Tracy J. O’Connor

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Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer of the cellular prion protein PrPC. Antibody-derived ligands to the globular domain of PrPC (collectively termed GDL) are also neurotoxic. Here we show that GDL and prion infections activate the same pathways. Firstly, both GDL and prion infection of cerebellar organotypic(More)
The cellular prion protein (PrPC) consists of a flexible N-terminal tail (FT, aa 23-128) hinged to a membrane-anchored globular domain (GD, aa 129-231). Ligation of the GD with antibodies induces rapid neurodegeneration, which is prevented by deletion or functional inactivation of the FT. Therefore, the FT is an allosteric effector of neurotoxicity. To(More)
Microinjection of DNA constructs into fertilized mouse oocytes typically results in random transgene integration at a single genomic locus. The resulting transgenic founders can be used to establish hemizygous transgenic mouse lines. However, practical and experimental reasons often require that such lines be bred to homozygosity. Transgene zygosity can be(More)
-Secretase [ -site amyloid precursor protein-cleaving enzyme 1 (BACE1)] is the key rate-limiting enzyme for the production of the -amyloid (A ) peptide involved in the pathogenesis of Alzheimer’s disease (AD). BACE1 levels and activity are increased in AD brain and are likely to drive A overproduction, but the cause of BACE1 elevation in AD is unknown.(More)
Elevated levels of pp6Oc s tyrosine kinase activity have been implicated in both tumorigenesis and cell differentiation. We have found a 2to 4-fold elevation in pp6Ocstc specific activity in certain human melanoma cell lines compared to human foreskin fibroblasts. This adivation of pp6Oc did not appear to be related to melanoma tumor progression, because(More)
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