Biology subjects

Jung, H.

Publications and source records attributed to Jung, H..

At least 19 recordsLinked to original sources

bioRxiv2026

MxtR/ErdR is a central regulator of short-chain fatty acid metabolism in Pseudomonas alloputida

Short-chain fatty acids (SCFAs) such as acetate and propionate represent important carbon and energy sources for environmental pseudomonads, requiring coordinated regulation to ensure efficient assimilation while maintaining metabolic homeostasis. In Pseudomonas alloputida KT2440, the two-component system MxtR/ErdR (CrbS/CrbR) is known to activate acetate assimilation through regulation of acsA-I. However, the full extent of the MxtR/ErdR regulon and its physiological role beyond acetate metabolism have remained unclear. We demonstrate that MxtR/ErdR directly regulates the methylcitrate cycle and coordinates both acetate and propionate metabolism. To define the MxtR/ErdR regulatory network, we combined comparative transcriptomics, physiological analyses, promoter-reporter assays, electrophoretic mobility shift assays (EMSAs) and targeted mutagenesis. Comparative transcriptomic analyses of the mxtR-H806N and {Delta}erdR mutants revealed extensive changes in gene expression, including coordinated downregulation of genes involved in propionate metabolism alongside genes associated with central carbon metabolism, transport, chemotaxis, and signal transduction. Consistent with these transcriptional changes, deletion of either mxtR or erdR abolished growth on propionate. Promoter-reporter assays and EMSAs demonstrated direct binding of ErdR to a conserved imperfect inverted repeat upstream of the prp gene cluster and prpE. Mutational analyses confirmed the functional importance of this binding motif for promoter activation. In addition, MxtR/ErdR contributed to pyruvate utilization through regulation of transport-associated genes, whereas deletion of downstream target genes only caused modest phenotypes, indicating that the physiological effects of MxtR/ErdR arise from coordinated regulation of multiple pathways. Our findings substantially expand the MxtR/ErdR regulon and identify this signaling system as a central regulator of SCFA homeostasis in P. alloputida KT2440.

microbiology↗

bioRxiv2026

A comprehensive atlas of somatic mutation rates and mutational signatures in normal human cells

Over the course of a lifetime, somatic mutations accrue in normal human cells, causing variation in cell phenotype and engendering somatic evolution with outcomes ranging from the adaptive immune system to cancer. To inform understanding of somatic evolution in the human body we report the mutation rates and mutational signatures of 53 normal cell types. Most show evidence of linear mutation accumulation over time with single base substitution mutation rates ranging from ~3.5/year/diploid genome in spermatogonia and sperm, to ~20/year in postmitotic neurons, ~50/year in mitotically active colorectal epithelial cells, ~60/year in kidney proximal tubule cells and hepatocytes, 100s/year in sun-exposed skin epidermal cells and 10-50/year in the remainder. Certain cell types, including skin epidermis, cardiac myocytes, bladder urothelium, kidney proximal tubule cells, and hepatocytes, show substantial variability in mutation burdens around the linear age trend, indicating the influence of additional factors which differ between individuals and modulate mutation accumulation, including exogenous mutagen exposures. At least 18 single-base substitution and nine small insertion and deletion mutational signatures are present, some in all cell types, some in a subset and others in a single cell type. Known exogenous mutagen exposures and endogenous mutational processes account for some mutational signatures, but the origins and mechanisms underlying many are uncertain. This comprehensive survey of mutagenesis provides a foundation for understanding somatic evolution of human cell populations in health and disease.

genomics↗

bioRxiv2026

Cell organization and disturbance-mapping using image activated cell-profiling (CODIAC)

Protein localization and abundance are tightly regulated to maintain cellular homeostasis, and their dysregulation is a hallmark of disease. However, methods that monitor the spatial localization changes of many proteins at once, and at scale, remain limited. Here we introduce CODIAC (Cell Organization and Disturbance-mapping using Image-Activated Cell-profiling), which couples image-enabled cell sorting (ICS) with improved Cas12a-assisted endogenous PCR tagging and machine-learning-guided gating to profile pools of fluorescently tagged proteins. Rather than isolating discrete cell populations, CODIAC reads the "phenotypic fingerprint" of each fluorescently tagged protein, defined by its distribution across a fixed set of image-defined sort bins. The method resolves localization-associated phenotypes, reproducibly profiles complex pools, generalizes to proteins absent from the training set, and detects shifts in protein localization and abundance following chemical perturbation. CODIAC thus extends ICS from outlier screening toward systematic profiling of the spatial proteome and its remodeling under perturbation.

cell biology↗

bioRxiv2026

Boltz-Perturb: Improving Diversity and Accuracy in Protein-Ligand Co-Folding through Training-Free Conditioning Perturbation

Protein-ligand co-folding models hold promise in structure-based drug discovery and small molecule interaction prediction, but often fail in predicting correct small molecule binding poses. We present Boltz-Perturb, a framework for addressing this through perturbing model conditioning signals during model inference, and show that such perturbations improve correct ligand binding mode predictions. We first show with true-coordinate injection experiments that the models learned energy landscape contains correct binding-mode basins, allowing us to reframe the problem as one of sampling deficiency. We then introduce two inference-time perturbation strategies, Token Bias Perturbation (TBP) and Token Conditioning Perturbation (TCP), which increase exploration of alternative binding poses. Across diverse protein-ligand systems, TCP improves top-20 oracle success rates by 2.6 to 7.8 fold. Boltz-Perturb attains higher oracle success rates compared to the Boltz-2 high diffusion temperature variant while requiring over 75% less compute. To our knowledge, this is the first systematic perturbation analysis of a co-folding architecture for small-molecule binding mode diversity. We demonstrate that inference-time perturbations can unlock latent structural diversity in generative co-folding models and improve protein-ligand predictions without costly retraining.

biophysics↗

bioRxiv2026

VizR: An Interactive Web Platform for End-to-End RNA-Seq Analysis and Visualization in Plant Biology

RNA sequencing (RNA-seq) is widely used to investigate transcriptional programs in plant biology, yet the need to combine multiple specialized tools and bioinformatics expertise to convert raw sequencing reads into biologically interpretable results remains a major technical barrier for many plant biologists. Here, we present VizR (VIsualiZation of Rna seq), a web- based platform that integrates end-to-end RNA-seq analysis and visualization within a single integrated environment. VizR automates upstream processing, including quality control, adapter trimming, genome alignment, and transcript quantification, and connects the resulting expression data to downstream exploratory analyses. Its interface is designed to make expression patterns immediately searchable and interpretable: users can query genes through an equalizer-style expression-pattern interface, inspect expression profiles using inline heatmaps embedded in gene tables, and perform context-integrated gene ontology analysis throughout the workflow. VizR also supports comparative analysis through interactive Venn diagram module, allowing users to transfer gene sets directly from result tables. As a Docker- based application, VizR can be deployed locally and accessed through a standard web browser. By unifying automated RNA-seq processing, interactive visualization, and functional interpretation, VizR lowers the technical barrier to transcriptome analysis and provides a practical platform for plant biology research.

bioinformatics↗

bioRxiv2026

Anisotropic Thermal Conductivity in Topologically Networked Protein-MXene Composites

Governing thermal transport in engineered materials creates opportunities to redirect and recover the excess heat generated in electronic and energy-conversion devices. Materials that pair low cross-plane thermal conductivity with high in-plane thermal conductivity are particularly valuable because they confine heat and channel it away from sensitive regions, preventing localized device failure. Two-dimensional crystals are efficient building blocks for such anisotropic thermal conductors, but they are brittle, and the polymer composites used to toughen them usually forfeit much of the intrinsic anisotropy: in conventional percolation-based design, filler fraction is the only handle available, and it governs both in-plane and cross-plane conduction. Here we report a composite of Ti3C2Tx (MXene) nanosheets and squid ring teeth (SRT) inspired recombinant tandem-repeat (TR) proteins in which the protein serves as a molecular template and bridge, setting the spacing between nanosheets with angstrom-level precision through the number of tandem-repeat units and independently of the filler fraction. This structural handle provides a second, independent design parameter. At a fixed MXene loading, the number of repeats tunes the cross-plane conductivity (0.30 to 0.93 W/mK) and, with it, the thermal anisotropy ratio over a wide range (from about 70 down to 17), while the in-plane conductivity stays high (16 to 21 W/mK). We rationalize these trends with a Gaussian Network Model (GNM) of the protein embedded in a two-phase layered medium, which reproduces the measured directional conductivities from a single structural parameter and identifies the protein gallery as the cross-plane bottleneck. Extending the model to a mechanically loaded five-period stack, we find that the anisotropy is robust to reversible compression and twist, changing by only a few percent, so the number of tandem repeats, not the applied strain, is the dominant design handle. Because anisotropy is tuned structurally rather than volumetrically, these protein-MXene composites decouple thermal anisotropy from filler content, pointing toward flexible thermal materials that are not bound by the rules of mixture and percolation.

bioengineering↗

bioRxiv2026

Persistence of tobacco-mutated alveolar progenitor cells after smoking cessation mirrors long term risk of lung adenocarcinoma

Tobacco smoke shapes mutations, selection and clonal expansion in lung epithelial cells. Smoking cessation leads to divergent epidemiology in the two most common lung cancers: squamous cell carcinoma risk declines sharply, while adenocarcinoma risk is preserved. To investigate this discrepancy, we analysed 806 genomes of alveolar type II (AT2) cells and found persistently elevated mutation burdens after cessation. In contrast, in the proximal airway, rare basal stem cells with near-normal mutation burden expand after cessation, protecting against squamous cell carcinoma. Targeted single-molecule DNA sequencing of AT2 cells revealed positive selection for TP53 and cell cycle and MAPK genes, supporting continued cancer risk. A multistage carcinogenesis model emphasised the importance of a small population of hypermutated cells in the alveoli and reproduced the divergent epidemiological trajectories following cessation due to distinct regenerative dynamics. Our findings suggest that differences in mutational burden and clonal regeneration explain post-cessation trends in lung cancer subtypes. One sentence summaryCancer risk reflects not only cumulative exposure to toxins, but the capacity of tissues to erase genomic damage through regeneration from protected cells with clonal advantage.

genomics↗

bioRxiv2026

Overexpression of magA in Acidithiobacillus ferrooxidans increases magnetosome production and pyrite bioleaching

Acidithiobacillus ferrooxidans, a chemolithoautotrophic iron- and sulfur-oxidizing acidophile, is a key contributor to industrial-scale copper metal bioleaching. These cells naturally produce magnetosomes, and they may serve as an emerging platform for magnetosome bioproduction, as magnetotactic bacteria (MTB) are difficult to cultivate and to genetically modify. Here we manipulated the expression of the endogenous homologs to the magA and mamB genes in A. ferrooxidans, which are implicated in iron transport required for magnetosome synthesis. Modulation of mamB had no impact on cell behavior. Overexpression of magA increased magnetosome formation and magnetic responsiveness and theses effects were attenuated by CRISPRi knockdown of magA. The augmented magnetosome formation in the magA overexpression cells also led to enhanced bioleaching of pyrite, which is weakly paramagnetic, and this could be further enhanced by addition of an external magnetic field. These results confirm that magA plays a critical role in magnetosome formation in A. ferrooxidans and that magnetosome expression can be enhanced through genetic engineering. In addition, these results demonstrate the potential to improve metal sulfide bioleaching through the manipulation of genes involved in magnetosome formation. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/727969v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1ac1822org.highwire.dtl.DTLVardef@1649140org.highwire.dtl.DTLVardef@17c0eccorg.highwire.dtl.DTLVardef@1afa828_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

Serial vaccination expands and refines human CD4+ T cell memory

CD4+ T cells coordinate protective immunity against pathogens. However, a major unresolved question is how human CD4+ T cell memory is established and evolves following primary and repeated vaccination. Using COVID-19 mRNA vaccination as a model, we tracked 50 distinct antigen-specific populations directly ex vivo with peptide-MHC class II tetramers in eight SARS-CoV-2-naive individuals from pre-vaccine baseline through memory time points after three mRNA doses. Our findings identify the primary vaccine series as the main driver of memory pool size. It leverages pre-existing memory while preferentially recruiting high-avidity T cells, establishing an immunodominance hierarchy dominated by a small subset of precursors. Booster vaccination refines both the magnitude and quality of T cell memory. It increases select populations and enhances differentiation of subdominant CD4+ T cells. Populations that did not become more abundant after boosting retained their polyfunctional potential. Beyond establishing memory to the ancestral spike, vaccinations broadened responses by recruiting cross-reactive T cells recognizing viral variants. Collectively, these findings reveal how human CD4+ T cell memory evolves through sequential immunizations to generate a functionally diverse and broadly responsive memory repertoire against future viral challenges.

immunology↗

bioRxiv2025

Structural basis of cyclic phytocytokine recognition by the HSL3/NUT receptor

Plant receptor kinases perceive diverse peptide signals to coordinate stress responses and developmental programs. The HAESA-LIKE 3 (HSL3/NUT) receptor recognizes CTNIP/SCREW phytocytokines--disulfide-stabilized cyclic peptides that regulate immune signaling and stress adaptation. However, how HSL3 distinguishes these structurally constrained cyclic peptides from linear signaling molecules remains unknown. Here we report near-atomic resolution cryo-EM structures of HSL3 in apo and CTNIP448-70-bound states at [~]2.6 [A], using Arabidopsis CTNIP4 as a representative family member, revealing distinct mechanisms for cyclic peptide recognition. The conserved CTNIP motif occupies a negatively charged pocket in HSL3s C-terminal region through a combination of polar contacts, hydrogen bonds, salt bridges, and van der Waals interactions. The receptor employs a two-step recognition mechanism--electrostatic steering followed by motif anchoring--that enables rapid ligand capture and release, consistent with the transient nature of stress signaling. Notably, an N-glycan at Asn449 directly contacts the CTNIP4 peptide, establishing glycosylation as an active participant in ligand recognition. Structure-guided mutagenesis combined with reactive oxygen species (ROS) burst assays confirmed the functional importance of key binding interfaces. N-terminal truncation experiments revealed a minimal active fragment: CTNIP451-70 supported both rapid ROS production and sustained seedling growth inhibition, whereas the shorter CTNIP454-70 variant retained ROS activity but failed to trigger long-term seedling growth inhibition. Structure-guided coevolutionary analysis across plant lineages reveals patterns of both conserved and variable receptor-ligand interfaces, highlighting evolutionary flexibility while preserving core features of recognition. These conserved recognition principles, mediated by receptor glycosylation and evolutionary plasticity, enable specificity in peptide signaling with implications for engineering stress-resilient crops.

plant biology↗

bioRxiv2025

The first comprehensive case study of early-emerging prosopometamorphopsia

Prosopometamorphopsia (PMO) is a rare perceptual disorder characterized by facial distortions. This report presents the first thorough study of a case of PMO that emerged early in life. Zed has experienced lifelong, dynamic facial distortions in which features move, droop, disappear, expand, shrink, and rotate. He also experiences identity misrecognitions, in which he perceives familiar faces as strangers and vice versa (e.g., seeing his grandfather when viewing a young woman). Behavioral assessments indicate that Zeds distortions occur across viewpoints, visual field positions, picture-plane orientations, and visual angles. Neuropsychological testing revealed face identity recognition deficits, yet, despite his facial distortions, Zed can make accurate fine-grained perceptual judgments about facial age and sex. Structural MRI showed no lesions, but face-selectivity in two right posterior face-selective areas was reduced, and diffusion tensor imaging revealed lower white matter integrity in the left inferior fronto-occipital fasciculus. Zeds case offers new insights into early-emerging PMO, its manifestations, co-occurrence with other face-processing disorders, and underlying neural correlates.

neuroscience↗

bioRxiv2025

Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells

Primary human myeloid cells are promising candidates for immunotherapy, yet efficient and scalable technologies for genetic engineering and screening in these cells are limited. Here we present a virus-like particle (VLP)-based toolkit that delivers diverse CRISPR genome editing modalities to human monocytes, macrophages, and dendritic cells with high efficiency while preserving viability and innate immune responsiveness. VLP-mediated delivery of ribonucleoprotein payloads supports gene knockout, base editing and epigenetic silencing, and enables site-specific integration of large DNA sequences when combined with AAV donors for homology-directed repair. Leveraging sgRNA delivery via VPX-lentivirus combined with Cas9 protein delivery via engineered virus-like particle (eVLP) treatment ("SLICeVLP"), we performed the first pooled loss-of-function screens in human macrophages. We uncovered regulators of TNF production and CD80 expression in human macrophages, converging on TNFAIP3 as a central regulator of inflammatory polarization. TNFAIP3 ablation promoted a pro-inflammatory cell state that is resistant to suppressive polarization, and augmented cytotoxicity of engineered HER2 CAR-macrophages. Taken together, this technology platform enables unbiased discovery and characterization of functional gene targets in primary human myeloid cells.

immunology↗

bioRxiv2025

MechanoMR microparticle (M3) sensors reveal dynamic stress loading as a driver of epithelial-mesenchymal transition

The dynamic mechanical response of tissues underlies their physiological function, yet direct, quantitative measurement of tissue stress in vivo has remained a major challenge. Here, we introduce the mechanoMR microparticle (M3, "M-cube") sensor, a hybrid soft-matter/nanoparticle probe that integrates directly into tissue mechanical networks while transducing local stress into quantitative magnetic resonance (MR) readouts with single-particle resolution. We demonstrate the utility of this platform across diverse model systems, including tumor spheroids, Xenopus embryos, and mouse xenografts, where the M3 sensor enables noninvasive, spatiotemporally resolved mapping of tissue stress dynamics during cancer development. Using this approach, we reveal that epithelial-mesenchymal transition (EMT) is accompanied by distinctive stress-remodeling patterns observable in vivo. Strikingly, we find that abrupt stress increases, rather than cumulative or peak stress magnitude, are the key determinants of EMT induction in cancer cells within the tumor microenvironment. Transcriptomic profiling under controlled stress-loading dynamics shows that sustained yet gradual stress escalation activates cytoprotective antioxidation pathways (e.g., FOXO/AMPK) that reinforce epithelial stability, whereas acute stress surges overwhelm these defense mechanisms, predisposing cells toward mesenchymal reprogramming. These findings establish the M3 sensor as a broadly applicable technology for linking dynamic mechanical cues to cell-state transitions in development, homeostasis, and disease.

bioengineering↗

bioRxiv2025

Sensitizing tumor response to topoisomerase I antibody drug conjugate by selective CDK7 inhibition

This study investigates the transcriptional impact of Q901, a highly selective CDK7 inhibitor in clinical development. Q901 primarily disrupted MYC and E2F-dependent transcription program, downregulating cell cycle control and DNA damage repair pathways. CDK7 binding at the promoter-proximal regions was dramatically stabilized by Q901, leading to reduced occupancy of MYC, E2F, and RNA Polymerase II (RNAPII). These findings offered a novel therapeutic strategy to enhance cancer susceptibility to TOP1-DNA protein crosslinks (TOP1-DPCs) induced by TOP1 inhibitors. Resistance to TOP1 inhibitors arises through activation of DNA repair pathway when elongating RNAPII encounters TOP1-DPCs. By suppressing RNAPII transition from initiation to elongation and DNA repair pathways, Q901 stabilizes TOP1-DPCs and sensitizes tumor to TOP1 inhibitors. Preclinical studies demonstrated enhanced tumor suppression when combining Q901 with TOP1 inhibitor-based antibody-drug conjugates (TOP1i-ADCs), highlighting its potential as a therapeutic option for cancers resistant to TOP1i-ADC therapy. TeaserOvercoming ADC cross-resistance through combination approach.

cancer biology↗

bioRxiv2025

The electrophilic metabolite of kynurenine, kynurenine-CKA, targets C151 in Keap1 to derepress Nrf2.

The Kelch-like ECH-associated protein 1 / Nuclear factor-erythroid 2 p45-related factor 2 (Keap1/Nrf2) system responds to a wide array of structurally diverse small molecules, of both exogenous and endogenous origin, by inducing a robust cytoprotective program that allows adaptation during oxidative, metabolic and inflammatory stress. Here, we report that exposure to the tryptophan metabolite kynurenine and its electrophilic derivative kynurenine-carboxyketoalkene (Kyn-CKA) leads to an increase in the abundance of transcription factor Nrf2 and induction of Nrf2-target genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), in murine and human cells. Additionally, both kynurenine and Kyn-CKA activate the aryl hydrocarbon receptor (AhR). Using cellular thermal shift assays, we found that Kyn-CKA increases the thermal stability of Keap1-mCherry fusion protein, but not free mCherry, indicating target engagement of Keap1, the principal repressor of Nrf2. The use of purified recombinant BTB domain of Keap1 and its C151S mutant counterpart revealed that Kyn-CKA reacts with wild-type, but not C151S mutant, Keap1-BTB, and at a much faster rate than with the small molecule thiol N-acetyl cysteine, demonstrating Kyn-CKA is targeted to react with C151 by the surrounding protein environment. In close agreement, Kyn-CKA increased the abundance of Nrf2 and expression of NQO1 in mouse embryonic fibroblast (MEF) cells expressing wild-type Keap1, but its inducer potency was greatly diminished in C151S-Keap1 mutant MEFs. Experiments in WT, AhR-knockout, and Nrf2-knockout primary murine bone marrow-derived macrophages showed that Nrf2 is required for the acute anti-inflammatory activity of Kyn-CKA, whereas AhR is dispensable. Together, these findings demonstrate that Kyn-CKA targets C151 in Keap1 to derepress Nrf2 and reveal that Nrf2, but not AhR, is a main contributor to the anti-inflammatory activity of Kyn-CKA in macrophages.

biochemistry↗

bioRxiv2025

Electrophysiological Brain Connectivity and Subjective States Evoked by Electrical Stimulation of the Human Mediodorsal Thalamus

Recent advances in human intracranial EEG (iEEG) have enabled new investigations into the role of the thalamus in human brain functions. In this study, we applied direct intracranial electrical stimulation (iES) to the mediodorsal (MD) subregion of the thalamus using both high-frequency (50 Hz, iESHF) and low-frequency (0.5 Hz, iESLF) procedures to examine its impact on conscious experience and causal brain connectivity in 30 patients with focal refractory epilepsy (128 electrode contacts; 4 {+/-} 1 MD sites per patient). iESHF of the MD elicited reportable changes in conscious experience in 11 of 12 patients (39 sites; 83 stimulations across 27 unique pairs) - predominantly in the visceral, emotional, or somatosensory domains and often described as unpleasant without any lateralization effect. Our connectivity analyses based on iESLF revealed that the cingulate and insular cortices produced stronger electrophysiological responses in the MD (inflow connectivity) than did the sites in the prefrontal cortex (PFC) within the same individuals. Moreover, MD stimulation showed its strongest outflow connectivity to the cingulate, insular, and PFC regions, all significantly stronger than to medial temporal lobe (MTL) structures. Notably, inflow from both MTL and insula sites to the MD were significantly stronger than their reverse directions, indicating clear asymmetry in connectivity. These findings provide direct evidence that stimulation of the human thalamus can modulate conscious experience. They also highlight the extensive bidirectional connectivity between the MD and cingulate and insular cortices along with asymmetric connectivity between the MD and MTL and insula sites in the human brain. SIGNIFICANCE STATEMENTOur findings provide a functional and causal map of the mediodorsal thalamus (MD) in the human brain. We provide direct evidence that stimulation of the human thalamus can modulate conscious experience. This study also holds clinical and translational value for identifying thalamic pathways involved in the propagation and generalization of seizures, especially seizures involving the medial temporal lobe, as well as for neuromodulation in epilepsy and other neuropsychiatric disorders, as MD stimulation may not be well-tolerated in human subjects.

neuroscience↗

bioRxiv2025

Site-specific replacement of large-scale DNA fragments in human cells

Despite advances in genome editing1-4, precisely replacing large-scale fragments in human cells remains a significant challenge. Here, we present a site-specific gene replacement tool, named Prime Assembly (PA), which adapts prime editors to produce one or two pairs of 3-flaps on both the genome and donor plasmids. These 3-flaps anneal to each other precisely, similar to "Gibson Assembly" in DNA oligonucleotides5, allowing megabase-scale genomic excision and/or kilobase-scale donor insertion at the gene of interest. The PA system achieves an efficiency of up to 57.8% in replacing endogenous sequences with a 2.9 kbp donor DNA fragment in HEK293T cells, and presents an accuracy of more than 99% for integrated PA fragments. Ultimately, the site-specific replacement of large-scale coding sequences (CDSs) in disease-related genes can restore gene function across numerous patients with different mutations, providing a gene implantation technique for genome editing and a universal therapeutic approach.

molecular biology↗

bioRxiv2025

Precision Functional Mapping of Imagined and Experienced Pain

Imagination is a principal human capacity, enabling simulation of sensations and situations for planning, learning, and empathy. We examined neural representations of experienced and imagined pain across eight body sites using deep-phenotyping, precision functional MRI with over seven hours of scanning per participant (N = 9). Here we show, using conventional mapping, pattern classification, and representational similarity analyses, that both imagined and experienced pain activated nociceptive regions (e.g., dorsoposterior insula) and non-nociceptive regions (e.g., premotor areas). However, imagined pain did not reliably reactivate body site-selective nociceptive patterns in any region. Instead, imagined and experienced pain shared multivariate representations across widespread cortical and subcortical regions, particularly transmodal cortical areas including dorsomedial and lateral prefrontal cortex, hippocampus, and thalamus. These findings suggest that imagination generates distributed pain-like activity while preserving a neural distinction from experienced pain. This distinction may explain the difficulty of vividly imagining pain and underlie its role in empathy, planning, and pain vulnerability.

neuroscience↗