Cell
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Last year marked the 25th anniversary of the recognition of what we now call AIDS. The AIDS pandemic has claimed more than 25 million lives, the majority of them in the developing world, and has exacerbated poverty and slowed human development. Although much has been accomplished in HIV/AIDS research, much remains to be done, especially regarding delivery of HIV/AIDS therapies and care and prevention interventions to the poorest countries that need them most.
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This year, the Lasker Foundation recognizes Albert Starr and Alain Carpentier for their development of effective treatments for valvular heart disease. Their innovative work is a model of interdisciplinary basic and clinical research and has benefited millions of people.
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Ralph Steinman is to receive the 2007 Albert Lasker Award for Basic Medical Research for his discovery of dendritic cells and his path-breaking work demonstrating their central role as the principal antigen-presenting cells of the immune system and key activators of T cell responses.
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TLR4 and MD-2 form a heterodimer that recognizes LPS (lipopolysaccharide) from Gram-negative bacteria. Eritoran is an analog of LPS that antagonizes its activity by binding to the TLR4-MD-2 complex. We determined the structure of the full-length ectodomain of the mouse TLR4 and MD-2 complex. ⋯ MD-2 binds to the concave surface of the N-terminal and central domains. The interaction with Eritoran is mediated by a hydrophobic internal pocket in MD-2. Based on structural analysis and mutagenesis experiments on MD-2 and TLR4, we propose a model of TLR4-MD-2 dimerization induced by LPS.
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Caspases are intracellular proteases that cleave substrates involved in apoptosis or inflammation. In C. elegans, a paradigm for caspase regulation exists in which caspase CED-3 is activated by nucleotide-binding protein CED-4, which is suppressed by Bcl-2-family protein CED-9. ⋯ When exposed to MDP, Bcl-2-deficient macrophages exhibit more caspase-1 processing and IL-1beta production, whereas Bcl-2-overexpressing macrophages demonstrate less caspase-1 processing and IL-1beta production. The findings reveal an interaction of host defense and apoptosis machinery.