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Author(s): K.-L. Laugwitz; A. Moretti; J. Lam; P. Gruber; Y. Chen; S. Woodard; L.-Z. Lin; C.-L. Cai; M. M. Lu; M. Reth; O. Platoshyn; J. X.-J. Yuan; S. Evans; K. [...]

Design: This study used single group repeated measures including a sample of 90 older adults. Three annual interviews were done. Methods: Repeated measure analysis of variance was used to test willingness to engage in care over time. Regression analyses were used to test the relationship between the predictor variables and ELTP annually. Findings: At baseline the majority did not want CPR (54%), to be on a respirator (53%), or dialysis (53%). The majority were willing to have surgery (53%), pain medication (80%), blood transfusions (69%), diagnositc tests (97%), and antibiotics (96%). Over the three years of testing, there was a significant decline in willingness to accept artificial nutrition and hydration, surgery, or to be on a respirator. There was no relationship between gender, marital status, mental or physical health, cognition, or religion with ELTP. Conclusions: ELTP changed over time. Implications: Nurse Practitioners should ask older adults about ELTP annually.

The BRAFV600E mutation is found in approximately 6% of human cancers and mimics the phosphorylation of the kinase domain activation segment. In wild-type B-Raf (B-Rafwt), activation segment phosphorylation is thought to cooperate with negative charges within the N-region for full activation. In contrast to Raf-1, the N-region of B-Raf is constitutively negatively charged owing to the presence of residues D447/D448 and the phosphorylation of S446. Therefore, it has been suggested that this hallmark predisposes B-Raf for oncogenic activation. In this study, we demonstrate that neutralizing mutations of these residues (in particular S446 and S447), or uncoupling of B-Raf from Ras-guanine 5′-triphosphate (GTP), strongly reduce the biological activity of B-Raf in a PC12 cell differentiation assay. We also confirm that S365 is a 14-3-3 binding site, and determine that mutation of this residue rescues the impaired biological activity of B-Raf proteins with a neutralized N-region, suggesting that the N-region opposes a 14-3-3-mediated transition into an inactive conformation. However, in the case of B-RafV600E, although complete N-region neutralization resulted in a 2.5-fold reduction in kinase activity in vitro, this oncoprotein strongly induced PC12 differentiation or transformation and epithelial–mesenchymal transition of MCF-10A cells regardless of its N-region charge. Furthermore, the biological activity of B-RafV600E was independent of its ability to bind Ras-GTP. Our analysis identifies important regulatory differences between B-Rafwt and B-RafV600E and suggests that B-RafV600E cannot be inhibited by strategies aimed at blocking S446 phosphorylation or Ras activation.Oncogene (2006) 25, 6262–6276. doi:10.1038/sj.onc.1209640; published online 15 May 2006 [ABSTRACT FROM AUTHOR]

Focuses on the initiation and processing of signals from the B cell antigen receptors. Information on the B cell antigen receptor; Functional definition of signaling elements; Evolution of receptors and signaling pathways.