Rac Inhibition Reverses the Phenotype of Fibrotic Fibroblasts

Background: Fibrosis, the excessive deposition of scar tissue by fibroblasts, is one of the largest groups of diseases for which there is no therapy. Fibroblasts from lesional areas of scleroderma patients possess elevated abilities to contract matrix and produce alpha-smooth muscle actin (alpha-SMA), type I collagen and CCN2 (connective tissue growth factor, CTGF). The basis for this phenomenon is poorly understood, and is a necessary prerequisite for developing novel, rational anti-fibrotic strategies.Methods and Findings: Compared to healthy skin fibroblasts, dermal fibroblasts cultured from lesional areas of scleroderma (SSc) patients possess elevated Rac activity. NSC23766, a Rac inhibitor, suppressed the persistent fibrotic phenotype of lesional SSc fibroblasts. NSC23766 caused a decrease in migration on and contraction of matrix, and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. SSc fibroblasts possessed elevated Akt phosphorylation, which was also blocked by NSC23766. Overexpression of rac1 in normal fibroblasts induced matrix contraction and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. Rac1 activity was blocked by PI3kinase/Akt inhibition. Basal fibroblast activity was not affected by NSC23766.Conclusion: Rac inhibition may be considered as a novel treatment for the fibrosis observed in SSc

Observations on measuring the differences between domestic accounting standards and IAS

In an earlier edition of this journal, Ding et al. use data in GAAP 2001 to assess determinants and effects of differences between domestic and international standards. This paper examines whether those data are suitable for the purposes of academic research by outlining the biases and particular features of GAAP 2001. The main problem with the data for research is that the differences from IAS that it records, which focus on rules, are of varying importance for accounting practice. This raises questions about the equal weighting applied by Ding et al. This paper also questions their distinction between absence of IAS requirements and divergence from those requirements. Some doubts are also raised about the independent variables.International accounting differences Rules versus practices Biases in data

Some mysteries relating to the prudence principle in the Fourth Directive and in German and British law

Article 31 of the Fourth Directive, which specifies the general valuation principles to be applied in the preparation of financial statements, shows a difference in emphasis between the different language versions. Except for the English version of the Directive, all others emphasize prudence, as opposed to the other valuation principles required by the article. The earlier drafts of the Directive are examined in an attempt to trace the development of this difference between the English and the other language versions. It seems that the particular wording of Article 31 with its relatively greater weight on prudence probably results from UK influence, more specifically from SSAP 2. A possible solution is then suggested as to why this particular emphasis on prudence was not retained in the English version of the Directive. Further, it is noted that German law did not explicitly make prudence an overriding concept before the Fourth Directive and nor does the German implementation of Article 31.