Committee Influence Over Controversial Policy: The Reproductive Policy Case

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74678/1/j.1541-0072.1999.tb01964.x.pd

How Intense Policy Demanders Shape Postreform Politics: Evidence from the Affordable Care Act

The implementation of the Affordable Care Act (ACA) has been a politically volatile process. The ACA\u27s institutional design and delayed feedback effects created a window of opportunity for its partisan opponents to launch challenges at both the federal and state level. Yet as recent research suggests, postreform politics depends on more than policy feedback alone; rather, it is shaped by the partisan and interest-group environment. We argue that “intense policy demanders” played an important role in defining the policy alternatives that comprised congressional Republicans\u27 efforts to repeal and replace the ACA. To test this argument, we drew on an original data set of bill introductions in the House of Representatives between 2011 and 2016. Our analysis suggests that business contributions and political ideology affected the likelihood that House Republicans would introduce measures repealing significant portions of the ACA. A secondary analysis shows that intense policy demanders also shaped the vote on House Republicans\u27 initial ACA replacement plan. These findings highlight the role intense policy demanders can play in shaping the postreform political agenda

Ezrin Is Highly Expressed in Early Thymocytes, but Dispensable for T Cell Development in Mice

Ezrin/radixin/moesin (ERM) proteins are highly homologous proteins that function to link cargo molecules to the actin cytoskeleton. Ezrin and moesin are both expressed in mature lymphocytes, where they play overlapping roles in cell signaling and polarity, but their role in lymphoid development has not been explored.We characterized ERM protein expression in lymphoid tissues and analyzed the requirement for ezrin expression in lymphoid development. In wildtype mice, we found that most cells in the spleen and thymus express both ezrin and moesin, but little radixin. ERM protein expression in the thymus was differentially regulated, such that ezrin expression was highest in immature thymocytes and diminished during T cell development. In contrast, moesin expression was low in early thymocytes and upregulated during T cell development. Mice bearing a germline deletion of ezrin exhibited profound defects in the size and cellularity of the spleen and thymus, abnormal thymic architecture, diminished hematopoiesis, and increased proportions of granulocytic precursors. Further analysis using fetal liver chimeras and thymic transplants showed that ezrin expression is dispensable in hematopoietic and stromal lineages, and that most of the defects in lymphoid development in ezrin(-/-) mice likely arise as a consequence of nutritional stress.We conclude that despite high expression in lymphoid precursor cells, ezrin is dispensable for lymphoid development, most likely due to redundancy with moesin

Adenoma Formation following Limited Ablation of p120-Catenin in the Mouse Intestine

p120 loss destabilizes E-cadherin and could therefore result in tumor and/or metastasis-promoting activities similar to those caused by E-cadherin downregulation. Previously, we reported that p120 is essential in the intestine for barrier function, epithelial homeostasis and survival. Conditional p120 ablation in the mouse intestine induced severe inflammatory bowel disease, but long-term cancer-related studies were impossible because none of the animals survived longer than 21 days. Here, we used a tamoxifen-inducible mouse model (Vil-Cre-ERT2;p120fl/fl) to limit the extent of p120 ablation and thereby enable long-term studies. Reducing p120 KO to ∼10% of the intestinal epithelium produced long-lived animals outwardly indistinguishable from controls. Effects of prolonged p120 absence were then evaluated at intervals spanning 2 to 18 months. At all time points, immunostaining revealed microdomains of p120-null epithelium interspersed with normal epithelium. Thus, stochastic p120 ablation is compatible with crypt progenitor cell function and permitted lifelong renewal of the p120-null cells. Consistent with previous observations, a barrier defect and frequent infiltration of neutrophils was observed, suggesting that focal p120 loss generates a microenvironment disposed to chronic inflammation. We report that 45% of these animals developed tumors within 18 months of tamoxifen induction. Interestingly, β-catenin was upregulated in the majority, but none of the tumors were p120 null. Although further work is required to directly establish mechanism, we conclude that limited p120 ablation can promote tumorigenesis by an indirect non-cell autonomous mechanism. Given that byproducts of inflammation are known to be highly mutagenic, we suggest that tumorigenesis in this model is ultimately driven by the lifelong inability to heal chronic wounds and the substantially increased rates of stochastic gene mutation in tissue microenvironments subjected to chronic inflammation. Indeed, although technical issues precluded direct identification of mutations, β-catenin upregulation in human colon cancer almost invariably reflects mutations in APC and/or β-catenin