SAR and biological evaluation of 3-azabicyclo[3.1.0]hexane derivatives as µ opioid ligands.

3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral µ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the µ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.

Contextual control by function and form of transfer of functions.

This study investigated conditions leading to contextual control by stimulus topography over transfer of functions. Three 4-member stimulus equivalence classes, each consisting of four (A, B, C, D) topographically distinct visual stimuli, were established for 5 college students. Across classes, designated A stimuli were open-ended linear figures, B stimuli were circular, C stimuli three-sided, and D stimuli four-sided. Three different computer tasks then were trained with the B stimuli. Differential reinforcement and punishment procedures were then used to establish control over function transfer by the topography of the class members. For Task 1, function transfer, responding to C and D stimuli as subjects had to B stimuli, was reinforced. For Task 2, function transfer was reinforced for C stimuli but punished for D stimuli. For Task 3, function transfer was punished for both C and D stimuli. New equivalence classes were then established and tests for generalized contextual control were presented. All 5 subjects showed generalized contextual control of transfer of functions by stimulus topography. Implications of contextual control over function transfer in natural settings are discussed.

Recreational ecstasy use and depression.

Research in laboratory animals has shown that 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) destroys serotonergic axons in the brain at certain doses. Serotonin is known to take part in the regulation of mood in humans. Many researchers have hypothesized that if recreational ecstasy use destroys serotonergic axons, then a corresponding decline in the mood of ecstasy users should be seen. The purpose of the present study was to look at the relationship between recreational ecstasy use and depression as measured by the Beck Depression Inventory-II. No significant differences were found between Beck Depression Inventory-II scores of heavy ecstasy users and ecstasy-naive college students. No significant relationships were found between Beck Depression Inventory-II scores and any of the measures of ecstasy use. Most ecstasy users who had been diagnosed with a psychiatric disorder reported that being diagnosed preceded their use of ecstasy.

A real-time PCR assay for the detection of Campylobacter jejuni in foods after enrichment culture.

A real-time PCR assay was developed for the quantitative detection of Campylobacter jejuni in foods after enrichment culture. The specificity of the assay for C. jejuni was demonstrated with a diverse range of Campylobacter species, related organisms, and unrelated genera. The assay had a linear range of quantification over six orders of magnitude, and the limit of detection was approximately 12 genome equivalents. The assay was used to detect C. jejuni in both naturally and artificially contaminated food samples. Ninety-seven foods, including raw poultry meat, offal, raw shellfish, and milk samples, were enriched in blood-free Campylobacter enrichment broth at 37 degrees C for 24 h, followed by 42 degrees C for 24 h. Enrichment cultures were subcultured to Campylobacter charcoal-cefoperazone-deoxycholate blood-free selective agar, and presumptive Campylobacter isolates were identified with phenotypic methods. DNA was extracted from enrichment cultures with a rapid lysis method and used as the template in the real-time PCR assay. A total of 66 samples were positive for C. jejuni by either method, with 57 samples positive for C. jejuni by subculture to selective agar medium and 63 samples positive in the real-time PCR assay. The results of both methods were concordant for 84 of the samples. The total time taken for detection from enrichment broth samples was approximately 3 h for the real-time PCR assay, with the results being available immediately at the end of PCR cycling, compared to 48 h for subculture to selective agar. This assay significantly reduces the total time taken for the detection of C. jejuni in foods and is an important model for other food-borne pathogens.

Contextual control of equivalence-based transformation of functions.

The transformation of functions refers to the untrained acquisition of stimulus functions among members of stimulus equivalence classes or relational frames. Although it is widely assumed that contextual control over the transformation of fuctions must exist, this has not yet been conclusively demonstrated in laboratory studies. Four experiments are reported in which (a) stimulus equivalence classes were established, (b) a conditional stimulus function was trained for one member of each of the classes, and (c) multiple-exemplar procedures were used to train and test for contextual control over the transformation of the stimulus function within the classes and to assess whether it generalized to new equivalence classes. Although a significant amount of training was required, the procedures ultimately resulted in the contextual control of function transformation for 9 of 10 participants and generalized contextual control for 4 of 5 participants.

Increased expression of the multidrug efflux genes acrAB occurs during slow growth of Escherichia coli.

Intrinsic antimicrobial resistance of Escherichia coli is elicited by the gene products of the multidrug efflux acrAB-tolC operon. In this paper, we have shown that acrAB is regulated as a function of the growth rate of E. coli during growth in batch and chemostat culture. In chemostat culture, expression of acrAB is inversely related to growth rate irrespective of the limiting nutrient. The level of expression of acrAB is greater under glucose limitation compared with either iron or nitrogen limitation. Increase in expression of acrAB confers a greater resistance to ciprofloxacin, and the implications for a clinical situation are discussed. Slow growth rate regulation of acrAB transcription does not require the presence of the stationary-phase sigma factor. A putative gearbox consensus sequence was identified at the -10 region of the acrAB promoter.