A predictive model for life expectancy curves

Life expectancy curves have a characteristic ominous shape that has fascinated scientists for centuries. Medawar was the first to explain this shape, specifically the steeply rising proneness of an average individual to die as a function of age, in evolutionary terms. The idea was that the "selective value" of the individual decreases as it has triggered other individuals taking its place (and carrying its genes) into existence. We demonstrate that this idea can be turned into a quantitative model. The resulting 4-parameter function reproduces well two well-known life expectancy curves from the first half of this century. Moreover, the easily interpretable parameters (3 of the 4) seem intuitively reasonable.     

Cloning and characterization of the HpaII methylase gene.

The HpaII restriction-modification system from Haemophilus parainfluenzae recognizes the DNA sequence CCGG. The gene for the HpaII methylase has been cloned into E. coli and its nucleotide sequence has been determined. The DNA of the clones is fully protected against cleavage by the HpaII restriction enzyme in vitro, indicating that the methylase gene is active in E. coli. The clones were isolated in an McrA-strain of E. coli; attempts to isolate them in an McrA+ strain were unsuccessful. The clones do not express detectable HpaII restriction endonuclease activity, suggesting that either the endonuclease gene is not expressed well in E. coli, or that it is not present in its entirety in any of the clones that we have isolated. The derived amino acid sequence of the HpaII methylase shows overall similarity to other cytosine methylases. It bears a particularly close resemblance to the sequences of the HhaI, BsuFI and MspI methylases. When compared with three other methylases that recognize CCGG, the variable region of the HpaII methylase, which is believed to be responsible for sequence specific recognition, shows some similarity to the corresponding regions of the BsuFI and MspI methylases, but is rather dissimilar to that of the SPR methylase.     

Distamycin inhibition of topoisomerase I-DNA interaction: a mechanistic analysis.

Inhibition of eukaryotic DNA topoisomerase I by the minor groove binding ligand, distamycin A, was investigated. Low concentrations of the ligand selectively prevented catalytic action at a high affinity topoisomerase I binding sequence. A restriction enzyme protection assay indicated that the catalytic cycle was blocked at the binding step. Distamycin binding sites on DNA were localized by hydroxyl radical footprinting. A strongly preferred site mapped to a homopolymeric (dA).(dT)-tract partially included in the essential topoisomerase I binding region. Mutational elimination of the stable helix curvature associated with this ligand binding site demonstrated that (i) the intrinsic bend was unessential for efficient binding of topoisomerase I, and (ii) distamycin inhibition did not occur by deformation of a stable band. Alternative modes of inhibition are discussed.     

Zinc-dependent angiotensin-converting enzyme in reactions with various enzymes

The effects of Zn2+ on the activity of the angiotensin-converting enzyme from bovine lung towards the substrates, FA-Phe-Gly-Gly and Cbz-Phe-His-Leu, have been studied. At pH below 7.0 zinc ions added to the reaction mixture increase the enzyme activity; this stimulating effect is changed to inhibition with a further rise in Zn2+ concentration. It was shown that the dissociation constant for the enzyme--Zn2+ complex and the "optimal" concentrations of Zn2+ needed for the manifestation of the maximal enzymatic activity depend on the nature of the substrate at all pH values studied.     

Leukaemia and transient leukaemia in Down syndrome

Summary We have reviewed 215 published cases of leukaemia and transient leukaemia in Down syndrome. There is an over-representation of mosaic trisomy 21, possibly the result, at least in part, of a survival effect. The most intriguing observation is a bimodal distribution of maternal age, produced largely because cases with true leukaemia have a significantly higher maternal age than cases with transient leukaemia (33.5 versus 29.5 years). In conjunction with evidence that meiosis I non-disjunction is infrequent in transient leukaemia, this suggests different mechanisms for the etiology of leukaemia and transient leukaemia, and favours a locus predisposing to transient leukaemia proximal to the centromere on the long arm of chromosome 21.