bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Dietary Protein Induces Changes in the Dental Proteome
Authors: Burroughs Robert W. , Percival Christopher J. , Vitek Natasha S. 
Published: January 2025

AbstractExperimental studies have demonstrated that nutritional changes during development can result in phenotypic changes to mammalian cheek teeth. This developmental plasticity of tooth morphology is an example of phenotypic plasticity. Because tooth development occurs through complex interactions between manifold processes, there are many potential mechanisms which can contribute to a tooth’s norm of reaction. Determining the identity of those mechanisms and the relative importance of each of them is one of the main challenges to understanding phenotypic plasticity. Quantitative proteomics combined with experimental studies allow for the identification of potential molecular contributors to a plastic response through quantification of expressed gene products. Here, we present the results of a quantitative proteomics analysis of mature upper first molars (M1s) inMus musculusfrom a controlled feeding experiment. Pregnant and nursing mothers were fed either a low-dietary protein (10%) treatment diet or control (20%) diet. Expression of tooth-related proteins, immune system proteins, and actin-based myosin proteins were significantly altered in our low-dietary protein sample. The recovery of expression change in tooth development proteins was anticipated and consistent with previous proteomic studies. We also identified differential immune protein response along with systematic reduction in actin-based myosin protein expression, which are novel discoveries for tooth proteomics studies. We propose that studies which aim to elucidate specific mechanisms of molar phenotypic plasticity should prioritize investigations into the relationships between IGF regulation and tooth development and actin-based myosin expression and tooth development.Research HighlightsA low-protein diet during development results in significantly altered protein expression for major dental building proteins, immune system proteins, and actin-based myosin proteins withinMus musculus.Graphical Abstract
Narrative ‘twist’ shifts within-individual neural representations of dissociable story features
Authors: Sava-Segal Clara , Grall Clare , Finn Emily S. 
Published: January 2025

AbstractGiven the same external input, one’s understanding of that input can differ based on internal contextual knowledge. Where and how does the brain represent latent belief frameworks that interact with incoming sensory information to shape subjective interpretations? In this study, participants listened to the same auditory narrative twice, with a plot twist in the middle that dramatically shifted their interpretations of the story. Using a robust within-subject whole-brain approach, we leveraged shifts in neural activity between the two listens to identify where latent interpretations are represented in the brain. We considered the narrative in terms of its hierarchical structure, examining how global situation models and their subcomponents–namely, episodes and characters–are represented, finding that they rely on partially distinct sets of brain regions. Results suggest that our brains represent narratives hierarchically, with individual narrative elements being distinct and dynamically updated as a part of changing interpretations of incoming information.
Krüppel-like Factors Play Essential Roles in Regulating Pluripotency and the Formation of Neural Crest Stem Cells
Authors: Rigney Sara , York Joshua R. , LaBonne Carole 
Published: January 2025

AbstractThe evolutionary transition from simple chordate body plans to complex vertebrate body plans was driven by the acquisition of the neural crest, a stem cell population that retains broad, multi-germ layer developmental potential long after most embryonic cells have become lineage restricted. We have previously shown that neural crest cells share significant gene regulatory architecture with pluripotent blastula stem cells. Here we examine the roles that Krüppel-like Family (Klf) transcription factors play in these stem cell populations. Although Klf4 has established roles in regulating pluripotency in mammalian stem cells cultures, we find that inXenopusit isklf2that is highly expressed in pluripotent blastula stem cells.klf2expression is down-regulated as cells transition to a neural crest state while a related klf factor, klf17, is significantly up regulated in response to neural crest induction. We used gain and loss of function studies to compare the activities of these closely related factors and found that they have both shared and distinct activities. Inhibition of either klf2 or klf17 activity led to significantly expanded expression of pluripotency, neural plate border and neural crest factors in neurula stage embryos, leading us to hypothesize that klf factors regulate the exit from pluripotency and proper establishment of the boundary of the neural crest domain. To gain further insights into the role of klf factors in the evolution of the neural crest, we examined their expression in the jawless vertebrate,Petromyzon marinus (sea lamprey). We find that lamprey have aklf2/4and aklf17gene, but that onlyklf17is expressed in blastula and neural crest stem cells. Moreover, ectopic expression of lampreyklf17inXenopusembryos phenocopiesXenopus klf17activity. These data suggest that klf17, rather than klf4, may have been the ancestral klf factor that functioned in these GRNs in stem vertebrates.
Eyes-closed resting state EEG reveals clearer and more stable group differences between autistic and neurotypical individuals than eyes-open resting state EEG
Authors: Xiao Wenyi , Jones Myles , Milne Elizabeth , Dede Adam J.O 
Published: January 2025

AbstractBackgroundResting-state electroencephalography (rs-EEG) has been widely used to explore neural dynamics in Autism Spectrum Condition (ASC). However, inconsistencies in findings across studies remain a challenge, partly due to variations in brain state, such as eye conditions (eyes-open vs. eyes-closed). This study aims to examine rs-EEG differences between ASC and neurotypical (NT) participants, focusing on the influence of eye condition.MethodsA total of 300 participants (126 ASC) were included. Rs-EEG data were analysed across eyes-open, eyes-closed, and difference between eye conditions, with 726 variables assessed per participant. Linear regression and effect size (η2partial) were used to identify group differences, complemented by cluster-based permutation testing and bootstrapped split-half validation for reliability.ResultsGroup differences were most pronounced in the eyes-closed condition, particularly for relative power and multiscale entropy (MSE). Compared to neurotypical participants, ASC participants exhibited reduced frontal coarse-scale MSE, increased delta power, and decreased alpha power, suggesting altered local-global neural dynamics. Cross-validation revealed greater reliability of effects in the eyes-closed condition compared to eyes-open or difference between eye conditions.ConclusionsEye condition plays a critical role in detecting rs-EEG differences between ASC and NT groups, with the eyes-closed condition yielding more consistent and pronounced effects. These findings highlight the importance of controlling brain state in rs-EEG studies and suggest that integrating eye condition effects with other biomarkers may improve identification of neural differences associated with ASC.
Individualized Phenotyping of Functional ALS Pathology in Sensorimotor Cortex
Authors: Kalyani Avinash , Northall Alicia , Schreiber Stefanie , Brüggemann Jascha , Vielhaber Stefan , Al Dubai Marwa , Benramadan Abrar , Mattern Hendrik , Speck Oliver , Reichert Christoph , Kuehn Esther 
Published: January 2025

AbstractAmyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons in primary motor cortex (MI), leading to muscle weakness, atrophy, and death within a median of three years. Even though ALS is characterized by different disease subtypes affecting different body parts, individiualized phenotyping of functional ALS pathology has so far not been achieved. We recorded 7 Tesla functional MRI (7T-fMRI) data while ALS patients and matched controls moved affected and non-affected body parts in the MR scanner. We applied robust Shared Response Modeling (rSRM) for capturing ALS-specific shared responses for group classification, and Partial Least Squares (PLS) regression for relating the latent variables to clinical subtypes and the degree of disease progression. We show that both functional connectivity and functional activation in MI are a predictor for disease onset site. However, disease severity could best be predicted by functional connectivity rather than pure activation changes. Critically, we show that functionally disease-defining information in MI is not strongest in the area that is behaviorally first-affected, deviating from the behavioral phenotype of the patients. When computing the model’s weight distribution of the King stage classification and projecting them back into voxel space, the highest mean weights are present in the foot and tongue/face regions that seem to drive disease progress. Our data highlight the importance of 7T-fMRI task-based functional connectivity measures for classifying ALS-patients, and provide evidence that a single 7T-MRI scan can be used for identifying a disease signature of each individual ALS patient.
ATR, a DNA damage kinase, modulates DNA replication timing inLeishmania major
Authors: da Silva Gabriel L. A. , Damasceno Jeziel D. , Black Jennifer A. , McCulloch Richard , Tosi Luiz R. O. 
Published: January 2025

AbstractAll cells possess mechanisms to maintain and replicate their genomes, whose integrity and transmission are constantly challenged by DNA damage and replication impediments. In eukaryotes, the protein kinase Ataxia-Telangiectasia and Rad3-related (ATR), a member of the phosphatidylinositol 3-kinase-like family acts as a master regulator of the eukaryotic response to DNA injuries, ensuring DNA replication completion and genome stability. Here we aimed to investigate the functional relevance of the ATR homolog in the DNA metabolism ofLeishmania major, a protozoan parasite with a remarkably plastic genome. CRISPR/cas9 genome editing was used to generate a Myc-tagged ATR cell line (mycATR), and a Myc-tagged C-terminal knockout of ATR (mycATRΔC-/-). We show that the nuclear localisation of ATR depends upon its C-terminus. Moreover, its deletion results in single-stranded DNA accumulation, impaired cell cycle control, increased levels of DNA damage, and delayed DNA replication restart after replication stress. In addition, we show that ATR plays a key role in maintainingL. major’sunusual DNA replication program, where larger chromosomes duplicate later than smaller chromosomes. Our data reveals loss of the ATR C-terminus promotes the accumulation of replication signal around replicative stress fragile sites, which are enriched in larger chromosomes. Finally, we show that these alterations to the DNA replication program promote chromosome instability. In summary, our work shows that ATR acts to moderate DNA replication timing thus limiting the plasticity of theLeishmaniagenome.
ATG-3 limits Orsay virus infection inC. elegansthrough regulation of collagen pathways
Authors: Kalugotla Gowri , Marmerstein Vivien , Schriefer Lawrence A. , Wang Leran , Morrison Stephanie , Perez Luis Casorla , Schedl Tim , Pak Stephen C. , Baldridge Megan T. 
Published: January 2025

ABSTRACTAutophagy is an essential cellular process which functions to maintain homeostasis in response to stressors such as starvation or infection. Here, we report that a subset of autophagy factors including ATG-3 play an antiviral role in Orsay virus infection ofCaenorhabditis elegans. Orsay virus infection does not modulate autophagic flux, and re-feeding after starvation limits Orsay virus infection and blocks autophagic flux, suggesting that the role of ATG-3 in Orsay virus susceptibility is independent of its role in maintaining autophagic flux.atg-3mutants phenocopyrde-1mutants, which have a defect in RNA interference (RNAi), in susceptibility to Orsay virus infection and transcriptional response to infection. However,atg-3mutants do not exhibit defects in RNAi. Additionally,atg-3limits viral infection at a post-entry step, similar torde-1mutants. Differential expression analysis using RNA sequencing revealed that antiviralsqt-2, which encodes a collagen trimer protein, is depleted in naïve and infectedatg-3mutants, as well as in infected WT animals, as are numerous other collagen genes. These data suggest that ATG-3 has a role in collagen organization pathways that function in antiviral defense inC. elegans.
Interindividual differences in caries potential of the salivary microbiome after mouthwash exposure
Authors: Mermans Fabian , Poelman Britt , Saghi Mehraveh , Teughels Wim , Boon Nico 
Published: January 2025

AbstractPrevention and treatment of dental caries is often achieved by fluoride mouthwashes. The most common forms of fluoride are Stannous fluoride (SnF2), amine fluoride (AmF) and sodium fluoride (NaF), each with differing activities against oral bacteria. Additionally, differences in oral microbiome between individuals are linked to differences in response to treatment and the phenotype of the microbiome can provide information on this response. Flow cytometry can successfully track microbial phenotypic heterogeneity and may prove useful for capturing the response to treatment. In this study, we compared the effect of three fluoride-containing mouthwashes, Elmex Anti Caries (AmF/NaF), Listerine Anticaries (NaF) and Meridol (AmF/SnF2), on the salivary microbiome and assessed their anticaries potential. Furthermore, we investigated if the flow cytometric fingerprint could be used to capture the response to treatment. Saliva samples of different donors were treated with the mouthwashes and the intact salivary community composition was assessed using 16S rRNA gene amplicon sequencing. Treated saliva samples were incubated in sucrose-rich medium to assess the organic acid production of the remaining microbiota. Moreover, flow cytometric fingerprints of the intact microbial population were used to track the response to treatment and to train a random forest classifier predicting the most suitable mouthwash for the donor. We found a mouthwash-dependent shift in the salivary microbiome composition and found different anticaries potential of the mouthwashes. Meridol affected more bacterial taxa and had the best overall anticaries potential, followed by Elmex. Finally, the response to treatment could be captured in the flow cytometric fingerprint of the initial intact salivary microbiota and a random forest classifier predicting the most suitable mouthwash for the donor was successfully trained.
CO2-dependent opening of Connexin 43 hemichannels
Authors: Dospinescu Valentin-Mihai , Mascarenhas Alexander , Butler Jack , Nijjar Sarbjit , de Oliveira Taborda Kyara , Connors Sean , Huang Lumei , Dale Nicholas 
Published: January 2025

AbstractSequence and structure comparisons between alpha and beta connexins, Cx43 and Cx26, revealed that Cx43 has a motif, the carbamylation motif, that confers CO2-sensitivity on a subset of beta connexins. By using a fluorescent dye loading assay, whole cell patch clamp recordings and real time measurement of ATP release via GRABATPwe have demonstrated that Cx43 hemichannels open in a highly CO2sensitive manner over the range 20 to 70 mmHg. Mutational analysis confirms that the equivalent residues to those in Cx26 that have been shown to be involved in mediating the effects of CO2on gating of hemichannels and gap junction channels, also mediate Cx43 hemichannel gating. Our data predicts that Cx43 will be partially open and able to release ATP at resting physiological levels of PCO2. We have tested this prediction in acute hippocampal slices, by showing that CO2-dependent enhancement of synaptic transmission can be blocked by the Cx43-selective mimetic peptide Gap26. Our data resolves an inconsistency in the literature betweenin vivostudies suggesting that Cx43 hemichannels are at least partially open at rest, andin vitrostudies, performed in the absence of HCO3−/CO2buffering that show Cx43 hemichannels are shut. Our evidence suggests that the ancestral gene that duplicated to give the alpha and beta connexin clades must have possessed the carbamylation motif. CO2sensitivity is thus a fundamental ancient characteristic of several connexins that has been lost in more recently derived members of this gene family.
Cerebellar transcranial alternating current stimulation in the theta band facilitates extinction of learned fear responses
Authors: Thieme Andreas , Spisak Zsofia , Zeidan Philippe , Klein Michael , Nio Enzo , Ernst Thomas M. , Diekmann Nicolas , Göricke Sophia , Cheng Sen , Merz Christian J. , Yavari Fatemeh , Nitsche Michael A. , Batsikadze Giorgi , Timmann Dagmar 
Published: January 2025

AbstractFear extinction is a major component of exposure therapy for anxiety disorders. There is initial evidence that the cerebellum contributes to fear extinction learning, i.e., the ability to learn that certain stimuli are no longer associated with an aversive outcome. So far, however, knowledge of the cerebellum’s role in extinction is scarce. In the present study, 6 Hz cerebellar transcranial alternating current stimulation (ctACS) was used to modulate cerebellar function during extinction learning in young and healthy human participants in an MRI study. A two- day differential fear conditioning paradigm was used with acquisition and extinction training being performed on day 1, and fear extinction recall being tested on day 2. 6 Hz ctACS reduced spontaneous recovery of the initial fear association during recall, stabilizing extinction effects compared to sham ctACS. fMRI data during recall revealed significantly reduced activation in cortical areas involved in initial fear acquisition, such as the anterior cingulate and insula, in the verum ctACS group compared to the sham group. During extinction training, on the other hand, the verum group exhibited more widespread cerebral activation compared to the sham group. Group differences were significant in occipital cortical areas. Although direct stimulation effects cannot be excluded, increased activation in the visual cortex may reflect enhanced encoding and processing of visual information during fear extinction learning. The findings suggest that theta-range oscillatory interactions between the cerebellum and cortical areas support extinction processes and provide causal evidence of the cerebellar role in the human fear extinction network.Significance StatementWhile the cerebellum is well known for its role in associative learning, its contribution to fear extinction learning remains underexplored. This study used 6 Hz cerebellar transcranial alternating current stimulation (ctACS) to modulate cerebellar function during extinction training in healthy participants. The present data demonstrate that ctACS enhances cerebral cortical activation during extinction training which is followed by enhanced recall of the extinction memory and subsequently reduced activation of cerebral cortical areas associated to spontaneous recovery of fear memory. These findings provide causal evidence for the cerebelluar involvement in the human fear extinction network and suggest that enhancing cerebellar theta oscillations may be useful to support exposure therapy.
Life as a Function: Why Transformer Architectures Struggle to Gain Genome-Level Foundational Capabilities
Authors: Hassan Hassan , Puhger Kyle , Saadat Ali , Sprang Maximilian 
Published: January 2025

AbstractRecent years have seen a flurry of generative nucleotide models, mostly of limited utility. In this paper, we use the functional representation of DNA as a complex, composite function on the plane of evolution to extend the theoretical unification of ecological and evolutionary change to the problem of synthetic DNA models. Through experiments on synthetic and real DNA sequences we show that next-token prediction decoder transformer architectures are limited in their capacity to learn such functions.
Continual familiarity decoding from recurrent connections in spiking networks
Authors: Zemliak Viktoria , Pipa Gordon , Nieters Pascal 
Published: January 2025

SummaryFamiliarity memory enables recognition of previously encountered inputs as familiar without recalling detailed stimuli information, which supports adaptive behavior across various timescales. We present a spiking neural network model with lateral connectivity shaped by unsupervised spike-timing-dependent plasticity (STDP) that encodes familiarity via local plasticity events. We show that familiarity can be decoded from network activity using both frequency (spike count) and temporal (spike synchrony) characteristics of spike trains. Temporal coding demonstrates enhanced performance under sparse input conditions, consistent with the principles of sparse coding observed in the brain. We also show how connectivity structure supports each decoding strategy, revealing different plasticity regimes. Our approach outperforms LSTM in temporal generalizability on the continual familiarity detection task, with input stimuli being naturally encoded in the recurrent connectivity without a separate training stage.
Courtship vocalizations in male ducks: spectral composition and resonance of the syringeal bulla
Authors: Mishkind Darcy , Lester Michael , Tabin Clifford J. , Goller Franz 
Published: January 2025

AbstractDucks display a unique and dramatic sexual dimorphism in their vocal organ, the syrinx. Males have a left-sided bulla that is not present in females and that has been long hypothesized to play a role in courtship vocalizations, though this connection has never been tested. The large, hollow morphology of the bulla and its proximity to the sound-producing vocal folds introduce the possibility that it may work as a Helmholtz resonator, which makes it possible to predict the resonance frequencies enhanced by this structure. We find that during early ontogeny, the distribution of energy across the harmonic spectrum of contact calls is not different between males and females. We then used micro-CT scans of duck syrinxes to estimate resonance frequencies of the bullae and compared these to spectral features of their vocalizations. This comparison overall supports the idea that the bulla resonance may specifically enhance aspects of courtship vocalizations, especially in species that have a tonal courtship whistle. We also see potential influence in non-courtship vocalizations, which could be explored further with a greater understanding of the input of other vocal tract features that influence vocalization. We observed that bulla size is positively correlated with bird body mass with the largest exception in the Common Eider, which had a small bulla for its body mass and for which we saw no evidence of bulla-input to its vocalizations. This study found support for the long-held hypothesis that the adult male duck bulla influences resonance frequencies, in particular in courtship vocalizations.