Biomedical subjects

Albert E Parker

Publications and source records attributed to Albert E Parker.

3 recordsLinked to original sources

PubMed2006

p53-mediated inhibition of angiogenesis through up-regulation of a collagen prolyl hydroxylase.

Recent evidence suggests that antiangiogenic therapy is sensitive to p53 status in tumors, implicating a role for p53 in the regulation of angiogenesis. Here we show that p53 transcriptionally activates the alpha(II) collagen prolyl-4-hydroxylase [alpha(II)PH] gene, resulting in the extracellular release of antiangiogenic fragments of collagen type 4 and 18. Conditioned media from cells ectopically expressing either p53 or alpha(II)PH selectively inhibited growth of primary human endothelial cells. When expressed intracellularly or exogenously delivered, alpha(II)PH significantly inhibited tumor growth in mice. Our results reveal a genetic and biochemical linkage between the p53 tumor suppressor pathway and the synthesis of antiangiogenic collagen fragments.

Angiogenesis Inhibitors↗

PubMed2004

The viral protein Apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53.

The chicken anemia virus protein Apoptin induces apoptosis in the absence of p53 by a mechanism that remains to be elucidated. Here we show that in transformed cells, Apoptin is associated with APC1, a subunit of the anaphase-promoting complex/cyclosome (APC/C). We demonstrate that Apoptin expression, or depletion of APC1 by RNA interference, inhibits APC/C function in p53 null cells, resulting in G2/M arrest and apoptosis. Our results explain the ability of Apoptin to induce apoptosis in the absence of p53 and suggest that the APC/C is an attractive target for anticancer drug development.

Anaphase-Promoting Complex-Cyclosome↗

PubMed2003

Analysis of neural coding through quantization with an information-based distortion measure.

We discuss an analytical approach through which the neural symbols and corresponding stimulus space of a neuron or neural ensemble can be discovered simultaneously and quantitatively, making few assumptions about the nature of the code or relevant features. The basis for this approach is to conceptualize a neural coding scheme as a collection of stimulus-response classes akin to a dictionary or 'codebook', with each class corresponding to a spike pattern 'codeword' and its corresponding stimulus feature in the codebook. The neural codebook is derived by quantizing the neural responses into a small reproduction set, and optimizing the quantization to minimize an information-based distortion function. We apply this approach to the analysis of coding in sensory interneurons of a simple invertebrate sensory system. For a simple sensory characteristic (tuning curve), we demonstrate a case for which the classical definition of tuning does not describe adequately the performance of the cell studied. Considering a more involved sensory operation (sensory discrimination), we also show that, for some cells in this system, a significant amount of information is encoded in patterns of spikes that would not be discovered through analyses based on linear stimulus-response measures.

Air↗