Molecular evolution of P transposable elements in the genus Drosophila. III. The melanogaster species group

Phylogenetic relationships were determined for 76 partial P-element sequences from 14 species of the melanogaster species group within the Drosophila subgenus Sophophora. These results are examined in the context of the phylogeny of the species from which the sequences were isolated. Sequences from the P-element family fall into distinct subfamilies, or clades, which are often characteristic for particular species subgroups. When examined locally among closely related species, the evolution of P elements is characterized by vertical transmission, whereby the P-element phylogeny traces the species phylogeny. On a broader scale, however, the P-element phylogeny is not congruent with the species phylogeny. One feature of P-element evolution in the melanogaster group is the presence of more than one P-element subfamily, differing by as much as 36%, in the genomes of some species. Thus, P elements from several individual species are not monophyletic, and a likely explanation for the incongruence between P-element and species phylogenies is provided by the comparison of paralogous sequences. In certain instances, horizontal transfer seems to be a valid alternative explanation for lack of congruence between species and P-element phylogenies. The canonical P-element subfamily, which represents the active, autonomous transposable element, is restricted to D. melanogaster. Thus, its origin clearly lies outside of the melanogaster species group, consistent with the earlier conclusion of recent horizontal transfer.     

Inhibition of eukaryote protein kinases and of a cyclic nucleotide-binding phosphatase by prenylated xanthones

A series of prenylated xanthones are variously potent inhibitors of the catalytic subunit (cAK) of rat liver cyclic AMP-dependent protein kinase (PKA), rat brain Ca2+ and phospholipid-dependent protein kinase C (PKC), chicken gizzard myosin light chain kinase (MLCK), wheat embryo Ca2+-dependent protein kinase (CDPK) and potato tuber cyclic nucleotide-binding phosphatase (Pase). The prenylated xanthones examined are mostly derivatives of alpha-mangostin in which the 3-hydroxyl and 6-hydroxyl are variously substituted with groups R or R', respectively, or derivatives of 3-isomangostin (mangostanol) in which the 9-hydroxyl is substituted with groups R' or the prenyl side chain is modified. The most potent inhibitors of cAK have non-protonatable and relatively small R' and R groups. Conversely, the most potent inhibitors of PKC and MLCK have bulkier and basic R' groups. Some prenylated xanthones are also potent inhibitors of CDPK. PKC and cAK are competitively inhibited by particular prenylated xanthones whereas the compounds that are the most potent inhibitors of MLCK and CDPK are non-competitive inhibitors. Prenylated xanthones having relatively small and non-protonatable R' and R groups inhibit a high-affinity cyclic nucleotide binding Pase in a non-competitive fashion.     

Safety of a temperature-sensitive clone of Mycoplasma synoviae as a live vaccine

A temperature-sensitive (ts+) clone derived from the Australian Mycoplasma synoviae (MS) field isolate 86079/7NS was produced by chemical mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine and assessed for safety as a live vaccine. This clone, designated MS-H, was assessed for pathogenicity in three different models with air sac lesions as the criterion. No air sac lesions were observed when MS-H was administered to specific-pathogen-free hybrid white leghorn (HWL) chickens by eyedrop at 10 times the normal dose or directly into the thoracic air sacs or as an aerosol administered to specific-pathogen-free Webster white leghorn chickens with concurrent intratracheal T-strain infectious bronchitis virus (IBV). MS-H did not revert to virulence or lose the ts+ phenotype when passaged through five in vivo and 10 in vitro passages. No adverse effects were seen when HWL chickens were vaccinated concurrently with MS-H and combinations of Mycoplasma gallisepticum ts-11 vaccine, IBV vaccine, and infectious laryngotracheitis virus vaccine. Lateral transmission of MS-H was found to occur when vaccinated HWL chickens were mixed with unvaccinated chickens 2 wk after vaccination. At 1 wk after mixing, one out of two unvaccinated chickens had seroconverted to MS and was culture positive for MS. At 2 wk after mixing, both contact chickens were positive for MS by culture and serology.     

Oral mucosal ulceration due to cytomegalovirus associated with human immunodeficiency virus infection. Case report and brief review

Reports of oral lesions associated with cytomegalovirus (CMV) infection in human immunodeficiency virus (HIV) infected patients are uncommon. In this article a case of CMV infection associated with oral mucosal ulceration and a brief review of the subject is presented. Establishing the cause of ulceration is important in determining a definitive diagnosis and prescribing appropriate therapy. It is important to recognize that CMV associated oral mucosal ulceration may be the initial manifestation of human immunodeficiency virus (HIV) infection.     

Bacteria lacking a multidrug pump: a sensitive tool for drug discovery

Microorganisms express multidrug resistance pumps (MDRs) that can confound antibiotic discovery. We propose the use of mutants deficient in MDRs to overcome this problem. Sensitivity to quinolones and to amphipathic cations (norfloxacin, benzalkonium chloride, cetrimide, pentamidine, etc.) was increased 5- to 30-fold in a Staphylococcus aureus mutant with a disrupted chromosomal copy of the NorA MDR. NorA was required both for increased sensitivity to drugs in the presence of an MDR inhibitor and for increased rate of cation efflux. This requirement suggests that NorA is the major MDR protecting S. aureus from the antimicrobials studied. A 15- to 60-fold increase in sensitivity to antimicrobials also was observed in wild-type cells at an alkaline pH that favors accumulation of cations and weak bases. This effect was synergistic with a norA mutation, resulting in an increase up to 1,000-fold in sensitivity to antimicrobials. The usefulness of applying MDR mutants for natural product screening was demonstrated further by increased sensitivity of the norA- strain to plant alkaloid antimicrobials, which might be natural MDR substrates.     

Statistical methods in psychiatric genetics

Most psychiatric disorders are determined by the complex interplay between genetic and environmental factors. Aetiological research into these complex disorders raises many different questions which require a variety of statistical methods. These include survival analysis for the estimation of morbid risk, structural equation models for the partitioning of phenotypic variances and covariances into genetic and other components, complex segregation analysis to detect loci of major effect, and linkage and association analysis for the localisation and identification of susceptibility genes. Future developments in psychiatric genetics will involve the integration of genetic and epidemiological statistics in order to study the interplay between genetic and environmental factors in the complex pathways which lead to mental disorders.     

William James and emotion: is a century of fame worth a century of misunderstanding?

During his lifetime William James's complex ideas about emotion were oversimplified to the point of caricature, and for the next half century scientific research on emotion was driven by the oversimplified version--by the idea that emotions are merely the sensation of bodily changes. In fact, the interpretation of the stimulus was an essential feature of James's ideas, but one that seemed so obvious that it did not require explanation. Three damaging scientific consequences of the mischaracterization of James's views were (a) the nearly exclusive focus on bodily process, (b) the reification of emotions as entities rather than processes, and (c) the linear thinking produced by the concern with the sequence of affect, interpretation, and bodily response.     

Subcutaneous nodules as a manifestation of onchocerciasis. A rare condition in the United States

Although infection with tissue nematodes is a significant health problem in many parts of the world, such cases are unusual in the continental United States. This report describes a case of Onchocerca volvulus infection, acquired by a 38-year-old female missionary in northern Brazil, that manifested as subcutaneous nodules in the groin and flank two years after the patient's return to the United States. A year previously, a wrong diagnosis of Wuchereria bancrofti was made at biopsy. At that time, treatment with diethylcarbamazine citrate had to be discontinued because of intense pruritus. Examination of a wet saline impression smear of a new biopsy specimen showed the adult worms to have regularly arranged outer annular ridges, which, together with the pruritus after treatment with diethylcarbamazine (a positive Mazzotti test), led to the diagnosis of onchocerciasis. Retreatment with diethylcarbamazine again caused pruritus, but this was tolerated as were subsequent treatments.     

Seasonal variations in urinary crystals

Individual urine samples from normal subjects and stone-formers with idiopathic hypercalciuria have been examined for crystals both qualitatively and quantitatively at 37 degrees C. The group as a whole showed a rise in incidence of urinary crystals in the summer months of June to August inclusive. This rise was seen most clearly in overnight urines, collected on rising in the morning, and the patients appeared to be at risk overnight during the summer. In the untreated patients the summer rise in incidence of phosphate crystals was quite dramatic but was only small in the cellulose phosphate treated group, who showed a rather constant and raised incidence of oxalate crystals right through the year. Seasonal crystal incidence has been compared with seasonal changes in urinary composition. The rise in crystal incidence during the summer was associated with increased creatinine concentration in the same urine samples and with increased oxalate concentration in 24-hour urine collections.