Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
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Question: ID4 gene is a member of the inhibitor of DNA binding (ID) family proteins that inhibit DNA binding of basic helix-loop-helix transcription factors. The epigenetic inactivation of ID4 gene on colorectal cancer (CRC) development and its clinical significance was assessed.', 'In CRC cell lines, ID4 methylation status of the promoter region was assessed by methylation-specific PCR and bisulfite sequencing. The mRNA expression level was assessed by quantitative real-time reverse transcription-PCR. The methylation status of 9 normal epithelia, 13 adenomas, 92 primary CRCs, and 26 liver metastases was assessed by methylation-specific PCR. ID4 protein expression was assessed by immunohistochemistry analysis of tissue specimen.', 'CRC cell lines were shown to be hypermethylated, and mRNA expression was suppressed and could be restored by 5-aza-cytidine treatment. In clinical specimens from normal epithelia, adenomas, primary CRCs, and liver metastases, the frequency of ID4 hypermethylation was 0 of 9 (0%), 0 of 13 (0%), 49 of 92 (53%), and 19 of 26 (73%), respectively, with a significant elevation according to CRC pathological progression. Methylation status of primary CRCs significantly correlated with histopathological tumor grade (P = 0.028). Immunohistochemistry analysis showed ID4 expression of normal colon epithelia, adenomas, and unmethylated primary CRCs but not hypermethylated CRC specimens. Among 76 American Joint Committee on Cancer stage I to IV patients who had undergone curative surgical resection, overall survival was significantly poorer in patients with hypermethylated ID4 bearing tumors (P = 0.0066).

Answer: Does epigenetic inactivation of ID4 in colorectal carcinomas correlate with poor differentiation and unfavorable prognosis?

Question: To investigate the inhibition of amyloid beta-protein 42 (Abeta42) production in M146L cells by gamma-schisandrin.', 'M146L cells which can produce considerable Abeta42 in vitro were treated with gamma-schisandrin (1.67, 5.00 and 15.00 microg x mL(-1)), beta-secretase inhibitor (S4562, 100.00 microg x mL(-1)) and gamma-secretase inhibitor (S2188, 13.68 microg x mL(-1)), separately. Cell counting kit-8 (CCK-8) was used to assess cell viability. Enzyme-linked immunosorbent assay (ELISA) was carried out to determine the amount of Abeta42. Western blotting was used to examine C99, an intermediary product of APP cleaved by beta-secretase. beta-Secretase and gamma-secretase activities were assayed by commercial kits.', 'The CCK-8 assay indicated that different concentrations of gamma-schisandrin had no neurotoxicity on the cultured M146L. And the ELISA test showed that the amount of Abeta42 secreted by M146L cells treated with gamma-schisandrin (5.00 and 15.00 microg x mL(-1)) decreased obviously as compared with solvent control. The results of Western blotting test indicated that there was no change of C99 contents and beta-secretase activity in gamma-schisandrin treated cells, while gamma-secretase activity decreased obviously.

Answer: Does [ Gamma-Schisandrin inhibit production of amyloid beta-protein 42 in M146L cells ]?

Question: The aim of this study was to investigate whether 14-3-3, a specific isoform of a family of proteins regulating processes such as cellular signalling, activates cell-signalling pathways and induces factors known to contribute to the pathophysiology of rheumatoid arthritis (RA). We also investigated whether 14-3-3 is associated with more severe disease in both early and established RA.', 'We investigated the effect of 14-3-3 on the activation of RA-relevant signalling cascades and induction of proinflammatory mediators that contribute to the joint damage process. 14-3-3 titres from 33 patients with early RA (mean RA duration=1.8 months) and from 40 patients with established RA were measured in serum drawn at the 3-year time point of the Behandel Strategieen study. The relationship between 14-3-3 titres and standard clinical variables was investigated by correlation analysis. The association with radiographic damage and radiographic progression over at least a 2-year period was investigated using univariate and multivariate regression analyses.', '14-3-3 activated selected members of the mitogen-activated protein kinase (MAPK) family, mainly extracellular regulated kinase 1/2 and c-Jun kinase, but not p38MAPK. Activation by 14-3-3, using levels spanning the concentration range found in RA patient serum, resulted in the induction of inflammatory transcripts such as interleukin 1 (IL-1) and IL-6 and factors linked to the joint damage process, such as receptor activator of nuclear factor B ligand and matrix metalloproteinase 1. Serum 14-3-3 correlated significantly with rheumatoid factor (RF) (r=0.43) and anticitrullinated protein antibodies (ACPAs) (r=0.31) in the early RA cohort, but not with C-reactive protein (CRP) or the Disease Activity Score in 28 joints in either cohort. Serum 14-3-3 concentrations were significantly higher in patients with radiographically assessed joint damage and in those who had radiographic progression. By multivariate analysis, we show that 14-3-3 complemented markers such as CRP, RF and ACPA in informing RA radiographic status and/or progression.

Answer:
Is 14-3-3 a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage?