bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease associated mutations in tau encode for changes in aggregate structure conformation
Authors: Sun Kerry , Patel Tark , Kang Sang-Gyun , Yarahmady Allan , Julien O. , Heras Jonathan , Mok Sue-Ann 
Published: April 2023

AbstractThe accumulation of tau aggregates is associated with neurodegenerative diseases collectively known as tauopathies. Tau aggregates isolated from different tauopathies such as Alzheimer’s disease, corticobasal degeneration and progressive supranuclear palsy have distinct cryo-electron microscopy structures with respect to their packed fibril cores. To understand the mechanisms by which tau can be sensitized to form distinct aggregate conformations, we created a panel of tau variants encoding for individual disease-associated missense mutations in full-length 0N4R tau (wild-type and 36 mutants). We developed a high-throughput protein purification platform for direct comparison of tau variants in biochemical assays. Structural analysis of the protease-resistant core of tau aggregates formedin vitroreveals that mutations can promote aggregate core packing distinct from that produced by WT tau. Comparing aggregate structure changes with aggregation kinetic parameters for tau mutants revealed no clear linkage between these two aggregation properties. We also found that tau mutation-dependent alterations of tau aggregate structure are not readily explained by current tau fibril structure data. This is the first study to show the broad potential of tau mutations to alter the packed core structures contained within aggregated tau and sheds new insights into the molecular mechanisms underlying the formation of tau aggregate structures that may drive their associated pathology in disease.
A single oscillating proto-hypothalamic neuron gates taxis behavior in the primitive chordateCiona
Authors: Chung Janeva , Newman-Smith Erin , Kourakis Matthew J. , Miao Yishen , Borba Cezar , Medina Juan , Laurent Tao , Gallean Benjamin , Faure Emmanuel , Smith William C 
Published: April 2023

SummaryCionalarvae display a number of behaviors, including negative phototaxis. In negative phototaxis, the larvae first perform short spontaneous rhythmic casting swims. As larvae cast in a light field, their photoreceptors are directionally shaded by an associated pigment cell, providing a phototactic cue. This then evokes an extended negative taxis swim. We report here that the larval forebrain ofCionahas a previously uncharacterized single slow-oscillating inhibitory neuron (neuroncor-assBVIN78) that projects to the midbrain, where it targets key interneurons of the phototaxis circuit known as thephotoreceptor relay neurons. The anatomical location, gene expression and oscillation of cor-assBVIN78 suggest homology to oscillating neurons of the vertebrate hypothalamus. Ablation of cor-assBVIN78 results in larvae showing extended phototaxis-like swims, but which occur in the absence of phototactic cues. These results indicate that cor-assBVIN78 has a gating activity on phototaxis by projecting temporally-oscillating inhibition to the photoreceptor relay neurons. However, in intact larvae the frequency of cor-assBVIN78 oscillation does not match that of the rhythmic spontaneous swims, indicating that the troughs in oscillations do not themselves initiate swims, but rather that cor-assBVIN78 may modulate the phototaxis circuit by filtering out low level inputs while restricting them temporally to the troughs in inhibition.
The enigma of the SARS-CoV-2 microcirculation dysfunction: evidence for modified endothelial junctions
Authors: Bouillet L , Benmarce M , Guérin C , Bouvet L , Garnier O , Martin D K , Vilgrain I 
Published: April 2023

AbstractPublished evidence indicates that Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection causes endothelial cell (EC) injury in the Coronavirus Disease 2019 (COVID-19). Endothelial junctions (EJ) are crucial to maintain EC integrity and normal microvascular functions due to the adhesive properties of Vascular endothelial (VE)-cadherin to glue EC together. Here we report studies in vitro and in vivo that indicate VE-cadherin to be a target for cleavage by ACE2. We have identified that the extracellular domain of VE-cadherin contains these two amino acid sequences at the positions256P-F257and321PMKP-325L for ACE2 substrate recognition. Incubation of purified sVE with ACE2 revealed a dose-dependent loss of immunoreactivity detected with an antibody directed against the Extracellular domain 1 (EC1) domain of sVE. We confirmed the presence of ACE2 on ECs using immunofluorescence studies, and by western blotting on ECs extracts. We also present evidence from patients with severe COVID-19 disease for a circulating form of ACE2. Its apparent molecular weight of 70 kDa is in agreement with a previously described extracellular form of ACE2 bearing the catalytic site of the ectopeptidase. Consistent with the experimental evidence for our hypothesis, the level of circulating soluble VE-cadherin fragments was increased in the blood of patients with severe COVID-19 disease. Further studies are needed to determine if increased circulating fragments of ACE2 and VE-cadherin may contribute to the future development of post-acute COVID-19 syndrome characterized by vascular endothelial injury, hypoxia, and inflammatory state.Impact StatementSARS-CoV-2 infection promotes vascular dysfunction but the processes are not completely understood. The vascular endothelium is composed of a monolayer of endothelial cells (ECs) that exclusively express VE-cadherin at adherens junctions (AJs). The published structure of VE-cadherin has revealed crucial residues in the domains EC1-2 for ECs adhesiveness. In this report, we demonstrate for the first time that VE-cadherin is a target for ACE2 ectoenzyme in the domains EC2-3. In addition, in COVID-19 patients’ blood, we identify truncated forms of ACE2 and VE-cadherin that are correlated with severe SARS-CoV-2 infection. Because the turnover rate of ECs is very low, this could provide part of the explanation for Long CoVID-19 disease. These exciting results highlight the role of proteases and AJs, and the need for continuing efforts to elucidate whether these circulating proteins might be of prime significance for clinicians to facilitate personalized medicine.
Supporting-cell vs. hair-cell survival in the human cochlea: Implications for regenerative therapies
Authors: Kaur Charanjeet , Van Orden McKayla , O’Malley Jennifer T. , Wu Pei-zhe , Liberman M. Charles 
Published: April 2023

AbstractAnimal studies have shown that the supporting-cells surviving in the organ of Corti after cochlear insult can be transdifferentiated into hair cells as a treatment for sensorineural hearing loss. Clinical trials of small-molecule therapeutics have been undertaken, but little is known about how to predict the pattern and degree of supporting-cell survival based on audiogram, hearing loss etiology or any other metric obtainable pre-mortem. To address this, we systematically assessed supporting-cell and hair cell survival, as a function of cochlear location in 274 temporal bone cases from the archives at the Massachusetts Eye and Ear and compared the histopathology with the audiograms and hearing-loss etiologies. Results showed that supporting-cell survival was always significantly greater in the apical half than the basal half of the cochlea, that inner pillars were more robust than outer pillars or Deiters’ cells, and that total replacement of all supporting cells with a flat epithelium was rare outside of the extreme basal 20% of the cochlea. Supporting cell survival in the basal half of the cochlea was better correlated with the slope of the audiogram than with the mean high-frequency threshold per se: i.e. survival was better with flatter audiograms than with steeply down-sloping audiograms. Cochlear regions with extensive hair cell loss and exceptional supporting cell survival were most common in cases with hearing loss due to ototoxic drugs. Such cases also tended to have less pathology in other functionally critical structures, i.e. spiral ganglion neurons and the stria vascularis.HighlightsSupporting cell survival was systematically assessed in 274 human cochleasSupporting cell survival was better with flat than with down-sloping audiogramsSupporting cell survival was most robust when hearing loss was from ototoxic drugsOtotoxic cases also showed less pathology in other critical cochlear structuresThe data can inform clinical trials for regeneration via supporting cell conversion
Nuclear receptor signaling via NHR-49/MDT-15 regulates stress resilience and proteostasis in response to reproductive and metabolic cues
Authors: Sala Ambre J. , Grant Rogan A. , Imran Ghania , Morton Claire , Brielmann Renee M. , Bott Laura C. , Watts Jennifer , Morimoto Richard I. 
Published: April 2023

AbstractThe ability to sense and respond to proteotoxic insults declines with age, leaving cells vulnerable to chronic and acute stressors. Reproductive cues modulate this decline in cellular proteostasis to influence organismal stress resilience inC. elegans. We previously uncovered a pathway that links the integrity of developing embryos to somatic health in reproductive adults. Here, we show that the nuclear receptor NHR-49, a functional homolog of mammalian peroxisome proliferator-activated receptor alpha (PPARα), regulates stress resilience and proteostasis downstream of embryo integrity and other pathways that influence lipid homeostasis, and upstream of HSF-1. Disruption of the vitelline layer of the embryo envelope, which activates a proteostasis-enhancing inter-tissue pathway in somatic tissues, also triggers changes in lipid catabolism gene expression that are accompanied by an increase in fat stores. NHR-49 together with its co-activator MDT-15 contributes to this remodeling of lipid metabolism and is also important for the elevated stress resilience mediated by inhibition of the embryonic vitelline layer as well as by other pathways known to change lipid homeostasis, including reduced insulin-like signaling and fasting. Further, we show that increased NHR-49 activity is sufficient to suppress polyglutamine aggregation and improve stress resilience in an HSF-1-dependent manner. Together, our results establish NHR-49 as a key regulator that links lipid homeostasis and cellular resilience to proteotoxic stress.
Higher education during crisis: a case study on organic resilience
Authors: Karlsson Paula Sonja , Offord Matt 
Published: April 2023

PurposeThe purpose of this paper is to explore the impact the pandemic had on higher education institutions (HEIs), the opportunities they were able to harness, and whether they are better prepared to deal with future disruptions as a result.Design/methodology/approachThe authors do this by presenting a reflective case study using a combination of crisis and resilience theories as their analytical framework. Case studies are flexible research instruments allowing researchers to draw on both subjective experience and also established theoretical frameworks. Case studies can be used to intensively analyse a specific case from an organisation, sector, or personal perspective. Although the results are not usually generalisable, they can be insightful (Bell et al., 2022).FindingsThe authors found that, in this case, a continuity strategy relevant to the sector, already existed. However, a lack of knowledge meant that the strategy was not used straight away. This was costly in terms of staff and student well-being but, ultimately, HEIs adapted by converging on a practical solution, showing inherent resilience. Further research is necessary to ascertain whether robust business continuity plans would have made the transition smoother.Originality/valueThis paper specifically investigates higher education teaching from a crisis and resilience perspective, using a theoretical framework not previously used for the analysis of Covid-19 in HEIs.
A typology of the collaboration willingness of carriers in hinterland logistics
Authors: Reinecke Pauline Charlotte , Wrona Thomas , Rückert Nicolas , Fischer Kathrin 
Published: April 2023

PurposeA large part of maritime container supply chain costs is generated by carriers in port hinterland logistics. Carriers which operate in the hinterland are under pressure to reduce costs and increase profitability, and they face challenges of fierce price competition. This study aims to explore how collaboration is perceived and implemented by carriers in truck container logistics in the port hinterland as a way to tackle these issues.Design/methodology/approachThis study adopts a qualitative multiple case study approach. Qualitative interviews with carriers in the port hinterland of Hamburg, Germany, were conducted and analyzed using grounded theory.FindingsThe study reveals two collaboration types in the hinterland, based on the different carriers' interpretation of market conditions as changeable or as given, driving their collaboration mindsets and strategic actions: The developer, who has a proactive collaboration mindset and practices strategic maneuvers toward changing poor market conditions through collaboration, and the adapter, who has a defensive collaboration mindset and perceives market conditions as given and constraining collaboration.Research limitations/implicationsThe qualitative results will help researchers better understand how collaboration practices depend on the carriers' subjective interpretations and perceptions of the market.Practical implicationsBased on the findings, managers of carriers gain an understanding of the different types of actors in their market and the relevance of acknowledging these types. Consequently, they can design appropriate strategic measures toward collaboration.Originality/valueThe findings for the first time provide exploratory insights of carriers' mindsets.
Social presence as means to humanizing online classroom
Authors: Murtafi'ah Banatul , Pradita Intan 
Published: April 2023

PurposeThe previous coronavirus disease 2019 (COVID-19) pandemic has forced pre-service English teachers to conduct their teaching simulation virtually. In the context of online teaching, social presence is vital for effective learning. This skill is perceived as a way to humanize the online learning process. This article explores how social presence is represented in the pre-service teacher's synchronous online classroom and how the development of social presence enables the pre-service teachers to develop their students' well-being and thus humanize online classrooms.Design/methodology/approachThe current study draws upon case study research. The data were collected from (1) synchronous online teaching simulation recordings of pre-service English teachers from the Language Classroom Management course and (2) interview transcripts from three participants. Both data sources were transcribed, coded and analyzed. A two-step coding scheme for pre-service English teachers' social presence was adapted from the Community of Inquiry (CoI) coding template.FindingsThis study reports that all the three social presence categories (i.e. cohesive, affective and interactive) emerged from their online teaching simulation. In addition, the development of social presence to humanize online classrooms from the pre-service teachers was found in these stages: (1) having a role model for teaching, (2) showing respect and being friendly and (3) adjusting the language of instructions to the students' level.Research limitations/implicationsThis study has been limited to the pre-service teachers in one university only. Therefore, this needs to be tested in wider settings and contexts.Practical implicationsTheoretically, this study has added students' well-being as the element that connects social presence to the humanizing online classroom. Meanwhile, practically, in relation to teacher education, this paper also recommends the teaching stages leading to a more humanized online learning.Originality/valueCurrent studies tend to describe social presence in experienced teachers' asynchronous online classrooms. Rarely did the studies explore social presence as practiced by pre-service teachers in the context of synchronous videoconferencing class. Furthermore, there has also been limited research connecting social presence with humanized classrooms.
Using keywords to link World Heritage research and practice: observations from the World Heritage Leadership Heritage Place Lab
Authors: Buckley Kristal 
Published: April 2023

PurposeThere is evidence of emerging silos separating research and practices in heritage. Creating spaces where researchers and practitioners collaborate and learn from their exchanges is therefore needed. This premise was the foundation of the pilot phase for the World Heritage Leadership Heritage Place Lab that allowed eight teams from different geocultural contexts to come together to develop research agendas. This paper provides observations about how these agendas relate to key strands in critical heritage research globally. It complements the other papers in this Special Issue that describe the case studies in detail.Design/methodology/approachA keywords approach has been used to identify areas where shared research agendas can advance both heritage practices and academic interest in the field of heritage studies. This was based on the observations made by the author during the pilot phase of the Heritage Place Lab and the research agendas produced by the research-practice teams. The approach is exploratory and experimental, inviting other contributions.FindingsTwenty keywords are identified and explored via both academic literature and the research priorities identified by the research-practice teams that participated in the pilot.Originality/valueA keywords approach is relatively untested in the field of heritage studies. Recognizing that commonly-used terms (or words) have fluid meanings across disciplines and practices potentially opens new dimensions to the dialogue between heritage practitioners and researchers.
Smart manufacturing maturity models and their applicability: a review
Authors: Vance David , Jin Mingzhou , Price Christopher , Nimbalkar Sachin U. , Wenning Thomas 
Published: April 2023

PurposeThe purpose of this paper is to review existing smart manufacturing (SM) maturity models' dimensions and maturity levels to assess their applicability and drawbacks. There are many maturity models available but many of them have not been validated or do not provide a useful guide or tool for applications. This gap creates the need for a review of the existing maturity model's applicability.Design/methodology/approachNineteen peer-reviewed maturity models related to “Digital Transformation,” “Industry 4.0” or “Smart Manufacturing” were selected based on a systematic literature review and five consulting firm models were selected based on the author's industry knowledge. The chosen models were analyzed to determine 10 categories of dimensions. Then they are assessed on a 1–5 scale for how applicable they are in the 10 categories of dimensions.FindingsThe five “consulting firm” models have a first-mover advantage, are more widely used in industry and are more applicable, but some require payment, and they lack published details and validation. The 19 “peer reviewed” models are not as widely used, lack awareness in the industry and are not as easy to apply because of no web tool for self-assessment, but they are improving. The categories defined to characterize the models and facilitate comparisons for users include “Information Technology (IT) and Cyber-Physical System (CPS) and Data,” “Strategy and Organization,” “Supply Chain and Logistics,” “Products and Services,” “Culture and Employees,” “Technology and Capabilities,” “Customer and Market,” “Cybersecurity and Risk,” “Leadership and Management” and “Governance and Compliance.” The analyzed maturity models were particularly weak in the areas of cybersecurity, leadership and governance.Practical implicationsResearchers and practitioners can use this review with consideration of their specific needs to determine if a maturity model is applicable or if a new model needs to be developed. The review can also aid in the development of maturity models through the discussion of each of the dimension categories.Originality/valueCompared to existing reviews of SM maturity models, this research determines comprehensive dimension categories and focuses on applicability and drawbacks.
The effectiveness of relationship quality on knowledge transfer in project teams: the roles of project organizational structure
Authors: Ren Xu , Xu Jing , Hao Yali , Wang Song 
Published: April 2023

PurposeThis paper aims to investigate the impact of relationship quality among team members in the project team on knowledge transfer effectiveness and analyze the role of organizational structure in the influencing process.Design/methodology/approachThe hypotheses are verified by the Structural Equation Modeling (SEM) analysis using Smart PLS 3 software with the data collected from 236 questionnaire samples in Chinese construction industry.FindingsThe results indicate that relationship quality has a direct impact on knowledge transfer in project teams and centralization has a negative impact on relationship quality. Moreover, relationship quality plays a mediating role between centralization and knowledge transfer effectiveness and formalization plays a negative moderating role in the effect of relationship quality on knowledge transfer effectiveness.Originality/valueThis paper studies intra-project knowledge transfer from the perspective of relationship quality of project teams and explores the antecedent and moderating role of organizational structure in the influence of relationship quality on knowledge transfer.
Training investment, human capital upgrading and firm innovation: the role of government training subsidies
Authors: Ni Huiqiang , Liu Wenlong , Yang Zhen 
Published: April 2023

PurposeHuman capital is acquired not only through formal education (e.g. general skills) but also through training at the workplace. Prior studies have ignored the role of government subsidies explicitly for on-the-job training, which may influence firm training decisions and firm innovation performance. Hence, the authors establish a comprehensive theoretical framework to consider these issues and fill these gaps.Design/methodology/approachConsidering the Chinese manufacturing firms listed in the Shanghai and Shenzhen Stock Exchange from 2010 to 2017, the authors investigate the influence of training investment on innovation performance by illustrating the role of human capital updating in enhancing firm innovation. The authors also explore serval mechanisms on how training investment influences innovation performance.FindingsThe authors propose that training investment promotes firm innovation performance, whereas government training subsidies negatively moderate this relationship. The authors also reveal how technicists' involvement and corporate culture mediate the relationship between training investment and innovation performance.Practical implicationsThis study provides policy implications for stimulating firm innovation by improving learning and absorption ability, strengthening cultural identity and implementing system norms. Effective policies should be adopted to provide subsidies for on-the-job training of enterprises, particularly for firms with technical executives and firms in diversified life-cycle.Originality/valueThis work contributes to the literature on the role of on-the-job training in promoting firm innovation and reveals the crowding-out effect of subsidies. This study also shows the heterogeneous effects of training investment on firm innovation.