Heterochrony and sexual dimorphism in the pigtailed macaque (Macaca nemestrina)

Somatic growth is not a simple linear process with a constant rate of growth. The most successful attempts to quantify growth as a function of age or size have employed nonlinear techniques. Sexual dimorphism of primate growth, weight vs. age, was examined using nonlinear models with Sirianni and Swindler's ([1985] Growth and Development of the Pigtailed Macaque, Boca Raton, FL: CRC Press) growth data on the pigtailed macaque (Macaca nemestrina). The best fit of several exponential growth models was the Gompertz curve: Different multiple phase models were also fit, where each phase represents a distinct exponential component. The two-phase models proved to be the best (R² = .0.84 for females, 0.91 for males), suggesting that there are two growth spurts, one in infancy and one at puberty. The timing of the beginning and end of the first spurt is the same in males and females, but the rate, and value of the asymptote for this phase, is greater in males. The timing of the second spurt is earlier, and the rate of growth for this spurt is smaller in females than males. The sexual dimorphism in these species is not a simple rate change, but a complex interaction of timing and rate over the entire period of growth. It would be impossible to separate these entities with a linear, polynomial, or single-phase model of the data. While these data and results complement much of the existing work on adult dimorphism, they also emphasize the vital role that ontogenetic data have in elucidating the underlying evolutionary mechanisms that generate sexual dimorphism. © 1994 Wiley-Liss, Inc.     

Mapping divalent metal ion binding sites in a group II intron by Mn(2+)- and Zn(2+)-induced site-specific RNA cleavage.

The function of group II introns depends on positively charged divalent metal ions that stabilize the ribozyme structure and may be directly involved in catalysis. We investigated Mn2+- and Zn2+-induced site-specific RNA cleavage to identify metal ions that fit into binding pockets within the structurally conserved bI1 group II intron domains (DI-DVI), which might fulfill essential roles in intron function. Ten cleavage sites were identified in DI, two sites in DIII and two in DVI. All cleavage sites are located in the center or close to single-stranded and flexible RNA structures. Strand scissions mediated by Mn2+/Zn2+ are competed for by Mg2+, indicating the existence of Mg2+ binding pockets in physical proximity to the observed Mn2+-/Zn2+-induced cleavage positions. To distinguish between metal ions with a role in structure stabilization and those that play a more specific and critical role in the catalytic process of intron splicing, we combined structural and functional assays, comparing wild-type precursor and multiple splicing-deficient mutants. We identified six regions with binding pockets for Mg2+ ions presumably playing an important role in bI1 structure stabilization. Remarkably, assays with DI deletions and branch point mutants revealed the existence of one Mg2+ binding pocket near the branching A, which is involved in first-step catalysis. This pocket formation depends on precise interaction between the branching nucleotide and the 5' splice site, but does not require exon-binding site 1/intron binding site 1 interaction. This Mg2+ ion might support the correct placing of the branching A into the 'first-step active site'.     

Quercinol, an anti-inflammatory chromene from the wood-rotting fungus Daedalea quercina (Oak Mazegill)

The fungus Daedalea quercina (oak mazegill) was examined for its capability of producing antioxidative and anti-inflammatory compounds. Bioactivity guided fractionation of the extract from a mycelial culture led to the isolation of quercinol, which was identified as (-)-(2S)-2-hydroxymethyl-2-methyl-6-hydroxychromene 1 by NMR and X-ray analyses. The cryptic hydroquinone 1 shows a broad anti-inflammatory activity against cyclooxygenase 2 (COX-2), xanthine oxidase (XO), and horseradish peroxidase (HRP) at micromolar concentrations.     

Biosynthesis and function of gliotoxin in <Emphasis Type="Italic">Aspergillus fumigatus</Emphasis>

Gliotoxin (GT) is the prototype of the epidithiodioxopiperazine (ETP)-type fungal toxins. GT plays a critical role in the pathobiology of Aspergillus fumigatus. It modulates the immune response and induces apoptosis in different cell types. The toxicity has been attributed to the unusual intramolecular disulfide bridge, which is the functional motif of all ETPs. Because of the extraordinary structure and activity of GT, this fungal metabolite has been the subject of many investigations. The biosynthesis of GT involves unprecedented reactions catalysed by recently discovered enzymes. Here, we summarize the recent progress in elucidating the GT biosynthetic pathway and its role in virulence.     

Photochemistry of dyes and fluorochromes used in biology and medicine: some physicochemical background and current applications

An overview of the basic principles of photochemistry is presented to facilitate discussion of fluorescence, quenching and quantum yields. These topics in turn provide the foundation for an account of fluorescence spectroscopy and its application to microscopy. A brief overview of light microscopy and the application of fluorescence microscopy is given. The influences of molecular features, such as aromatic character and substitution patterns, on color and fluorescence are described. The concept of color fading is considered with particular reference to its effect on microscopic preparations. A survey of representative fluorescent probes is provided, and their sensitivity, application, and limitations are described. The phototoxicity of fluorescent molecules is discussed using biomembranes and DNA as examples of targets of toxicity. Photodynamic therapy, a relatively new clinical application of phototoxicity, is described. Both anticancer and antimicrobial applications are noted, and an assessment is given of the current ideas on the ideal physicochemical properties of the sensitizing agents for such applications.     

Inhibition of nuclear pre-mRNA splicing by antibiotics in vitro.

A number of antibiotics have been reported to disturb the decoding process in prokaryotic translation and to inhibit the function of various natural ribozymes. We investigated the effect of several antibiotics on in vitro splicing of a eukaryotic nuclear pre-mRNA (beta-globin). Of the eight antibiotics studied, erythromycin, Cl-tetracycline and streptomycin were identified as splicing inhibitors in nuclear HeLa cell extract. The K(i) values were 160, 180 and 230 microm, respectively. Cl-tetracycline-mediated and streptomycin-mediated splicing inhibition were in the molar inhibition range for hammerhead and human hepatitis delta virus ribozyme self-cleavage (tetracycline), of group-I intron self-splicing (streptomycin) and inhibition of RNase P cleavage by some aminoglycosides. Cl-tetracycline and the aminocyclitol glycoside streptomycin were found to have an indirect effect on splicing by unspecific binding to the pre-mRNA, suggesting that the inhibition is the result of disturbance of the correct folding of the pre-mRNA into the splicing-compatible tertiary structure by the charged groups of these antibiotics. The macrolide, erythromycin, the strongest inhibitor, had only a slight effect on formation of the presplicing complexes A and B, but almost completely inhibited formation of the splicing-active C complex by binding to nuclear extract component(s). This results in direct inhibition of the second step of pre-mRNA splicing. To our knowledge, this is the first report on specific inhibition of nuclear splicing by an antibiotic. The functional groups involved in the interaction of erythromycin with snRNAs and/or splicing factors require further investigation.