bluuebunny/crossref_metadata_2025_split huggingface dataset:
SHIP2 controls matrix mineralization by regulation of the RhoA/ROCK pathway and remodeling of the actin cytoskeleton
Authors: Fradet Anais , Fitzgerald Jamie 
Published: October 2022

AbstractMutations inINPPL1, the gene coding for SH2 Domain-Containing Inositol 5’-Phosphatase 2 (SHIP2), cause Opsismodysplasia, a severe chondrodysplasia characterized by delayed bone maturation. The mechanism by which the loss of an inositol phosphatase causes a major skeletal developmental defect is unclear. To investigate the role of SHIP2 in mineralization, theINPPL1gene was deletedin vitroin chondrocyte and osteoblast differentiation models and the effect of the loss of SHIP2 on cell differentiation, subsequent mineralization, and on actin cytoskeleton formation was investigated. The loss of SHIP2 does not impact differentiation but, consistent with the disease phenotype, induces a significant reduction in extracellular matrix mineralization in both cell types. Absence of SHIP2 also altered the actin cytoskeleton to increase cell adhesion and focal adhesion formation. Furthermore, inhibition of actin polymerization in SHIP2-deficient cells rescued the mineralization phenotype. RhoA/ROCK, Cdc42 and Rac1 are the three main RhoGTPases responsible for actin cytoskeleton regulation in bone cells. Specific inhibitors of these RhoGTPases were used to determine the pathways involved in SHIP2-mediated mineralization. Since only the ROCK pathway inhibitor rescued the mineralization phenotype, it is concluded that SHIP2 regulates actin cytoskeleton remodeling and consequently extracellular matrix mineralization by inhibiting the RhoA/ROCK pathway.
Morphoelastic modeling of pattern development in the petal epidermal cell cuticle
Authors: Lugo Carlos A. , Airoldi Chiara , Chen Chao , Crosby Alfred J. , Glover Beverley J. 
Published: October 2022

AbstractWe use the model systemHibiscus trionumas a vehicle to study the origin and propagation of surface nano-ridges in plant petal epidermal cells by tracking the development of the cell shape and the cuticle. In this system, the cuticle develops two distinct subdomains, (i) an uppermost layer which increases in thickness and in-plane extension and (ii) a substrate. We quantify the pattern formation and geometrical changes and then postulate a mechanical model assuming that the cuticle behaves as a growing bi-layer. The model is a quasi-static morpho-elastic system and it is numerically investigated in two and three dimensional settings, using different laws of film and substrate expansion and boundary conditions. We recreate several features of the observed developmental trajectories in petals. We establish the respective roles of the layers’ stiffness mismatch, the underlying cell-wall curvature, the cell in-plane expansion and the thickness growth rates of the layers in determining the observed pattern features, such as the variance observed in amplitude and wavelength. Our observations provide evidence which justify the growing bi-layer description, and provide valuable insights into why some systems develop surface patterns and others do not.
Epigenetically silencing gluconeogenic enzyme PCK1 by EZH2 promotes renal tubulointerstitial fibrosis
Authors: Wu Ming , Chen Dongping , Wang Yanzhe , Lin Pinglan , Yang Feng , Lin Junyan , Tan Bo , Sheng Guangyu , Yang Xuejun , Huang Di , Ye Chaoyang 
Published: October 2022

AbstractRenal fibrosis is the common pathological pathway of various chronic kidney diseases (CKD) in progression to the end stage of renal failure. Impaired renal gluconeogenesis has been recently identified as a hallmark of CKD. The role of gluconeogenesis in renal fibrosis is currently unknown. Through RNA sequencing and cleavage under targets and tagmentation (CUT&Tag) sequencing analysis, we found that the phosphoenolpyruvate carboxykinase 1 (PCK1), a critical enzyme in gluconeogenesis, is negatively regulated by the methyltransferase enhancer of zeste homolog 2 (EZH2) in fibrotic kidneys, which was further confirmed by quantitative PCR, CUT&Tag and Western blotting analysis in unilateral ureteral obstruction (UUO) kidneys and renal cells. We further showed that pharmaceutical inhibition or conditional knockout of EZH2 increased PCK1 expression and attenuated renal fibrosis in two other mouse models. Moreover, the concentration of lactate, a glucogenic metabolic intermediate, was increased in mouse fibrotic kidneys, which was reduced by EZH2 inhibition. We further showed that glucose production was impaired in folic acid induced nephrotic mice and restored by EZH2 inhibition as assessed by pyruvate tolerance test. Importantly, the direct anti-gluconeogenesis effect of EZH2 on renal proximal epithelial cells was shown in human HK2 cells by analysis of gluconeogenic gene expression and production of glucose or lactate. Finally, inhibition of PCK1 by 3-mercaptopropionic acid abrogated the anti-fibrotic effect of EZH2 inhibitor in UUO kidneys. We conclude that EZH2 promotes renal tubulointerstitial fibrosis through epigenetic inhibition of PCK1. Our study suggests that therapeutic restoration of the impaired renal gluconeogenesis is beneficial to CKD patients.Translational StatementRenal fibrosis is the common pathological pathway of various chronic kidney diseases (CKD) in progression to the end stage of renal failure. Impaired renal gluconeogenesis has been recently identified as a hallmark of CKD. In this study, we found that the methyltransferase EZH2 is negatively correlated with the expression of the gluconeogenic enzyme PCK1 in fibrotic kidneys. Epigenetic inhibition of PCK1 by EZH2 promotes renal tubulointerstitial fibrosis. Our study indicates that renal gluconeogenesis in CKD can be epigenetically regulated and therapeutically targeted. Epigenetic restoration of renal gluconeogenesis is a potential therapeutic strategy to treat CKD patients with tubulointerstitial fibrosis.
Slice-PASEF: fragmenting all ions for maximum sensitivity in proteomics
Authors: Szyrwiel Lukasz , Sinn Ludwig , Ralser Markus , Demichev Vadim 
Published: October 2022

AbstractWe present Slice-PASEF, a novel mass spectrometry technology based on trapped ion mobility separation of ions. Slice-PASEF allows to achieve the theoretical maximum of MS/MS sensitivity and boosts proteomics of low sample amounts. Leveraging Slice-PASEF, we show, for the first time, that comprehensive profiling of single cell-level peptide amounts is possible using ultra-fast microflow chromatography and a general-purpose mass spectrometer, allowing quantification of 1417 proteins from 200 picograms of a HeLa cell peptide standard on an Evosep One LC system coupled to a timsTOF Pro 2, at a 200 samples per day throughput. We implemented a Slice-PASEF module in our DIA-NN data processing software, to make it readily available for the proteomics community.
A widespread methylotroph acyl-homoserine lactone synthase produces an atypical quorum sensing signal
Authors: Cummings Dale A. , Wallace Mike , Roberts Andrew G. , Puri Aaron W. 
Published: October 2022

ABSTRACTPink pigmented facultative methylotrophs of the generaMethylorubrumandMethylobacteriumare omnipresent bacteria often found associated with plants. Despite their widespread occurrence, the molecular details of how these organisms interact with each other and their environment remain understudied. We analyzed genes encodingN-acylhomoserine lactone quorum sensing signal synthases in published genomes of these bacteria and determined that the product of the largest group of signal synthases had not been characterized. We subsequently identified thisN-acylhomoserine lactone product using inverse stable isotopic labeling (InverSIL), which revealed an atypical signal. We then demonstrate in one representative strain that this signal activates its cognate LuxR-family transcription factor and is produced in a positive feedback loop. These results reveal a previously undescribed yet widespread signal used by pink pigmented facultative methylotrophs, which helps us understand the chemical ecology of these important bacteria.
Policy implementation for extreme hazard events in Caribbean Small Island Developing States: a case study – Trinidad and Tobago and Grenada
Authors: Murray Marlene , Watson Patrick K. 
Published: October 2022

PurposeExtreme natural hazard events in the Caribbean continue to result in major adverse consequences. Studies of disaster experiences have identified operational deficiencies that limited the effectiveness of disaster management policies in live emergencies. This paper reports on a study of the implementation characteristics of specific public disaster risk reduction and response measures in two Caribbean Small Island Developing States (SIDS), Trinidad and Tobago and Grenada, which may impact the success of these measures. The purpose of this paper is to examine these characteristics and their potential impacts.Design/methodology/approachThe authors collected data on specific aspects of disaster risk management (DRM) policy implementation from policy documents and interviews with public DRM agencies. A sample of business entities also provided data on their interactions with public risk management measures. The data focussed on operational aspects of implementation to identify likely impacts on hazard event outcomes.FindingsThe study identifies implementation deficiencies that may hamper achievement of risk reduction objectives and limit the effectiveness of emergency response.Research limitations/implicationsThe findings may be instructive for other Caribbean SIDS which share similar economic and social characteristics, natural hazard exposures and potential catastrophic outcomes.Practical implicationsThe findings suggest tactical areas of focus to enhance the operationalisation of policy.Social implicationsImproved operational effectiveness will support the efforts of Caribbean SIDS to reduce the scale of adverse outcomes on people and property.Originality/valueThe findings of this study broaden the scope of Caribbean disaster studies to provide an insight into operational weaknesses that may be recognised and addressed prior to hazard events.
Competitive or collaborative? Customer concentration and real earnings management
Authors: Zhu Lei , Chen Wanyi , Zheng Qianwen 
Published: October 2022

PurposeEmerging markets are characterized by weak institutions and strong relationships, which give rise to different market characteristics in supply chain relationships. This study investigates the impact of customer concentration on suppliers' real earnings management.Design/methodology/approachBased on China's relationship-based transaction, this study selects 2007–2019 Shenzhen and Shanghai Stock Exchange A-share manufacturing listed companies as the research samples. The empirical analysis is derived from the ordinary least square regression model with industry and year fixed effects, and cross-sectional analysis is used for further analysis.FindingsIt is found that the higher the degree of customer concentration, the more likely a company is to engage in real earnings management mainly through discretionary expenses instead of accrual-based earnings management. Further research shows that when suppliers provide customers with higher commercial credit and make more relationship-specific investments, and when major customers are also major suppliers, the effect of customer concentration on real earnings management is more significant. It can be seen from the results that high customer concentration is beneficial for suppliers to cooperate with major customers in emerging markets.Originality/valueThis research expands the relationship between customer relationship-based transaction and earnings management from the perspective of collaboration. These conclusions are of great significance for market regulators to reform information disclosure related to customers and for participants to pay attention to the composition of major customers of the company.
Turn calamities into blessings: the impact of resource reconfiguration and firm resilience on the company's recovery and growth in the COVID-19 times
Authors: Zhang Shujie , Sun Qian , Dai Lejiao , Wang Xingyuan 
Published: October 2022

PurposeThe purpose of this paper is to construct an integrated theoretical framework of firm resilience, and examine the relationship between resource reconfiguration, firm resilience, disruption impact, profit growth, innovation and environmental uncertainty in the context of COVID-19.Design/methodology/approachA survey was distributed to 220 companies and a total of 207 respondents returned the survey. chief executive officer (CEO) and chief financial officer (CFO) of each company participants in the survey. The hypotheses are tested using structural equation modeling (SEM) technique.FindingsThe results showed that firm resilience can be stimulated through the reconstruction of existing resources, and environmental uncertainty played a moderating role in this process; in turn, the improvement of firm resilience enabled companies to reduce the impact of disruptions, achieve profit growth and promote innovation.Practical implicationsThis study provides practical implications for how business management shapes firm resilience and promotes organization recovery and development.Originality/valueThis study expands the literature of firm resilience by providing an integrated theoretical framework of firm resilience. Firstly, based on the perspective of dynamic capabilities, this study reveals that resource reconfiguration plays a key role in shaping firm resilience. Secondly, this study enriches the boundary research on firm resilience by incorporating environmental uncertainty into the research framework. Thirdly, this study validates the impact of firm resilience on disruption impact, profit growth and innovation of companies, providing sufficient empirical evidence for the outcomes of firm resilience.
Brand equity and stock performance in time of crisis: evidence from the COVID-19 pandemic
Authors: Farhang Maryam , Kamran-Disfani Omid , H. Zadeh Arash 
Published: October 2022

Purpose
This paper aims to investigate the impact of brand equity (BE) on stock performance (i.e. stock return, volatility and beta), and compare the performance of a high brand equity stocks (HBES) portfolio with that of the overall market during market downturn, market upturn and total disturbance periods of the COVID-19 pandemic in 2020.

Design/methodology/approach
Stock performance data and brand valuation estimates are obtained from various sources to assemble a portfolio of HBES and conduct the analyses. Econometric models are estimated to examine the impact of BE on stock performance and compare the HBES portfolio performance versus the overall market.

Findings
BE was positively associated with stock return and negatively associated with both types of risk (volatility and beta) during the COVID-19 pandemic. Specifically, during the market downturn period, BE was positively related to stock return and negatively related to stock volatility; during the market upturn period, BE was negatively associated with both types of risk; and during the total disturbance period, BE was positively associated with stock return and negatively associated with both types of risk. Finally, the HBES portfolio outperformed the market (S&P 500 index).

Research limitations/implications
The findings advance the extant research by providing evidence pertaining to brands' role in mitigating the impact of unpredictable market shocks and crises, such as the COVID-19 pandemic, on stock performance. While brands are mostly viewed as drivers of sustained competitive advantage and profitability, their protective role in crisis times is noteworthy.

Practical implications
The research findings potentially help marketing and brand managers to justify marketing spending and craft their strategies to enhance firm performance during crises similar to COVID-19.

Originality/value
The marketing–finance interface can benefit from insights offered by the COVID-19 pandemic, as such crises are becoming prevalent and are capable of damaging various stakeholders' outcomes (firms, investors and customers). The empirical examination is separately conducted on the market downturn, market upturn and total disturbance period attributable to the COVID-19 pandemic.
How B&B experience affects customer value cocreation under the social servicescape: an emotional psychological perspective
Authors: Wang Mei-Yu , Li Yong-Quan , Ruan Wen-Qi , Zhang Shu-Ning 
Published: October 2022

Purpose
This study aims to analyze how bed and breakfast (B&B) experience influences customer value cocreation (CVCC) through emotional psychological factors under the social servicescape (SSC).

Design/methodology/approach
A moderated chain mediation model was constructed based on the SSC framework. This study collected 722 valid questionnaires through convenience sampling in Xiamen, China, and tourists with B&B experiences were taken as samples. A structural equation model analysis was used to test relevant hypotheses.

Findings
Results reveal that B&B experience is the core factor to stimulate CVCC. In this process, the individual emotional psychological factors [pleasant arousal (PAL) and place attachment (PAT)] play the critical chain mediating role. In addition, localness positively moderates the reinforcing effect of B&B experience on PAL and strengthens the positive effect of PAL on PAT.

Practical implications
The findings can provide useful CVCC strategies for B&B operators. They can achieve CVCC by enhancing customer experiences, strengthening emotional interactions and building local culture, thereby improving the competitiveness of B&Bs.

Originality/value
Current research lacks an in-depth analysis on the internal relationship and logic between B&B experience and CVCC, especially from emotional psychological perspectives. To the best of the authors’ knowledge, this study is one of the first studies to reveal the mechanism of the CVCC process of B&Bs under the SSC from an emotional psychological perspective. It provides a new theoretical model for research on the CVCC of experience-dominant logic.
Preconditioned transmission + reflection joint traveltime tomography with adjoint‐state method for subsurface velocity model building
Authors: Zhang Jianming , Dong Liangguo , Wang Jianhua , Huang Chao 
Published: October 2022

AbstractAdjoint‐state‐based transmission and reflection traveltime inversion are promising approaches for reconstructing a macro velocity field in both shallow and deep depths. However, the contaminated gradient by the uneven illumination impedes the recovery of an optimal velocity model and results in slow convergence rate in inversion. To mitigate this issue, we propose a novel preconditioned transmission + reflection joint traveltime tomography method with transmission and reflection illumination compensation. The proposed illumination compensation operator is theoretically demonstrated as the diagonal elements of the approximated Hessian, which can be efficiently computed in a way similar to gradient calculation. The proposed method can construct a more accurate velocity model compared to the uncompensated counterpart. Convergence is also accelerated by the relatively uniform velocity updates from the shallow to the deep parts. Furthermore, velocity updating and reflector imaging are simultaneously iterated during the inversion. Synthetic numerical example based on the inclusion model indicates that the proposed preconditioned method can result in uniform gradient values of both transmitted and shot/receiver‐side reflected traveltime. The complex foothill model test shows the improved inversion accuracy of the proposed method with an increased convergence rate and improved reflection traveltime predictions using the inverted velocity model. Experiment on the small foothill model indicates that the reflector and velocity can be updated simultaneously, and the inversion accuracy can be significantly improved by selecting multi reflectors. Finally, the effectiveness and practicality of the proposed method are demonstrated by a field data application in East China Sea.
Staggered arrangement and sequential dehiscence of anthers in didynamous stamens facilitate reproductive fitness of Brandisia hancei
Authors: Ren Yongquan , Huang Chengling , Zhang Rui , Zhu Shouxue , Yang Jialin 
Published: October 2022

AbstractDidynamous stamens are separated into two pairs of different length, and the implication of this arrangement has not been well understood. The functional advantages of didynamous stamens were investigated in Brandisia hancei. Change of stamens during floral aging was recorded; the quantity, viability, and siring ability of pollen grains were tested; the anther arrangement was manipulated into four types based on stamen category and number, and fruit set and number of seeds per fruit were measured. Didynamous stamens exhibited staggered anther arrangement, and pollen sacs dehisced gradually. There was no difference for quantity, viability, and siring ability of pollen grains between the two pairs of anthers. Seed production after the removal of one long and one short stamen was higher than that of two long or two short stamens. Through prolonging pollen presentation and promoting delayed self‐pollination, staggered arrangement and sequential dehiscence of anthers in didynamous stamens facilitate reproductive fitness of B. hancei.
Heterogeneous treatment effects of dexamethasone 12 mg versus 6 mg in patients with COVID‐19 and severe hypoxaemia—Post hoc exploratory analyses of the COVID STEROID 2 trial
Authors: Granholm Anders , Munch Marie Warrer , Andersen‐Ranberg Nina , Myatra Sheila Nainan , Vijayaraghavan Bharath Kumar Tirupakuzhi , Venkatesh Balasubramanian , Jha Vivekanand , Wahlin Rebecka Rubenson , Jakob Stephan M. , Cioccari Luca , Møller Morten Hylander , Perner Anders 
Published: October 2022

AbstractBackgroundCorticosteroids improve outcomes in patients with severe COVID‐19. In the COVID STEROID 2 randomised clinical trial, we found high probabilities of benefit with dexamethasone 12 versus 6 mg daily. While no statistically significant heterogeneity in treatment effects (HTE) was found in the conventional, dichotomous subgroup analyses, these analyses have limitations, and HTE could still exist.MethodsWe assessed whether HTE was present for days alive without life support and mortality at Day 90 in the trial according to baseline age, weight, number of comorbidities, category of respiratory failure (type of respiratory support system and oxygen requirements) and predicted risk of mortality using an internal prediction model. We used flexible models for continuous variables and logistic regressions for categorical variables without dichotomisation of the baseline variables of interest. HTE was assessed both visually and with p and S values from likelihood ratio tests.ResultsThere was no strong evidence for substantial HTE on either outcome according to any of the baseline variables assessed with all p values >.37 (and all S values <1.43) in the planned analyses and no convincingly strong visual indications of HTE.ConclusionsWe found no strong evidence for HTE with 12 versus 6 mg dexamethasone daily on days alive without life support or mortality at Day 90 in patients with COVID‐19 and severe hypoxaemia, although these results cannot rule out HTE either.