Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3β in cellular and animal models of neuronal degeneration

Inactivation of glycogen synthase kinase-3β (GSK3β) by S9 phosphorylation is implicated in mechanisms of neuronal survival. Phosphorylation of a distinct site, Y216, on GSK3β is necessary for its activity; however, whether this site can be regulated in cells is unknown. Therefore we examined the regulation of Y216 phosphorylation on GSK3β in models of neurodegeneration. Nerve growth factor withdrawal from differentiated PC12 cells and staurosporine treatment of SH-SY5Y cells led to increased phosphorylation at Y216, GSK3β activity, and cell death. Lithium and insulin, agents that lead to inhibition of GSK3β and adenoviral-mediated transduction of dominant negative GSK3β constructs, prevented cell death by the proapoptotic stimuli. Inhibitors induced S9 phosphorylation and inactivation of GSK3β but did not affect Y216 phosphorylation, suggesting that S9 phosphorylation is sufficient to override GSK3β activation by Y216 phosphorylation. Under the conditions examined, increased Y216 phosphorylation on GSK3β was not an autophosphorylation response. In resting cells, Y216 phosphorylation was restricted to GSK3β present at focal adhesion sites. However, after staurosporine, a dramatic alteration in the immunolocalization pattern was observed, and Y216-phosphorylated GSK3β selectively increased within the nucleus. In rats, Y216 phosphorylation was increased in degenerating cortical neurons induced by ischemia. Taken together, these results suggest that Y216 phosphorylation of GSK3β represents an important mechanism by which cellular insults can lead to neuronal death.

Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors

Endometrial stromal tumors are divided into three types: benign stromal nodules, endometrial stromal sarcomas, and undifferentiated endometrial sarcomas. A variety of cytogenetic abnormalities involving chromosome 7 have been reported in endometrial stromal sarcomas, including a recurrent t(7;17)(p15;q21). We have identified two zinc finger genes, which we have termed JAZF1 and JJAZ1, at the sites of the 7p15 and 17q21 breakpoints. Analyses of tumor RNA indicate that a JAZF1/JJAZ1 fusion is present in all types of endometrial stromal tumors; however, the fusion appears to be rarer among endometrial stromal sarcomas that would be considered high-grade according to certain classification schemes. These findings suggest that the less malignant endometrial stromal tumors may evolve toward more malignant types, but that some endometrial stromal sarcomas with relatively abundant mitotic activity may compose a biologically distinct group.

Manager Training and Development Strategy: A Methodology to Link Strategic Initiatives at Washington and Lee University

Washington and Lee University has developed and implemented a strategic plan and performance development initiative for 2007-2017. In concert with the strategic plan and performance development initiative, supportive manager core competencies have been identified. The deliverable for this capstone project is a documented methodology that supports the strategy for the design and implementation of a manager training and development program that ensures needed competencies are available. The author uses survey data to determine training needs and priorities and, through a review of literature, investigates effective strategies to arrive at a successful implementation methodology. The author presents findings and conclusions regarding design implementation methodology for manager training and development.

A new method of making foliage for miniature dioramas / Alfred Lee Rowell --.

no.8(1953)

Archaeological research at Tumatumani, Juli, Peru / Charles Stanish, Lee Steadman ; with a contribution by Matthew T. Seddon.

n.s. no.23(1994)

Letter from George Gardner Lee to Loammi Baldwin, 10 January 1814

Lee, a Boston merchant who often represented the city as deputy in the Massachusetts General Court, asks Baldwin if the laborers laying the bricks and stone for University Hall could be loaned for a few days to work on the construction of the South meeting house [New South Church].

[Letter from Jason Haven to the Corporation of Harvard College], 1780 July 15

Handwritten letter from Jason Haven requesting the Corporation to grant Draper a degree.

...Scientific results of the cruises of the yachts "Eagle" and "Ara", 1921-1928, William K. Vanderbilt, commanding. Crustacea... By Lee Boone.

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...Scientific results of the cruises of the yachts "Eagle" and "Ara", 1921-1928, William K. Vanderbilt, commanding. Crustacea... By Lee Boone.

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