IFN-γ is a potent pleiotropic Th1 cytokine, the production of which is tightly regulated during fetal development. Negative control of fetal/neonatal IFN-γ production is generally attributed to the Th1-antagonistic effect of mediators produced by the placenta, but evidence exists of additional and more direct transcriptional regulation. We report that neonatal (cord blood) CD3+/CD45RO− T cells, in particular the CD4+/CD45RO− subset, are hypermethylated at CpG and non-CpG (CpA and CpT) sites within and adjacent to the IFN-γ promoter. In contrast, CpG methylation patterns in cord blood IFN-γ-producing CD8+/CD45RO− T cells and CD56+/CD16+/CD3− NK cells did not differ significantly from those in their adult counterparts. Consistent with this finding, IFN-γ production by stimulated naive cord blood CD4+ T cells is reduced 5- to 10-fold relative to adult CD4+ T cells, whereas production levels in neonatal and adult CD8+ T cells are of a similar order. Evidence of significant CpA and CpT methylation was not discovered in promoter sequence from other cytokines (IL-4, TNF-α, or IFN-γR α-chain). We additionally demonstrate that overexpression of DNA methyltransferase 3a in embryonic kidney carcinoma cells is accompanied by CpA methylation of the IFN-γ promoter.
Purpose: to investigate the key drivers and level of voluntary disclosures in biotechnology company annual reports. Methodology/Approach: using an intellectual capital disclosure index score voluntary disclosures in a large sample of listed biotechnology companies, and test the relationship between voluntary disclosures of intangible firm value with traditional Agency Theory variables. The relationships were tested statistically using correlation and multipleregression analysis. Findings: The key drivers of voluntary intellectual capital disclosures were the level of board independence, firm age, level of leverage and firm size. Multiple regression analysis demonstrated that board independence, leverage and size had a significant relationship with the level of voluntary intellectual capital disclosure. Separate regression controlling for large-sized and small-sized firms demonstrated that voluntary intellectual capital disclosure was only driven by board independence and the levels of firm leverage in large firms. The small firms did not demonstrate this relationship. Research limitations/implications: Implications of this research are that smaller biotechnology companies' managers are not motivated by external debt-holder demands to make voluntary disclosures about intangible firm-value. In addition large biotechnology companies, better able to establish independent board oversight, appear more effective at driving voluntary intellectual capital disclosures; perhaps in response to greater demand by owners. A limitation of this study is its Australian context and that data is analysed only from 2005 financial year annual reports. Originality/value: To our knowledge this is an original paper whose findings have valuable implications for managing intellectual capital at the firm level. We clearly demonstrate that disclosures about intangible firm value is being driven by traditional Agency Theory Variables and more contemporary corporate governance issues, and that Drivers of Voluntary Intellectual Capital Disclosure in Listed Biotechnology Companies 1-Research Paper 3 small firms may be ignoring the importance of disclosing more about their intellectual capital.
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