bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-supervised image restoration in coherent X-ray neuronal microscopy
Authors: Laugros Alfred , Cloetens Peter , Bosch Carles , Schoonhoven Richard , Pavlovic Liam , Kuan Aaron T. , Livingstone Jayde , Zhang Yuxin , Kim Minsu , Hendriksen Allard , Holler Mirko , Wanner Adrian A. , Azevedo Anthony , Batenburg K. Joost , Tuthill John C. , Lee Wei-Chung Allen , Schaefer Andreas T. , Vigano Nicola , Pacureanu Alexandra 
Published: February 2025

ABSTRACTCoherent X-ray microscopy is emerging as a transformative technology for neuronal imaging, with the potential to offer a scalable solution for reconstruction of neural circuits in millimeter sized tissue volumes. Specifically, X-ray holographic nanoto-mography (XNH) brings together outstanding capabilities in terms of contrast, spatial resolution and data acquisition speed. While recent XNH developments already enabled generating valuable datasets for neuro-sciences, a major challenge for reconstruction of neural circuits remained overcoming resolving power limits to distinguish smaller neurites and synapses in the reconstructed volumes. Here we present a self-supervised image restoration approach that simultaneously improves spatial resolution, contrast, and data acquisition speed. This enables revealing synapses with XNH, marking a major milestone in the quest for generating connectomes of full mammalian brains. We demonstrate that this method is effective for various types of neuronal tissues and acquisition schemes. We propose a scalable implementation compatible with multi-terabyte image volumes. Altogether, this work brings large-scale X-ray nanotomography to a new precision level.
Identifying regulators of aged fibroblast activation in 3D tissue models
Authors: Liu Hui , Yuan Luezhen , Shivashankar G.V. 
Published: February 2025

AbstractRobust 3D tissue culture models to activate aged fibroblasts for cell-based therapies and identify regulators of such activation are still missing. In our previous study, we showed that aged fibroblasts can be activated simply through applying compressive force, without the need for exogenous factors, leading to increased migration. In this study, we develop a pipeline to evaluate the role of specific pharmacological inhibitors for transcription factor inference and cell migration involved in aged fibroblast activation. By integrating RNA-seq data with bioinformatic tools (prize collecting Steiner tree method and iRegulon) we inferred 15 candidates. In addition, we used cell migration and heterochromatin content as readouts for validating these candidates. Furthermore, we identified three potential master regulators of fibroblast activation and rejuvenation: FOXO1, STAT3, and PDK1. These findings offer valuable insights for future drug discovery, disease modeling, and regenerative medicine.
Tracing social mechanisms and interregional connections in Early Bronze Age Societies in Lower Austria
Authors: Furtwängler Anja , Rebay-Salisbury Katharina , Neumann Gunnar , Kanz Fabian , Ringbauer Harald , Bianco Raffaela , Schmidt Tanja , Semerau Lena , Radzeviciute Rita , Barquera Rodrigo , Rohland Nadin , Stewardson Kristin , Workman J. Noah , Curtis Elizabeth , Zalzala Fatma , Callan Kim , Iliev Lora , Qiu Lijun , Cheronet Olivia , Wagner Anna , Morante Guillermo Bravo , Spannagel Michaela , Teschler-Nicola Maria , Novotny Friederike , Verdianu Domnika , Pinhasi Ron , Reich David , Krause Johannes , Stockhammer Philipp W. , Mittnik Alissa 
Published: February 2025

AbstractIn this study, we present the results of archaeogenetic investigations of Early Bronze Age individuals from Lower Austria, specifically associated with the Únětice and Unterwölbling cultural groups. Through analysing newly generated genome-wide data of 138 individuals, we explore the social structure and genetic relationships within and between these communities. Our results reveal a predominantly patrilocal society with non-strict female exogamic practices. Additionally, Identity-by-Descent (IBD) analysis detects long-distance genetic connections, emphasizing the complex network of interactions in Central Europe during this period. Despite shared social dynamics, notable genetic distinctions emerge between the Únětice and Unterwölbling groups. These insights contribute to our understanding of Bronze Age population interconnections and call for a nuanced interpretation of social dynamics in this historical context.
Rigid Control of Motor Unit Firing Rates in the Human Tibialis Anterior Muscle Persists during Neurofeedback
Authors: Lee Meng-Jung , Ofner Patrick , Huang Hsien-Yung , Mulder Joris , Ibanez Jaime , Farina Dario , Mehring Carsten 
Published: February 2025

AbstractThe conventional framework of motor-unit (MU) control assumes that MUs in a MU pool are constrained by a fixed recruitment order and a common input. This rigid-control framework has been challenged by recent findings suggesting that MU activity could be flexibly modulated, potentially mediated by descending cortical inputs. In this study, rather than evaluating flexibility from the perspective of recruitment thresholds, we investigated control flexibility by assessing if human participants can voluntarily modulate MU firing rates beyond rigid-control constraints. Specifically, we examined whether participants could voluntarily modulate the firing rates of a pair of MUs from the tibialis anterior muscle during real-time feedback. Two tasks involving target-reach with different visual feedback derived from the MUs firing rates were conducted. In both tasks, there was no evidence that participants were able to change MU firing rates in a way that would violate rigid control robustly. Our findings demonstrate limited flexibility in MU control in human tibialis anterior muscle within single-session training, even when real-time MU activity feedback was provided. The results suggest that MU flexibility is not inherently present in the human lower limb.
Dopaminergic mechanisms of dynamical social specialization in mouse microsocieties
Authors: Solié C. , Nicolson A. , Justo R. , Layadi Y. , Morin B. , Batifol C. , Reynolds LM , Le Borgne T. , Fayad SL , Gulmez A. , Allegret--Vautrot J. , de Chaumont F. , Viollet C. , Didienne S. , Debray N. , Hardelin J-P. , Girard B. , Mourot A. , Naudé J. , Marti F. , Delord B. , Faure P. 
Published: February 2025

SummarySocial organization and division of labor are fundamental to animal societies, but how do these structures emerge from individual interactions, and what role does neuromodulation play in shaping them? Using behavioral tracking in a semi-natural environment, neural recordings, and computational models integrating reinforcement and social learning, we show that groups of three isogenic mice spontaneously develop specialized roles while solving a foraging task requiring individual decisions under social constraints. Moreover, these roles are shaped by dopaminergic activity in the ventral tegmental area. Strikingly, despite minor sex-differences in behavior when mice were tested alone, male triads formed stable worker-scrounger relationships driven by competition, whereas female triads adopted uniform, cooperative strategies. Model analysis revealed how intra- and inter-sex parameter differences in resource exploitation, combined with contingent and dynamic social interactions, drive behavioral specialization and labor division. Most notably, it highlighted how contingency, amplified by competition, magnifies individual differences and shapes social profiles. The plastic, adaptive nature of social organization within triads was confirmed by manipulating dopaminergic cell activity, which reshaped social roles and altered group structure. Our findings support a feedback loop where social context shapes neural states, which in turn reinforce behavioral specialization and stabilize social structures.
Whole genome sequencing reveals how plasticity and genetic differentiation underlie sympatric morphs of Arctic charr
Authors: Kurta Khrystyna , Fedi Mariano Olivera , Baker Kendall , Barker Tom , Catchpole Leah , Ciofi Claudio , Cocco Arianna , Diedericks Genevieve , Diroma Maria Angela , Hindar Kjetil , Iannucci Alessio , Irish Naomi , Knitlhoffer Vanda , Laikre Linda , Leitão Henrique G. , Lucchini Sacha , McTaggart Seanna , Pálsson Arnar , Pettersson Mats E. , Ryman Nils , Snorrason Sigurður S. , Svardal Hannes , Swarbreck David , Waterhouse Robert M. , Watkins Christopher , Xiao Han H. , Gharbi Karim , Jónsson Zophonías O. , Andersson Leif 
Published: February 2025

AbstractSalmonids have a remarkable ability to form sympatric morphs after postglacial colonization of freshwater lakes. These morphs often exhibit differences in morphology, feeding, and spawning behaviour. Here we explore the genetics of morph differentiation by establishing a high-quality, annotated reference genome for the Arctic charr and use this as a resource for population genomic analysis of morphs from two Norwegian and two Icelandic lakes. The four lakes represent the spectrum of genetic differentiation between morphs from one lake with no genetic differentiation between morphs, implying phenotypic plasticity only, to two lakes with locus-specific genetic differentiation, implying incomplete reproductive isolation, and one lake with strong genome-wide divergence consistent with complete reproductive isolation. As many as 12 putative inversions ranging from 0.45 to 3.25 Mbp in size segregated among the four morphs present in one lake, Thingvallavatn, and these contributed significantly to the genetic differentiation among morphs. None of the putative inversions was found in any of the other lakes, but there were cases of partial haplotype sharing in similar morph contrasts in other lakes. The results are consistent with a highly polygenic basis of morph differentiation with limited genetic parallelism between lakes. The results support a model where morph differentiation is usually first established due to phenotypic plasticity that results in niche expansion and separation, followed by gradual development of reproductive isolation and locus-specific differentiation and eventually complete reproductive isolation and genome-wide divergence. A major explanation for salmonids ability to diversify into multiple sympatric morphs is likely the genome complexity caused by their ancient whole genome duplication that enhances evolvability.
Long-range genomic loci stochastically assemble into combinatorial forms of chromosome skeleton
Authors: Zhang Jingyu , Wang Siyuan , Watkins Simon C , Xing Jianhua 
Published: February 2025

AbstractOne fundamental yet open question is how eukaryotic chromosomes fold into segregated territories, a process essential for gene transcription and cell fate. Through analyzing Hi-C and chromatin-tracing DNA-FISH data, we identify long-range chromo skeleton loop structures that span over 100 Mb, extending beyond the reach of loop extrusion models. Spatial density analyses point to assembly formation independent of major nuclear structures. A subset of genomic loci serves as nucleation centers, driving loop clustering. These complexes are highly stable, as shown by live-cell imaging with sequence-specific fluorescent labeling, and biophysical model analyses reveal a multivalent binding mechanism. Our findings suggest a redundant, distributed cluster mechanism that ensures robustness across cell types and against mutations, guiding both chromosome compaction and the formation of smaller-scale chromosomal structures.
3-D Reconstruction of Fingertip Deformation during Contact Initiation
Authors: Doumont Donatien , Kao Anika R , Lambert Julien , Wielant François , Gerling Gregory J , Delhaye Benoit P , Lefèvre Philippe 
Published: February 2025

AbstractDexterous manipulations rely on tactile feedback from the fingertips, which provides crucial information about contact events, object geometry, interaction forces, friction, and more. Accurately measuring skin deformations during tactile interactions can shed light on the mechanics behind such feedback. To address this, we developed a novel setup using 3-D digital image correlation (DIC) to both reconstruct the bulk deformation and local surface skin deformation of the fingertip under natural loading conditions. Here, we studied the local spatiotemporal evolution of the skin surface during contact initiation. We showed that, as soon as contact occurs, the skin surface deforms very rapidly and exhibits high compliance at low forces (<0.05 N). As loading and thus the contact area increases, a localized deformation front forms just ahead of the moving contact boundary. Consequently, substantial deformation extending beyond the contact interface was observed, with maximal amplitudes ranging from 5% to 10% at 5 N, close to the border of the contact. Furthermore, we found that friction influences the partial slip caused by these deformations during contact initiation, as previously suggested. Our setup provides a powerful tool to get new insights into the mechanics of touch and opens avenues for a deeper understanding of tactile afferent encoding.
PU.1 and TGF-β signaling transactivate CD103 expression in mast cells and dendritic cells: Opposite roles of GATA2 in the expression of mucosal mast cell-specific genes
Authors: Ishii Kenta , Nagata Kazuki , Akimoto Yuta , Zhao Weiting , Inoue Mariko , Ito Naoto , Kasakura Kazumi , Nishiyama Chiharu 
Published: February 2025

AbstractMucosal mast cells (MMCs) are distinguished from connective tissue MCs by the specific expression of integrin CD103 (αE/β7) and MC proteases Mcpt1 and Mcpt2. Although the expression of theMcpt1andMcpt2genes is cooperatively regulated by the transcription factor GATA2 and TGF-β signaling in MMCs, the transcriptional mechanism of CD103 expression remains unknown. Here, we found that surface CD103 andItgaemRNA levels were significantly increased by the knockdown (KD) ofGata2in bone marrow-derived MCs (BMMCs), which was accelerated by a TGF-β stimulation. Since the mRNA levels ofSpi1(encoding PU.1) were increased inGata2KD BMMCs, we examined the effects of PU.1 on CD103 expression. As expected, CD103 levels on BMMCs were significantly decreased bySpi1KD and increased bySpi1overexpression.Spi1KD suppressedItgaeexpression even in the presence of TGF-β in BMMCs and peritoneal MCs, whereasGata2KD amplified the TGF-β-induced increase inItgaeexpression. The amount of PU.1 binding to thecis-element in theItgaegene was significantly and moderately increased byGata2KD and the TGF-β stimulation, respectively. Since PU.1 is an essential transcription factor for dendritic cells (DCs), we examined the role of PU.1 in CD103 expression on DCs. The KD experiment using BMDCs showed a significant decrease in CD103 levels inSpi1siRNA-transfected BMDCs.We concluded that PU.1 affected CD103 expression on MMCs and DCs by transactivating theItgaegene, and also that GATA2, which positively regulated the MMC-specific expression of Mcpt1 and 2, inhibited CD103 expression by repressing PU.1.
Intrinsic immunity against HAdV is achieved by a novel epigenetic silencing complex
Authors: Mai Julia , Karimi Maryam , Kuderna Anna , Heider Anna , Günther Thomas , Friedel Caroline C. , Grundhoff Adam , Stamminger Thomas , Schreiner Sabrina 
Published: February 2025

AbstractThe DNA double-stranded genome of human adenoviruses (HAdV) is preferentially targeted by host factors involved in chromatin remodeling, such as SPOC1 and KAP1 to inhibit efficient viral gene expression. HAdV genomes undergo alterations through association with host histones and epigenetic modifications; however, the precise underlying mechanism remains elusive. A recently discovered silencing mechanism for retrotransposons and retroviruses involves the Human Silencing Hub (HUSH) complex. This complex of MPP8, TASOR, and PPHLN1 safeguards the human genome by utilizing histone H3 Lys9 trimethylation (H3K9me3) to block transcription. Through the recruitment of SETDB1 and MORC2, the HUSH complex silences host genes and condenses target genomes to combat infections such as HIV, MLV, and AAV. Here, we present evidence that the HUSH complex effectively restricts HAdV infection. To counteract the repressive function of this epigenetic silencing complex, HUSH factors are inhibited through binding of HAdV proteins and subsequent relocalization. We observe that MPP8 is targeted by the adenoviral E3 ubiquitin ligase, thus recruited by the viral early proteins E1B-55K and E4orf6 for proteasomal degradation. In summary, we provide evidence that the HUSH complex is a previously unrecognized host factor that restricts HAdV gene expression and replication. Based on these novel findings, we propose that HUSH represents a promising therapeutic target to combat HAdV infection.
Dissecting the role of RNA-binding proteins in early herpes simplex virus 1 transcription using acute protein depletion
Authors: Barke Niclas , Masser Sawinee , Stalling Doerte , Wyler Emanuel , Zinzen Robert Patrick , Schreiner Sabrina , Bosse Jens , Landthaler Markus 
Published: February 2025

AbstractHerpes simplex virus 1 (HSV-1) infects about 50-80% of the entire human population and persists in the neurons of affected individuals. A fraction of affected individuals suffer from recurrent cold sores caused by reactivating virus, in rare but severe cases the virus can cause encephalitis.During lytic infection, the virus relies on host factors such as RNA polymerase II and accessory proteins involved in transcription to express its genes and ensure successful replication. In general, RNA molecules in cells are bound by RNA-binding proteins (RBPs) during their entire lifecycle. Importantly, RBPs are increasingly described to also regulate transcription, an aspect long time outside the scope of investigations, especially during viral infections. Here, we examined the impact of five nuclear proteins (FUBP1, SLBP, SFPQ, SPT5 and SAF-B) with known RNA-binding activities on HSV-1 transcription. Additionally, we evaluated their importance for human adenovirus C5 (HAdV) growth to assess whether these host factors are specific to HSV-1 infections or might have broader relevance for the general transcription of dsDNA viruses.We show that the transcriptional elongation factor SPT5 coded by SUPT5H accumulates on HSV-1 genomes early during the infection and is required for the transcription of the immediate-early gene UL54. Its depletion affects also HAdV replication, indicating a general role in transcription of viruses that depend on the host transcriptional machinery.In contrast, depletion of the transcriptional repressor and paraspeckle protein SFPQ reduces UL54 RNA levels in HSV-1 infection, but does not cause significant changes in HAdV growth. Since SFPQ does not co-localize with HSV-1 genomes, this suggests a function not directly associated to viral DNA.
Eye blinks synchronize with musical beats during music listening
Authors: Wu Yiyang , Teng Xiangbin , Du Yi 
Published: February 2025

AbstractAuditory-motor synchronization, the alignment of body movements with rhythmic patterns in music, is a universal human behavior, yet its full scope remains incompletely understood. Through four experiments with 123 young non-musicians, integrating eye-tracking, neurophysiological recordings, white matter structural imaging, and behavioral analysis, we reveal a previously unrecognized form of synchronization: spontaneous eye blinks synchronize with musical beats. Blinks robustly synchronized with beats across a range of tempi and independently of melodic cues. EEG recordings revealed a dynamic correspondence between blink timing and neural beat tracking. Individual differences in blink synchronization were linked to white matter microstructure variation in the left arcuate fasciculus, a key sensorimotor pathway. Additionally, the strength of blink synchronization reflected the modulation of dynamic auditory attention. These findings establish blink synchronization as a novel behavioral paradigm, expanding the auditory-motor synchronization repertoire and highlighting the intricate interplay between music rhythms and oculomotor activity. This discovery underscores a cross-modal active sensing mechanism, offering new insights into embodied music perception, rhythm processing, and their potential clinical applications.
Deep Learning Derived Adipocyte Size Reveals Adipocyte Hypertrophy is under Genetic Control
Authors: Jørsboe Emil , Kubitz Phil , Honecker Julius , Flaccus Andrea , Mvondo Dagmar , Raggi Matthias , Hansen Torben , Hauner Hans , Blüher Matthias , Charles Philip D. , Lindgren Cecilia M. , Nellåker Christoffer , Claussnitzer Melina 
Published: February 2025

AbstractFat distribution and macro structure of white adipose tissue are important factors in predicting obesity-associated diseases, but cellular microstructure of white adipose tissue has been less explored. To investigate the relationship between adipocyte size and obesity-related traits, and their underlying disease-driving genetic associations, we performed the largest study of automatic adipocyte phenotyping linking histological measurements and genetics to date. We introduce deep learning based methods for scalable and accurate semantic segmentation of subcutaneous and visceral adipose tissue histology samples (N=2,667) across 5 independent cohorts, including data from 9,000 whole slide images, with over 27 million adipocytes. Estimates of mean size of adipocytes were validated against Glastonbury et al. 2020. We show that adipocyte hypertrophy correlates with an adverse metabolic profile with increased levels of leptin, fasting plasma glucose, glycated hemoglobin and triglycerides, and decreased levels of adiponectin and HDL cholesterol. We performed the largest GWAS (NSubcutaneous= 2066, NVisceral= 1878) and subsequent meta-analysis of mean adipocyte area, and find two genome-wide significant loci (rs73184721, rs200047724) associated with increased 95%-quantile adipocyte size in respectively visceral and subcutaneous adipose tissue. Stratifying by sex, in females we find two genome-wide significant loci, with one variant (rs140503338) associated with increased mean adipocyte size in subcutaneous adipose tissue, and the other (rs11656704) is associated with decreased 95%-quantile adipocyte size in visceral adipose tissue.
Astrocytic PI3Kα controls synaptic plasticity and cognitive function via serine metabolism
Authors: Fernández-Rodrigo Alba , García-Vilela Celia , Eraso-Pichot Abel , López-Merino Esperanza , Maroto Irene B. , Gutiérrez-Eisman Silvia , Sánchez-Castillo Carla , Boers-Escuder Cristina , Merino-Casamayor Eneko , Graupera Mariona , Cuartero María I. , Quintana Albert , Marsicano Giovanni , Esteban José A. 
Published: February 2025

SUMMARYAstrocytes are known to modulate neuronal activity by gliotransmission and through metabolic regulation. However, the connection between these two processes is still poorly defined. In this work we show that the p110α isoform of the phosphatidylinositol 3-kinase (PI3K) in astrocytes is required for long-term potentiation (LTP) and has an impact on learning and memory. Using a specific deletion of p110α from hippocampal astrocytes in adult mice, we found that LTP depends on astrocytic p110α to sustain D-serine levels for the activation of NMDA receptors during LTP induction. This requirement is based on the L-serine biosynthetic pathway of the astrocyte, which is defective in the absence of p110α because of a reduced glycolytic flux. Accordingly, the behavioral impairment in mice lacking p110α can be rescued byin vivoadministration of L-serine. These results link for the first time the function of PI3K in astrocytes to cerebral metabolism and its influence in synaptic plasticity and cognition.