UC-82

Nitrogen (N) supply usually limits crop production and optimizing N-use efficiency (NUE) to minimize fertilizer loss is important. NUE is a complex trait that can be dissected into crop N uptake from the soil (NUpE) and N utilization (NUtE). We compared NUE in 14 genotypes of three week old tomatoes grown in sand or hydroponic culture supplied with nitrate (NO3(-)). Culture method influenced measured NUE for some cultivars, but Regina Ostuni (RO) and UC82 were consistently identified as high and low NUE genotypes. To identify why these genotypes had contrasting NUE some traits were compared growing under 0.1 and 5 mM NO3(-) supply. UC82 showed greater root (15)NO3(-) influx at low and high supply, and stronger SlNRT2.1/NAR2.1 transporter expression under low supply when compared with RO. Conversely, RO showed a higher total root length and thickness compared to UC82. Compared with UC82, RO showed higher shoot SlNRT2.3 expression and NO3(-) storage at high supply, but similar NO3(-) reductase activity. After N-starvation, root cell electrical potentials of RO were significantly more negative than UC82, but nitrate elicited similar responses in both root types. Overall for UC82 and RO, NUtE may play a greater role than NUpE for improved NUE.

A series of compounds related to oxathiin carboxanilide has been identified as nonnucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1, and structure-activity relationships have been described (Buckheit RW, et al.: Antimicrob Agents Chemother 1995;39:2718-2727). Three new analogs (UC040, UC82, and UC781) inhibited laboratory and clinical isolates of HIV-1, including isolates representative of the various clades of HIV-1 found worldwide, in both established and fresh human cells. Virus isolates with the amino acid changes L100I, K103N, V106I, and Y181C in the reverse transcriptase were partially resistant to these compounds. However, UC781 inhibited these virus isolates at low nontoxic concentrations, presenting a broad in vitro therapeutic index. As with other NNRTIs, each of the compounds synergistically interacted with AZT to inhibit HIV-1 replication. UC781 possesses a favorable pharmacokinetic profile in mice with a high level of oral bioavailability. Plasma concentrations reached maximum levels within 2 to 4 hr of oral administration and remained in excess of those required for in vitro anti-HIV activity for at least 24 hr after a single oral dose. When evaluated in a murine hollow fiber implant model of HIV infection, UC781 dosed orally or parenterally was able to suppress HIV replication completely in this model system, providing evidence of the in vivo efficacy of the compound.