SummaryIt has previously been shown that the frequency of pilin antigenic variation in Neisseria gonorrhoeae (the gonococcus, Gc) is regulated by iron availability. To identify factors involved in pilin variation in an irondependent or an iron-independent manner, we conducted a genetic screen of transposon-mutated gonococci using a pilus-dependent colony morphology phenotype to detect antigenic variation deficient mutants. Forty-six total mutants representing insertions in 30 different genes were shown to have reduced colony morphology changes resulting from impaired pilin variation. Five mutants exhibited an iron-dependent decrease in pilin variation, while the remaining 41 displayed an iron-independent decrease in pilin variation. Based on the levels of antigenic variation impairment, we defined the genes as being essential for, important for, or involved in antigenic variation. DNA repair and DNA transformation frequencies of each mutant were measured to determine whether other recombination-based processes were also affected in the mutants. Each mutant was placed into one of six classes based on their pilin variation, DNA repair and DNA transformation phenotypes. Among the many genes identified, recR is shown to be an additional member of the gonococcal RecF-like recombination pathway. In addition, recG and ruvA represent the first evidence that the processing of Holliday junctions is required for pilin antigenic variation. Moreover, two independent insertions in a noncoding region upstream of the pilE gene suggest that cis -acting sequences important for pilin variation are found in that region. Finally, insertions that effect expression of the thrB and thrC genes suggest that molecules in the threonine biosynthetic pathway are important for pilin variation. Many of the other genes identified in this genetic screen do not have an obvious role in pilin variation, DNA repair, or DNA transformation.

The effects of cigarette smoking result from the delivery of nicotine, other components of smoke, and sensory stimulation. In the present study, pharmacological effects of new tobacco-derived de-nicotinized cigarettes (controls) were compared with standard cigarettes. The de-nicotinized cigarettes had the appearance, draw and taste of standard cigarettes but contained and delivered virtually no nicotine (< 0.06 mg), but delivered tar and carbon monoxide (CO). They were compared with cigarettes that delivered nicotine, CO and tar. Subjects (n = 20: 10 men, 10 women) participated in four experimental sessions in which they smoked either a standard cigarette or a de-nicotinized cigarette after either 3 or 12 h of tobacco deprivation. Heart rate, blood pressure, and EEG were recorded before, and for 1 h after, ad lib smoking. Plasma nicotine concentrations verified that de-nicotinized cigarettes did not deliver nicotine. The de-nicotinized cigarettes did not increase heart rate or activate the EEG. The subjects preferred the cigarettes that delivered nicotine compared to the de-nicotinized cigarettes. However, both types of cigarettes reduced subjective measures of tobacco craving and withdrawal. These data extend previous research that suggested the process of smoking and components of tobacco smoke other than nicotine mediate some effects of cigarette smoking. The de-nicotinized cigarettes may prove useful in evaluating effects of smoking independent of the delivery of nicotine.

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Some abused drugs have been reported to alter performance on naturalistic tasks such as driving and also on laboratory tasks. The performance effects of several drug classes were examined using a repeated measures design. Eight volunteers were administered 2 doses of ethanol, marijuana, amphetamine, hydromorphone, pentobarbital, or placebo on separate days. The larger dose of each increased subjective drug strength; however, only ethanol and pentobarbital impaired performance on circular lights, digit symbol substitution, and serial math tasks. Both ethanol and pentobarbital impaired performance on card-sorting tasks; impairment was evident at lower doses as the cognitive load increased. Results illustrate differences among drugs in producing performance impairment at doses that cause subjective effects. Increasing cognitive requirements uncovered performance impairment at lower doses.