bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic engineering of anthocyanin pathway inArtemisia annuacells does not exclude the expression of artemisinin pathway
Authors: Judd Rika , Dong Yilun , Sun Xiaoyan , Zhu Yue , Li Mingzhuo , Xie De-Yu 
Published: January 2023

AbstractArtemisia annuais the only medicinal crop to produce artemisinin for the treatment of malignant malaria. Unfortunately, hundreds of thousands of people still lose their life every year due to the lack of sufficient artemisinin. Artemisinin is considered to result from the spontaneous autoxidation of dihydroartemisinic acid in the presence of reactive oxygen species (ROS) in an oxidative condition of glandular trichomes (GTs),; however, whether increasing antioxidative compounds can inhibit artemisinin biosynthesis in plant cells is unknown. Anthocyanins are potent antioxidants that can remove ROS in plant cells. To date, no anthocyanins have been structurally elucidated fromA. annua. In this study, our goals were to engineer anthocyanins inA. annuacells and to understand the artemisinin biosynthesis in anthocyanin-producing cells. ArabidopsisPAP1(AtPAP1) was used to engineer four types of transgenic anthocyanin-producingA. annua(TAPA1 to 4) cells. Three wild type cell types were developed as controls. TAPA1 cells produced the highest contents of total anthocyanins. LC-MS analysis detected 17 anthocyanin or anthocyanidin compounds. Crystallization, LC/MS/MS and NMR analyses identified cyanidin, pelargonidin, one cyanin, and one pelargonin. An integrative analysis characterized that four types of TAPA cells expressed the artemisinin pathway and TAPA1 cells produced the highest artemisinin and artemisinic acid. The contents of arteannuin B were similar in seven cell types. These data showed that the engineering of anthocyanins does not eliminate the biosynthesis of artemisinin in cells. These data allow us to propose a new hypothesis that enzymes catalyze the formation of artemisinin from DHAA in non-GT cells. These findings show a new platform to increase artemisinin production via non-GT cells ofA. annua.
Bacterial muropeptides promote OXPHOS and suppress mitochondrial stress in normal and human mitochondrial disease models
Authors: Tian Dong , Cui Mingxue , Han Min 
Published: January 2023

Mitochondrial dysfunction critically contributes to many major human diseases but effective therapeutic methods to combat mitochondrial dysfunction are lacking1,2. Mitochondria of animal cells are sites of interaction between gut microbial metabolites and host factors, and many such interactions may be beneficial to mitochondrial health and host physiology3, albeit that specific beneficial interactions and the underlying mechanisms remain to be uncovered. Here we report the role of muropeptides derived from bacterial cell wall peptidoglycan (PG) in promoting mitochondrial functions in mammalian models. We found that muropeptides directly bind to ATP synthase, which stabilizes the complex and promotes its activity. The benefit is seen in increased oxidative respiration and mitochondrial membrane potential, as well as decreased oxidative stress in human intestinal epithelial cells (IECs). Strikingly, we also found that muropeptide treatment can recover mitochondrial structure and functions, as well as inhibit several pathological phenotypes of mutant fibroblast cells derived from mitochondrial disease patients. In mice, we show muropeptides accumulate in mitochondria of IECs and promote small intestinal homeostasis and nutrient absorption by modulating energy metabolism. This study identifies ATP synthase as a muropeptide receptor and the corresponding physiological function in mammals, and points to a potential treatment for human mitochondrial dysfunction diseases.HighlightsBacterial muropeptides bind and stabilize ATP synthase complex and enhance its activityMuropeptides enhance mitochondrial OXPHOS in human IECsMuropeptides recover mitochondrial structure and functions in mitochondrial disease cellsMuropeptides promote small intestinal epithelial homeostasis and nutrient uptake in mice
Low dimensional criticality embedded in high dimensional awake brain dynamics
Authors: Fontenele Antonio J. , Sooter J. Samuel , Norman V. Kindler , Gautam Shree Hari , Shew Woodrow L. 
Published: January 2023

AbstractWhether cortical neurons operate in a strongly or weakly correlated dynamical regime determines fundamental information processing capabilities and has fueled decades of debate. Here we offer a resolution of this debate; we show that two important dynamical regimes, typically considered incompatible, can coexist in the same local cortical circuit by separating them into two different subspaces. In awake mouse motor cortex, we find a low-dimensional subspace with large fluctuations consistent with criticality – a dynamical regime with moderate correlations and multi-scale information capacity and transmission. Orthogonal to this critical subspace, we find a high-dimensional subspace containing a desynchronized dynamical regime, which may optimize input discrimination. The critical subspace is apparent only at long timescales, which explains discrepancies among some previous studies. Using a computational model, we show that the emergence of a low-dimensional critical subspace at large timescale agrees with established theory of critical dynamics. Our results suggest that cortex leverages its high dimensionality to multiplex dynamical regimes across different subspaces.TeaserTemporal coarse-graining reveals a low-dimensional critical subspace coexistent with a desynchronized subspace in awake cortex.
Modulation of protein-DNA binding reveals mechanisms of spatiotemporal gene control in earlyDrosophilaembryos
Authors: Syed Sahla , Duan Yifei , Lim Bomyi 
Published: January 2023

AbstractIt is well known that enhancers regulate the spatiotemporal expression of their target genes by recruiting transcription factors (TFs) to the cognate binding sites in the region. However, the role of multiple binding sites for the same TFs and their specific spatial arrangement in determining the overall competency of the enhancer has yet to be fully understood. In this study, we utilized the MS2-MCP live imaging technique to quantitatively analyze the regulatory logic of thesnaildistal enhancer in earlyDrosophilaembryos. Through systematic modulation of Dorsal and Twist binding motifs in this enhancer, we found that a mutation in any one of these binding sites causes a drastic reduction in transcriptional amplitude, resulting in a reduction in total mRNA production of the target gene. We provide evidence of synergy, such that multiple binding sites with moderate affinities cooperatively recruit more TFs to drive stronger transcriptional activity than a single site. Moreover, a Hidden Markov-based stochastic model of transcription reveals that embryos with mutated binding sites have a higher probability of returning to the inactive promoter state. We propose that TF-DNA binding regulates spatial and temporal gene expression and drives robust pattern formation by modulating transcriptional kinetics and tuning bursting rates.
Dihydroxy-Metabolites of Dihomo-gamma-linolenic Acid Drive Ferroptosis-Mediated Neurodegeneration
Authors: Sarparast Morteza , Pourmand Elham , Hinman Jennifer , Vonarx Derek , Reason Tommy , Zhang Fan , Paithankar Shreya , Chen Bin , Borhan Babak , Watts Jennifer L. , Alan Jamie , Lee Kin Sing Stephen 
Published: January 2023

AbstractEven after decades of research, the mechanism of neurodegeneration remains understudied, hindering the discovery of effective treatments for neurodegenerative diseases. Recent reports suggest that ferroptosis could be a novel therapeutic target for neurodegenerative diseases. While polyunsaturated fatty acid (PUFA) plays an important role in neurodegeneration and ferroptosis, how PUFAs may trigger these processes remains largely unknown. PUFA metabolites from cytochrome P450 and epoxide hydrolase metabolic pathways may modulate neurodegeneration. Here, we test the hypothesis that specific PUFAs regulate neurodegeneration through the action of their downstream metabolites by affecting ferroptosis. We find that the PUFA, dihomo gamma linolenic acid (DGLA), specifically induces ferroptosis-mediated neurodegeneration in dopaminergic neurons. Using synthetic chemical probes, targeted metabolomics, and genetic mutants, we show that DGLA triggers neurodegeneration upon conversion to dihydroxyeicosadienoic acid through the action of CYP-EH, representing a new class of lipid metabolite that induces neurodegeneration via ferroptosis.
Impaired migration and premature differentiation underlie the neurological phenotype associated with PCDH12 loss of function
Authors: Rakotomamonjy Jennifer , Rylaarsdam Lauren , Fares-Taie Lucas , McDermott Sean , Davies Devin , Yang George , Fagbemi Fikayo , Epstein Maya , Guemez-Gamboa Alicia 
Published: January 2023

SummaryProtocadherins (PCDHs) are cell adhesion molecules that regulate many essential neurodevelopmental processes related to neuronal maturation, dendritic arbor formation, axon pathfinding, and synaptic plasticity. Bi-allelic loss-of-function variants inPCDH12are associated with several neurodevelopmental disorders (NDDs) such as diencephalic-mesencephalic dysplasia syndrome, cerebral palsy, cerebellar ataxia, and microcephaly. Despite the highly deleterious outcome resulting from loss of PCDH12, little is known about its role during brain development and disease. Here, we show that PCDH12 loss severely impairs cerebral organoid development with reduced proliferative areas and disrupted laminar organization. 2D models further show that neural progenitor cells lacking PCDH12 prematurely exit cell cycle and differentiate earlier when compared to wildtype. Furthermore, we show that PCDH12 regulates neuronal migration through a mechanism requiring ADAM10-mediated ectodomain shedding and membrane recruitment of cytoskeleton regulators. Our data demonstrate a critical and broad involvement of PCDH12 in cortical development, revealing the pathogenic mechanisms underlying PCDH12-related NDDs.
Omicron Spike Protein Is Vulnerable to Reduction
Authors: Yao Zhong , Geng Betty , Marcon Edyta , Pu Shuye , Tang Hua , Merluza John , Bello Alexander , Snider Jamie , Lu Ping , Wood Heidi , Stagljar Igor 
Published: January 2023

AbstractSARS-CoV-2 virus spike (S) protein is an envelope protein responsible for binding to the ACE2 receptor, driving subsequent entry into host cells. The existence of multiple disulfide bonds in the S protein makes it potentially susceptible to reductive cleavage. Using a tri-part split luciferase-based binding assay, we evaluated the impacts of chemical reduction on S proteins from different virus variants and found that those from the Omicron family are highly vulnerable to reduction. Through manipulation of different Omicron mutations, we found that alterations in the receptor binding module (RBM) are the major determinants of this vulnerability. Specifically we discovered that Omicron mutations facilitate the cleavage of C480-C488 and C379-C432 disulfides, which consequently impairs binding activity and protein stability. The vulnerability of Omicron S proteins suggests a mechanism that can be harnessed to treat specific SARS-CoV-2 strains.
‘Be a game changer and keep the ball rolling’: exploring linkages between football clubs, charitable foundations and doing good
Authors: Hyndman Noel , Liguori Mariannunziata 
Published: January 2023

PurposeThere has been limited research on why football clubs contribute to charity. This paper examines how football clubs and their charitable conduits report information when discussing their connectedness. In addition, it explores reasons why, and the extent to which, football clubs support altruism via such charitable vehicles.Design/methodology/approachCase studies of four major football teams (Manchester City/Manchester United in England and AC Milan/Inter Milan in Italy) are discussed, with formal reports of the clubs and their associated charitable conduits being analysed.FindingsBoundaries between the clubs and their charitable conduits are frequently blurred. Evidence suggests that acknowledging the co-existence of different factors may help to understand what is reported by these organisations and address some of the caveats in terms of autonomy and probity of their activities and reporting practices.Research limitations/implicationsThe research uses case studies of four major ‘powerhouses’ of the game and their associated charitable spinoffs. While this is innovative and novel, expanding the research to investigate more clubs and their charitable endeavours would allow greater generalisations.Practical implicationsThe study provides material that can be used to reflect on the very topical subject of ‘sportswashing’. This has the potential to input to deliberations relating to the future governance of the game.Originality/valueThe paper explores relationships between businesses and charities/nonprofits in a sector so far little investigated from a charitable accountability perspective. It suggests that motives for engaging in charitable activity and highlighting such engagement may extend beyond normal altruism or warm-glow emotions.
Factors related to corporate social responsibility implementation: the case of mobile operators in the Kingdom of Bahrain
Authors: Al-Alawi Adel Ismail , BinZaiman Fatima Abdulrahman , Elnaggar Nehal F. 
Published: January 2023

PurposeThis paper aims to examine the factors affecting the implementation of corporate social responsibility (CSR) sustainably in mobile operators in the kingdom of Bahrain.Design/methodology/approachThe research relies on the existing literature as a secondary data source. The primary data was collected through questionnaires distributed to three leading mobile operators in the Kingdom of Bahrain. The research's population numbered 1,689, and the sample size was 313; the simple random sampling method was used for data collection with a response rate of 87.2% out of a total sample size of 273 respondents. In addition, the responses were analyzed using statistical package for the social sciences (SPSS) software version 24.0; specifically, Spearman's rank correlation was used to test the hypotheses. The research design was quantitative, so a nonparametric procedure was applied to test the hypotheses.FindingsThe research produced positive relationships between the independent variables (economic, legal, ethical, philanthropic and environmental responsibilities) and the dependent variable: CSR implementation by Bahrain mobile operators; therefore, the five proposed hypotheses were accepted; furthermore, the highest positive correlation coefficient was 0.735 for environmental responsibility, and the lowest correlation coefficient was 0.533 for economic responsibility.Research limitations/implicationsThe research produced positive relationships between the independent variables (economic responsibility, legal responsibility, ethical responsibility, philanthropic responsibility and environmental responsibility) and the dependent variable: CSR implementation by Bahrain mobile operators; therefore, the five proposed hypotheses were accepted; furthermore, the highest positive correlation coefficient was 0.735 for environmental responsibility, and the lowest correlation coefficient was 0.533 for economic responsibility.Social implicationsThe outcomes of the research mainly suggest that mobile operators assign employees who have been working with the company for more than 7 years to implement CSR; due to their engagement to implement CSR as a sustainable practice more than others with less than 3 years or 3-6 years in Bahrain mobile operators. Besides, the research provides a starting point by which other researchers could investigate CSR in other sectors in the Kingdom of Bahrain.Originality/valueThe research provided a framework for Bahrain mobile operators to assist them in enhancing the implementation of CSR in a sustainable manner, which are economic, legal, ethical, philanthropic and environmental responsibilities.
Evaluation of the integration of industrialization and information-based entropy AHP–cross-efficiency DEA model
Authors: Zhu Jianhua , Wan Luxin , Zhao Huijuan , Yu Longzhen , Xiao Siyu 
Published: January 2023

Purpose
The purpose of this paper is to provide scientific guidance for the integration of industrialization and information (TIOII). In recent years, TIOII has promoted the development of intelligent manufacturing in China. However, many enterprises blindly invest in TIOII, which affects their normal production and operation.

Design/methodology/approach
This study establishes an efficiency evaluation model for TIOII. In this paper, entropy analytic hierarchy process (AHP) constraint cone and cross-efficiency are added based on traditional data envelopment analysis (DEA) model, and entropy AHP–cross-efficiency DEA model is proposed. Then, statistical analysis is carried out on the integration efficiency of enterprises in Guangzhou using cross-sectional data, and the traditional DEA model and entropy AHP–cross-efficiency DEA model are used to analyze the integration efficiency of enterprises.

Findings
The data show that the efficiency of enterprise integration is at a medium level in Guangzhou. The efficiency of enterprise integration has no significant relationship with enterprise size and production type but has a low negative correlation with the development level of enterprise integration. In addition, the improved DEA model can better reflect the real integration efficiency of enterprises and obtain complete ranking results.

Originality/value
By adding the entropy AHP constraint cone and cross-efficiency, the traditional DEA model is improved. The improved DEA model can better reflect the real efficiency of TIOII and obtain complete ranking results.
Design and dimensioning of a test bench for investigating the relationship between critical temperature and axial mechanical stress of GdBaCuO tape conductors
Authors: Liebrich Johannes , Kreischer Christian 
Published: January 2023

Purpose
Superconductors offer several advantages compared with conventional conductors. However, it is not clear at this stage whether these types of conductors provide the same durability. For this reason, tape conductors under mechanical forces need to be studied in detail. The purpose of this paper is to investigate the relationship between critical temperature and axial mechanical stress of GdBaCuO tape conductors.

Design/methodology/approach
The paper investigates the influence of axial mechanical stresses on the critical temperature of superconductors. For these investigations, a multi-physical test rig was developed, which makes it possible to perform these types of investigations. With the presented measurement methodology, the influence of mechanical stresses on the tape conductor can be determined.

Findings
The investigations show a correlation between the critical temperature and the acting mechanical stresses. The analytically presented approach to describe the transition temperature is valid for the investigated samples. In addition, it is determined that the effects are not reversible, and therefore, permanent damage to the tape conductor is observed.

Originality/value
The presented investigations make it possible to create more accurate models of GdBaCuO tape conductors. This enables to extend the superconducting state space, which so far depends on three critical quantities, by the quantity of the axial stress.
Glasgow climate pact and the global clean energy index constituent stocks
Authors: Pandey Dharen Kumar , Kumar Rahul , Kumari Vineeta 
Published: January 2023

PurposeThis study examined the impact of the Glasgow Climate Pact on the abnormal returns of global clean energy stocks. Further, this study examines which country-specific and firm-specific variables drive the cumulative abnormal returns (CARs) of clean energy stocks.Design/methodology/approachThe authors used the event study method and cross-sectional multivariate regression model. The clean energy stocks in this study are limited to 81 constituent firms of the S&P Global Clean Energy Index across 17 nations. The final sample includes 80 firms and the sample period ranges from January 26, 2021, to December 07, 2021.FindingsThe study finds that the Glasgow Climate Pact negatively affects the stock returns of clean energy firms. Moreover, the climate change performance index (CCPI) positively impacts cumulative abnormal returns (CARs), signifying that clean energy investors react positively to firms in nations with good CCPI scores. The environmental, social and governance (ESG) measure for the shorter window (−1, +1) exhibited a negative relationship with CARs. The firm-specific variables (BTM, stock liquidity, size and past returns) exhibit a negative relationship with CARs in different event windows.Research limitations/implicationsThe authors use the CCPI as a proxy for the stringency of environmental policies in any nation. The authors extend the existing literature by employing firm-specific variables and supporting previous findings. Their findings have policy implications for clean energy investors, policymakers and other market participants.Practical implicationsClimate risks impact the global financial market, so the findings have implications for global regulatory bodies. Currently, there are bankruptcy cases due to climate risks. Because financial markets must play a critical role in shifting the economy toward a green one, regulators can use the cross-sectional drivers of this study to shape policy. It is also critical for regulators to reduce stock price volatility in the event of the implementation of environmental regulations and improve environmental disclosures by publicly traded companies. Furthermore, governments are interested in researching the effects of environmental regulations to protect stakeholders' interests. These regulations significantly impact emerging markets because they lack the same solid institutional frameworks as developed markets.Originality/valueThe authors provide evidence that firms with better ESG scores and larger firm sizes have experienced fewer abnormal returns, as these firms have stable financial and non-financial fundamentals. This timely study on the ongoing regulatory shift in environmental policy will help investors, policymakers, firms and other stakeholders make relevant decisions.