RochePlasma_Combined_33
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Plasma Non-glyco
SUBMITTER:
PROVIDER: PAe003726 | PeptideAtlas |
REPOSITORIES: PeptideAtlas
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Project description:Human healthy donor CD8+ T cell lysates were analyzed by RPPA
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Project description:Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naive mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, the introduction of genes encoding immunomodulatory functions into a candidate LAIV can serve as natural adjuvants to improve overall vaccine safety and efficacy.
2021-07-05 | GSE179334 | GEO
Project description:Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention.
2021-04-21 | GSE172471 | GEO
Project description:To identify immunodominant antigens that elicit a humoral immune response following a primary genital infection, rhesus monkeys were inoculated cervically with Chlamydia trachomatis serovar D. Serum samples were collected and probed with a protein microarray expressing 864/894 (96.4%) of the open reading frames of the C. trachomatis serovar D genome. The antibody response was analyzed in 72 serum samples from 12 inoculated monkeys. The following criteria were utilized to identify immunodominant antigens: proteins found to be recognized by at least 75% (9/12) of the infected monkeys with at least 15% elevations in normalized signal intensity from week 0 to week 8 post infection. All infected monkeys developed Chlamydia specific serum antibodies. Eight proteins satisfied the selection criteria for immunodominant antigens: CT242 (OmpH-like protein), CT541 (mip), CT681 (ompA), CT381 (artJ), CT443 (omcB), CT119 (incA), CT486 (fliY), and CT110 (groEL). Of these, three antigens, CT119, CT486 and CT381, were not previously identified as immunodominant antigens using non-human primate sera. In conclusion, these immunodominant antigens can now be tested for their ability to identify individuals with a primary C. trachomatis genital infection and to design a vaccine strategy to protect against a primary infection with this pathogen.
2020-05-27 | GSE151183 | 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
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:Background: Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in animal models of diabetes. Human studies have also revealed loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages in full thickness gastric biopsies from gastroparesis patients. Aim: We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in full thickness gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying and symptoms. Methods: Full-thickness gastric antrum biopsies were obtained from nine DG, seven IG patients and five non-diabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1300 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity Pathway Analysis and correlations were carried out. Multiple-testing corrected p-values <0.05 were considered statistically significant. Results: 73 proteins were differentially expressed in DG, 132 proteins in IG and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway (DG FDR: 7.9x10-9; IG FDR: 6.3x10-12). In DG, properdin expression correlated with GCSI-bloating (r: -0.99, FDR: 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C zeta type and complement C2 correlated with 4 hr gastric retention (r: -0.97, FDR: 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Conclusions: Protein expression changes suggest a central role of macrophage-driven immune dysregulation and complement activation in gastroparesis.
2019-09-15 | GSE130672 | GEO
Project description:Endoglin (EDG) is a cell surface protein with an important role in the establishment of neo-angiogenesis and vasculogenic mimicry. EDG is part of the transforming growth factor-β (TGF-β) family, acting as an important co-receptor. EDG is shed from the cell surface into the extracellular compartment by matrix metalloproteinase 14 (MMP14), in its soluble form (sEDG). Both transmembrane and soluble forms of EDG exert important signaling functions in the development of new blood vessels and tumour progression. To better understand the role of EDG in Ewing sarcoma (ES), a deadly neoplasm of late childhood and adolescence, we test the efficacy of OMTX703, an endoglin-targeting antibody-drug conjugate in ES8 xenograft. Having determined an optimal dose for OMTX703, an additional experiment was conducted to assess the mechanism(s) of OMTX703 action and its potential mechanism(s) of resistance following a 2-week exposure to OMTX703 at 0, 10, 30, and 60 mg/kg; 246 proteins were assessed by reverse-phase protein array (RPPA). Analysis of variance (ANOVA), Pearson’s correlation as distance metric and Ward’s linkage as the clustering method using a false discovery rate (FDR) of 0.01, identified 60 proteins that discriminated between treatment groups (Matrix#1-Normalized Values). To investigate the proteomic changes associated with the heightened clinical activity of the 60 mg/kg dose, a secondary analysis was performed, which grouped the 10 mg/kg OMTX703 samples and the 10 mg/kg OMTX003 ones with the placebo-treated samples (Matrix#2-Normalized Values). Using a FDR of 0.0001, an absolute log2 fold change of 1.5, Pearson’s correlation as distance metric and Ward’s linkage as the clustering method, 22 proteins were discriminately identified between the 3 treatment groups (Matrix#2-Normalized Values). Notably, a protein regulator of altered metabolism (RPS6) was exclusively upregulated following OMTX703 (60mg/kg), and a second metabolism biomarker (LDHA) was down-expressed in the 30 and 60 mg/kg-treated groups. Conversely, BRD4 was one of about a dozen proteins that were preferentially down-regulated in samples treated only by 60 mg/kg.
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