Nurses recognized the significance of their input into processes of change. Transformational leadership and frontline projects provide a vehicle for innovation through application of human capital.
In a setting of rural MVC, increased EMS response time, time on scene and distance to the scene are associated with higher rural trauma mortality rates.
Background:The role of Merlin in breast cancer is unknown. Results: Merlin protein is degraded in advanced breast cancer due to osteopontin-initiated signaling. Conclusion: Merlin is regulated at the post-translational level in breast tumors. Significance: We have defined a functional role for Merlin in limiting breast tumor growth and elucidated the utility of Merlin as an important biomarker in breast cancer.
As BMI increases, obese patients undergoing induction with misoprostol have a longer time to delivery, require more doses of misoprostol, require a longer duration of oxytocin and have higher cesarean delivery rate.
Elevated levels of the oncoprotein, osteopontin (OPN), are associated with poor outcome of several types of cancers including melanoma. We have previously reported an important involvement of DNAJB6, a member of heatshock protein 40 (HSP40) family, in negatively impacting tumor growth. The current study was prompted by our observations reported here which revealed a reciprocal relationship between DNAJB6 and OPN in melanoma specimens. The ‘J domain’ is the most conserved domain of HSP40 family of proteins. Hence, we assessed the functional role of the J domain in activities of DNAJB6. We report that the J domain of DNAJB6 is involved in mediating OPN suppression. Deletion of the J domain renders DNAJB6 incapable of impeding malignancy and suppressing OPN. Our mechanistic investigations reveal that DNAJB6 binds HSPA8 (heat-shock cognate protein, HSC70) and causes dephosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9 by recruiting protein phosphatase, PP2A. This dephosphorylation activates GSK3β, leading to degradation of β-catenin and subsequent loss of TCF/LEF (T cell factor1/lymphoid enhancer factor1) activity. Deletion of the J domain abrogates assembly of this multiprotein complex and renders GSK3β inactive, thus, stabilizing β-catenin, a transcription coactivator for OPN expression. Our in-vitro and in-vivo functional analyses show that silencing OPN expression in the background of deletion of the J domain renders the resultant tumor cells less malignant despite the presence of stabilized β-catenin. Thus, we have uncovered a new mechanism for regulation of GSK3β activity leading to inhibition of Wnt/β-catenin signaling.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.