bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloride intracellular channel (CLIC) protein function in S1P-induced Rac1 activation requires membrane localization of the C-terminus, but not thiol-transferase nor ion channel activities
Authors: Mao De Yu , Jesse Jordan J. , Shaye Daniel D. , Kitajewski Jan 
Published: January 2025

AbstractWe have established a novel and evolutionarily-conserved function for chloride intracellular channel proteins (CLICs) in regulating Rho/Rac GTPases downstream of G protein-coupled receptors (GPCRs). Endothelial CLIC1 and CLIC4 are rapidly and transiently re-localized from the cytoplasm to the plasma membrane in response to the GPCR ligand sphingosine-1-phosphate (S1P), and both CLICs are required to activate Rac1 in response to S1P, but how they perform this function remains unknown. Biochemical studies suggest that CLICs act as non-specific ion channels and/or as glutathione-S-transferases, dependent on N-terminal features,in vitro. Here we investigate CLIC functional domains and membrane localization requirements for their function in S1P-mediated Rac1 signaling. Structure-function analyses of CLIC function in endothelial cells demonstrate that CLIC1 and CLIC4-specific functions reside at their C-termini, and that the CLIC4 N-terminus encodes determinants required for S1P-induced re-localization to the plasma membrane but is dispensable for S1P-induced Rac1 activation when the C-terminus is localized to the plasma membrane via a heterologous signal. Our results demonstrate that the postulated ion channel and thiol-transferase activities of CLICs are not required for Rac1 activation and suggests that sequences in the CLIC C-termini are critical for this function. Given the importance of S1P signaling in vascular biology and disease, our work establishes a platform to further our understanding of the membrane-localized proteins required to link GPCR activity to Rho/Rac regulation.
Erythropoietin decreases apoptosis and promotes Schwann cell repair and phagocytosis following nerve crush injury in mice
Authors: Govindappa Prem Kumar , Ellur Govindaraj , Hegarty John P. , Gupta Akash , Rahul V. G. , Elfar John C. 
Published: January 2025

ABSTRACTAfter peripheral nerve trauma, insufficient clearance of phagocytic debris significantly hinders nerve regeneration. Without sufficient myelin debris clearance, Schwann cells (SCs) undergo increased apoptosis, impairing functional recovery. There is no treatment for peripheral nerve crush injury (PNCI). Erythropoietin (EPO) is an FDA-approved drug for anemia, which may help in the treatment of PNCI by transdifferentiating resident SCs into repair SCs (rSCs) and enhancing phagocytosis to facilitate the removal of cellular debris. For the first time, we conducted bulk RNA sequencing on mice with calibrated sciatic nerve crush injuries (SNCIs) on days 3, 5, and 7 post-SNCI to uncover transcriptomic changes with and without EPO treatment. We found EPO altered several biological pathways and associated genes, particularly those involved in cell apoptosis, differentiation, proliferation, phagocytosis, myelination, and neurogenesis. We validated the effects of EPO on SNCI on early (days 3/5) and intermediate (day 7) post-SNCI, and found EPO treatment reduced apoptosis (TUNEL), and enhanced SC repair (c-Jun and p75-NTR), proliferation (Ki67), and the phagocytosis of myelin debris by rSCs at crush injury sites. This improvement corresponded with an enhanced sciatic functional index (SFI). We also confirmed these findingsin-vitro. EPO significantly enhanced SC repair during early de-differentiation, marked by high c-Jun and p75-NTR protein levels, and later re-differentiation with high EGR2 and low c-Jun and p75-NTR levels. These changes occurred under lipopolysaccharide (LPS) stress at 24 and 72h, respectively, compared to LPS treatment alone. Under LPS stress, EPO also significantly increased rSCs proliferation and phagocytosis of myelin or dead SCs. In conclusion, our findings support EPO may enhance the function of rSCs in debris clearance as a basis for its possible use in treating nerve trauma.
History shapes regulatory and evolutionary responses to tigecycline in strains ofAcinetobacter baumanniifrom the pre- and post-antibiotic eras
Authors: Rokes Alecia B , Santos-Lopez Alfonso , Cooper Vaughn S 
Published: January 2025

ABSTRACTEvolutionary history encompasses genetic and phenotypic bacterial differences, but the extent to which history influences drug response and antimicrobial resistance (AMR) adaptation is unclear. Historical contingencies arise when elements from an organism’s past leave lasting effects on the genome, altering the paths available for adaptation. We utilize strains isolated before and after widespread antibiotic use to study the impact of deep historical differences shaped by decades of evolution in varying antibiotic and host pressures. We evaluated these effects by comparing immediate and adaptive responses of two strains ofAcinetobacter baumanniito the last-resort antibiotic, tigecycline (TGC). When grown in subinhibitory TGC, the two strains demonstrated divergent transcriptional responses suggesting that baseline transcript levels may dictate global responses to drug and their subsequent evolutionary trajectories. Experimental evolution in TGC revealed clear differences in population-genetic dynamics – with hard sweeps in populations founded by one strain and no mutations reaching fixation in the other strain. Transcriptomes of evolved populations no longer showed signatures of drug response, as was seen in the ancestors, suggesting that genetic adaptation may outweigh preexisting differences in transcriptional networks. Genetically, AMR was acquired through predictable mechanisms of increased efflux and drug target modification; however, the two strains adapted by mutations in different efflux regulators. Fitness tradeoffs of AMR were only observed in lineages evolved from the pre-antibiotic era strain, suggesting that decades of adaptation to antibiotics resulted in preexisting compensatory mechanisms in the more contemporary isolate, an important example of a beneficial effect of historical contingencies.SIGNIFICANCE STATEMENTAcinetobacter baumanniiis a high priority pathogen often causing multidrug resistant nosocomial infections. Many healthcare systems experience clonal outbreaks ofA. baumanniiinfections, yet treatment strategies are often strain-agnostic, ignoring the importance of strain differences. We show that historical differences between two strains, one isolated prior to widespread antibiotic use and the other following decades of selection to clinical conditions, dictate transcriptional patterns and response to a last-resort antibiotic and influence the genetic and phenotypic routes of resistance adaptation. While our study focuses on two reference strains ofA. baumannii,these findings can be more broadly applicable to other pathogenic organisms in which a better understanding of the forces influencing resistance adaptation is essential for combating the antimicrobial resistance crisis.
First genomic resource of ‘CandidatusPhytoplasma pyri’ associated to pear
Authors: Alessio Florencia Ivette , Bongiorno Vanina Aylen , von Backzo Oscar Hernan , Conci Luis Rogelio , Fernandez Franco Daniel 
Published: January 2025

AbstractThis study reports the draft genome ofCandidatusPhytoplasma pyri strain P1, isolated from Argentina, marking the first global sequencing of this species. The genome assembly consisted of 16 contigs, with a total length of 575,431 bp, a GC content of 20.35%, and 125X coverage. A total of 536 genes were annotated, including those related to metabolism, genetic information processing, and signaling. Phylogenetic analysis placed ‘CandidatusPhytoplasma pyri’ within the 16SrX group, supporting its classification as a distinct species from ‘CandidatusPhytoplasma mali’ and ‘CandidatusPhytoplasma prunorum’, despite their close evolutionary proximity. The investigation also identified 17 secreted proteins, including homologs of known effectors such as SAP39 and SAP41, as well as conserved proteins associated with virulence mechanisms. A homologue of the Imp immunodominant membrane protein was also characterized, revealing conserved gene organization across related strains. These findings contribute to the understanding of ‘CandidatusPhytoplasma pyri’ pathogenic and provide valuable genomic data for future research. This study highlights the importance of expanding phytoplasma genomics, as it provides a crucial first step in understanding ‘CandidatusPhytoplasma pyri’ and its role in plant pathology
Proximity labeling and orthogonal nanobody pulldown (ID-oPD) approaches to map the spinophilin interactome uncover a putative role for spinophilin in protein homeostasis
Authors: Claeboe Emily T. , Blake Keyana L. , Shah Nikhil R. , Morris Cameron W. , Hens Basant , Atwood Brady K. , Absalon Sabrina , Mosley Amber L. , Doud Emma H. , Baucum Anthony J. 
Published: January 2025

ABSTRACTSpinophilin is a dendritic spine enriched scaffolding and protein phosphatase 1 targeting protein. To detail spinophilin interacting proteins, we created an Ultra-ID and ALFA-tagged spinophilin encoding construct that permits proximity labeling and orthogonal nanobody pulldown (ID-oPD) of spinophilin-associated protein complexes in heterologous cells. We identified 614 specific, and 312 specific and selective, spinophilin interacting proteins in HEK293 cells and validated a subset of these using orthogonal approaches. Many of these proteins are involved in mRNA processing and translation. In the brain, we determined that spinophilin mRNA is highly neuropil localized and that spinophilin may normally function to limit its own expression but promote the expression of other PSD-associated proteins. Overall, our use of an ID-oPD approach uncovers a novel putative role for spinophilin in mRNA translation and synaptic protein expression specifically within dendritic spines.
Pancreatic injury induces β−cell regeneration in axolotl
Authors: Powell Connor J. , Singer Hani D. , Juarez Ashley R. , Kim Ryan T. , Payzin-Dogru Duygu , Savage Aaron M. , Lopez Noah J. , Blair Steven J. , Abouelela Adnan , Dittrich Anita , Akeson Stuart G. , Jain Miten , Whited Jessica L. 
Published: January 2025

AbstractBackgroundDiabetes is a condition characterized by a loss of pancreatic β−cell function which results in the dysregulation of insulin homeostasis. Using a partial pancreatectomy model in axolotl, we aimed to observe the pancreatic response to injury.ResultsHere we show a comprehensive histological assessment of pancreatic islets in axolotl. Following pancreatic injury, no apparent blastemal structure was observed. We found a significant, organ-wide increase in cellular proliferation post-resection in the pancreas compared to sham-operated controls. This proliferative response was most robust at the site of injury. We found that β−cells actively contributed to the increased rates of proliferation upon injury. β−cell proliferation manifested in increased β−cell mass in injured tissue at two weeks post injury. At four weeks post injury, we found organ-wide proliferation to be extinguished while proliferation at the injury site persisted, corresponding to pancreatic tissue recovery. Similarly, total β−cell mass was comparable to sham after four weeks.ConclusionsOur findings suggest a non-blastema-mediated regeneration process takes place in the pancreas, by which pancreatic resection induces whole-organ β−cell proliferation without the formation of a blastemal structure. This process is analogous to other models of compensatory growth in axolotl, including liver regeneration.
Microscopy-Guided Spatial Proteomics Reveals Novel Proteins at the Mitochondria-Lipid Droplet Interface and Their Role in Lipid Metabolism
Authors: Lin Yen-Ming , Chong Weng Man , Huang Chun-Kai , Chang Hsiao-Jen , Cheung Chantal Hoi Yin , Liao Jung-Chi 
Published: January 2025

AbstractMitochondria-lipid droplet (LD) interactions play a critical role in lipid metabolism and the progression of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD). However, the dynamic nature of these interactions has hindered the identification of novel protein constituents and their functional roles. Here, we employed Microscoop Mint, an advanced microscopy-guided spatial proteomics platform, to isolate proteins localized at mitochondria-LD contact sites in oleic acid (OA)-treated HepG2 cells, an in vitro model for studying fatty liver disease. Microscoop Mint integrates high-resolution image analysis and two-photon illumination to achieve precise biotinylation of proteins at subcellular regions of interest. Coupled with mass spectrometry, this approach identified a proteome enriched at the mitochondria-LD interface, including both well-characterized lipid-associated proteins and previously unrecognized candidates. Among the 373 common proteins identified across replicates, five novel candidates with no prior association to lipid metabolism were selected for validation. Immunofluorescence staining confirmed their localization at mitochondria-LD contact sites, with more pronounced association in OA-treated cells. Notably, suppression of one candidate, FHL3, led to reduced LD size, elongated mitochondrial morphology, and diminished mitochondria-LD interactions, suggesting its role in regulating fatty acid β-oxidation. Our findings demonstrate the utility of Microscoop Mint in unveiling novel molecular players at organelle contact sites. This study not only provides insights into the functional dynamics of mitochondria-LD interactions but also highlights potential therapeutic targets for lipid metabolic disorders and NAFLD.
Confinement-Higgs and deconfinement-Higgs transitions in three-dimensional Z(2) LGT
Authors: Allés B. , Borisenko O. , Papa A. 
Published: January 2025

We reexamine by numerical simulation the phase structure of the three-dimensional Abelian lattice gauge theory with Z(2) gauge fields coupled to Z(2)-valued Higgs fields. Concretely, we explore two different order parameters which are able to distinguish the three phases of the theory: (i) the Fredenhagen-Marcu operator used to discriminate between deconfinement and confinement/Higgs phases and (ii) the Greensite-Matsuyama overlap operator proposed recently to distinguish confinement and Higgs phases. The latter operator is an analog of the overlap Edwards-Anderson order parameter for spin glasses. According to it, the Higgs phase is realized as a glassy phase of the gauge system. For this reason standard tricks for simulations of spin-glass phases are utilized in this work, namely tempered Monte Carlo and averaging over replicas. In addition, we also present results for a certain definition of distance between Higgs field configurations. Finally, we calculate various gauge-invariant correlation functions in order to extract the corresponding masses.

Published by the American Physical Society
2025
Neural Density Functional Theory of Liquid-Gas Phase Coexistence
Authors: Sammüller Florian , Schmidt Matthias , Evans Robert 
Published: January 2025

We use supervised machine learning together with the concepts of classical density functional theory to investigate the effects of interparticle attraction on the pair structure, thermodynamics, bulk liquid-gas coexistence, and associated interfacial phenomena in many-body systems. Local learning of the one-body direct correlation functional is based on Monte Carlo simulations of inhomogeneous systems with randomized thermodynamic conditions, randomized planar shapes of the external potential, and randomized box sizes. Focusing on the prototypical Lennard-Jones system, we test predictions of the resulting neural attractive density functional across a broad spectrum of physical behavior associated with liquid-gas phase coexistence in bulk and at interfaces. We analyze the bulk radial distribution function g(r) obtained from automatic differentiation and the Ornstein-Zernike route and determine (i) the Fisher-Widom line, i.e., the crossover of the asymptotic (large distance) decay of g(r) from monotonic to oscillatory, (ii) the (Widom) line of maximal correlation length, (iii) the line of maximal isothermal compressibility, and (iv) the spinodal by calculating the poles of the structure factor in the complex plane. The bulk binodal and the density profile of the free liquid-gas interface are obtained from density functional minimization and the corresponding surface tension from functional line integration. We also show that the neural functional describes accurately the phenomena of drying at a hard wall and of capillary evaporation for a liquid confined in a slit pore. Our neural framework yields results that improve significantly upon standard mean-field treatments of interparticle attraction. Comparison with independent simulation results demonstrates a consistent picture of phase separation even when restricting the training to supercritical states only. We argue that phase coexistence and its associated signatures can be discovered as emerging phenomena via functional mappings and educated extrapolation.

Published by the American Physical Society
2025
Applications of lean principles in the operations of architectural and engineering design firms: an exploratory study in Singapore
Authors: Gao Shang , Low Sui Pheng , Tok Samuel Keen Wei 
Published: January 2025

Purpose The Toyota Way was developed as an efficiency framework to streamline Toyota Motor Corporation’s operational procedures. The collection of Toyota Way principles is often termed “lean”. Over the last few years, nonmanufacturing organisations have begun to recognise the value and applicability of lean methods for their operations. Architectural and engineering design (AED) firms are no exception. This study aims to explore the perspectives of employees at AED firms on the implementation of lean production principles (LPPs) into their operations. Due to the limited resources available to facilitate our measurement of employees’ views regarding the adoption of lean approaches, this study adopts a more scoped approach to employees’ perceptions of these principles within AED firms.Design/methodology/approach Fifty-two respondents participated in the survey. The interviewees were from firm A and firm B, an architecture firm and an engineering firm, and were chosen to help us gain a more in-depth understanding of their views regarding the LPPs.Findings Our study indicates that AED offices were unfamiliar with the concepts of lean principles, even though they were aware of its importance in their daily operations. Despite their scepticism about the implementation of lean concepts, some lean principles are implemented in their own fields of work.Originality/value This study complements earlier work on lean design that investigated the use of a particular lean technique by looking at the lean principles where some are implemented to a large extent, and some are not.
Digital platforms in intermodal freight transport: an analysis of emerging business models and their future dynamics
Authors: Bossong Paul , Reinhardt Anne , Elbert Ralf 
Published: January 2025

PurposeIntermodal freight transport (IFT) promises to reduce freight transport emissions by combining multiple transport modes. Emerging digital platforms seek to address the increasing complexity that arises from a combination of transport modes, yet the understanding of their business models remains limited. This study provides in-depth insights into the current characteristics and future dynamics of IFT platform business models.Design/methodology/approachUsing an inductive qualitative research approach, we gathered data from 19 semi-structured interviews. Based on this empirical data, we derived a comprehensive business model taxonomy, identified distinct platform archetypes and explored their future dynamics.FindingsFour platform archetypes are identified: Marketplaces and Self-Brokers facilitate easy booking by matching supply and demand. Data Hubs and Collaboration Hubs digitize data exchange between IFT actors. While Marketplaces and Data Hubs are operated by digitally dominated entrants, Collaboration Hubs and Self-Brokers are launched by intermodal incumbents as a digital extension of their physical transport services. Platforms operated by intermodal incumbents with a considerable customer base possess strategic advantages, potentially outperforming the business models of digitally dominated entrants in the future.Research limitations/implicationsAlthough this study focuses on the German IFT market, the developed taxonomy sets the ground for qualitative research of other platform-based business models and encourages the validation of our findings through quantitative research.Originality/valueBy being the first to comprehensively systematize IFT platform business models and their future dynamics, our study creates an in-depth understanding of how digital platforms can contribute to a modal shift from road freight transport to environmentally friendly IFT.
How do TQM’s critical success factors affect organisational performance? A configurational approach
Authors: Ahsan Ramjanul , Ullah Muhammad Shariat 
Published: January 2025

PurposeThis paper aims to illustrate a possible combination of critical success factors (CSFs) that best enhance firm performance and compare configurations of CSFs in ISO-9001-2015-certified and non-ISO firms in Bangladesh.Design/methodology/approachThe study sample comprises individuals from the service and manufacturing sectors and ISO-9001-2015-certified and non-ISO firms. We have collected data from 229 respondents from 134 firms, including 64.5% from ISO-certified and the remaining 35.5% from non-ISO-certified categories. In this exploratory study, we performed a fuzzy-set qualitative comparative analysis (fsQCA) to identify the combinations of success factors that enhance performance.FindingsThe results of this study capture the causal complexity surrounding the CSFs and firm performance. We found six configurations for ISO firms and five for non-ISO firms that enhance firm performance. Besides, the necessary conditions for firm performance of ISO firms slightly differ from those of non-ISO firms. Thus, the empirical results highlight the importance of equifinality and complementary relationships between conditions relating to quality management systems to increase firm performance. A significant difference was found between ISO-9001:2015-certified firms and non-ISO firms.Research limitations/implicationsA significant limitation arises from the sample’s inclusion of only Bangladeshi firms; a cross-cultural study could add new dimensions to the configurations. Understanding how these CSFs vary and need a longitudinal approach is essential.Originality/valueOur configurational approach provides new insights into the complex dynamics of eight CSFs with a holistic approach. Instead of focusing on the additive linear net effects of CSFs on firm performance, we explain how the CSFs of TQM implementation combine into multiple combinations. By doing so, we show multiple equifinal pathways to firm performance.