Cell-cell communication helps to coordinate tissue development, homeostasis, and immune responses, but identifying signaling interactions within intact tissues remains difficult. Although single-cell transcriptomics has enabled systematic inference of ligand-receptor interactions, dissociation disrupts spatial context and limits the identification of bona fide local signaling and region-specific communication programs. Spatial transcriptomics and spatial multi-omics offer the opportunity […]
Analytical Choices Drive Toxicogenomic Potency Estimates: A Systematic Evaluation of Transcriptomic Points of Departure
Omics technologies are increasingly integrated into next-generation risk assessment, yet quantitative toxicogenomics outcomes remain highly dependent on analytical choices, motivating a systematic evaluation of how bioinformatics workflows influence hazard characterization and transcriptomic Points of Departure (tPOD). Here, we applied five independent transcriptomics pipelines to a shared dataset of RPTEC-TERT1 kidney cells exposed to cisplatin across […]
Ultra-Slow Rhythmic Movement in the Elongating Tail of Xenopus Tadpoles
Since Darwin’s time, ultra-slow oscillatory movements have been recognized as a characteristic feature of axis elongation in plant organs such as shoots and tendrils, yet have not been reported in elongating animal body axes. Here, using long-term imaging of multiple anesthetized Xenopus laevis embryos with a modified document scanner, we identify a previously unrecognized ultra-slow […]
Instance-Wise Contrastive Graph Neural Network Enables the Discovery of Novel Aedes aegypti Larvicidal Compounds
Aedes aegypti remains a major arboviral vector, making larval control a critical strategy to reduce mosquito populations. However, resistance to commercial larvicides has reduced the long-term effectiveness of current interventions, reinforcing the need for new compounds with improved potency and selectivity. Here, we present an instance-wise contrastive graph neural network (GNN) framework to accelerate the […]
Functional Characterization of Myeloid Neoplasm-associated DDX41 Variants Reveals Pathogenic Interaction with Acquired Hotspot Mutation
Germline variants in DDX41 are the most frequent genetic predisposition to adult hematologic malignancies. The most common variants are truncating, implicating loss of function in the pathogenesis. However, non-truncating variants account for 30-40% of cases, and their impact on essential DDX41 functions remains unknown. We utilized a genetic complementation assay to assess the functionality of […]
Identifying a cooperative catalytic network for efficient esterase catalysis
Active-site redesign frequently yields modest improvements because residues controlling physical steps like substrate binding and product release lie outside the active site. Efficient catalysis requires a cooperative catalytic network of residues that support both the chemical and physical steps of catalysis. Using ancestral hydroxynitrile lyase HNL1, an /beta-hydrolase with poor esterase activity, we tested this […]
Antibody maturation increases rigidity in protein-contacting regions and flexibility at glycan interfaces
Antibody design is a challenging task that could be improved by understanding the conformational changes accompanying affinity maturation. Antibody maturation is a critical immune system process by which antibodies gain mutations that improve affinity and specificity for antigen targets. However, how these mutations change antibody dynamics, specifically whether antibodies become more rigid as they mature, […]
Antibiotics and copper drive compartment-specific dysbiosis and functional reprogramming in tomato microbiomes
Plant-associated microbiomes help sustain plant immunity and productivity, yet the degree to which agricultural antimicrobials reshape these microbial networks and alter disease outcomes remains poorly characterized. Here, we quantified how chemical inputs such as copper and streptomycin trigger distinct, compartment-specific dysbiosis in tomato (Solanum lycopersicum), fundamentally decoupling microbiome-mediated immunity from pathogen defense. We demonstrated that […]
Carbamylome analysis reveals regulatory roles for lysine carbamylation in β-cell glycolytic and insulin-processing enzymes
In type 1 diabetes (T1D), insulin-producing beta cells are destroyed by an autoimmune response driven by pro-inflammatory cytokines, including interferons. beta-cell cytokine signaling is mediated in part by post-translational modifications, such as phosphorylation and acetylation. However, the role of other post-translational modifications in beta-cell cytokine signaling represents an important knowledge gap. In the context of […]
SuFEx and macrocyclic chelation define orthogonal reactivity domains enabling isotopically versatile radiopharmaceuticals from a single peptide precursor
The design of radiotheranostic agents has been constrained by a fundamental chemical incompatibility: existing strategies for fluorine-18 incorporation — nucleophilic substitution, silicon-fluoride exchange, aluminum fluoride chelation, and prosthetic conjugation — either require conditions incompatible with macrocyclic metal coordination, consume the chelator site needed for radiometal labeling, or introduce non-native structural appendages that alter pharmacokinetic behavior. […]
Organoid-T cell co-cultures functionally stratify tumor-reactive T cells and their responses to immune checkpoint inhibitors
Tumor-reactive T cells (TRTs) are critical for anti-tumor immunity but are incompletely captured by current assays, which fail to reproduce tumor-specific antigen diversity. Here, we show that multiplex functional profiling of patient-derived tumor organoid-T cell co-cultures (PDOTs) enables robust identification of TRTs across CD8, CD4, and double-negative (DN) T cell populations. Single activation markers underestimated […]
Auranofin potentiates cisplatin response through context-dependent NOTCH-associated signaling states in endometrial cancer
Therapeutic resistance remains a major challenge in advanced and recurrent endometrial cancer (EC). Aberrant NOTCH signaling has been associated with aggressive tumor behavior and therapeutic resistance across multiple malignancies, yet its therapeutic significance in EC remains incompletely defined. We investigated whether auranofin (AuR), a noncanonical modulator of NOTCH signaling through the transcriptional effector RBPJ, alters […]