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We isolated a mammalian gene whose expression transiently increased in response to intimal denudation of rabbit aorta. It was identical to a gene encoding a zinc transporter, ZNT5, reported very recently by others. Mice deficient for this gene showed poor growth and a decrease in bone density due to impairment of osteoblast maturation to osteocyte. More than 60% of male null mice died suddenly because of the bradyarrhythmias. Analysis of gene-expression profiles in murine hearts by means of an oligonucleotide microarray disclosed that a subset of genes encoding immediate-early response factors (IEGs) and heat shock proteins (HSPs) were down-regulated in Znt5-null mice. These results indicate that Znt5 protein plays an important role in maturation of osteoblasts and in maintenance of the cells involved in the cardiac conduction system, partly owing to dysregulated expression of IEGs and HSPs.

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In the course of screening for new antibiotics active against fungi, an actinomycete strain No. PI57-2 that had been isolated from a soil sample collected in Fiji Island was found to produce novel antibiotics, pradimicins A and B1*^. Pradimicin A, the major component showed moderate in vitro activity against a wide variety of fungi and yeasts including clinically important pathogens. More interestingly, it exhibited marked in vivo therapeutic activity against systemic fungal infections caused by Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans strains in mice. Degradation studies revealed that pradimicin A has a unique structure containing the following moieties : D-Alanine, D-xylose, 4 ,6-dideoxy-4-methylamino-D-galactose and a substituted 5,6-dihydrobenzo[a]naphthacenequinone. This communicationpresents production, isolation, chemical and biological properties and structures of pradimicins A and B. Based on the taxonomic studies performed, strain PI57-2 is classified as a heretofore undescribed species of the genus Actinomaduraand named Actinomadurahibisca sp. nov. (ATCC 53557), and the details will be reported in a separate pap er. Pradimicin was produced in a 200-liter tank fermentor using a mediumconsisting of glucose 3%, soybean meal 3%, Pharmamedia 0.5%, yeast extract 0.1 % and CaCO3 0.3%. The tank was operated at 28°C with agitation of 250 rpm and aeration of 120 liters/minute. Antibiotic production was monitored by bioassay using C, albicans A9540 as a test organism and visible absorption at 500 nm in 0.01 n NaOH-MeOH (1 :1). After 5~6 days of fermentation, antibiotic potency reached the maximum of 500~700 /*g/ml.