Venom down under: Dynamic evolution of Australian elapid snake toxins

Despite the unparalleled diversity of venomous snakes in Australia, research has concentrated on a handful of medically significant species and even of these very few toxins have been fully sequenced. In this study, venom gland transcriptomes were sequenced from eleven species of small Australian elapid snakes, from eleven genera, spanning a broad phylogenetic range. The particularly large number of sequences obtained for three-finger toxin (3FTx) peptides allowed for robust reconstructions of their dynamic molecular evolutionary histories. We demonstrated that each species preferentially favoured different types of α-neurotoxic 3FTx, probably as a result of differing feeding ecologies. The three forms of α-neurotoxin [Type I (also known as (aka): short-chain), Type II (aka: long-chain) and Type III] not only adopted differential rates of evolution, but have also conserved a diversity of residues, presumably to potentiate prey-specific toxicity. Despite these differences, the different α-neurotoxin types were shown to accumulate mutations in similar regions of the protein, largely in the loops and structurally unimportant regions, highlighting the significant role of focal mutagenesis. We theorize that this phenomenon not only affects toxin potency or specificity, but also generates necessary variation for preventing/delaying prey animals from acquiring venom-resistance. This study also recovered the first full-length sequences for multimeric phospholipase A2 PLA2) ‘taipoxin/paradoxin’ subunits from non-Oxyuranus species, confirming the early recruitment of this extremely potent neurotoxin complex to the venom arsenal of Australian elapid snakes. We also recovered the first natriuretic peptides from an elapid that lack the derived C-terminal tail and resemble the plesiotypic form (ancestral character state) found in viper venoms. This provides supporting evidence for a single early recruitment of natriuretic peptides into snake venoms. Novel forms of kunitz and waprin peptides were recovered, including dual domain kunitz-kunitz precursors and the first kunitz-waprin hybrid precursors from elapid snakes. The novel sequences recovered in this study reveal that the huge diversity of unstudied venomous Australian snakes are of considerable interest not only for the investigation of venom and whole organism evolution but also represent an untapped bioresource in the search for novel compounds for use in drug design and development.Timothy N. W. Jackson , Kartik Sunagar, Eivind A. B. Undheim, Ivan Koludarov, Angelo H. C. Chan, Kate Sanders, Syed A. Ali, Iwan Hendrikx, Nathan Dunstan and Bryan G. Fr

From Predicting Solar Activity to Forecasting Space Weather: Practical Examples of Research-to-Operations and Operations-to-Research

The successful transition of research to operations (R2O) and operations to research (O2R) requires, above all, interaction between the two communities. We explore the role that close interaction and ongoing communication played in the successful fielding of three separate developments: an observation platform, a numerical model, and a visualization and specification tool. Additionally, we will examine how these three pieces came together to revolutionize interplanetary coronal mass ejection (ICME) arrival forecasts. A discussion of the importance of education and training in ensuring a positive outcome from R2O activity follows. We describe efforts by the meteorological community to make research results more accessible to forecasters and the applicability of these efforts to the transfer of space-weather research.We end with a forecaster "wish list" for R2O transitions. Ongoing, two-way communication between the research and operations communities is the thread connecting it all.Comment: 18 pages, 3 figures, Solar Physics in pres

Oxalyltransferase, a plant cell-wall acyltransferase activity, transfers oxalate groups from ascorbate metabolites to carbohydrates

In the plant apoplast, ascorbate is oxidised, via dehydroascorbic acid, to O-oxalyl esters [oxalyl-l-threonate (OxT) and cyclic oxalyl-l-threonate (cOxT)]. We tested whether OxT and cOxT can donate the oxalyl group in transacylation reactions to form oxalyl-polysaccharides, potentially modifying the cell wall. [oxalyl-14 C]OxT was incubated with living spinach (Spinacia oleracea) and Arabidopsis cell-suspension cultures in the presence or absence of proposed acceptor substrates (carbohydrates). In addition, [14 C]OxT and [14 C]cOxT were incubated in vitro with cell-wall enzyme preparations plus proposed acceptor substrates. Radioactive products were monitored electrophoretically. Oxalyltransferase activity was detected. Living cells incorporated oxalate groups from OxT into cell-wall polymers via ester bonds. When sugars were added, [14 C]oxalyl-sugars were formed, in competition with OxT hydrolysis. Preferred acceptor substrates were carbohydrates possessing primary alcohols e.g. glucose. A model transacylation product, [14 C]oxalyl-glucose, was relatively stable in vivo (half-life >24 h), whereas [14 C]OxT underwent rapid turnover (half-life ~6 h). Ionically wall-bound enzymes catalysed similar transacylation reactions in vitro with OxT or cOxT as oxalyl donor substrates and any of a range of sugars or hemicelluloses as acceptor substrates. Glucosamine was O-oxalylated, not N-oxalylated. We conclude that plants possess apoplastic acyltransferase (oxalyltransferase) activity that transfers oxalyl groups from ascorbate catabolites to carbohydrates, forming relatively long-lived O-oxalyl-carbohydrates. The findings increase the range of known metabolites whose accumulation in vivo indicates vitamin C catabolism. Possible signalling roles of the resulting oxalyl-sugars can now be investigated, as can the potential ability of polysaccharide oxalylation to modify the wall's physical properties

A Statistical Study of Solar Particle Events in Flux and Dose

The high-energy protons from solar energetic particle (SEP) events present a hazard to space systems: damage to science instruments/electronics/materials or to astronauts. A reliable estimate of the high-energy proton environment is critical to assure mission success. Important characteristics of an SEP event are fluence, peak flux, energy spectrum, time to reach the peak flux, time to reach peak dose, and properties of the cumulative dose profile after an event starts. All of these characteristics are important to understand in order to design space missions properly for both robotic and human missions. Because of the unpredictable and sporadic nature of SEP events, statistical models are often used to represent the SEP parameters described above. In a study by Jun et al. (2007), the statistics of event fluences, durations, and time intervals between events were investigated using the then available historical SEP dataset obtained from the instruments onboard the IMP-8 spacecraft. Since then, a more comprehensive SEP dataset based off of IMP-8 and GOES called Reference Data Set Version 2.0 (RDSv2.0) has become available covering the SEP events up to Year 2015 under a framework of the European Space Agency's (ESA's) Solar Energetic Particle Environment Modelling (SEPEM) project (Jiggens et al., 2018). The main objectives of this statistical study of SEP events are two-fold: First, the statistics of peak fluxes, event fluences, durations, and time intervals will be re-visited by using RDSv2.0; Second, the statistical analyses of flux and dose timing will be performed using the same dataset RDSv2.0. The results of this study will address the statistical properties of all key parameters for designing a spacecraft or a human mission where the SEP environment is an important consideration

Venom gland transcriptomes of two elapid snakes (Bungarus multicinctus and Naja atra) and evolution of toxin genes

<p>Abstract</p> <p>Background</p> <p>Kraits (genus <it>Bungarus</it>) and cobras (genus <it>Naja</it>) are two representative toxic genera of elapids in the old world. Although they are closely related genera and both of their venoms are very toxic, the compositions of their venoms are very different. To unveil their detailed venoms and their evolutionary patterns, we constructed venom gland cDNA libraries and genomic bacterial artificial chromosome (BAC) libraries for <it>Bungarus multicinctus </it>and <it>Naja atra</it>, respectively. We sequenced about 1500 cDNA clones for each of the venom cDNA libraries and screened BAC libraries of the two snakes by blot analysis using four kinds of toxin probes; <it>i.e</it>., three-finger toxin (3FTx), phospholipase A2 (PLA2), kunitz-type protease inhibitor (Kunitz), and natriuretic peptide (NP).</p> <p>Results</p> <p>In total, 1092 valid expressed sequences tags (ESTs) for <it>B. multicinctus </it>and 1166 ESTs for <it>N. atra </it>were generated. About 70% of these ESTs can be annotated as snake toxin transcripts. 3FTx (64.5%) and <it>β </it>bungarotoxin (25.1%) comprise the main toxin classes in <it>B. multicinctus</it>, while 3FTx (95.8%) is the dominant toxin in <it>N. atra</it>. We also observed several less abundant venom families in <it>B. multicinctus </it>and <it>N. atra</it>, such as PLA2, C-type lectins, and Kunitz. Peculiarly a cluster of NP precursors with tandem NPs was detected in <it>B. multicinctus</it>. A total of 71 positive toxin BAC clones in <it>B. multicinctus </it>and <it>N. atra </it>were identified using four kinds of toxin probes (3FTx, PLA2, Kunitz, and NP), among which 39 3FTx-postive BACs were sequenced to reveal gene structures of 3FTx toxin genes.</p> <p>Conclusions</p> <p>Based on the toxin ESTs and 3FTx gene sequences, the major components of <it>B. multicinctus </it>venom transcriptome are neurotoxins, including long chain alpha neurotoxins (<it>α</it>-ntx) and the recently originated <it>β </it>bungarotoxin, whereas the <it>N. atra </it>venom transcriptome mainly contains 3FTxs with cytotoxicity and neurotoxicity (short chain <it>α</it>-ntx). The data also revealed that tandem duplications contributed the most to the expansion of toxin multigene families. Analysis of nonsynonymous to synonymous nucleotide substitution rate ratios (<it>dN</it>/<it>dS</it>) indicates that not only multigene toxin families but also other less abundant toxins might have been under rapid diversifying evolution.</p

Network adaptation improves temporal representation of naturalistic stimuli in drosophila eye: II Mechanisms

Retinal networks must adapt constantly to best present the ever changing visual world to the brain. Here we test the hypothesis that adaptation is a result of different mechanisms at several synaptic connections within the network. In a companion paper (Part I), we showed that adaptation in the photoreceptors (R1-R6) and large monopolar cells (LMC) of the Drosophila eye improves sensitivity to under-represented signals in seconds by enhancing both the amplitude and frequency distribution of LMCs' voltage responses to repeated naturalistic contrast series. In this paper, we show that such adaptation needs both the light-mediated conductance and feedback-mediated synaptic conductance. A faulty feedforward pathway in histamine receptor mutant flies speeds up the LMC output, mimicking extreme light adaptation. A faulty feedback pathway from L2 LMCs to photoreceptors slows down the LMC output, mimicking dark adaptation. These results underline the importance of network adaptation for efficient coding, and as a mechanism for selectively regulating the size and speed of signals in neurons. We suggest that concert action of many different mechanisms and neural connections are responsible for adaptation to visual stimuli. Further, our results demonstrate the need for detailed circuit reconstructions like that of the Drosophila lamina, to understand how networks process information

Physiology of invasion: Cane toads are constrained by thermal effects on physiological mechanisms that support locomotor performance

Understanding the mechanisms that constrain the invasiveness of introduced animals is essential for managing invasions and for predicting their limits. In most vertebrate species, the capacity for invasion relies upon the physiological systems that support locomotion, and oxygen transport and metabolism may become limiting as environmental temperatures increase as predicted by the oxygen limitation hypothesis. Here we test the oxygen limitation hypothesis and propose the alternative hypothesis that within-individual plasticity will compensate for thermal variation. We show that during exercise in the invasive cane toad (Rhinella marina) oxygen transport by the cardiovascular system was maximised in warm-acclimated toads at high (30 degrees C) temperatures, and that oxygen content of arterial blood was not affected by temperature. Resting oxygen consumption remained stable across a 10 degrees C temperature range (20-30 degrees C) when toads were allowed to acclimate, so that there was no increase in resting oxygen demand that could lead to a decrease in aerobic scope at high temperatures. Additionally, temperature acclimation had no effect on arterial-venous differences in oxygen partial pressures. Toads relied more on glycolytic ATP production at low temperatures to support locomotor activity. Mitochondrial capacities (citrate synthase and cytochrome c oxidase activities) were greatest at warmer temperatures. Interestingly, the metabolic cost of exercise increased at low temperatures. In contradiction to predictions by the oxygen limitation hypothesis, aerobic performance was not limited by high temperatures. On the contrary, the relatively slow advance of cane toads to cooler climates can be explained by the constraints of low temperatures on the physiological systems supporting locomotion. It is likely that human-induced global warming will facilitate invasions of environments that are currently too cool to support cane toads

Lignin biomarkers as tracers of mercury sources in lakes water column

This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems