bluuebunny/crossref_metadata_2025_split huggingface dataset:
Region-specific mean field models enhance simulations of local and global brain dynamics
Authors: Lorenzi Roberta Maria , Palesi Fulvia , Casellato Claudia , Gandini Wheeler-Kingshott Claudia A.M. , D’Angelo Egidio 
Published: January 2025

AbstractBrain dynamics can be simulated using virtual brain models, in which a standard mathematical representation of oscillatory activity is usually adopted for all cortical and subcortical regions. However, some brain regions have specific microcircuit properties that are not recapitulated by standard oscillators. Moreover, magnetic resonance imaging (MRI)-based connectomes may not be able to capture local circuit connectivity. Region-specific models incorporating computational properties of local neurons and microcircuits have recently been generated using the mean field (MF) approach and proposed to impact large-scale brain dynamics. Here we have used a MF of the cerebellar cortex to generate a mesoscopic model of the whole cerebellum featuring a prewired connectivity of multiple cerebellar cortical areas with deep cerebellar nuclei. This multi-node cerebellar mean field model was then used to substitute the corresponding standard oscillators and build up a cerebellar mean field virtual brain (cMF-TVB), for a group of healthy human subjects. Simulations revealed that electrophysiological and fMRI signals generated by the cMF-TVB significantly improved the fitness of local and global dynamics with respect to a homogeneous model made solely of standard oscillators. The cMF-TVB reproduced the rhythmic oscillations and coherence typical of the cerebellar circuit and allowed to correlate electrophysiological and functional MRI signals to specific neuronal populations. In aggregate, region-specific models based on MF technology and pre-wired circuit connectivity can significantly improve virtual brain simulations fostering the generation of effective brain digital twins that could be used for physiological studies and clinical applications.
Computationally designed stem-epitope mimetics elicit broadly reactive antibodies
Authors: Wehrle Sarah , Scheck Andreas , Reusch Laura , Matassoli Flavio , Georgeon Sandrine , Castro Karla M. , Cramer Johannes , Harshbarger Wayne , Rosset Stéphane , Andrews Sarah F. , Schön Karin , Bouzya Badiaa , Rouxel Ronan , Blais Normand , Malito Enrico , McDermott Adrian , Krey Thomas , Mallett Corey P. , Vassilev Ventzislav , Angeletti Davide , Correia Bruno E. 
Published: January 2025

AbstractBroad protection against diverse influenza viruses can be conferred by broadly neutralizing antibodies (bnAbs) targeting a conserved site on the hemagglutinin (HA) stem domain. However, the low immunogenicity of this antigenic region hinders the robust induction of such antibodies. Here, we showcase a structure-based immunogen design strategy focusing on the surface mimicry of antigenic sites. By leveraging the structural definition of a stem epitope, we apply computational protein design to develop epitope mimetics to focus the immune response against this site of viral vulnerability. The structurally complex antigenic site is displayed on heterologous protein scaffolds, retaining excellent binding towards known HA stem-specific bnAbs. Our epitope-mimetic induces stem-specific antibodies against highly divergent group 1 and 2 subtypes. The results provide a general framework for the design of novel immunogens eliciting focused immune responses which may be a valuable tool in the development of effective vaccine candidates against other variable pathogens.
Oxidative stress leads to Fur-mediated activation offtnAinEscherichia coliindependently of OxyR/SoxRS regulators
Authors: Matveeva Valeriia O. , Grebennikova Anna D. , Sakharov Daniil I. , Fomin Vadim V. , Manukhov Ilya V. , Bazhenov Sergey V. 
Published: January 2025

AbstractFerritin FtnA is the main scavenger of Fe2+and storage of Fe3+in bacterial cells, together with Dps and Bfr preventing the Fenton reaction and thus protecting the cell from iron-induced oxidative stress. However, until now, it was not known how its expression is regulated under conditions of oxidative stress, and the available evidence was contradictory. To study the regulation ofE. coli ftnAexpression in response to oxidative stress, PftnA-luxCDABEtranscriptional fusion in different strains was used. It has been shown that PftnAis induced after the addition of oxidative stress inducers. The maximum amplitude of this activation did not depend on the presence of functional genesoxyRandsoxRin the cell, but completely disappeared in the absence offur. The response is amplified in theftnAmutant and is diminished in the FtnA-overproducing strain, which indicates that iron sequestration blocks the response. Exposure of a cell to H2O2initially inactivates Fur and a number of iron-utilizing proteins, and derepresses iron uptake. This results in an increase in the cellular iron content with the consequent Fur reactivation, which leads to the induction offtnAexpression. Thus, oxidative stress leads to PftnAactivation, which is mediated by Fur and time-delayed in comparison with OxyR-response.
A pan-cancer atlas of T cell targets
Authors: Li Guangyuan , Guzman-Bringas Omar Uriel , Sharma Aman , Harpaz Zachary , Tardio Ethan , Natarajan Aswin , Liu Xinya , Taylor Darren , Yamin Rachel , Dellacherie Maxence , Krogsgaard Michelle , Cruz C. Russell Y. , Yarmarkovich Mark 
Published: January 2025

AbstractT-cell-based immunotherapies have revolutionized cancer treatment, yet only a minority of patients respond to these approaches, significantly constrained by the limited knowledge of tumor-specific antigens. Here we present a comprehensive map of T cell targets across 21 cancer types, revealing actionable tumor-specific targets in 86% of tumors. To define the repertoire of actionable T cell targets, we conducted a comprehensive pan-cancer analysis integrating data from 7,473 RNA-Seq datasets, 1,564 immunopeptidomes and 208 cancer single-cell datasets, comparing these against 17,384 normal samples covering 51 tissues. Our analysis uncovered 88 viable surface protein targets and 15,079 tumor-specific HLA-presented antigens, deriving from 11 distinct molecular events, across 21 tumor types, providing a comprehensive resource for T-cell-based immunotherapy development. We highlight 128 promising new tumor targets and validate 20 targets across five antigen classes. Among the antigens uncovered, we highlight 339 previously uncharacterized neoantigens, a new PMEL splicing peptide that we expect to be a superior antigen to the clinical target, novel self-antigens, peptides derived from ORFs previously unknown to encode proteins, and novel tumor-specific microbial targets. These findings significantly expand the therapeutic landscape of T cell therapies. To catalyze therapeutic development, we have made our pan-cancer target atlas and accompanying toolkit available to the scientific community and expect these resources will pave the way for immunotherapies across multiple cancers.SignificanceWe identified 88 viable membrane proteins and 15,079 tumor-specific HLA-presented antigens across 21 cancer types through a pan-cancer analysis of RNA-Seq, immunopeptidomes, and normal tissues. This comprehensive atlas highlights diverse antigen classes and key HLA presentation factors, providing a vital resource to catalyze T-cell based immunotherapy development and enhance understanding of antigen presentation and tumor biology.
Ultra-deep sequencing of somatic mutations induced by a maize transposon
Authors: Scherer Justin , Hinczewski Michael , Nelms Brad 
Published: January 2025

AbstractCells accumulate mutations throughout development, contributing to cancer, aging, and evolution. Quantitative data on the abundance ofde novomutations within plants or animals are limited, as new mutations are often rare within a tissue and fall below the limits of current sequencing depths and error rates. Here, we show that mutations induced by the maize Mutator (Mu) transposon can be reliably quantified down to a detection limit of 1 part in 12,000. We measured the abundance of millions ofde novoMu insertions across four tissue types. Within a tissue, the distribution ofde novoMu allele frequencies was highly reproducible between plants, showing that, despite the stochastic nature of mutation, repeated statistical patterns of mutation abundance emerge. In contrast, there were significant differences in the allele frequency distribution between tissues. At the extremes, root was dominated by a small number of highly abundantde novoinsertions, while endosperm was characterized by thousands of insertions at low allele frequencies. Finally, we used the measured pollen allele frequencies to reinterpret a classic genetic experiment, showing that evidence for late Mu activity in pollen are better explained by cell division statistics. These results provide insight into the complexity of mutation accumulation in multicellular organisms and a system to interrogate the factors that shape mutation abundance.
A framework for constructing insect steering circuits
Authors: Mitchell Robert , Webb Barbara 
Published: January 2025

AbstractInsects perform a variety of goal-directed navigation behaviours, each of which requires a comparison between their current and desired heading direction. Recent work has uncovered such a steering circuit in the fruit flyDrosophila melanogaster. We used the available neuroanatomical and physiological descriptions to derive six general rules which can be used to construct a class of steering circuits which operate in the same way. These rules are surprisingly permissive, suggesting that across insect species, steering circuits may have differing wiring while remaining functionally identical. We simulate an extreme example and demonstrate that it is functionally identical to the reported fruit fly circuit. Further, we argue that the principled approach we apply here could be applied more generally in performing comparative analyses across different insect species.
Regulation of B cell tolerance and autoimmunity by miR-130b
Authors: Herrero-Fernández Beatriz , González-Molina María del Pilar , Gámez-Reche Laura , Prieto-Muñoz Ana M , Sanz Javier , Gonzalo Tania , Moreno Alba , Nemazee David , Xiao Changchun , Mañas Laura , González-Martín Alicia 
Published: January 2025

AbstractAutoimmune diseases represent a timely health challenge due to their increasing incidence and lack of definitive cures. Autoreactive B cells play essential roles in several autoimmune diseases, including lupus erythematosus, rheumatoid arthritis and multiple sclerosis. However, the molecular mechanisms regulating these cells remain largely unknown. In this study, we identified miR-130b as a critical regulator of B cell tolerance through an unbiased bioinformatic motif enrichment analysis of lymphocyte-expressed miRNAs. Elevated levels of miR-130b impaired the elimination of autoreactive B cells during their development, enabling their escape to peripheral tissues. Mechanistically, miR-130b hindered clonal deletion by suppressing the expression of its targets Estrogen receptor alpha (ERα) and PTEN. Notably, ERα deficiency alone was sufficient to compromise B cell tolerance, allowing autoreactive B cells to reach the periphery, where they can contribute to the development and progression of autoimmune diseases. Overall, this study advances our understanding of B cell tolerance and provides new insights into the gender differences frequently observed in autoimmunity. The identification of miR-130b and ERα as regulators of B cell tolerance opens new avenues to improve the diagnosis and treatment of autoimmune diseases.
Single-molecule tweezers decoding hidden dimerization patterns of membrane proteins within lipid bilayers
Authors: Sadongo Victor W. , Kim Eojin , Kim Seoyoon , Wijesinghe W.C. Bhashini , Lee Tae Seung , Choi Jeong-Mo , Min Duyoung 
Published: January 2025

AbstractDimerization of transmembrane (TM) proteins is an essential biological process within cellular membranes, playing a key role in diverse pathophysiological pathways and serving as a promising therapeutic target. Although often simplified as a two-state transition from freely diffusing monomers to fully formed dimers, the dimerization process after monomer diffusion—the post-diffusion dimerization—is likely more complex due to intricate inter-residue interactions. Here, we introduce a single-molecule tweezer platform to map detailed profiles of the post-diffusion transitions in TM protein dimerization. This approach captures reversible dimerization events of a single TM dimer, revealing hidden intermediate states that emerge following the quiescent phase of monomer diffusion. Profiling the post-diffusion intermediates, kinetics, and energy landscapes—integrated with molecular dynamics simulations—uncovers the dimerization pathway, the effects of residue interactions and lipid bilayers, and the kinetic and energetic contributions of distinct dimerization domains. Furthermore, this platform characterizes selective and localized modulations via peptide binding, underscoring its potential to elucidate the mechanisms of action of TM dimer-targeting drugs at single-molecule resolution.
Demonstrating the need for long inter-stimulus intervals when studying the post-movement beta rebound following a simple button press
Authors: Bailey Lyam M. , Bardouille Timothy 
Published: January 2025

AbstractVoluntary movements reliably elicit event-related synchronization of oscillatory neuronal rhythms in the beta (15-30 Hz) range immediately following movement offset, as measured by magneto/electroencephalography (M/EEG). This response has been termed the post-movement beta rebound (PMBR). While early work on the PMBR advocated for long inter-stimulus intervals (ISIs)—arguing that the PMBR might persist for several seconds—these concerns have since fallen by the wayside, with many recent studies employing very short (< 5 s) ISIs. In this work we interrogated sensor-level MEG time courses in 635 individuals who participated in a cued button- pressing paradigm as part of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) project. We focussed on a subset of trials in which button presses were separated by at least 15 seconds and, using curve modelling and Bayesian inference, estimated the point at which beta power returned to baseline levels. We show that beta power takes around 4-5 seconds to return to baseline levels following movement. These results have important implications for experimental design. The PMBR is ubiquitously defined relative to a preceding baseline period; we argue that short ISIs preclude true baseline estimation and, in turn, accurate estimation of PMBR magnitude. We recommend that future studies targeting the PMBR use ISIs of at least 7 seconds—5 seconds for beta power to return to baseline, plus a 1-2 second period for proper baseline estimation. Further work is needed to clarify PMBR duration in the context of different sensorimotor paradigms and clinical populations.
Intraluminal pressure triggers a rapid and persistent reinforcement of endothelial barriers
Authors: Bancaud Aurélien , Nakajima Tadaaki , Suehiro Jun-Ichi , Alric Baptiste , Morfoisse Florent , Cacheux Jean , Matsunaga Yukiko T. 
Published: January 2025

AbstractIn response to mechanical cues, endothelial cells elicit highly sensitive cellular response pathways that contribute to the regulation of the physiology and disorders of the vascular system. However, it remains relatively unexplored how endothelial tissues process and integrate the intraluminal pressure, and in turn regulate the permeation flow across the vessel wall. Leveraging a tissue engineering approach to create microvessels (MVs), we measured real-time permeation flow induced by intraluminal pressures ranging from 0.1 to 2.0 kPa. Our findings reveal that mechanically stimulated MVs strengthen their barrier function within seconds of exposure to pressures below 1 kPa, with this enhanced barrier function persisting for 30 minutes. We demonstrate that this barrier reinforcement is linked to the closure of paracellular gaps. Additionally, we observe that it is associated with, and depends on, actin cytoskeleton reorganization, including the accumulation of stress fibers near intercellular junctions and the broadening of adherence junction protein localization. These findings provide insights into the ability of endothelial tissues to regulate interstitial fluid flow in response to sudden increases in blood pressure.
Integrative spatial transcriptomic analysis pinpoints the role of TaMCO3 encoding ferroxidase in wheat root tip iron mobilization
Authors: Joon Riya , Singh Gourav , Tyagi Deepshikha , Meena Varsha , Shukla Vishnu , Agrwal Kanupriya , Banoo Hamida , Satbhai Santosh , Singh Jagtar , Long Terri , Ramireddy Eswarayya , Pandey Ajay K 
Published: January 2025

SummaryIron (Fe) deficiency triggers molecular responses in plant roots, but the specific involvement of root tips in nutrient responses remains unclear. Therefore, in this study, we conducted a transcriptome analysis of wheat root tips under Fe deficiency, and a comparative transcriptome analysis was performed with the total root dataset. Gene ontology analysis highlighted the significance of oxidoreductase activity and metal/ion transport in the root tip tissue, which are critical for iron mobilisation. Interestingly, wheat displayed varying gene expression levels arising from the three genomes (A, B, and D) yet contributed to similar molecular functions. Detailed analysis of the oxidoreductase function in the root tip identified multiplemulti-copperoxidase (MCO) proteins possibly contributing to the total ferroxidase activity. Detailed characterisation of Fe-responsiveTaMCO3shows that it complements the yeast FET3 mutant and rescues the Fe-deficiency sensitivity phenotype ofArabidopsis atmco3mutants by enhancing vascular iron loading. Transgenic wheat lines overexpressing TaMCO3 exhibited increased root iron accumulation and improved tolerance to Fe deficiency by augmenting the expression of Fe-mobilizing genes. Our findings highlight the role of spatially resolved gene expression in Fe deficiency responses, suggesting strategies to reprogram cells for improved nutrient stress tolerance.
Towards a monograph of marine Verrucariaceae in Southern South America and maritime Antarctica: Integrative taxonomy reveals a previously unknown diversity
Authors: Fernández-Costas Daniel , Schiefelbein Ulf , Sancho Leopoldo G. , de los Ríos Asunción , Pérez-Ortega Sergio 
Published: January 2025

ABSTRACTThe family of predominantly lichen-forming Verrucariaceae, contains several lineages that have adapted to live in the stressful conditions of the intertidal and supralittoral zones of rocky seashores in both hemispheres. The marine Verrucariaceae has been the subject of several systematic and taxonomic studies over the past few decades, although these studies have primarily concentrated on groups from the northern hemisphere. This study aims to address the paucity of taxonomic studies in the southern hemisphere by examining a substantial number of specimens collected in Southern South America and maritime Antarctica over the past two decades by the authors. We opted for an integrative taxonomic approach that joins the characterization and measurement of morpho-anatomical characters, coupled together with molecular barcoding to produce species delimitations to overcome the difficulties derived by the scarcity of taxonomic characters and the high plasticity of those characters. We barcoded a total of 301 specimens using the universal barcode un fungi (nrITS) and used single-locus species delimitation algorithms (ASAP, PTP, GMYC) to produce candidate species hypothesis that were corroborated with the morphological data. Our findings indicate that the taxonomic diversity of the Southern HemisphereVerrucariamarina group has been significantly underestimated in previous studies. A total of 27 species were found in the region, 21 of which represent new taxa for science. Thorough descriptions together with illustrations showing the main characters of the species are provided for each taxon. In addition, we explored the systematics of the new taxa. We reconstructed the phylogenetic relationships of the family based on on six molecular markers (ITS, mcm7, nrSSU, nrLSU, mtSSU, RPB1). Our results showed that marine Verrucariaceae from the studied area belong to two distinct and non-related clades. A small group of species were related to the northern hemisphere speciesTurgidosculum ulvae. The second and more numerous group, which included the characteristic speciesMastodia tessellatafor a clade sister to the European genusVerrucariopsis. The systematic consequences of our findings are discussed. None of the previously reported species from the northern hemisphere and considered bipolar were found during our study.
Simulation and quantitative analysis of spatial centromere distribution patterns
Authors: Keikhosravi Adib , Guin Krishnendu , Pegoraro Gianluca , Misteli Tom 
Published: January 2025

AbstractA prominent feature of eukaryotic chromosomes are centromeres, which are specialized regions of repetitive DNA required for faithful chromosome segregation during cell division. In interphase cells centromeres are non-randomly positioned in the three-dimensional space of the nucleus in a cell-type specific manner. The functional relevance and the cellular mechanisms underlying this observation are unknown, and quantitative methods to measure distribution patterns of centromeres in 3D space are needed. Here we have developed an analytical framework that combines robust clustering metrics and advanced modeling techniques for the quantitative analysis of centromere distributions at the single cell level. To identify a robust quantitative measure for centromere clustering, we benchmarked six metrics for their ability to sensitively detect changes in centromere distribution patterns from high-throughput imaging data of human cells, both under normal conditions and upon experimental perturbation of centromere distribution. We find that Ripley’s K Score has the highest accuracy with minimal sensitivity to variations in centromeres number, making it the most suitable metric for measuring centromere distributions. As a complementary approach, we also developed and validated spatial models to replicate centromere distribution patterns, and we show that a radially shifted Gaussian distribution best represents the centromere patterns seen in human cells. Our approach creates tools for the quantitative characterization of spatial centromere distributions with applications in both targeted studies of centromere organization as well as in unbiased screening approaches.