Structure and organization of the bovine beta-globin genes

Genomic clones spanning the entire cow beta-globin gene locus have been isolated and characterized. These clones demonstrate that the linkage of embryonic-like (epsilon) genes and pseudogenes (psi) to the previously described fetal (gamma) and adult (beta) genes is as follows: 5'-epsilon 3-epsilon 4-psi 3-beta-epsilon 1-epsilon 2-psi 1- psi 2-gamma-3'. Present data indicate that, like that of the goat, the fetal and adult genes arose via block duplication of an ancestral four- gene set: epsilon-epsilon-psi-beta. This duplication event preceded the divergence of cows and goats, which occurred greater than or equal to 18-20 Myr ago. However, cows do not have the additional four-gene block containing a preadult/stress globin gene (beta C). Furthermore, the cow fetal cluster contains an extra beta-like pseudogene, which apparently arose by a small-scale duplication. The fixation of this duplication may indicate a possible evolutionary role for pseudogenes.      

Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size

The distributions of allele sizes at eight simple-sequence repeat (SSR) or microsatellite loci in chimpanzees are found and compared with the distributions previously obtained from several human populations. At several loci, the differences in average allele size between chimpanzees and humans are sufficiently small that there might be a constraint on the evolution of average allele size. Furthermore, a model that allows for a bias in the mutation process shows that for some loci a weak bias can account for the observations. Several alleles at one of the loci (Mfd 59) were sequenced. Differences between alleles of different lengths were found to be more complex than previously assumed. An 8-base-pair deletion was present in the nonvariable region of the chimpanzee locus. This locus contains a previously unrecognized repeated region, which is imperfect in humans and perfect in chimpanzees. The apparently greater opportunity for mutation conferred by the two perfect repeat regions in chimpanzees is reflected in the higher variance in repeat number at Mfd 59 in chimpanzees than in humans. These data indicate that interspecific differences in allele length are not always attributable to simple changes in the number of repeats.      

Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

Background  

Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia) and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections.     

Efficient one‐pot synthesis of N‐ethyl amino acids

Mono‐N‐ethylated α‐amino acid esters are obtained in high yields using reductive amination procedures. Formation of imine is achieved by excess of acetaldehyde, followed by removal of acetaldehyde and reduction by NaBH(OAc)₃. The elaborated one‐pot synthesis allows for the efficient synthesis of side‐chain protected amino acid derivatives. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.     

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain

To elucidate a role for the cytoskeletal protein actin in post-traumatic apoptotic cell death, the ability of actin-containing tissue extracts to inhibit exogenous DNase I was evaluated. In addition, cortical, hippocampal and thalamic extracts were examined for caspase-mediated actin cleavage and changes in actin polymerization state. Rats were anesthetized, subjected to lateral fluid percussion brain injury of moderate severity, and euthanized at 1 h, 6 h, 24 h, 1 week or 3 weeks post-injury (n = 3 per time-point). Tissue extracts from all brain regions of sham (uninjured) animals inhibited exogenous DNase I activity to a significant extent. However, inhibition of DNase I was significantly reduced at 1 h and 6 h in the injured hippocampus, and at 1 h, 6 h and 3 weeks in the thalamus. DNase I in cortical extracts of all injured animals was inhibited to a similar extent as that in uninjured animals. Actin fragments consistent with caspase-mediated proteolysis were observed in immunoblots of the injured hippocampus and thalamus at 1 h and 24 h, respectively, and were present up to 3 weeks post-injury. Transient actin hyperpolymerization was observed at 1 and 6 h post-injury in the thalamus and hippocampus, while actin depolymerization was observed at 1 and 3 weeks in the cortex and thalamus. Collectively our data suggest that DNase I disinhibition following brain trauma is associated predominantly with actin hyperpolymerization but also with actin depolymerization and concomitant caspase-mediated actin proteolysis.