The HIV-1 trans-activator protein Tat binds the trans-activation response element (TAR) to facilitate recruitment of the super elongation complex (SEC) to enhance transcription of the integrated pro-viral genome. The Tat–TAR interaction is critical for viral replication and the emergence of the virus from the latent state, therefore, inhibiting this interaction has long been pursued to discover new anti-viral or latency reversal agents. However, discovering active compounds that directly target RNA with high affinity and selectivity remains a significant challenge; limiting pre-clinical development. Here, we report the rational design of a macrocyclic peptide mimic of the arginine rich motif of Tat, which binds to TAR with low pM affinity and 100-fold selectivity against closely homologous RNAs. Despite these unprecedented binding properties, the new ligand (JB181) only moderately inhibits Tat-dependent reactivation in cells and recruitment of positive transcription elongation factor (P-TEFb) to TAR. The NMR structure of the JB181–TAR complex revealed that the ligand induces a structure in the TAR loop that closely mimics the P-TEFb/Tat1:57/AFF4/TAR complex. These results strongly suggest that high-affinity ligands which bind the UCU bulge are not likely to inhibit recruitment of the SEC and suggest that targeting of the TAR loop will be an essential feature of effective Tat inhibitors.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. American Geographical Society is collaborating with JSTOR to digitize, preserve and extend access to Geographical Review. HE opening sentence in "The American Heritage Cookbook" serves as a beacon and a challenge for scholars interested in the variety of American society. "Ours is not a 'cuisine' such as homogeneous nations boast, but a rich potpourri of dishes and drinks that have evolved from the native bounty of this country and the cultures of dozens of others."' A host of terms suggests the regional expression in this potpourri. Boston baked beans, Southern fried chicken, Cajun crawfish, San Francisco sourdough, Maine lobster, Texas chili, and Virginia ham immediately come to mind. Foodways clearly can tell much about the people of the United States and their cultural geography.The focus of this article is the consumption of rice, one of the few foodstuffs for which detailed data are available. We survey state patterns for 1955 and 1980 with an emphasis on the process of change between the two years. Our basic argument is that these patterns are important not only in their own right but also as general cultural indicators. The eating of rice like food habits in general is both tenacious and dynamic.2 Changing intensities of regional usage may provide important clues about hearths of innovation, diffusion routes, and the relative strengths of processes creating diversity and homogeneity in society.The lack of data is the bane of research on foodways in the United States. Detailed information exists for the production of most crops and animals at the state and county levels, but for some reason data on consumption by human beings are usually summarized for the country as a whole. Some detailed information on consumption may be found in the work of nutritionists, folklorists, and anthropologists, but their samples tend to be limited either in terms of population (for example, pregnant women) or area (for example, an urban neighborhood). Nutritionists frequently translate "food eaten" into some dietary equivalent like proportion of protein. The National Food Consumption Survey, conducted three times since 1955, avoided these problems, but the sample is adequate only for a gross, four-part regional division of the country.3 Another measure of food consumption is needed, something between the individual dietary surveys and the countrywide statistics.Unique and almost ideal data for geographical analysis exist for rice. Thirteen times since 1955-56 officials of the U.S. Department of Agriculture have surveyed rice mills and repackagers to ascertain shipments of rice made to each state.4 The studies, intended to help the traditionally regional rice industry to expand domestic consum...