Stress responses, including the unfolded protein response (UPR), are commonly studied via induction with harsh exogenous stressors, leaving endogenous functions of these pathways less well understood. We found that the endogenous UPR that precedes meiosis in budding yeast is required for gamete production but diverges dramatically from previously defined UPR outputs, with only a few […]
Ceramide Synthases Regulate Myristate-Induced Intestinal IRE1α Activation
Background & Aims: High-fat diets (HFDs) are a major modifiable risk factor for intestinal health. Current research focuses primarily on palmitate (C16:0); however, myristate (C14:0, rich in dairy products) has been minimally investigated. HFDs increase ceramide generation which drives endoplasmic reticulum (ER) stress; with both sphingolipids and ER stress being key contributors to intestinal biology. […]
The UPR drives gametogenesis via an unexpected response, coordinating translation and ER structure
Stress responses, including the unfolded protein response (UPR), are commonly studied via induction with harsh exogenous stressors, leaving endogenous functions of these pathways less well understood. We found that the endogenous UPR that precedes meiosis in budding yeast is required for gamete production but diverges dramatically from previously defined UPR outputs, with only a few […]
Ceramide Synthases Regulate Myristate-Induced Intestinal IRE1α Activation
Background & Aims: High-fat diets (HFDs) are a major modifiable risk factor for intestinal health. Current research focuses primarily on palmitate (C16:0); however, myristate (C14:0, rich in dairy products) has been minimally investigated. HFDs increase ceramide generation which drives endoplasmic reticulum (ER) stress; with both sphingolipids and ER stress being key contributors to intestinal biology. […]
Expanded Proteome Coverage Powered by Advanced Ion Processing Enables Deep Single-Cell Drug Response Subtyping in Human Stem Cell Derived Cardiomyocytes
Single-cell proteomics (SCP) enables the study of cellular heterogeneity at the functional level but remains limited by incomplete proteome coverage and high data missingness. Here, we present an enhanced label-free SCP workflow that leverages the timsUltra AIP mass spectrometry platform equipped with the Athena Ion Processor (AIP). Across a controlled dilution series of human induced […]
iSsus3744: A Genome-Scale Model-Guided Strategy for Rational Media Design for Cultivated Pork
Cultivated meat production is currently limited by high production costs and an incomplete understanding of cellular metabolism in agriculturally relevant species. Genome-scale metabolic models (GEMs) have successfully guided media optimization in biopharmaceutical systems but have not been widely applied to cultivated meat. In this study, we present iSsus3744, the first genome-scale metabolic reconstruction for Sus […]
Expanded Proteome Coverage Powered by Advanced Ion Processing Enables Deep Single-Cell Drug Response Subtyping in Human Stem Cell Derived Cardiomyocytes
Single-cell proteomics (SCP) enables the study of cellular heterogeneity at the functional level but remains limited by incomplete proteome coverage and high data missingness. Here, we present an enhanced label-free SCP workflow that leverages the timsUltra AIP mass spectrometry platform equipped with the Athena Ion Processor (AIP). Across a controlled dilution series of human induced […]
iSsus3744: A Genome-Scale Model-Guided Strategy for Rational Media Design for Cultivated Pork
Cultivated meat production is currently limited by high production costs and an incomplete understanding of cellular metabolism in agriculturally relevant species. Genome-scale metabolic models (GEMs) have successfully guided media optimization in biopharmaceutical systems but have not been widely applied to cultivated meat. In this study, we present iSsus3744, the first genome-scale metabolic reconstruction for Sus […]
Systematic In Silico Off-Target Assessment of siRNAs: Integrated Tissue-Specific Scoring and Cross-Species Preclinical Model Selection with TargetSureR
Small interfering RNAs (siRNAs) have become a transformative class of nucleic acid therapeutics for clinical disease treatment, yet sequence-dependent off-target silencing continues to pose a major safety barrier that hinders their preclinical refinement and large-scale translational application. Existing bioinformatics tools only support partial off-target evaluation, either focusing on basic sequence optimization or simple seed-region scanning, […]
GAPVD1 regulates CSNK1D-dependent PER2 FASP phosphorylation
The mammalian circadian clock relies on precisely timed transcriptional and post-translational events to generate ~24-hour rhythms. A key post-translational mechanism is phosphorylation of PER2 by CSNK1D, governed by a phosphoswitch that integrates stabilizing and destabilizing phosphorylation marks at the FASP and Degron sites to control PER2 stability and circadian period. Here, a novel role for […]
Targeted Analysis of >1500 Plasma Proteoforms via Individual Ion Mass Spectrometry
Plasma proteomics has long sought to accessibly sense human biology, precisely detect disease states, and advance diagnostics through clinical translation. In recent years, companies with defined panels such as Olink and Somascan have entered the field to complement bottom-up mass spectrometry (BUP). This study leverages a novel mass spectrometry platform to capture targeted proteoform information […]
Clinical isolates of Mycobacterium avium complex reveal an M. intracellulare-associated IL-17/neutrophilic pulmonary immune program in a murine disease model
Mycobacterium avium complex (MAC) is the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) and mainly comprises M. avium (MAV) and M. intracellulare (MI). Host-pathogen interactions may contribute to the heterogeneous clinical course of MAC pulmonary disease (MAC-PD); however, species- or isolate-associated differences in virulence and host immune responses induced by MAC strains remain poorly […]