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.

Preliminary Results of a Prospective Randomized Trial of Restrictive Versus Standard Fluid Regime in Elective Open Abdominal Aortic Aneurysm Repair

Background: Open abdominal aortic aneurysm (AAA) repair is associated with a significant morbidity (primarily respiratory and cardiac complications) and an overall mortality rate of 4% to 10%. We tested the hypothesis that perioperative fluid restriction would reduce complications and improve outcome after elective open AAA repair.

Novel bioadhesive patch-type system for photodynamic vulvodynia therapy after delivery of 5-aminolevulinic acid - Preliminary evaluation

OBJECTIVE: To assess the applicability of photodynamic therapy (PDT) in the management of vulvodynia whereby a novel, patch-type system, loaded with 5-aminolevulinic acid (ALA), was used to administer PDT to vulvar regions displaying the characteristics of vulvodynia.

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.

A PRELIMINARY ASSESSMENT OF THE DISTRIBUTION OF THE SEA LAMPREY (PETROMYZON MARINUS L.), RIVER LAMPREY (LAMPETRA FLUVIATILIS (L.)) AND BROOK LAMPREY (LAMPETRA PLANERI (BLOCH)) IN NORTHERN IRELAND

Lampreys are endangered in Europe, and European states are legally required to take measures to ensure their protection. However, there is currently little information on the distribution of the three species present in Northern Ireland. Anecdotal records of adult lampreys were collated from anglers and other sources, and a systematic electrofishing survey was undertaken to establish the distribution of lamprey ammocoetes. Lampreys were found in seven of the nine Northern Irish river catchments. Brook lampreys (Lampetra planeri (Bloch)) were widely distributed, but the two anadromous species, sea lamprey (Petromyzon marinus L.) and river lamprey (Lampetra fluviatilis (L.)), were more limited in their distribution, possibly due to barriers restricting migration.

Helokinestatins: A novel family of bioactive peptides with drug-lead potential fromthe venomof the Gila Monster (Heloderma suspectum)

Venom of the Gila Monster (Heloderma suspectum) has proven to be an unlikely source of lead compounds (exendins) for the development of new injectable peptide therapeutics for the treatment of Type 2 diabetes. However, no systematic searches for new classes of bioactive peptides in lizard venom have appeared until recently. Here we describe the discovery of a new class of peptides – the helokinestatins – from H. suspectum venom, their structural characterisation and that of their biosynthetic precursors from cloned cDNA. In addition, we have subjected members of the family to preliminary pharmacological characterisation. Helokinestatins 1–6 are a family of proline-rich peptides containing 10–15 amino acid residues terminating in a common -Pro-Arg.OH motif. They are encoded in tandem within two virtually identical biosynthetic precursors of 177 and 178 amino acid residues, differing by only a single Pro residue. Each precursor also encodes a single copy of a C-type natriuretic peptide located at the C-terminus. Synthetic replicates of all helokinestatins were shown to be devoid of any direct action on the smooth muscle of rat tail artery but were found to be potent inhibitors of bradykinin-induced relaxation in this preparation in a manner that is suggestive of a non-competitive mechanism. Helokinestatin-3 (VPPPPLQMPLIPR) and helokinestatin-5 (VPPPLQMPLIPR) were found to be most potent in this respect causing almost complete inhibition of bradykinin-induced relaxation. Helokinestatins and BPPs may have a shared evolutionary history but the former do not inhibit ACE. The bradykinin inhibitory potential of helokinestatins may be exploited in the local control of chronic inflammation.

Discovery of novel Agonists and antagonists of the free fatty acid receptor 1 (FFAR1) using virtual screening

The G-protein-coupled receptor free fatty acid receptor 1 (FFAR1), previously named GPR40, is a possible novel target for the treatment of type 2 diabetes. In an attempt to identify new ligands for this receptor, we performed virtual screening (VS) based on two-dimensional (2D) similarity, three-dimensional (3D) pharmacophore searches, and docking studies by using the structure of known agonists and our model of the ligand binding site, which was validated by mutagenesis. VS of a database of 2.6 million compounds followed by extraction of structural neighbors of functionally confirmed hits resulted in identification of 15 compounds active at FFAR1 either as full agonists, partial agonists, or pure antagonists. Site-directed mutagenesis and docking studies revealed different patterns of ligand-receptor interactions and provided important information on the role of specific amino acids in binding and activation of FFAR1.

Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable gamma-Secretase Inhibitor

During the course of our research efforts to develop a potent and selective gamma-secretase inhibitor for the treatment of Alzheimer's disease, we investigated a series of carboxamide-substituted sulfonamides. Optimization based on potency, Notch/amyloid-beta precursor protein selectivity, and brain efficacy after oral dosing led to the discovery of 4 (BMS-708163). Compound 4 is a potent inhibitor of gamma-secretase (A beta 40 IC50 = 0.30 nM), demonstrating a 193-fold selectivity against Notch. Oral administration of 4 significantly reduced A beta 40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs.

Wasp-17b: An Ultra-Low Density Planet in a Probable Retrograde Orbit

We report the discovery of the transiting giant planet WASP-17b, the least-dense planet currently known. It is 1.6 Saturn masses, but 1.5-2 Jupiter radii, giving a density of 6%-14% that of Jupiter. WASP-17b is in a 3.7 day orbit around a sub-solar metallicity, V = 11.6, F6 star. Preliminary detection of the Rossiter-McLaughlin effect suggests that WASP-17b is in a retrograde orbit (? ˜ -150°), indicative of a violent history involving planet-planet or star-planet scattering. WASP-17b's bloated radius could be due to tidal heating resulting from recent or ongoing tidal circularization of an eccentric orbit, such as the highly eccentric orbits that typically result from scattering interactions. It will thus be important to determine more precisely the current orbital eccentricity by further high-precision radial velocity measurements or by timing the secondary eclipse, both to reduce the uncertainty on the planet's radius and to test tidal-heating models. Owing to its low surface gravity, WASP-17b's atmosphere has the largest scale height of any known planet, making it a good target for transmission spectroscopy.