bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell Cycle-Dependent TICRR/TRESLIN and MTBP Chromatin Binding Mechanisms and Patterns
Authors: Noble Tyler D. , Sansam Courtney G. , Wittig Kimberlie A. , Majchrzycka Blanka , Sansam Christopher L. 
Published: February 2024

AbstractThe selection of replication origins is a defining characteristic of DNA replication in eukaryotes, yet its mechanism in humans has not been well-defined. In this study, we use Cut&Run to examine genomic binding locations for TICRR/TRESLIN and MTBP, the human orthologs for the yeast DNA replication initiation factors Sld3 and Sld7. We mapped TRESLIN and MTBP binding in HCT116 colorectal cancer cells using asynchronous and G1 synchronized populations. Our data show that TRESLIN and MTBP binding patterns are more defined in a G1 synchronized population compared to asynchronously cycling cells. We also examined whether TRESLIN and MTBP are dependent on one another for binding. Our data suggest MTBP is dependent on TRESLIN for proper association with chromatin during G1 but not S phase. Finally, we asked whether TRESLIN and MTBP binding to chromatin requires licensed origins. Using cell lines with a non-degradable inducible Geminin to inhibit licensing, we show TRESLIN and MTBP binding does not require loaded MCMs. Altogether, our Cut&Run data provides evidence for a chromatin binding mechanism of TRESLIN-MTBP during G1 that is dependent on TRESLIN and does not require interactions with licensed origins.
A ZBP1 isoform blocks ZBP1-mediated cell death
Authors: Cai Zhi-Yu , Wu Puqi , Mo Wei , Yang Zhang-Hua 
Published: February 2024

SummaryZBP1 is an interferon-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA), a type of left-handed nucleic acid. More than that, the binding of ZBP1 with Z-NA promotes cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppresser of the inflammatory signaling mediated by full-length ZBP1. Compared with ZBP1, ZBP1-S protein has Zα domains but no RHIM domains. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Rip1D325A/D325A) with Cleavage-resistant RIP1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-depedent cell death. Intriguingly,Rip1D325A/D325Acells go death spontaneously when ZBP1-S was deleted, indicating the cell death driven by ZPB1 is under the check of ZBP1-S. Thus, our findings reveal that alternative splicing ofZbp1represents an autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against auto-inflammations.HighlightZBP1-short isoform is expressed synchronously with ZBP1.ZBP1-short isoform counteracts ZBP1 mediated cell death.ZBP1-S suppresses ZBP1 signaling in an Zα-domain dependent manner.ZBP1-S prevents the autoactivation of ZBP1 inRip1D325A/D325Acells.
Meiotic drive against chromosome fusions in butterfly hybrids
Authors: Boman Jesper , Wiklund Christer , Vila Roger , Backström Niclas 
Published: February 2024

AbstractSpecies frequently differ in karyotype, but heterokaryotypic individuals may suffer from reduced fitness. Chromosomal rearrangements like fissions and fusions can thus serve as a mechanism for speciation between incipient lineages but their evolution poses a paradox. How does underdominant rearrangements evolve? One solution is the fixation of underdominant chromosomal rearrangements through genetic drift. However, this requires small and isolated populations. Fixation is more likely if a novel rearrangement is favored by a transmission bias, such as meiotic drive. Here, we investigate transmission ratio distortion in hybrids between two wood white (Leptidea sinapis) butterfly populations with extensive karyotype differences. Using data from two different crossing experiments, we uncover a transmission bias favoring the fused state at chromosome with unknown polarization in one experiment and a transmission bias favoring the unfused state of derived fusions in both experiments. The latter result support a scenario where chromosome fusions can fix in populations despite counteracting effects of meiotic drive. This means that meiotic drive not only can promote runaway chromosome number evolution and speciation, but also that this transmission bias can be a conservative force acting against karyotypic change and the evolution of reproductive isolation. Based on our results, we suggest a mechanistic model for why derived fusions may be opposed by meiotic drive and discuss factors contributing to karyotype evolution in Lepidoptera.
Energetics of the Transmembrane Peptide Sorting by Hydrophobic Mismatch
Authors: Fábián Balázs , Javanainen Matti 
Published: February 2024

AbstractHydrophobic mismatch between a lipid membrane and embedded transmembrane peptides or proteins plays a role in their lateral localization and function. Earlier studies have resolved numerous mechanisms through which the peptides and membrane proteins adapt to mismatch, yet the energetics of lateral sorting due to hydrophobic mismatch has remained elusive due to the lack of suitable computational or experimental protocols. Here, we pioneer a molecular dynamics simulation approach to study the sorting of peptides along a membrane thickness gradient. Peptides of different lengths tilt and diffuse along the membrane to eliminate mismatch with a rate directly proportional to the magnitude of mismatch. We extract the 2-dimensional free energy profiles as a function of local thickness and peptide orientation, revealing the relative contributions of sorting and tilting, and suggesting their thermally accessible regimes. Our approach can readily be applied to study other membrane systems of biological interest where hydrophobic mismatch, or membrane thickness in general, plays a role.TOC Graphic
Transdifferentiation of Human Dental Pulp Mesenchymal Stem Cells into Spiral Ganglion-like Neurons
Authors: Messat Yassine , Martin-Fernandez Marta , Assou Said , Chung Keshi , Guérin Frederic , Gergely Csilla , Cuisinier Frederic , Zine Azel 
Published: February 2024

AbstractSpiral ganglion neurons (SGN) carry auditory information from sensory hair cells (HCs) to the brain. These auditory neurons, which are the target neurons of cochlear implants, degenerate following sensorineural hearing loss (SNHL). Prosthetic devices such as cochlear implants function by bypassing lost HCs and stimulating the residual SGNs, allowing restoration of hearing in deaf patients. Emerging cell-replacement therapies for SNHL include replacing damaged SGNs using stem cell-derived otic neuronal progenitors (ONPs). However, the availability of renewable, accessible, and patient-matched sources of human stem cells constitutes a major prerequisite towards cell replacement for auditory nerve recovery. Human dental pulp stem cells (hDPSCs) extracted from human wisdom teeth are self-renewing stem cells that originate from the neural crest during development.In this study, we developed a stepwisein vitroguidance procedure to differentiate hDPSCs into ONPs and then to SGNs. The procedure relies on the modulation of BMP and TGF-β pathways for neurosphere formation as a first step, then a differentiation step based on two culture paradigms exploiting major signaling pathways (Wnt, Shh, RA) and neurotrophic factors involved in early otic neurogenesis.Gene and protein expression analyses revealed efficient induction of a comprehensive panel of known ONP and SGN-like cell markers over the course ofin vitrodifferentiation. The use of atomic force microscopy revealed that hDPSC-derived SGN-like cells exhibit similar nanomechanical properties compared to theirin vivoSGN counterparts. Furthermore, neurites extended between hDPSC-derived ONPs and rat SGN explants 4-6 days after co-culturing, suggesting the formation of neuronal contacts. These data indicate that thein vitrodifferentiated cells closely replicate the phenotypic and nanomechanical characteristics of human SGNs, advancing our culture differentiation system to the level to be used in next-generation cochlear implants and/or inner ear cell-based strategies for SNHL.
Cancer-associated fibroblasts reveal aberrant DNA methylation across different types of cancer
Authors: Schmidt Marco , Maié Tiago , Costa Ivan G. , Wagner Wolfgang 
Published: February 2024

SummaryCancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment. Several studies demonstrated molecular differences between CAFs and normal tissue-associated fibroblasts (NAFs). In this study, we isolated CAFs and NAFs from liver tumors and analyzed their DNA methylation profiles. A subset of the CAFs exhibited aberrant DNA methylation, which was also reflected on gene expression level. The DNA methylation at liver-CAF-specific CG dinucleotides (CpGs) was associated with survival in liver cancer data. An integrative analysis with public datasets of CAFversusNAF in different cancer types, including lung, prostate, esophagus, and gastric cancer, revealed overlapping epigenetic aberrations. CpGs with common aberrations in DNA methylation included cg09809672 (EDARADD), cg07134930 (HDAC4), and cg05935904 (intergenic). Aberrant DNA methylation at these sites was associated with prognosis in several cancer types. Thus, activation of CAFs by the tumor environment is associated with characteristic epigenetic modifications that could be used as biomarkers for disease stratification.
EnhancerNet: a model for enhancer selection in dense regulatory networks recapitulates the dynamics of cell type acquisition
Authors: Karin Omer 
Published: February 2024

AbstractUnderstanding how cell identity is encoded in the genome and acquired during differentiation is a central challenge in cell biology. We derive a theoretical framework called “EnhancerNet” that models dense feedback networks involving transcription factors and enhancers, which can be parameterized from terminal cell identities without fitting unobserved variables. EnhancerNet recapitulates the dynamics of enhancer selection and cell type specification via two distinct pathways: direct reprogramming or differentiation through transient, multipotent progenitor states. These pathways capture the hallmarks of their respective counterparts in animal cells, with the model reproducing known reprogramming recipes and the complex hematopoietic differentiation hierarchy. Using EnhancerNet, we show that hierarchical progenitors emerge as transient states during differentiation and propose a method to predict their identity from terminal states. The model explains how new cell types could evolve and highlights the functional importance of distal regulatory elements with dynamic chromatin in multicellular evolution.
Beyond over- or under-sampling: autistic children’s inflexibility in sampling costly information
Authors: Lu Haoyang , Zhang Hang , Yi Li 
Published: February 2024

AbstractBackgroundEfficient information sampling is crucial for human inference and decision-making, even for young children. Information sampling is also closely associated with the core symptoms of autism spectrum disorder (ASD), since both the social interaction difficulties and repetitive behaviors suggest that autistic people may sample information from the environment distinctively. Previous research on information sampling in ASD focused mainly on adolescents and adults, and on whether they over- or under-sample. The specific ways in which autistic children sample information, especially when facing explicit costs and adapting to environmental changes, remain unclear.MethodsWe employed an adapted bead task to investigate the sampling behavior of 24 autistic and 41 neurotypical children, matched for age and IQ. In each trial of our experiment, children gathered information about an unknown target isle by drawing samples from it and then guessed the target between two isles based on their samples. In conditions where sampling was costly, children needed to weigh the benefits of information against the costs of acquiring additional samples. Through computational modeling and intricate behavioral measures, we revealed how the two groups of children differed in sampling decisions and underlying cognitive mechanisms.ResultsUnder conditions involving costs, autistic children showed less efficient sampling than their neurotypical peers. This inefficiency was due to their increased variability in the number of samples taken across trials rather than a systematic bias. Computational models indicated that while both groups shared a similar decision process, autistic children’s sampling decisions were less influenced by dynamic changes and more driven by recent evidence, thus leading to their increased sampling variation and reduced efficiency.LimitationsTo refine ASD subtyping and correlate symptom severity with behavioral characteristics and computational findings, future research may need larger participant groups and more comprehensive clinical assessments.ConclusionsThis study reveals an inefficiency of autistic children in information sampling and tracks down this inefficiency to their increased sampling variability, primarily due to their cognitive preference for more local and static information. These findings are consistent with several influential behavioral theories of ASD and highlight the needs of a multi-level understanding of cognitive flexibility in ASD.
Stressor-evoked brain activity, cardiovascular reactivity, and subclinical atherosclerosis in midlife adults
Authors: Rasero Javier , Verstynen Timothy D. , DuPont Caitlin M. , Kraynak Thomas E. , Barinas-Mitchell Emma , Scudder Mark R. , Kamarck Thomas W. , Sentis Amy I. , Leckie Regina L. , Gianaros Peter J. 
Published: February 2024

ABSTRACTBackgroundCardiovascular responses to psychological stressors have been separately associated with preclinical atherosclerosis and hemodynamic brain activity patterns across different studies and cohorts; however, what has not been established is whether cardiovascular stress responses reliably link indicators of stressor-evoked brain activity and preclinical atherosclerosis that have been measured in the same individuals. Accordingly, the present study used cross-validation and predictive modeling to test for the first time whether stressor-evoked systolic blood pressure (SBP) responses statistically mediated the association between concurrently measured brain activity and a vascular marker of preclinical atherosclerosis in the carotid arteries.Methods624 midlife adults (aged 28-56 years, 54.97% female) from two different cohorts underwent two information-conflict fMRI tasks, with concurrent SBP measures collected. Carotid artery intima-media thickness (CA-IMT) was measured by ultrasonography. A mediation framework that included harmonization, cross-validation, and penalized principal component regression was then employed, while significant areas in possible direct and indirect effects were identified through bootstrapping. Sensitivity analysis further tested the robustness of findings after accounting for prevailing levels of cardiovascular disease risk and brain imaging data quality control.ResultsTask-averaged patterns of hemodynamic brain responses exhibited a generalizable association with CA-IMT, which was mediated by an area-under-the-curve measure of aggregate SBP reactivity. Importantly, this effect held in sensitivity analyses. Implicated brain areas in this mediation included the ventromedial prefrontal cortex, anterior cingulate cortex, insula and amygdala.ConclusionsThese novel findings support a link between stressor-evoked brain activity and preclinical atherosclerosis accounted for by individual differences in corresponding levels of stressor-evoked cardiovascular reactivity.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Household Transmission during the Omicron Era in Massachusetts: A Prospective, Case-Ascertained Study using Genomic Epidemiology
Authors: Banga Jaspreet , Brock-Fisher Taylor , Petros Brittany A. , Dai Eric Y. , Leonelli Ariana T. , Dobbins Sabrina T. , Messer Katelyn S. , Nathanson Audrey B. , Capone Amelia , Littlehale Nancy , Appiah-Danquah Viola , Dim Siang , Moreno Gage K. , Crowther Maura , Lee Kannon A. , DeRuff Katherine C. , MacInnis Bronwyn L. , Springer Michael , Sabeti Pardis C. , Stephenson Kathryn E. 
Published: February 2024

AbstractBackgroundHouseholds are a major setting for SARS-CoV-2 infections, but there remains a lack of knowledge regarding the dynamics of viral transmission, particularly in the setting of widespread pre-existing SARS-CoV-2 immunity and evolving variants.MethodsWe conducted a prospective, case-ascertained household transmission study in the greater Boston area in March-July 2022. Anterior nasal swabs, along with clinical and demographic data, were collected for 14 days. Nasal swabs were tested for SARS-CoV-2 by PCR. Whole genome sequencing was performed on high-titer samples.ResultsWe enrolled 33 households in a primary analysis set, with a median age of participants of 25 years old (range 2-66); 98% of whom had received at least 2 doses of a COVID-19 vaccine. 58% of households had a secondary case during follow up and the secondary attack rate (SAR) for contacts infected was 39%. We further examined a strict analysis set of 21 households that had only 1 PCR+ case at baseline, finding an SAR of 22.5%. Genomic epidemiology further determined that there were multiple sources of infection for household contacts, including the index case and outside introductions. When limiting estimates to only highly probable transmissions given epidemiologic and genomic data, the SAR was 18.4%.ConclusionsHousehold contacts of a person newly diagnosed with COVID-19 are at high risk for SARS-CoV-2 infection in the following 2 weeks. This is, however, not only due to infection from the household index case, but also because the presence of an infected household member implies increased SARS-CoV-2 community transmission. Further studies to understand and mitigate household transmission are needed.Key PointsWhen community transmission of SARS-CoV-2 is high, distinguishing household transmissions from independent introductions is difficult with either epidemiologic or genomic data alone. Here, we conducted daily nasal sampling with genomic sequencing to understand the dynamics of viral transmission within households.
Perineuronal nets in the rat medial prefrontal cortex alter hippocampal-prefrontal oscillations and reshape cocaine self-administration memories
Authors: Wingert Jereme C. , Ramos Jonathan D. , Reynolds Sebastian X. , Gonzalez Angela E. , Rose R. Mae , Hegarty Deborah M. , Aicher Sue A. , Bailey Lydia G. , Brown Travis E. , Abbas Atheir I. , Sorg Barbara A. 
Published: February 2024

AbstractThe medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement behavior in rodent models of cocaine use disorder. Output from the mPFC is modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets (PNNs). Here we tested whether chondroitinase ABC (ABC)- mediated removal of PNNs prevented the acquisition or reconsolidation of a cocaine self-administration memory. ABC injections into the dorsal mPFC prior to training attenuated the acquisition of cocaine self-administration. Also, ABC given 3 days prior to but not 1 hr after memory reactivation blocked cue-induced reinstatement. However, reduced reinstatement was present only in rats given anovelreactivation contingency, suggesting that PNNs are required for the updating of a familiar memory. In naive rats, ABC injections into mPFC did not alter excitatory or inhibitory puncta on PV cells but reduced PV intensity. Whole-cell recordings revealed a greater inter-spike interval 1 hr after ABC, but not 3 days later.In vivorecordings from the mPFC and dorsal hippocampus (dHIP) during novel memory reactivation revealed that ABC in the mPFC prevented reward-associated increases in beta and gamma activity as well as phase-amplitude coupling between the dHIP and mPFC. Together, our findings show that PNN removal attenuates the acquisition of cocaine self-administration memories and disrupts reconsolidation of the original memory when combined with a novel reactivation session. Further, reduced dHIP/mPFC coupling after PNN removal may serve as a key biomarker for how to disrupt reconsolidation of cocaine memories and reduce relapse.
A retinotopic reference frame for space throughout human visual cortex
Authors: Szinte Martin , de Hollander Gilles , Aqil Marco , Veríssimo Inês , Dumoulin Serge , Knapen Tomas 
Published: February 2024

SummaryWe perceive a stable visual world across eye movements, despite the drastic retinal transients these movements produce. To explain vision’s spatial stability, it has been suggested that the brain encodes the location of attended visual stimuli in an external, or spatiotopic, reference frame. However, spatiotopy is seemingly at odds with the fundamental retinotopic organization of visual inputs. Here, we probe the spatial reference frame of vision using ultra-high-field (7T) fMRI and single-voxel population receptive field mapping, while independently manipulating both gaze direction and spatial attention. To manipulate spatial attention, participants performed an equally demanding visual task on either a bar stimulus that traversed the visual field, or a small foveated stimulus. To dissociate retinal stimulus position from its real-world position the entire stimulus array was placed at one of three distinct horizontal screen positions in each run. We found that population receptive fields in all cortical visual field maps shift with the gaze, irrespective of how spatial attention is deployed. This pattern of results is consistent with a fully retinotopic reference frame for visual-spatial processing. Reasoning that a spatiotopic reference frame could conceivably be computed at the level of entire visual areas rather than at the level of individual voxels, we also used Bayesian decoding of stimulus location from the BOLD response patterns in visual areas. We found that decoded stimulus locations also adhere to the retinotopic frame of reference, by shifting with gaze position. Again, this result holds for all visual areas and irrespective of the deployment of spatial attention. We conclude that visual locations are encoded in a retinotopic reference frame throughout the visual hierarchy.
Wearable Neural Interfaces: Real-Time Identification of Motor Neuron Discharges in Dynamic Motor Tasks
Authors: Mendez Guerra Irene , Barsakcioglu Deren Y. , Farina Dario 
Published: February 2024

AbstractObjectiveRobustness to non-stationary conditions is essential to develop stable and accurate wearable neural interfaces.ApproachWe propose a novel adaptive electromyography (EMG) decomposition algorithm that builds on blind source separation methods by leveraging the Kullback-Liebler divergence and kurtosis of the signals as metrics for online learning. The proposed approach provides a theoretical framework to tune the adaptation hyperparameters and compensate for non-stationarities in the mixing matrix, such as due to dynamic contractions, and to identify the underlying motor neuron (MN) discharges. The adaptation is performed in real-time (∼22 ms of computational time per 100-ms batches).Main resultsThe proposed adaptation algorithm significantly improved all decomposition performance metrics with respect to the absence of adaptation in a wide range of motion of the wrist (80°). The rate of agreement, sensitivity, and precision were ≥ 90% in ≥ 80% of the cases in both simulated and experimentally recorded data, according to a two-source validation approach.SignificanceThe findings demonstrate the feasibility of accurately decoding MN discharges in real-time during dynamic contractions from wearable systems mounted at the wrist and forearm. Moreover, the study proposes an experimental validation method for EMG decomposition in dynamic tasks.