Hailey-Hailey disease (HHD) is a genetic skin blistering disorder lacking approved treatments despite linkage to ATP2C1 variants 25 years ago. Since knockout mice did not replicate HHD, we ablated ATP2C1 in human keratinocytes or chemically inhibited its encoded Golgi calcium pump SPCA1. In organotypic epidermis, SPCA1 deficiency or inhibition reproduced HHD pathology, disrupting desmosomal cadherins […]

Fatty acid biosynthesis is a central metabolic process required for membrane formation, organelle maintenance, and cellular proliferation, yet its broader relationship with stress responses and cellular aging remains incompletely understood. Here, we combined human and yeast interactome analyses with transcriptomic profiling and chronological lifespan assays to investigate the systems-level organization of fatty acid metabolic pathways […]

Accurate in vivo prediction of neuropathology is critical for advancing diagnosis and treatment of Alzheimer’s disease and related dementias (ADRDs). As many individuals with ADRDs have mixed pathologies (beta-amyloid, pathologic tau, cerebrovascular disease, vascular brain injury, pathologic TDP-43, hippocampal sclerosis, Lewy bodies), there is interest in determining how accurately we can infer these pathologic changes […]

Parasitism is one of the most widespread trophic strategies in nature, though its diversity and ecological distribution in marine ecosystems remain poorly characterized. Apicomplexa are a major clade of obligate parasites best known for medically important taxa, yet their diversity and distribution in the ocean is still largely unresolved. Here, we used metabarcoding data from […]

Native mass spectrometry (nMS) is well established for measuring protein masses and stoichiometries using nano-electrospray ionization (nESI), yet salt adduction and source activation energies can limit routine measurements. In this study, we benchmark submicron quartz nanopipette nESI emitters (<50 nm internal diameter) across three mass spectrometry platforms (quadrupole-time-of-flight, quadrupole-Orbitrap, and tribrid-Orbitrap platforms) and a wide […]

Anxiety disorders are highly prevalent and often refractory to existing treatments, motivating the development of alternative neuromodulatory strategies. Peripheral bioelectronic approaches targeting the gut-brain axis, such as vagus nerve stimulation (VNS), demonstrate that modulation of visceral afferent pathways can influence central emotional circuits. Gastric electrical stimulation (GES) is a clinically established therapy for gastrointestinal motility […]

Glioblastoma (GBM) comprises a complex ecosystem of malignant, immune, vascular and neural transcriptional states. However, it remains difficult to determine which gene expression programmes are reproducibly recovered across independent cohorts and profiling platforms, because programme-level analyses are sensitive to cohort composition, technical context and factorization rank. Here, we analyzed three public GBM datasets–GLASS and IVYGAP […]

Proteins fold through ensembles of competing pathways, yet the kinetic contribution of each route remains difficult to quantify. Structure-prediction methods such as AlphaFold identify folded endpoints, but do not resolve folding kinetics, pathway heterogeneity, or how flux partitions among competing mechanisms. Here, we introduce a framework that directly decomposes folding flux into pathway-specific kinetic contributions […]

Chemotherapy and radiation reduce tumor burden but leave behind residual cells that survive via therapy-induced senescence (TIS). These cells constitute a latent reservoir fueling recurrence, yet strategies for their selective elimination are lacking. Here, we identify lysosomal ferrous iron accumulation as a conserved hallmark and actionable vulnerability of TIS tumor cells. Across diverse models, senescent […]

Gammaherpesvirus reactivation drives a collapse of host mRNA splicing fidelity that extends across the transcriptome, with exon skipping affecting up to ~57% of expressed genes, exceeding the effects of depletion of any of 186 splicing factors. Combining five Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) reactivation systems across B cell and epithelial models with […]