On the evolution of functional secondary metabolites (natural products)

It is argued that organisms have evolved the ability to biosynthesize secondary metabolites (natural products) because of the selectional advantages they obtain as a result of the functions of the compounds. The clustering together of antibiotic biosynthesis, regulation, and resistance genes implies that these genes have been selected as a group and that the antibiotics function in antagonistic capacities in nature. Pleiotropic switching, the simultaneous expression of sporulation and antibiotic biosynthesis genes, is interpreted in terms of the defence roles of antibiotics. We suggest a general mechanism for the evolution of secondary metabolite biosynthesis pathways, and argue against the hypothesis that modern antibiotics had prebiotic effector functions, on the basis that it does not account for modern biosynthetic pathways.     

Quantitative association between altered plasma esterified omega-6 fatty acid proportions and psychological stress.

Medical students (MS) tested during the first year of medical school showed both greater stress on the Brief Symptom Inventory and lower plasma proportions of total esterified arachidonic acid (AA, C20:4n-6), and its omega-6 fatty acid (FA) precursor, linoleic acid (C18:2n-6) than control laboratory workers. This association suggests that omega-6 FA metabolism may be affected during stress. Low AA values might result from depletion of plasma stores for immunoregulatory prostenoids formation or from modification of metabolic pathways by cortisol or other cytokine compounds implicated in stress. Values for other major FA and the omega-3 neuronal metabolic substrate, docosahexaenoic acid (DHA, C22:6n-3) were similar between students and controls. The clear preservation of the omega-3 FA pathway suggests their programmed availability for neuronal function during stress. Since plasma FA proportions may affect immune cell membrane function(s), we suggest that altered values of plasma FAs may be an important component of the physiological effects of psychological stress.     

Apoptosis: final control point in cell biology

The discovery of apoptosis, a widespread and morphologically distinct form of physiological cell death, has had an extraordinary impact on cell biology. The importance of apoptosis stems from its active nature and its potential for controlling biological systems. The growing appreciation of the significance of this process has stimulated intense investigation into the molecular mechanisms involved and into its fundamental implications for developmental biology, immunology and oncology.     

Morphometry of feline neutrophil granule genesis

During neutrophil granule genesis, the formation of primary granules is generally thought to be limited to the promyelocyte stage; whereas synthesis of secondary granules is thought to occur only at the myelocyte stage. This hypothesis was tested morphometrically in feline neutrophils that are known to contain both granule types. Marrow specimens obtained from six cats were stained with peroxidase for identification of neutrophil primary granules and counterstained with periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) for identification of secondary granules. By regression analysis using arithmetic models, numbers of cytoplasmic granules in 311 cells were correlated with the degree of nuclear chromatin condensation, which was shown to be an adequate parameter for cell maturation. Promyelocytes and myelocytes had similar mean numbers of peroxidase-positive granules per unit area. A significant increase (p less than or equal to 0.0001) in the numbers of peroxidase-positive granules was noted between the metamyelocyte and the mature neutrophil stage, despite the lack of peroxidase activity in endoplasmic reticulum and Golgi lamellae. By contrast, a significant increase of peroxidase-negative granules between the metamyelocyte and the mature neutrophil stage was not clearly established with these methods. The increase in peroxidase-positive granules may indicate continued production of peroxidase-containing granules and/or redistribution of peroxidase among lysosomal organelles in late feline neutrophils.     

Two-dimensional 1H-NMR studies of the solution structure of plasminogen kringle 4

Native kringle 4 from human plasminogen has been studied by two-dimensional 1H-NMR methods in order to obtain new structural information about the kringle fold. Two-dimensional scalar correlated spectroscopy (COSY), two-dimensional dipolar correlated spectroscopy (NOESY) and two-dimensional relayed coherance transfer spectroscopy (RCT) experiments were recorded, allowing most resonances arising from the aromatic and methyl-containing residues to be assigned in the spectrum. From an analysis of NOE data, a small segment of double-stranded beta-sheet has been identified near residues Phe63 and Thr64. Further analysis of the NOESY spectrum has allowed detailed study of the conformation of sidechains located in regions near Leu45 and Val69. A model has been constructed of the polypeptide segment comprising residues 40-49 which accounts for the observed NOE interactions.