Kun Zhao Similar Datasets
Project description:Explore the expression profiles of amyloid signature proteins (serum amyloid P component, SAP; apolipoprotein E, ApoE; apolipoprotein A-IV) in various types of renal amyloidosis by mass spectrometry
2025-07-07 | PXD065833 |
Project description:Stop-loss mutations cause over twenty different diseases. The effects of stop-loss mutations can have multiple consequences that are, however, hard to predict. Stop-loss in ITM2B/BRI2 results in C-terminal extension of the encoded protein and, upon furin cleavage, in the production of two 34 amino acid long peptides, ADan and ABri, that accumulate as amyloids in the brains of patients affected by familial Danish and British Dementia. To systematically explore the consequences of Bri2 C-terminal extension, here, we measure amyloid formation for 676 ADan substitutions and identify the region that forms the putative amyloid core of ADan fibrils, located between positions 20 and 26, where stop-loss occurs. Moreover, we measure amyloid formation for ~18,000 random C-terminal extensions of Bri2 and find that ~32% of these sequences can nucleate amyloids. We find that the amino acid composition of these nucleating sequences varies with peptide length and that short extensions of 2 specific amino acids (Aliphatics, Aromatics and Cysteines) are sufficient to generate novel amyloid cores. Overall, our results show that the C-terminus of Bri2 contains an incomplete amyloid motif that can turn amyloidogenic upon extension. C-terminal extension with de novo formation of amyloid motifs may thus be a widespread pathogenic mechanism resulting from stop-loss, highlighting the importance of determining the impact of these mutations for other sequences across the genome.
2024-08-02 | GSE270792 | GEO
Project description:This dataset was utilized to assess the performance of a novel de novo metaproteomics pipeline, which performs sequence alignment of de novo sequences from complete metaproteomics experiments. Traditionally, metaproteomics data annotation relies on database searching that requires sample-specific databases derived from whole metagenome sequencing experiments. Creating these databases, however, is a complex, time-consuming, and error prone process, which can introduce biases affecting the outcomes and conclusions, highlighting the need for alternative methods. The evaluated approach offers rapid and orthogonal insights into metaproteomics data.
2024-10-10 | PXD050548 | Pride
Project description:In stable renal transplant recipients with hyperparathyroidism, the vitamin D agonist paricalcitol reduces the level of proteinuria. Animal studies have indicated possible anti-fibrotic and anti-inflammatory effects of paricalcitol. We hypothesised that early introduction of paricalcitol in de novo renal transplant recipients would reduce proteinuria and counteract development of fibrosis in the allograft.
2017-09-01 | GSE83486 | GEO
Project description:The amyloidoses constitute a group of diseases occurring in humans and animals that are characterized by abnormal deposits of aggregated proteins in organs, affecting their structure and function. In the Abyssinian cat breed, a familial form of renal amyloidosis has been described. In this study, multi-omics analyses were applied and integrated to explore some aspects of the unknown pathogenetic processes in cats. Whole-genome sequences of two affected Abyssinians and 195 controls of other breeds (part of the 99 Lives initiative) were screened to prioritize potential disease-associated variants. Proteome and miRNAome from formalin-fixed paraffin-embedded kidney specimens of fully necropsied Abyssinian cats, three affected and three non-amyloidosis affected were characterized. While the trigger of the disorder remains unclear, overall, i) 35,960 genomic variants were detected; ii) 215 and 56 proteins were identified as exclusive or overexpressed in the affected and control kidneys, respectively; iii) 60 miRNAs were differentially expressed, 20 of which are newly described. With omics data integration, the general conclusions are:i) the familial amyloid renal form in Abyssinians is not a simple monogenic trait ii) amyloid deposition is not triggered by mutated amyloidogenic proteins but is a mix of proteins codified by wild-type genes iii) the form is biochemically classifiable as AA amyloidosis.
2021-09-10 | PXD024140 | Pride
Project description:Immunoglobulin light chain (LC) amyloidosis (AL) is one of the most common types of systemic amyloidosis. The lack of reliable in vivo models hinders the study of the disease in its physiological context. We developped a transgenic mouse model producing high amounts of a human AL free light chain (LC). While mice exceptionnaly develop spontaneous AL amyloidosis and do not exhibit organ toxicity due to the circulating amyloidogenic LC, a single injection of amyloid fibrils, made up of the variable domain (VL) of the human LC, or soluble VL led to amyloid deposits, mainly in heart. The biochemical composition and the fragmentation pattern of the LC in the fibrils are highly similar to that of human AL fibrils, arguing for a conserved mechanism of amyloid fibrils formation. Amyloidosis positive mice also develop an early cardiac dysfunction, with increased NT-proBNP, diastolic dysfunction and remodeling of the extracellular matrix. Overall, this transgenic mice closely reproduces human cardiac AL amyloidosis and shows that a partial degradation of the LC initiate amyloid fibril formations in vivo. Accumulation of AL amyloid fibrils, rather than the soluble LC, drive the initial cardiac dysfunction. This model fills an important gap for research on AL amyloidosis and preclinical evaluation of new therapies.
2025-01-17 | GSE286368 | GEO
Project description:We identified the protein in purified AL amyloid fibrils extracted from heart tissues from transgenic mice developing AL amyloidosis.
2025-01-17 | PXD059000 | Pride
Project description:Amyloid deposition and neighboring tissue responses remain poorly understood. Twenty percent of patients with systemic light-chain amyloidosis (AL) have interstitial marrow amyloid containing clonal Ig light-chain fibrils and apolipoprotein chaperone proteins. We compared CD138-depleted aspirate mononuclear cells (MNC) from marrows of AL patients with (+MA) and without (-MA) interstitial amyloid by gene expression profiling (GEP) and single-cell RNA-sequencing (scRNA seq). GEP showed no differential expression of genes for proteolytic enzymes or apolipoproteins between the groups but +MA cases had significantly up-regulated erythroid genes involved in oxygen transport, including transmembrane and coiled-coil domain family 2 (TMCC2). In +MA marrows at the single-cell level, CD14+ monocytes were increased by 22%, granulocyte-monocyte progenitors decreased by 66%, and erythroid-megakaryocyte progenitors and early and late erythroid progenitors increased up to five-fold. Gene enrichment studies showed that in +MA marrows pathways for TNFα signaling, immune activation, monocyte hypoxia and erythropoiesis were significantly enriched. We also compared peripheral blood and marrow plasma by immunoprecipitation and immunoblot with respect to apolipoproteins and light chains in complex with the erythroid protein TMCC2, and by ELISA for marrow apolipoprotein E and J levels. Apolipoprotein J is strongly associated with light chains in blood and E is not, while in +MA marrow plasma J and E are strongly present in association with light chains. There is also significantly more apolipoprotein E and J in +MA marrow plasma. In summary, marrows with interstitial amyloid provide opportunities to study amyloid’s impact on cellular and regenerative activity and chaperone involvement in amyloid formation.
2023-12-01 | GSE239717 | GEO
Project description:In stable renal transplant recipients with hyperparathyroidism, the vitamin D agonist paricalcitol reduces the level of proteinuria. Animal studies have indicated possible anti-fibrotic and anti-inflammatory effects of paricalcitol. We hypothesised that early introduction of paricalcitol in de novo renal transplant recipients would reduce proteinuria and counteract development of fibrosis in the allograft. A single centre, prospective, randomized, open label trial investigating the additional effect of paricalcitol 2ug/day to standard care was performed. Participants were included 8 weeks after engraftment irrespective of PTH-level and followed for 44 weeks. Microarray analyses were performed in kidney biopsies at study end for the investigation of potential effects on gene expression profile. This dataset is part of the TransQST collection.
2017-09-01 | E-GEOD-83486 | biostudies-arrayexpress
Project description:Transcriptome profiling of de novo-derived ccRCC cell cultures and their matching parental tumours. VHL-mutant and VHL wild-type cultures were established by isolating CA9+ and CA9- cells from tumor samples using FACS. RNASeq expression profiling of 18 renal cell carcinoma samples, including 6 patient tumours, 6 VHL mutant and 6 VHL WT derivative cell cultures
2016-06-01 | E-GEOD-74958 | biostudies-arrayexpress