Project description:Lipid alterations in the brain have been implicated in many neurodegenerative diseases. To facilitate comparative lipidomic research across brain diseases here we establish a data common named the Neurolipid Atlas, that we have pre-populated with isogenic induced pluripotent stem cell (iPSC)-derived lipidomics data for different brain diseases. Additionally, the resource contains lipidomics data of human and mouse brain tissue. Leveraging multiple datasets, we demonstrate that iPSC-derived neurons, microglia, and astrocytes exhibit distinct lipid profiles that recapitulate in vivo lipotypes. Notably, the AD risk gene ApoE4 drives cholesterol ester (CE) accumulation specifically in human astrocytes, and we also observe CE accumulation in whole human AD brain lipidomics. Multi-omics interrogation of iPSC-derived astrocytes revealed that altered cholesterol metabolism plays a major role in astrocyte interferon-dependent pathways such as the immunoproteasome and major histocompatibility complex class I antigen presentation. Our data commons, available at neurolipidatlas.com, and allows for data deposition by the community and provides a user-friendly tool and knowledge base for a better understanding of lipid dyshomeostasis in neurodegenerative diseases.
Project description:Here we used functional proteomics approaches to identify an upstream transcription complex (USTC) that is required for piRNA biogenesis. The complex contains PRDE-1, SNPC-4, TOFU-4, and TOFU-5, all of which are enriched on the two piRNA clusters on chromosome IV and form distinct piRNA foci in the nucleus.
Project description:Pseudouridine (Ψ) is the most abundant RNA modification in nature; however, the exact biological functions of Ψ remain largely elusive. By employing an unbiased quantitative proteomics method, we identified multiple candidate reader proteins of Ψ in RNA, including a cytoskeleton protein profilin-1, whose mutations are linked with amyotrophic lateral sclerosis (ALS). We purified recombinant PFN1 and showed that it can bind directly and selectively to Ψ-containing RNA. We also found that PFN1 binds to thousands of transcripts in human cells, including a known Ψ site in the mRNA of TPI1. We showed that PFN1-Ψ interaction is crucial for regulating the stability and translation efficiency of TPI1 mRNA. Together, our data unveiled PFN1 as a reader protein of Ψ in RNA and illustrated the functions of PFN1-Ψ interaction in modulating the stability and translation efficiency of TPI1 mRNA, which provides new insights into the functions of Ψ in RNA biology and lays a strong foundation for the discovery of new mechanisms in disease pathogenesis
Project description:This project contains data of RP-LC-MS lipidomics of protein complex pull-downs (CoQ7, CoQ9, and CoQ7:CoQ9); data are associated with the manuscript titled "Structure and functionality of a multimeric human COQ7:COQ9 complex".
Project description:Lipidomics, proteomics and metabolomics characterization of the ontogeny of lipid, protein and metabolite changes during normal postnatal lung development
Project description:Interventions: Nutrition intervention group 1:Perioperative oral general sugar clear liquid diet (200 ml/bag) at time points;Nutrition intervention group 2:Perioperative Oral Complex Carbohydrate Purified Liquid Food (200ml/bag);Blank control group 3:Fasting from food and water 12 hours before surgery and 24 hours after surgery
Primary outcome(s): Intestinal barrier function;Semiquantitative typing of intestinal flora;Gut flora 16sRNA assay;albumin;Length of stay in hospital;Hospitalisation costs
Study Design: Parallel