Steps toward computer analysis of nucleotide sequences

Advances in recombinant DNA technology have allowed the isolation of large numbers of biologically interesting fragments of DNA. Concomitant improvements in methods for nucleic acid sequencing have led many investigators to characterize their clones by sequencing them. This has resulted in the accumulation of such large amounts of sequence data that computer-assisted methods, with programs directed toward the manipulation of nucleic acid sequences, have become indispensable during the collection and analysis of that data.     

Cell cycle control of DNA replication by a homologue from human cells of the p34cdc2 protein kinase

The regulation of DNA replication during the eukaryotic cell cycle was studied in a system where cell free replication of simian virus 40 (SV40) DNA was used as a model for chromosome replication. A factor, RF-S, was partially purified from human S phase cells based on its ability to activate DNA replication in extracts from G1 cells. RF-S contained a human homologue of the Schizosaccharomyces pombe p34cdc2 kinase, and this kinase was necessary for RF-S activity. The limiting step in activation of the p34 kinase at the G1 to S transition may be its association with a cyclin since addition of cyclin A to a G1 extract was sufficient to start DNA replication. These observations suggest that the role of p34cdc2 in controlling the start of DNA synthesis has been conserved in evolution.     

Middle Paleolithic assemblages from the Indian subcontinent before and after the Toba super-eruption

The Youngest Toba Tuff (YTT) eruption, which occurred in Indonesia 74,000 years ago, is one of Earth's largest known volcanic events. The effect of the YTT eruption on existing populations of humans, and accordingly on the course of human evolution, is debated. Here we associate the YTT with archaeological assemblages at Jwalapuram, in the Jurreru River valley of southern India. Broad continuity of Middle Paleolithic technology across the YTT event suggests that hominins persisted regionally across this major eruptive event.     

Rational design of peptide-based HIV proteinase inhibitors

A series of peptide derivatives based on the transition-state mimetic concept has been designed that inhibit the proteinase from the human immunodeficiency virus (HIV). The more active compounds inhibit both HIV-1 and HIV-2 proteinases in the nanomolar range with little effect at 10 micromolar against the structurally related human aspartic proteinases. Proteolytic cleavage of the HIV-1 gag polyprotein (p55) to the viral structural protein p24 was inhibited in chronically infected CEM cells. Antiviral activity was observed in the nanomolar range (with one compound active below 10 nanomolar) in three different cell systems, as assessed by p24 antigen and syncytium formation. Cytotoxicity was not detected at 10 and 5 micromolar in C8166 and JM cells, respectively, indicating a high therapeutic index for this new class of HIV proteinase inhibitors.     

L-glutamic acid decarboxylase: a new type in glial cells and human brain gliomas

Human glial cells grown in culture and gliomas and white matter contain an l-glutamic acid decarboxylase which is stimulated markedly by carbonyl-trapping agents. In contrast, L-glutamic acid decarboxylase activity of human cerebral gray matter is strongly inhibited by carbonyl-trapping agents. These results suggest a glial localization of the new type of l-glutamic acid decarboxylase.