NIDA technical review: nitrite inhalants

Nitrite inhalants are commonly abused substances in the US and Europe. "Nitrite inhalants and AIDS" was a popular topic in the early 1980s when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use wained. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in laboratory studies, and remains a candidate "cofactor" in the pathogenesis of AIDS-related Karposi sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal. Participants recommend specific research efforts.     

Production of human normal adult and fetal hemoglobins in Escherichia coli

A hemoglobin expression system in Escherichia coli is described. In order to produce authentic human hemoglobin, we need to co-express both methionine aminopeptidase and globin genes under the control of a strong promoter. We have constructed three plasmids, pHE2, pHE4 and pHE7, for the expression of human normal adult hemoglobin and a plasmid, pHE9, for the expression of human fetal hemoglobin, in high yields. The globin genes can be derived from either synthetic genes or human globin cDNAs. The extra amino-terminal methionine residues of the expressed globins can be removed by the co-expressed methionine aminopeptidase. The heme is inserted correctly into the expressed alpha- globin from our expression plasmids. A fraction (approximately 25%) of the heme is not inserted correctly into the expressed beta- or gamma- globin. However, the incorrectly inserted hemes can be converted into the correct conformation by carrying out a simple oxidation-reduction process on the purified hemoglobin molecule. We have investigated the functional properties of the expressed hemoglobins by measuring their oxygen-binding properties and their structural features by obtaining their 1H-NMR spectra. Our results show that authentic human normal adult and fetal hemoglobins can be produced from our expression plasmids in E. coli and in high yields. Our expression system allows us to design and to produce any recombinant hemoglobins needed for our research on the structure-function relationship in hemoglobin.      

Relations between anxiety sensitivity, distress tolerance, and fear reactivity to bodily sensations to coping and conformity marijuana use motives among young adult marijuana users.

The present investigation examines anxiety sensitivity, distress tolerance, and fear reactivity to bodily sensations in relation to Coping and Conformity marijuana use motives among a sample of young adult marijuana users (n = 135; 46.7% women; Mage = 20.45, SD = 5.0). After controlling for current marijuana use frequency (past 30 days), daily cigarette smoking rate, average volume of alcohol used over the past year, negative affectivity, and other marijuana use motives, anxiety sensitivity was significantly and uniquely associated with Coping and Conformity motives for marijuana use. Distress tolerance evidenced significant and unique incremental relations to Coping motives, whereas fear reactivity to bodily sensations was unrelated to any marijuana use motive. These results provide novel information related to the role of emotional sensitivity and tolerance factors as they pertain to specific types of motives for marijuana use among young adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pseudouridine synthase 7 impacts Candida albicans rRNA processing and morphological plasticity

RNA can be modified in over 100 distinct ways, and these modifications are critical for function. Pseudouridine synthases catalyse pseudouridylation, one of the most prevalent RNA modifications. Pseudouridine synthase 7 modifies a variety of substrates in Saccharomyces cerevisiae including tRNA, rRNA, snRNA, and mRNA, but the substrates for other budding yeast Pus7 homologues are not known. We used CRISPR-mediated genome editing to disrupt Candida albicans PUS7 and find absence leads to defects in rRNA processing and a decrease in cell surface hydrophobicity. Furthermore, C. albicans Pus7 absence causes temperature sensitivity, defects in filamentation, altered sensitivity to antifungal drugs, and decreased virulence in a wax moth model. In addition, we find C. albicans Pus7 modifies tRNA residues, but does not modify a number of other S. cerevisiae Pus7 substrates. Our data suggests C. albicans Pus7 is important for fungal vigour and may play distinct biological roles than those ascribed to S. cerevisiae Pus7.