bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candida albicansenhances melanoma cell aggressiveness through p38-MAPK and HIF-1α pathways and metabolic reprogramming
Authors: Aparicio-Fernandez Leire , Cazalis-Bereicua Nahia , Areitio Maialen , Rodriguez-Erenaga Oier , Abio-Dorronsoro Lucia , Martin-Souto Leire , Buldain Idoia , Márquez Joana , Benedicto Aitor , Arteta Beatriz , Macias-Cámara Nuria , Gonzalez Monika , Martin Rodriguez Jose Ezequiel , Aransay Ana , Pellon Aize , Moyes David L. , Anguita Juan , Rementeria Aitor , Antoran Aitziber , Ramirez-Garcia Andoni 
Published: January 2025

AbstractRecent studies have increasingly focused on the role of fungi, includingCandida albicans, in carcinogenesis. SinceC. albicansis a component of the human microbiota, particularly on the skin, we investigated its effect on the phenotype and signalling pathways of melanoma cells. Assays for migration, adhesion, angiogenesis, and hepatic metastasis showed thatC. albicanspromotes a more malignant phenotype in melanoma cells. At the transcriptomic level,C. albicansincreased the expression of VEGF (Vegfa), and genes associated with MAPK and HIF-1 signalling pathways, and with aerobic glycolysis. Further in vitro analysis revealed that TLRs and EphA2 receptors are involved in the recognition of liveC. albicans, stimulating VEGF secretion and expression of the AP-1 transcription factor component c-Fos through p38-MAPK and HIF-1α. These pathways also regulate the expression of other AP-1 constituents such asAtf3,Jun, andJund. Moreover, p38-MAPK regulates glycolytic genes likeHk2,Slc2a1, andEno2. In conclusion,C. albicansactivates the p38-MAPK/c-Fos/AP-1 and HIF-1/HIF-1α/c-Fos/AP-1 pathways in melanoma cells, promoting a pro-angiogenic environment and metabolic reprogramming. Therefore, this study clarifies the impact ofC. albicanson melanoma cells, which can lead to the use of antifungal therapies as complementary to traditional treatments for melanoma.
Astrocyte Ca2+activity regulates node of Ranvier length in the white matter
Authors: Lezmy Jonathan , Quintela-Lopez Tania , Woermann Nicholas , Mao Shuying , Thompson Caleb , Attwell David 
Published: January 2025

AbstractNodes of Ranvier generate action potentials along myelinated axons, but it is unclear whether they can modulate neural circuit function. Computer modelling previously predicted that adjusting node length can control axonal conduction speed1, but it is unknown whether mechanisms controlling nodal structure operate in the healthy brain. Here, in brain slices and in intact white matter tracts of live mice, we found that nodes elongate and shorten, while an overall stable mean node length is maintained. Changes in node length were only detected in nodes that were flanked by compact myelin sheaths, and more motile nodes were observed as myelination progressed during development. In the developing brain, but not in adult mice, neuronal activity caused the nodes to elongate. This occurred via astrocyte Ca2+-mediated adenosine generation, targeting A2breceptors expressed in myelin sheaths which raised cyclic AMP levels in oligodendrocytes. This activated NKCC1 cotransporters present in the myelin of the paranodes and internodes, the expression of which was upregulated in the developing brain compared to adults. NKCC1 activation elevated the membrane conductance and reduced the length of internodal myelin sheaths. Thus, nodal dynamics may continuously tune information flow along myelinated axons and drive activity-dependent white matter plasticity.
The Baldwin effect reloaded: Intermediate levels of phenotypic plasticity favor evolutionary rescue
Authors: Lambert Amaury , Achaz Guillaume , Le Rouzic Arnaud , Loison Laurent 
Published: January 2025

AbstractSince the late 1890s and until today, how phenotypic plasticity interacts with genetic adaptation is a debated issue. Proponents of a positive causal role of phenotypic plasticity –James M. Bald-win in the first place– supported the view that, in altered environmental conditions, phenotypic plasticity is a key factor allowing a population to avoid extinction and then genetic evolution to catch up (“Original Baldwin Effect”, thereafter OBE). Opponents, like for instance Ernst Mayr, regularly pointed out that phenotypic plasticity, by masking genetic variation, slows gene-level evolution (“Mayr Effect”, thereafter ME). For decades this opposition remained only verbal and qualitative. To resolve it, we propose here a stochastic model that, following Baldwin’s intuitive take, combines the minimal number of ingredients to account for extinction, selection, mutation and plasticity. We study evolutionary rescue of the population (arrival and invasion of an adaptive genetic mutant) in the altered environment for different values of phenotypic plasticity, here quantified as the probabilitypthat the maladapted genotype develops into the adapted phenotype. Our claim is that OBE can be a genuine evolutionary mechanism, depending on the level of phenotypic plasticity with respect to a threshold valuep⋆: whenp < p⋆, increasingppromotes evolutionary rescue by delaying extinction (“Strong” OBE); whenp > p⋆, plasticity sustains population survival and increasingphas two antagonistic effects: to accelerate adaptation by increasing the supply of adaptive mutants (“Weak” OBE, intermediate values ofp), and to slow down adaptation by decreasing their fitness advantage (ME, high values ofp).
Identification of Evolutionary Trade-Offs Associated with High-Level Colistin Resistance inAcinetobacter baumannii
Authors: Acharya Kusumita , Bhattacharya Upasana , Biswas Shatarupa , Ghosh Mallika , Bhattacharya Arijit 
Published: January 2025

ABSTRACTColistin (COL) belongs to the polymyxin group of drugs which possesses a positive charge and interacts with lipopolysaccharide (LPS) of Gram-negative bacterial outer membrane. Additionally, it can penetrate the cell membrane and disrupt the integrity of the phospholipid leading to cell death. Resistance against COL has been reported inAcinetobacter baumannii, a bacteria in the ‘ESKAPE’ group of ‘priority pathogens’ of the World Health Organization. Multiple and pan-drug-resistant strains ofA. baumanniiare rising in many medical facilities and they are becoming resistant to last-resort antibiotics including colistin. Though plasmid-encoded acquisition ofmcr-1 has been associated with clinical resistance, drug efflux, complete loss of LPS by inactivation of the biosynthetic pathway (lpxACD), and modifications of target LPS by-products of chromosomalpmrCAB genes has been ascribed with resistance evolution against COL. To further delve into the evolutionary dynamics of COL-resistance here we report experimental evolution of extreme COL-resistance by adaptive evolution of the reference strainA. baumannii ATCC19606. Phenotypic characterization has been performed for the evolved strains, which demonstrated hyperbiofilm phenotype and striking decrease in fitness. A comprehensive antibiotic susceptibility profiling has been performed on the evolved strains. Whole genome sequencing of the resistant strains led to the identification of mutations prospectively associated with COL resistance. Phenotypic characterization of three COL-resistant clinical isolates ofA. baumanniirevealed similarity with experimentally evolved resistant mutants at least in one of the isolates.
Multiple Types of Context-Specific Brain Causal Regulatory Networks and their Applications to Autism Spectrum Disorder
Authors: Wang Li , Yang Eric , Stolovitzky Gustavo , Schadt Eric , Zhu Jun 
Published: January 2025

AbstractOne of the primary goals of systems biology is to understand how different cell types are regulated at various developmental stages and how dysregulation in these cells contributes to disease. With advances in high-throughput omics profiling technologies, vast amounts of both bulk tissue and single-cell data have been generated to study cellular regulation. To investigate the types of gene-gene regulatory interactions that can be uncovered from bulk versus single-cell profiling data, we constructed multiple context-specific brain gene regulatory networks using brain bulk and single-cell RNA-seq datasets and applied two distinct computational methods: an integrative Bayesian Network (BN) and a deep learning model, Geneformer. A total of 39 networks were generated, comprising 13 brain region-specific Bayesian networks from bulk RNA-seq data (bulk_BNs), 13 cell-type and developmental stage-specific Bayesian networks, and 13 corresponding Geneformer-based networks from scRNA-seq data (sc_BNs and sc_GFs, respectively).We compared these networks in terms of their topological features, biological pathway regulation, and known regulatory relationships among disease-related genes. Our analysis revealed distinct network properties driven by data source type (bulk vs. single-cell RNA-seq) and network inference method (integrative Bayesian Network vs. deep learning Geneformer). Neurodegenerative disease-related pathways were co-regulated in bulk_BNs, while sc_BNs and sc_GFs captured pathways associated with neuroactive ligand-receptor interactions. To demonstrate the utility of these networks, we leveraged them to investigate potential disease mechanisms of Autism Spectrum Disorder (ASD). We found that ASD risk genes were enriched among hub genes common across networks but were more frequently hubs in context-specific networks, underscoring the significance of inhibitory interneurons during early developmental stages in ASD. Additionally, we showed that these networks could effectively recapitulate context-specific ASD gene signatures.In summary, this study highlights the complementary value of integrating multiple data types through different computational approaches to advance our understanding of disease-related molecular mechanisms, such as those involved in ASD. Our findings provide a framework for using context-specific gene regulatory networks to identify disease-causal genes and key regulators of signaling pathways, potentially guiding future therapeutic strategies.
The coordinated action of UFMylation and ribosome-associated quality control pathway clears arrested nascent chains at the endoplasmic reticulum
Authors: Mihailovic Milica , Anisimova Aleksandra S , Erte Bu , Zhan Ni , Styliara Ioanna , Dagdas Yasin , Karagöz G Elif 
Published: January 2025

AbstractClearance of incomplete nascent polypeptides resulting from ribosomal stalling is essential for protein homeostasis. While ribosome-associated quality control (RQC) mechanisms that degrade these polypeptides are well-characterized in the cytosol, how stalled endoplasmic reticulum (ER)-bound ribosomes are cleared remains poorly understood. Stalled ER-bound ribosomes are marked by ubiquitin-fold modifier 1 (UFM1) on large ribosomal subunit protein RPL26, but the precise function and regulation of this process are unclear. Here, we demonstrate that canonical RQC factors associate with ribosomes stalled at the ER. Functional cellular assays using ER-targeted stalling reporters reveal that while ribosome splitting is a prerequisite for UFMylation of RPL26, the UFMylation persists without late RQC components that are involved in the clearance of arrested nascent chains (NEMF and LTN1). The UFM1 E3 ligase complex binds to and UFMylates the 60S-peptidyl-tRNA complex and, in concert with the canonical RQC pathway, facilitates the clearance of arrested polypeptides. Our findings reveal that UFMylation acts to maintain translational integrity at the ER.
Fentanyl blockade of K+channels contribute to Wooden Chest Syndrome
Authors: Wei Aguan D. , Burgraff Nicholas J. , Oliveira Luiz M. , Moreira Thiago S. , Ramirez Jan-Marino 
Published: January 2025

AbstractFentanyl is a potent synthetic opioid widely used perioperatively and illicitly as a drug of abuse1,2. It is well established that fentanyl acts as a μ-opioid receptor agonist, signaling through Gαi/ointracellular pathways to inhibit electrical excitability, resulting in analgesia and respiratory depression3,4. However, fentanyl uniquely also triggers muscle rigidity, including respiratory muscles, hindering the ability to execute central respiratory commands or to receive external resuscitation. This potentially lethal condition is termed Wooden Chest Syndrome (WCS), the mechanisms of which are poorly understood5–7. Here we show that fentanyl directly blocks a subset of EAG-class potassium channels8. Our results also demonstrate that these channels are widely expressed in cervical spinal motoneurons, including those innervating the diaphragm. A significant fraction of these motoneurons is excited by fentanyl, concomitant with blockade of voltage-dependent non-inactivating K+currents. In vivoelectromyography revealed a persistent tonic component of diaphragmatic muscle activity elicited by fentanyl, but not morphine. Taken together our results identify a novel off-target mechanism for fentanyl action, independent of μ-opioid receptor activation, with a paradoxical excitatory effect that may underlie WCS. We anticipate these findings may inform the design of safer analgesics and generalize to other neuronal circuits implicated in fentanyl-related maladaptive behaviors.
Pediococcus pentosaceusdecreases α-synuclein accumulation and alleviates parkinsonism inCaenorhabditis elegansandOryzias latipes
Authors: Komura Tomomi , Yoshida Masayuki , Kurihara Rio , Kinoshita Masato , Yoshida Masaru , Nishikawa Yoshikazu 
Published: January 2025

AbstractIn Parkinson’s disease (PD), α-synuclein (αSyn) accumulation drives neuropathological progression, establishing it as a potential therapeutic target. Lactic acid bacteria (LAB) provide various health benefits to the host and are expected to offer protective effects on neurological functions through the brain–gut connection, as indicated by animal studies. However, the protective effects of LAB against αSyn are not well understood. We investigated whether LAB feeding could reduce αSyn accumulation and improve mobility in transgenicCaenorhabditis elegans, an invertebrate model organism that expresses human αSyn in muscle. Among the nine screened strains,Pediococcus pentosaceussuppressed αSyn accumulation and the decrease in bending counts, a locomotion index in nematodes. Additionally, feedingP. pentosaceustoOryzias latipes(medaka), a vertebrate model organism, alleviated PD-like behavioral defects induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.P. pentosaseusacts as a probiotic against PD, and PD model worms and medaka can be used to screen effective LAB for prevention.
Can we trigger radical lifestyle change in sustainable consumption? Exploring motivations, abilities and triggers of dietary changes
Authors: Csutora Maria , Vetőné Mózner Zsófia 
Published: January 2025

PurposeReducing meat consumption requires significant effort from individuals. Such shifts in diet can be compelling examples of radical lifestyle change. The article explores factors that may trigger radical behavioural change. Decreased meat consumption yields environmental and health advantages; nevertheless, individuals often neglect to adopt this change in their diet.Design/methodology/approachThe conceptual model is based on Fogg’s behavioural framework. The research is based on a survey, where respondents have already changed their lifestyles and reduced their meat consumption in the past. Respondents were recruited from social media groups in Hungary. Particular emphasis is put on the deeper analysis of open-ended questions. The coding process proposed by Strauss and Corbin was followed. Coding and analysis were supported by NVivo software.FindingsMotivations, abilities and triggers of dietary changes were identified. Results revealed the prominent role of content creators. Influencers and social media can play an incubator role in diffusing new consumption patterns. Strong emotional experiences can also trigger radical lifestyle changes. Discouraging voices were mainly those of family and close acquaintances. Children tend to encourage parents, while parents tend to discourage children when it comes to reducing meat consumption.Originality/valueBehaviour change theories primarily focus on incremental changes, yet there is a growing need to understand radical lifestyle changes related to food consumption. This article explores the triggering factors of such radical dietary changes. The study is a rare example of large-scale qualitative sustainable consumption research.
Exploring the implications of using parent-teacher associations (PTAs) as a pathway for school-community development
Authors: Agyekum Boadi , Salifu Inusah , Eshun Samuel Nuamah , Asamoah Moses Kumi 
Published: January 2025

PurposeThe purpose of this article is to increase understanding of the relationship between parent-teacher associations (PTAs) activities and school-community development, with a particular emphasis on the ways in which PTAs are utilized as supplemental or alternative sources of funding or support for school self-development initiatives.Design/methodology/approachThe article is based on a case study conducted in two Ghanaian elementary schools. Field notes, in-depth interviews and observations of PTA members (n = 21) and activities make up the data. The article theoretically adopts a community development practice that is predicated on promoting solidarity and agency by upholding the ideas of felt needs, self-help and participation.FindingsThe study revealed that PTA initiatives can improve the diversity of activities available within a school while also building the skills and capacity of local communities and enabling individuals to make social connections. The study mainly recommended that in making educational systems resilient, such school-community-based resources of resilience should be preserved, fostered and valued.Practical implicationsThe findings are practically relevant to local school managers and other stakeholders involved in school leadership, promoting the relationships between PTAs, school management, children’s well-being and community development, particularly in sub-Saharan African schools like those in Ghana.Originality/valueThis article explores PTA’s involvement in school-community development in Ghana, a relatively under-researched area in this approach, using a community development practice approach, highlighting PTA’s impacts, implementation and challenges at elementary schools in the post-COVID era.
Street lighting maintenance management system based on fuzzy logic
Authors: Barrios Martínez Francisco Alexei , Sierra Gil Eduardo , Borges Vasconcellos Davel Eduardo , Gondres Torné Israel 
Published: January 2025

PurposeThis research was carried out in response to the need to find new alternative ways of maintaining public lighting with high pressure sodium vapor lamps. The objective was to develop a public lighting maintenance management system based on fuzzy logic that guarantees maximum energy efficiency and is economically feasible.Design/methodology/approachA preliminary study was carried out on the complaints due to failures of public lighting for three years in the municipality of Camagüey, Cuba, determining the failure rate of each control and the time between failures, a statistical evaluation of the time between failures was carried out identifying that this variable responds to a Weibull distribution, the membership functions of the proposed four linguistic variables and the rule base for their fuzzy sets were created, obtaining as output linguistic variable the mass replacement and cleaning time.FindingsThe fuzzy logic maintenance model developed is effective in making better use of the useful life of high-pressure sodium vapor lamps, increasing the time between maintenance operations of mass lamp replacement and mass cleaning of luminaires up to 8 and 9 years, without compromising the required lighting levels and energy efficiency.Originality/valueThe literature contains very few references to the use of condition-based maintenance in this type of system, so a novel approach by a robust heuristic model of street lighting condition-based maintenance management driven by data is proposed, the model integrates through fuzzy logic all the factors that influence the progressive deterioration of these installations and maintenance actions that guarantee compliance with the established service quality standards, with the maximum energy efficiency that is economically justified.
A game theory perspective to power acquisition during CEO transition period
Authors: Elias Rida , Farah Bassam 
Published: January 2025

PurposeThis study examines how CEOs-elect navigate power dynamics with incumbent CEOs during leadership transitions, focusing on their strategic choices – cooperate, defect or disengage – based on perceptions of the incumbent’s behavior.Design/methodology/approachUsing the game theory framework and insights from 22 interviews with executives from large Canadian organizations, we analyze CEOs-elect’s decision-making from nomination to ascension.FindingsCEOs-elect cooperate when they anticipate the incumbent to cooperate and defect when they anticipate defection. When faced with uncertainty or signs of disengagement from the incumbent, CEOs-elect strategically choose to disengage, adopting a “No Play” strategy to preserve board trust and organizational stability.Research limitations/implicationsFindings are based on large Canadian organizations, which may limit applicability to smaller firms, family businesses or different cultural contexts. Future research should examine CEO transitions across diverse organizational and cultural settings.Practical implicationsBoards should recognize proactively manage power struggles during transitions, ensuring support for CEOs-elect and promoting cooperation with incumbents. Understanding perceived incumbent strategies can improve transition planning, minimize conflicts and improve organizational outcomes.Originality/valueThis research introduces “No Play” as a novel strategic option in CEO transitions, contributing to game theory and power dynamics literature. It also bridges gaps in understanding by linking strategic choices of CEOs-elect to perceptions of incumbent behavior and stakeholder trust.
Revaluing management work in leadership: the frontline supervisor perspective
Authors: Perry Samuel , Davis Claire 
Published: January 2025

PurposeLeadership and management have typically been defined as separate and distinct activities. This study examined the everyday management and leadership practices of police sergeants and inspectors in one UK police constabulary. Findings reveal the prominence of management work in frontline supervision, combined with aspects of leadership. However, frontline supervisors describe themselves and their work in leadership terms. The authors argue, therefore, for a revaluing of management in frontline supervision to better reflect the everyday practices of frontline supervisors.Design/methodology/approachThe study adopted a mixed-method approach, comprising an online self-administered survey and semi-structured interviews. The survey achieved 43 responses from sergeants and inspectors, and interviews were conducted with 10 police supervisors, recruited via purposive sampling and analysed using Braun and Clarke’s (2006) thematic analysis principles.FindingsFrontline supervisors in the study defined themselves as leaders and described their work in leadership terms. However, the findings reveal that the activities performed by frontline supervisors were predominately management work, such as performance, resource management and welfare, combined with some aspects of leadership, such as change planning. Rather than conceptualising management and leadership as separate activities, the work of the frontline supervisors reveals, therefore, a blended practice of management/leadership.Originality/valueDespite the prominence of management in their everyday work, frontline supervisors describe themselves and their work in leadership terms. The authors call for a revaluing of management work and reconceptualise the work of frontline supervisors as “managerial leadership” to better reflect management and leadership as equally valuable, interconnected and mutually dependent activities.