Australian bush medicines harbour diverse microbial endophytes with broad-spectrum antibacterial activity.

AIMS: Microbial endophytes produce specialized metabolites, including antibiotics and other compounds of pharmaceutical and agricultural value. This study aimed to investigate the diversity and bioactivity of endophytes from medicinal plants used by the Dharawal People of Gamay (Botany Bay), Australia. METHODS AND RESULTS: Of the 48 endophytes isolated, 19 tested positive for polyketide synthase or non-ribosomal peptide synthetase genes via a PCR incorporating degenerate primers. The biosynthetically talented endophytes were identified by 16S rRNA gene sequencing and included 4 bacteria species belonging to the orders Bacillales, Rhizobiales and Burkholderiales and 15 Ascomycota fungi species belonging to the orders Botryosphaeriales, Cladosporiales, Glomerellales, Microascales and Eurotiales. Antimicrobial testing using the disc diffusion assay demonstrated that 15 of the 19 isolates had broad-spectrum activity against a range of Gram-positive and Gram-negative bacteria. CONCLUSIONS: Taken together, these results suggest that Australian bush medicines harbour diverse biosynthetically talented microbial endophytes capable of producing broad-spectrum antibacterial compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that compounds produced by microbial endophytes likely contribute to the collective medicinal properties of Australian bush medicines. Significantly, it highlights that Indigenous botanical knowledge and modern molecular approaches can be used in tandem to prioritize microorganisms that produce pharmaceutically relevant compounds.

Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors.

As the obligate member of most nuclear receptor heterodimers, retinoid X receptors (RXRs) can potentially perform two functions: cooperative binding to hormone response elements and coordinate regulation of target genes by RXR ligands. In this paper we describe allosteric interactions between RXR and two heterodimeric partners, retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs); RARs and PPARs prevent and permit activation by RXR-specific ligands, respectively. By competing for dimerization with RXR on response elements consisting of direct-repeat half-sites spaced by 1 bp (DR1 elements), the relative abundance of RAR and PPAR determines whether the RXR signaling pathway will be functional. In contrast to RAR, which prevents the binding of RXR ligands and recruits the nuclear receptor corepressor N-CoR, PPAR permits the binding of SRC-1 in response to both RXR and PPAR ligands. Overexpression of SRC-1 markedly potentiates ligand-dependent transcription by PPARgamma, suggesting that SRC-1 serves as a coactivator in vivo. Remarkably, the ability of RAR to both block the binding of ligands to RXR and interact with corepressors requires the CoR box, a structural motif residing in the N-terminal region of the RAR ligand binding domain. Mutations in the CoR box convert RAR from a nonpermissive to a permissive partner of RXR signaling on DR1 elements. We suggest that the differential recruitment of coactivators and corepressors by RAR-RXR and PPAR-RXR heterodimers provides the basis for a transcriptional switch that may be important in controlling complex programs of gene expression, such as adipocyte differentiation.

Variable refractive index and birefringent waveguides by sputtering tantalum in O(2)-N(2) mixtures.

Optical waveguides with losses <1 dB/cm at 632.8 nm have been prepared by sputtering tantalum in O(2)-N(2) mixtures. As the fraction of N(2) in the sputtering atmosphere increases, the refractive index of the guides exhibit a sharp maximum and then decreases to a much lower value, and the films become birefringent. Using an oxygen discharge, the indices at 632.8 nm for both TE and TM modes are 2.083 +/- 0.003, but the values are 1.850 and 1.877, respectively, for the highest fraction of nitrogen used. The indices have been measured at wavelengths down to 457.9 nm. For low fractions of N(2), the results are consistent with a decreasing film density and a constant molecular polarizability, but a number of effects, including the birefringence, are inconsistent with this picture. Waveguide structures, such as interconnects, branching waveguides, and layered directional couplers, have been demonstrated using films with different indices. The birefringence has also been verified by observation of interference between TE and TM modes simultaneously coupled into the guide.