Synthesis, topoisomerase I inhibition and antitumor cytotoxicity of 2,2':6',2"-, 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives

For the development of new anticancer agents, 2,2':6',2"-, 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were designed and evaluated for their topoisomerase I inhibitory activity and antitumor cytotoxicity. Structure-activity relationship studies indicated that 2,2':6',2"-terpyridine derivatives were highly cytotoxic toward several human tumor cell lines, whereas 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were potent topoisomerase I inhibitors.     

"p53: Twenty Years On" in Trieste, Italy, May 20-22, 1999.

Study of the p53 tumor suppressor has blossomed into a field of its own. From analysis of its mutations in several different cancers to deciphering the function of the protein in human cells, publications describing research on p53 annually number in the thousands. In the interest of presenting the most up-to-date information on the progress of cancer research involving p53, the workshop "p53: Twenty Years On" was organized in Trieste, Italy over May 20-22, 1999. The meeting highlighted some of the most exciting basic and clinical scientific findings on p53 within the last year.     

Colonial "Reformation" in the Highlands of Central Sulawesi, Indonesia, 1892-1995

Colonial "Reformation" in the Highlands of Central Sulawesi, Indonesia, 1892-1995. Albert Schrauwers. Toronto: University of Toronto Press, 2000. 279 pp.     

"I'm all right,John": voting patterns and mortality in England and Wales, 1981-92.

OBJECTIVE: To investigate the association between voting patterns, deprivation, and mortality across England and Wales. DESIGN: Ecological study. SETTING: All the electoral constituencies of England and Wales. MAIN OUTCOME MEASURES: Combined and sex specific standardised mortality ratios. RESULTS: For the years surrounding the three elections of 1983, 1987, and 1992 overall standardised mortality ratios showed substantial negative correlations of -0.74 to -0.76 with Conservative voting and substantial positive correlations of 0.73 to 0.77 with Labour voting (all P < 0.0001). Correlations were higher for male than female mortality. Conservative voting was strongly negatively correlated (r = -0.84) with the Townsend deprivation score, while Labour voting was positively correlated (r = 0.74) with this. Labour and Conservative voting explained more of the variance in mortality than did the Townsend score. In multiple regression analyses for the 1992 election Labour voting (P < 0.0001), Conservative voting (P < 0.0001), the Townsend score (P = 0.016), and abstentions (P = 0.032) were all associated with mortality. Labour and conservative voting explained 61% of the variance in mortality between constituencies; when Townsend score and abstentions were added this increased to 63%. CONCLUSIONS: Conservative and Labour voting are at least as strongly associated with mortality as is a standard deprivation index. Voting patterns may add information above that provided by indicators of material deprivation. People living in better circumstances and who have better health, who are least likely to require unemployment benefit and free school meals or to rely on a state pension in old age, and who are most able to opt out of state subsidised provision of transport, education, and the NHS, vote for the party that is most likely to dismantle the welfare state.     

Metalloproteinase from Bacillus subtilis: - "intracellular" and extracellular enzymes

"Intracellular" metalloproteinase was purified to homogeneity from Bacillus subtilis 103 crude cell extract, using affinity chromatography on bacitracin-Sepharose 4B. The degree of purification and the yield of the enzyme were about 260-fold and 3%, respectively. In its physico-chemical properties and the amino acid composition the enzyme is very similar, if not identical, to the extracellular metalloproteinase isolated from the culture filtrate of the same strain. Extracellular metalloproteinase-deficient mutant strain Bacillus subtilis SMY-512 does not produce the "intracellular" enzyme either. THe activity of "intracellular" metalloproteinase in the periplasmic space of the cells is about 70% of that in the cytoplasm, thus being indicative of a rather regular distribution of the enzyme throughout the cell compartment.     

Asymmetric cell divisions in flowering plants - one mother, "two-many" daughters

Plant development shows a fascinating range of asymmetric cell divisions. Over the years, however, cellular differentiation has been interpreted mostly in terms of a mother cell dividing mitotically to produce two daughter cells of different fates. This popular view has masked the significance of an entirely different cell fate specification pathway, where the mother cell first becomes a coenocyte and then cellularizes to simultaneously produce more than two specialized daughter cells. The "one mother - two different daughters" pathways rely on spindle-assisted mechanisms, such as translocation of the nucleus/spindle to a specific cellular site and orientation of the spindle, which are coordinated with cell-specific allocation of cell fate determinants and cytokinesis. By contrast, during "coenocyte-cellularization" pathways, the spindle-assisted mechanisms are irrelevant since cell fate specification emerges only after the nuclear divisions are complete, and the number of specialized daughter cells produced depends on the developmental context. The key events, such as the formation of a coenocyte and migration of the nuclei to specific cellular locations, are coordinated with cellularization by unique types of cell wall formation. Both one mother - two different daughters and the coenocyte-cellularization pathways are used by higher plants in precise spatial and time windows during development. In both the pathways, epigenetic regulation of gene expression is crucial not only for cell fate specification but also for its maintenance through cell lineage. In this review, the focus is on the coenocyte-cellularization pathways in the context of our current understanding of the asymmetric cell divisions. Instances where cell differentiation does not involve an asymmetric division are also discussed to provide a comprehensive account of cell differentiation.     

"Infant mortality in Armenia 1992-2003": a comment.

The purpose of this comment is to counsel caution in some of the conclusions drawn in an otherwise fine article recently published in Economics and Human Biology on infant mortality in Armenia by Hakobyan, Mkrtchyan and Yepiskoposyan. These relate first, to the reliability of estimates and trends in infant mortality estimated from DHS data; second, to the interpretation of what the authors consider to be a 'low' infant mortality rate in former communist countries given their level of economic development; and third, to the role of the health care infrastructure in countries of the former Soviet Union in producing these 'low' infant mortality levels. This comment argues that trends in infant mortality in Armenia and other CIS countries, although probably declining, are perhaps less certain than the authors allow, that existing evidence does not suggest that they are uniformly low by global standards, or that the health care systems in CIS countries are uniformly effective in reducing infant deaths.