Cyclic MrIA: A stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter

Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the, beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET. Furthermore, the cyclic version has increased resistance to trypsin digestion relative to the native peptide, an intriguing result because the cleavage site for the trypsin is not close to the cyclization site. The use of peptides as drugs is generally hampered by susceptibility to proteolysis, and so, the increase in enzymatic stability against trypsin observed in the current study may be useful in improving the therapeutic potential of MrIA. Furthermore, the structure reported here for cyclic MrIA represents a new topology among a growing number of circular disulfide-rich peptides.

Irreducible 2-fold cycle systems

In this paper, it is shown that for any pair of integers (m, n) with 4 ≤ m ≤ n, if there exists an m-cycle system of order n, then there exists an irreducible 2-fold m-cycle system of order n, except when (m, n) = (5,5). A similar result has already been established for the case of 3-cycles. © 2005 Wiley Periodicals, Inc.

The relationship between chronic cough and paradoxical vocal fold movement: A review of the literature

Chronic cough (CC) and paradoxical vocal fold movement (PVFM) are debilitating conditions. PVFM has been given many labels,(1) including vocal cord dysfunction, Munchausen's stridor, functional inspiratory stridor, nonorganic functional or psychogenic upper airway obstruction, factitious asthma, psychogenic stridor, emotional laryngeal wheezing, and episodic laryngeal dyskinesia. 3 Although CC and PVFM have been considered separate entities in many reports, there is preliminary support for the notion that there may be an underlying link between these two conditions. Speech pathologists have become increasingly involved in the treatment of these patients and therefore need to understand the theoretical background of these disorders, the pathophysiological links between the two, and the impact of voice disorders on these populations. The aim of this article is to review the current literature on CC and PVFM from a speech pathology perspective to provide a model for defining and conceptualizing the disorders and to provide a framework for management and future research.

Cattle, crops and clearing: Regional drivers of landscape change in the Brigalow Belt, Queensland, Australia, 1840-2004

Landscape change occurs through the interaction of a multitude of natural and human driving forces at a range of organisational levels, with humans playing an increasingly dominant role in many regions of the world. Building on the current knowledge of the underlying drivers of landscape change, a conceptual framework of regional landscape change was developed which integrated population, economic and cultural values, policy and science/technology. Using the Southern Brigalow Belt biogeographic region of Queensland as a case study, the role of natural and human drivers in landscape change was investigated in four phases of settlement since 1840. The Brigalow Belt has experienced comparable rates of vegetation clearance over the past 50 years to areas of tropical deforestation. Economic factors were important during all phases of development, but the five regional drivers often acted in synergy. Environmental constraints played a significant role in slowing rates of change. Temporal trends of deforestation followed a sigmoidal curve, with initial slow change accelerating though the middle phases then slowing in recent times. Future landscape management needs to take account of the influence of all the components of the conceptual framework, at a range of organisational levels, if more ecologically sustainable outcomes are to be achieved. (c) 2006 Elsevier B.V. All rights reserved.