Browsing by Author "Ryan, T"

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    The ANSTO contribution to a project to provide experimental standards for SAS profile prediction
    (Australian Institure of Nuclear Sicence and Engineering (AINSE), 2020-11-11) Duff, AP; Kirby, N; Ryan, T; Trewhella, J; Whitten, AE; Wood, K
    The program CRYSOL1, was the first method developed to rapidly calculate small-angle scattering (SAS) profiles from atomic coordinates of biomolecules. It was a major breakthrough, providing the missing link between high-resolution structures and solution SAS data. The importance of this breakthrough is evident in the fact that decades later, alternate methods continue to be published with various claims of improvement. To date, each of the alternate methods published have been validated using different data sets and models. A consensus set of high quality data would be of considerable value in benchmarking the different approaches. In order to evaluate different approaches to including the hydration layer contribution to the SAS profile, it is desirable to have data obtained using X-rays (SAXS) and neutrons (SANS), the latter in H2O and D2O, as the hydration layer contribution differs significantly for each of these measurements. To develop a consensus set of high quality data, an international project involving the efforts of 37 researchers from 11 different X-ray and 3 different neutron scattering facilities across Asia, Europe and North Ⓒ The Authors.
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    Guanidine hydrochloride denaturation of dopamine-induced α-synuclein oligomers: a small-angle x-ray scattering study
    (Wiley Online Library, 2013-06-4) Pham, CLL; Kirby, N; Wood, K; Ryan, T; Roberts, B; Sokolova, AV; Barnham, KJ; Masters, CL; Knott, RB; Cappai, R; Curtain, CC; Rekas, A
    Alpha-synuclein (α-syn) forms the amyloid-containing Lewy bodies found in the brain in Parkinson's disease. The neurotransmitter dopamine (DA) reacts with α-syn to form SDS-resistant soluble, non-amyloid, and melanin-containing oligomers. Their toxicity is debated, as is the nature of their structure and their relation to amyloid-forming conformers of α-syn. The small-angle X-ray scattering technique in combination with modeling by the ensemble optimization method showed that the un-reacted native protein populated three broad classes of conformer, while reaction with DA gave a restricted ensemble range suggesting that the rigid melanin molecule played an important part in their structure. We found that 6 M guanidine hydrochloride did not dissociate α-syn DA-reacted dimers and trimers, suggesting covalent linkages. The pathological significance of covalent association is that if they are non-toxic, the oligomers would act as a sink for toxic excess DA and α-syn; if toxic, their stability could enhance their toxicity. We argue it is essential, therefore, to resolve the question of whether they are toxic or not. © 2013,Wiley Periodicals, Inc.