OEX_Jia_2106210548
Ontology highlight
ABSTRACT:
TISSUE(S): ['tissues']
SUBMITTER: Jia Wu
PROVIDER: OEX00013809 | NODE | 2024-01-11
REPOSITORIES: NODE
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Project description:Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, we interrogated serum from subjects who received 2 doses of inactivated monovalent influenza A/Indonesia/05/2005 vaccine with or without AS03 or MF59 using hemagglutinin (HA) microarrays (NCT01317758 and NCT01317745). The arrays were designed to reflect both full length and globular head HA derived from 17 influenza A subtypes (H1 to H16 and H18) and influenza B strains. We observed significantly increased strain-specific and broad homo- and hetero-subtypic antibody responses with both AS03 and MF59 adjuvanted vaccination with AS03 achieving a higher titer and breadth of IgG responses relative to MF59. Adjuvanted vaccine was also associated with the elicitation of stalk directed antibody. We established good correlation of the array antibody responses to H5 antigens with standard HA inhibition and microneutralization titers.
2022-07-01 | GSE202387 | GEO
Project description:We developed three different protein arrays to measure IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers.
2021-07-24 | GSE180737 | GEO
Project description:Combining variant antigens into a multivalent vaccine is a traditional approach used to provide broad coverage against antigenically variable pathogens, such as polio, human papilloma and influenza viruses. However, strategies for increasing the breadth of antibody coverage beyond the vaccine are not well understood, but may provide more anticipatory protection. Influenza virus hemagglutinin (HA) is a prototypic variant antigen. Vaccines that induce HA-specific neutralizing antibodies lose efficacy as amino acid substitutions accumulate in neutralizing epitopes during influenza virus evolution. Here we studied the effect of a potent combination adjuvant (CpG/MPLA/squalene-in-water emulsion) on the breadth and maturation of the antibody response to a representative variant of HA subtypes H1, H5 and H7. Using HA protein microarrays and antigen-specific B cell labelling, we show when administered individually, each HA elicits a cross-reactive antibody profile for multiple variants within the same subtype and other closely-related subtypes (homosubtypic and heterosubtypic cross-reactivity, respectively). Despite a capacity for each subtype to induce heterosubtypic cross-reactivity, broader coverage was elicited by simply combining the subtypes into a multivalent vaccine. Importantly, multiplexing did not compromise antibody avidity or affinity maturation to the individual HA constituents. The use of adjuvants to increase the breadth of antibody coverage beyond the vaccine antigens may help future-proof vaccines against newly-emerging variants.
2021-06-26 | GSE178932 | GEO
Project description:Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer from cachexia, characterized by severe muscle and fat loss and yet, there are no biomarkers identified for this debilitating condition. Our objective was to identify circulating protein biomarkers using serum for human PDAC cachexia and understand their biological functions. Serum from 30 patients with PDAC was collected and protein profiles were generated using SOMAscan. The protein profiles were correlated with clinical variables such as Cancer associated weight loss (CAWL), body composition measurements of skeletal muscle index (SMI), skeletal muscle density (SMD), total adipose index (TAI) using Spearman’s correlation. Overall, 110 proteins of 1294 correlated with these clinical measures - 47 proteins for CAWL, 19 for SMI, 14 for SMD, and 30 for TAI (r-value 0.5, p<0.05). LYVE1, a homolog of CD44 implicated in tumor metastasis, was the top CAWL-associated protein (r= 0.67, p=0.0001). Protein co-expression network analysis identified immune system related pathways such as B-cell signaling, natural killer cell signaling, IL6 signaling in addition to identifying other known pathways in cachexia. Taken together, these data identify both immune system molecules and additional secreted factors and pathways not previously associated with PDAC and confirm the activation of previously identified pathways.
2020-12-31 | GSE119483 | GEO
Project description:Sex determination is mediated by two antagonistic genetic pathways. Sox9 activation or repression governs testis or ovary development, respectively. The remote enhancer Enh13 is critical for testicular Sox9 regulation, with its deletion or mutation causing XY female sex reversal. Here, we demonstrate that specific Enh13 mutations (1 bp insertion or 3 bp deletion) induce complete XX male sex reversal, with embryos exhibiting ovotestes and adults presenting with small testes. Transcriptomic analysis reveals elevated testicular gene expression, including Sox9, and repressed ovarian genes. These mutations disrupt cooperative binding of bipotential transcription factors to Enh13, preventing Sox9 repression in the ovary. Our findings establish Enh13 as a dual regulatory element essential for both testicular and ovarian development, positioning it at a critical intersection of sexual differentiation pathways.
2026-02-21 | GSE298334 | GEO
Project description:Using high-throughput antibody microarray, through cross-sectional sample detection and verification of samples that had undergone physical changes over time, it was found that people with balanced constitution and dampness constitution in Chinese medicine showed differences in serum protein expression. The differences were expressed as the level changes of 19 proteins such as Dectin-2, Siglec-7, AIF and TACI. The research results provided the basis for the scientific expression of traditional Chinese medicine (TCM) constitution.
2019-11-22 | GSE140769 | GEO
Project description:Kidney fibrosis represents an urgent unmet clinical need due to the lack of effective therapies and inadequate understanding of the molecular pathogenesis. We have generated a comprehensive and integrated multi-omics data set (proteomics, mRNA and small RNA transcriptomics) of fibrotic kidneys that is searchable through a user-friendly web application. Two commonly used mouse models were utilized: a reversible chemical-induced injury model (folic acid (FA) induced nephropathy) and an irreversible surgically-induced fibrosis model (unilateral ureteral obstruction (UUO)). mRNA and small RNA sequencing as well as 10-plex tandem mass tag (TMT) proteomics were performed with kidney samples from different time points over the course of fibrosis development. The bioinformatics workflow used to process, technically validate, and integrate the single data sets will be described. In summary, we present temporal and integrated multi-omics data from fibrotic mouse kidneys that are accessible through an interrogation tool to provide a searchable transcriptome and proteome for kidney fibrosis researchers.
2019-05-07 | GSE126182 | GEO
Project description:The type II nuclear receptors (NRs) function as heterodimeric transcription factors with the retinoid X receptor (RXR) to regulate diverse biological processes in response to endogenous ligands and therapeutic drugs. DNA-binding specificity has been proposed as a primary mechanism for NR gene regulatory specificity. We use protein-binding microarrays (PBMs) to comprehensively analyze the DNA binding of 12 NR:RXRα heterodimers. We find more promiscuous NR-DNA binding than has been reported, challenging the view that NR binding specificity is defined by half-site spacing. We show that NRs bind DNA using two distinct modes, explaining widespread NR binding to half-sites in vivo. Finally, we show that the current models of NR specificity better reflect binding-site activity rather than binding-site affinity. Our rich dataset and revised NR binding models provide a framework for understanding NR regulatory specificity and will facilitate more accurate analyses of genomic datasets.
2019-01-12 | GSE124910 | GEO
Project description:Background: Stress cardiomyopathy (SCM) is a unique form of LV dysfunction that more often occurs in women. Patients with SCM have a higher Troponin I/B-type natriuretic peptide ratio than AMI, but little is known about other circulating proteins. The goals of this study were to compare plasma proteins in SCM and AMI to learn about the pathophysiology of SCM and also to identify putative biomarkers of SCM. Methods: Blood was drawn in normal controls (n=6), women with AMI (n=12) or women with acute SCM (n=15). Two-week follow up samples were available in AMI (n=4) and SCM patients (n=11). Relative concentrations of 1310 serum proteins were measured in each of the 48 samples using the SOMAscan aptamer based assay. Women with AMI tended to be younger (57.87 ± 16.0 vs. 65.08 ± 9.11 years, p=0.12) and had a higher peak troponin I (AMI 32.03 ± 29.46 vs. SCM 2.68 ± 2.6 ng/mL, p=0.02). No differentially expressed proteins were detected (absolute log2 fold change>1; q<0.05) between AMI and SCM in the acute or recovery phase. In the normal vs. AMI comparison there was differential expression of 35 proteins. In the normal vs. SCM comparison there were 45 proteins with differential expression. Pathway analysis demonstrated activation of complement, coagulation, and inflammation in both AMI and SCM. Conclusions: The acute phase of SCM is characterized by a severe inflammatory response similar to AMI. Despite recovery of LV function in SCM at two weeks, differences in circulating proteins remain in comparison to normal controls.
2017-08-03 | GSE95368 | GEO
Project description:Hematopoietic stem cells (HSCs) primarily reside in the bone marrow, where they receive external cues from their local microenvironment. The complex milieu of biophysical cues, cellular components, and cell-secreted factors regulates the process by which HSC produce the blood and immune system. We previously showed direct co-culture of primary murine hematopoietic stem and progenitor cells with a population of marrow-derived mesenchymal stromal and progenitor cells (MSPCs) in a methacrylamide-functionalized gelatin (GelMA) hydrogel improves hematopoietic progenitor maintenance. However, the mechanism by which MSPCs influenced HSC fate decisions remained unknown. Herein, we report the use of proteomic analysis to correlate HSC phenotype to a broad candidate pool of 200 soluble factors produced by combined mesenchymal and hematopoietic progeny. Partial Least Squares Regression (PLSR), along with an iterative filter method, identified TGFβ-1, MMP-3, c-RP, and TROY as positively correlated with HSC maintenance. Experimentally, we then observe exogenous stimulation of HSC monocultures in GelMA hydrogels with these combined cytokines increases the ratio of hematopoietic progenitors to committed progeny after a 7-day culture 7.52 ± 3.65 fold compared to non-stimulated monocultures. Findings suggest a cocktail of the downselected cytokines amplify hematopoietic maintenance potential of HSCs beyond that of MSPC-secreted factors alone. This work integrates empirical and computation methods to identify cytokine combinations to improve HSC maintenance within an engineered HSC niche, suggesting a route towards identifying feeder-free culture platforms for HSC expansion.
2020-01-22 | GSE143987 | GEO