bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scale-free flocking and giant fluctuations in epithelial active solids
Authors: Shen Yuan , O’Byrne Jérémy , Schoenit Andreas , Maitra Ananyo , Mege Rene-Marc , Voituriez Raphael , Ladoux Benoit 
Published: October 2024

AbstractThe collective motion of epithelial cells is a fundamental biological process which plays a significant role in embryogenesis, wound healing and tumor metastasis. While it has been broadly investigated for over a decade bothin vivoandin vitro, large scale coherent flocking phases remain underexplored and have so far been mostly described as fluid. In this work, we report a mode of large-scale collective motion for different epithelial cell types in vitro with distinctive new features. By tracking individual cells, we show that cells move over long time scales coherently not as a fluid, but as a polar elastic solid with negligible cell rearrangements. Our analysis reveals that this solid flocking phase exhibits signatures of long-range polar order, unprecedented in cellular systems, with scale-free correlations, anomalously large density fluctuations, and shear waves. Based on a general theory of active polar solids, we argue that these features result from massless Goldstone modes, which, in contrast to polar fluids where they are generic, require the decoupling of global rotations of the polarity and in-plane elastic deformations in polar solids. We theoretically show and consistently observe in experiments that the fluctuations of elastic deformations diverge for large system size in such polar active solid phases, leading eventually to rupture and thus potentially loss of tissue integrity at large scales.Significance statementDuring embryonic development and wound healing, epithelial cells usually display in-plane polarity over large spatial scales and move coherently. However, over years, mostin vitrostudies have examined the fluid-like chaotic dynamics of epithelial cells, in which collective cellular flows self-organize into recurring transient vortices and jets similar to those observed in classical fluid turbulence. Little is known about the large-scale coherent dynamics of epithelial cells. We demonstrate that such coherent motions are not simply turbulent-like flows with larger correlation lengths, but a new mode of collective motion with a solid-like behavior, accompanied by an emergent global order, scale-free correlations, anomalous density fluctuations and propagating Goldstone modes. Our work suggests that such a collective motion of epithelial cells falls outside the scope of traditional active fluids, which may shed new light on the current studies of collective cell migration as well as active matter physics.
Admixed populations in the neighbor-joining algorithm: a geometric analysis with five taxa
Authors: Zhang Joy Z. , ‘Jack’ Lo Wai Tung , Stillman Michael , Kim Jaehee 
Published: October 2024

AbstractThe Neighbor-Joining (NJ) algorithm is a widely used method for constructing phylogenetic trees from genetic distances. While NJ is known to perform well with tree-like data, its behavior under admixture remains understudied. In this work, we present a geometric framework for analyzing the NJ algorithm under a linear admixture model. We focus on three key properties related to clustering order, distance, and topological path length in the resulting NJ trees involving five taxa. Our approach leverages polyhedral geometry to define NJ cones, which correspond to distinct cherry-picking orders and partition the space of dissimilarity vectors. We project dissimilarity vectors with admixture into a lower-dimensional space without admixture, defining polyhedral regions induced by NJ cones that satisfy specified properties. We compute the exact probabilities that these properties hold by directly calculating the volumes of the induced NJ cones and compare them with Monte Carlo integration and standard NJ simulation methods. Our results show that the property on clustering order is always satisfied, while the other properties are highly probable but depend on the admixture fraction. We also prove that certain induced NJ cones have zero volume, indicating that the corresponding NJ tree topologies are infeasible under admixture. We have implemented our methods as a publicly available moduleNeighborJoiningwithinMacaulay2, providing an efficient tool for analyzing NJ cones and their properties. This work provides new insights into the geometric structure inherent to the NJ algorithm in the presence of admixture, identifying the conditions under which admixture influences the resulting phylogenetic trees.
Structural compromise in spiking cortex and connected networks
Authors: Sahlas Ella , Avigdor Tamir , Ngo Alexander , Royer Jessica , Larivière Sara , Chen Judy , Xie Ke , Wang Yezhou , Lam Jack , Rodríguez-Cruces Raúl , Arafat Thaera , Pana Raluca , Bernasconi Andrea , Bernasconi Neda , Frauscher Birgit , Bernhardt Boris C. 
Published: October 2024

ABSTRACTINTRODUCTIONEpilepsy is increasingly conceptualized as a network disorder, and advancing methods for its diagnosis and treatment requires characterizing both the epileptic generator and related networks. We combined multimodal magnetic resonance imaging (MRI) and high-density electroencephalography (HD-EEG) to interrogate alterations in cortical microstructure, morphology, and intrinsic local function within and beyond spiking tissue in focal epilepsy.METHODSWe studied 25 patients with focal epilepsy (12F, mean ± SD age = 31.28 ± 9.30 years) and 55 age- and sex-matched healthy controls, subdivided into a group of 30 for imaging feature normalization (15F, 31.40 ± 8.74 years) and a group of 25 for replication (12F, 31.04 ± 5.65 years). The 3T MRI acquisition included T1-weighted, diffusion, quantitative T1 relaxometry, and resting-state functional imaging. Open-access MRI processing tools derived cortex-wide maps of morphology and microstructure (cortical thickness, mean diffusivity, and quantitative T1 relaxometry) and intrinsic local function and connectivity (timescales, connectivity distance, and node strength) for all participants. Multivariate approaches generated structural and functional alteration scores for each cortical location. Using HD-EEG electrical source imaging, the most prominent spike type was localized and we quantified MRI alterations within spike sources, as well as in proximal and connected networks.RESULTSRegions harboring spike sources showed increased structural MRI alterations compared to the rest of the brain in patients. Structural compromise extended to all regions with close functional coupling to spike sources, but not to anatomical neighbors of spike sources. This finding was replicated using average control functional and anatomical matrices instead of patient-specific matrices.CONCLUSIONSpiking regions contain more marked alterations in microstructure and morphology than the remaining cortex, and combining imaging with neurophysiology techniques may ultimately help identify the epileptogenic zone non-invasively. There are nevertheless broader networks effects, which may relate to a cascading of structural changes to functionally connected cortices. These results underscore the utility of combining high-definition MRI and EEG approaches for characterizing epileptogenic tissue and assessing distributed network effects.
Ultrastructural viscoelastic behavior of collagen identified by AFM nano-dynamic mechanical analysis
Authors: Asgari Meisam , Mirzarazi Elahe , Vali Hojatollah , Frisina Robert D. , Espinosa Horacio D. 
Published: October 2024

AbstractSoft tissues exhibit predominantly time-dependent mechanical behavior critical for their biological function in organs like the lungs and aorta, as they can deform and stretch at varying rates depending on their function. Collagen type I serves as the primary structural component in these tissues. The viscoelastic characteristics of such tissues, stemming from diverse energy dissipation mechanisms across various length scales, remains poorly characterized at the nanoscale. Furthermore, prior experimental investigations have predominantly centered on analyzing tissue responses largely attributed to interactions between cells and fibers. Despite many studies on tissue viscoelasticity from scaffolds to single collagen fibrils, the time-dependent mechanics of collagen fibrils at the sub-fibrillar level remain poorly understood. This pioneering study employs atomic force microscopy (AFM) nano-rheometry to examine the viscoelastic characteristics of individual collagen type I fibrils at the ultrastructural level within distinct topographical zones, specifically focusing on gap and overlap regions. Our investigation has unveiled that collagen fibrils obtained viain-vitrofibrillogenesis from human placenta display a viscoelastic response that replicates the mechanical behavior of the tissue at the macroscale. Further, our findings suggest a distinct viscoelastic behavior between the gap and overlap regions, likely stemming from variances in molecular organization and cross-linking modalities within these specific sites. The results of our investigation furnish unequivocal proof of the temporal dependence of mechanical properties and provides unique data to be compared to atomistic models, laying a foundation for refining the precision of macroscale models that strive to capture tissue viscoelasticity across varying length scales.
Mosaic of Somatic Mutations in Earth’s Oldest Living Organism, Pando
Authors: Pineau Rozenn M. , Mock Karen E. , Morris Jesse , Kraklow Vachel , Brunelle Andrea , Pageot Aurore , Ratcliff William C. , Gompert Zachariah 
Published: October 2024

Understanding how mutations arise and spread through individuals and populations is fundamental to evolutionary biology. Most organisms have a life cycle with unicellular bottlenecks during reproduction. However, some organisms like plants, fungi, or colonial animals can grow indefinitely, changing the manner in which mutations spread throughout both the individual and the population. Furthermore, clonally reproducing organisms may also achieve exceedingly long lifespans, making somatic mutation an important mechanism of creating heritable variation for Darwinian evolution by natural selection. Yet, little is known about intra-organism mutation rates and evolutionary trajectories in long-lived species. Here, we study the Pando aspen clone, the largest known quaking aspen (Populus tremuloides) clone founded by a single seedling and thought to be one of the oldest studied organisms. Aspen reproduce vegetatively via new root-borne stems forming clonal patches, sometimes spanning several hectares. To study the evolutionary history of the Pando clone, we collected and sequenced over 500 samples from Pando and neighboring clones, as well as from various tissue types within Pando, including leaves, roots, and bark. We applied a series of filters to distinguish somatic mutations from the pool of both somatic and germline mutations, incorporating a technical replicate sequencing approach to account for uncertainty in somatic mutation detection. Despite root spreading being spatially constrained, we observed only a modest positive correlation between genetic and spatial distance, suggesting the presence of a mechanism preventing the accumulation and spread of mutations across units. Phylogenetic models estimate the age of the clone to between ~16,000-80,000 years. This age is generally corroborated by the near-continuous presence of aspen pollen in a lake sediment record collected from Fish Lake near Pando. Overall, this work enhances understanding of mutation accumulation and dispersal within and between ramets of long-lived, clonally-reproducing organisms.Significance StatementThis study enhances our understanding of evolutionary processes in long-lived clonal organisms by investigating somatic mutation accumulation and dispersal patterns within the iconic Pando aspen clone. The authors estimated the clone to be between 10,000 and 80,000 years old and uncovered a modest spatial genetic structure in the 42.6-hectare clone, suggesting localized mutation build-up rather than dispersal along tissue lineages. This work sheds light on an ancient organism and how plants may evolve to preserve genetic integrity in meristems fueling indefinite growth, with implications for our comprehension of adaptive strategies in long-lived perennials.
Layer-specific dynamics of local field potentials in monkey V1 during electrical stimulation
Authors: Lee Sangjun , Zhao Zhihe , Alekseichuk Ivan , Shirinpour Sina , Linn Gary , Schroeder Charles E. , Falchier Arnaud Y. , Opitz Alexander 
Published: October 2024

AbstractThe mammalian neocortex, organized into six cellular layers or laminae, forms a cortical network within layers. Layer specific computations are crucial for sensory processing of visual stimuli within primary visual cortex. Laminar recordings of local field potentials (LFPs) are a powerful tool to study neural activity within cortical layers. Electric brain stimulation is widely used in basic neuroscience and in a large range of clinical applications. However, the layer-specific effects of electric stimulation on LFPs remain unclear. To address this gap, we conducted laminar LFP recordings of the primary visual cortex in monkeys while presenting a flash visual stimulus. Simultaneously, we applied a low frequency sinusoidal current to the occipital lobe with offset frequency to the flash stimulus repetition rate. We analyzed the modulation of visual-evoked potentials with respect to the applied phase of the electric stimulation. Our results reveal that only the deeper layers, but not the superficial layers, show phase-dependent changes in LFP components with respect to the applied current. Employing a cortical column model, we demonstrate that these in vivo observations can be explained by phase-dependent changes in the driving force within neurons of deeper layers. Our findings offer crucial insight into the selective modulation of cortical layers through electric stimulation, thus advancing approaches for more targeted neuromodulation.
Targeted deletions in human mitochondrial DNA engineered by Type V CRISPR-Cas12a system
Authors: Nikitchina Natalia , Heckel Anne-Marie , Shebanov Nikita , Mazunin Ilya , Tarassov Ivan , Entelis Nina 
Published: October 2024

AbstractMutations in mitochondrial DNA (mtDNA) contribute to various neuromuscular diseases, with severity depending on heteroplasmy level when mutant and wild-type mtDNA coexist within the same cell. Developing methods to model mtDNA dysfunction is crucial for experimental therapies. Here, we adapted the Type V CRISPR-AsCas12a system, which recognizes AT-rich PAM sequences, for targeted editing of human mtDNA. We show that AsCas12a effector, fused with a mitochondrial targeting sequence (MTS) fromNeurospora crassaATPase subunit 9, is efficiently addressed into human mitochondria and induces specific mtDNA cleavage in human cells. As a proof-of-concept, we demonstrate that AsCas12a, complexed with two crRNAs targeting distant regions of human mtDNA, introduces specific deletions in mtDNA. For the first time, we provide experimental data proving that a CRISPR system can be used not only for mtDNA degradation but also for precise mtDNA manipulation, offering a potential therapeutic avenue to address mitochondrial disorders.
scAGCI: an anchor graph-based method for cell clustering from integrated scRNA-seq and scATAC-seq data
Authors: Dong Yao , Zhang Jiaxue , Shi Jin , Hu Yushan , Cao Xiaowen , Xing Li , Dong Yongfeng , Zhang Xuekui 
Published: October 2024

AbstractCell clustering plays a crucial role in the analysis of single-cell multi-omics research. Despite many methods for multi-omics integrated clustering, challenges such as noise, data sparsity, and biointerpretability analysis hider effective clustering. Recent studies have demonstrated that anchor graph learning clustering in the multiview graph domain can help alleviate sparsity and high noise, reducing runtime costs. However, addressing the heterogeneity and high noise levels in multi-omics data is crucial for obtaining a more representative anchor graph. Furthermore, the existing methods often directly obtain surface information from multi-omics for clustering purposes, neglecting the mining and utilization of higher-order correlations among different features within shared information. In response to these challenges, we propose scAGCI, a cell clustering method based on anchor graphs that integrates both scRNA-seq and scATAC-seq data. Our method captures specific and shared anchor graphs representing the properties of omics data in the process of dynamic anchor unification, and mines high-order shared information to complete the omics representation. Subsequently, clustering results are obtained by integrating the specific and shared omics representation. Extensive experiments show that our method not only outperforms 13 state-of-the-art methods in terms of clustering metrics and running time, but also that the completed omics retains the biological meaning of the original omics.
Validation of a simplified HPV genotyping assay designed for cervical screening in low-resource settings
Authors: Desai Kanan T. , Ajenifuja Kayode O. , Adepiti Clement A. , Inturrisi Federica , Dagnall Casey , Hoffman Amanda C. , Egemen Didem , Gage Julia C. , Wentzensen Nicolas , de Sanjose Silvia , Schiffman Mark 
Published: October 2024

AbstractIntroductionHuman papillomavirus (HPV) genotype predicts cervical cancer risk, and genotyping could help guide management of HPV positives as part of cervical screening. An isothermal amplification HPV extended genotyping test (ScreenFire HPV RS assay) can assay up to 96 controls/samples in one hour plus preparation time. A novel format with pre-aliquoted reagents and an anti-contamination component (Zebra BioDome™) could simplify the HPV testing process by substantially reducing the assay preparation time and the chances of post-amplification contamination. We validated Zebra BioDome formulation prior to its clinical use.MethodsResidual provider-collected cervical samples (n=450) from a population-based study in rural Nigeria were retested with ScreenFire, once using the standard assay version (liquid reagents combined onsite) and twice with Zebra BioDome. HPV results with adequate DNA (N=427) were analyzed channel-by-channel and using the cervical cancer risk-based hierarchy of HPV type channels (HPV16, else 18/45, else 31/33/35/52/58, else 39/51/56/59/68, else high-risk HPV negative) to evaluate Zebra BioDome repeatability and accuracy against the standard version.ResultsZebra BioDome reduced the number of pipetting steps to run the ScreenFire HPV assay. Following amplification, the BioDome material formed a sealant layer above the reaction components. Zebra BioDome had excellent repeatability and agreement with the standard version, both at the channel-specific analysis [positive percent agreement between 88.4% (HPV39/51/56/59/68) and 100% (HPV16); negative percent agreement between 97.8% (HPV31/33/35/52/58) and 100% (HPV39/51/56/59/68)] and hierarchical analysis (overall agreement 97.2%).ConclusionsThe assay version utilizing Zebra BioDome performed similarly to the previously validated standard version of the ScreenFire HPV assay and is now undergoing field evaluation. This solution has the potential to reduce assay preparation time and risk of contamination, providing a simpler, low-cost, near-point-of-care HPV testing and extended genotyping solution for cervical screening in lower-resource settings. Potential application of Zebra BioDome technology to other DNA amplification assays should be considered.
Synaptic accumulation of GluN2B-containing NMDA receptors mediates the effects of BDNF-TrkB signalling on synaptic plasticity and in epileptogenesis
Authors: De Luca Pasqualino , Mele Miranda , Tanqueiro Sara , Napoli Francesca , Butkevičiūtė Ugné , Souto Arthur C. , Costa Rui O. , Schwarz Alexander , Drexel Meinrad , Sebastião Ana M. , Diógenes Maria J. , Duarte Carlos B. 
Published: October 2024

AbstractBrain-derived neurotrophic factor (BDNF) is a key mediator of synaptic plasticity and memory formation in the hippocampus. However, the BDNF-induced alterations in the glutamate receptors coupled to the plasticity of glutamatergic synapses in the hippocampus have not been elucidated. In this work we investigated the putative role of GluN2B-containing NMDA receptors in the plasticity of glutamatergic synapses induced by BDNF. Stimulation of hippocampal synaptoneurosomes with BDNF led to a significant time-dependent increase in the synaptic surface expression of GluN2B-containing NMDA receptors as determined by immunocytochemistry with colocalization with pre- (vesicular glutamate transporter) and post-synaptic markers (PSD95). Similarly, BDNF induced the synaptic accumulation of GluN2B-containing NMDA receptors at the synapse in cultured hippocampal neurons, by a mechanism sensitive to the PKC inhibitor GӦ6983. The effects of PKC may be mediated by phosphorylation of Pyk2, as suggested by western blot experiments analyzing the phosphorylation of the kinase on Tyrosine 402. GluN2B-containing NMDA receptors mediated the effects of BDNF in the facilitation of the early phase of long-term potentiation (LTP) of hippocampal CA1 synapses induced by θ-burst stimulation, since the effect of the neurotrophin was abrogated in the presence of the GluN2B inhibitor Co 101244. In the absence of BDNF, the GluN2B inhibitor did not effect LTP. Surface accumulation of GluN2B-containing NMDA receptors was also observed in hippocampal synaptoneurosomes isolated from rats subjected to the pilocarpine model of temporal lobe epilepsy, after reaching Status epilepticus, an effect that was inhibited by administration of the TrkB receptor inhibitor ANA-12. Together, these results show that the synaptic accumulation of GluN2B-containing NMDA receptors mediate the effects of BDNF in the plasticity of glutamatergic synapses in the hippocampus.
H2O2repurposes the plant oxygen-sensing machinery to control the transcriptional response to oxidative stress
Authors: Akter Salma , Perri Monica , Lavilla-Puerta Mikel , Ferretti Beatrice , Dalle Carbonare Laura , Shukla Vinay , Telara Yuri , Zhang Daai , Gunawardana Dona M. , Myers William K. , Giuntoli Beatrice , Flashman Emily , Licausi Francesco 
Published: October 2024

SummaryPlants sense reduced oxygen availability (hypoxia) through Plant Cysteine Oxidases (PCOs). Reduced PCO activity in hypoxia, as seen during submergence, stabilises Group VII Ethylene Response Factors (ERFVIIs), master regulators of adaptive metabolic and anatomic responses. Equally important is timely arrest of these responses upon reoxygenation, assumed to occur through ERFVII degradation. Reoxygenation involves reactive oxygen species (ROS) production. Here, we report that instead of degradation, reoxygenation results in ERFVII nuclear stabilisation, an effect mimicked by direct H2O2treatment. Interestingly, typical hypoxia marker genes are repressed while genes involved in ROS homeostasis and oxidative stress protection are upregulated. Usingin planta, heterologous and biochemical assays, we reveal that ROS-related ERFVII stabilisation is caused by PCO inactivation. Stabilised ERFVIIs are retained at hypoxia-responsive promoters but become repressors. Our findings suggest that by responding to both oxygen and ROS, PCOs coordinate ERFVII stability to regulate timely responses to damaging fluctuations in oxygen availability.