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Published data were used to model the transfer of ciguatoxins (CTX) across three trophic levels of a marine food chain on the Great Barrier Reef (GBR), Australia, to produce a mildly toxic common coral trout (Plectropomus leopardus), one of the most targeted food fishes on the GBR. Our model generated a 1.6 kg grouper with a flesh concentration of 0.1 µg/kg of Pacific-ciguatoxin-1 (P-CTX-1 = CTX1B) from 1.1 to 4.3 µg of P-CTX-1 equivalents (eq.) entering the food chain from 0.7 to 2.7 million benthic dinoflagellates (Gambierdiscus sp.) producing 1.6 pg/cell of the P-CTX-1 precursor, P-CTX-4B (CTX4B). We simulated the food chain transfer of ciguatoxins via surgeonfishes by modelling Ctenochaetus striatus feeding on turf algae. A C. striatus feeding on ≥1000 Gambierdiscus/cm2 of turf algae accumulates sufficient toxin in <2 days that when preyed on, produces a 1.6 kg common coral trout with a flesh concentration of 0.1 µg/kg P-CTX-1. Our model shows that even transient blooms of highly ciguatoxic Gambierdiscus can generate ciguateric fishes. In contrast, sparse cell densities of ≤10 Gambierdiscus/cm2 are unlikely to pose a significant risk, at least in areas where the P-CTX-1 family of ciguatoxins predominate. The ciguatera risk from intermediate Gambierdiscus densities (~100 cells/cm2) is more difficult to assess, as it requires feeding times for surgeonfish (~4–14 days) that overlap with turnover rates of turf algae that are grazed by herbivorous fishes, at least in regions such as the GBR, where stocks of herbivorous fishes are not impacted by fishing. We use our model to explore how the duration of ciguatoxic Gambierdiscus blooms, the type of ciguatoxins they produce, and fish feeding behaviours can produce differences in relative toxicities between trophic levels. Our simple model indicates thresholds for the design of risk and mitigation strategies for ciguatera and the variables that can be manipulated to explore alternate scenarios for the accumulation and transfer of P-CTX-1 analogues through marine food chains and, potentially, for other ciguatoxins in other regions, as more data become available. [ABSTRACT FROM AUTHOR]

To begin to understand the impact of food chain dynamics on ciguatera risk, we used published data to model the transfer of ciguatoxins across four trophic levels of a marine food chain in Platypus Bay, Australia. The data to support this first attempt to conceptualize the scale of each trophic transfer step was limited, resulting in broad estimates. The hypothetical scenario we explored generated a low-toxicity 10 kg Spanish mackerel (Scomberomorus commerson) with a flesh concentration of 0.1 µg/kg of Pacific-ciguatoxin-1 (P-CTX-1, also known as CTX1B) from 19.5–78.1 µg of P-CTX-1 equivalents (eq.) that enter the marine food chain from a population of 12–49 million benthic dinoflagellates (Gambierdiscus sp.) producing 1.6 × 10−12 g/cell of the P-CTX-1 precursor, P-CTX-4B. This number of Gambierdiscus could be epiphytic on 22–88 kg of the benthic macroalgae (Cladophora) that carpets the bottom of much of Platypus Bay, with the toxin transferred to an estimated 40,000–160,000 alpheid shrimps in the second trophic level. This large number of shrimps appears unrealistic, but toxic shrimps would likely be consumed by a school of small, blotched javelin fish (Pomadasys maculatus) at the third trophic level, reducing the number of shrimps consumed by each fish. The Spanish mackerel would accumulate a flesh concentration of 0.1 µg/kg P-CTX-1 eq. by preying upon the school of blotched javelin and consuming 3.6–14.4 µg of P-CTX-1 eq. However, published data indicate this burden of toxin could be accumulated by a 10 kg Spanish mackerel from as few as one to three blotched javelin fish, suggesting that much greater amounts of toxin than modelled here must at certain times be produced and transferred through Platypus Bay food chains. This modelling highlights the need for better quantitative estimates of ciguatoxin production, biotransformation, and depuration through marine food chains to improve our understanding and management of ciguatera risk. [ABSTRACT FROM AUTHOR]

Debate 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. [ABSTRACT FROM AUTHOR]

We review and develop conceptual models for the bio-transfer of ciguatoxins in food chains for Platypus Bay and the Great Barrier Reef on the east coast of Australia. Platypus Bay is unique in repeatedly producing ciguateric fishes in Australia, with ciguatoxins produced by benthic dinoflagellates (Gambierdiscus spp.) growing epiphytically on free-living, benthic macroalgae. The Gambierdiscus are consumed by invertebrates living within the macroalgae, which are preyed upon by small carnivorous fishes, which are then preyed upon by Spanish mackerel (Scomberomorus commerson). We hypothesise that Gambierdiscus and/or Fukuyoa species growing on turf algae are the main source of ciguatoxins entering marine food chains to cause ciguatera on the Great Barrier Reef. The abundance of surgeonfish that feed on turf algae may act as a feedback mechanism controlling the flow of ciguatoxins through this marine food chain. If this hypothesis is broadly applicable, then a reduction in herbivory from overharvesting of herbivores could lead to increases in ciguatera by concentrating ciguatoxins through the remaining, smaller population of herbivores. Modelling the dilution of ciguatoxins by somatic growth in Spanish mackerel and coral trout (Plectropomus leopardus) revealed that growth could not significantly reduce the toxicity of fish flesh, except in young fast-growing fishes or legal-sized fishes contaminated with low levels of ciguatoxins. If Spanish mackerel along the east coast of Australia can depurate ciguatoxins, it is most likely with a half-life of ≤1-year. Our review and conceptual models can aid management and research of ciguatera in Australia, and globally. [ABSTRACT FROM AUTHOR]

Terrestrial 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. • Bayesian approach based chronological model includes combined 14C and OSL dates. • Calibrated scanning XRF identifies dust variation in highly organic sediment. • Independently dated terrestrial palaeoenvironmental archive in Australia. • Dust flux contemporaneous with MIS3/4 deflation events at central Australian lakes. [ABSTRACT FROM AUTHOR]

Abstract: Despite the in vivo lethality of venom, neurotoxicity has not previously been considered a significant complication of envenoming by the Australian pygmy copperhead (Austrelaps labialis). However, recent evidence has emerged demonstrating that this venom contains potent presynaptic and postsynaptic neurotoxicity. The present study describes the isolation and pharmacological characterization of the first postsynaptic neurotoxin, α-EPTX-Al2a, from the venom of A. labialis. α-EPTX-Al2a (8072.77Da) caused a concentration-dependent block of twitch contractions and a complete block of responses to cholinergic agonists in the chick biventer cervicis nerve–muscle preparation. This action is consistent with postjunctional neurotoxicity. Monovalent tiger snake antivenom prevented the onset of neurotoxicity if applied prior to toxin administration, but was only able to partially reverse neurotoxicity once muscle paralysis had developed. α-EPTX-Al2a produced a potent pseudo-irreversible antagonism of chick muscle nicotinic acetylcholine receptors (nAChRs), with an estimated pA2 value of 7.902 (K B =12.5nM). Interestingly, the toxin only produced a modest block of neuronal α7 nAChRs, with an IC50 of 1.2μM, and failed to inhibit ganglionic α3β2/α3β4 nAChRs in a fluorescence-based FLIPR assay using SH-SY5Y cells. α-EPTX-Al2a contained 75 amino acid residues with five disulfide bonds that had significant homology to classical long-chain α-neurotoxins. While α-EPTX-Al2a retains most pharmacophore residues critical for binding to muscle-type (α1)2βγδ nAChRs it lacks the key Ala28 and Arg36 residues important for α7 nAChR affinity. Given that A. labialis venom contains both irreversible presynaptic and postsynaptic neurotoxins, clinicians need to be aware of potential neurotoxic complications associated with pygmy copperhead envenomation. [Copyright &y& Elsevier]

Australian funnel-web spiders are amongst the most dangerous venomous animals. Their venoms induce potentially deadly symptoms, including hyper- and hypotension, tachycardia, bradycardia and pulmonary oedema. Human envenomation is more frequent with the ground-dwelling species, including the infamous Sydney funnel-web spider ( Atrax robustus ); although, only two tree-dwelling species induce more severe envenomation. To unravel the mechanisms that lead to this stark difference in clinical outcomes, we investigated the venom transcriptome and proteome of arboreal Hadronyche cerberea and H. formidabilis . Overall, Hadronyche venoms comprised 44 toxin superfamilies, with 12 being exclusive to tree-dwellers. Surprisingly, the major venom components were neprilysins and uncharacterized peptides, in addition to the well-known ω- and δ-hexatoxins and double-knot peptides. The insecticidal effects of Hadronyche venom on sheep blowflies were more potent than Atrax venom, and the venom of both tree- and ground-dwelling species potently modulated human voltage-gated sodium channels, particularly Na V 1.2. Only the venom of tree-dwellers exhibited potent modulation of voltage-gated calcium channels. H. formidabilis appeared to be under less diversifying selection pressure compared to the newly adapted tree-dweller, H. cerberea . Thus, this study contributes to unravelling the fascinating molecular and pharmacological basis for the severe envenomation caused by the Australian tree-dwelling funnel-web spiders.

Australian funnel-web spiders are infamous for causing human fatalities, which are induced by venom peptides known as δ-hexatoxins (δ-HXTXs). Humans and other primates did not feature in the prey or predator spectrum during evolution of these spiders, and consequently the primate lethality of δ-HXTXs remains enigmatic. Funnel-web envenomations are mostly inflicted by male spiders that wander from their burrow in search of females during the mating season, which suggests a role for δ-HXTXs in self-defense since male spiders rarely feed during this period. Although 35 species of Australian funnel-web spiders have been described, only nine δ-HXTXs from four species have been characterized, resulting in a lack of understanding of the ecological roles and molecular evolution of δ-HXTXs. Here, by profiling venom-gland transcriptomes of 10 funnel-web species, we report 22 δ-HXTXs. Phylogenetic and evolutionary assessments reveal a remarkable sequence conservation of δ-HXTXs despite their deep evolutionary origin within funnel-web spiders, consistent with a defensive role. We demonstrate that δ-HXTX-Ar1a, the lethal toxin from the Sydney funnel-web spider Atrax robustus , induces pain in mice by inhibiting inactivation of voltage-gated sodium (Na V ) channels involved in nociceptive signaling. δ-HXTX-Ar1a also inhibited inactivation of cockroach Na V channels and was insecticidal to sheep blowflies. Considering their algogenic effects in mice, potent insecticidal effects, and high levels of sequence conservation, we propose that the δ-HXTXs were repurposed from an initial insecticidal predatory function to a role in defending against nonhuman vertebrate predators by male spiders, with their lethal effects on humans being an unfortunate evolutionary coincidence., Competing Interests: The authors declare no competing interest.

Fractionation of a cytotoxic extract obtained from a southern Australian marine sponge, Phorbas sp., yielded the known diterpenes phorbasins B-F () together with five new members of the phorbasin family, phorbasins G-K (). Structures were assigned to the new phorbasins based on detailed spectroscopic analysis. A preliminary structure activity relationship (SAR) evaluation based on the co-metabolites phorbasins B-K () revealed aspects of the phorbasin pharmacophore.

Ciguatera is a global disease caused by the consumption of certain warm-water fish that have accumulated orally effective levels of sodium channel activator toxins (ciguatoxins) through the marine food chain. Symptoms of ciguatera arising from the consumption of ciguateric fish include a range of gastrointestinal, neurological and cardiovascular disturbances. This review examines progress in our understanding of ciguatera from an Australian perspective, especially the laboratory-based research into the problem that was initiated by the late "Bob" Endean at the University of Queensland.