bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble LIGHT (TNFSF14) activates endothelial cells, thereby priming the first vessel-occlusive events in acute sickle cell disease
Authors: Chadebech Philippe , Nguyen-Peyre Kim-Anh , Liberto Gaétana Di , Bodivit Gwellaouen , Pirenne France , Bartolucci Pablo 
Published: June 2023

ABSTRACTIn sickle cell disease (SCD), the red blood cells carry a mutated form of hemoglobin (HbS) leading to altered shape and deformability. The mutation causes abnormal hemorheological properties, mechanical hemolysis, and adhesion. The chronic vascular inflammation observed in SCD and hemolysis-related endothelium activation may trigger the vaso-occlusion of blood vessels.The prothrombotic and pro-inflammatory LIGHT/TNFSF14 is a tumor necrosis factor (TNF)- superfamily cytokine implicated in various inflammatory diseases. It is expressed by various immune cells and is considered an actor in T cell-mediated immunity and immune cell recruitment. LIGHT has also been shown to activate endothelial cells (ECs) strongly. LIGHT levels are high in the plasma of SCD patients, and platelets are a major source of its circulating form.We studied a cohort of 82 homozygous adult patients with SCD (n=108 samples) to determine whether LIGHT levels were linked to the clinical state of patients included in the ‘Basal’ steady state or during an ‘Acute’ crisis. Soluble LIGHT levels were high in the plasma of SCD patients during acute phases of the disease, particularly during painful occlusive crises. LIGHT levels were associated with Hb levels and inflammatory markers (mainly interferon-γ and tumor necrosis factor-α, specifically in acute SCD patients). Our findings confirm that LIGHT is a strong activator of cultured ECs, inducing a type II inflammatory cytokine profile and the expression of adhesion molecules. Using a physiological flow adhesion test on biochips, we showed that the LIGHT-induced activation of ECs led to the adhesion of both sickle platelets (but not their AA counterparts), and in a less extend sickle RBCs to activated HUVECs, potentially constituting the first step in vaso-occlusion. Indeed, the pretreatment of HUVECs with neutralizing polyclonal Abs against LIGHT, but not the non-specific counterpart, showed a reversal of both the inflammation process activated by LIGHT treatment and platelet adhesion to endothelial cells.Soluble LIGHT appears to be a promising therapeutic target for preventing adverse occlusive events in SCD through the blockade of its receptor, to prevent the adhesion of blood cell components to the endothelium. Future studies should consider whether soluble LIGHT contributes to other clinical complications in SCD.HIGHLIGHTSIn patients with SCD, plasma LIGHT is mainly secreted during acute phases, including VOCs.Both Hb levels and IFNγ levels are correlated with plasma LIGHT with SCD patients in acute phase disease.The LIGHT-induced activation of endothelial cells leads to the flow adherence of both sickle (SS) platelets and red blood cells.Both endothelial priming by LIGHT and platelet adherence are abolished by anti-LIGHT polyclonal Abs.
Cryptococcosis, tuberculosis, and a kidney cancer fail to fit the atherosclerosis paradigm for foam cell lipid content
Authors: Guerrini Valentina , Prideaux Brendan , Khan Rehan , Subbian Selvakumar , Wang Yina , Sadimin Evita , Pawar Siddhi , Ukey Rahul , Singer Eric A. , Xue Chaoyang , Gennaro Maria Laura 
Published: June 2023

AbstractFoam cells are dysfunctional, lipid-laden macrophages associated with chronic inflammation of diverse origin. The long-standing paradigm that foam cells are cholesterol-laden derives from atherosclerosis research. We previously showed that, in tuberculosis, foam cells surprisingly accumulate triglycerides. Here, we utilized bacterial (Mycobacterium tuberculosis), fungal (Cryptococcus neoformans), and human papillary renal cell carcinoma (pRCC) models to address the need for a new explanation of foam cell biogenesis. We applied mass spectrometry-based imaging to assess the spatial distribution of storage lipids relative to foam-cell-rich areas in lesional tissues, and we characterized lipid-laden macrophages generated under correspondingin vitroconditions. Thein vivodata and thein vitrofindings showed that cryptococcus-infected macrophages accumulate triglycerides, while macrophages exposed to pRCC- conditioned-medium accumulated both triglycerides and cholesterol. Moreover, cryptococcus- and mycobacterium-infected macrophages accumulated triglycerides in different ways. Collectively, the data show that the molecular events underlying foam cell formation are specific to disease and microenvironment. Since foam cells are potential therapeutic targets, recognizing that their formation is disease-specific opens new biomedical research directions.
Quorum-sensingagrsystem ofStaphylococcus aureusprimes gene expression for protection from lethal oxidative stress
Authors: Podkowik Magdalena , Perault Andrew I. , Putzel Gregory , Pountain Andrew , Kim Jisun , Dumont Ashley , Zwack Erin , Ulrich Robert J. , Karagounis Theodora K. , Zhou Chunyi , Haag Andreas F. , Shenderovich Julia , Wasserman Gregory A. , Kwon Junbeom , Chen John , Richardson Anthony R. , Weiser Jeffrey N. , Nowosad Carla R. , Lun Desmond S. , Parker Dane , Pironti Alejandro , Zhao Xilin , Drlica Karl , Yanai Itai , Torres Victor J. , Shopsin Bo 
Published: June 2023

AbstractTheagrquorum-sensing system linksStaphylococcus aureusmetabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense againstS. aureus. We now report that protection byagrsurprisingly extends beyond post-exponential growth to the exit from stationary phase when theagrsystem is no longer turned on. Thus,agrcan be considered a constitutive protective factor. Deletion ofagrincreased both respiration and fermentation but decreased ATP levels and growth, suggesting that Δagrcells assume a hyperactive metabolic state in response to reduced metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in theagrmutant than in wild-type cells, thereby explaining elevated susceptibility of Δagrstrains to lethal H2O2doses. Increased survival of wild-typeagrcells during H2O2exposure requiredsodA, which detoxifies superoxide. Additionally, pretreatment ofS. aureuswith respiration-reducing menadione protected Δagrcells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate thatagrhelps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived “memory” ofagr-mediated protection, which is uncoupled fromagractivation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Nox2−/−) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.
Identification and functional characterization of the putative members of the CTDK-1 kinase complex as regulators of growth and development in the genusAspergillus
Authors: Agirrezabala Z. , Guruceaga X. , Martin-Vicente A. , Otamendi A. , Fagoaga A. , Fortwendel J.R. , Espeso E.A. , Etxebeste O. 
Published: June 2023

AbstractThe genusAspergillusincludes industrially, medically and agriculturally important species. All of them, as do fungi in general, disperse to new niches principally by means of asexual spores. Regarding the genetic/molecular control of asexual development,Aspergillus nidulansis the main reference. In this species, two pathways control the production of conidiophores, the structures bearing asexual spores (conidia). The Upstream Developmental Activation (UDA) pathway transduces environmental signals, determining whether the Central Developmental Pathway (CDP) and the required morphological changes are induced. The transcriptional regulator BrlA links both pathways as loss-of-function mutations inflb(UDA) genes blockbrlAtranscription and, consequently, conidiation. However, the aconidial phenotype of specificflbmutants is reverted under salt-stress conditions. Previously, we generated a collection of ΔflbBmutants unable to conidiate on culture medium supplemented with NaH2PO4(0.65M). Here, we identified a Gly347Stop mutation withinflpAas responsible for the FLIP57 phenotype. The putative cyclin FlpA and the remaining putative components of the C-terminal domain kinase-1 (CTDK-1) complex are necessary for proper germination, growth and developmental patterns in bothA. nidulansandA. fumigatus. Cellular localization and functional interdependencies of the three proteins are also analyzed. Overall, this work links the putative CTDK-1 complex of aspergilli with growth and developmental control.One-sentence summaryIdentification of a mutation inflpAas inhibitor of conidiation inA. nidulansand functional characterization of FlpA, Stk47 and FlpB as putative members of the C-terminal domain kinase complex CTDK-1 in the genusAspergillus.
A conserved and druggable pocket in class B G protein coupled receptors for orally active small molecule agonists
Authors: Zhao Li-Hua , He Qian , Yuan Qingning , Gu Yimin , He Xinheng , Li Junrui , Wang Kai , Li Yang , Shen Jianhua , Xu H. Eric 
Published: June 2023

AbstractClass B G protein-coupled receptors (GPCRs), including glucagon-like receptor 1 (GLP-1R) and parathyroid hormone receptor 1 (PTH1R), are peptide hormone receptors and important drug targets. Injectable peptide drugs targeting class B GPCRs have been developed for the treatment of many diseases, including type 2 diabetes, obesity, and osteoporosis, but orally available small molecule drugs are hotly pursued in the field, especially small molecule agonists of GLP-1R and PTH1R. Here we report the first high-resolution structure of the human PTH1R in complex with the stimulatory G protein (Gs) and a small molecule agonist, PCO371, which reveals an unexpected binding mode of PCO371 at the interface of PTH1R and Gs. The binding site of PCO371 is totally different from all binding sites previously reported for small molecules or peptide ligands in GPCRs. Residues that make up the PCO371 binding pocket are mostly conserved in class B GPCRs and a single mutation in PTH type 2 receptor (PTH2R) and two residue mutations in GLP-1R convert these receptors to respond to PCO371 activation. Functional assays reveal that PCO371 is a G-protein biased agonist that is defective in promoting PTH1R-mediated arrestin signaling. Together, these results uncover a distinct binding site for designing small molecule agonists for PTH1R and possible other members of class B GPCRs and define a receptor conformation that is only specific for G protein activation but not arrestin signaling. These insights should facilitate the design of distinct types of class B GPCR small molecule agonists for various therapeutic indications.
DNA-targeting short Argonaute triggers effector nuclease to protect bacteria from invaders
Authors: Prostova Maria , Kanevskaya Anna , Panteleev Vladimir , Lisitskaya Lidia , Tugaeva Kristina V. , Sluchanko Nikolai N. , Esyunina Daria , Kulbachinskiy Andrey 
Published: June 2023

AbstractTwo prokaryotic defence systems, Argonautes (pAgos) and CRISPR-Cas, detect invader nucleic acids using complementary guides. Upon recognition, the target is cleaved through nuclease activities of pAgo or Cas proteins thus protecting the cell from invasion. However, not all pAgos are active nucleases. Members of a large clade of short pAgos bind nucleic acid guides but lack nuclease activity suggesting a different mechanism of action. Here, we have investigated short pAgo fromNovosphingopyxis baekryungensis(NbaAgo). We have shown that NbaAgo forms a heterodimeric complex, SPARDA, with a co-encoded effector nuclease. RNA-guided target DNA recognition unleashes the nuclease activity of SPARDA leading to indiscriminate collateral cleavage of DNA and RNA. Activation of SPARDA results in cell death during plasmid transformation or phage infection, thus protecting bacterial population from invaders. The collateral activity of SPARDA allows highly sensitive detection of specific DNA targets. SPARDA expands the list of prokaryotic immune systems that elicit suicidal cell response with a unique range of nuclease activities, creating additional opportunities for biotechnologies.
The perceived value of digital fashion product and purchase intention: the mediating role of the flow experience in metaverse platforms
Authors: Park Yeonseo , Ko Eunju , Do Boram 
Published: June 2023

PurposeThis paper aims to explore digital fashion products in the metaverse platform contexts and empirically examine the effect of the metaverse platform characteristics on the purchase intention of digital fashion products through users' flow experience and perceived value of the products.Design/methodology/approachA survey method was used in this study. Answers from 314 metaverse users were analyzed, and the hypotheses were tested using the structural equations modeling and bootstrapping analysis.FindingsThe analyses showed that telepresence, social interaction and economic flow had significant effects on users' flow experience among the metaverse platform characteristics, while the continuity and content creation of the metaverse platform did not have significant effects. The flow experience also appeared to have significant effects on multiple consumption values, including pleasure value, self-expression value and economic value. Last, the perceived pleasure value and economic value of digital fashion products had a positive effect on purchase intention.Originality/valueThe main contribution of this research is that it is one of the first empirical attempts to investigate individual consumers' perceptions and experiences of digital fashion products in the context of metaverse platforms.
Asymmetric market efficiency of the Eurozone using the MF-DFA: a comparison between global financial crisis and COVID-19 era
Authors: Ali Sajid , Raza Syed Ali , Khan Komal Akram 
Published: June 2023

PurposeThis research paper aims to explore asymmetric market efficiency of the 13 Euro countries, i.e. Austria, Belgium, Finland, France, Germany, Greece, Ireland, Italy, Netherland, Portugal, Slovakia, Slovenia and Spain, concerning the period before global financial crisis (GFC), after GFC and period of COVID-19 pandemic.Design/methodology/approachMultifractal detrended fluctuation analysis (MF-DFA) is applied to examine the persistence and anti-persistency. It also discusses the random walk behavior hypothesis of these 13 countries non-stationary time series. Additionally, generalized Hurst exponents are applied to estimate the relative efficiency between short- and long-run horizons and small and large fluctuations.FindingsThe current study results suggest that most countries' markets are multifractal and exhibit long-term persistence in the short and long run. Moreover, the results with respect to full sample confirm that Portugal is the most efficient country in short run and Austria is the least efficient country. However, in long run, Austria appeared to be highly efficient, and Slovakia is the least efficient. In the pre-GFC period, Greece is said to be the relatively most efficient market in the short run, whereas Austria is the most efficient market in the long run. In the case of Post-GFC, Netherland and Ireland are the most efficient markets in short and long run, respectively. Lastly, COVID-19 results indicate that Finland's stock market is the most efficient in short run. Whereas, in the long run, the high efficiency is illustrated by Germany. In contrast, the most affected stock market due to COVID-19 is Belgium.Originality/valueThis study will add value to the present knowledge on efficient market hypothesis (EMH) with the MF-DFA approach. Also, with the MF-DFA approach, potential investors will be capable of ranking the stock markets of Eurozone countries based on their efficiency in the period before and after GFC and then specifically in the period of COVID-19.
The impacts of pandemic-related media coverage on workplace ageism among younger hospitality and tourism employees
Authors: Zhong Yun Ying , Leung Xi Yu , Sun Jie , Ng Boon Peng 
Published: June 2023

Purpose
This study aims to investigate the impacts of pandemic-related media coverage on younger hospitality and tourism employees’ ageist attitudes toward older people by applying the media priming theory and the terror management theory.

Design/methodology/approach
This study takes a mixed-method approach through an online survey. A total of 416 usable responses are collected from current US hospitality and tourism employees under 55 years. Qualitative data were analyzed using word cloud. Partial least squares structural equation modeling is then used to test the hypothesized model.

Findings
The study’s results show that younger employees' cognitive reaction negatively affects aging anxiety and intergenerational tension, which subsequently influence their willingness to work with older people. Negative media-induced emotions are positively associated with aging anxiety, whereas positive emotions exert no significant impact. Intergenerational contact frequency moderates the effect of intergenerational tension on younger employees’ willingness to work with older people.

Research limitations/implications
This study’s findings contribute to the hospitality and tourism workforce literature by considering the priming effects of media coverage on younger employees’ attitudes toward self-aging and the older group. This study also offers managerial insights on developing effective age-inclusion interventions to reduce workplace ageism in the post-pandemic era.

Originality/value
Existing hospitality and tourism studies on older workers are scant and largely descriptive. To the best of the authors’ knowledge, this study is the first study that assesses the effects of pandemic-related media coverage on workplace ageism toward older people among the current hospitality and tourism workforce.
The spillover effects of supply chain corruption practices on stock returns
Authors: Wang Geng , Xiong Yangchun , Cheng Yang , Lam Hugo K.S. 
Published: June 2023

PurposeThis study aims to explore the spillover effects of supply chain corruption practices (SCCPs) on stock returns along the supply chain and within the industry. Specifically, it investigates how SCCPs affect the stock returns of corrupt firms' bystander supply chain partners and industry peers, both of which are not involved in the SCCPs.Design/methodology/approachThe authors employ the event study methodology to quantify SCCPs' spillover effects in terms of abnormal stock returns. The analysis is based on 117 SCCPs occurring in China between 2014 and 2021.FindingsThe event study results show that SCCPs have negative effects on the stock returns of corrupt firms' bystander supply chain partners. Such negative effects are more pronounced for bystander buyers than bystander suppliers. However, SCCPs do not have a significant impact on the stock returns of corrupt firms' industry peers. Additional analysis further suggests that SCCPs are more likely to affect the stock returns of domestic rather than overseas bystander supply chain partners.Originality/valueThis study is the first attempt to thoroughly examine the spillover effects of SCCPs along the supply chain and within the industry, advancing the understanding of the financial consequences of SCCPs and providing important implications for future research and practices related to supply chain corruption.
Metaverse applications in education: a systematic review and a cost-benefit analysis
Authors: Camilleri Mark Anthony 
Published: June 2023

Purpose
Many educators are increasingly acquainting themselves and becoming adept with interactive technologies like augmented reality and virtual reality. Some of them are also looking forward to using Metaverse applications, as they want to benefit from its immersive three-dimensional capabilities. Therefore, the purpose of this study is to critically review the extant literature to investigate how, why, where and when the Metaverse can be used for educational purposes. This study also discusses opportunities, challenges and risks related to this disruptive technology.

Design/methodology/approach
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses rigorous protocol is used to search, extract, scrutinize and synthesize content from high-impact articles focused on the use of the Metaverse technology in the realms of education. Afterwards, this study theorizes on the costs and benefits of using this interactive technology with students.

Findings
A number of researchers are already experimenting with virtual technologies that are very similar to the Metaverse, in different contexts. This research indicates that most students are lured by immersive multi-sensory three-dimensional environments as well as by virtual reality applications that could simulate real-life situations and provide engaging experiences with virtual representations of people, places and objects. On the other hand, this study reveals that educators ought to consider the potential pitfalls of the Metaverse, including privacy breaches and security risks, as well as possible addictions and the development of mental health issues, among others.

Practical implications
Students and educators can use the Metaverse to catapult themselves in a simulated digital universe that could reconfigure their sensory inputs, definitions of space, time and points of access to information. This research calls for the development of regulatory instruments, including sound principles, guidelines and procedures that are intended to safeguard and protect Metaverse users.

Originality/value
This contribution implies that there is scope for educators to continue developing the Metaverse’s virtual spaces to improve their students’ motivations, aptitudes and learning outcomes. This study clarifies that the use of the Metaverse in education can create infinite possibilities to enhance their knowledge, competences and abilities through its immersive applications. Yet this paper also raises awareness about possible challenges in the short term as well on other risks associated to the prolonged use of this captivating technology.