

Findings
Under laboratory conditions, MoS2-based solid lubricants have the best effect in reducing wheel/rail wear, compared to the control group without lubrication, at 2 × 105 revolutions, the total wheel-rail wear decreased by 95.07%. However, when three types of solid lubricants are used separately, the hardness evolution of the wheel-rail contact surface exhibits different characteristics.

Practical implications
The research results provide important support for improving the lifespan of wheel and rail, extending the service cycle of wheel and rail, reducing the operating costs of subway systems, improving the safety of subway systems and providing wear reduction maintenance for other high wear mechanical components.

Originality/value
The experiment was conducted through the design and modification of a GPM-60 testing machine for wear testing. The experiment simulated the wheel-rail contact situation under actual subway operation and evaluated the effects of three different solid lubricants, MoS2-based and graphite-based, on the wear performance and surface hardening evolution of subway wheel-rail.
Supporting learners self-management for self-directed language learning: a study within Duolingo
Authors: Li Zixi , Bonk Curtis J. , Zhou Chen 
Published: September 2023

Purpose
This study aims to investigate a unique approach to learning languages through self-directed online learning. Specifically, it explores the self-management abilities and skills learners need while learning a language outside traditional classroom settings when using mobile-assisted learning technology.

Design/methodology/approach
A mixed-methods approach was used in this study, including an online survey of 84 people and 10 semi-structured interviews.

Findings
Findings reveal the significant role of specific and well-defined learning goals in enhancing learners’ performance. These goals can be either self-initiated by the learners themselves or defined by the technological features of the learning platform. However, the presence of distractions in learners’ daily lives presents challenges to effective time management, affecting learners both physically and psychologically. A key aspect of self-directed language learning lies in the learners’ ability to seek out relevant human and material resources beyond the confines of a single mobile-assisted language learning (MALL) tool. The authenticity of these resources is crucial in ensuring meaningful and effective learning experiences.

Research limitations/implications
Understanding how learners navigate and discover valuable resources is a central focus of this study. This research offers valuable insights into the field of self-directed language learning, revealing the pivotal role of self-management skills with mobile-assisted learning technology. The findings contribute to the broader field of language education and offer practical implications for educators and developers seeking to optimize self-directed language learning experiences through innovative and technologically driven approaches.

Originality/value
MALL is often ideal for individualized informal learning, but the existing literature focuses heavily on formal learning situations, underestimating the importance of MALL practices in various informal settings. Most research reports on MALL-based self-directed learning primarily sample traditional English-learning university students. Therefore, there is a need for research on how nontraditional older adult learners self-direct their language learning with mobile technology outside the classroom.
Does training content matter? Differences between soft- and hard-skill trainings in transfer motivation
Authors: Boere Nienke A. , de Jong Bastian , Jansen in de Wal Joost , Cornelissen Frank 
Published: September 2023

Purpose
Transfer motivation has been identified as a pivotal factor influencing transfer of training. However, the role of training content has often been overlooked as explanatory variable for the rate of transfer motivation. This study aims to examine to what extent experiences in transfer motivation and its personal and contextual antecedents depend on whether the training content is soft or hard skill. To this end, this study used the perspective of the unified model of task-specific motivation.

Design/methodology/approach
A total of 1,122 trainees (462 soft skill and 660 hard skill) filled out a questionnaire representing the components of transfer motivation and its personal- and contextual antecedents. Data were analyzed by means of multi group structural equation modeling.

Findings
The results showed mean differences between soft- and hard-skill trainings in personal- and contextual antecedents of transfer motivation and for different types of transfer motivation. However, no differences in transfer intention were found.

Practical implications
The outcomes provide insight as to what practitioners and trainers could do in training design and work environments to raise personal and contextual antecedents and to what extent a differentiation should be made between soft- and hard-skill trainings. This can eventually help them in raising transfer motivation among trainees.

Originality/value
To the best of the authors’ knowledge, this study is the first that examines whether experiences in personal and contextual antecedents of transfer motivation, transfer motivation and transfer intention differ for trainings consisting of different characteristics.
Exploring theoretical lineages on collaborative consumption: trends and future research paths
Authors: Ferreira João J.M. , Fernandes Ana Joana C. 
Published: September 2023

PurposeThis study reviews the literature on collaborative consumption (CC), depicting the main theoretical lineages of the CC approach while leveraging the findings to suggest promising paths for advancing the literature.Design/methodology/approachThis review is based on a bibliometric approach. The strict research protocol employed led to the inclusion of 249 articles in the descriptive and bibliometric analyses. The co-citation analysis led to the inclusion of 50 co-cited articles in the content analysis.FindingsThe descriptive analysis depicts the research profile on CC in terms of main features, yearly evolution of publications and citations, most influential articles and most influential journals. The systematization of the co-citation analysis led to the identification of three complementary theoretical lineages of research on CC: (1) theoretical roots of CC, (2) drivers of CC and (3) the sharing economy: consequences/outcomes. An integrative framework of research on CC schematizing the main theoretical lineages identified is proposed. Based on the critical gaps identified in the literature in CC, an agenda for future research is suggested.Originality/valueDespite the burgeoning interest in the CC approach, the literature has yet to fully grasp the CC concept's real implications. This study portrays a comprehensive review of the literature on CC; an integrative framework of the main theoretical lineages of research on CC is proposed, and an agenda for future research is suggested based on the critical gaps identified and implications for literature, policy and practice are stated.
Is ESG disclosure associated with bank performance? Evidence from the Visegrad Four countries
Authors: Lamanda Gabriella , Tamásné Vőneki Zsuzsanna 
Published: September 2023

PurposeThe purpose of this paper is to investigate the relationship between ESG disclosure and banks performance and to discuss how banks are committed to the implementation of sustainability issues.Design/methodology/approachThe authors examined the annual, risk and sustainability reports published by 26 banks located in four Central European countries (Czech Republic, Hungary, Poland and Slovakia) in the period of 2017–2021. The authors applied the methodology of content analysis and developed indexes. Panel regression was performed to improve and ensure the robustness of this study.FindingsThe results show that social and governance aspects dominate the ESG preparedness; however, after 2019, there was a significant improvement in the integration of environmental issues. This study confirms a strong association between bank size (total assets) and ESG reporting, and between capital adequacy and ESG reporting. The results demonstrate that there is no connection between banks' operational and financial performance and ESG disclosure. Finally, this study concludes that the integration of ESG risks into the risk management framework is at an early stage.Practical implicationsThis study also adds to the existing research in the field of sustainability reporting. For regulators, this research proves their essential role in the facilitation of sustainable development. For practitioners, the ESG disclosure index could serve as a “detection tool” in the sustainability self-assessment process.Originality/valueThe authors examined – through a self-developed multidimensional ESG disclosure index – the sustainability reporting of the banking sector in four countries from the Central European region.