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This study has explored the role of the pneumococcal toxin, pneumolysin (Ply), in activating human platelets. Following exposure to Ply (10-80 ng/ml), platelet activation and cytosolic Ca.sup.2+ concentrations were measured flow cytometrically according to the level of expression of CD62P (P-selectin) and spectrofluorimetrically, respectively. Exposure to Ply resulted in marked upregulation of expression of platelet CD62P, achieving statistical significance at concentrations of 40 ng/ml and higher (P < 0.05), in the setting of increased influx of Ca.sup.2+. These potentially pro-thrombotic actions of Ply were attenuated by depletion of Ca.sup.2+ from the extracellular medium or by exposure of the cells to a pneumolysoid devoid of pore-forming activity. These findings are consistent with a mechanism of Ply-mediated platelet activation involving sub-lytic pore formation, Ca.sup.2+ influx, and mobilization of CD62P-expressing [alpha]-granules, which, if operative in vivo, may contribute to the pathogenesis of associated acute lung and myocardial injury during invasive pneumococcal disease., Author(s): Jan Gert Nel[sup.1] , Chrisna Durandt[sup.2] , Timothy J. Mitchell[sup.4] , Charles Feldman[sup.5] , Ronald Anderson[sup.2] , Gregory R. Tintinger[sup.3] Author Affiliations: (1) Department of Haematology, Faculty of Health [...]

Web enjoyment has been regarded as a component of system experience. However, there has been little targeted research considering the role of web enjoyment alone in student learning using web-based systems. To address this gap, this study aims to examine the influence of web enjoyment on learning performance and perceptions by controlling system experience as a variable in the study. 74 students participated in the study, using a web-based tutorial covering subject matter in the area of "Computation and algorithms". Their learning performance was assessed with a pre-test and a post-test and their learning perceptions were evaluated with a questionnaire. The results indicated that there are positive relationships between the levels of web enjoyment and perceived usefulness and non-linear navigation for users with similar, significant levels of system experience. The implications of these findings in relation to web-based learning are explored and ways in which the needs of students who report different levels of web enjoyment might be met are discussed.

Prior knowledge is often argued to be an important determinant in hypermedia learning, and may be thought of as including two important elements: domain expertise and system expertise. However, there has been a lack of research considering these issues together. In an attempt to address this shortcoming, this paper presents a study that examines how domain expertise and system expertise influence students' learning performance in, and perceptions of, a hypermedia system. The results indicate that participants with lower domain knowledge show a greater improvement in their learning performance than those with higher domain knowledge. Furthermore, those who enjoy using the Web more are likely to have positive perceptions of non-linear interaction. Discussions on how to accommodate the different needs of students with varying levels of prior knowledge are provided based on the results.

A variety of bacterial cellular responses to environmental signals are mediated by two-component signal transduction systems comprising a membrane-associated histidine protein kinase and a cytoplasmic response regulator (RR), which interpret specific stimuli and produce a measured physiological response. In RR activation, transient phosphorylation of a highly conserved aspartic acid residue drives the conformation changes needed for full activation of the protein. Sequence homology reveals that RR02 from Streptococcus pneumoniae belongs to the OmpR subfamily of RRs. The structures of the receiver domains from four members of this family, DrrB and DrrD from Thermotoga maritima, PhoB from Escherichia coli, and PhoP from Bacillus subtilis, have been elucidated. These domains are globally very similar in that they are composed of a doubly wound [[alpha].sub.5][[beta].sub.5]; however, they differ remarkably in the fine detail of the [[beta]4-[alpha]4 and [alpha]4 regions. The structures presented here reveal a further difference of the geometry in this region. RR02 is has been shown to be the essential RR in the gram-positive bacterium S. pneumoniae R. Lange, C. Wagner, A. de Saizieu, N. Flint, J. Molnos, M. Stieger, P. Caspers, M. Kamber, W. Keck, and K. E. Amrein, Gene 237:223-234, 1999; J. P. Throup, K. K. Koretke, A. P. Bryant, K. A. Ingraham, A. F. Chalker, Y. Ge, A. Marra, N. G. Wallis, J. R. Brown, D. J. Holmes, M. Rosenberg, and M. K. Burnham, Mol. Microbiol. 35:566-576, 2000). RR02 functions as part of a phosphotransfer system that ultimately controls the levels of competence within the bacteria. Here we report the native structure of the receiver domain of RR02 from serotype 4 S. pneumoniae (as well as acetate- and phosphate-bound forms) at different pH levels. Two native structures at 2.3 [Angstrom] phased by single-wavelength anomalous diffraction (xenon SAD), and 1.85 [Angtsrom], and a third structure at pH 5.9 revealed the presence of a phosphate ion outside the active site. The fourth structure revealed the presence of an acetate molecule in the active site.

Research demonstrates a two-component system of bacteriocin-like peptide that controls its own genes and a regulon. Data indicate that the peptide is part of a quorum-sensing regulon which shares many features of competence-stimulating peptide controlled regulon.