bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prevalent Krt8-to-Krt5 cellular state transition in skin is co-opted by p63 for enamel organ development
Authors: Tang Qinghuang , Lee Jung-Mi , Li Liwen , Cai Chunmiao , Jung Hunmin , Kwon Hyuk-Jae Edward 
Published: February 2025

AbstractTooth enamel, the hardest tissue in vertebrates, is crucial for mastication and dental protection. Its formation depends on the enamel organ (EO), a specialized epithelial structure derived from oral epithelium. A fundamental question persists: how does uniform oral epithelium differentiate into diverse EO cell types? While p63, a master regulator of ectodermal development, coordinates multiple signaling pathways essential for dental placode formation, its specific roles in EO development remain unclear due to the early developmental arrest inp63knockout mice. Using single-cell RNA sequencing data from mouse incisors, we demonstrate thatp63is expressed across all EO cell types, serving both shared and distinct functions. Through trajectory reconstruction, we identify the role of p63 in regulating both amelogenic (AmG) and non-AmG lineage commitment during EO development. Our comparative transcriptome analyses reveal that p63 regulates the Krt8-to-Krt5 transition during AmG cell differentiation, paralleling its function in skin development. This parallel is reinforced by comparative motif discovery, revealing shared transcription factor usage, particularly p63 and AP-2 family members, in both AmG and skin epidermal cells during this transition. Chromatin accessibility analysis further illustrate that p63 mediates this transition through chromatin landscape remodeling. Together, these findings demonstrate that p63 co-opts the Krt8-to-Krt5 transition mechanism from skin development for EO development, providing novel insights into the molecular mechanisms underlying EO development and potential therapeutic targets for enamel disorders.
Gpnmb Defines a Phagocytic State of Microglia Linked to Neuronal Loss in Prion Disease
Authors: Caredio Davide , Mariutti Giovanni , Cerisoli Martina , Polzer Lisa , Laimeche Yasmine , Miracca Giulia , Emmenegger Marc , Schmitz Matthias , Zerr Inga , De Cecco Elena , Aguzzi Adriano 
Published: February 2025

AbstractThe reaction of different cell types to prion infections is highly heterogeneous. While neurons experience spine retraction and eventually death, astrocytes and microglia undergo strong activation and proliferation. Here we analyzed the cell-type specific responses to prion diseases by establishing a spatiotemporal transcriptomic atlas of mice infected with RML prion strain. Brain areas with severe neuronal loss, such as the thalamus and cerebellum, experienced intense microgliosis. Starting from 30 weeks post-inoculation, we observed the accumulation of a novel microglial subpopulation characterized by strong expression ofGpnmbin these brain regions. The molecular profile ofGpnmb+microglia reflected a state of enhanced phagocytic activity with upregulation of genes associated with lysosomal function and degradation, including vacuolar ATPase V0 domain subunit d2 (Atp6v0d2) and Galectin-3 (Lgals3). In microglial-like, murine BV2 cells, Gpnmb upregulation was induced by soluble find-me signals released during apoptosis, but not by apoptotic bodies or prion accumulation. Gpnmb ablation in BV2 cells impaired their ability to phagocytose apoptotic cells, underscoring its essential role in maintaining microglial phagocytosis. Our findings defineGpnmb⁺ microglia as a distinct, apoptosis-driven phagocytic state, linking neuronal loss to microglial activation in prion disease. The upregulation of GPNMB in sCJD patients, along with its role in apoptotic clearance and lysosomal function, positions it as both a key regulator of microglial responses and a potential biomarker of disease progression.
ReaxFF-guided Optimisation of VIRIP-based HIV-1 Entry Inhibitors
Authors: Zech Fabian , Jung Christoph , Rodríguez-Alfonso Armando Alexei , Köhler Janet , Ständker Ludger , Weidinger Gilbert , Jacob Timo , Kirchhoff Frank 
Published: February 2025

AbstractPeptides hold great promise for safe and effective treatment of viral infections. However, their use is often constrained by limited efficacy and high production costs, especially for long or complex peptide chains. Here, we used ReaxFF molecular dynamics (MD) simulations to optimize the size and activity of VIRIP (Virus Inhibitory Peptide), a naturally occurring 20-residue fragment of α1-antitrypsin that binds the HIV-1 GP41 fusion peptide (FP), thereby blocking viral fusion and entry into host cells. Specifically, we used the NMR structure of the complex between an optimized VIRIP derivative (VIR-165) and the HIV-1 gp41 FP for ReaxFF-guidedin silicoanalysis, evaluating the contribution of each amino acid in the interaction of the inhibitor with its viral target. This approach allowed us to reduce the size of the HIV-1 FP inhibitor from 20 to 10 amino acids (2.28 to 1.11 kDa). HIV-1 infection assays showed that the size-optimized VIRIP derivative (soVIRIP) retains its broad-spectrum anti-HIV-1 capability and is non-toxic in the vertebrate zebrafish model. Compared to the original VIRIP, soVIRIP displayed more than 100-fold higher antiviral activity (IC50of ∼120 nM). Thus, it is more potent than a dimeric 20-residue VIRIP derivative (VIR-576) that was proven safe and effective in a phase I/II clinical trial. Our results show that ReaxFF-based MD simulations represent a suitable approach for the optimization of therapeutic peptides.
Cryo-EM analysis of theBacillus thuringiensisextrasporal matrix identifies F-ENA as a widespread family of endospore appendages across the Firmicutes phylum
Authors: Sleutel Mike , Sogues Adrià , Gerven Nani Van , Jonsmoen Unni Lise , Molle Inge Van , Fislage Marcus , Theunissen Laurent Dirk , Bellis Nathan F. , Baquero Diana P. , Egelman Edward H. , Krupovic Mart , Wang Fengbin , Aspholm Marina , Remaut Han 
Published: February 2025

AbstractFor over 100 years,Bacillus thuringiensis(Bt) has been used as an agricultural biopesticide to control pests caused by insect species in the orders of Lepidoptera, Diptera and Coleoptera. Under nutrient starvation, Bt cells differentiate into spores and associated toxin crystals that can adopt biofilm-like aggregates. We reveal that such Bt spore/toxin biofilms are embedded in a fibrous extrasporal matrix (ESM), and using cryoID, we resolved the structure and molecular identity of an uncharacterized type of pili, referred to here asFibrillarENdosporeAppendages or ‘F-ENA’. F-ENA are monomolecular protein polymers tethered to the exosporium of Bt and are decorated with a flexible tip fibrillum. Phylogenetic analysis reveals that F-ENA is widespread not only in the class Bacilli, but also in the class Clostridia, and the cryoEM structures of F-ENA filaments fromBacillus, AnaerovoraxandPaenibaccilusreveal subunits with a generic head-neck domain structure, where the β-barrel neck of variable length latch onto a preceding head domain through short N-terminal hook peptides. InBacillus, two collagen-like proteins (CLP) respectively tether F-ENA to the exosporium (F-Anchor), or constitute the tip fibrillum at the distal terminus of F-ENA (F-BclA). Sedimentation assays point towards F-ENA involvement in spore-spore clustering, likely mediated via F-BclA contacts and F-ENA bundling through the antiparallel interlocking of the head-neck units.
The Influence of Spatial Frequencies, Orientation and Familiarity on Face Stimuli Integration
Authors: Cuomo Maria , Federico Giovanni , Fracasso Alessio , Buonocore Antimo 
Published: February 2025

AbstractWhen we observe an object, our visual system identifies its shape and integrates it with specific details to form a coherent representation. Thiscoarse-to-fineapproach involves rapid processing of low spatial frequency (LSF) content to generate a basic template, which aids the integration of the more detailed high spatial frequency (HSF) information. Here we explore with two experiments how the contribution of LSF and HSF integration extends to face processing. To do so, we leveraged the face inversion effect, whereby inverted faces are more difficult to recognize than upright ones. In Experiment 1, ten participants matched two familiar faces displayed in rapid succession (template and probe face, respectively). The template and the probe shared either the same SF (congruent) or had complementary SF (incongruent). In congruent conditions, HSF templates yielded better matching accuracy than LSF templates. However, in incongruent conditions, mapping LSF probes onto HSF templates was more effective, but only for upright faces. We propose that, depending on the task, holistic processing may be facilitated by detailed information. In Experiment 2, twelve participants performed the same task with both familiar and unfamiliar faces. While for familiar faces the effects were the same as Experiment 1, for unfamiliar faces the overall accuracy was better for congruent than incongruent conditions, and, crucially, it was independent of the template SF. Our results challenge the view that LSF content provides a foundational template for integrating HSF information, and instead suggest a flexible encoding of SF information, that depends on image contingencies.
Mouse scalp development requires Rac1 and SRF for the maintenance of mechanosensing mesenchyme
Authors: Rathnakar Bharath H. , Rackley Alex , Kwon Hae Ryong , Berry William L. , Olson Lorin E. 
Published: February 2025

ABSTRACTRegulation of essential cellular responses like proliferation, migration, and differentiation is crucial for normal development. Rac1, a ubiquitously expressed small GTPase, executes these responses under the regulation of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GTPases). Mutations in specific GEFs (DOCK6) and GTPases (AHGAP31) that regulate Rac1 are associated with Adams-Oliver syndrome (AOS), a developmental syndrome characterized by congenital scalp defects and limb truncations. Genetic ablation ofRac1in the mouse embryonic limb ectoderm results in limb truncation. However, the etiology of Rac1-associated cranial defects is unknown. To investigate the origin and nature of cranial defects, we used a mesenchymal Cre line (Pdgfra-Cre) to deleteRac1in cranial mesenchyme.Rac1-KO mice died perinatally and lacked the apical portion of the calvarium and overlying dermis, resembling cranial defects seen in severe cases of AOS. In control embryos, α-smooth muscle actin (αSMA) expression was spatially restricted to the apical mesenchyme, suggesting a mechanical interaction between the growing brain and the overlying mesenchyme. InRac1-KO embryos there was reduced proliferation of apical mesenchyme, and reduced expression of αSMA and its regulator, serum response factor (SRF). Remarkably,Srf-KO mice generated withPdgfra-Crerecapitulated the cranial phenotype observed inRac1-KO mice. Together, these data suggest a model where Rac1 and SRF are critical to maintaining apical fibroblasts in a mechano-sensitive and proliferative state needed to complete cranial development.
Disruption of Mitochondrial Dynamics and Stasis Leads to Liver Injury and Tumorigenesis
Authors: Ma Xiaowen , Wei Xiaoli , Niu Mengwei , Zhang Chen , Peng Zheyun , Liu Wanqing , Yan Junrong , Su Xiaoyang , Lu Shaolei , Cui Wei , Sesaki Hiromi , Zong Wei-Xing , Ni Hong-Min , Ding Wen-Xing 
Published: February 2025

AbstractBackground & AimsMitochondrial dysfunction has been implicated in aging and various cancer development. As highly dynamic organelles, mitochondria constantly undergo fission, mediated by dynamin-related protein 1 (DRP1, gene nameDnm1l), and fusion, regulated by mitofusin 1 (MFN1), MFN2, and optic atrophy 1 (OPA1). However, whether and how dysregulation of mitochondria dynamics would be involved in liver pathogenesis and tumorigenesis is unknown.MethodsDnm1lFlox/Flox (Dnm1lF/F),Mfn1F/FandMfn2F/Fmice were crossed with albumin-Cre mice to generate liver-specificDnm1lknockout (L-Dnm1lKO), L-Mfn1KO, L-Mfn2KO, L-Mfn1, Mfn2double KO (DKO), and L-Mfn1, Mfn2, Dnm1ltriple KO (TKO) mice. These mice were housed for various periods up to 18 months. Some mice also received hydrodynamic tail vein injections of a Sleeping Beauty transposon-transposase plasmid system withc-MYCandYAP. Blood and liver tissues were harvested for biochemical and histological analysis.ResultsL-Dnm1lKO mice had elevated serum alanine aminotransferase levels and increased hepatic fibrosis as early as two months of age. By 12 to 18 months, male L-Dnm1lKO mice developed spontaneous liver tumors, primarily hepatocellular adenomas. While female L-Dnm1lKO mice also developed liver tumors, their incidence was much lower.In contrast, neither L-Mfn1KO nor L-Mfn2KO mice had notable liver injury or tumorigenesis. However, a small portion of DKO mice developed tumors at 15-18 month-old. Increased DNA damage, senescence and compensatory proliferation were observed in L-Dnm1lKO mice but were less evident in L-Mfn1KO, L-Mfn2KO or DKO mice, indicating that mitochondrial fission is more important to maintain hepatocyte homeostasis and prevent liver tumorigenesis. Interestingly, further deletion ofMfn1andMfn2in L-Dnm1lKO mice markedly abolished liver injury, fibrosis, and both spontaneous and oncogene-induced tumorigenesis. RNA sequencing and metabolomics analysis revealed significant activation of the cGAS-STING-interferon pathway and alterations in the tumor microenvironment pathways, alongside increased pyrimidine synthesis and metabolism in the livers of L-Dnm1lKO mice. Notably, the changes in gene expression and pyrimidine metabolism were considerably corrected in the TKO mice.ConclusionsMitochondrial dynamics and stability are essential for maintaining hepatic mitochondrial homeostasis and hepatocyte functions. Loss of hepatic DRP1 promotes liver tumorigenesis by increasing pyrimidine metabolism and activating the cGAS-STING-mediated innate immune response.
Processingof Clostridium perfringensEnterotoxin by Intestinal Proteases
Authors: Shrestha Archana , Gonzales Jessica L. , Beingesser Juliann , Uzal Francisco A. , McClane Bruce A. 
Published: February 2025

AbstractC. perfringenstype F isolates are a leading cause of food poisoning and antibiotic-associated diarrhea. Type F isolate virulence requires production ofC. perfringensenterotoxin [CPE], which acts by forming large pore complexes in host cell plasma membranes. During disease, CPE is produced in the intestines when type F strains undergo sporulation. The toxin is then released into the intestinal lumen when the mother cell lyses at the completion of sporulation. Once present in the lumen, CPE encounters intestinal proteases. This study examinedin vitro,ex vivoandin vivoprocessing of CPE by intestinal proteases and the effects of this processing on CPE activity. Results using purified trypsin or mouse intestinal contents detected rapid cleavage of CPE to a major band of ∼32 kDa and studies with Caco-2 cells showed this processed CPE still forms large complexes and retains cytotoxic activity. When mouse small intestinal loops were challenged with CPE, the toxin caused intestinal histologic damage despite rapid proteolytic processing of most CPE to 32 kDa within 15 min. Intestinal large CPE complexes became more stable with longer treatment times. These results indicate that CPE processing involving trypsin occurs in the intestines and the processed toxin retains enterotoxicity.
Borax-Based Gel Electrophoresis: A Novel Approach for RNA Integrity Analysis
Authors: Albaser Abdulhadi 
Published: February 2025

AbstractThis study explores the feasibility of using borax-based agarose gel electrophoresis for RNA integrity assessment. Multiple independent experiments demonstrated that borax, in addition to its buffering properties, exhibits denaturing-like behavior, effectively separating RNA molecules with comparable resolution to formaldehyde-based methods. This finding is surprising, given that theoretically, no evidence for borax denaturing activity exists, as it is typically considered a non-denaturing buffer. This method offers a compelling alternative to traditional formaldehyde-based methods for RNA analysis in various research and clinical settings, offering several advantages, including enhanced safety, simplified protocols, and reduced electrophoresis time. By eliminating the need for pre-treatment steps and utilizing borax as both a buffer and denaturant, this method simplifies RNA analysis. While the precise mechanism underlying this denaturing-like effect remains to be elucidated, further studies are needed to fully characterize these properties and explore its broader applicability.
Enhanced Neural Plasticity of the Primary Visual Cortex in Visual Snow Syndrome: Evidence from MEG Gamma Oscillations
Authors: Orekhova E.V. , Naumova S.M , Obukhova T.S. , Plieva A.M. , Prokofiev A.O. , Petrokovskaia A.V. , Artemenko A.R. , Stroganova T.A. 
Published: February 2025

AbstractVisual Snow Syndrome (VSS) is a neurological disorder characterized by persistent visual disturbances and associated symptoms. Although the neural basis of VSS remains poorly understood, it may involve increased neuronal excitability and/or altered neuroplasticity in the visual cortex, which could, in turn, affect visual gamma oscillations. An altered excitation-inhibition (E-I) balance is hypothesized to alter the modulation of gamma power and frequency by stimulation intensity, while maladaptive neuroplasticity may impact time-dependent changes in gamma power during repeated stimulation.To investigate potential alterations in E-I balance and neuroplasticity in VSS, we magnetoencephalography to record visual gamma oscillations in 26 VSS patients and 27 healthy controls. Participants were exposed to repeatedly presented high-contrast annular gratings, which were either static or drifting at varying speeds to systematically manipulate stimulation intensity. We also measured heart rate variability (HRV) during rest and repetitive visual stimulation to explore the relationship between time-dependent gamma changes and parasympathetic activation, which is known to promote activity-dependent plasticity.Our results showed no significant group differences in gamma power or frequency, nor in their modulation by drift rate, suggesting that the excitation-inhibition (E-I) balance in the primary visual cortex remains largely intact in VSS. Both groups exhibited an initial brief decrease in gamma power followed by a sustained linear increase with stimulus repetition, likely reflecting activity-dependent plasticity. HRV parameters were comparable across groups, with the parasympathetic-sympathetic balance index correlating with repetition-related increase in gamma power, further supporting the link between time-dependent gamma changes and neuroplasticity. Notably, VSS patients exhibited a steeper repetition-related increase in gamma power, indicating atypically heightened activity-dependent plasticity in this group.These findings provide the first experimental evidence suggesting that altered activity-dependent neuroplasticity plays a role in the pathophysiology of VSS. Furthermore, they identify repetition-related increases in gamma power as a potential biomarker of aberrant neuroplasticity, offering novel insights into VSS pathophysiology and potential avenues for targeted therapeutic interventions.
High-energy-density acoustofluidic device using a double-parabolic ultrasonic transducer
Authors: Corato Enrico , Jakobsson Ola , Qiu Wei , Morita Takeshi , Augustsson Per 
Published: February 2025

High-acoustic-energy-density acoustofluidic devices are necessary to make this technology a viable option for clinical applications in the biomedical field. We present a mechanical interface that enables delivery of a high-amplitude acoustic field inside a fluid cavity by translating the vibrations from two large piezoelectric elements into a microfluidic chip. The study comprises both experimental characterization of a double-parabolic metallic acoustic waveguide and simulations of its working mechanism in two dimensions. We could focus 4.9-µm polystyrene particles at a flowrate of 5 ml/min, corresponding to an average retention time of 13.5 ms for particles in the actuated area. Moreover, we measured the acoustic energy density in the channel at stopped-flow condition, obtaining an average value of 1207 J/m3 and a maximum value of 2977 J/m3 with an input electrical power of 1.5 W. By comparing the simulation results with laser-Doppler vibrometer measurements, we confirmed that transverse sound waves play a significant role in the working mechanism of the double-parabolic structure, thus paving the way for further future optimization of the waveguide design.

Published by the American Physical Society
2025
Chiral perturbation theory and Bose-Einstein condensation in QCD
Authors: Andersen Jens O. , Johnsrud Martin Kjøllesdal , Yu Qing , Zhou Hua 
Published: February 2025

We present recent results in three-flavor chiral perturbation theory at finite isospin μI and strangeness μS chemical potentials at zero temperature. The tree-level spectrum for the mesons and gauge bosons in the pion-condensed phase is derived. The phase diagram to O(p2) in the μI–μS plane is mapped out with and without electromagnetic effects. The phase diagram consists of a vacuum phase and three Bose-condensed phases with condensates of π±, K±, and K0/K¯0, respectively. Including electromagnetic interactions, the charged Bose-condensed phases become Higgs phases via the Higgs mechanism. We calculate the pressure, energy density, isospin density, and speed of sound in the pion-condensed phase to O(p4). The results are compared with recent lattice simulations and the agreement is very good for isospin chemical potentials up to approximately 180 MeV. Moreover, by integrating out the s-quark, we show that the thermodynamic quantities can be mapped onto their two-flavor counterparts with renormalized parameters. The breaking of the U(1) symmetry in the Bose-condensed phases gives rise to a Goldstone boson, whose dispersion is linear for small momenta. We use Son’s prescription to construct an effective theory for the Goldstone mode in the pion-condensed phase, which is valid for momenta p≪μI. It is shown that its damping rate is of order p5 in the nonrelativistic limit, which is Beliaev’s result for a dilute Bose gas. It is also shown that in the nonrelativistic limit the energy density can be matched onto the classic result by Lee, Huang and Yang (LHY) for a dilute Bose, with an s-wave scattering length that includes radiative corrections.

Published by the American Physical Society
2025
Neutral Sulfur Atom Formation in Decay of Deep Core Holes in
SF6
Authors: Travnikova Oksana , Trinter Florian , Agåker Marcus , Visentin Giorgio , Andersson Joakim , Kjellsson Ludvig , Ismail Iyas , Velasquez Nicolas , Koulentianos Dimitris , Harder Manuel , Yin Zhong , Söderström Johan , Marchenko Tatiana , Guillemin Renaud , McGinnis O. Dennis , Ågren Hans , Fritzsche Stephan , Simon Marc , Rubensson Jan-Erik , Nordgren Joseph 
Published: February 2025

Dissociation upon sulfur K-shell excitation or ionization of SF6 is studied by sulfur L-shell emission spectroscopy using synchrotron radiation and multiconfiguration Dirac-Hartree-Fock calculations of emission energies and transition rates. The decay path involves in particular Auger emission with the ejection of one or more electrons, leading to singly or multiply charged intermediate states. Nevertheless, the results of the study show that the observed photon emission at 151–152 eV following excitation at 2485–2489 eV originates dominantly from transitions in neutral sulfur. This clearly indicates that the central atom retains its electrons in a dissociation process where all fluorine atoms detach before the S 2p decay.

Published by the American Physical Society
2025