Browsing by Author "Lewis, RJ"
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- ItemAnalgesic ω-conotoxins CVIE and CVIF selectively and voltage-dependently block recombinant and native n-type calcium channels(American Society for Pharmacology and Experimental Therapeutics (ASPET), 2010-02-01) Berecki, G; Motin, L; Haythornthwaite, A; Vink, S; Bansal, PS; Drinkwater, R; Wang, CI; Moretta, M; Lewis, RJ; Alewood, PF; Christie, MJ; Adams, DJNeuronal (N)-type Ca2+ channel-selective ω-conotoxins have emerged as potential new drugs for the treatment of chronic pain. In this study, two new ω-conotoxins, CVIE and CVIF, were discovered from a Conus catus cDNA library. Both conopeptides potently displaced 125I-GVIA binding to rat brain membranes. In Xenopus laevis oocytes, CVIE and CVIF potently and selectively inhibited depolarization-activated Ba2+ currents through recombinant N-type (α1B-b/α2δ1/β3) Ca2+ channels. Recovery from block increased with membrane hyperpolarization, indicating that CVIE and CVIF have a higher affinity for channels in the inactivated state. The link between inactivation and the reversibility of ω-conotoxin action was investigated by creating molecular diversity in β subunits: N-type channels with β2a subunits almost completely recovered from CVIE or CVIF block, whereas those with β3 subunits exhibited weak recovery, suggesting that reversibility of the ω-conotoxin block may depend on the type of β-subunit isoform. In rat dorsal root ganglion sensory neurons, neither peptide had an effect on low-voltage-activated T-type channels but potently and selectively inhibited high voltage-activated N-type Ca2+ channels in a voltage-dependent manner. In rat spinal cord slices, both peptides reversibly inhibited excitatory monosynaptic transmission between primary afferents and dorsal horn superficial lamina neurons. Homology models of CVIE and CVIF suggest that ω-conotoxin/voltage-gated Ca2+ channel interaction is dominated by ionic/electrostatic interactions. In the rat partial sciatic nerve ligation model of neuropathic pain, CVIE and CVIF (1 nM) significantly reduced allodynic behavior. These N-type Ca2+ channel-selective ω-conotoxins are therefore useful as neurophysiological tools and as potential therapeutic agents to inhibit nociceptive pain pathways. © 2010, American Society for Pharmacology and Experimental Therapeutics (ASPET)
- ItemThe application of pollen radiocarbon dating and bayesian age-depth modeling for developing robust geochronological frameworks of wetland archives(Cambridge University Press for the Arizona Board of Regents on behalf of the University of Arizona, 2022-04-27) Cadd, HR; Sherborne-Higgins, B; Becerra-Valdivia, L; Tibby, J; Barr, C; Forbes, MS; Cohen, TJ; Tyler, JJ; Vandergoes, MJ; Francke, A; Lewis, RJ; Jacobsen, GE; Marjo, CE; Turney, CSM; Arnold, LJWetland sediments are valuable archives of environmental change but can be challenging to date. Terrestrial macrofossils are often sparse, resulting in radiocarbon (14C) dating of less desirable organic fractions. An alternative approach for capturing changes in atmospheric 14C is the use of terrestrial microfossils. We 14C date pollen microfossils from two Australian wetland sediment sequences and compare these to ages from other sediment fractions (n = 56). For the Holocene Lake Werri Berri record, pollen 14C ages are consistent with 14C ages on bulk sediment and humic acids (n = 14), whilst Stable Polycyclic Aromatic Carbon (SPAC) 14C ages (n = 4) are significantly younger. For Welsby Lagoon, pollen concentrate 14C ages (n = 21) provide a stratigraphically coherent sequence back to 50 ka BP. 14C ages from humic acid and >100 µm fractions (n = 13) are inconsistent, and often substantially younger than pollen ages. Our comparison of Bayesian age-depth models, developed in Oxcal, Bacon and Undatable, highlight the strengths and weaknesses of the different programs for straightforward and more complex chrono-stratigraphic records. All models display broad similarities but differences in modeled age-uncertainty, particularly when age constraints are sparse. Intensive dating of wetland sequences improves the identification of outliers and generation of robust age models, regardless of program used. © The Author(s), 2022. Published by Cambridge University Press for the Arizona Board of Regents on behalf of the University of Arizona
- ItemIndependent Bayesian age modelling in subtropical wetlands to assess the influence of global climate drivers across Australia(Australasiain Quaternary Association Inc, 2018-12-10) Lewis, RJ; Tibby, J; Arnold, LJ; Barr, C; Marshall, JC; McGregor, GB; Gadd, PSRigorously dated, continuous sedimentological records capturing multiple glacial/interglacial cycles are important for evaluating the magnitude and range of drivers influencing ecosystem change in Australia. Multi-proxy palaeoenvironmental reconstructions are commonly used to identify changes in long-term environmental conditions, particularly when exploring the climatic backdrop to Australia’s large scale faunal extinctions. However, interpretations of these records may not be straightforward as local and regional climate signals are often mixed in proxy records. In order to evaluate whether improved temporal constraint can help with differentiating such convoluted signals, thereby increasing the confidence placed in the role of teleconnections across the Southern Hemisphere, we present a comprehensively dated 12.7 m (basal age ~130 ka) wetland core consisting of 21 optically stimulated luminescence and seven radiocarbon ages from North Stradbroke Island. The amalgamation of stratigraphic information and independent age constraints within a Bayesian framework, highlights the complex depositional history of Welsby Lagoon between late MIS 5 and MIS 2. ITRAX core scanning data reveals fluctuations in elemental abundance through time, in particular the decrease in the amount of aeolian sediment following MIS 3. Variability is attributed to regional environmental regime changes controlled by global drivers, including Heinrich events, and the influence of moisture across mainland Australia. The comprehensive dating approach undertaken at Welsby Lagoon highlights the role that the terrestrial palaeoenvironmental records of North Stradbroke Island can play in assessing long-term climate drivers across continental Australia, without relying exclusively on isotopic tuning of remote (ice core or marine) records. © The Authors
- ItemInsights into subtropical Australian aridity from Welsby Lagoon, North Stradbroke Island, over the past 80,000 years(Elsevier, 2020-04-15) Lewis, RJ; Tibby, J; Arnold, LJ; Barr, C; Marshall, JC; McGregor, GB; Gadd, PS; Yokoyama, YTerrestrial sedimentary archives that record environmental responses to climate over the last glacial cycle are underrepresented in subtropical Australia. Limited spatial and temporal palaeoenvironmental record coverage across large parts of eastern Australia contribute to uncertainty regarding the relationship between long-term climate change and palaeoecological turnover; including the extinction of Australian megafauna during the late Pleistocene. This study presents a new, high-resolution, calibrated geochemical record and numerical dating framework from Welsby Lagoon, a wetland from North Stradbroke Island that records key periods of late Pleistocene environmental change. Single-grain optically stimulated luminescence and radiocarbon dating are integrated into a Bayesian age-depth model for the sedimentary sequence spanning Marine Isotope Stage (MIS) 5 to the present. Scanning micro X-ray fluorescence (XRF) and bulk sediment XRF assays are used to infer past dust dynamics, with changes in the abundance of silica and potassium interpreted as proxies for aridity across local and regional sources. Variations in dust flux were contemporaneous with hydrological change, concordant with changes in vegetation cover on the island and, relate to deflation events at major dust source regions on the Australian continent. The Welsby Lagoon record supports the notion of a variable MIS4 within which an increased dust flux (71–67 ka), may be indicative of drier climate. Additionally, the record also shows a lower dust flux through the Last Glacial Maximum (LGM) than is evident in other Australian aeolian records. However, this low LGM flux is attributed to the wetland’s evolution, rather than a reduction in total dust flux. ©2020 Elsevier Ltd
- ItemPatterns of aeolian deposition in subtropical Australia through the last glacial and deglacial periods(Cambridge University Press, 2021-02-08) Lewis, RJ; Tibby, J; Arnold, LJ; Gadd, PS; Jacobsen, GE; Barr, C; Negus, PM; Mariani, M; Penny, D; Chittleborough, D; Moss, EDebate about the nature of climate and the magnitude of ecological change across Australia during the last glacial maximum (LGM; 26.5–19 ka) persists despite considerable research into the late Pleistocene. This is partly due to a lack of detailed paleoenvironmental records and reliable chronological frameworks. Geochemical and geochronological analyses of a 60 ka sedimentary record from Brown Lake, subtropical Queensland, are presented and considered in the context of climate-controlled environmental change. Optically stimulated luminescence dating of dune crests adjacent to prominent wetlands across North Stradbroke Island (Minjerribah) returned a mean age of 119.9 ± 10.6 ka; indicating relative dune stability soon after formation in Marine Isotope Stage 5. Synthesis of wetland sediment geochemistry across the island was used to identify dust accumulation and applied as an aridification proxy over the last glacial-interglacial cycle. A positive trend of dust deposition from ca. 50 ka was found with highest influx occurring leading into the LGM. Complexities of comparing sedimentary records and the need for robust age models are highlighted with local variation influencing the accumulation of exogenic material. An inter-site comparison suggests enhanced moisture stress regionally during the last glaciation and throughout the LGM, returning to a more positive moisture balance ca. 8 ka. © 2021 University of Washington
- ItemScientific drilling of sediments at Darwin Crater, Tasmania(Copernicus Publications, 2019-06-12) Lisé-Pronovost, A; Fletcher, MS; Mallett, T; Mariani, M; Lewis, RJ; Gadd, PS; Herries, AIR; Blaauw, M; Heijnis, H; Hodgson, DA; Pedro, JBA 70 m long continental sediment record was recovered at Darwin Crater in western Tasmania, Australia. The sediment succession includes a pre-lake silty sand deposit overlain by lacustrine silts that have accumulated in the ∼816 ka meteorite impact crater. A total of 160 m of overlapping sediment cores were drilled from three closely spaced holes. Here we report on the drilling operations at Darwin Crater and present the first results from petrophysical whole core logging, lithological core description, and multi-proxy pilot analysis of core end samples. The multi-proxy dataset includes spectrophotometry, grain size, natural gamma rays, paleo- and rock magnetism, loss on ignition, and pollen analyses. The results provide clear signatures of alternating, distinctly different lithologies likely representing glacial and interglacial sediment facies. Initial paleomagnetic analysis indicate normal magnetic polarity in the deepest core at Hole B. If acquired at the time of deposition, this result indicates that the sediment 1 m below commencement of lacustrine deposition post-date the Matuyama–Brunhes geomagnetic reversal ∼773 ka. © Author(s) 2019.