bluuebunny/crossref_metadata_2025_split huggingface dataset:
The catalase contributes to microaerophilic H2O2 priming and the peroxiredoxins AhpC, Tpx and Bcp confer resistance to organic hydroperoxides in Staphylococcus aureus
Authors: Linzner Nico , Van Loi Vu , Antelmann Haike 
Published: July 2022

ABSTRACTStaphylococcus aureus is a major human pathogen, which has to cope with oxidative stress as part of the host innate immune defense under macrophage and neutrophil infections. In this study, we have investigated the role of the catalase KatA and the peroxiredoxins AhpC, Tpx, and Bcp for priming and resistance under oxidative stress in S. aureus during aerobic and microaerophilic growth. The results revealed that S. aureus is resistant to high doses of up-to 100 mM H2O2 during the aerobic growth. While KatA is essential for this high aerobic H2O2 resistance, the peroxiredoxin AhpC contributes to detoxification of 0.4 mM H2O2 in the absence of KatA. In addition, AhpC, Tpx and Bcp were shown to be required for detoxification of cumene hydroperoxide (CHP) and regeneration of the reduced state of the bacillithiol (BSH) redox potential during recovery from CHP stress in S. aureus. The high H2O2 tolerance of aerobic S. aureus cells was associated with priming by endogenous H2O2 levels, which was supported by an oxidative shift of the basal level of EBSH (−291 mV) compared to that in microaerophilic cells (−310 mV). In contrast, S. aureus can be primed by sub-lethal doses of 100 µM H2O2 during the microaerophilic growth to acquire an improved resistance towards the otherwise lethal triggering stimulus of 10 mM H2O2. This microaerophilic priming was dependent on increased katA transcription and elevated KatA activity, whereas aerobic control cells showed already constitutive high KatA activity. Thus, KatA is the major player contributing to the high H2O2 resistance of aerobic cells and to microaerophilic H2O2 priming to survive the subsequent lethal triggering doses of H2O2, allowing the adaptation of S. aureus to oxidative stress under infections in different oxygen environments.
Epinephrine inhibits PI3K alpha via the Hippo kinases
Authors: Lin Ting-Yu , Ramsamooj Shakti , Liberatore Katarina , Lantier Louise , Vasan Neil , Karukurichi Kannan , Hwang Seo-Kyoung , Kesicki Edward A. , Kastenhuber Edward R. , Wiederhold Thorsten , Yaron Tomer M. , Zhu Mengmeng , Ma Yilun , Paddock Marcia N. , Zhang Guoan , Hopkins Benjamin D. , McGuinness Owen , Schwartz Robert E. , Cantley Lewis C. , Johnson Jared L. , Goncalves Marcus D. 
Published: July 2022

SUMMARYThe phosphoinositide 3-kinase, p110α, is an essential mediator of insulin signaling and glucose homeostasis. We systematically interrogated the human serine, threonine, and tyrosine kinome to search for novel regulators of p110α and found that the Hippo kinases phosphorylate and completely inhibit its activity. This inhibitory state corresponds to a conformational change of a membrane binding domain on p110α, which impairs its ability to engage membranes. In human primary hepatocytes, cancer cell lines, and rodent tissues, activation of the Hippo kinases, MST1/2, using forskolin or epinephrine is associated with phosphorylation and inhibition of p110α, impairment of downstream insulin signaling, and suppression of glycolysis and glycogen synthesis. These changes are abrogated when MST1/2 are genetically deleted or inhibited with small molecules. Our study reveals a novel inhibitory pathway of PI3K signaling and a previously unappreciated link between epinephrine and insulin signaling.
Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron subvariants BA.2, BA.2.12.1 and BA.5
Authors: Fang Zhenhao , Chen Sidi 
Published: July 2022

AbstractAs the immune protection conferred by first booster shot wanes over time and new Omicron subvariant emerges with stronger immune evasion, the need for variant-adapted COVID vaccine booster is increasingly imminent. However, the rapid replacement of dominant Omicron subvariants (from BA.1 to BA.2, then BA.2.12.1 and now BA.4/5) poses a great challenge to update COVID vaccine targeting the fast-evolving variants while maintaining potency against existing variants. It is a crucial question to ask which variant-based antigen(s) to use in the next generation COVID vaccine to elicit potent and broad response to past, present, and potential rising variants. Bivalent vaccine candidates have been under active clinical testing such as Modern mRNA-1273.214. In this study, we generate a Delta + BA.2 bivalent mRNA vaccine candidate and tested in animals. We compare the antibody response elicited by ancestral (wild type, WT), Delta, BA.2 spike based monovalent or Delta & BA.2 bivalent mRNA boosters against Omicron BA.2, BA.2.12.1 and BA.4/5 subvariants. In mice pre-immunized with two doses of WT lipid nanoparticle mRNA (LNP-mRNA), all three monovalent and one bivalent boosters elevated Omicron neutralizing antibody titers to various degree. The boosting effect of Delta and BA.2 specific monovalent or bivalent LNP-mRNAs is universally higher than that of WT LNP-mRNA, which modestly increased antibody titer in neutralization assays of Omicron BA.5, BA.2.12.1 and BA.2. The Delta & BA.2 bivalent LNP-mRNA showed better performance of titer boosting than either monovalent counterparts, which is especially evident in neutralization of Omicron BA.4 or BA.5. Interestingly compared to the neutralizing titers of BA.2 and BA.2.12.1 pseudovirus, BA.2 monovalent but not Delta & BA.2 bivalent booster suffered a significant loss of BA.4/5 neutralizing titer, indicative of broader activity of bivalent booster and strong neutralization evasion of Omicron BA.4 or BA.5 even in the BA.2 mRNA vaccinated individuals. These data provide evaluation of WT, Delta, BA.2 monovalent and bivalent boosters antibody potency against Omicron BA.2, BA.2.12.1 and BA.4/5 subvariants.
Coordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC
Authors: Snelling Tom , Shpiro Natalia , Gourlay Robert , Lamoliatte Frederic , Cohen Philip 
Published: July 2022

SummaryADP-heptose activates the protein kinase ALPK1 triggering TIFA phosphorylation at Thr9, the recruitment of TRAF6 and the subsequent production of inflammatory mediators. Here, we demonstrate that ADP-heptose also stimulates the formation of Lys63- and Met1-linked ubiquitin chains to activate the TAK1 and canonical IKK complexes, respectively. We further show that the E3 ligases TRAF6 and c-IAP1 operate redundantly to generate the Lys63-linked ubiquitin chains required for pathway activation, which we demonstrate are attached to TRAF6, TRAF2 and c-IAP1, and that c-IAP1 is recruited to TIFA by TRAF2. ADP-heptose also induces activation of the kinase TBK1 by a TAK1-independent mechanism, which require TRAF2 and TRAF6. We establish that ALPK1 phosphorylates TIFA directly at Thr177 as well as Thr9 in vitro. Thr177 is located within the TRAF6-binding motif and its mutation to Asp prevents TRAF6 but not TRAF2 binding, indicating a role in restricting ADP-heptose signalling. We conclude that ADP-heptose signalling is controlled by the combined actions of TRAF2/c-IAP1 and TRAF6.
mTORC2 couples fasting to mitochondrial fission
Authors: Martinez-Lopez Nuria , Mattar Pamela , Toledo Miriam , Bains Henrietta , Kalyani Manu , Aoun Marie Louise , Sharma Mridul , McIntyre Laura Beth J. , Gunther-Cummins Leslie , Macaluso Frank P. , Aguilan Jennifer T. , Sidoli Simone , Bourdenx Mathieu , Singh Rajat 
Published: July 2022

SummaryFasting triggers diverse cellular and metabolic adaptations to facilitate organismal survival1,2. During nutrient deprivation, increases in circulating fatty acids support mitochondrial respiration2. The mechanisms driving mitochondrial adaptations and respiratory sufficiency during nutrient deprivation remain incompletely understood. Here we show that extended periods of fasting, or lipid availability stimulates mTORC2 activity. Activation of mTORC2 and phosphorylation of its target NDRG13 at S336 sustains mitochondrial fission and respiratory sufficiency. Timelapse imaging reveals that wildtype NDRG1, but not phosphorylation-deficient NDRG1S336A mutant, engages with mitochondria to facilitate its scission. Using proteomics, and an siRNA screen, we show that mTORC2-phosphorylated NDRG1 cooperates with the small GTPase Cdc424 and Cdc42-specific effectors and regulators to orchestrate fission. Accordingly, RictorKO, NDRG1S336A mutants, and Cdc42-deficient cells each display mitochondrial phenotypes reminiscent of fission failure. During nutrient surplus, mTOR complexes perform anabolic functions5; however, paradoxical reactivation of mTORC2 during fasting plays an unexpected role in driving mitochondrial fission and respiration.
Modified active power-MRAS for limited range variable speed sensorless brushless doubly-fed reluctance machine drive
Authors: Kumar Mukesh , Das Sukanta 
Published: July 2022

Purpose
This paper aims to suggest a parameter independent and simple speed estimator for primary field-oriented control of a promising electro-mechanical energy conversion device in the form of brushless doubly-fed reluctance machine (BDFRM) drive.

Design/methodology/approach
The speed estimation algorithm, in this context, is formulated using a modified secondary winding active power (mPs)-based model reference adaptive system (MRAS). The performance of the proposed estimator is verified through computer aided MATLAB simulation study, compared with conventional active power-based MRAS and further supported with experimental validation using a 1.6 kW BDFRM prototype run by a dSPACE-1103 controller.

Findings
The formulation of mPs-MRAS is insensitive to any machine parameters and does not involve any integration/differentiation terms. Thus, any deviation therein does not hinder the performance of the mPs-MRAS-based speed estimator. The proposed speed estimator shows stable behavior for variable speed-constant load torque operation in all the four quadrants.

Originality/value
The formulation of mPs-MRAS is insensitive to any machine parameter and does not involve any integration/differentiation terms.
The mediating role of real earnings management in the relationship between CSR practices and cost of equity: evidence from European ESG data
Authors: Chouaibi Yamina , Zouari Ghazi 
Published: July 2022

PurposeThe goal of this article was to look into the direct and indirect links between corporate social responsibility (CSR) activities and the cost of equity, using real earnings management (REM) as a mediator.Design/methodology/approachTo test the hypotheses, the authors applied linear regressions with panel data using the Thomson Reuters ASSET4 and I/B/E/S database on a sample of 540 European companies selected from the environmental, social and governance (ESG) index over the period 2011–2019.FindingsThe results show that REM partially mediates the relationship between CSR practices and the cost of equity in European firms belonging to the ESG index.Practical implicationsInstead of beautifying their business, companies should make efficient managerial and organizational improvements to meet their social duty. Regulators in Europe must strive for tighter enforcement while also attempting to raise public awareness of CSR. CSR can be profitable and helpful for primary stakeholders, according to the research.Originality/valueAlthough previous literature has investigated the direct correlation between CSR practices and the cost of equity, the present work focuses on considering the direct and indirect association between CSR and cost of equity through the mediating effect of REM, which has not been widely used in CSR studies so far.
Developing entrepreneurial competencies through deliberate practice
Authors: Van Gelderen Marco 
Published: July 2022

PurposeIn the context of the question of how entrepreneurship education can contribute to entrepreneurial competency development, this paper aims to outline the deliberate practice (DP) method and showcase how it can be applied in entrepreneurship education. To this end, this paper presents a learning innovation in which DP improves entrepreneurial competencies.Design/methodology/approachThe paper describes an entrepreneurship training in which participants, over a seven-week period, learn about DP and use this approach to develop an aspect of an entrepreneurial competency of their choosing.FindingsEvaluations show that participants find both short- and long-term gains in their competency development, and value having learnt a competency development method as well.Practical implicationsThe presented format is designed in accordance with the DP principles as originally described in the literature on expert performance, and shows that DP can be applied in the context of entrepreneurial competency development at lower levels of proficiency. Entrepreneurship educators interested in competency development can consider to adopt (aspects of) the described approach.Originality/valueThe format applies DP principles as described in the literature on expert performance. The value lies in the short- and long term effects of the training.
The effect of health expenditure on average life expectancy: does government effectiveness play a moderating role?
Authors: Bunyaminu Alhassan , Mohammed Ibrahim , Yakubu Ibrahim Nandom , Shani Bashiru , Abukari Abdul-Lateef 
Published: July 2022

PurposeThis study investigates the impact of total health expenditure on life expectancy in a panel of 43 African countries from 2000 to 2018.Design/methodology/approachThe dynamic panel generalized method of moments (GMM) estimation method developed by Arellano and Bond (1991) is used in this study. This approach generates estimates that are heteroskedasticity and autocorrelation consistent, as well as controls for unobserved time-invariant country-specific effects and eliminates any endogeneity in the panel model.FindingsThe results reveal that health expenditure on its own has a positive significant influence on life expectancy. However, health expenditure via the moderating effect of government effectiveness reduces life expectancy. The authors also observe that school enrollment and the level of economic activity significantly drive life expectancy.Research limitations/implicationsThe study is limited to 43 out of 54 African countries, and it covers a period of 18 years: 2000 to 2018.Practical implicationsThe authors argue that larger health expenditure will aid in improving the life expectancy rate in Africa. However, in practice, this would be difficult given the needs of other priority sectors.Social implicationsSince most developing countries' health expenditures are small, a policy option is that healthcare services should be subsidized such that the poorest people can also access them.Originality/valueThe study differs from the previous attempts, and with this, the authors contribute significantly to the literature. First, to the best of the authors’ knowledge, the authors are unaware of any study considering the role of government effectiveness as a moderating factor in investigating the effect of health expenditure on life expectancy in the African context. Thus, the authors fill a yawning gap in the literature. Second, the authors employ a recent dataset with larger sample size. Finally, to address the problem of endogeneity and simultaneity bias, the authors use the system GMM technique.
Maqasid-based consumption intelligence: an empirical model of its application to the intention of halal purchase
Authors: Sholihin Muhammad , Shalihin Nurus , Ilhamiwati Mega , Hendrianto Hendrianto 
Published: July 2022

Purpose
This study aims to gain new insight into how a set of maqasid-based consumption intelligence variables mediates exogenous variables (i.e. religiosity, Islamic university role and normative belief) and halal purchase intention as an endogenous variable.

Design/methodology/approach
The research model is empirically tested with a data set of 370 responses retrieved from the students of the millennial generation from the cross Islamic state university in Indonesia. Data were analysed with Partial Least Square Structural Equation Modelling (PLS-SEM). The sample size of this study is computed with preliminary power analysis.

Findings
The SEM finding revealed that two maqasid-based consumption intelligence variables had mediated the exogenous and endogenous variables, i.e. halal purchase intention. These variables mediating the exogenous and endogenous variables have explained 63.5 R2 variances in halal purchase intention. Concerning individual impact size of cognition and motivation as a component of maqasid-based consumption intelligence has shown medium-level effect size (f2) in mediating the halal purchase intention. Interestingly, the exogenous variable does not directly affect halal purchase intention but must be mediated with maqasid-based consumption intelligence variables. However, before including variables of maqasid-based consumption intelligence, the R2 was relatively small. It is just 30.4% in R2 that explains the variance of halal purchase intention.

Research limitations/implications
This study explores maqasid-based consumption intelligence as a relatively new model to explain the variable halal purchase intention. Therefore, it takes many types of exogenous variables to test how relevant maqasid-based consumption intelligence variables can define endogenous variables. Notwithstanding, this study does not do that because it only limits three exogenous variables (i.e. religiosity, Islamic university role and normative belief). Therefore, in further research, these limitations seem to be perfected by other scholars concerned about halal purchase intention.

Practical implications
The findings of this study allow Islamic universities to mainstream halal issues as a subject of learning, especially concerning consumption ethics. In addition, the empirical results of this study encourage the industry to pay attention to the essential components in determining the halal quality of the products offered because the millennial generation is now very aware of the importance of halal products.

Originality/value
This study contributes to the existing literature on halal purchase intention by testing maqasid-based consumption intelligence variables as mediators. Moreover, this is a pioneer study to consider and construct maqasid-based consumption intelligence as a model that explains halal purchase intention.
Lean Six Sigma case studies literature overview: critical success factors and difficulties
Authors: Francescatto Matheus , Neuenfeldt Júnior Alvaro , Kubota Flávio Issao , Guimarães Gil , de Oliveira Bruna 
Published: July 2022

PurposeRecently, several areas are successfully applying the Lean Six Sigma methodology, specifically in healthcare, public services, higher education institutions and manufacturing industries. This study aims to present an extensive literature review involving Lean Six Sigma practical applications in the last five years, described in a case studies format.Design/methodology/approachA systematic literature review was conducted, and 39 articles were selected and analyzed.FindingsAn increase in Lean Six Sigma applications in healthcare and higher education institutions was identified. Furthermore, Lean Six Sigma is effectively applied in several areas and is continuously used in traditional industries. The main critical success factor identified was leadership and management involvement, project management and organizational infrastructure, as well as training and education. Also, the main difficulties found are related to the organization's culture and developing communication with leaders and managers.Research limitations/implicationsThe main difficulties found in this research are related to the lack of data presented in some articles analyzed, where only information about how the Lean Six Sigma application was conducted is shown, not mentioning difficulties or success factors identified.Originality/valueCase studies are fundamental to help popularize Lean Six Sigma applications, showing a real-life scenario of how the methodology is implemented, the main difficulties encountered and critical success factors found. Thus, the value of this study is promoting and developing research involving Lean Six Sigma case study applications to guide new researchers and practitioners on the subject.
Dynamics of relationship between stock markets of SAARC countries during COVID-19 pandemic
Authors: Arya Vandana , Singh Shveta 
Published: July 2022

PurposeThe paper investigates the dynamic relationship among the stock markets of South Asian Association of Regional Cooperation (SAARC) countries during the COVID-19 pandemic.Design/methodology/approachDaily time-series data of four SAARC countries: India, Bangladesh, Pakistan, and Sri Lanka, from February 13th, 2013 to March 31st, 2021 are used. The study considers stock prices prior to the blowout of COVID-19 and during the onset of the pandemic. The novel estimation procedure of the autoregressive distributed lag model is used while the results are also confirmed by post-estimation techniques.FindingsThe study confirms that the COVID-19 contagion has adversely influenced the stock returns of SAARC countries. The findings signify that the pattern of cointegration has significantly different regularities in the pattern of causality in the long run and short run during the COVID-19 crisis. Overall, the study revealed that the COVID-19 pandemic has weakened the dynamic connection among the stock markets of SAARC countries.Practical implicationsTo dampen uncertainties generated by the COVID-19 pandemic, the authorities and central banks should be equipped with efficient strategies and guidelines to cope with the crisis created by the pandemic. Further, governments should focus on assuaging the panic faced by investors and enhancing the confidence of domestic as well as foreign investors. Further, the weakened integration of financial markets during the crisis offers opportunities for speculative and arbitrage gains for investors.Originality/valueThe research work is an innovative effort to analyze the impression led by COVID-19 on the SAARC stock markets integration.