Fibroblasts of healthy control and COA5 mutation carrying patient
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: 
Tuula Nyman
LAB HEAD: Tuula Nyman
PROVIDER: PXD050891 | Pride | 2025-01-07
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| LC-MS_files_metabo_COA5.zip | Other | |||
| report_COX5A_metabo2532.zip | Other |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:A major challenge in the field of mechanobiology relates to the lack of methods that enable identification of mechanically active cells and force transmitting receptors for subsequent biochemical analysis. For example, potent T cell activation requires the transmission of biophysical forces between the T cell receptor (TCR) and its peptide-loaded major histocompatibility complex (pMHC) antigens. Therefore, methods that can chemically tag mechanically active T cells and TCRs are highly desirable, as these techniques will enable a deeper understanding of the mechanisms governing immune responses and may also have broad applications in immunotherapy. Herein, we report a technique dubbed mechano-ID, which allows for mechanically selective proximity tagging by leveraging DNA-based molecular force probes that recruit proximity tagging enzymes. We demonstrate mechano-ID tagging of T cells using microscopy and flow cytometry and this is further confirmed using western blotting of mechanically active T cell receptors.
2025-09-26 | PXD066067 | Pride
Project description:HIGHTLIGHTS-Improved protocol for ISF collection using microdialysis and CSF sampling in mice.-Combined LC‒MS/MS proteomics ISF and CSF analyses for the validation and description of potential new AD biomarkers.-ISF proteomics analysis to track disease progression at the neuronal and glial levels.-Identification of new biomarker candidates for Alzheimer’s disease.ABSTRACTBackground: Mass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain.New method: We performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice.Results: We identified up to 625 proteins in ISF and 4,483 proteins in CSF samples. By comparing the biofluid profiles of APPtg and C57Bl/6J mice, we detected 37 and 108 significantly up- and downregulated candidates, respectively. In ISF, 7 highly regulated proteins, such as Gfap, Aldh1l1, Gstm1, and Txn, have already been implicated in AD progression, whereas in CSF, 9 out of 14 highly regulated proteins, such as Apba2, Syt12, Pgs1 and Vsnl1, have also been validated to be involved in AD pathogenesis. In addition, we also detected new interesting regulated proteins related to the control of synapses and neurotransmission (Kcna2, Cacng3, and Clcn6) whose roles as AD biomarkers should be further investigated.Comparison with existing methods: This newly established combined protocol provides better insight into the mutual communication between ISF and CSF as an analysis of tissue or CSF compartments alone.Conclusions: The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.KEYWORDSAlzheimer’s disease, CSF, ISF, proteomics, biomarkers, microdialysis, mass spectrometry, protein identification, neurodegeneration, brain fluids, expression profilesDATA AVAILABILITYDOI: 10.17605/OSF.IO/VWQ58PUBLICATIONS using this dataset:1)Gorska et al. 2024, Journal of Neuroscience Methodshttps://doi.org/10.1016/j.jneumeth.2024.1102392) to come
2024-08-28 | PXD048864 | Pride
Project description:SARS-CoV-2 encodes numerous virulence factors, yet their precise mechanisms of action remain unknown. We provide evidence that the SARS-CoV-2 non-structural protein 15 (nsp15) enhances viral virulence by suppressing the production of viral double-stranded (dsRNA), a potent inducer of antiviral signaling. The viral variants lacking nsp15 endoribonuclease (EndoU) activity elicited higher innate immune responses and exhibited reduced replication in human stem cell-derived lung type II alveolar epithelial cells, as well as in the lungs of infected hamsters. Consistent with these findings, the catalytically inactive EndoU mutants caused significantly less mortality compared to the wild-type virus in K18-hACE2 mice. Mechanistically, the cells infected with EndoU mutants accumulated more viral double-stranded RNA, causing enhanced stimulation of antiviral pathways. The depletion of proteins involved in viral RNA sensing dampened immune responses to EndoU mutants. These findings indicate that the nsp15 EndoU activity contributes to viral virulence by antagonizing the host antiviral defense mechanisms.
2025-06-30 | PXD056702 | Pride
Project description:The data-independent acquisition (DIA)-based mass spectrometry was conducted to analyze salivary proteomics of patients with catathrenia.
2025-07-02 | PXD051324 | Pride
Project description:Spatial tissue proteomics combining microscopy-based cell phenotyping with ultrasensitive mass spectrometry (MS)-based proteomics is an emerging and powerful concept for the study of cell function and heterogeneity in health and disease. However, optimized workflows that preserve morphological information for image-based phenotype discovery and maximize proteome coverage of few or even single cells from laser microdissected archival tissue, are currently lacking. Here, we report a robust and scalable workflow for the proteomic analysis of ultra-low input formalin-fixed, paraffin-embedded (FFPE) material. Benchmarking in the murine liver resulted in up to 2,000 quantified proteins from single hepatocyte contours and nearly 5,000 proteins from 50-cell regions with high quantitative reproducibility. Applied to human tonsil, we profiled 146 microregions including spatially defined T and B lymphocyte niches and quantified cell-type specific markers, cytokines, immune cell regulators and transcription factors. These rich data also highlighted proteome dynamics in spatially defined zones of activated germinal centers, illuminating sites undergoing active B-cell proliferation and somatic hypermutation. Our results demonstrate the power of spatially-resolved proteomics for tissue phenotyping by integrating high-content imaging, laser microdissection, and ultrasensitive mass spectrometry. This approach has broad implications for a wide range of biomedical applications, including early disease profiling, drug target discovery and biomarker research.
2023-11-08 | PXD042367 | Pride
Project description:Background & Aims Recent studies showed that patients suffering from lysosomal acid lipase-deficiency (LAL-D) benefit tremendously from enzyme replacement therapy (ERT), however, the outcomes on liver histology in treated patients were inconsistent. The promising results of the pan-PPAR agonist lanifibranor in alleviating liver inflammation in patients with nonalcoholic steatohepatitis prompted us to investigate the effects of lanifibranor on liver pathology in LAL knockout (Lal-/-) mice. Methods Lal-/- mice were daily gavaged with lanifibranor or vehicle for 21 days. The effects of the treatment were assessed by measuring body and organ weights, plasma lipids and lipoproteins, as well as hematological parameters, followed by liver proteomics and metabolomics. Results Lanifibranor treatment slightly altered organ weights without affecting the total body weight of Lal-/- mice. We observed major changes in the proteome, with multiple proteins related to lipid metabolism, peroxisomal, and mitochondrial activities being upregulated and inflammation-related proteins being downregulated in the livers of treated mice. Hepatic lipid levels and histology remained unaltered, whereas plasma triglyceride and total cholesterol levels were decreased and the lipoprotein profile of lanifibranor-treated Lal-/- mice improved. Conclusions Lanifibranor treatment positively affected liver inflammation and lipoprotein homeostasis in Lal-/- mice. These findings support further evaluation of lanifibranor in combination with ERT for phenotype improvement in Lal-/- mice and a possible exploration avenue for the treatment of LAL-D in humans.
2024-06-12 | PXD047957 | Pride
Project description:dia-PASEF analysis of human amygdala in Alzheimer’s disease
2023-06-28 | PXD038322 | Pride
Project description:dia-PASEF analysis of human amygdala in Parkinson’s disease
2024-01-26 | PXD043503 | Pride
Project description:Objective Development of novel treatments for coeliac disease (CeD) is dependent on precise tools to monitor changes in gluten-induced mucosal damage. Current histology measures are subjective and difficult to standardise. Biopsy proteome scoring is an objective alternative to histology which is based on robust changes in biological pathways that directly reflect gluten-induced mucosal damage. In this study we aimed to evaluate biopsy proteome scoring as effect measure in a clinical trial setting by measuring intestinal remodeling in response to oral gluten challenge. Design We analyzed biopsies from a gluten challenge trial of treated CeD patients that consumed 3 g (n=6) or 10 g (n=7) gluten per day for 14 days. Sections from individually embedded biopsies collected before and after challenge were processed for proteome scoring (n = 109) and measurement of Vh:Cd ratio (n = 58). Proteome scores were compared to histology, intraepithelial lymphocyte (IEL) frequency and plasma interleukin-2 (IL-2). Results Change in proteome scores were significant for the group of patients who consumed 10 g gluten, but not for the group who consumed 3 g gluten. Altogether, 8 of 13 patients had changes in delta proteome scores above cut-off. Proteome scores correlated with Vh:Cd ratios both at run-in and at day 15. Proteome scores at day 15 correlated with IEL frequency and with serum IL-2 levels measured 4 hours post gluten intake. Conclusion Biopsy proteome scoring is a simple and reliable measure of gluten-induced mucosal remodeling in response to 14-day oral gluten challenge.
2025-04-08 | PXD050655 | Pride
Project description:M2-polarized tumor-associated macrophages (TAMs) are a key factor contributing to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). While various factors within the tumor microenvironment drive their formation, the role of PDAC-derived exosomes in this process remains unclear. We aim to clarify the regulatory impacts of tumor-derived exosomes to TAMs. Through multi-Omics analysis, we identified CCT6A as a novel tumor-derived exosomal protein, bridging TAMs M2 polarization and PDAC prognosis. Co-culture with exosomes derived from CCT6Ahigh PDAC leads to greater M2 phenotype of TAMs via PI3K-AKT signaling. According to proteomics data, chemokines’ abundance reduces over tenfold once exosomal CCT6A absence, including CXCL1, CXCL3, CXCL20 and CCL5, whose interaction with CCT6A in PDAC cells was confirmed by interactomics data. Morever, we found CCT6A clearance abrogated the antagonism effects of CD47 antibody immunotherapy. The subunit of the T-complex protein Ring Complex (TRiC) CCT6A serves as a matchmaker, during exosomes-mediated chemokines transfer from PDAC to TAMs.
2025-05-26 | PXD056403 | Pride