bluuebunny/crossref_metadata_2025_split huggingface dataset:
The N-terminal PAS domain directly regulates hERG channel gating in excised, inside-out patch-clamp fluorometry (PCF) recordings
Authors: Trudeau Matthew C. 
Published: July 2024

ABSTRACTHuman ERG is a voltage-activated, K-selective channel whose physiological role is to drive action potential repolarization in cardiac myocytes. To carry out its role in the heart, hERG has specialized gating (opening and closing) transitions that are regulated by the internal N-terminal PAS and C-terminal CNBH domains. The PAS and CNBHD domains interact directly and this interaction is required for the characteristic slow deactivation (closing) of hERG channels. But it is unclear whether PAS remains globally attached or dislodges from the CNBHD during gating. Interestingly the direct PAS-CNBHD interaction can be formedin transby co-expression of the PAS domain and hERG channels with a deleted PAS domain (hERG ΔPAS) in which the PAS domain is not attached to the channel with a peptide bond.In transexpression allows us to probe the biophysical mechanism for PAS domain attachment to the rest of the channel and in a broader sense allows us to test the mechanism for intracellular domain function in an ion channel, and test whether the PAS domain detaches or remains attached to the channel during gating. We report here that in excised patches from cells containing the hERG PAS domain fused to CFP and hERG ΔPAS channels fused to Citrine that 1) regulation of deactivation (slow deactivation conveyed by the PAS domain) was similar in on-cell and excised, inside-out patch configurations, 2) that regulation of deactivation persists for the lifetime of the patch (up to 30 minutes) in excised, inside-out mode, 3) that channel activity measured by activation of the channel with voltage pulses did not alter channel deactivation and 4) dual fluorescence and ionic current measurements using patch-clamp fluorometry (PCF) showed that only membrane patches containing PAS-CFP + hERG ΔPAS-Citrine had CFP and Citrine fluorescence and slow (regulated) deactivation, whereas control patches with hERG ΔPAS -Citrine had fast (unregulated) deactivation and Citrine fluorescence (but not CFP fluorescence) and control patches from hERG PAS-CFP - injected cells had neither currents nor CFP or Citrine fluorescence. Moreover, in PCF mode, we detected FRET from PAS-CFP + hERG ΔPAS-Citrine channels. Taken together, these results suggested that PAS - CFP remained associated with hERG ΔPAS-Citrine channels after membrane excision. We interpret these results to mean that the PAS domain was not dislodged from the channel despite mechanical (excised patch) and conformational (voltage) challenges and suggests that the PAS domain remained firmly attached to the hERG channel during gating.
Identification of Juglone, a ‘first-in-class’ inhibitor of the human glutathione degrading enzyme, ChaC1, using yeast-based high throughput screens
Authors: Suyal Shradha , Choudhury Chinmayee , Kaur Deepinder , Bachhawat Anand K. 
Published: July 2024

AbstractThe cytosolic glutathione-degrading enzyme, ChaC1, is highly upregulated in several cancers, with the upregulation correlating to poor prognosis. The ability to inhibit ChaC1 thus becomes important in pathophysiological situations where elevated glutathione levels would be beneficial. As no inhibitors of ChaC1 are known, in this study we have focussed on this goal. We have initially taken a computational approach where a systemic structure-based virtual screening was performed. However, none of the predicted hits proved to be effective inhibitors. We also evaluated synthetic substrate analogs, but these too were not inhibitory. As both these approaches targeted the active site, we shifted to developing two high-throughput, robust, yeast-based assays that were active site independent. A small molecule compound library was screened using an automated liquid handling system using these screens. The hits were further analyzed usingin vitroassays. Among them, juglone, a naturally occurring naphthoquinone, completely inhibited ChaC1 activity with an IC50of 8.7 µM. It was also effective against the ChaC2 enzyme. Kinetic studies indicated that the inhibition was not competitive with the substrate. Juglone is known to form adducts with glutathione and is also known to selectively inhibit enzymes by covalently binding to their active site cysteine residues. However, juglone continued to inhibit a cysteine-free ChaC1 variant, indicating that it was acting through a novel mechanism. We evaluated different inhibitory mechanisms, and also analogues of juglone, and found plumbagin effective as an inhibitor. These compounds represent the ‘first-in-class’ inhibitors of the ChaC enzymes discovered using a robust yeast screen.
Structural Basis for RNA-guided DNA degradation by Cas5-HNH/Cascade complex
Authors: Liu Yanan , Wang Lin , Zhang Qian , Fu Pengyu , Zhang Lingling , Zhang Heng , Zhu Hongtao 
Published: July 2024

AbstractType I-E CRISPR (clustered regularly interspaced short palindromic repeats)–Cas (CRISPR-associated) system is the most widely investigated RNA-guided adaptive immune system in prokaryotes against the foreign genetic elements. Unlike the previously characterized Cas3 nuclease in the typical Type I-E system that exhibits uncontrolled progressive DNA cleavage, a recently discovered HNH domain linked to the Cas5 subunit functions as the nuclease for precise DNA cleavage, highlighting the potential of this new Type I-E variant system as a precise genome editing tool. Here, we present five near- atomic cryo-EM (cryo-electron microscopy) structures ofCandidatus Cloacimonetes bacteriumCas5-HNH/Cascade complex either bound or unbound to DNA. We revealed that the HNH domain extensively interacts with the adjacent subunits, including Cas6, Cas8 and Cas11. The related mutations of the crucial identified interactions can significantly weaken the performance of the enzyme. Upon the binding of DNA, the Cas-HNH/Cascade complex adopts a more compacted conformation with the subunits moving towards the center of the nuclease, thus activating the nuclease. We further identified four conserved cysteines that form a zinc-finger structure in the HNH domain and the mutations of these four cysteines can totally abolish the enzyme activity. Interestingly, we also discovered that the divalent ions such as zinc, cobalt and nickel down-regulate the enzyme performance by decreasing the stability of the Cascade complex. Together, our findings provide first structural insights into the assembly and activation of the Cas5-HNH/Cascade complex, opening new avenues for engineering this system for precise genome editing.
Dark matter phenomenology and phase transition dynamics of the next-to-minimal composite Higgs model with a dilaton
Authors: Zhang Borui , Zhang Zhao , Cai Chengfeng , Zhang Hong-Hao 
Published: July 2024

In this paper, we conduct a comprehensive study of the next-to-minimal composite Higgs model (NMCHM) extended with a dilaton field χ (denoted as NMCHMχ). A pseudo-Nambu-Goldstone boson (pNGB) η, resulting from the SO(6)→SO(5) breaking, serves as a dark matter (DM) candidate. The inclusion of the dilaton field is helpful for evading the stringent constraints from dark matter direct detection, as it allows for an accidental cancellation between the amplitudes of DM-nucleon scattering, an outcome of the mixing between the dilaton and Higgs fields. The presence of the dilaton field also enriches the phase transition patterns in the early universe. We identify two types of phase transitions: (i) a 1-step phase transition, where the chiral symmetry and electroweak symmetry breaking (EWSB) occur simultaneously, and (ii) a 2-step phase transition, where the chiral symmetry breaking transition takes place first, followed by a second phase transition corresponding to EWSB. Since the first-order phase transitions can be strong due to supercooling in our model, we also examine the stochastic background of gravitational waves generated by these phase transitions. We find that these gravitational waves hold promise for detection in future space-based gravitational wave experiments, such as LISA, Taiji, BBO, and DECIGO.

Published by the American Physical Society
2024
New framework to follow up candidates from continuous gravitational-wave searches
Authors: Covas P. B. , Prix R. , Martins J. 
Published: July 2024

Searches for continuous gravitational waves from unknown neutron stars are limited in sensitivity due to their high computational cost. For this reason, developing new methods or improving existing ones can increase the probability of making a detection. In this paper we present a new framework that uses Markov chain Monte Carlo (MCMC) or nested sampling methods to follow up candidates of continuous gravitational-wave searches. This framework aims to go beyond the capabilities of (which is limited to the sampler), by allowing a flexible choice of sampling algorithm (using as a wrapper) and multidimensional correlated prior distributions. We show that MCMC and nested sampling methods can recover the maximum posterior point for much bigger parameter-space regions than previously thought (including for sources in binary systems), and we present tests that examine the capabilities of the new framework: a comparison between the , , and samplers, the usage of correlated priors, and its improved computational cost.

Published by the American Physical Society
2024
How do emotions influence healthy food choice? Investigating an extended framework of the social-cognitive theory
Authors: Brückner Katrin , Emberger-Klein Agnes , Menrad Klaus 
Published: July 2024

PurposeThe purpose of this study was to investigate how and through which social-cognitive constructs, emotions influence healthy food shopping behaviors. Direct effects of those constructs, as well as indirect effects of consumer emotions are considered.Design/methodology/approachAn altered version of the Social Cognitive Theory, including intention, socio-structural factors, outcome expectancies and self-efficacy with the addition of consumer emotions was analyzed using structural equation modeling. Data of 1,181 volunteers were collected in Germany in 2021 through an online survey.FindingsIntention was the most important positive predictor of food choice, while socio-structural factors had the biggest impact on intentions. Those were mostly influenced by self-efficacy, which was strongly predicted by consumer emotions. Outcome expectancies did not influence the current model in any way. Consumer emotions did not directly influence intention, nor actual choice, however showed to be influencing those variables through indirect effects.Practical implicationsMarketers could benefit from these results by incorporating the current findings into existing marketing strategies through targeting a combination of social cognitive constructs, as well as consumer emotions to facilitate healthier food shopping behavior.Originality/valueAffect has received increasing attention in regards to its impact on healthy eating behaviors in recent years. Less attention has been paid to the mechanisms through which emotions influence healthy nutrition behavior, specifically how consumer emotions influence healthy food shopping behavior.
Risk coupling analysis of causal factors in construction fall-from-height accidents
Authors: Niu Hongying , Yang Xiaodong , Zhang Jiayu , Guo Shengyu 
Published: July 2024

PurposeConstruction fall-from-height accidents are not only caused by a single factor but also by the risk coupling between two or more factors. The purpose of this paper is to quantitatively analyze the risk coupling relationships between multiple factors and identify critical factors in construction fall-from-height accidents.Design/methodology/approachA cause analysis framework was established from the perspective of human, machine, material, management and environmental factors. The definition, the classification and the process of risk coupling were proposed. The data from 824 historical accident reports from 2011 to 2021 were collected on government websites. A risk coupling analysis model was constructed to quantitatively analyze the risk coupling relationships of multiple factors based on the N-K model. The results were classified using K-means clustering analysis.FindingsThe results indicated that the greater the number of causal factors involved in risk coupling, the higher the risk coupling value and the higher the risk of accidents. However, specific risk coupling combinations occurred when the number of their coupling factors was not large. Human, machine and material factors were determined to be the critical factors when risk coupling between them tended to pose a greater risk of accidents.Originality/valueThis study established a cause analysis framework from five aspects and constructed a theoretical model to quantitatively analyze multi-factor coupling. Several suggestions were proposed for construction units to manage accident risks more effectively by controlling the number of factors and paying more attention to critical factors coupling and management and environmental factors.
Validation of knowledge hiding measurement in South Korea
Authors: Joo Jaehong , Lee Yunsoo , Song Ji Hoon 
Published: July 2024

Purpose
Given that knowledge hiding hampers the management of employee knowledge, it is important to measure the phenomena before applying the intervention to alleviate it. This paper aims to validate knowledge hiding measurements in South Korea.

Design/methodology/approach
The research collected 420 and 415 different Korean employee samples for each study, and they responded to their quality of knowledge hiding. The research conducted factor analysis using Mplus software and the Rasch model using JMetrik software based on the item response theory.

Findings
The research validated Korean versions of knowledge hiding measurements consisting of three factors and ten items. The study also found that knowledge hiding has a negative relationship with knowledge sharing and an unexpectedly positive relationship with team creativity. The study confirmed that the modified measurement yields acceptable discriminant and convergent validity.

Research limitations/implications
The research relied on self-reported data and may have an issue measuring their knowledge hiding generously. Therefore, researchers are encouraged to measure it from others, including supervisors and colleagues. This research has theoretical implications for psychometrically and systematically validating the measurement.

Practical implications
The research includes practical implications for contributing to Human resource development practitioners could assess employee traits accurately and manage their negative knowledge behavior.

Social implications
The research suggests the implications for detecting a positive relationship between knowledge hiding and team creativity. The study discussed that the specific climate could contribute to team creativity in Eastern contexts.

Originality/value
The research identified the importance of a psychometric validating process in the development of measurements.
Empowering women: navigating work environment challenges with mental toughness
Authors: Subramanian Prabha , Gallant Monica , Pani Pranab K. 
Published: July 2024

Purpose
This literature review examines women’s significant workplace challenges and explores mental toughness, a distinct non-cognitive ability associated with peak athletic performance. This study aims to understand this concept and its potential for women professionals facing similar challenges in an organisational context.

Design/methodology/approach
Based on a systematic literature review, this exploratory paper is an integrative literature review synthesising pre-existing knowledge using secondary scientific databases. This literature analysis will pave the way for comprehension of the existing body of research, identification of research gaps, and opportunities for further studies. Different typologies of mental toughness (MT) have been identified, and a new typology will emerge from this research study.

Findings
The study analyses over 100 articles based on MT typology and complex gender dynamics at work, especially the “broken rung” concept of trapping women in lower or mid-level roles in an organisation. This content analyses the recent emergence of the MT typology in academic research, with articles published after 2019 and a few earlier key works that shaped the concept of MT. In addition to contributing a comprehensive typology of MT and its impact on women professionals, this paper also provides recommendations for future research and individual-level development of MT to help women overcome workplace barriers globally.

Research limitations/implications
Understanding MT’s impact on women’s ability to overcome workplace barriers has HR implications, including hiring, retention, career advancement, training and closing gender gaps. This research may help individual women professionals adopt MT as a psychological resource to navigate work environment challenges. Further research is needed for practical insights, given this discussion is based on a literature review.

Practical implications
The practical implications of this study have a profound impact on human resource management practices within organisations, highlighting the multifaceted approach required to tackle gender disparity. A more inclusive and supportive work environment can be created by ensuring MT training is accessible to all employees. A comprehensive career development plan for women professionals, including but not limited to mentoring, executive sponsorship, skill-building training or stretched assignments, leadership coaching, networking opportunities, and increased visibility in the organisation are critical for career advancement and retention.

Originality/value
This study is a novel attempt to examine whether MT, which has proven effective in helping athletes achieve their goals, can be applied in a workplace environment. It is also a new endeavour to investigate whether women could use MT as a psychological tool to help them overcome obstacles in a diverse professional setting.
The relationship between emotional biases and investment decisions: a meta-analysis
Authors: Kumar Shailendra , Chaurasia Akash 
Published: July 2024

PurposeThe study attempts to investigate the relationship between emotional biases (loss aversion bias, overconfidence bias, and regret aversion bias) and investment decisions through a meta-analysis approach.Design/methodology/approachA meta-correlation analysis was done using sample size and correlation (r) data from several relevant studies that look at how emotional biases (loss aversion bias, regret aversion bias, and overconfidence bias) affect investment decisions. Additionally, beta coefficients (ß) were also converted to correlation coefficients (r) from six studies.FindingsThis study analysed 31 empirical studies and found a significant positive correlation between emotional biases and investment decisions [loss aversion bias (r = 0.492), regret aversion bias (r = 0.401), and overconfidence bias (r = 0.346)]. We set the statistical significance threshold at 0.05.Research limitations/implicationsThe review covered 31 online research publications that showed significant heterogeneity, possibly influenced by various methodological, population, or other factors. Furthermore, the use of correlational data restricts the ability to establish causation.Originality/valueThis is a novel attempt to integrate the results of various studies through meta-analysis on the relation between these emotional biases (loss aversion, overconfidence, and regret aversion) and investment decisions.
Digital leadership in the digital era of education: enhancing knowledge sharing and emotional intelligence
Authors: Anwar Sadia , Saraih Ummi Naiemah 
Published: July 2024

PurposeEstablishing an effective educational system is directly tied to academic leadership, a multifaceted concept that differs from one environment to another. The purpose of this research is to investigate the role of digital leadership (DL) aspects in the enhancement of technical knowledge sharing (KS) and dealing with emotional intelligence (EI) among the teaching faculty of higher education institutions (HEIs).Design/methodology/approachFollowing a quantitative and cross-sectional research design, convenient sampling is employed for data collection via a self-administered questionnaire from 320 faculty members of private HEIs in Pakistan.FindingsStructural equation model (SEM) is used for path analysis. The results reveal a positive and significant effect of DL, aspects like visionary leadership (VL), digital citizenship (DC), systematic improvement (SI), on knowledge sharing (KS), and emotional intelligence (EI).Practical implicationsThis study has highlighted the significance of DL in private HEIs. The findings of the study imply that institutional heads of higher education institutions (HEIs) can successfully manage the knowledge assets that they have and those of their staff members, ensure the successful adoption of technology and foster product and process innovation that improves organizational performance and integrates successful strategies into the educational system by demonstrating DL aspects. The research also analyzes institutional heads' present leadership strategies to enhance response to technological change and innovations, which are considered fundamental pillars of organizational success. Ultimately, this will extend the literature on adopting DL techniques towards digital transformation in the education system.Originality/valueThis study empirically confirms the role of DL aspects such as VL, DC, and SI towards KS and EI. Most of the research demonstrates the direct impact of DL on EI, whereas the aspects of DL are not directly related to KS and EI. Studies have also shown how DL enhances its role in incorporating leadership in organizations, industries, and education, mainly in Western countries. This research addresses the gap in understanding the direct effects of DL aspects on KS and EI in non-Western countries, particularly within the education sector.