TECPR2 HSAN9 Mutation CSF analysis Mouse
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Cerebrospinal Fluid
SUBMITTER: 
Karsten Nalbach
LAB HEAD: Stefan Lichtenthaler
PROVIDER: PXD059057 | Pride | 2025-10-23
REPOSITORIES: Pride
Dataset's files
Items per page: 5 1 - 5 of 13 |
Similar Datasets
Project description:Analysis of proteome changes in medulla in mice expressing a disease-mimicking TECPR2 variant
2025-10-23 | PXD065944 | Pride
Project description:In this work, changes in the proteome level during a step-wise adaptation of an adherent Madin Darby canine kidney (MDCK) cell line to suspension growth and chemically defined medium were analyzed.
2015-04-22 | PXD001306 | Pride
Project description:The beta-secretase BACE1 is a central drug target for Alzheimer’s disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. Here, we performed discovery proteomics to identify substrates of the protease BACE2 in plasma of mice. Therefore, we analysed plasma from BACE2 KO, and WT controls. Inactivation of BACE2 inhibited shedding of VEGFR3/FLT4. Thus, sVEGFR3 represents a pharmacodynamic plasma marker for BACE2 activity in vivo.
2024-06-27 | PXD041579 | Pride
Project description:The Beta-secretase BACE1 is a central drug target for Alzheimer’s disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. To discover potential BAC2 substrates in plasma, mice were treated with a non-specific BACE inhibitor (Cpd89) and a BACE1 preferring inhibitor (LY2811376). Plasma proteomics using DIA showed a reduced abundance of soluble FLT4 (sVEGFR3) for the non-specific inhbtor but not for the BACE1 preferring inhibitor. Conclusively, sVEGFR3 is a potential marker for BACE2 inhibition in plasma.
2024-06-27 | PXD042669 | Pride
Project description:CLPB is a mitochondrial intermembrane space AAA+ domain–containing disaggregase. CLPB mutations are associated with 3-methylglutaconic aciduria and neutropenia; however, the molecular mechanism underscoring disease and the contribution of CLPB substrates to disease pathology remains unknown. Interactions between CLPB and mitochondrial quality control (QC) factors, including PARL and OPA1, have been reported, hinting at dysregulation of organelle QC in disease. Utilizing proteomic and biochemical approaches, we define a stress-specific aggregation phenotype in a CLPB-null environment and define the CLPB substrate profile. We show an interplay between intermembrane space proteins including CLPB, HAX1, HTRA2, and the inner membrane quality control proteins (STOML2, PARL, YME1L1; SPY complex), with CLPB deficiency impeding SPY complex function by virtue of protein aggregation in the intermembrane space. We conclude that there is an interdependency of mitochondrial QC components at the intermembrane space/inner membrane interface, and perturbations to this network may underscore CLPB disease pathology.
2024-01-18 | PXD042313 | Pride
Project description:Small non coding RNA molecules (sncRNAs) are key mediators of virulence and stress inducible gene expressions in some pathogens. In this work we identify sncRNAs in the Gram positive opportunistic pathogen Enterococcus faecalis. Enterococcus faecalis. We characterized 11 sncRNAs by tiling microarray analysis, 5’ and 3’ RACE-PCR, and Northern blot analysis. Six sncRNAs were specifically expressed at exponential phase, two sncRNAs were observed at stationary phase, and three were detected during both phases. This is the first experimental genome-wide identification of sncRNAs in E. faecalis and provides impetus to the understanding of gene regulation in this important human pathogen. Identification of sncRNA candidates transcribed by E. faecalis V583 was undertaken with two samples of cells harvested in mid-log growth phase and stationary phase after 24h of incubation at 37°C in M17 glucose media.
2011-04-21 | E-GEOD-28741 | biostudies-arrayexpress
Project description:Bottom-up proteomic analyses rely on efficient protein extraction from tissue and proteolysis into peptides for mass spectrometry. Commonly used detergent-based strategies aid cell lysis and protein solubilization but are poorly compatible with downstream protein digestion and liquid chromatography-coupled mass spectrometry. Consequently, additional sample purification and buffer exchange steps are required, which are time-consuming and introduce additional technical variability. This study provides the first direct quantitative comparison of two well-established detergent-based methods for protein extraction and solubilization (In-solution and suspension trapping, S-Trap) with the recently developed Sample Preparation by Easy Extraction and Digestion (SPEED) method, which uses a strong acid for denaturation. Identification rates and quantitative performance of each method were compared with data-dependent acquisition (DDA) and label-free SWATH-MS (sequential window acquisition of all theoretical mass spectra) in both sheep kidney cortical tissue and plasma. In kidney tissue, SPEED outperformed In-solution and S-Trap by quantifying the highest number of unique proteins (SPEED 1,250; S-Trap 1,202; In-solution 1,197) and displayed the most efficient proteolysis (SPEED 93.8% of peptides fully tryptic in DDA; S-Trap 88.5%; In-solution 87.3%). In plasma, S-Trap produced the most unique protein quantifications (S-Trap 151; In-solution 148; SPEED 138), indicating it may be the optimal method for this biofluid. Protein quantifications were reproducible across biological replicates in both tissue (R2 from 0.85 to 0.90), and in plasma (SPEED R2=0.84; In-solution R2=0.76, S-Trap R2=0.65). Our data suggest SPEED as the optimal method for proteomic preparation in kidney tissue and S-Trap or SPEED as the optimal method for plasma, depending on whether a higher number of protein quantifications or greater reproducibility is desired.
2023-03-30 | PXD030797 | Pride
Project description:Abstract of associated menuscript; Quinones and alpha,beta-unsaturated carbonyls are naturally occurring electrophiles that target cysteine residues via thiol-(S)-alkylation. We analyzed the global expression profile of Bacillus subtilis to the toxic carbonyls methylglyoxal (MG) and formaldehyde (FA). Both carbonyl compounds cause a stress response characteristic for thiol-reactive electrophiles as revealed by the induction of the Spx, CtsR, CymR, PerR, ArsR, CzrA, CsoR and SigmaD regulons. MG and FA triggered also a SOS response which indicates DNA damage. Protection against FA is mediated by both the hxlAB operon, encoding the ribulose monophosphate pathway for FA fixation, and a thiol-dependent formaldehyde dehydrogenase (AdhA) and DJ-1/PfpI-family cysteine proteinase (YraA). The adhA-yraA operon and the yraC gene, encoding gamma-carboxymuconolactone decarboxylase, are positively regulated by the MerR-family regulator, YraB(AdhR). AdhR binds specifically to its target promoters which contain a 7-4-7 inverted repeat (CTTAAAG-N4-CTTTAAG) between the -35 and -10 elements. Activation of adhA-yraA transcription by AdhR requires the conserved Cys52 residue in vivo. We speculate that AdhR is redox-regulated via thiol-(S)-alkylation by aldehydes and that AdhA and YraA are specifically involved in reduction of aldehydes and degradation or repair of damaged thiol-containing proteins, respectively. WT (-FA) vs. WT (+ 1 mM FA), WT (-MG) vs. WT (+ 2.8 mM MG), WT (-MG) vs. WT (+ 5.6 mM MG). Each experiement was conducted triplicates using three independent total RNA preparations. For all datasets used for final analysis, untreated samples were labeled with Cy3 and treated samples with Cy5.
2010-05-15 | E-GEOD-13925 | biostudies-arrayexpress
Project description:The redox-sensing MarR/DUF24-type repressor YodB controls expression of the azoreductase AzoR1 and the nitroreductase YodC that are involved in detoxification of quinones and diamide in Bacillus subtilis. In the present paper, we identified YodB and its paralog YvaP (CatR) as repressors of the yfiDE (catDE) operon encoding a catechol-2,3-dioxygenase that also contributes to quinone resistance. Inactivation of both paralogs, CatR and YodB, results in full derepression of catDE transcription. DNA-binding assays and promoter mutagenesis studies showed that CatR protects two inverted repeats with the consensus sequence TTAC-N5-GTAA overlapping the -35 promoter region (BS1) and the transcriptional start site (BS2). The BS1 operator was required for binding of YodB in vitro. CatR and YodB share the conserved N-terminal Cys residue that is essential for redox-sensing of CatR in vivo as shown by Cys-to-Ser mutagenesis. Our data suggest that CatR is modified by intermolecular disulfide formation in response to diamide and quinones in vitro and in vivo. Redox-regulation of CatR occurs independently of YodB and no protein interaction was detected between CatR and YodB in vivo using protein-crosslinking and mass spectrometry. Control of Bacillus subtilis 168 wild type (Ko_WT) vs. DyvaP mutant (Ko_DyvaP). The experiment was conducted in duplicates using two independent total RNA preparations. For all datasets used for final analysis, wild-type samples were labeled with Cy3 and DyvaP mutant samples were labeled with Cy5.
2010-06-29 | E-GEOD-22603 | biostudies-arrayexpress
Project description:We performed unbiased quantitative mass spectrometry (MS)-based analysis to measure changes in protein abundance and oxidation in cerebrospinal fluid (CSF) from a cohort of Amyotrophic Lateral Sclerosis (ALS) patients and healthy controls at two time points (approximately four months apart) to capture disease progression. In addition, we developed a sensitive and targeted quantitative MS method to measure glutathione oxidation state in the same sets of CSF samples.
2025-07-14 | PXD053913 | Pride