Biology subjects

Sun, C.

Publications and source records attributed to Sun, C..

At least 19 recordsLinked to original sources

bioRxiv2026

In Utero MRI of Radial Glial Fibers Highlights Their Role in Modulating Fetal Cortical Folding

The process of cortical folding is fundamental to early human brain development. While the differential growth of the cortical layers is a known driver, the biomechanical contribution of key cellular microstructures remains unclear, and there is a lack of direct in vivo markers of cortical microstructures for time-resolved observations. Using a multimodal approach combining in utero and ex vivo fetal brain MRI, histology, and computational mechanical simulation, we investigated whether developmental reorganization of cortical radial microstructures, particularly the radial glial cell (RGC)-associated scaffold, is linked to cortical folding and may modulate its mechanical progression. We characterized this radial organization noninvasively using diffusion MRI-based radial fiber density (FDrad). ex vivo fetal brain MRI and histology supported that regional variations in FDrad were strongly associated with vimentin-labelled radial architecture. Our in utero MRI data revealed closely coordinated developmental changes in cortical FDrad and curvature, with their regional timings and spatial patterns significantly coupled across the cortex. Longitudinal in utero MRI data further supported the synchronized within-individual co-development of FDrad and curvature. Furthermore, biomechanical simulations showed that reducing radial reinforcement modulated differential-growth-driven buckling, producing earlier folding and a greater cortical curvature under otherwise matched model conditions. Collectively, this study introduces FDrad as a noninvasive in utero MRI measure sensitive to radial glial fibers. By integrating spatial, temporal, histological, and computational evidence, our findings suggested a model in which developmental disassembly of the radial scaffold may modulate the mechanical response of the fetal cortex to differential growth, thereby contributing to cortical folding.

neuroscience↗

bioRxiv2026

AI-guided discovery of natural pocket proteins for portable small-molecule sensing

Recognition-element development remains an important practical challenge in small-molecule biosensing. Here, we present DWCLASS, an AI-guided workflow that combines screening of natural pocket proteins, molecular dynamics simulations, experimental binding assessment, and portable metasurface plasmonic sensing. Using thiamine (vitamin B1, thiamine) and 25-hydroxyvitamin D3 [25(OH)D3] as model analytes, the workflow identified binding responses in 7 of 16 tested analyte-protein pairs (43.8%). Selected proteins were incorporated into a competitive MetaSPR assay with gold nanoparticle amplification and acoustic mixing. The portable device provided a 240 s measurement step for prepared samples. Serum LODs were 2.98 ppt for thiamine and 3.82 ppt for 25(OH)D. Preliminary measurements of human serum specimens were compared with commercial ELISA to explore performance in biological samples. This study establishes an integrated route from AI-assisted screening of natural proteins to portable assay development for two chemically distinct vitamin analytes. Applicability to additional targets and clinical reference accuracy remain to be established.

bioinformatics↗

bioRxiv2026

Preclinical Evaluation of Itareparib, a brain penetrant PARP1-selective radioligand, in Glioma Rat Model and Nonhuman Primate

Rationale: Poly(ADP-ribose) polymerase-1 (PARP1) is a central mediator of DNA damage response and is upregulated in glioma, supporting it as a molecular imaging biomarker. However, quantitative PET assessment of PARP1 in infiltrative tumors with a preserved blood-brain barrier remains an unmet need. In this study, we evaluated if [18F]Itareparib, a brain-penetrant, non-trapping, PARP1-selective radioligand with reversible kinetics, could improve brain tumor diagnosis and enable target occupancy studies in neurooncology. Methods: [18F]Itareparib was synthesized and evaluated in an orthotopic rat model of BT142 IDH1-mutant gliomas. Dynamic PET scans were performed with or without the administration of the PARP1-selective inhibitor AZD9574. Standardized uptake value ratios (SUVRs) for tumors were calculated using the contralateral region as reference and compared with distribution volume ratios (DVRs) calculated using kinetic modeling. PARP1-specific binding and tracer stability were assessed using autoradiography, immunofluorescence, biodistribution, and radiometabolite analysis. Brain kinetics of [18F]Itareparib were evaluated in a healthy nonhuman primate (NHP) at baseline and blocking conditions. Results: [18F]Itareparib rapidly entered the rat brains and showed 4-fold higher uptake in BT142 tumors than in the contralateral brain. AZD9574 reduced tumor uptake by 77%, supporting the PARP1-specific binding of [18F]Itareparib in the tumors. SUVR(30-60 min) showed the closest agreement with DVR. Autoradiographic tumor-to-reference mean ratio was 7.3, and AZD9574 reduced the tumor-to-reference ratio by 56%. PARP1 immunofluorescence was higher in tumor than the rest of the brain and correlated with autoradiographic results. In rats, the parent fraction of [18F]Itareparib exceeded 99% in brain through 60 min post tracer injection (p.i.) and was approximately 88% in plasma at 60 min p.i. In the NHP, [18F]Itareparib showed rapid brain uptake, and VT decreased by 21+/-6 % after blocking with AZD9574. Conclusion: [18F]Itareparib showed brain penetration, high in vivo metabolic stability, reversible binding kinetics, and PARP1-specific tumor uptake. These findings support further development of [18F]Itareparib for the quantitative PET imaging of PARP1 in brain tumors.

cancer biology↗

bioRxiv2026

Evidence-resolved benchmarks separate biological context recognition from direct-partner specificity in protein interaction models

Sequence-based models enable scalable protein-protein interaction (PPI) prediction, but whether high scores identify direct physical partners or broader biological compatibility remains unclear. Here we show that biological-context recognition and direct-partner specificity are separable prediction capabilities. We introduce ProtNegDB (http://protnegdb.bjmu.edu.cn/), an evidence-resolved resource distinguishing experimentally supported non-binding from coordinate-verified noncontact within PDB biological assemblies. Using context-matched benchmarks, we find that five sequence-based predictors show limited ability to distinguish direct partners from noncontacting members of the same assembly, whereas PLM-Interact readily ranks both above unrelated proteins. Representation analyses reveal that adaptation to PPI prediction can strengthen biological-context encoding without yielding transferable direct-contact specificity. AlphaFold3 shows greater, though still incomplete, direct-partner resolution, suggesting that explicit multimer modeling can help refine partner specificity. In PLM-Interact, negatives defined by reconstituted direct-binding, cellular binary/proximity and co-complex assays occupy distinct score regimes. Across independent datasets and multiple models, experimental direct non-binding and assembly noncontact further show reproducible, model-dependent scoring patterns. High sequence-based PPI scores should not be interpreted as direct-interface probabilities. Mechanistically interpretable evaluation instead requires explicit consideration of interaction-evidence semantics and partner specificity.

bioinformatics↗

bioRxiv2026

A robust and scalable image analysis framework for phenotyping human thoracic aorta

Large-scale phenotyping of the thoracic aorta requires a workflow in which every step, from segmentation to phenotype extraction, runs without manual intervention. We present a robust and scalable framework that converts contrast-enhanced CT into anatomical landmarks, a patient-specific quadrilateral mesh, a wall-stress field and regional phenotypes of the thoracic aorta. Four nnU-Net segmentation tasks delineate the aorta, its anatomical regions and two partitions of the aortic root. A surface-curve-point procedure derives the annulus, the sinotubular junction, the ostia of the supra-aortic branches, the cusp nadirs and the commissures from the interfaces between segmented regions. We fit a structured template of 24,882 quadrilateral elements to the segmented aortic surface by staged, differentiable mesh deformation and compute the transmural mean wall stress with PyTorch-FEA. The structured mesh provides node-to-node correspondence across patients, anchored to the anatomy by the landmarks, from which the framework extracts regional morphological and biomechanical phenotypes.

bioengineering↗

bioRxiv2026

HSF1 inhibition potentiates the antifungal activity and proteome instability induced by the fungal Hsp110 inhibitor 2H

Fungal infections remain a major cause of morbidity and mortality worldwide; however, therapeutic options are limited and are increasingly compromised by antifungal resistance. Heat Shock Protein 110 kDa (Hsp110) is an essential molecular chaperone required for protein homeostasis (proteostasis) and fungal viability and has recently emerged as a promising antifungal target. We previously identified 2H, a first-in-class inhibitor of fungal Hsp110 proteins that exhibits broad-spectrum antifungal activity through disruption of proteostasis. Heat Shock Transcription Factor 1 (HSF1), the master regulator of cellular stress responses and chaperone expression, has also been proposed as a potential antifungal target, although direct pharmacological evidence supporting this strategy remains limited. Here, we investigated the effects of combining the HSF1 inhibitor DTHIB with the fungal Hsp110 inhibitor 2H in Cryptococcus neoformans and Candida albicans. Although DTHIB alone exhibited minimal antifungal activity, it significantly enhanced the growth-inhibitory and fungicidal effects of 2H. Notably, this potentiating effect was specific to 2H and was not observed with fluconazole. Consistent with the roles of Hsp110 and HSF1 in proteostasis, 2H induced extensive accumulation of detergent-insoluble protein aggregates in C. neoformans, whereas HSF1 inhibition further increased both the abundance and diversity of aggregated proteins. Quantitative proteomic analyses demonstrated that 2H induces proteome-wide protein aggregation, impacting proteins involved in a broad range of essential cellular processes, with high-molecular-weight proteins exhibiting particular susceptibility. Together, these findings provide pharmacological evidence supporting HSF1 as a promising antifungal sensitization target and demonstrate the utility of 2H as a chemical probe for studying Hsp110-dependent proteostasis. Simultaneous disruption of both HSF1-mediated stress responses and Hsp110-dependent proteostasis promotes extensive proteome instability and enhances antifungal activity, highlighting a potential new strategy for antifungal drug development.

microbiology↗

bioRxiv2026

Long-form hibernation-promoting factor coordinates 100S assembly and translational repression

Ribosome hibernation mediated by long-form hibernation-promoting factor (HPF) requires coordination of ribosome dimerization and translational repression, but how these functions are integrated remains unclear. Here, we present cryo-EM structures of native 100S from a deep-sea Bacillus isolate, revealing a conformationally heterogeneous 100S population. Beyond the established roles of the HPF N-terminal domain (NTD) in decoding-center occlusion and the C-terminal domain (CTD) in dimerization, our analyses reveal additional contributions from the Linker and a charged CTD surface near the 16S rRNA 3' terminus containing the anti-Shine-Dalgarno (aSD) sequence. Linker substitutions differentially affect translational repression while retaining 100S formation, with distinct effects of the two Linker segments. Mutation of the charged CTD surface enhances translational repression while retaining robust 100S formation, suggesting an additional role beyond CTD-mediated ribosome dimerization. Functional analyses in an E. coli cell-free translation system further show that the inhibitory activity of individual HPF regions varies with translational context. Together, these findings support a modular model in which the NTD, Linker, and CTD make distinct but interconnected contributions to 100S assembly and translational repression.

biochemistry↗

bioRxiv2026

Consensus Formation History Shapes Collective Updating

Consensus is rarely a one-off achievement. In a changing world, groups must repeatedly update judgments they have already agreed upon, making consensus updating a common feature of real-world collective decisions. However, previous research on collective decision-making has focused mainly on how groups reach a single consensus, leaving the updating of established consensus largely unexamined. This raises two unanswered questions: does consensus updating involve biases analogous to sunk cost, and are such biases related to the cost of the previous consensus? Building a Fake Consensus paradigm, we manipulated consensus-formation cost and examined how dyads updated a subjectively established consensus after new information arrived. An independent individual experiment provided information-matched updating baselines, allowing us to determine whether dyads updated less or more than individuals responding to the same evidence. Contrary to sunk-cost predictions, low-cost consensus led dyads to update less than the individual baseline, whereas medium- and high-cost consensus led them to update more. The pathway through perceived consensus sharedness was significant, and the association between sharedness and updating was stronger at higher left temporoparietal junction inter-brain synchrony. These findings indicate that the history of consensus formation shapes subsequent updating by altering the psychological meaning of shared endorsement, while interpersonal alignment determines how this shared experience translates into coordinated behavior. To our knowledge, this is the first experimentally controlled study of consensus updating in teams to isolate formation history from actual disagreement, providing a new paradigm for studying how collective judgments change after agreement.

neuroscience↗

bioRxiv2026

Combination of ALK2 and cholesterol targeting agents exploits linked genetic and metabolic dependencies in diffuse midline glioma

Diffuse midline glioma is an epigenetically driven disease defined by alterations targeting the histone post-translational modification H3K27me3 resulting in epigenetic rewiring and imposing unique metabolic dependencies. ACVR1-mutations arise in ~25% of DMG H3K27-altered patients and impart a selective dependency on the kinase it encodes (ALK2), however ALK2 inhibitors show modest single-agent efficacy in vivo. In an attempt to better understand the cellular consequences of ALK2 inhibition to identify mechanistically-driven drug combinations, integrated multi-omics analysis was performed and revealed a novel role for ALK2 in cholesterol homeostasis while CRISPR and high-throughput drug screens identified hits targeting cholesterol metabolism as sensitisers to ALK2i. In vivo assessment of ALK2i plus clinically well-tolerated statins revealed a significant increase in the median survival compared to vehicle. Forced differentiation of DMG cells from an oligodendrocyte precursor-like to an astrocyte-like cell-state and led to a significant decrease in ALK2i sensitivity and synergy with statins, which was phenocopied when DMG cells were co-cultured with normal astrocytes. We identify a previously unappreciated role for ALK2 signalling in cholesterol homeostasis, showing cell-state dependency, and identify a rational combinatorial strategy for clinical translation.

cancer biology↗

bioRxiv2026

Unifying physical and molecular coordinate systems across modalities in spatial biology

Establishing a unified physical and molecular coordinate system from fragmented multi-modal data is a longstanding challenge in biology. Here, we present MAPS, a modality-agnostic platform for spatial biology comprising (1) MAPS-alignment for ultrafast alignment of any modality, (2) MAPS-integration for both anchored and unanchored integration across orthogonal modalities for 3D multi-modal reconstruction, and (3) MAPS-Explorer for large-scale interactive 3D analysis. MAPS outperformed existing methods across extensive benchmarks on 34 datasets spanning 16 technology platforms and 6 modalities, while delineating fine-grained multi-modal tissue architectures across diverse biological systems in mouse and human. At cross-consortium scale, MAPS integrated 434 slices comprising 21 million cells from 18 atlases and 5 modalities to construct the most comprehensive 3D multi-modal mouse brain atlas. At individual laboratory scale, MAPS empowered routine 2D spatial assays to reconstruct continuous 3D multi-modal landscapes of human hepatocellular carcinoma, revealing the limitations of 2D spatial relationships and uncovering depth-dependent immune-state transitions.

bioinformatics↗

bioRxiv2026

De novo design of CR2 binder as vaccine scaffold

Efficient B cell activation during vaccine-induced humoral immunity relies on both B cell receptor (BCR) antigen recognition and synergistic signaling from co-receptors. Complement receptor 2 (CR2), the primary BCR co-receptor on B cells, lowers the activation threshold and amplifies downstream kinase signaling by orders of magnitude when engaged by complement fragment C3d decorated antigens. Targeting CR2 therefore represents a rational vaccine enhancement strategy, yet native C3d suffers from low affinity, poor stability, and manufacturing challenges. Here, we report the de novo design of a highly stable, high-affinity CR2 binder using deep learning driving protein design methods. Biophysical characterization, high-resolution cryoEM structural determination, and functional assays in vitro and in vivo confirm that the designed binder matches computational design models and specifically engages CR2 to boost B cell activation. When fused to antigen as a vaccine scaffold, the trimeric CR2 binder elicits robust humoral immune responses comparable to nanoparticle vaccines, while retaining the simplicity of single-chain protein production. Our work establishes a modular CR2 targeting vaccine scaffold platform with broad translational potential for next-generation protein vaccines.

immunology↗

bioRxiv2026

A patient-centric therapeutic paradigm uncouples prostate cancer suppression from systemic metabolic collapse

The clinical benefits of cancer therapies are often compromised by the tolerable adverse effects that impair systemic organismal health and may evolve into latent life threats. Here, we identified profound abiraterone-induced but androgen-independent metabolic perturbations in prostate cancer patients and developed Lifehug-9892 to balance tumor therapy with systemic metabolic homeostasis. By integrating population cohorts with high-resolution metabolomics, we demonstrate that abiraterone induces profound systemic lipidomic dysregulation, characterized by the massive, pathological accumulation of desmosterol. Abiraterone inhibits but stabilizes DHCR24, leading to a metabolic trap in patients showing elevated levels of both desmosterol and cholesterol. Desmosterol accumulation is highly lipotoxic, potently triggering endothelial cell senescence and necrosis, macrophage foam cell formation, murine atherosclerosis, and hepatic senescence. To mechanistically uncouple and therapeutically rescue this systemic metabolic collapse, Lifehug-9892 was rationally designed to selectively retain on-target CYP17A1 inhibition while completely sparing DHCR24 function. Lifehug-9892 maintains potent tumor-suppressive activity while fully preserving the desmosterol-cholesterol metabolic axis and preventing systemic cardiovascular and hepatic damage. Our study uncovers a critical mechanistic link between drug-induced metabolic dysregulation and organismal health in cancer patients, providing a biochemical framework for developing patient-centric targeted therapies that preserve host homeostasis.

cancer biology↗

bioRxiv2026

Increased activity in the somatosensory and insular cortex during the transition from acute to chronic neuropathic pain

Pathophysiological mechanisms underlying the transition from acute to chronic neuropathic pain remain incompletely understood. The somatosensory and insular cortices are key cortical components of the pain matrix. We examined changes in activation of these cortical regions during the transition from acute to chronic neuropathic pain. The right sciatic nerve was ligated in activity reporter TRAP mice using standard procedures. Mechanical allodynia was confirmed after CCI or sham surgery using von Frey monofilaments applied to the hind paws. To label active neurons, 4-hydroxytamoxifen was administered to separate cohorts at 1, 3, and 6 weeks following nerve ligation. Passive tissue clearing of brain sections and confocal imaging was used to assess active neurons. Progressive reduction of ipsilateral hind paw in CCI mice indicated mechanical allodynia development. CCI mice showed robust neuronal activation in the bilateral somatosensory and insular cortices. The somatosensory cortical activation peaked at 3 weeks post-CCI, whereas insular cortical activity increased during the transition from acute to chronic neuropathic pain. These studies revealed that CCI induced progressive mechanical allodynia and distinct temporal patterns of cortical neuronal activation, with transient peak neuronal activity in the somatosensory cortex and sustained, increasing activation in the insular cortex during acute-to-chronic pain transformation.

neuroscience↗

bioRxiv2026

Assessing the Reliability of LLM-Generated Phenotype-Genotype Associations Through External Validation

BackgroundPhenotype-genotype associations underpin precision medicine by enabling disease prevention, early diagnosis, risk stratification, therapeutic target discovery, and personalized treatment. However, the rapid growth of scientific evidence has made manual curation of these associations increasingly labor-intensive, time-consuming, and incomplete. Large Language Models (LLMs) offer a potential path to scalable genomic generation and synthesis of this knowledge, but their ability to accurately identify phenotype-genotype associations and the extent to which these outputs are supported by established genomic knowledge bases remain unclear. Materials and MethodsFour LLMs, Claude Sonnet 4.6, DeepSeek V4 Flash, Gemini 3 Flash Preview, and GPT-5.5, were benchmarked on six zero-shot task categories covering forward and reverse phenotype-gene and phenotype-SNP generation. A total of 4,196 associations were identified from curated inputs and evaluated through a multistage external verification pipeline comprising phenotype normalization, ontology mapping, genomic identifier validation against Ensembl, and evidence verification using both the GWAS Catalog and OMIM. Associations were assigned a fused evidence level of strong, moderate, weak, or none. ResultsOverall, 74.19% of generated associations were matched to at least one external genomic knowledge base; 9.15% received strong support and 54.46% moderate support. Phenotype-gene associations were more verifiable than phenotype-SNP associations (strong or moderate: 67.19% vs 54.06%). Among existing associations, Claude Sonnet 4.6 achieved the highest overall strong or moderate rate (69.2%), followed by GPT-5.5 (65.1%), DeepSeek V4 Flash (61.7%), and Gemini 3 Flash Preview (56.9%). ConclusionLLMs can support scalable generation of candidate phenotype-genotype associations. Performance varied substantially by relation type and was lower for SNP-level and rare disease associations, highlighting both the limitations of current genomic resources and the need for rigorous validation pipelines.

bioinformatics↗

bioRxiv2026

An intact primordial interferon antiviral signalling network in amphioxus illuminates the basal chordate origin of vertebrate IFN immunity

The evolutionary origin of the complete interferon (IFN) antiviral signalling cascade across chordates has long remained elusive, as fully functional IFN machinery had not been biochemically reconstituted in basal cephalochordates. Here we combine phylogenetics, AlphaFold3 structural prediction, multi-omic profiling and a full panel of in vitro and in vivo functional assays to characterize an intact primordial IFN network in amphioxus Branchiostoma japonicum, the extant sister group of all vertebrates. Amphioxus encodes a pair of undifferentiated BjTBK1/IKK{varepsilon} paralogs that form cytoplasmic heterodimers, whose conserved kinase-domain phosphorylation residues are mandatory for downstream IRF-driven IFN promoter activation. Despite minimal primary sequence homology with vertebrate IFNs, BjIFN1/2 possess compact -helical core folds that hint at potential structural analogy to vertebrate mucosal type III IFN-{lambda}. We identify two primitive class II cytokine receptors BjCRFB1 and BjCRFB2 that act as functional IFN sensors. Phylogenetic and tertiary structural validations confirm these undiversified ancestral receptor prototypes arose before vertebrate IFN receptor subfunctionalization, and their distinct temporal induction profiles upon viral challenge closely mirror the mucosal immune surveillance orchestrated by vertebrate IFN-{lambda}-IFNLR signalling. AlphaFold3 ligand-receptor docking identifies BjIFN2-BjCRFB2 as the optimal binding pair among all tested combinations, yet all modelled complexes yield low interface scores indicative of weak ancestral intermolecular interactions. Downstream signal transduction relies on two STAT paralogs, BjSTATa and BjSTATb, which jointly mediate transcriptional activation of core antiviral effector genes. The conserved GTPase BjMx serves as a central IFN-stimulated effector to suppress viral replication and maintain tissue immune homeostasis. Collectively, our structural and functional evidence demonstrates that the full hierarchical IFN signalling apparatus was fully assembled in basal cephalochordates prior to vertebrate radiation. The amphioxus IFN cascade preserves core ancestral molecular traits including structure-dependent ligand conservation and primitive low-affinity ligand-receptor interactions. This study resolves a long-standing evolutionary gap and provides definitive functional evidence demonstrating that IFN-mediated innate immunity constitutes an ancestral chordate trait, rather than a vertebrate-specific evolutionary innovation. It also puts forward the hypothesis that mucosal surveillance may represent the ancestral mode of chordate IFN defence.

evolutionary biology↗

bioRxiv2026

When Deeper Analysis Weakens Aesthetic Experience: Behavioral and Brain Network Evidence

Analysis does not always enhance aesthetic experience. Philosophical accounts have long suggested that decomposing an aesthetic experience into determinate components may weaken it, yet this possibility has rarely been tested experimentally. To examine whether, when, and how analysis produces divergent effects on aesthetic experience, we conducted two experiments manipulating analysis depth. Experiment 1 showed that, during affective analysis of visual art, deep analysis produced a significantly weaker increase in aesthetic ratings than shallow analysis. In Experiment 2, we selected this condition to investigate the underlying mechanism. The behavioral effect was replicated: deep analysis removed the increase produced by shallow analysis without reducing ratings below the image baseline. Frequency-resolved brain network analysis further revealed a stronger task-related component and higher spatial entropy within the default mode network under deep analysis. Network-behavior correlations observed under shallow analysis were absent under deep analysis, suggesting reduced correspondence between the default-mode network (DMN) organization and aesthetic experience. Exploratory analyses further showed that spatial weights in the lateral temporal cortex and inferior parietal lobule were associated with smaller increases in aesthetic ratings. Together, these findings indicate that deeper analysis can selectively weaken improvements in aesthetic experience by altering how affective information is organized within the DMN.

neuroscience↗

bioRxiv2026

Closed-loop optical optimization enables patterned retinal stimulation in vivo at cellular scales

Visual neuroscience requires precise spatiotemporal projection of optical stimulation onto the retina, especially in experimental mouse models. However, in vivo patterned stimulation in mice is profoundly hindered by the extreme optical power and severe anatomical aberrations of the eye. Consequently, visual stimulation relies mainly on unverifiable, open-loop approximations that often lack spatial precision. Here, we introduce a closed-loop, spatially modulated stimulation platform that overcomes these barriers. By integrating a digital micromirror device (DMD) with electronically tunable lenses (ETLs) and a real-time, fundus camera-guided focus optimization module, we directly verify the location of patterned stimuli on the retina while dynamically correcting for chromatic and geometric defocus. This platform delivers quantitatively verified static and dynamic patterned stimuli to the living retina with lateral resolutions as fine as 6.7 {micro}m. Guided by ray-tracing optical analysis, our work establishes a technological foundation that enables highly reproducible, cellular-scale interrogations of the visual pathway.

bioengineering↗

bioRxiv2026

ABC1K7: A 350-Myr chloroplast rheostat fine-tuned during coconut domestication

Perennial crops follow different domestication trajectories from annuals, yet the molecular basis of slow-variable domestication--subtle tuning of conserved regulatory hubs--remains poorly characterized. We reconstructed the evolutionary history of the chloroplast kinase ABC1K7 across 9 seed plant species spanning [~]350 Myr, employing PAML codon models, IQ-TREE robust codon models, and protein-level phylogenetic inference, with AlphaFold2 structural modeling. ABC1K7 was under extreme purifying selection ({omega} = 0.073-0.104) across all seed plants. In coconut, a single Y[->]F substitution at residue 652--located >30 [A] from the catalytic core in a predicted intrinsically disordered region--represents the only non-synonymous change differentiating coconut from 7 of 8 angiosperm orthologs, and exhibits perfect co-segregation with domestication traits across a 17-year breeding panel (n = 327). These findings provide population-level evidence consistent with the slow-variable domestication model, identifying ABC1K orthologs as targets for perennial crop improvement.

genomics↗