bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral opioid tolerance involves skin keratinocytes and platelet-derived growth factor type B signaling
Authors: Posa Luca , Miracle Sophia A. , McDonald Ashley K. , Gamble Mackenzie , Albers Kathryn M. , Logan Ryan W. , Freyberg Zachary , Puig Stephanie 
Published: May 2024

AbstractOpioid analgesic tolerance is a deleterious side-effect that requires escalation of dose to overcome reduced analgesia overtime. Dose-escalation dramatically reduces opioid safety due to centrally-mediated life-threatening side-effects, including respiratory depression or addiction. Peripheral opioid delivery is a safer alternative as it provides effective local analgesia with limited central penetration. However, tolerance also occurs peripherally, via mechanisms that remain unknown. Centrally, activation of the mu-opioid receptor (MOPr) by opioids induces release of platelet-derived growth factor-B (PDGF-B); and inhibition of PDGF receptor beta (PDGFRβ) prevents opioid tolerance. In the periphery, MOPr and PDGF-B are expressed in skin keratinocytes, and PDGFRβ is expressed in peripheral sensory neurons (PSNs), known to convey tolerance. Previous studies also showed that optogenetic stimulation of keratinocytes modulates PSNs via release of keratinocytes-derived factors. Thus, we hypothesized that mechanisms of peripheral opioid tolerance could involve keratinocytes and PDGFRβ signaling. Using behavioral pharmacology, optogenetics and in situ hybridization in mice, we found that selective inhibition of PDGFRβ at the periphery, prevents peripheral morphine tolerance caused by repeated intraplantar (i.pl.) morphine injections. In addition, we show that PDGF-B is necessary and sufficient to cause peripheral morphine tolerance and repeated peripheral morphine injections lead to an increase in PDGF-B mRNA in MOPr-expressing keratinocytes. In parallel, we discovered that repeated optogenetic activation of keratinocytes is sufficient to induce peripheral morphine tolerance in a PDGF-B/PDGFRβ-dependent manner. Together, these data show that keratinocytes and PDGF-B/PDGFRβ signaling are essential components in the mechanisms of peripheral opioid tolerance.
Multimodal analysis of RNA sequencing data powers discovery of complex trait genetics
Authors: Munro Daniel , Ehsan Nava , Esmaeili-Fard Seyed Mehdi , Gusev Alexander , Palmer Abraham A. , Mohammadi Pejman 
Published: May 2024

AbstractTranscriptome data is commonly used to understand genome function via quantitative trait loci (QTL) mapping and to identify the molecular mechanisms driving genome wide association study (GWAS) signals through colocalization analysis and transcriptome-wide association studies (TWAS). While RNA sequencing (RNA-seq) has the potential to reveal many modalities of transcriptional regulation, such as various splicing phenotypes, such studies are often limited to gene expression due to the complexity of extracting and analyzing multiple RNA phenotypes. Here, we present Pantry (Pan-transcriptomic phenotyping), a framework to efficiently generate diverse RNA phenotypes from RNA-seq data and perform downstream integrative analyses with genetic data. Pantry currently generates phenotypes from six modalities of transcriptional regulation (gene expression, isoform ratios, splice junction usage, alternative TSS/polyA usage, and RNA stability) and integrates them with genetic data via QTL mapping, TWAS, and colocalization testing. We applied Pantry to Geuvadis and GTEx data, and found that 4,768 of the genes with no identified expression QTL in Geuvadis had QTLs in at least one other transcriptional modality, resulting in a 66% increase in genes over expression QTL mapping. We further found that QTLs exhibit modality-specific functional properties that are further reinforced by joint analysis of different RNA modalities. We also show that generalizing TWAS to multiple RNA modalities (xTWAS) approximately doubles the discovery of unique gene-trait associations, and enhances identification of regulatory mechanisms underlying GWAS signal in 42% of previously associated gene-trait pairs. We provide the Pantry code, RNA phenotypes from all Geuvadis and GTEx samples, and xQTL and xTWAS results on the web.
Predation by nematode-trapping fungus triggers mechanosensory-dependent quiescence inCaenorhabditis elegans
Authors: Lin Tzu-Hsiang , Chang Han-Wen , Tay Rebecca J. , Hsueh Yen-Ping 
Published: May 2024

AbstractPredation can induce behavioral changes in prey, yet the molecular and neuronal mechanisms underlying prey responses remain poorly understood. Here, we investigated how the nematodeCaenorhabditis elegansresponds to predation by the nematode-trapping fungus,Arthrobotrys oligospora. We found thatA. oligosporapredation induced quiescence inC. elegansshowing rapid cessation of pharyngeal pumping and movement. Calcium imaging revealed that this quiescence was regulated by the activation of sleep-promoting neurons, ALA and RIS. Genetic analyses demonstrated that ALA were essential for pharyngeal pumping inhibition, whereas both ALA and RIS contributed to movement cessation. Transcriptomic analysis inC. elegansshowed the upregulation of immune defense genes in response toA. oligosporapredation. We demonstrated that mechanosensation was required for pumping inhibition and transcriptomic regulation uponA. oligosporatrapping. These findings suggest that physical constraints imposed by fungal traps trigger a stress-induced quiescence and the upregulation of defense genes inC. elegans. We suggest that trapping-induced quiescence might be a predation strategy used by sessile predators to prevail in the evolutionary arms race.
Modelling the influence of climate and vector control interventions on arbovirus transmission
Authors: Fairbanks Emma L , Daly Janet M , Tildesley Michael J 
Published: May 2024

AbstractMost mathematical models that assess the vectorial capacity of disease-transmitting insects typically focus on the influence of climatic factors to predict variations across different times and locations, or examine the impact of vector control interventions to forecast their potential effectiveness. We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle and incorporates host availability and preference. Applying this model to arboviruses of veterinary importance in Europe, we show that African horse sickness virus (AHSV) has a higher peak predicted vectorial capacity than bluetongue virus (BTV), Schmallenberg virus (SBV) and epizootic haemorrhagic disease virus (EHDV). However, AHSV has a shorter average infectious period, due to high mortality, therefore AHSV’s overall basic reproduction number is similar to BTV. A comparable relationship exists between SBV and EHDV, with both viruses showing similar basic reproduction numbers. Focusing on AHSV transmission in the UK, insecticide-treated stable netting is shown to significantly reduce vectorial capacity ofCulicoideseven at low coverage levels. However, untreated stable netting is likely to have limited impact. Overall, this model can be used to consider both climate and vector control interventions either currently utilised or for potential use in an outbreakand could help guide policy makers seeking to mitigate the impact of climate change on disease control.Author summaryIn our study, we developed an advanced mathematical model that integrates the influences of climate and vector control strategies to predict the transmission of arboviruses. This is then used to highlight the increase in vectorial capacity African horse sickness, bluetongue, epizootic haemorrhagic disease and Schmallenberg virus, which are transmitted by theCuli-coidesspecies, in a European climate over the last 50 years.Our research provides valuable insights into how strategic use of insecticide-treated netting, even at low coverage levels, can substantially reduce the transmission potential of African horse sickness virus. This model offers a powerful tool for policymakers and health professionals, aiding in the formulation of more effective vector management strategies that could mitigate the impact of these diseases, especially in the context of changing global climates. This approach not only enhances our understanding of vector-borne disease dynamics but also supports the development of targeted interventions and prevent outbreaks.
Protease-activated receptor 2 links protease activity with calcium waves during egg activation and blastomere cleavage
Authors: Ma Jiajia , Carney Tom J. 
Published: May 2024

AbstractSuccessful initiation of animal development requires activation of the egg immediately prior to fusion of gamete pronucleii. In all taxa, this is initiated by waves of calcium transients which transverse across the egg. Calcium waves also occur at cleavage furrows during later blastula cytokinesis. Calcium is released from the endoplasmic reticulum through activation of 1,4,5-trisphosphate (IP3) receptors. Only a subset of the mechanisms employed to generate IP3during vertebrate egg activation are defined, with strong evidence that other critical mechanisms exist. Serine proteases have been long implicated in egg activation and fertilisation. Here we report that treatment of zebrafish eggs with serine protease inhibitors leads to defective calcium wave propagation and failed egg activation. We further show that mutation of zebrafish Protease-activated receptor 2a (Par2a) also results in severe disruption of egg activation, leading to failed chorion elevation and ooplasmic segregation. Milderpar2amutants progress further, but then show abnormal blastomere cleavage. We observed thatpar2amutants show decreased amplitude and duration of calcium transients. Restoring Ca++or direct injection of IP3ligand rescues egg activation aborted by either serine protease inhibitor treatment or by mutation of Par2a. We thus show that serine protease activity is a critical regulator of IP3and subsequent calcium wave amplification during zebrafish egg activation, and link this to intracellular calcium release via the protease receptor, Par2a. This constitutes a novel signalling pathway critical for successful fertilisation.Significance StatementBoth sperm and egg must undergo a series of important steps to become competent for successful fertilisation. Defining these steps is central to our understanding of reproductive biology and our ability to improve fertility treatments. As the process of gamete maturation and fertilisation has highly conserved principles across the animal kingdom, there are also important implications for aqua- and agriculture. One of the first signalling events of your life leads to the release of bursts of calcium in the egg. We know the importance of this for fertilisation but have only a partial picture of how this occurs. Our work here, using fish genetics, identifies a new signalling pathway regulating these first important flashes of calcium in the egg.
Inter- and intra-subject similarity in network functional connectivity across a full narrative movie
Authors: Mochalski Lisa N. , Friedrich Patrick , Li Xuan , Kröll Jean-Philippe , Eickhoff Simon B. , Weis Susanne 
Published: May 2024

AbstractNaturalistic paradigms, such as watching movies during functional magnetic resonance imaging (fMRI), are thought to prompt the emotional and cognitive processes typically elicited in real life situations. Therefore, naturalistic viewing (NV) holds great potential for studying individual differences. However, in how far NV elicits similarity within and between subjects on a network level, particularly depending on emotions portrayed in movies, is currently unknown.We used the studyforrest dataset to investigate the inter– and intra-subject similarity in network functional connectivity (NFC) of 14 meta-analytically defined networks across a full narrative, audio-visual movie split into 8 consecutive movie segments. We characterized the movie segments by valence and arousal portrayed within the sequences, before utilizing a linear mixed model to analyze which factors explain inter– and intra-subject similarity.Our results showed that the model best explaining inter-subject similarity comprised network, movie segment, valence and a movie segment by valence interaction. Intra-subject similarity was influenced significantly by the same factors and an additional three-way interaction between movie segment, valence and arousal.Overall, inter– and intra-subject similarity in NFC were sensitive to the ongoing narrative and emotions in the movie. Lowest similarity both within and between subjects was seen in the emotional regulation network and networks associated with long-term memory processing, which might be explained by specific features and content of the movie. We conclude that detailed characterization of movie features is crucial for NV research.
Structure of the turnover-ready state of an ancestral respiratory complex I
Authors: Ivanov Bozhidar S. , Bridges Hannah R. , Jarman Owen D. , Hirst Judy 
Published: May 2024

AbstractRespiratory complex I is pivotal for cellular energy conversion, harnessing energy from NADH:ubiquinone oxidoreduction to drive protons across energy-transducing membranes for ATP synthesis. Despite detailed structural information on complex I, its mechanism of catalysis remains elusive due to lack of accompanying functional data for comprehensive structure-function analyses. Here, we present the 2.3-Å resolution structure of complex I from the α-proteobacteriumParacoccus denitrificans, a close relative of the mitochondrial progenitor, in phospholipid-bilayer nanodiscs. Three eukaryotic-type supernumerary subunits (NDUFS4, NDUFS6 and NDUFA12) plus a novel L-isoaspartyl-O-methyltransferase are bound to the core complex. Importantly, the enzyme is in a single, homogeneous resting state that matches the closed, turnover-ready (active) state of mammalian complex I. Our structure reveals the elements that stabilise the closed state and completesP. denitrificanscomplex I as a unified platform for combining structure, function and genetics in mechanistic studies.
Immunotherapy-related cognitive impairment after CAR T cell therapy in mice
Authors: Geraghty Anna C. , Acosta-Alvarez Lehi , Rotiroti Maria , Dutton Selena , O’Dea Michael R. , Woo Pamelyn J. , Xu Haojun , Shamardani Kiarash , Mancusi Rebecca , Ni Lijun , Mulinyawe Sara B. , Kim Won Ju , Liddelow Shane A. , Majzner Robbie G. , Monje Michelle 
Published: May 2024

SummaryPersistent central nervous system (CNS) immune dysregulation and consequent dysfunction of multiple neural cell types is central to the neurobiological underpinnings of a cognitive impairment syndrome that can occur following traditional cancer therapies or certain infections. Immunotherapies have revolutionized cancer care for many tumor types, but the potential long-term cognitive sequelae are incompletely understood. Here, we demonstrate in mouse models that chimeric antigen receptor (CAR) T cell therapy for both CNS and non-CNS cancers can impair cognitive function and induce a persistent CNS immune response characterized by white matter microglial reactivity and elevated cerebrospinal fluid (CSF) cytokines and chemokines. Consequently, oligodendroglial homeostasis and hippocampal neurogenesis are disrupted. Microglial depletion rescues oligodendroglial deficits and cognitive performance in a behavioral test of attention and short-term memory function. Taken together, these findings illustrate similar mechanisms underlying immunotherapy-related cognitive impairment (IRCI) and cognitive impairment following traditional cancer therapies and other immune challenges.
Research on the impact of innovation investment on operating efficiency of listed forest product processing companies
Authors: Li Huifang , Pang Xinsheng 
Published: May 2024

PurposeThe forest products processing industry is a key component of the forestry economy, and the level of companies’ operating efficiency directly affects its profitability and market competitiveness.Design/methodology/approachIn order to deeply study the operation status of forest product processing industry, this paper takes the panel data of 70 listed forest product processing companies from 2015 to 2022 as the basis, and adopts BBC, CCR and DEA-Malmquist models to measure the operating efficiency of these companies. Meanwhile, the Tobit model is applied to deeply explore the impact of innovation input on operating efficiency.FindingsThe results of the paper show that: (1) the overall operating efficiency of listed forest product processing companies performs well, and the improvement of technology level promotes the growth of total factor productivity; (2) innovation input plays a significant positive role in listed forest product processing companies, which positively affects the operating efficiency.Practical implicationsA scientific and reasonable evaluation of the operating efficiency of listed forest product companies is of great practical significance to the development of the forestry industry The study of forest product processing industry is of key significance to the social economy.Originality/valueThis paper explores the improvement of production and operation efficiency of forest products processing enterprises for the purpose of in-depth analysis of the current situation of China's forest products processing enterprises, which is conducive to improving the innovation and operation efficiency of China's forest products processing enterprises, and realizing the high-quality development of China's forest products processing industry.
The gendered plate: gender-specific food perceptions and sport sponsorship
Authors: Hussain Umer , Ma Han 
Published: May 2024

PurposeThis study aimed to investigate the relationship between food sponsorships and gender stereotypes, focusing on how patriarchal beliefs influence consumers’ purchase intentions in sports.Design/methodology/approachThe research comprised two studies. In Study 1, n = 161 participants participated via Amazon’s Mechanical Turk platform. Study 2 involved n = 250 participants who completed a cross-sectional and self-administered survey.FindingsStudy 1 indicated an apparent gender-based categorization of certain foods and beverages: beer and red meat were predominantly perceived as masculine, while yogurt, salads, and wine were seen as feminine. Further, brands like Budweiser and Red Bull were mainly seen as masculine, while Chobani and Smoothie King were perceived as feminine. Moreover, findings indicate that foods, especially those rich in protein or linked to BBQ and spicy tastes, are considered more masculine by men than women in sports settings. Further, Study 2 findings unveiled a significant relationship between patriarchal beliefs and both attitudes (ß = 0.327, p < 0.01) and subjective norms (ß = 0.525, p < 0.01) towards masculine brands.Originality/valueThe two studies’ results underscore the profound impact of gender stereotypes shaping sports fans’ perceptions of food items and the brands sponsoring them. This inquiry significantly augments the current understanding of the nuanced interrelation between the paradigms of social role theory and the theory of planned behavior, particularly within the ambit of sports-related sponsorship by food and beverage brands and its consequent influence on consumer purchasing inclinations.
The interaction between the anchor and customers in live-streaming E-commerce
Authors: Chen Aihui , Chen Yaning , Li Ruohan , Lu Yaobin 
Published: May 2024

PurposeLive-streaming e-commerce is becoming a new way for many consumers to shop. During the live broadcast process, the interaction between anchors and customers plays a decisive role on consumers' purchasing decisions. This study aims to explore how two types of interaction between the anchor and the customers (i.e. task-oriented interaction and relationship-oriented interaction) affect customers' purchase decisions.Design/methodology/approachThe study establishes a model based on online trust theory and multi-sensor interaction theory. To validate the model, we carried out five simulated live-streaming events and collected data through a scenario-based survey of the viewers participating in the live-streaming (N = 244). Structural equation modeling was employed to test the hypotheses.FindingsBoth task-oriented interaction and relationship-oriented interaction have a positive impact on users' purchase decisions through the mediation of virtual touch, emotional trust and cognitive trust. Sense of power has opposite moderating effects on the impacts of relationship-oriented interaction on emotional trust and cognitive trust.Originality/valueThis study enriches the theory of live-streaming e-commerce by demonstrating the decisive roles of two types of anchor–customer interaction, the mediation roles of virtual touch, cognitive trust, and emotional trust in customer purchase decisions, as well as the moderating effect of sense of power on customer decision-making processes. The findings provide practical insights for anchors and live-streaming platforms about how they should arrange live-streaming content to enhance consumer purchasing decisions.
Entrepreneurial ecosystem patterns and its determinants and outputs: a necessary condition analysis to the Brazilian entrepreneurial cities
Authors: Inacio Junior Edmundo , Dionisio Eduardo Avancci , Gimenez Fernando Antonio Padro 
Published: May 2024

Purpose
This study aims to identify necessary conditions for innovative entrepreneurship in cities and determine similarities in entrepreneurial configurations among them.

Design/methodology/approach
The authors assessed the necessary conditions for various levels of entrepreneurial output and categorized cities based on similar patterns by applying necessary condition analysis (NCA) and cluster analysis in a sample comprised of 101 cities from the entrepreneurial cities index, representing a diverse range of urban environments in Brazil. A comprehensive data set, including both traditional indicators from official Bureau of statistics and nontraditional indicators from new platforms of science, technology and innovation intelligence, was compiled for analysis.

Findings
Bureaucratic complexity, urban conditions, transport infrastructure, economic development, access to financial capital, secondary education, entrepreneurial intention, support organizations and innovation inputs were identified as necessary for innovative entrepreneurship. Varying levels of these conditions were found to be required for different entrepreneurial outputs.

Research limitations/implications
The static nature of the data limits understanding of dynamic interactions among dimensions and their impact on entrepreneurial city performance.

Practical implications
Policymakers can use the findings to craft tailored support policies, leveraging the relationship between city-level taxonomy and direct outputs of innovative entrepreneurial ecosystems (EEs).

Social implications
The taxonomy and nontraditional indicators sheds light on the broader societal benefits of vibrant EEs, emphasizing their role in driving socioeconomic development.

Originality/value
The cluster analysis combined with NCA’s bottleneck analysis is an original endeavor which made it possible to identify performance benchmarks for Brazilian cities, according to common characteristics, as well as the required levels of each condition by each city group to achieve innovative entrepreneurial outputs.