Synthesis and characterization of delta-atracotoxin-ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus)

delta-Atracotoxin-Ar1a (delta-ACTX-Ar1a) is the major polypeptide neurotoxin isolated from the venom of the male Sydney funnel-web spider, Atrax robustus. This neurotoxin targets both insect and mammalian voltage-gated sodium channels, where it competes with scorpion alpha-toxins for neurotoxin receptor site-3 to slow sodium-channel inactivation. Progress in characterizing the structure and mechanism of action of this toxin has been hampered by the limited supply of pure toxin from natural sources. In this paper, we describe the first successful chemical synthesis and oxidative refolding of the four-disulfide bond containing delta-ACTX-Ar1a. This synthesis involved solid-phase Boc chemistry using double coupling, followed by oxidative folding of purified peptide using a buffer of 2 M GdnHCl and glutathione/glutathiol in a 1:1 mixture of 2-propanol (pH 8.5). Successful oxidation and refolding was confirmed using both chemical and pharmacological characterization. Ion spray mass spectrometry was employed to confirm the molecular weight. H-1 NMR analysis showed identical chemical shifts for native and synthetic toxins, indicating that the synthetic toxin adopts the native fold. Pharmacological studies employing whole-cell patch clamp recordings from rat dorsal root ganglion neurons confirmed that synthetic delta-ACTX-Ar1a produced a slowing of the sodium current inactivation and hyperpolarizing shifts in the voltage-dependence of activation and inactivation similar to native toxin. Under current clamp conditions, we show for the first time that delta-ACTX-Ar1a produces spontaneous repetitive plateau potentials underlying the clinical symptoms seen during envenomation. This successful oxidative refolding of synthetic delta-ACTX-Ar1a paves the way for future structure-activity studies to determine the toxin pharmacophore.

Alright: a distinctive pathway of change from the 18th century to the present day

The origins of the vast majority of the words we use in contemporary English go back as far as Old or Middle English. In contrast, alright and all right in their present-day application appear to be the result of a more recent evolution, as there is no evidence of their use, not even in the two-word form, in the published fiction before the 18th century. Furthermore, there are not in the research literature, at least to my knowledge, any previous linguistic studies on this specific subject matter. The present article is simply an attempt to describe the various processes of diachronic change that brought about the emergence of alright.

Why did London become the main money market? Monetary Policy, Arbitrage and European Money Market Integration in 18th century

How did the leading capital market start to attract international bullion? Why did London become the main money market? Monetary regulations, including the charges for minting money and the restrictions on bullion exchange, have played the key role in defining the direction of the flow of international bullion. Countries that abolished minting charges and permitted the free movement of bullion were able to attract international bullion, and countries that applied minting taxes suffered an outflow of bullion. In these cases monetary authorities tried to limit bullion movement through prohibitions on domestic bullion exchange at a free price, and tariffs and quantitative restrictions on bullion exports. The paper illustrates the logic of international monetary flow in the 18th century, using empirical evidence for England, France and Spain. The first section defines and measures monetary policy, and the second section introduces minting charges into the arbitrage equation in order to explain the logic of bullion flow between the pairs of nations England-France, England-Spain and France-Spain. The conclusion emphasises the importance of monetary policy in the creation of leading money markets.

Leveraging the Sydney Olympics for tourism

Paper presented at the 2000 seminar of the International Chair in Olympism. Key issues of the seminar included references to the concern for legacy in terms of tourism, benefits and challenges of the Olympic Games and strategic needs, among others.

Socio-economic impact of the Sydney 2000 Olympic Games

Paper presented at the 2001 seminar of the International Chair in Olympism (IOC-UAB). The seminar offers a general reflection, from the time of the bid onwards, of the 2000 Games experience in Sydney and Australia.

Keys to interpret the Games: Sydney 2000 Olympics

Document published by the CEO-UAB, corresponding to the results of the research undertaken by the author during the celebration of the Sydney 2000 Games.

Claves para interpretar los Juegos: Sydney 2000

Documento publicado como parte de la colección Working Papers incluyendo los resultados de la investigación llevada a cabo por el autor durante la celebración de los Juegos Olímpicos de Sydney 2000.

Detection of the pandemic norovirus variant GII.4 Sydney 2012 in Rio Branco, state of Acre, northern Brazil

Noroviruses (NoVs) are important cause of gastroenteritis in humans worldwide. Genotype GII.4 is responsible for the majority of outbreaks reported to date. This study describes, for the first time in Brazil, the circulation of NoV GII.4 variant Sydney 2012 in faecal samples collected from children aged less than or equal to eight years in Rio Branco, state of Acre, northern Brazil, during July-September 2012.

Report of Recommendations to the Iowa Department of Workforce Development on a Review of Selected General Controls, April 18th, 2005 to May 13th, 2005

State Audit Reports