bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLASPs stabilize the intermediate state between microtubule growth and catastrophe
Authors: Lawrence EJ , Chatterjee S , Zanic M 
Published: December 2022

ABSTRACTCLASPs regulate microtubules in many fundamental cellular processes. CLASPs stabilize dynamic microtubules by suppressing catastrophe and promoting rescue, the switch-like transitions between microtubule growth and shrinkage. However, the molecular mechanisms underlying CLASP’s activity are not understood. Here, we investigate the effects of CLASPs on distinct microtubule substrates in the absence of tubulin to gain insight into how CLASPs regulate microtubule dynamics. Surprisingly, we find that human CLASP1 depolymerizes stable microtubules in the presence of GTP, but not in the absence of nucleotide. Conversely, CLASP1 stabilizes dynamic microtubules upon tubulin dilution in the presence of GTP. Our results demonstrate that CLASP1 drives microtubule substrates with different inherent stabilities into the same slowly-depolymerizing state in the absence of tubulin in a nucleotide-dependent manner. We interpret this state as the pre-catastrophe intermediate state between microtubule growth and shrinkage. Thus, we conclude that CLASPs stabilize the intermediate state between microtubule growth and shrinkage to suppress microtubule catastrophe and promote rescue.
Cooperativity between Cas9 and hyperactive AID establishes broad and diversifying mutational footprints in base editors
Authors: Berríos Kiara N. , Barka Aleksia , Gill Jasleen , Serrano Juan C. , Bailer Peter F. , Parker Jared B. , Evitt Niklaus H. , Gajula Kiran S. , Shi Junwei , Kohli Rahul M. 
Published: December 2022

ABSTRACTThe partnership of DNA deaminase enzymes with CRISPR-Cas nucleases is now a well-established method to enable targeted genomic base editing. However, an understanding of how Cas9 and DNA deaminases collaborate to shape base editor (BE) outcomes has been lacking. Here, we support a novel mechanistic model of base editing by deriving a range of hyperactive activation-induced deaminase (AID) base editors (hBEs) and exploiting their characteristic diversifying activity. Our model involves multiple layers of previously underappreciated cooperativity in BE steps including: (1) Cas9 binding can potentially exposebothDNA strands for ‘capture’ by the deaminase, a feature that is enhanced by guide RNA mismatches; (2) after strand capture, the intrinsic activity of the DNA deaminase can tune window size and base editing efficiency; (3) Cas9 defines the boundaries of editing on each strand, with deamination blocked by Cas9 binding to either the PAM or the protospacer; and (4) non-canonical edits on the guide RNA bound strand can be further elicited by changing which strand is nicked by Cas9. Leveraging insights from our mechanistic model, we create novel hBEs that can remarkably generate simultaneous C>T and G>A transitions over >65 bp with significant potential for targeted gene diversification.
A hostile context, very limited intervention theory and almost no change in outcomes: findings from a systematic realist review of health passports for Autistic adults
Authors: Ellis Rebecca , Williams Kathryn , Brown Amy , Healer Eleanor , Grant Aimee 
Published: December 2022

AbstractBackgroundAutism is a normal part of cognitive diversity, resulting in communication and sensory processing differences, which can become disabling in a neurotypical world. Autistic people have an increased likelihood of physical and mental co-occurring conditions and die earlier than neurotypical peers. Inaccessible healthcare may contribute to this. Autism Health Passports (AHPs) are paper-based or digital tools which can be used to describe healthcare accessibility needs; they are recommended in UK clinical guidance. However, questions remained as to the theoretical underpinnings and effectiveness of AHPs.MethodsWe undertook a systematic literature search identifying studies focused on AHPs for adults (aged over 16 years) from five databases. Included literature was subjected to realist evaluation. Data were extracted using a standardised form, developed by the research team, which considered research design, study quality for realist review and theContext,Mechanisms andOutcomes (CMOs) associated with each AHP tool.Findings162 unique records were identified, and 13 items were included in the review. Only one item was considered high quality. Contextual factors focused on the inaccessibility of healthcare to Autistic patients and staff lack of confidence and training in supporting Autistic needs.Interventions were heterogeneous, with most sources reporting few details as to how they had been developed. The most frequently included contents were communication preferences.Mechanisms were often not stated or were inferred by the reviewers and lacked specificity.Outcomes were included in four studies and were primarily focused on AHP uptake, rather thanOutcomes which measured impact.ConclusionThere is insufficient evidence to conclude that AHPs reduce the health inequalities experienced by Autistic people. Using an AHP tool alone, without the inclusion of the local Autistic community developing the tool, and a wider intervention, such as training for staff or the use of local champions, may mean that AHPs do not trigger anyMechanisms, and thus cannot affectOutcomes.
Near-critical tuning of cooperativity revealed by spontaneous switching in a protein signalling array
Authors: Keegstra Johannes M , Avgidis Fotios , Mulla Yuval , Parkinson John S , Shimizu Thomas S 
Published: December 2022

Dynamic properties of allosteric complexes are crucial for cellular information processing. However, direct observations of allosteric switches have been limited to compact molecular assemblies. Here, we reportin vivoFRET measurements of spontaneous discrete-level fluctuations in the activity of theEscherichia colichemosensory array — an extensive membrane-associated assembly comprising thousands of molecules. Finite-size scaling analysis of the temporal statistics by a two-dimensional conformational spread model revealed nearest-neighbor coupling strengths within 3% of the Ising second-order phase transition, indicating that chemosensory arrays are poised at criticality. Our analysis yields estimates for the intrinsic timescale of conformational changes (~ 10 ms) of allosteric units, and identifies near-critical tuning as a design principle for balancing the inherent tradeoff between response amplitude and response speed in higher-order signaling assemblies.One-setence summaryIn vivomeasurements of protein signaling array fluctuations reveal an allosteric system poised at criticality.
Transcriptome and biochemical analysis pinpoint multi-layered molecular processes associated with iron deficiency tolerance in hexaploid wheat
Authors: Meena Varsha , Kaur Gazaldeep , Joon Riya , Shukla Anuj , Choudhary Promila , Singh Palvinder , Roy Joy K , Singh Bhupinder , Pandey Ajay K 
Published: December 2022

AbstractIron (Fe) is an essential nutrient for plants that is indispensable for many physiological activities. Although few genotypes were identified with contrasting tolerance to Fe deficiency, the molecular insight into the distinct biochemical and transcriptional responses determining the trait is poorly known. This study aimed to identify the molecular and biochemical basis for the contrasting Fe deficiency tolerance in wheat genotype showing tolerance to Fe deficiency (cv. Kanchan-KAN) compared to susceptible (cv. PBW343-PBW) cultivar. Under Fe deficiency, the KAN show delayed chlorosis, high SPAD values and low malondialdehyde activity compared to PBW. The shoot transcriptomics studies show that a large set of genes for photosynthetic pathways were highly induced in PBW, suggesting its sensitivity to Fe deficiency. Although, under Fe deficiency, both the cultivars show distinct molecular re-arrangements, including high expression of genes involved in Fe uptake (including membrane transporters) and mobilization, the gene expression level was higher in KAN. Furthermore, the KAN cultivar also shows high ubiquitination activity in the shoot tissue suggesting a high turnover of proteins in the tolerant cultivar. These observations were also co-related with the high root phytosiderophores biosynthesis and its release that contributes to the enhanced Fe translocation index in KAN. Overall, our work provides the key link to understanding the mechanistic insight for the Fe deficiency tolerance in hexaploid wheat. This will enable wheat breeders to select genotypes for better Fe use efficiency for agriculture.
Single-molecule visualization of stalled replication-fork rescue by theEscherichia coliRep helicase
Authors: Whinn Kelsey S. , Xu Zhi-Qiang , Jergic Slobodan , Sharma Nischal , Spenkelink Lisanne M. , Dixon Nicholas E. , van Oijen Antoine M. , Ghodke Harshad 
Published: December 2022

ABSTRACTGenome duplication occurs while the template DNA is bound by numerous DNA-binding proteins. Each of these proteins act as potential roadblocks to the replication fork and can have deleterious effects on cells. InEscherichia coli, these roadblocks are displaced by the accessory helicase Rep, a DNA translocase and helicase that interacts with the replisome. The mechanistic details underlying the coordination with replication and roadblock removal by Rep remain poorly understood. Through real-time fluorescence imaging of the DNA produced by individualE. colireplisomes and the simultaneous visualization of fluorescently-labeled Rep, we show that Rep continually surveils elongating replisomes. We found that this association of Rep with the replisome is stochastic and occurs independently of whether the fork is stalled or not. Further, we visualize the efficient rescue of stalled replication forks by directly imaging individual Rep molecules as they remove a model protein roadblock, dCas9, from the template DNA. Using roadblocks of varying DNA-binding stabilities, we conclude that replication restart is the rate-limiting step of stalled replication rescue.
Biased activation of the receptor tyrosine kinase HER2
Authors: Catapano Claudia , Rahm Johanna V , Omer Marjan , Teodori Laura , Kjems Jørgen , Dietz Marina S , Heilemann Mike 
Published: December 2022

AbstractHER2 belongs to the ErbB sub-family of receptor tyrosine kinases and regulates cellular proliferation and growth. Different from other ErbB receptors, HER2 has no known ligand. Activation occurs through heterodimerization with other ErbB receptors and their cognate ligands. This suggests several possible activation paths of HER2 with ligand-specific, differential response, which so far remained unexplored. Using single-molecule tracking and the diffusion profile of HER2 as a proxy for activity, we measured the activation strength and temporal profile in live cells. We found that HER2 is strongly activated by EGFR-targeting ligands EGF and TGFα, yet with a distinguishable temporal fingerprint. The HER4-targeting ligands EREG and NRGβ1 showed weaker activation of HER2, a preference for EREG, and a delayed response to NRGβ1. Our results indicate a selective ligand response of HER2 that may serve as a regulatory element. Our experimental approach is easily transferable to other membrane receptors targeted by multiple ligands.HighlightsHER2 exhibits heterogeneous motion in the plasma membraneThe fraction of immobile HER2 correlates with phosphorylation levelsDiffusion properties serve as proxies for HER2 activationHER2 exhibits ligand-specific activation strength and temporal profilesGraphical Abstract
Trust and performance: a contextual study of management change in private and public organisation
Authors: Karhapää Sari-Johanna , Savolainen Taina , Malkamäki Kirsti 
Published: December 2022

PurposeAlthough previous studies have addressed the positive relationship between trust and performance, existing research has paid limited attention to management that shapes valued organisation behaviours important for effectiveness and wellbeing. This paper examines how organisational trust and performance unfold in the context of one private and one public sector case organisation in management change.Design/methodology/approachA multiple case study design using qualitative methods is applied to analyse textual data gathered from management and employee perspectives, juxtaposing private and public organisations.FindingsManagement change renewed decision-making in both organisations through role clarification. Through clearer roles, expectations were better managed in the collaborating units of a private organisation case and of the employees in a public organisation case impacting on organisational ability and predictability. Along with organisational communication, these develop trust which seems to be reflected in employee job performance at the organisational level.Originality/valueThis paper contributes to the gap in qualitative, empirical and contextual research by providing understanding about how intra-organisational trust is related to performance. Further, this paper sheds light on the vulnerability within an organisation during management change and adds to the somewhat scarce studies of relationships between trust and performance by juxtaposing the two contexts. Consequently, this enables one to reveal different approaches to trust and performance between the two sectors.
BIM guidance to optimise the operational phase: defining information requirements based on ISO 19650
Authors: Ashworth Simon , Dillinger Michelle , Körkemeyer Karsten 
Published: December 2022

Purpose
This paper aims to describe the development of guidance to help clients and operational teams to clearly define information requirements for projects using building information modelling (BIM). ISO 19650 standards highlight this as a critical first step to ensure adequate information is available to optimise built assets over their whole life cycle.

Design/methodology/approach
A document analysis of existing BIM guidance supported by literature was undertaken to answer the research questions: “What guidance already exists specific to clients? and Would additional guidance help clients to better fulfil their role as the ‘appointing party’ in line with ISO 19650?”

Findings
A research gap was established highlighting a lack of guidance specifically aimed to help clients formulate information requirements as the appointing party. This research makes recommendations for an approach to define the requirements and support successful outcomes for BIM projects.

Practical implications
This paper provides a standardised approach and a starting point for an appointing party to gather and structure information requirements in line with ISO 19650.

Originality/value
This paper considers BIM information requirements specifically from an operations perspective with a focus on the client and facility management team.
Achieving agreement on service needs in child protection. Comparing children’s, mothers’ and practitioners’ views over time and between approaches
Authors: Aaltio Elina , Kannasoja Sirpa 
Published: December 2022

Purpose
While studies on service users’ participation and their perceptions on the quality of services exist, agreement between family members’ and practitioners’ assessments of the family’s situation has received less interest. The purpose of this paper is to investigate agreement and its effect on outcomes by comparing the viewpoints of three groups of informants (children, mothers and practitioners) in the context of statutory child protection in two study groups – one applying a systemic approach (SPM) and a service-as-usual control group (SAU).

Design/methodology/approach
A quasi-experimental repeated-measures study design was applied. Outcome data comprised 112 cases (SPM cases n = 56 and SAU cases n = 56) at three sites. Data was collected from all participants at baseline and six months later.

Findings
First, practitioners’ analyses of a child’s need for protection did not meet family members’ expressed need for help. Second, child–mother agreement on the need for service intervention at T1 predicted a decrease in practitioner-assessed abuse or neglect from T1 to T2. In this sample, no differences were found between the two groups.

Originality/value
This study highlights the importance of making explicit the viewpoints of children, parents and practitioners in casework and research to improve understanding of how their perspectives differ over the course of the process and how possible initial disagreements affect outcomes.
Identity work in the backstage: exploring the role of expatriate bubbles in identity work of self-initiated expatriate engineers through a Goffmanian lens
Authors: Papafilippou Vanda , Efthymiadou Christina 
Published: December 2022

PurposeWhile there is vast research on expatriate adjustment, it is still known very little on how self-initiated expatriates (SIEs) in particular might cope with identity conflicts and how they engage with identity work. What is more, although there is some literature on the existence of expatriate bubbles, this does not cover how these bubbles might impact identity work. The purpose of this paper is to explore identity work that is taking place within expatriate bubbles and thus advance our knowledge on both expatriate bubbles and expatriate adjustment.Design/methodology/approachThe study reports on the analysis of in-depth, semi-structured interview data collected from 37 self-initiated expatriate engineers from Greece, Spain and Italy, currently residing in Bristol, UK.FindingsPrevious studies have argued that expatriate bubbles impede adjustment. The study analysis, however, shows that expatriate bubbles can be not only a powerful mechanism for coping with foreignness and strengthening their sense of belonging but also act as identity workspaces where SIEs engaged with identity work and navigated identity conflicts.Originality/valueThe present study addresses two empirical gaps: the paucity of literature on the identity work that self-initiated expatriates engage with and the paucity studies on self-initiated expatriate engineers. The study also has a theoretical contribution as, drawing upon a Goffmanian dramaturgical framework sheds light on the back regions of performance taking place within expatriate bubbles. Thus, showing how SIEs relax but also rehearse their performances in order to reduce any identity gaps triggered by the new organisational and national context.
The dark side of leave: how voluntary leave shapes preferences for male and female supervisors
Authors: Motro Daphna , Pittarello Andrea , Nolan Kevin P. , Shahani-Denning Comila , Lenaghan Janet A. 
Published: December 2022

PurposeTo determine how different voluntary leaves of absence (parental vs. community service) affect individuals’ preferences for working with either male or female supervisors. Drawing on role congruity theory, the authors examined whether individuals would least prefer supervisors who took voluntary leave that violated role expectations.Design/methodology/approachIn Study 1, participants (n = 372) evaluated supervisors who took different forms of leave (none vs. parental vs. community service). In Study 2 (n = 202), the authors tested an intervention to reduce negative bias toward males taking community service leave. In both studies the authors examined the sex of the supervisor (male vs. female) on perceptions of typicality and supervisor preference.FindingsMales who took community service leave were perceived as most atypical and were least preferred as supervisors. However, providing relevant research-based information about typicality reduced this bias.Practical implicationsThe results show that people respond negatively toward males who take community service leave. Managers can help reduce this bias by providing relevant research-based information regarding community service leave.Originality/valueThis work is among the first to explore the consequences of community service leave and how it interacts with supervisor sex. The authors also identify a simple way to reduce bias against males who take community service leave.
Cultural tourist and user experience with artificial intelligence: a holistic perspective from the Industry 5.0 approach
Authors: Orea-Giner Alicia , Muñoz-Mazón Ana , Villacé-Molinero Teresa , Fuentes-Moraleda Laura 
Published: December 2022

PurposeThe purpose of this paper is to analyse the future of the implementation of artificial intelligence (AI) technologies in services experience provided by cultural institutions (e.g. museums, exhibition halls and cultural centres) from experts’, cultural tourists’ and users’ point of view under the Industry 5.0 approach.Design/methodology/approachThe research was conducted using a qualitative approach, which was based on the analysis of the contents obtained from two roundtable discussions with experts and cultural tourists and users. A thematic analysis using NVivo was done to the data obtained.FindingsFrom a futuristic Industry 5.0 approach, AI is considered to be more than a tool – it as an integral part of the entire experience. AI aids in connecting cultural institutions with users and is beneficial since it allows the institutions to get to know the users better and provide a more integrated and immersive experience. Furthermore, AI is critical in establishing a community and nurturing it daily.Originality/valueThe most important contribution of this research is the theoretical model focused on the user experience and AI application in services experiences of museums and cultural institutions from an Industry 5.0 approach. This model includes the visitors’ and managers’ points of view through the following dimensions: the pre-experience, experience and post-experience. This model is focused on human–AI coworking (HAIC) in museums and cultural institutions.
Defected microstrip structure-based near-end and far-end crosstalk mitigation in high-speed PCBs for mixed signals
Authors: V. Yokesh , Alsath Gulam Nabi , Kanagasabai Malathi 
Published: December 2022

Purpose
The design, fabrication and experimental validation of defected microstrip structure (DMS) are proposed to address the problem of near-end crosstalk (NEXT) and far-end crosstalk (FEXT) between the microstrip transmission lines in a printed circuit board.

Design/methodology/approach
The proposed DMS evolved with the combination of spur line (L-shaped DMS) and U-shaped DMS topologies. This technique reduces the strength of electromagnetic coupling and suppresses crosstalk by optimizing the capacitive and inductive coupling ratio between the linked microstrip lines. The practical inductance value is much more significant in DMS than in defected ground structures (DGS), but the capacitance value remains the same.

Findings
A DMS unit is etched on the aggressor microstrip line instead of the DGS circuit. Because there is no leakage via the ground plane and the circuit size is far smaller than with DGS, the enclosure issue is disregarded. DMS structures have a larger effective inductance and are resistant to electromagnetic interference. A tightly coupled transmission line structure with minimal separation between the coupled microstrip line is designed using DMS. Further research must be conducted to improve the NEXT, FEXT and spacing between the transmission lines.

Originality/value
Simulation and actual measurement results show that the proposed DMS structure can effectively suppress crosstalk by analysing the S-parameters, namely, S_12, S_13 and S_14, with measured values of 1.48 dB, 20.65 dB and 21.099 dB, respectively. The data rate is measured to be 1.34 Gbps as per the eye diagram characterization. The results show that the NEXT and FEXT are reduced by approximately 20 dB in the frequency range of 1–11 GHz for mixed signals. The substantial measured results in the vector network analyser coincide with the computer simulation technology microwave studio suite simulation results.