TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: The BXD2 mouse strain spontaneously develops glomerulonephritis and erosive arthritis. The goal of this study was to identify the antigenic target proteins and epitopes and to unravel the mechanisms by which the related conditions arise in BXD2 mice.', 'Individual hybridomas isolated from the spleen of a 10-month-old BXD2 mouse were injected intraperitoneally into nonautoimmune mice for evaluation of pathogenicity of each autoantibody. Autoantigens were immunoprecipitated with the pathogenic autoantibody L3A4. Autoantigens were identified using enzyme-linked immunosorbent assay, Western blotting, 2-dimensional gel electrophoresis, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS) and tandem MS. Antigenic epitopes were determined using a high-throughput epitope mapping method.', 'The production of autoantibodies in BXD2 mice occurred in an orderly progression, with peak levels of autoantibodies to nitrotyrosine (NT)-modified enolase, Ro, alpha-actin, and heat-shock proteins (HSPs) preceding peak levels of antihistone, anti-DNA, and rheumatoid factor. Two monoclonal autoantibodies, L3A4 and T56G10, were identified that could induce immune complexes, renal disease, and/or arthritis. Both L3A4 and T56G10 were polyreactive, and each reacted with separate sets of autoantigens. The antigenic targets of L3A4 consisted of NT-modified enolase, ATP5b, alpha-actin, and Hsp70 family proteins including Hspa5 and Hsp74. The antigenic epitopes of NT-modified enolase and Hspa5 exhibited sequence homology and cross-reactivity, suggesting that epitope spreading may occur through a molecular mimicry mechanism.\Question: Does production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice cause glomerulonephritis and arthritis?

SOLUTION: The polyreactivity of autoantibodies that target a novel class of autoantigens may enable these autoantibodies to induce erosive arthritis or glomerulonephritis either by direct pathogenic mechanisms or indirectly via Fc or immune complex deposition.

PROBLEM: Context: Platelet concentrates are important for support of patients with malignancies requiring myelotoxic chemotherapy. During storage, 10% to 15% of platelets may become activated resulting in the release of alpha-granules, which contain growth factors. We hypothesize that, during storage, growth factors accumulate in the plasma, specifically platelet-derived growth factor, vascular endothelial growth factor (VEGF), transforming growth factor-beta, and fibroblast growth factor-2, which may adversely affect cancer patients.', 'The concentrations of growth factors were measured by ELISA from the plasma of apheresis platelets serially throughout storage (days 1, 3, 5, and 7) and compared with concentrations in fresh plasma from healthy blood donors. Washing was evaluated as a method of growth factor removal, and an in vitro model of platelet transfusion in a patient receiving Bevacizumab (Avastin) using immunoprecipitation was employed to determine if Bevacizumab would be bound by the VEGF in apheresis platelets.', 'VEGF, platelet-derived growth factor, and transforming growth factor-beta were increased on day 1 versus fresh plasma and throughout storage reaching a relative maximum at outdate (P < 0.01, day 5 or 7). Fibroblast growth factor-2 concentrations were significantly increased on day 7 alone versus day 1 or to fresh plasma (P < 0.01). Washing removed 41 +/- 11% to 56 +/- 2% of the growth factors. Bevacizumab effectively bound the VEGF from apheresis platelets, with significant amounts of VEGF remaining in the supernatant.\Question: Do oncogenic and angiogenic growth factors accumulate during routine storage of apheresis platelet concentrates?

SOLUTION: Significant amounts of growth factors are present in apheresis platelets due to the isolation procedures, and these concentrations increase over storage, which may be partially removed by washing. In addition, apheresis platelet transfusion could affect cancer treatment by binding monoclonal antibodies directed against growth factors of tumor origin.

PROBLEM: Context: Allergic asthma is characterized by inflammation and airway remodeling. Bronchial epithelium is considered a key player in coordinating airway wall remodeling. In mild asthma, the epithelium is damaged and fails to proliferate and to repair, whereas in severe asthma, the epithelium is highly proliferative and thicker. This may be due to different regulatory mechanisms. The purpose of our study was to determine the role of miRNAs in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison with cells obtained from mild asthmatics and healthy controls.', 'Human bronchial epithelial cells (BEC) were isolated by bronchoscopy from bronchial biopsies of healthy donors and patients with mild and severe asthma. MiRNA expression was evaluated using the TaqMan low-density arrays and qRT-PCR. Transfection studies of bronchial epithelial cells were performed to determine the target genes. Cell proliferation was evaluated by BrdU incorporation test.', 'MiR-19a was upregulated in epithelia of severe asthmatic subjects compared with cells from mild asthmatics and healthy controls. Functional studies based on luciferase reporter and Western blot assays suggest that miR-19a enhances cell proliferation of BEC in severe asthma through targeting TGF-β receptor 2 mRNA. Moreover, repressed expression of miR-19a increased SMAD3 phosphorylation through TGF-β receptor 2 signaling and abrogated BEC proliferation.\Question: Does microRNA-19a enhance proliferation of bronchial epithelial cells by targeting TGFβR2 gene in severe asthma?

SOLUTION:
Our study uncovers a new regulatory pathway involving miR-19a that is critical to the severe phenotype of asthma and indicates that downregulating miR-19a expression could be explored as a potential new therapy to modulate epithelium repair in asthma.