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Wayne Clarence Hodgson - One of the best experts on this subject based on the ideXlab platform.
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Venoms of related mammal-eating species of Taipans (Oxyuranus) and brown snakes (Pseudonaja) differ in composition of toxins involved in mammal poisoning
bioRxiv, 2018Co-Authors: Jure Skejic, Nathan Dunstan, David L. Steer, Wayne Clarence HodgsonAbstract:Background: Differences in venom composition among related snake lineages have often been attributed primarily to diet. Australian elapids belonging to Taipans (Oxyuranus) and brown snakes (Pseudonaja) include a few specialist predators as well as generalists that have broader dietary niches and represent a suitable model system to investigate this assumption. Here, shotgun high-resolution mass spectrometry (Q Exactive Orbitrap) was used to compare venom proteome composition of several related mammal-eating species of Taipans and brown snakes. Results: Venoms of the mammal-eating lineages of Oxyuranus and Pseudonaja differed greatly in the composition of proteins toxic to mammals. Venom of mammalivorous Western Desert Taipan Oxyuranus temporalis consisted predominately of postsynaptic alpha-neurotoxins and was deficient in presynaptic phospholipase A2 neurotoxins. In contrast, presynaptic PLA2 neurotoxins (taipoxin and paradoxin) were abundant in the venoms of closely related mammal-eating specialists coastal Taipan O. scutellatus and inland Taipan O. microlepidotus. Significant expression of venom prothrombinase was not detected in O. temporalis venom despite the toxin being found at substantial levels in most other mammal-eating lineages. Presynaptic PLA2 neurotoxins (textilotoxin) were present at high levels in the venoms of some mammal-consuming brown snakes, specifically the eastern P. textilis and northern brown snake P. nuchalis, but surprisingly were not discovered in the venom of a related mammal-eating species, Ingrams brown snake P. ingrami. Expression of an alpha-neurotoxin that is toxic to rodents (pseudonajatoxin b) was profoundly down-regulated in Queensland P. textilis venom and highly up-regulated in South Australian P. textilis venom despite both populations consuming this type of prey. Conclusion: Very different expression patterns of mammal-toxic venom procoagulants and neurotoxins across Oxyuranus and Pseudonaja phylogeny suggest that prey type preference cannot fully account for interlineage differences in venom proteome composition. Keywords: Snake venom, venom proteome evolution, predatory toxin expression, mammal prey, Oxyuranus, Pseudonaja
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isolation and pharmacological characterization of α elapitoxin ot1a a short chain postsynaptic neurotoxin from the venom of the western desert Taipan oxyuranus temporalis
Toxins, 2016Co-Authors: Carmel M Barber, Muhamad Rusdi Ahmad Rusmili, Wayne Clarence HodgsonAbstract:Taipans (Oxyuranus spp.) are elapids with highly potent venoms containing presynaptic (β) and postsynaptic (α) neurotoxins. O. temporalis (Western Desert Taipan), a newly discovered member of this genus, has been shown to possess venom which displays marked in vitro neurotoxicity. No components have been isolated from this venom. We describe the characterization of α-elapitoxin-Ot1a (α-EPTX-Ot1a; 6712 Da), a short-chain postsynaptic neurotoxin, which accounts for approximately 30% of O. temporalis venom. α-Elapitoxin-Ot1a (0.1–1 µM) produced concentration-dependent inhibition of indirect-twitches, and abolished contractile responses to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The inhibition of indirect twitches by α-elapitoxin-Ot1a (1 µM) was not reversed by washing the tissue. Prior addition of Taipan antivenom (10 U/mL) delayed the neurotoxic effects of α-elapitoxin-Ot1a (1 µM) and markedly attenuated the neurotoxic effects of α-elapitoxin-Ot1a (0.1 µM). α-Elapitoxin-Ot1a displayed pseudo-irreversible antagonism of concentration-response curves to carbachol with a pA2 value of 8.02 ± 0.05. De novo sequencing revealed the main sequence of the short-chain postsynaptic neurotoxin (i.e., α-elapitoxin-Ot1a) as well as three other isoforms found in O. temporalis venom. α-Elapitoxin-Ot1a shows high sequence similarity (i.e., >87%) with other Taipan short-chain postsynaptic neurotoxins.
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comparative studies of the venom of a new Taipan species oxyuranus temporalis with other members of its genus
Toxins, 2014Co-Authors: Carmel M Barber, Frank Madaras, Richard K Turnbull, Terry Morley, Nathan Dunstan, Luke Allen, Tim Kuchel, Peter Mirtschin, Wayne Clarence HodgsonAbstract:Taipans are highly venomous Australo-Papuan elapids. A new species of Taipan, the Western Desert Taipan (Oxyuranus temporalis), has been discovered with two specimens housed in captivity at the Adelaide Zoo. This study is the first investigation of O. temporalis venom and seeks to characterise and compare the neurotoxicity, lethality and biochemical properties of O. temporalis venom with other Taipan venoms. Analysis of O. temporalis venom using size-exclusion and reverse-phase HPLC indicated a markedly simplified “profile” compared to other Taipan venoms. SDS-PAGE and agarose gel electrophoresis analysis also indicated a relatively simple composition. Murine LD50 studies showed that O. temporalis venom is less lethal than O. microlepidotus venom. Venoms were tested in vitro, using the chick biventer cervicis nerve-muscle preparation. Based on t90 values, O. temporalis venom is highly neurotoxic abolishing indirect twitches far more rapidly than other Taipan venoms. O. temporalis venom also abolished responses to exogenous acetylcholine and carbachol, indicating the presence of postsynaptic neurotoxins. Prior administration of CSL Taipan antivenom (CSL Limited) neutralised the inhibitory effects of all Taipan venoms. The results of this study suggest that the venom of the O. temporalis is highly neurotoxic in vitro and may contain procoagulant toxins, making this snake potentially dangerous to humans.
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inhibition of presynaptic neurotoxins in Taipan venom by suramin
Neurotoxicity Research, 2014Co-Authors: Sanjaya Kuruppu, Janeyuth Chaisakul, Ian A Smith, Wayne Clarence HodgsonAbstract:Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a major life-threatening symptom of envenoming by these snakes. Three species of Taipans exist, and the venom from each species contains a presynaptic neurotoxin which accounts for much of the neurotoxicity observed following human envenoming. The high cost of antivenom used to treat neurotoxicity has resulted in the need to develop alternative but effective therapies. Therefore, in this study, we examined the ability of the P2Y receptor antagonist suramin to prevent the in vitro neurotoxic effects of the three presynaptic neurotoxins in Taipan venoms: taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources or purified in house, using multiple steps of gel filtration chromatography. All three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer cervicis nerve–muscle preparation within 300 min. The presence of suramin (0.3 mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve-mediated twitches within the course of the experiment (P < 0.0001). However, paradoxin induced a 32 % decrease in twitch height even in the presence of suramin within 360 min. This was significantly different compared to toxin alone (P < 0.0001). We also examined the effect of suramin on the neurotoxic effects of textilotoxin and the products of phospholipase A2 action. Each toxin alone or in the presence of suramin failed to inhibit the responses to exogenous agonists ACh, CCh or KCl. Our results warrant clinical studies aimed determining the efficacy of suramin in preventing the onset of neurotoxicity following Taipan envenoming.
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cross neutralisation of australian brown snake Taipan and death adder venoms by monovalent antibodies
Vaccine, 2010Co-Authors: Geoffrey K Isbister, Wayne Clarence Hodgson, Margaret A Oleary, Jessica Hagan, Kearney Nichols, Tammy Jacoby, Kathleen Davern, Jennifer SchneiderAbstract:An understanding of the cross-neutralisation of snake venoms by antibodies is important for snake antivenom development. We investigated the cross-neutralisation of brown snake (Pseudonaja textilis) venom, Taipan (Oxyuranus scutellatus) venom and death adder (Acanthophis antarcticus) with commercial antivenoms and monovalent anti-snake IgG, using enzyme immunoassays, in vitro clotting and neurotoxicity assays. Each commercial antivenom bound all three venoms, and neutralised clotting activity of brown snake and Taipan venoms and neurotoxicity of death adder venom. The 'in-house' monovalent anti-snake venom IgG raised against procoagulant brown snake and Taipan venoms, did not neutralise the neurotoxic effects of death adder venom. However, they did cross-neutralise the procoagulant effects of both procoagulant venoms. This supports the idea of developing antivenoms against groups of snake toxins rather than individual snake venoms.
Jose Maria Gutierrez - One of the best experts on this subject based on the ideXlab platform.
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coagulotoxic effects by brown snake pseudonaja and Taipan oxyuranus venoms and the efficacy of a new antivenom
Toxicology in Vitro, 2019Co-Authors: Christina N Zdenek, Terry Morley, Nathan Dunstan, Luke Allen, Kevin Arbuckle, Timothy N W Jackson, Bianca Op Den Brouw, Jordan Debono, Maria Herrera, Jose Maria GutierrezAbstract:Abstract Snakebite is a neglected tropical disease that disproportionately affects the poor. Antivenom is the only specific and effective treatment for snakebite, but its distribution is severely limited by several factors, including the prohibitive cost of some products. Papua New Guinea (PNG) is a snakebite hotspot but the high costs of Australian antivenoms (thousands of dollars per treatment) makes it unaffordable in PNG. A more economical Taipan antivenom has recently been developed at the Instituto Clodomiro Picado (ICP) in Costa Rica for PNG and is currently undergoing clinical trials for the treatment of envenomations by coastal Taipans (Oxyuranus scutellatus). In addition to potentially having the capacity to neutralise the effects of envenomations of non-PNG Taipans, this antivenom may have the capacity to neutralise coagulotoxins in venom from closely related brown snakes (Pseudonaja spp.) also found in PNG. Consequently, we investigated the cross-reactivity of Taipan antivenom across the venoms of all Oxyuranus and Pseudonaja species. In addition, to ascertain differences in venom biochemistry that influence variation in antivenom efficacy, we tested for relative cofactor dependence. We found that the new ICP Taipan antivenom exhibited high selectivity for Oxyuranus venoms and only low to moderate cross-reactivity with any Pseudonaja venoms. Consistent with this genus level distinction in antivenom efficacy were fundamental differences in the venom biochemistry. Not only were the Pseudonaja venoms significantly more procoagulant, but they were also much less dependent upon the cofactors calcium and phospholipid. There was a strong correlation between antivenom efficacy, clotting time and cofactor dependence. This study sheds light on the structure-function relationships of the procoagulant toxins within these venoms and may have important clinical implications including for the design of next-generation antivenoms.
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development of a chicken derived antivenom against the Taipan snake oxyuranus scutellatus venom and comparison with an equine antivenom
Toxicon, 2016Co-Authors: Diego Navarro, Maria Herrera, Mariangela Vargas, Alvaro Segura, Aaron Gomez, Mauren Villalta, Nils Ramirez, David J Williams, Jose Maria GutierrezAbstract:A chicken-derived antivenom (ChDAv) towards Taipan snake (Oxyuranus scutellatus) venom was produced by purifying anti-Taipan IgY from egg yolks of hens immunized with Taipan venom. The productivity, antivenomic profile, neutralization ability, pharmacokinetic properties and immunogenicity of the ChDAv were compared with those of an antivenom produced in horses (EDAv). We found that 382 eggs are required to produce the mass of anti-Taipan antibodies contained in one liter of equine hyperimmune plasma, and that 63 chickens would be needed to generate the amount of anti-Taipan antibodies annually produced by one horse. It was estimated that, in Costa Rica, the production of anti-Taipan antibodies could be 40% cheaper if chickens were used as immunoglobulin source, instead of horses. During antivenomic assessment, ChDAv showed lower ability to immunocapture the α subunit of taipoxin, the most important neurotoxin in the venom. ChDAv showed a lower ability to neutralize the coagulant and lethal activities of Taipan venom. ChDAv was more immunogenic in rabbits than EDAv, probably due to the fact that chickens are phylogenetically more distant to rabbits than horses. This finding may explain why clearance from rabbit bloodstream was faster for chicken-IgY than for equine-IgG in a pharmacokinetic study. In conclusion, the production of anti-Taipan antivenom was less effective when chicken egg yolks were used as source of immunoglobulins instead of horses.
Andreas Podelski - One of the best experts on this subject based on the ideXlab platform.
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ultimate Taipan with dynamic block encoding
Tools and Algorithms for Construction and Analysis of Systems, 2018Co-Authors: Daniel Dietsch, Marius Greitschus, Matthias Heizmann, Alexander Nutz, Christian Schilling, Andreas Podelski, Jochen Hoenicke, Tanja SchindlerAbstract:Ultimate Taipan is a software model checker that uses trace abstraction and abstract interpretation to prove correctness of programs. In contrast to previous versions, Ultimate Taipan now uses dynamic block encoding to obtain the best precision possible when evaluating transition formulas of large block encoded programs.
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TACAS (2) - Ultimate Taipan with Dynamic Block Encoding
Tools and Algorithms for the Construction and Analysis of Systems, 2018Co-Authors: Daniel Dietsch, Marius Greitschus, Matthias Heizmann, Alexander Nutz, Christian Schilling, Andreas Podelski, Jochen Hoenicke, Tanja SchindlerAbstract:Ultimate Taipan is a software model checker that uses trace abstraction and abstract interpretation to prove correctness of programs. In contrast to previous versions, Ultimate Taipan now uses dynamic block encoding to obtain the best precision possible when evaluating transition formulas of large block encoded programs.
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ultimate Taipan trace abstraction and abstract interpretation
Tools and Algorithms for Construction and Analysis of Systems, 2017Co-Authors: Marius Greitschus, Daniel Dietsch, Matthias Heizmann, Alexander Nutz, Claus Schatzle, Christian Schilling, Frank Schussele, Andreas PodelskiAbstract:Ultimate Taipan is a software model checker for C programs. It is based on a CEGAR variant, trace abstractioni¾?[7], where program abstractions, counterexample selection and abstraction refinement are based on automata. Ultimate Taipan constructs path programs from counterexamples and computes fixpoints for those path programs using abstract interpretation. If the fixpoints are strong enough to prove the path program to be correct, they are guaranteed to be loop invariants for the path program. If they are not strong enough, Ultimate Taipan uses an interpolating SMT solver to obtain state assertions from the original counterexample, thus guaranteeing progress.
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TACAS (2) - Ultimate Taipan: Trace Abstraction and Abstract Interpretation
Tools and Algorithms for the Construction and Analysis of Systems, 2017Co-Authors: Marius Greitschus, Daniel Dietsch, Matthias Heizmann, Alexander Nutz, Claus Schatzle, Christian Schilling, Frank Schussele, Andreas PodelskiAbstract:Ultimate Taipan is a software model checker for C programs. It is based on a CEGAR variant, trace abstractioni¾?[7], where program abstractions, counterexample selection and abstraction refinement are based on automata. Ultimate Taipan constructs path programs from counterexamples and computes fixpoints for those path programs using abstract interpretation. If the fixpoints are strong enough to prove the path program to be correct, they are guaranteed to be loop invariants for the path program. If they are not strong enough, Ultimate Taipan uses an interpolating SMT solver to obtain state assertions from the original counterexample, thus guaranteeing progress.
Daniel Dietsch - One of the best experts on this subject based on the ideXlab platform.
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ultimate Taipan with dynamic block encoding
Tools and Algorithms for Construction and Analysis of Systems, 2018Co-Authors: Daniel Dietsch, Marius Greitschus, Matthias Heizmann, Alexander Nutz, Christian Schilling, Andreas Podelski, Jochen Hoenicke, Tanja SchindlerAbstract:Ultimate Taipan is a software model checker that uses trace abstraction and abstract interpretation to prove correctness of programs. In contrast to previous versions, Ultimate Taipan now uses dynamic block encoding to obtain the best precision possible when evaluating transition formulas of large block encoded programs.
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TACAS (2) - Ultimate Taipan with Dynamic Block Encoding
Tools and Algorithms for the Construction and Analysis of Systems, 2018Co-Authors: Daniel Dietsch, Marius Greitschus, Matthias Heizmann, Alexander Nutz, Christian Schilling, Andreas Podelski, Jochen Hoenicke, Tanja SchindlerAbstract:Ultimate Taipan is a software model checker that uses trace abstraction and abstract interpretation to prove correctness of programs. In contrast to previous versions, Ultimate Taipan now uses dynamic block encoding to obtain the best precision possible when evaluating transition formulas of large block encoded programs.
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ultimate Taipan trace abstraction and abstract interpretation
Tools and Algorithms for Construction and Analysis of Systems, 2017Co-Authors: Marius Greitschus, Daniel Dietsch, Matthias Heizmann, Alexander Nutz, Claus Schatzle, Christian Schilling, Frank Schussele, Andreas PodelskiAbstract:Ultimate Taipan is a software model checker for C programs. It is based on a CEGAR variant, trace abstractioni¾?[7], where program abstractions, counterexample selection and abstraction refinement are based on automata. Ultimate Taipan constructs path programs from counterexamples and computes fixpoints for those path programs using abstract interpretation. If the fixpoints are strong enough to prove the path program to be correct, they are guaranteed to be loop invariants for the path program. If they are not strong enough, Ultimate Taipan uses an interpolating SMT solver to obtain state assertions from the original counterexample, thus guaranteeing progress.
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TACAS (2) - Ultimate Taipan: Trace Abstraction and Abstract Interpretation
Tools and Algorithms for the Construction and Analysis of Systems, 2017Co-Authors: Marius Greitschus, Daniel Dietsch, Matthias Heizmann, Alexander Nutz, Claus Schatzle, Christian Schilling, Frank Schussele, Andreas PodelskiAbstract:Ultimate Taipan is a software model checker for C programs. It is based on a CEGAR variant, trace abstractioni¾?[7], where program abstractions, counterexample selection and abstraction refinement are based on automata. Ultimate Taipan constructs path programs from counterexamples and computes fixpoints for those path programs using abstract interpretation. If the fixpoints are strong enough to prove the path program to be correct, they are guaranteed to be loop invariants for the path program. If they are not strong enough, Ultimate Taipan uses an interpolating SMT solver to obtain state assertions from the original counterexample, thus guaranteeing progress.
P J Mirtschin - One of the best experts on this subject based on the ideXlab platform.
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a comparative study of the biological properties of venoms from juvenile and adult inland Taipan oxyuranus microlepidotus snake venoms
Toxicon, 1993Co-Authors: Gnanajothy Ponnudurai, P J MirtschinAbstract:N.-H. Tan, G. Ponnudurai and P.J. Mirtschin. A comparative study of the biological properties of venoms from juvenile and adult inland Taipan (Oxyuranus microlepidotus) snake venoms. Toxicon31, 363–367, 1993.—The biological properties of adult and juvenile inland Taipan (Oxyuranus microlepidotus) snake venoms were examined. The enzymatic activities, intravenous median lethal dose and procoagulant activity of the juvenile venom samples were not significantly different from those of the adult venom samples. Also, the juvenile and adult venoms exhibited similar electrophoretic patterns, indicating that they possessed similar protein composition.
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the biological properties of venoms from juvenile and adult Taipan oxyuranus scutellatus snakes
Comparative Biochemistry and Physiology B, 1992Co-Authors: Arunmozhiarasi Armugam, P J MirtschinAbstract:Abstract 1. 1. The biological properties of four venom pooled samples from adult Taipan ( Oxyuranus scutellatus ) snakes and one pooled venom sample from six juvenile Taipan snakes (11 months old) were compared. 2. 2. The intravenous ld 50 (median lethal dose), procoagulant activity and enzymatic activities of the juvenile venom were not significantly different from those of the adult venoms. 3. 3. The juvenile and adult venoms exhibited similar polyacrylamide gel electrophoretic (PAGE) and SDS-PAGE patterns, indicating that they possessed a similar protein composition. 4. 4.The results suggest that there is no significant age-dependency in the biological properties of Taipan venom.