Growth restriction in the rat alters expression of cardiac JAK/STAT genes in a sex-specific manner.

Uteroplacental insufficiency resulting in intrauterine growth restriction has been associated with the development of cardiovascular disease, coronary heart disease and increased blood pressure, particularly in males. The molecular mechanisms that result in the programming of these phenotypes are not clear. This study investigated the expression of cardiac JAK/STAT signalling genes in growth restricted offspring born small due to uteroplacental insufficiency. Bilateral uterine vessel ligation was performed on day 18 of pregnancy to induce growth restriction (Restricted) or sham surgery (Control). Cardiac tissue at embryonic day (E) 20, postnatal day (PN) 1, PN7 and PN35 in male and female Wistar (WKY) rats (n=7-10 per group per age) was isolated and mRNA extracted. In the heart, there was an effect of age for males for all genes examined there was a decrease in expression after PN1. With females, JAK2 expression was significantly reduced after E20, while PI3K in females was increased at E30 and PN35. Further, mRNA expression was significantly altered in JAK/STAT signalling targets in Restricteds in a sex-specific manner. Compared with Controls, in males, JAK2 and STAT3 were significantly reduced in the Restricted, while in females SOCS3 was significantly increased and PI3K significantly decreased in the Restricted offspring. Finally, there were specific differences in the levels of gene expression within the JAK/STAT pathway when comparing males to females. Thus, growth restriction alters specific targets in the JAK/STAT signalling pathway, with altered JAK2 and STAT3 potentially contributing to the increased risk of cardiovascular disease in the growth restricted males.

Panel cointegration and the neutrality of money

Most econometric methods for testing the proposition of long-run monetary neutrality rely on the assumption that money and real output do not cointegrate, a result that is usually supported by the data. This paper argues that these results can be attributed in part to the low power of univariate tests, and that a violation of the noncointegration assumption is likely to result in a nonrejection of the neutrality proposition. To alleviate this problem, two new and more powerful panel cointegration tests are proposed that can be used under quite general conditions. The empirical results obtained from applying these tests to a panel covering ten countries between 1870 and 1986 suggest money and real output are cointegrated, and hence that the neutrality proposition must be rejected. © Springer-Verlag 2007.