Biomedical subjects
Publications and source records attributed to J Raper.
Proposed changes in training and development means that it is time to stand up and be counted, writes SOHN chair, JEAN RAPER. She examines the work, to date, on National Vocational Qualifications and asks what affect they might have on the future of occupational health nursing.
Trypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, evades the host immune response through the process of antigenic variation. The variant antigen, known as the variant surface glycoprotein (VSG), is anchored to the cell surface by a glycosyl phosphatidylinositol (GPI) structure that contains myristate (n-tetradecanoate) as its only fatty acid component. The utilization of heteroatom-containing analogs of myristate was studied both in a cell-free system and in vivo. Results indicated that the specificity of fatty acid incorporation depends on chain length rather than on hydrophobicity. One analog, 10-(propoxy)decanoic acid, was highly toxic to trypanosomes in culture although it is nontoxic to mammalian cells.
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The trypanosome variant surface glycoprotein (VSG) is anchored to the plasma membrane via a glycosyl phosphatidylinositol (GPI). The GPI is synthesized as a precursor, glycolipid A, that is subsequently linked to the VSG polypeptide. The VSG anchor is unusual, compared with anchors in other cell types, in that its fatty acid moieties are exclusively myristic acid. To investigate the mechanism for myristate specificity we used a cell-free system for GPI biosynthesis. One product of this system, glycolipid A', is indistinguishable from glycolipid A except that its fatty acids are more hydrophobic than myristate. Glycolipid A' is converted to glycolipid A through highly specific fatty acid remodeling reactions involving deacylation and subsequent reacylation with myristate. Therefore, myristoylation occurs in the final phase of trypanosome GPI biosynthesis.
An analysis of equilibria and dynamics of the means, variances, and covariances of female mating preference for a quantitative male secondary sexual character following a Gaussian model is presented. For many combinations of viability and sexual selection parameters the evolving Gaussian distribution of phenotypes can diverge. The results on the cases of convergence and their limiting forms suggest some reinterpretations of Fisher's "runaway" process of sexual selection. One possibility is to interpret Fisher's postulated "initial advantage not due to female preference" as a shift in viability selection where runaway evolution occurs if the mean preferred trait evolves beyond its new viability optimum (due to sexual selection). This definition is contrasted with situations in which the new viability optimum is undershot. The quantitative and qualitative conclusions differ from models that approximate genetic covariance evolution involving a constant covariance.
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The solution properties of the membrane form and soluble form of variant surface glycoproteins from Trypanosoma brucei have been compared. Solution cross-linking studies established that both forms are dimers, although dissociation of membrane-form variant surface glycoprotein can be promoted by certain ionic and zwitterionic detergents. Sedimentation coefficients were measured under a range of conditions, and the results were comparable with the results of solution cross-linking. Stokes radii were measured by gel filtration, allowing a value for the frictional coefficient to be calculated. The two forms show no differences other than those consistent with binding of detergent micelles to the hydrophobic moiety present on membrane form surface glycoprotein. This validates the use of soluble variant surface glycoprotein in X-ray crystallography experiments.
Membrane-form variant surface glycoprotein of Trypanosoma brucei can be prepared in the presence of para-chloromercuriphenylsulphonic acid. The membrane-bound enzyme that usually cleaves a lipid from this glycoprotein, thus producing the soluble variant surface glycoprotein, is inhibited by a range of sulphydryl reagents. The effect of such inhibitors, both on cell lysates and on semi-purified enzyme, reveals that the enzyme may have a sulphydryl at or near its active site. Fatty acid analysis and isoelectric point measurements of membrane form and soluble form are presented.
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