bluuebunny/crossref_metadata_2025_split huggingface dataset:
Converging evidence for differential regulatory control of APOEε4 on African versus European haplotypes
Authors: Nuytemans Karen , Lipkin Marina , Wang Liyong , Van Booven Derek , Griswold Antony J. , Rajabli Farid , Celis Katrina , Oron Oded , Hofmann Natalia , Rolati Sophie , Garcia-Serje Catherine , Zhang Shanshan , Jin Fulai , Argenziano Mariana , Grant Struan F.A. , Chesi Alessandra , Brown Christopher D. , Young Juan I. , Dykxhoorn Derek M. , Pericak-Vance Margaret A. , Vance Jeffery M. 
Published: August 2021

AbstractINTRODUCTIONThe difference in APOEε4 risk for Alzheimer disease (AD) between different populations is associated with APOEε4 local ancestry (LA). We examined LA SNPs with significant frequency differences between African and European/Japanese APOEε4 haplotypes for areas of differential regulation.METHODSWe performed two enhancer Massively Parallel Reporter Assay (MPRA) approaches, supplemented with single fragment reporter assays. We utilized Capture C analyses to support interactions with the APOE promoter.RESULTSThe TOMM40 intron 2 and 3 region showed increased enhancer activity in the European/Japanese versus African LA haplotypes in astrocytes and microglia. This region overlaps with APOE promoter interactions as assessed by Capture C analysis. Single variant analyses pinpoints rs2075650/rs157581, and rs59007384 as functionally different on these haplotypes.DISCUSSIONBoth differential regulatory function and Capture C data support an intronic region in TOMM40 as contributing to the differential APOE expression between African and European/Japanese LA.
Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory T cells
Authors: Martini Veronica , Edmans Matthew , Gubbins Simon , Jayaraman Siddharth , Paudyal Basu , Morgan Sophie , McNee Adam , Morin Théo , Rijal Pramila , Gerner Wilhelm , Sewell Andrew K. , Inoue Ryo , Bailey Mick , Connelley Timothy , Charleston Bryan , Townsend Alain , Beverley Peter , Tchilian Elma 
Published: August 2021

AbstractWe defined naïve, central memory, effector memory and terminally differentiated porcine CD8 T cells and analyzed their phenotype in lymphoid and respiratory tissues after influenza infection or immunization using peptide-MHC tetramers of three influenza nucleoprotein (NP) epitopes. The hierarchy of response to the three epitopes changes during the response in different tissues. Most NP-specific CD8 T cells in broncho-alveolar lavage (BAL) and lung are tissue resident memory cells (TRM), that express CD69 and have an effector memory or terminally differentiated phenotype. NP-specific cells isolated from BAL express genes characteristic of TRM, but gene expression differs at 7, 21 and 63 days post infection. The frequency of NP-specific cells declines over 63 days in all tissues but is best maintained in BAL. The pig is a powerful model for understanding how best to induce and harness local immunity to respiratory viruses.One sentence summaryInfluenza NP-specific porcine tissue resident memory CD8 T cells persist in the lung with major changes in gene expression.
Cell Sex and Sex Hormones Modulate Kidney Glucose and Glutamine Metabolism in Health and Diabetes
Authors: Clotet-Freixas S , Zaslaver O , Pastrello C , Kotlyar M , McEvoy C , Farkona S , Saha A , Boshart A , Chan M , Riera M , Soler MJ , Isenbrandt A , Lamontagne-Proulx J , Pradeloux S , Coulombe K , Soulet D , Dart AB , Wicklow B , McGavock JM , Blydt-Hansen TD , Jurisica I , Woo M , Scholey JW , Röst H , Konvalinka A 
Published: August 2021

ABSTRACTMale sex is a risk factor for progression of diabetic kidney disease, but the reasons for this predilection are unclear. Here, we demonstrate that cell sex and sex hormones alter the metabolic phenotype of human proximal tubular epithelial cells (PTECs). Male PTECs displayed increased glycolysis, mitochondrial respiration, oxidative stress, apoptosis, and high glucose-induced injury, compared to female PTECs. This phenotype was enhanced by dihydrotestosterone (DHT) and linked to increased mitochondrial utilization of glucose and glutamine. Studies in vivo pointed towards increased glutamine anaplerosis in diabetic male kidneys. Male sex was linked to increased levels of glutamate, TCA cycle, and glutathione cycle metabolites, in PTECs and in the blood metabolome of healthy youth and youth with type 2 diabetes. Conversely, female PTECs displayed increased levels of pyruvate, glutamyl-cysteine, cysteinylglycine, and a higher GSH/GSSG ratio than male PTECs, indicative of enhanced redox homeostasis. Finally, we identified transcriptional mechanisms that control kidney metabolism in a sex-specific fashion. While X-linked demethylase KDM6A facilitated metabolic homeostasis in female PTECs, transcription factor HNF4A mediated the deleterious effects of DHT in male PTECs. This work uncovers the role of sex in glucose/glutamine metabolism, that may explain the roots of sex dimorphism in the healthy and diabetic kidney.
Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration
Authors: Cao Yingxi , Xia Yu , Balowski Joseph B. , Ou Jianhong , Song Lingyun , Safi Alexias , Curtis Timothy , Crawford Gregory E. , Poss Kenneth D. , Cao Jingli 
Published: August 2021

ABSTRACTThe epicardium is a mesothelial tissue layer that envelops the heart. Cardiac injury activates dynamic gene expression programs in epicardial tissue, which in the case of zebrafish enables subsequent regeneration through paracrine and vascularizing effects. To identify tissue regeneration enhancer elements (TREEs) that control injury-induced epicardial gene expression during heart regeneration, we profiled transcriptomes and chromatin accessibility in epicardial cells purified from regenerating zebrafish hearts. We identified hundreds of candidate TREEs, defined by increased chromatin accessibility of non-coding elements near genes with increased expression during regeneration. Several of these candidate TREEs were incorporated into stable transgenic lines, with 5 of 6 elements directing injury-induced epicardial expression but not ontogenetic epicardial expression in hearts of larval animals. Whereas two independent TREEs linked to the gene gnai3 showed similar functional features of gene regulation in transgenic lines, two independent ncam1a-linked TREEs directed distinct spatiotemporal domains of epicardial gene expression. Thus, multiple TREEs linked to a regeneration gene can possess either matching or complementary regulatory controls. Our study provides a new resource and principles for understanding the regulation of epicardial genetic programs during heart regeneration.
Forest growth responds more to air pollution than soil acidification
Authors: Hruška Jakub , Oulehle Filip , Chuman Tomáš , Kolář Tomáš , Rybníček Michal , McDowell William H. 
Published: August 2021

AbstractThe forests of central Europe have undergone remarkable transitions in the past 40 years as air quality has improved dramatically. Retrospective analysis of Norway spruce (Picea abies) tree rings in the Czech Republic shows that air pollution (e.g. SO2concentrations, high acidic deposition to the forest canopy) plays a dominant role in driving forest health. Extensive soil acidification occurred in the highly polluted “Black Triangle” in Central Europe, and upper mineral soils are still acidified. In contrast, acidic atmospheric deposition declined by 80% and atmospheric SO2concentration by 90% between the late 1980s and 2010s. Annual tree ring width (TRW) declined in the 1970s and subsequently recovered in the 1990s, tracking SO2concentrations closely. Furthermore, recovery of TRW was similar in unlimed and limed stands. Despite large increases in soil base saturation, as well as soil pH, as a result of repeated liming starting in 1981, TRW growth was similar in limed and unlimed plots. TRW recovery was interrupted in 1996 when highly acidic rim (originating from more pronounced decline of alkaline dust than SO2from local power plants) injured the spruce canopy, but recovered soon to the pre-episode growth. Across the long-term site history, changes in soil chemistry (pH, base saturation, Bc/Al soil solution ratio) cannot explain observed changes in TRW at the two study sites at which we tracked soil chemistry. Instead, statistically significant recovery in TRW is linked to the trajectory of annual SO2concentrations or sulfur deposition at all three stands.
Coupled small molecules target RNA interference and JAK/STAT signaling to reduce Zika virus infection in Aedes aegypti
Authors: Trammell Chasity E. , Ramirez Gabriela , Sanchez-Vargas Irma , Luckhart Shirley , Perera Rushika , Goodman Alan G. 
Published: August 2021

ABSTRACTThe recent global Zika epidemics have revealed the significant threat that mosquito-borne viruses pose. There are currently no effective vaccines or prophylactics to prevent Zika virus (ZIKV) infection. Limiting exposure to infected mosquitoes is best way to reduce disease incidence. Recent studies have focused on targeting mosquito reproduction and immune responses to reduce transmission. In particular, previous work evaluated the effect of insulin signaling on antiviral JAK/STAT and RNAi in vector mosquitoes. In this work, we demonstrate that targeting insulin signaling through the repurposing of small molecule drugs results in the activation of both of these antiviral pathways. Activation of this coordinated response additively reduced ZIKV levels in Aedes aegypti mosquitoes. This effect included a quantitatively greater reduction in salivary gland ZIKV levels relative to single pathway activation, indicating the potential for field delivery of these small molecules to substantially reduce virus transmission.
c-di-AMP signaling is required for bile salts resistance and long-term colonization by Clostridioides difficile
Authors: Oberkampf Marine , Hamiot Audrey , Altamirano-Silva Pamela , Bellés-Sancho Paula , Tremblay Yannick D. N. , DiBenedetto Nicholas , Seifert Roland , Soutourina Olga , Bry Lynn , Dupuy Bruno , Peltier Johann 
Published: August 2021

ABSTRACTTo cause disease, the important human enteropathogen Clostridioides difficile must colonize the gastro-intestinal tract but little is known on how this organism senses and responds to the harsh host environment to adapt and multiply. Nucleotide second messengers are signaling molecules used by bacteria to respond to changing environmental conditions. In this study, we showed for the first time that c-di-AMP is produced by C. difficile and controls the uptake of potassium, making it essential for growth. We found that c-di-AMP is involved in biofilm formation, cell wall homeostasis, osmotolerance as well as detergent and bile salt resistance in C. difficile. In a colonization mouse model, a strain lacking GdpP, a c-di-AMP degrading enzyme, failed to persist in the gut in contrast to the parental strain. We identified OpuR as a new regulator that binds c-di-AMP and represses the expression of the compatible solute transporter OpuC. Interestingly, an opuR mutant is highly resistant to a hyperosmotic or bile salt stress compared to the parental strain while an opuCA mutant is more susceptible A short exposure of C. difficile cells to bile salts resulted in a decrease of the c-di-AMP concentrations reinforcing the hypothesis that changes in membrane characteristics due to variations of the cellular turgor or membrane damages constitute a signal for the adjustment of the intracellular c-di-AMP concentration. Thus, c-di-AMP is a signaling molecule with pleiotropic effects that controls osmolyte uptake to confer osmotolerance and bile salt resistance in C. difficile and that is important for colonization of the host.One Sentence Summaryc-di-AMP is an essential regulatory molecule conferring resistance to osmotic and bile salt stresses by controlling osmolyte uptake and contributing to gut persistence in the human enteropathogen Clostridioides difficile.
TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia
Authors: Jairaman Amit , McQuade Amanda , Granzotto Alberto , Kang You Jung , Chadarevian Jean Paul , Gandhi Sunil , Parker Ian , Smith Ian , Cho Hansang , Sensi Stefano L. , Othy Shivashankar , Blurton-Jones Mathew , Cahalan Michael 
Published: August 2021

AbstractThe membrane protein TREM2 (Triggering Receptor Expressed on Myeloid cells 2) regulates key microglial functions including phagocytosis and chemotaxis. Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer’s disease (AD). Because abnormalities in Ca2+signaling have been observed in several AD models, we investigated TREM2 regulation of Ca2+signaling in human induced pluripotent stem cell-derived microglia (iPSC-microglia) with genetic deletion of TREM2. We found that iPSC-microglia lacking TREM2 (TREM2 KO) show exaggerated Ca2+signals in response to purinergic agonists, such as ADP, that shape microglial injury responses. This ADP hypersensitivity, driven by increased expression of P2Y12and P2Y13receptors, results in greater release of Ca2+from the endoplasmic reticulum (ER) stores, which triggers sustained Ca2+influx through Orai channels and alters cell motility in TREM2 KO microglia. Using iPSC-microglia expressing the genetically encoded Ca2+probe, Salsa6f, we found that cytosolic Ca2+tunes motility to a greater extent in TREM2 KO microglia. Despite showing greater overall displacement, TREM2 KO microglia exhibit reduced directional chemotaxis along ADP gradients. Accordingly, the chemotactic defect in TREM2 KO microglia was rescued by reducing cytosolic Ca2+using a P2Y12receptor antagonist. Our results show that loss of TREM2 confers a defect in microglial Ca2+response to purinergic signals, suggesting a window of Ca2+signaling for optimal microglial motility.
Modeling and analysis of variable reluctance resolver using magnetic equivalent circuit
Authors: Rostami Mohsen , Naderi Peyman , Shiri Abbas 
Published: August 2021

Purpose
The purpose of this paper is to propose a saturable model based on the magnetic equivalent circuit (MEC) for evaluating the electromagnetic performance of the variable area resolver.

Design/methodology/approach
The equivalent circuit is developed where three different reluctance types are used to calculate permeances based on geometrical approximations. The proposed model typically has two types of equations, including the magnetic and electrical equations. The magnetic and electrical equations are related to the resolver core and the windings, respectively. Applying the well-known trapezoidal method, the magnetic and electrical equations can be simultaneously solved. A nonlinearity of the magnetic equations, the algebraic equations system, which is obtained from Kirchhoff’s laws, should be solved by the Newton-Raphson technique in each step-time.

Findings
The flexible MEC model, in which the number of flux tubes in different parts of the resolver can be arbitrarily selected, is proposed to analyze the variable reluctance resolver. Besides, the design parameters such as geometrical dimensions, windings arrangement and a number of the rotor saliencies can be chosen as desired. To consider the effect of time harmonics, a new nonlinear function is used for the core magnetization. Furthermore, different winding layouts can be implemented in the model to take space harmonics into account. The model obtained results are compared with the finite element method in terms of accuracy and simulation time.

Originality/value
Generally, the accuracy of the predictions in the MEC method is dependent on the number of flux tubes; therefore, the flexibility of the proposed MEC model in its capability to choose the desired number of flux paths is the advantage of this work. Moreover, the proposed model can analyze both wound and saliency rotor resolvers by changing the design parameters.
Gender diversity on corporate boards: How Asian and African women contribute on sustainability reporting activity
Authors: Cicchiello Antonella Francesca , Fellegara Anna Maria , Kazemikhasragh Amirreza , Monferrà Stefano 
Published: August 2021

PurposeThis study aims to investigate the influence of organisations’ board gender diversity on the adoption of the United Nations sustainable development goals (SDGs) and on the use of external assurance.Design/methodology/approachThe paper combines data from the Global Reporting Initiative’s Sustainability Disclosure Database and the Orbis database from Bureau van Dijk. The study uses logit models based on a sample of 366 large Asian and African companies which have addressed the SDGs in their sustainability reports published in 2017.FindingsThe results reveal that board gender diversity is positively associated with sustainability reporting and the involvement of an external assurance provider.Originality/valueThis study adds to the growing literature on the relationship between women’s participation on corporate boards and SDG reporting. Additionally, it addresses the understudied question of how the gender diversity of board resources affects the adoption of the external assurance of sustainability reporting.
Digital business models in cultural tourism
Authors: Ammirato Salvatore , Felicetti Alberto Michele , Linzalone Roberto , Carlucci Daniela 
Published: August 2021

PurposeDigitalization had a relevant impact on the cultural tourism sector, both demand and supply. If, on the one hand, advances in digital technologies provided tourists with new mobile services able to amplify the cultural experience, on the other hand, they catalyzed the development of new business models by digital enterprises. This paper has a twofold purpose: to detect business models and key characteristics of mobile apps for cultural tourism and to analyze the offering of app-based services in this sector.Design/methodology/approachThe authors defined a methodology to identify, characterize and analyze a particular category of digital products for cultural tourism: app-based services. They are studied in terms of value creation, proposition and capture with the aim to identify the distinctive features of business models. As a result, the authors identified a classification framework on three main dimensions, namely “how to exploit mobile app features to create value for cultural tourists” (value creation), “which valuable services are delivered to cultural tourists” (value proposition) and “how companies are rewarded for the value they offered” (value capture). The authors apply the framework to perform a situation analysis of app-based services in the cultural tourism market.FindingsThe analysis highlights that digital enterprises offering app-based services do not fully exploit advances in technologies about users' value requirements. Hence, the results of our work suggest some directions that digital enterprises may follow to better exploit mobile app technology.Originality/valueTo date, little research has been devoted to investigating cultural tourism business models involving the exploitation of mobile app-based services. This research provides a useful framework to analyze fundamental aspects of business models in this sector. Such a framework represents a practical tool that provides fruitful insights for the design of a new generation of app-based services within the so-called “Internet of things” domain.
The provenance and effects of entrepreneurial inspiration
Authors: Van Ewijk Anne Rienke , Nabi Ghulam , Weber Wiebke 
Published: August 2021

PurposeBuilding on authoritative studies on inspiration in the field of psychology (e.g. Thrash and Elliot, 2013, 2014), this study aims to clarify how entrepreneurial inspiration – an emotional state of personal attraction toward entrepreneurship – is created and how it affects entrepreneurial intentions. First, receptiveness to inspiration is introduced as a potential entrepreneurial feeling trait that constitutes a universal enabler of entrepreneurial inspiration alongside typically idiosyncratic inspirational triggers. Second, this study proposes to reinforce the theoretical base of the relation between entrepreneurial inspiration and entrepreneurial intentions by applying the affect infusion model (AIM) and empirically testing its explanatory power.Design/methodology/approachHypotheses are tested through independent and dependent samplet-tests and hierarchical regression analyses with an interaction effect. Data originate from a pre-post course survey among 342 entrepreneurship students from various countries and institutions.FindingsThe results confirm a positive relation between receptiveness to inspiration and entrepreneurial inspiration. Receptiveness to inspiration precedes and increases with entrepreneurial experience, suggesting that it can be both inborn and cultivated. In line with the AIM, entrepreneurial inspiration stimulates only the entrepreneurial aspirations of participants without entrepreneurial experience. Experienced individuals, on the other hand, derived more entrepreneurial inspiration from their courses, but this was not translated to higher entrepreneurial intentions. Instead, they could benefit from this inspiration in other ways proposed in the literature, such as enhanced opportunity recognition.Originality/valueThis study provides much needed, theory-informed, insight into the formation of entrepreneurial inspiration. Furthermore, it is the first research to propose and test a specific theoretical underpinning of the relation between entrepreneurial inspiration and entrepreneurial intentions, which also accounts for the moderating role of entrepreneurial experience. Finally, the rare multi-country, multi-institution nature of the sample reinforces the external validity of the findings.
A multi-level analysis of sustainability practices in Ghana: examining the timber, cocoa, and gold mining industries
Authors: Hess James P. 
Published: August 2021

Purpose
The purpose of this paper is to examine the macro-, meso- and micro-level approaches to building sustainability in Ghana's timber, cocoa and goldmining industries s Ghana works to align sustainability efforts with the sustainable development goals proposed by the United Nations.

Design/methodology/approach
Using qualitative content analysis, a synthesis of contemporary literature on Ghana's timber, cocoa and gold mining industries was conducted to provide a descriptive evaluation of sustainability efforts in those industries.

Findings
At the macro-level, Ghana continues to invest in infrastructure, privatize industries and develop an urban development agenda to encourage foreign direct investment (FDI); improved forest management and green building policies and reduction of galamsey are also implemented. At the meso-level, the timber industry encourages land reclamation and green building technologies; the cocoa industry works to replenish lost trees, develop supply-chain partnerships, and encourage certifications; the goldmining industry works to regulate informal mining and reduce galamsey and the use of toxins in exploration. At the micro-level, alignment has developed between the micro- and meso-levels in the timber and cocoa industries, whereas micro-level players in the timber industry are less successful, given its large, unregulated informal sector.

Originality/value
Existing literature is missing discussion on the alignment of macro-, meso- and micro-level approaches to sustainability in Ghana's timber, cocoa and gold mining industries with attention to the United Nations' Sustainable Development Goals as the premise for the work.