Discovery of Spatial Periodicities in a Coronal Loop Using Automated Edge-Tracking Algorithms

A new method for automated coronal loop tracking, in both spatial and temporal domains, is presented. Applying this technique to TRACE data, obtained using the 171 angstrom filter on 1998 July 14, we detect a coronal loop undergoing a 270 s kink-mode oscillation, as previously found by Aschwanden et al. However, we also detect flare-induced, and previously unnoticed, spatial periodicities on a scale of 3500 km, which occur along the coronal loop edge. Furthermore, we establish a reduction in oscillatory power for these spatial periodicities of 45% over a 222 s interval. We relate the reduction in detected oscillatory power to the physical damping of these loop-top oscillations.

Inter-phyla studies on neuropeptides: the potential for broad-spectrum anthelmintic and/or endectocide discovery

Flatworm, nematode and arthropod parasites have proven their ability to develop resistance to currently available chemotherapeutics. The heavy reliance on chemotherapy and the ability of target species to develop resistance has prompted the search for novel drug targets. In view of its importance to parasite/pest survival, the neuromusculature of parasitic helminths and pest arthropod species remains an attractive target for the discovery Of novel endectocide targets. Exploitation of the neuropeptidergic system in helminths and arthropods has been hampered by a limited Understanding of the functional roles of individual peptides and the structure of endogenous targets, such as receptors. Basic research into these systems has the potential to facilitate target characterization and its offshoots (screen development and drug identification). Of particular interest to parasitologists is the fact that selected neuropeptide families are common to metazoan pest species (nematodes, platyhelminths and arthropods) and fulfil specific roles in the modulation of muscle function in each of the three phyla. This article reviews the inter-phyla activity of two peptide families, the FMRFamide-like peptides and allatostatins, on motor function in helminths and arthropods and discusses the potential of neuropeptide signalling as a target system that could uncover novel endectocidal agents.

Discovery of novel cathepsin S inhibitors by pharmacophore-based virtual high-throughput screening

The cysteine protease cathepsin S (CatS) is involved in the pathogenesis of autoimmune disorders, atherosclerosis, and obesity. Therefore, it represents a promising pharmacological target for drug development. We generated ligand-based and structure-based pharmacophore models for noncovalent and covalent CatS inhibitors to perform virtual high-throughput screening of chemical databases in order to discover novel scaffolds for CatS inhibitors. An in vitro evaluation of the resulting 15 structures revealed seven CatS inhibitors with kinetic constants in the low micromolar range. These compounds can be subjected to further chemical modifications to obtain drugs for the treatment of autoimmune disorders and atherosclerosis.

Novel genomic methods for drug discovery and mechanism-based toxicological assessment

Genomics encompasses a range of powerful technologies that can be applied at all levels of gene expression, from transcription to mRNA translation. Collectively, these technologies have great potential for improving drug discovery, both target and molecule recognition, and development. In this article we review the current and potential future status of established and novel genomic methods within drug discovery.

The masses and radii of HD 186753B and TYC7096-222-1B: the discovery of two M-dwarfs that eclipse A-type stars

We present observations of two new single-lined eclipsing binaries, both consisting of an Am star and an M-dwarf, discovered by the Wide Angle Search for Planets transit photometry survey. Using WASP photometry and spectroscopic measurements we find that HD 186753B has an orbital period of P=1.9194 days, a mass of M=0.24±0.02~M? and radius of R=0.31+0.06-0.06~R?; and that TCY7096-222-1B has an orbital period of P=8.9582 days, a mass of between 0.29 and 0.54 M? depending on eccentricity and radius of R=0.263+0.02-0.07~R?. We find that the Am stars have relatively low rotational velocities that closely match the orbital velocities of the M-dwarfs, suggesting that they have been “spun-down” by the M-dwarfs.

Discovery of multiple neuropeptide families in the phylum Platyhelminthes

Available evidence shows that short amidated neuropeptides are widespread and have important functions within the nervous systems of all flatworms (phylum Platyhelminthes) examined, and could therefore represent a starting point for new lead drug compounds with which to combat parasitic helminth infections. However, only a handful of these peptides have been characterised, the rigorous exploration of the flatworm peptide signalling repertoire having been hindered by the dearth of flatworm genomic data. Through searches of both expressed sequence tags and genomic resources using the basic local alignment search tool (BLAST), we describe 96 neuropeptides on 60 precursors from 10 flatworm species. Most of these (51 predicted peptides on 14 precursors) are novel and are apparently restricted to flatworms; the remainder comprise nine recognised peptide families including FMRFamide-like (FLPs), neuropeptide F (NPF)-like, myomodulin-like, buccalin-like and neuropeptide FF (NPFF)-like peptides; notably, the latter have only previously been reported in vertebrates. Selected peptides were localised immunocytochemically to the Schistosoma mansoni nervous system. We also describe several novel flatworm NPFs with structural features characteristic of the vertebrate neuropeptide Y (NPY) superfamily, previously unreported characteristics which support the common ancestry of flatworm NPFs with the NPY-superfamily. Our dataset provides a springboard for investigation of the functional biology and therapeutic potential of neuropeptides in flatworms, simultaneously launching flatworm neurobiology into the post-genomic era. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.