ItemSel1L‐Hrd1‐Mediated OS9 Degradation During Endoplasmic Reticulum StressShu, Xin (2014-04)Misfolded or unfolded proteins generated by inefficient protein folding or ER stress is translocated from the ER to cytosol for proteasome degradation, a process termed endoplasmic reticulum associated degradation (ERAD). OS9, a lectin protein, has been shown to deliver misfolded or unfolded glycoproteins to the most conserved ERAD complexes in the mammalian system, the Sel1L-Hrd1 ERAD complex (Mehnert et al., 2010). Our study on OS9 shows that despite being an effector of the complex, OS9 itself is degraded by the same complex in response to ER stress. OS9 protein level decreases drastically upon the treatment of Tunicamycin (TM), Thapsigargin (Tg) or Dithiothreitol (DTT) . The addition of MG132 completely blocked the degradation, showing OS9 is degraded by proteasome. We then show the degradation of OS9 is abolished in Hrd1 knock-out (Hrd1-/- ) MEF cells, and significantly attenuated in Sel1L-/- cells when cells were treated with 6hr of cycloheximide (CHX), suggesting both Sel1L and Hrd1 are required for the degradation of OS9, but Hrd1 plays a more important role in the process. We also find that the protein level of OS9 is significantly higher in Sel1L-inducible knock out (IKO) mice than in WT mice, confirming that OS9 is degraded by Sel1L-Hrd1 complex in vivo. Using co-immunoprecipitation (CO-IP), we find that Sel1L associates with OS9 in a glycosylation independent manner and that it can be ubiquitinated by overexpressed Hrd1. In addition, our data suggest the protein stability of OS9 is mediated through the XBP1-Hrd1 axis. These data suggest that OS9 is degraded through the Sel1L-Hrd1 complex under ER stress. Not only does this study identifies a potential endogenous substrate of the Sel1L-Hrd1 complex, given the fact that OS9 is an effector of the complex, this study may also provide insights into a possible self-regulatory mechanism of the complex through regulating OS9. ItemSatisfaction with an Online Weight Gain Intervention for Women during Pregnancy: e-Moms of RochesterXu, Jiayi (2014-05)Weight management during pregnancy is critical to health of both mothers and infants. Online weight management interventions have advantages of convenience, accessibility, and flexibility. Objective: This paper examines the satisfaction of pregnant women with the weight management online intervention in the e-Moms of Rochester project and evaluates the satisfaction level by study arm and by demographic characteristic. Methods: e-Moms of Rochester is a randomized controlled trial designed to help pregnant women achieve a recommended weight gain during pregnancy via an online intervention. The satisfaction survey was available online to the participants after their delivery. 942 out of 1512 pregnant women completed the satisfaction survey. Among the 942 participants, 621 women were in the intervention arm while the other 321 were in the control arm. The satisfaction level was measured on a 10-point Likert-scale from “0-strongly disagree” to “10-strongly agree”. A score of 0-4 was counted as low satisfaction, 5-7 as medium satisfaction and 8-10 as high satisfaction. Chi-square test and Mann-Whitney U test were used for evaluating representativeness, satisfaction level across website features, and comparison of satisfaction by study arm and by demographic characteristic. Results: 70%-91.2% participants had a moderate to high satisfaction with different website features. However, 59.3% participants rated social support negatively. The Resources (mean=7.29) and Articles & FAQ (mean=7.28) had the highest satisfaction levels on helpfulness. The weight gain tracker was rated highest in terms of ease of use (mean= 8.35). The satisfaction levels of helpfulness of Resources and Reminder were significantly different by arm (p= 0.035; p= 0.002). Satisfaction levels for some website features were significantly different as well by demographic characteristic. Conclusion: Overall, participants felt satisfied with the project website except for the aspect of social support. The sections of Articles & FAQ and Resources were the most helpful. Weight gain tracker was the easiest to use in the intervention group. The intervention group had higher satisfaction level with Resources and Reminder. Pregnant women, who were low-income, young, Hispanic, African American or had a lower education level, were more satisfied with the website features. And these women who were African American, young, with lower education, or with lower income, had significantly higher ratings of social support in this e-Moms Roc project.