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R L Powell

Publications and source records attributed to R L Powell.

61 records · Page 4Linked to original sources
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Swimming of spermatozoa in a linear viscoelastic fluid.

A modified resistive force theory is developed for a spermatozoon swimming in a general linear viscoelastic fluid. The theory is based on a Fourier decomposition of the flagellar velocity, which leads to solving the Stokes flow equations with a complex viscosity. We use a model spermatozoon with a spherical head which propagates small amplitude sinusoidal waves along its flagellum. Results are obtained for the velocity of propulsion and the rate of working for a free swimming spermatozoon and the thrust on a fixed spermatozoon. There is no change in propulsive velocity for a viscoelastic fluid compared to a Newtonian fluid. The rate of working does change however, decreasing with increasing elasticity of the fluid, for a Maxwell fluid. Thus the theory predicts that a spermatozoon can swim faster in a Maxwell fluid with the same expenditure of energy for a Newtonian fluid.

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Tamoxifen resistant breast cancer: coregulators determine the direction of transcription by antagonist-occupied steroid receptors.

Pharmacological antagonists of steroid receptor action had been thought to exert their effects by a passive mechanism driven principally by the ability of the antagonist to compete with agonist for the ligand binding site. However, recent analyses of antagonist-occupied receptor function suggest a more complex picture. Antagonists can be subdivided into two groups, type I, or pure antagonists, and type II, or mixed antagonists that can have variable transcriptional activity based upon differential dimerization and DNA binding properties. This led us to propose that receptor antagonism may not simply be a passive competition for the ligand binding site, but may, in some cases, involve active recruitment of corepressor or coactivator proteins to produce a mixed transcriptional phenotype. We used a yeast two-hybrid screen to identify proteins that interact specifically with antagonist-occupied receptors. Two proteins have been characterized: L7/SPA, a ribosome-associated protein that is localized in both the cytoplasm and nucleus, but with no known extranucleolar nuclear function; and hN-CoR, the human homolog of the mouse thyroid receptor corepressor mN-CoR. In in vivo transcription assays we show that L7/SPA enhances the partial agonist activity of type II mixed antagonists, and that N-CoR and the related corepressor, SMRT, suppresses it. The coregulators do not affect agonists or pure antagonists. Moreover, the net agonist activity seen with mixed antagonists is a function of the ratio of coactivator to corepressor. Based upon these results, we proposed that in breast tumors the inappropriate agonist activity seen with therapeutic antagonists such as tamoxifen is responsible for the hormone-resistant state. To confirm this, we are quantitating coactivator/corepressor ratios in breast tumor cells lines and clinical breast cancers. Results should provide new insights into the mechanisms underlying the progression of breast cancer to hormone resistance, and may suggest strategies for delaying or reversing this process.

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