bluuebunny/crossref_metadata_2025_split huggingface dataset:
p115RhoGEF activates RhoA to support tight junction maintenance and remodeling
Authors: Chumki Shahana A. , van den Goor Lotte M. , Hall Benjamin N. , Miller Ann L. 
Published: June 2022

AbstractIn vertebrates, epithelial cell-cell junctions must rapidly remodel to maintain barrier function as cells undergo dynamic shape-change events. Consequently, localized leaks sometimes arise within the tight junction (TJ) barrier, which are repaired by short-lived activations of RhoA, called “Rho flares”. However, what activates RhoA at leak sites remains unknown. Here, we asked which guanine nucleotide exchange factor (GEF) localizes to TJs to initiate Rho activity at Rho flares. We find that p115RhoGEF locally activates Rho flares at sites of barrier leaks and TJ loss. Knockdown of p115RhoGEF leads to diminished Rho flare intensity and impaired TJ remodeling. p115RhoGEF knockdown also decreases junctional active RhoA levels, thus compromising the apical actomyosin array and junctional complex. Furthermore, p115RhoGEF is necessary to preserve global TJ barrier function by promoting local leak repair and preventing repeating leaks. In all, our work demonstrates a central role for p115RhoGEF in activating junctional RhoA to preserve barrier function and direct local TJ remodeling.
Phenotypic Heterogeneity in the DNA Replication Stress Response Revealed by Quantitative Protein Dynamics Measurements
Authors: Ho Brandon , Loll-Krippleber Raphael , Torres Nikko P. , Cuny Andreas , Rudolf Fabian , Brown Grant W. 
Published: June 2022

AbstractCells respond to environmental stressors by activating programs that result in protein abundance and localization changes. The DNA damage and DNA replication stress responses have been heavily studied and provide exemplars of the roles of protein localization and abundance regulation in proper cellular stress response. While vast amounts of data have been collected to describe the dynamics of yeast proteins in response to numerous external stresses, few have assessed and compared both protein localization kinetics and phenotypic heterogeneity in the same context, particularly during DNA replication stress. We developed a robust yet simple quantification scheme to identify and measure protein localization change events (re-localization) and applied it to the 314 yeast proteins whose subcellular distribution changes following DNA replication stress. We captured different kinetics of protein re-localization, identified proteins with localization changes that were not detected in previous analyses, and defined the extent of heterogeneity in stress-induced protein re-localization. Our imaging platforms and analysis pipeline enables efficient measurements of protein localization phenotypes for single cells over time and will guide future work in elucidating the biological parameters that govern cellular heterogeneity.
Discovery of a Gut Bacterial Metabolic Pathway that Drives α-Synuclein Aggregation and Neurodegeneration
Authors: Ortiz de Ora Lizett , Uyeda Kylie S. , Bess Elizabeth 
Published: June 2022

AbstractParkinson’s disease (PD) etiology is associated with aggregation and accumulation of α-synuclein (α- syn) proteins in midbrain dopaminergic neurons. Emerging evidence suggests that in certain subtypes of PD, α-syn aggregates originate in the gut and subsequently spread to the brain. However, the mechanisms that instigate α-syn aggregation in the gut have remained elusive. In the brain, the aggregation of α-syn is induced by oxidized dopamine. Such a mechanism has not been explored in the gastrointestinal (GI) tract, a niche harboring 46% of the body’s dopamine reservoirs. Here, we report that gut bacteria Enterobacteriaceae induce α-syn aggregation. More specifically, our in vitro data indicate that respiration of nitrate by Escherichia coli K-12 yields nitrite, a potent oxidizing agent that creates an oxidizing redox potential in the bacterial environment. In these conditions, Fe2+ was oxidized to Fe3+, enabling formation of dopamine-derived quinones and α-syn aggregates. Exposing nitrite, but not nitrate, to enteroendocrine STC-1 cells induced aggregation of α-syn that is natively expressed in these cells, which line the intestinal tract. Finally, we examined the in vivo relevance of bacterial nitrate respiration to the formation of α-syn aggregates using Caenorhabditis elegans models of PD. We discovered that nematodes exposed to nitrate-reducing E. coli K-12 displayed significantly enhanced neurodegeneration as compared to an E. coli K-12 mutant that could not respire nitrate. This neurodegenerative effect was absent when α-syn was mutated to prevent interactions with dopamine-derived quinones. Taken together, our findings indicate that gut bacterial nitrate reduction may be critical to initiating intestinal α- syn aggregation.Table of Contents Graphic
A conserved membrane protein negatively regulates Mce1 complexes in mycobacteria
Authors: Chen Yushu , Wang Yuchun , Chng Shu-Sin 
Published: June 2022

AbstractTuberculosis continues to pose a serious threat to global health.Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen that relies on various mechanisms to survive and persist within the host. Among their many virulence factors, mycobacteria encode Mce systems. Some of these systems are implicated in lipid uptake, but the molecular basis for Mce function(s) is poorly understood. To gain insights into the composition and architecture of Mce systems, we characterized the putative Mce1 complex involved in fatty acid transport. We show that the Mce1 system inMycobacterium smegmatiscomprises a canonical ATP-binding cassette transporter, associated with functionally redundant heterohexameric assemblies of substrate-binding proteins. Furthermore, we establish that the conserved membrane protein Mce1N negatively regulates Mce1 function via a unique mechanism involving blocking transporter assembly. Our work offers molecular understanding of Mce complexes, sheds light on mycobacterial lipid metabolism and its regulation, and informs future anti-mycobacterial strategies.
Molecular mechanism of phospholipid transport at the bacterial outer membrane interface
Authors: Yeow Jiang , Luo Min , Chng Shu-Sin 
Published: June 2022

AbstractThe outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer with outer leaflet lipopolysaccharides (LPS) exposed to extracellular milieu and inner leaflet phospholipids (PLs) facing the periplasm. This unique lipid asymmetry is the key to its innate drug resistance, rendering the OM impermeable to external insults, including antibiotics and bile salts. To maintain this OM barrier, the OmpC-Mla system removes mislocalized PLs from the OM outer leaflet, and transports them back to the inner membrane (IM); in the first step, the OM OmpC-MlaA complex transfers PLs to the periplasmic chaperone MlaC. This process likely occurs via a hydrophilic channel in MlaA, yet mechanistic details have remained elusive. Here, we biochemically and structurally characterize the architecture of the MlaA-MlaC transient complex. We map the interaction surfaces between MlaA and MlaC inEscherichia coli, revealing that MlaC binds MlaA at the periplasmic face in a manner that possibly juxtaposes the MlaA channel and the MlaC lipid binding cavity. In addition, we show that electrostatic interactions between the putative C-terminal tail helix of MlaA and a surface patch on MlaC are important for recruitment of the latter to the OM. We further provide biochemical evidence for conformational changes in the MlaA channel that correlate with interactions with MlaC and OM porins, as well as functional states of MlaA. Finally, we solve a 2.9-Å cryo-EM structure of OmpC-MlaA in nanodiscs in a disulfide-trapped complex with MlaC, reinforcing the mechanism of MlaC recruitment, and highlighting membrane thinning as a plausible strategy for directing lipids into the MlaA channel. Our work offers critical insights into how the OmpC-MlaA complex catalyzes retrograde transport of PLs to the IM to maintain OM lipid asymmetry.
Markov State Modelling Reveals Heterogeneous Drug-Inhibition Mechanism of Calmodulin
Authors: Westerlund Annie M. , Sridhar Akshay , Dahl Leo , Andersson Alma , Bodnar Anna-Yaroslava , Delemotte Lucie 
Published: June 2022

AbstractCalmodulin (CaM) is a calcium sensor which binds and regulates a wide range of target-proteins. This implicitly enables the concentration of calcium to influence many downstream physiological responses, including muscle contraction, learning and depression. The antipsychotic drug trifluoperazine (TFP) is a known CaM inhibitor. By binding to various sites, TFP prevents CaM from associating to target-proteins. However, the molecular and state-dependent mechanisms behind CaM inhibition by drugs such as TFP are largely unknown. Here, we build a Markov state model (MSM) from adaptively sampled molecular dynamics simulations and reveal the structural and dynamical features behind the inhibitory mechanism of TFP-binding to the C-terminal domain of CaM. We specifically identify three major TFP binding-modes from the MSM macrostates, and distinguish their effect on CaM conformation by using a systematic analysis protocol based on biophysical descriptors and tools from machine learning. The results show that depending on the binding orientation, TFP effectively stabilizes features of the calcium-unbound CaM, either affecting the CaM hydrophobic binding pocket, the calcium binding sites or the secondary structure content in the bound domain. The conclusions drawn from this work may in the future serve to formulate a complete model of pharmacological modulation of CaM, which furthers our understanding of how these drugs affect signaling pathways as well as associated diseases.Author summaryCalmodulin (CaM) is a calcium-sensing protein which makes other proteins dependent on the surrounding calcium concentration by binding to these proteins. Such protein-protein interactions with CaM are vital for calcium to control many physiological pathways within the cell. The antipsychotic drug trifluoperazine (TFP) inhibits CaM’s ability to bind and regulate other proteins. Here, we use molecular dynamics simulations together with Markov state modeling and machine learning to understand the structural and dynamical features by which TFP bound to the one domain of CaM prevents association to other proteins. We find that TFP encourages CaM to adopt a conformation that is like the one stabilized in absence of calcium: depending on the binding orientation of TFP, the drug indeed either affects the CaM hydrophobic binding pocket, the calcium binding sites or the secondary structure content in the domain. Understanding TFP binding is a first step towards designing better drugs targeting CaM.
YaHS: yet another Hi-C scaffolding tool
Authors: Zhou Chenxi , McCarthy Shane A. , Durbin Richard 
Published: June 2022

ABSTRACTWe present YaHS, a user-friendly command-line tool for construction of chromosome-scale scaffolds from Hi-C data. It can be run with a single-line command, requires minimal input from users (an assembly file and an alignment file) which is compatible with similar tools, and provides assembly results in multiple formats, thereby enabling rapid, robust and scalable construction of high-quality genome assemblies with high accuracy and contiguity. YaHS is implemented in C and licensed under the MIT License. The source code, documentation and tutorial are available at https://github.com/c-zhou/yahs.
The starring role of crowdfunding in GCC: a structured literature review
Authors: Thottoli Mohammed Muneerali 
Published: June 2022

PurposeThe purpose of this study is to understand and analyze the key topics on which scholars have engaged in relation to crowdfunding and its starring role in the Gulf Cooperation Council (GCC) countries from an Islamic perspective. A Structured Literature Review (SLR) is used in this study to assess how scholars carried out their studies in order to better understand future research directions.Design/methodology/approachThe study adopted a SLR methodology and considered 89 peer-reviewed studies published between 1981 and 2021 in GCC countries.FindingsThe study identified the starring role of crowdfunding from the Islamic perspective, its role in economic development and its role as a source of finance for new business startups in GCC countries.Research limitations/implicationsBecause the research was conducted by a single person, his subjective interpretation might have an impact on the results. Furthermore, only journal papers limited to GCC and published between 1981 and 2021 were examined.Practical implicationsCountries in GCC might recognize the starring role of crowdfunding for their SMEs and economic development.Originality/valueThe authors draw avenues for future research by considering the starring role of crowdfunding using SLR from the Islamic perspective. This helps future researchers to identify the starring role of crowdfunding to contextualize in GCC countries.
ISM-based analysis of VR-AEC adoption barriers and their inner mechanisms
Authors: Chen Zhengyi , Chen Keyu , Cheng Jack C.P. 
Published: June 2022

Purpose As an emerging visualization technology, virtual reality (VR) falls into the dilemma of having great potential but a low adoption degree in the architectural, engineering and construction (AEC) industry. However, few studies paid attention to studying barriers affecting VR’s adoption and their inner mechanisms. This makes AEC users hard to catch the key points for VR’s implementations. This study aims to get a clear structure of these barriers and provide insights for the improvement.Design/methodology/approach First, 12 major VR-AEC adoption barriers were identified by a systematic literature review and expert interviews (EI). Second, EI and similarity aggregation method were conducted to achieve reliable barrier relationships. Third, interpretive structural modeling was used to establish a multi-level model for barriers. Finally, ten crucial barriers were targeted with a comprehensive strategy framework.Findings The findings help AEC stakeholders get a thorough understanding of the VR-AEC adoption barriers. Besides, the inner mechanism among barriers is revealed and analyzed, followed by a systematic strategy framework. It is anticipated that users could conduct more effective VR-AEC promotions in the future.Originality/value This paper is the first to propose a comprehensive literature review on the VR-AEC adoption barriers. In addition, this paper is novel in building a hierarchy model that explores barriers’ inner mechanism, where structural strategies are proposed.
Sport fans' nostalgia and revisit intention to stadiums during the Covid-19 pandemic
Authors: Takata Kosuke , Hallmann Kirstin 
Published: June 2022

PurposeThis study aimed to examine how sport fans' nostalgia influenced their revisit intention to stadiums. Using data collected during the Covid-19 pandemic, the study further analyzed the moderation effect of sport fans' match attendance on the relationship between nostalgia and revisit intention.Design/methodology/approachThe study used an online survey querying baseball and football fans in Japan (n = 863). These leagues completed their 2020 regular season with and without crowds due to the pandemic. Nostalgia was measured using three dimensions: sports team, environment and socialization. The model was tested using confirmatory factor analysis and structural equation modeling (SEM). Multigroup SEM also investigated the moderating effect of match attendance in 2020.FindingsIn the proposed model, nostalgia for sport teams significantly influenced sport fans' intention to revisit stadiums. Nostalgia for sport teams encouraged fans who attended live sport matches during the pandemic more than fans who did not attend the live matches. Nostalgia for sport environment and socialization did not significantly affect sport fans' intentional behavior. However, the results revealed that non-attending fans were stimulated to return to stadiums by nostalgia for the environment.Originality/valueThis study examined the individual impacts of the sport fans' nostalgia dimensions. These nostalgia dimensions were omitted in previous studies. Our findings and proposed model may be used by practitioners in sports teams and leagues to deal with fans' perceived loss of the sport during the Covid-19 pandemic.
Respiratory pandemic preparedness learnings from the June 2020 COVID-19 outbreak at San Quentin California State Prison
Authors: Kwan Ada , Sklar Rachel , Cameron Drew B. , Schell Robert C. , Bertozzi Stefano M. , McCoy Sandra I. , Williams Brie , Sears David A. 
Published: June 2022

Purpose
This study aims to characterize the June 2020 COVID-19 outbreak at San Quentin California State Prison and to describe what made San Quentin so vulnerable to uncontrolled transmission.

Design/methodology/approach
Since its onset, the COVID-19 pandemic has exposed and exacerbated the profound health harms of carceral settings, such that nearly half of state prisons reported COVID-19 infection rates that were four or more times (and up to 15 times) the rate found in the state’s general population. Thus, addressing the public health crises and inequities of carceral settings during a respiratory pandemic requires analyzing the myriad factors shaping them. In this study, we reported observations and findings from environmental risk assessments during visits to San Quentin California State Prison. We complemented our assessments with analyses of administrative data.

Findings
For future respiratory pathogens that cannot be prevented with effective vaccines, this study argues that outbreaks will no doubt occur again without robust implementation of additional levels of preparedness – improved ventilation, air filtration, decarceration with emergency evacuation planning – alongside addressing the vulnerabilities of carceral settings themselves.

Originality/value
This study addresses two critical aspects that are insufficiently covered in the literature: how to prepare processes to safely implement emergency epidemic measures when needed, such as potential evacuation, and how to address unique challenges throughout an evolving pandemic for each carceral setting.
Minimum disturbance control based on synchronous and adaptive acceleration planning of dual-arm space robot to capture a rotating target
Authors: Liu Qiang , Shi Shicai , Jin Minghe , Fan Shaowei , Liu Hong 
Published: June 2022

Purpose
This study aims to design a controller which can improve the end-effector low-frequency chattering resulting from the measurement noise and the time delay in the on-orbit tasks. The rendezvous point will move along the rendezvous ring owing to the error of the camera, and the manipulators’ collision need be avoided. In addition, owing to the dynamics coupling, the manipulators’ motion will disturb the spacecraft, and the low tracking accuracy of the end-effector needs to be improved.

Design/methodology/approach
This paper proposes a minimum disturbance controller based on the synchronous and adaptive acceleration planning to improve the tracking error and the disturbance energy. The synchronous and adaptive acceleration planning method plans the optimal rendezvous point and designs synchronous approaching method and provides an estimation method of the rendezvous point acceleration. A minimum disturbance controller is designed based on the energy conservation to optimize the disturbance resulting from the manipulator’s motion.

Findings
The acceleration planning method avoids the collision of two end-effectors and reduces the error caused by the low-frequency chattering. The minimum disturbance controller minimizes the disturbance energy of the manipulators’ motion transferred to the spacecraft. Experiment results show that the proposed method improves the low-frequency chattering, and the average position tracking error reduces by 30%, and disturbance energy reduces by 30% at least. In addition, it has good performances in the synchronous motion and adaptive tracking.

Originality/value
Given the immeasurability of the target satellite acceleration in space, this paper proposes an estimation method of the acceleration. This paper proposes a synchronous and adaptive acceleration planning method. In addition, the rendezvous points are optimized to avoid the two end-effectors collisions. By the energy conservation, the minimum disturbance controller is designed to ensure a satisfying tracking error and reduce the disturbance energy resulting from the manipulators’ motion.
Are socially responsible firms responsible to accounting? A meta-analysis of the relationship between corporate social responsibility and earnings management
Authors: Shi Hao , Liu Haijian , Wu Yixue 
Published: June 2022

Purpose
This study aims to analyze the relationship between corporate social responsibility (CSR) and quality of accounting report, especially on earnings management (EM). In addition, potential moderators of this relationship are examined.

Design/methodology/approach
After a comprehensive study of potential mechanisms, the authors obtain plenty of empirical results to open the black box of the link between CSR and EM. Meta-analysis is applied on 51 studies from 35 papers. Further analysis is also carried out to determine the moderating effects, such as the cultural and sample selection differences in these papers.

Findings
CSR is negatively associated with EM. In addition, this effect is moderated by cultural difference, CSR measurement, and year of sample selection.

Research limitations/implications
Two patterns of the hypothesis between CSR and EM are confirmed based on agency cost theory, a theoretical shift of corporate ethics based on organizational moral perspective. Several useful suggestions are also provided for future studies on the empirical model and sample selection. Further research is necessary to clarify the agency cost behind the two theoretical patterns.

Practical implications
CSR is not a tool for firms to market but rather a strategy to ensure their consistency with moral principles, indicating that management should pay more attention to the potential damage of the incongruence between CSR and accounting reporting quality. CSR reporting quality remains an important issue for legislature to guarantee continued firm operations.

Originality/value
To the best of the authors’ knowledge, this study is the first to analyze the CSR and EM link using a meta-analysis and to consider its underlying mechanism under the global environment. Previous method design and sample selection are reviewed to provide reference for future studies.