Trends in the Quantiles of the Life Table Survivorship Function.

We offer a new approach for modeling past trends in the quantiles of the life table survivorship function. Trends in the quantiles are estimated, and the extent to which the observed patterns fit the unit root hypothesis or, alternatively, an innovative outlier model, are conducted. Then a factor model is applied to the detrended data, and it is used to construct quantile cycles. We enrich the ongoing discussion about human longevity extension by calculating specific improvements in the distribution of the survivorship function, across its full range, and not only at the central-age ranges. To illustrate our proposal, we use data for the UK from 1922 to 2013. We find that there is no sign in the data of any reduction in the pace of longevity extension during the last decades.

Interferon-gamma activates EGF receptor and increases TGF-alpha in T84 cells: implications for chloride secretion.

IFN-gamma inhibits intestinal Cl(-) secretion, in part via downregulation of CFTR and Na(+)-K(+)-ATPase activity and expression, but the proximal signaling events were unknown. We have shown that transforming growth factor-alpha (TGF-alpha) inhibits calcium-activated Cl(-) secretion, and effects of IFN-gamma in other systems are mediated via EGF family members. We tested whether IFN-gamma inhibits Cl(-) secretion via EGF receptor (EGFr) activation. IFN-gamma increased tyrosine phosphorylation in T84 cells at 24 h, including the EGFr. IFN-gamma also increased cell-associated pro-TGF-alpha, as well as free TGF-alpha in the bathing media. However, whereas IFN-gamma significantly inhibited carbachol-induced Cl(-) secretion, neither neutralizing antibodies to TGF-alpha nor an EGFr inhibitor (1 microM tyrphostin AG 1478) were able to reverse this inhibitory effect. AG 1478 also failed to reverse IFN-gamma-induced tyrosine phosphorylation of the EGFr, but receptor phosphorylation was attenuated by both the neutralizing antibody to TGF-alpha and PP2, a Src kinase inhibitor. Moreover, PP2 reversed the inhibitory effect of IFN-gamma on Cl(-) secretion. In total, our findings suggest an increase in functional TGF-alpha and activation of the EGFr in response to IFN-gamma. The release of TGF-alpha and intracellular Src activation likely combine to mediate EGFr phosphorylation, but only Src appears to contribute to the inhibition of transport. Nevertheless, because TGF-alpha plays a role in restitution and repair of the intestinal epithelium after injury, we speculate that these findings reflect a feedback loop whereby IFN-gamma modulates the extent of cytokine-induced intestinal damage.