The goal of this study was to investigate the role of the disulphide bond of staphylococcal enterotoxin C1 (SEC1) in the structure and activity of the toxin. Mutants unable to form a disulphide bond were generated by substituting alanine or serine for cysteine at positions 93 and/or 110. Although we did not directly investigate the residues between the disulphide linkage, tryptic lability showed that significant native structure in the cystine loop is preserved in the absence of covalent bonding between residues 93 and 110. Since no correlation was observed between the behaviour of these mutants with regard to toxin stability, emesis and T cell proliferation we conclude that SEC1-induced emesis and T cell proliferation are dependent on separate regions of the molecule. The disulphide bond itself is not an absolute requirement for either activity. However, conformation within or adjacent to the loop is important for emesis. Although mutants with alanine substitutions were not emetic, those with serine substitutions retained this activity, suggesting that the disulphide linkage stabilizes a crucial conformation but can be replaced by residues which hydrogen bond.

The type C staphylococcal enterotoxins (SEC) are a group of highly conserved proteins with significant immunological cross-reactivity. Although three antigenically distinct SEC subtypes (SEC1, SEC2, and SEC3) have been reported in the literature, we observed that the isoelectric points of SEC from several Staphylococcus aureus isolates are different from those of any of these three subtypes. This observation led us to propose that additional SEC molecular variants exist. For assessment of this possibility, the sec genes from representative human, animal, and food isolates were cloned and sequenced. The toxins encoded by the 18 isolates used in this study included five unique SEC proteins in addition to SEC1, SEC2, and SEC3. Six of the SEC proteins (including SEC1, SEC2, and SEC3) were produced by human and food isolates. Analysis of seven bovine and ovine isolates showed that isolates from each animal species produced a unique host-specific SEC. All of the SEC caused lymphocyte proliferation, although some of the toxins differed in their ability to stimulate cells from several animal species. An explanation for these results, which is supported by our phenotypic analysis of Sec+ staphylococcal isolates, is that toxin heterogeneity is due to selection for modified SEC sequences that

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The Space Interferometry Mission (SIM) will be the first in-space, long-baseline Michelson Stellar Interferometer. SIM will perform precision astrometry at the micro-arcsecond accuracy level, which will be used to characterize planetary systems around stars within about ten parsecs of Earth and address a number of other key astrophysics projects. This paper provides a broad overview of the SIM Mission. Topics covered include: the science objectives, key top level requirements, how the mission will be implemented (technical and programmatic), technology development status, an assessment of where the project is today, and prognosis for the future.

We ask if Earth-like planets (terrestrial mass and habitable-zone orbit) can be detected in multi-planet systems, using astrometric and radial velocity observations. We report here the preliminary results of double-blind calculations designed to answer this question.