Hot Papers

The articles listed below, all less than two years old, have received a substantially greater number of citations than others of the same type and vintage, according to data from the Science Citation Index of the Institute for Scientific Information, Philadelphia. Why have these research reports become such standouts? A comment following each reference, supplied to The Scientist by one of the authors, attempts to provide an answer. L. Osborn, S. Kunkel, G.J. Nabel, "Tumor necrosis factor à and interleukin-1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kB," PNAS, 86, 2336-40, April 1989. Gary J. Nabel (University of Michigan Medical Center, Ann Arbor): "Replication of the human immunodeficiency virus (HIV) is affected by both cellular and viral genes. A major interest of our laboratory is the definition of cellular factors that contribute to the activation of HIV. We have shown previously that the nuclear factor-kB (NF-kB) stimulates the HIV enhancer in T cells activated by mitogens. Since viral replication can also be increased by mitogens, it is thought that this transcription factor contributes to HIV activation. The physiologic activators of NF-kB and the HIV enhancer, however, are not known. In this paper, we systematically analyzed the ability of several cytokines to stimulate the HIV enhancer. Two such cytokines--tumor necrosis factor-à (TNF-à) and interleukin-1--were found to exert such an effect by induction of NF-kB. Because increased levels of TNF-à are found in the circulation of AIDS patients, this finding suggests a possible means of intervention with the activation of HIV in vivo. We also showed that activation of interleukin-2 was unaffected by TNF-à, suggesting that the activation of HIV can be dissociated from immunologic activation of T cells. Several groups have now also shown that TNF-à will activate the replication of HIV in latently infected cells. Taken together, this study and others have implicated tumor necrosis factor as a likely physiologic activator of the AIDS virus and have suggested that this cytokine may be a suitable target for therapeutic interventions in AIDS." G.A. Gonzalez, K.K. Yamamoto, W.H. Fischer, D. Karr, et al., "A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequences," Nature, 337, 749-52, 23 February 1989. Gustavo Gonzalez (The Salk Institute, La Jolla, Calif.): "How are extracellular signals transduced into real physiological responses? Many of these events occur through altered patterns of gene expression mediated by second messenger pathways and their associated protein kinases. The cloning of the transcription factor CREB has enabled our laboratory and others to elucidate mechanisms by which protein kinases govern gene transcription. The CREB protein has a cluster of phosphorylation sites situated between the putative N-terminal activator region and the C-terminal DNA binding and dimerization domains. This architecture suggests that protein kinase A allosterically regulates the transcriptional efficacy of CREB through the direct phosphorylation of a single serine (SER 133). Furthermore, the proximity of these sites to one another indicate that multiple signal transduction pathways may act within the centrally located `kinase inducible domain' to regulate CREB activity. "The leucine-zipper dimerization domain of CREB shares substantial homology with other leucine-zipper proteins,including c-fos, c-myc, c-jun, and several of the recently cloned but uncharacterized factors that fall into the CREB/ATF family. The prevalence of such dimerization domains among nuclear factors illustrates yet another potential mode of regulation through the combinatorial formation of zipper-mediated heterodimers. This report thus provides the first direct evidence that an effector kinase responding to hormonal stimulation can directly regulate the activity of a transcription factor in mammalian cells." S. Chakravarty, B.I. Halperin, D.R. Nelson, "Two- dimensional quantum Heisenberg antiferromagnet at low temperatures," Physical Review B, 39, 2344-71, 1 February 1989. Sudip Chakravarty (University of California, Los Angeles): "To this day the mechanism for the recently discovered high-temperature supercon- ductors remains unknown despite intense activity in this field. However, Philip W. Anderson (Princeton) suggested that a magnetic mechanism may be operative. Since then much effort has been spent in elucidating the magnetic properties of the parent compounds of these superconductors. Two-dimensional quantum Heisenberg antiferromagnet appears to be a good model to study in this context. This is an interesting and challenging model in its own right and has been around for many years. The present paper provides, for the first time, what we believe to be a reasonably complete understanding of this model. Our theory is in excellent agreement with the results of the neutron scattering experiments performed at the Brookhaven National Lab. The implications of this work for the mechanism of high-temperature supercon- ductivity remain to be seen." W.E. Pickett, "Electronic structure of the high- temperature oxide superconductors," Review of Modern Physics, 61, 433-512, April 1989. Warren E. Pickett (Naval Research Laboratory, Washington, D.C.): "Review articles, widely valued in mature fields, can also be crucial to the development of `hot topics.' The remarkable discovery by J. Georg Bednorz and K. Alex Müller of a new class of materials that become superconducting at unprecedentedly high temperatures sparked high interest in determining its cause (and an immediate Nobel Prize!). Although there have been numerous suggestions about the underlying mechanisms, there is one common type of information that is necessary to enable a theory to be constructed. This common thread is the underlying quantum- mechanically determined electronic structure. Within the first several months of the discovery, band structure theorists from several groups around the world had produced detailed calculations that provided this information. In this article, I provided a comprehensive review and discussion of the first two years' work. The vital information, which was scattered throughout the literature, now is available in one paper, including a comprehensive reference list. Recent experiments are demonstrating the overriding importance of these band calculations."

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September 1990

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