bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Agent-Based Model of Metabolic Signaling Oscillations inBacillus subtilisBiofilms
Authors: Mulder Obadiah J. , Kostman Maya Peters , Almodaimegh Abdulrahmen , Edge Michael D. , Larkin Joseph W. 
Published: December 2024

AbstractMicrobes of nearly every species can form biofilms, communities of cells bound together by a self-produced matrix. It is not understood how variation at the cellular level impacts putatively beneficial, colony-level behaviors, such as cell-to-cell signaling. Here we investigate this problem with an agent-based computational model of metabolically driven electrochemical signaling inBacillus subtilisbiofilms. In this process, glutamate-starved interior cells release potassium, triggering a depolarizing wave that spreads to exterior cells and limits their glutamate uptake. More nutrients diffuse to the interior, temporarily reducing glutamate stress and leading to oscillations. In our model, each cell has a membrane potential coupled to metabolism. As a simulated biofilm grows, collective membrane potential oscillations arise spontaneously as cells deplete nutrients and trigger potassium release, reproducing experimental observations. We further validate our model by comparing spatial signaling patterns and cellular signaling rates with those observed experimentally. By oscillating external glutamate and potassium, we find that biofilms synchronize to external potassium more strongly than to glutamate, providing a potential mechanism for previously observed biofilm synchronization. By tracking cellular glutamate concentrations, we find that oscillations evenly distribute nutrients in space: non-oscillating biofilms have an external layer of well-fed cells surrounding a starved core, whereas oscillating biofilms exhibit a relatively uniform distribution of glutamate. Our work shows the potential of agent-based models to connect cellular properties to collective phenomena and facilitates studies of how inheritance of cellular traits can affect the evolution of group behaviors.
SMAD4 Mutation Drives Gut Microbiome Shifts Toward Tumor Progression in Colorectal Cancer
Authors: Gates Travis J , Wangmo Dechen , Boorsma Bergerud Kyra M , Keel Bridget , Staley Christopher , Subramanian Subbaya 
Published: December 2024

ABSTRACTColorectal cancer (CRC) progression is driven by a series of sequential mutations in key driver genes, yet the factors underpinning tumor advancement and metastasis remain incompletely understood. Mutations in TP53 and SMAD4, in particular, are associated with poor treatment response and enhanced CRC pathogenesis. Although gut microbiome dysbiosis is implicated in CRC initiation and inflammation, the interactions between the microbiome and specific CRC driver mutations, especially those promoting metastasis, are poorly defined. In this study, we used triple mutant (Apc, Kras, Tp53; AKP) and quadruple mutant (Apc, Kras, Tp53, Smad4; AKPS) organoid-based orthotopic mouse models of CRC to examine the impact of SMAD4 mutation on tumor progression, metastasis, and microbiome composition. AKP and AKPS organoids were endoscopically implanted into the colons of individually housed C57BL/6 mice, and fecal samples were collected weekly over an 8-week period. Our results reveal significant differences in metastatic potential and microbial community dynamics between the two tumor models. AKPS tumors exhibited metastasis to the lymph nodes, liver, and lungs, whereas AKP tumors remained confined to the colon. Longitudinal microbiome analysis showed shifts in microbial composition within each tumor model. Both AKP and AKPS models demonstrated enrichment ofFaecalibaculumand a decrease inDubosiellaover time; however, additional shifts were observed with distinct taxa associated with late-stage tumors in each group. Notably, the AKPS model exhibited higher relative abundances of pro-inflammatory taxa, includingTuricibacter, Romboutsia, and Akkermansia, suggesting that SMAD4 mutation promotes a more immunosuppressive and pro-metastatic microbiome profile. These findings underscore the role of SMAD4 in modulating the microbiome in a manner that favors CRC metastasis and suggests potential microbial targets for therapeutic intervention to slow CRC progression. This work provides new insights into the microbiome’s role in CRC mutagenesis and metastasis, highlighting the interplay between host genetics and gut microbiota in driving cancer aggressiveness.
A Vulnerable Subtype of Dopaminergic Neurons Drives Early Motor Deficits in Parkinson’s Disease
Authors: Fushiki Akira , Ng David , Lewis Zachary R. , Yadav Archana , Saraiva Tatiana , Hammond Luke A. , Wirblich Christoph , Tasic Bosiljka , Menon Vilas , da Silva Joaquim Alves , Costa Rui M. 
Published: December 2024

AbstractIn Parkinson’s disease, dopaminergic neurons (DANs) in the midbrain gradually degenerate, with ventral substantia nigra pars compacta (SNc) DANs exhibiting greater vulnerability.However, it remains unclear whether specific molecular subtypes of ventral SNc DANs are more susceptible to degeneration in PD, and if they contribute to the early motor symptoms associated with the disease. We identified a subtype ofSox6+DANs,Anxa1+, which are selectively lost earlier than other DANs, and with a time course that aligns with the development of motor symptoms in MitoPark mice. We generated a knock-in Cre mouse line forAnxa1+DANs and showed differential anatomical inputs and outputs of this population. Further, we found that the inhibition of transmitter release inAnxa1+neurons led to bradykinesia and tremor. This study uncovers the existence of a selectively vulnerable subtype of DANs that is sufficient to drive early motor symptoms in Parkinson’s disease.
Dynamic Grouping of Ongoing Activity in V1 Hypercolumns
Authors: Zhang Rui , Wang Jiayu , Cai Xingya , Tang Rendong , Lu Haidong D. 
Published: December 2024

AbstractNeurons’ spontaneous activity provides rich information about the brain. A single neuron’s activity has close relationships with the local network. In order to understand such relationships, we studied the spontaneous activity of thousands of neurons in macaque V1 and V2 with two-photon calcium imaging. In V1, the ongoing activity was dominated by global fluctuations in which the activity of majority of neurons were correlated. Neurons’ activity also relied on their relative locations within the local functional architectures, including ocular dominance, orientation, and color maps. Neurons with similar preferences dynamically grouped into co-activating ensembles and exhibited spatial patterns resembling the local functional maps. Different ensembles had different strengths and frequencies. This observation was consistent across all hypercolumn-sized V1 locations we examined. In V2, different imaging sites had different orientation and color features. However, the spontaneous activity in the sampled regions also correlated with the underlying functional architectures. These results indicate that functional architectures play an essential role in influencing neurons’ spontaneous activity, and can be explained by a network model that integrates diverse horizontal connections among similar functional domains.
EnsembleFlex: Protein Structure Ensemble Analysis Made Easy
Authors: Schneider Melanie , Marquez José Antonio , Leach Andrew R 
Published: December 2024

AbstractEnsembleFlex is a novel tool designed to perform dual-scale flexibility analysis of protein structure ensembles, encompassing both backbone and side-chain dynamics. It integrates dedicated superposition methodologies, two dimension reduction techniques, customizable clustering, an automated ligand binding site analysis and analysis of conserved water molecules, enhancing the accuracy of ensemble flexibility analysis and visualisation. With a user-friendly, no-coding graphical interface as well as a code-based option, EnsembleFlex is accessible to a broad range of researchers. The tool complements experimental ensemble data analysis with predictive methods based on elastic network models, bridging the gap between experimental and computational approaches in protein flexibility analysis, and does so from a global backbone-based perspective, as well as from a focused side-chain and binding site-centred point of view. The need for reliable, streamlined, fast, and user-friendly tools for structural ensemble analysis is critical in today’s research environment, and EnsembleFlex addresses these needs efficiently, offering an accessible solution that integrates powerful analysis methods in a single package. Its wide applicability across various domains of molecular design underscores the importance of streamlined flexibility analysis in scientific research.
Testing various combinations of cryoprotective agents for human skin cryopreservation by vitrification method
Authors: Riabinin Andrei , Pankratova Maria , Rogovaya Olga , Vorotelyak Ekaterina , Vasiliev Andrey 
Published: December 2024

AbstractModern translational medicine, pharmacology and other fields require effective skin cryopreservation technology. Vitrification is promising technology for this aim. This rapid freezing technique minimizes hexagonal ice crystals formation, time of stress condition for cells in samples and dehydration both in the cytoplasm of cells and in the extracellular space. This study is aimed at finding the optimal combination of extracellular (sucrose, mannitol, polyethylene glycol and FBS) and intracellular (DMSO, glycerol, ethylene glycol) cryoprotective agents to achieve the highest viability and tissue structure preservation of skin samples after vitrification.
Xolography for Biomedical Applications: Dual-color Light-sheet Printing of Hydrogels with Local Control over Shape and Stiffness
Authors: Stoecker Lena , Cedillo-Servin Gerardo , König Niklas F. , Graaf Freek V. de , Jiménez Marcela García , Hofmann Sandra , Ito Keita , Wentzel Annelieke S. , Castilho Miguel 
Published: December 2024

AbstractCurrent challenges in tissue engineering include creation of extracellular environments that support and interact with cells using biochemical, mechanical, and structural cues. Spatial control over these cues is currently limited due to a lack of suitable fabrication techniques. This study introduces Xolography, an emerging dual-color light-sheet volumetric printing technology, to achieve control over structural and mechanical features for hydrogel-based photoresins at micro-to macroscale while printing within minutes. We propose a water-soluble photoswitch photoinitiator system and are the first to demonstrate Xolography with a library of naturally-derived, synthetic, and thermoresponsive hydrogels. Centimeter-scale, three-dimensional constructs with positive features of 20 µm and negative features of ∼ 100 µm are fabricated with control over mechanical properties (compressive moduli 0.2 kPa – 6.5 MPa). Notably, switching from binary to grayscaled light projection enables spatial control over stiffness (0.2 – 16 kPa). As a proof of concept, grayscaled Xolography is leveraged with thermoresponsive hydrogels to introduce reversible anisotropic shape changes beyond isometric shrinkage. We finally demonstrate Xolography of viable cell aggregates, laying the foundation for cell-laden printing of dynamic, cell-instructive environments with tunable structural and mechanical cues in a fast one-step process. Overall, these innovations unlock unique possibilities of Xolography across multiple biomedical applications.
A critical role of FAK signaling in Rac1-driven melanoma cell resistance to MAPK pathway inhibition
Authors: Riordan Jesse D. , Nathanson Teagan A. , Varzavand Afshin , Hawkins Adeline A. , Peplinski Rebekah M. , Hannan Elizabeth C. , Bibeau Faith A. , Freesmeier Nathaniel J. , Jilek Madison C. , Coma Silvia , Pachter Jonathan A. , Dupuy Adam J. , Stipp Christopher S. 
Published: December 2024

AbstractThe Rac1 P29S hotspot mutation in cutaneous melanoma is associated with resistance to MAPK pathway inhibitors (MAPKi) and worse clinical outcomes. Moreover, activation of Rac1 guanine exchange factors (GEFs) also promotes MAPKi-resistance, particularly in undifferentiated melanoma cells. Here we delineate mechanisms of Rac1-driven MAPKi-resistance and identify strategies to inhibit the growth of this class of cutaneous melanomas. We find that Rac1-driven melanomas manifest pleiotropic resistance mechanisms including (i) reduced dependence on BRAF/MEK, (ii) activation of alternative MAPK pathways utilizing Jun kinase and p38 MAP kinase, and (iii) a partial reliance on YAP/TAZ signaling. Importantly, although Rac1-driven melanoma cells display reduced dependence on BRAF/MEK, they are not completely ERK-independent. Additionally, the presence of activated Rac1 appears to create a dependency on focal adhesion kinase (FAK) signaling in undifferentiated melanoma cells. Therefore, despite the pleiotropic mechanisms of Rac1-driven MAPKi resistance, we find that combined inhibition of RAF and MEK with the RAF/MEK clamp auvotometinib and FAK with the FAK inhibitor defactinib is a promising approach for suppressing the growth of Rac1-driven melanoma cells. Thus, the avutometinib plus defactinib combination, which is currently being investigated for brain metastatic cutaneous melanoma may also have utility against Rac1-driven MAPKi-resistance in heavily pre-treated, advanced disease.
Temperature-based MHC class-I multimer peptide exchange for human HLA-A, B and C
Authors: Pothast Cilia R. , Derksen Ian , van der Plas – van Duijn Anneloes , el Hebieshy Angela , Huisman Wesley , Franken Kees L.M.C. , Neefjes Jacques , Luimstra Jolien J. , Griffioen Marieke , Kester Michel , Vermeer Maarten H. , Heemskerk Mirjam H.M. , Scheeren Ferenc A. 
Published: December 2024

AbstractT cell recognition of specific antigens presented by major histocompatibility complexes class-I (MHC-I) can play an important role during immune responses against pathogens and cancer cells. Detection of T cell immunity is based on assessing the presence of antigen-specific cytotoxic CD8+ T cells using MHC class-I (MHC-I) multimer technology. Previously we have designed conditional peptides for HLA-A*02:01, H-2Kband HLA-E that form stable peptide-MHC-I-complexes at low temperatures and dissociate when exposed to a defined elevated temperature. The resulting conditional MHC-I complex can easily and without additional handling be exchanged with a peptide of interest, allowing to exchange peptides in a ready-to-use multimer and a high-throughput manner. Here we present data that this peptide-exchange technology is a general applicable, ready-to-use and fast approach to load many different peptides in MHC-I multimers for alleles of the HLA-A, HLA-B and HLA-C loci. We describe the development of conditional peptides for HLA-A*03:01, HLA-A*11:01, HLA-B*07:02 and HLA-C*07:02 that only form stable peptide-MHC-I complexes at low temperatures, allowing peptide exchange at higher defined temperature. We document the ease and flexibility of this technology by monitoring CD8+ T cell responses to virus-specific peptide-MHC complexes in patients.Graphical abstractHighlightsT cell immunity relies on antigen-specific CD8+ T cells recognizing peptide MHC-I complexes.Establishing temperature-based peptide exchange across multiple HLA alleles, resulting in a robust, easy, and fast system to generate peptide MHC-I complexes.Temperature-based MHC class-I multimer demonstrate applicability across major MHC-I gene families for monitoring CD8+ T cell responses.Easy high-throughput peptide exchange potential, enhancing clinical utility of MHC multimer technology.
Adaptive Optics Rolling Slit Ophthalmoscope: Combining cellular-resolution, high-speed and large field-of-view in a multimodal retinal imager
Authors: Krafft Léa , Senee Pierre , Brad Ana Alexandra , Atlan Michael , Paques Michel , Thouvenin Olivier , Mecê Pedro , Meimon Serge 
Published: December 2024

AbstractLabel-free optical imaging systems capable of monitoring dynamic biological processes over a large field-of-view (FOV) are essential for advancing our understanding of retinal and neurovascular health. However, existing imaging modalities often involve trade-offs between spatial resolution, contrast, FOV, and frame rate. In this study, we present the Adaptive Optics Rolling Slit Ophthalmoscope (AO-RSO), a novel imaging system that integrates the high-speed, wide-FOV capabilities of camera-based systems with the enhanced contrast and multimodal functionality of point-scanning techniques—without compromising resolution or speed. The AO-RSO utilizes line illumination synchronized with the rolling shutter of a high-speed sCMOS camera, enabling precise and dynamic spatial selection of detected photons: back-scattered photons for near-confocal bright-field imaging and forward-scattered photons for phase-contrast imaging of translucent retinal features. This system successfully visualizes diverse retinal structures, including cone and rod photoreceptors, nerve fiber bundles, red blood cells, vessel walls, and ganglion cells, across a wide retinal area (4.5°× 2.5°). With a large FOV and frame rates up to 200 Hz, the AO-RSO enables the quantification of blood flow, tracking of red blood cells within hundreds of capillaries, and evaluation of thousands of photoreceptors in the living human retina. This capability opens new opportunities for functional neuronal imaging, neurovascular coupling studies, and the early detection of retinal and neurodegenerative diseases.
Effect of thermal longitudinal spin fluctuations on the elastic properties of
Ni3Nb
Authors: Xiong Ziyi , Li Wei , Dong Zhihua , Xu Weiwei , Vitos Levente 
Published: December 2024

Using an efficient first-principles computational approach, we investigate the influence of the thermal longitudinal spin fluctuations (LSFs) within the nickel sublattices on the thermoelastic properties of Ni3Nb with D022 structure. Leveraging the mean magnetic moment values to represent the spin-fluctuation state at respective temperatures and incorporating the lattice vibration contributions via the Debye model, the equilibrium bulk parameters and elastic constants are derived. We find that, although the volume expansion remains the primary mechanism behind the softening of the elastic constants with increasing temperature, the LSFs effect contributes significantly to the temperature dependence of c11 and c33. Our analysis reveals that including the LSFs makes the theoretical thermal-expansion coefficient highly anisotropic, in line with the experiments. Quantitative agreement between theory and experiment is obtained for the thermal expansion along the c axis at temperatures up to 500 K, whereas the measured thermal expansion along the a axis is underestimated by theory. The present results provide theoretical thermoelastic data for free-standing Ni3Nb precipitates with D022 structure, which can be used to estimate the lattice strains around such precipitates in Ni-based superalloys.

Published by the American Physical Society
2024
Food consumption norms based on age and income in the UK
Authors: van den Heuvel Emmy , Guy Danielle J. , Taylor Zoe , Appleton Katherine M. 
Published: December 2024

PurposeConsumption norms describe an individual’s perception of what or how much most other people typically eat. While gendered consumption norms are well known, consumption norms linked to other demographic variables are yet to be reported. This study aimed to investigate which food consumption norms in relation to gender, age and income are currently held by the UK population. A secondary research objective was to investigate whether these consumption norms were held equally across people in different age groups and genders within the sample population.Design/methodology/approachA sample of 498 adults participated in an online survey composed of statements on consumption patterns based on gender, age and income for nine foods (e.g. red meat) and five meal patterns (e.g. take-away meals). E.g. “Men tend to eat more red meat than women.” Participants reported their agreement/disagreement with these statements.FindingsThe results indicate that participants have perceived consumption norms that are associated with gender, age and income. Lower energy-dense foods and smaller meal patterns were generally associated with females, older persons and individuals with a higher income. In contrast, more energy-dense foods and meal patterns were generally associated with males, younger adults and individuals with a lower income. These consumption norms were held consistently across the population sample.Originality/valueTo the best of our knowledge, this is the first explicit demonstration of food consumption norms based on age and income.
Food well-being: a review of its conceptualization and measurement
Authors: Zeng Tian , Montesinos Sansaloni Eduard Xavier 
Published: December 2024

PurposeThis study aimed to improve understanding of the phenomenon of food well-being (FWB) (conceptualization, measurement, antecedents and outcomes) so as to lead future empirical work on measurement, development and theory testing. The hope is to improve the societal benefits of FWB and sustainable food system transformation.Design/methodology/approachA domain-based systematic review of FWB was conducted using databases (Web of Science, ABI/INFORM, EBSCO and Scopus). The well-established theory, context, characteristics and methodology framework were used to structure the review.FindingsThis study synthesized conceptual definitions and measurements of consumer FWB from hedonic, eudemonistic and mixed research streams and a nomological network that distinguishes this construct from its antecedents and outcomes.Practical implicationsThis study provides recommendations for consumers, food designers, retailers and policymakers to improve FWB.Originality/valueThis study assessed the conceptualizations of FWB from hedonic, eudemonistic and mixed perspectives for conceptual clarity. It summarized ten measurement tools for FWB-allied concepts (Well-being Related to Food Questionnaires, Satisfaction with Food-Related Life Scale and World Health Organization-Five Well-Being Index), which revealed the need for novel measurement. This study developed a holistic nomological network of FWB by identifying the categories of antecedents (food-related, consumer-related and contextual factors) and outcomes (general well-being, life satisfaction and food consumption). This study provides a research agenda for FWB measurement and theoretical development.