Effect of select media supplements on motility and development of Eimeria nieschulzi in vitro.

A technique was developed to examine the effects of exogenous substances on apicomplexan sporozoite motility in vitro. Sporozoites of Eimeria nieschulzi were placed in the top compartments of blind well chemotactic chambers and separated from potential chemoattractant/chemokinetic agents by 8.0-microns pore size Millipore filters. After 3-hr incubations, the number of sporozoites migrating through the filters was assessed using a hemacytometer. Results revealed that several substances, especially albumin and fetuin, enhanced motility of coccidial sporozoites. Cell culture assays supported these data, with higher numbers of parasites found in cultures supplemented with albumin and/or fetuin.     

Motif effects in Affymetrix GeneChips seriously affect probe intensities

An Affymetrix GeneChip consists of an array of hundreds of thousands of probes (each a sequence of 25 bases) with the probe values being used to infer the extent to which genes are expressed in the biological material under investigation. In this article, we demonstrate that these probe values are also strongly influenced by their precise base sequence. We use data from >28 000 CEL files relating to 10 different Affymetrix GeneChip platforms and involving nearly 1000 experiments. Our results confirm known effects (those due to the T7-primer and the formation of G-quadruplexes) but reveal other effects. We show that there can be huge variations from one experiment to another, and that there may also be sizeable disparities between batches within an experiment and between CEL files within a batch.     

Structure-activity relationships for analogs of the tuberculosis drug bedaquiline with the naphthalene unit replaced by bicyclic heterocycles

Replacing the naphthalene C-unit of the anti-tuberculosis drug bedaquiline with a range of bicyclic heterocycles of widely differing lipophilicity gave analogs with a 4.5-fold range in clogP values. The biological results for these compounds indicate on average a lower clogP limit of about 5.0 in this series for retention of potent inhibitory activity (MIC₉₀s) against M.tb in culture. Some of the compounds also showed a significant reduction in inhibition of hERG channel potassium current compared with bedaquiline, but there was no common structural feature that distinguished these.     

Population, Gender and Politics: Demographic Change in Rural North India

Population, Gender and Politics: Demographic Change in Rural North India. Roger Jeffery and Patricia Jeffery. New York: Cambridge University Press, 1997. 278 pp.     

Dietary Management of the Malabsorption Syndrome

The purpose of this report is to emphasize the importance of strict dietary control of patients suffering from the malabsorption syndrome and to announce the availability of a gluten-free bread-substitute, called “Unimix”, from the Scientific Development Committee, Room 14, Medical Building, University of Toronto. Science a gluten-free diet is difficult to follow because of the widespread use of wheat flour and other cereals in the production of many common foods, a suggested gluten-free meal pattern is presented, which conforms with Canada''s Food Guide and permits a number of choices of menu within certain limits.     

The Prodomain-bound Form of Bone Morphogenetic Protein 10 Is Biologically Active on Endothelial Cells

BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality because of impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular, it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.