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Biomedical subjects
Publications and source records attributed to R Smith.
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We assessed the expression and distribution of p21/Waf-1 in TLM1 melanoma cells that exhibit contact inhibition and require serum for growth. The growth stage of cells stimulated to enter the mitotic cell cycle synchronously and grow to confluence was characterized by distinct, yet consistent levels and patterns of distribution of p21/Waf-1. Significantly, sustained accumulation of p21/Waf-1 in the nuclear compartment was seen only after 4 days in culture when cell-to-cell contacts were established, leading to a diminished rate of cell growth. Overexpression of wild-type waf-1 in melanoma cells reduced growth of subconfluent cells, decreased Cdk4 activity with a concomitant increase in hypophosphorylated Rb, and promoted cell death by apoptosis. The data support the premise that cell-to-cell contacts provide signals that mediate sustained nuclear localization of p21/Waf-1 leading to cell growth arrest; furthermore, an elevation in the activity of this protein can lead to apoptosis.
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The Permian-Triassic transition in the Karoo Basin of South Africa was characterized by a rapid and apparently basin-wide change from meandering to braided river systems, as evidenced by preserved sedimentary facies. This radical changeover in river morphology is consistent with geomorphic consequences stemming from a rapid and major die-off of rooted plant life in the basin. Evidence from correlative nonmarine strata elsewhere in the world containing fluvial Permian-Triassic boundary sections suggests that a catastrophic terrestrial die-off of vegetation was a global event, producing a marked increase in sediment yield as well as contributing to the global delta(13)C excursion across the Permian-Triassic boundary.
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The sixth ligand-binding module of the low-density lipoprotein receptor contributes to the binding of apolipoprotein B100-containing lipoproteins. 1H NMR spectroscopy, DYANA and X-PLOR structure calculations were used to determine that this module has a well defined structure with a backbone conformation similar to other modules. Structures from calculations that simulated the presence of a calcium ion showed increased resolution without large increases in energy, increased deviations from idealised geometry or violations of experimental constraints. Investigation of the surface properties of this module indicates there are significant differences from the fifth module, which binds apolipoprotein E-containing lipoproteins in addition to apolipoprotein B100-containing lipoproteins.
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HIV-1 Tat protein activates resting cells, rendering them permissive for viral replication. Replication of HIV-1 in vitro is enhanced by intercellular passage of Tat protein and inhibited by anti-Tat antibodies. Tat dependence of HIV-1 replication in vivo during acute, chronic asymptomatic and AIDS stages of infection was assessed by comparisons of plasma viremia in Tat-immunized or control monkeys challenged with SHIV(33) or SHIV(33A). Chronic plasma viremia became undetectable or minimized in Tat-immunized asymptomatic SHIV(33)-infected monkeys (p<0.008) while the high viral loads of acute infection or SHIV(33A)-induced simian AIDS were unaffected by Tat immunization. Active or passive immunotherapies targeting Tat provide potential approaches to controlling chronic HIV-1 viremia and preventing AIDS.
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