The potential of marine natural products to become new drugs is vast; however, research is still in its infancy. The chemical and biological diversity of marine toxins is immeasurable and as such an extraordinary resource for the discovery of new drugs. With the rapid development of next-generation sequencing (NGS) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), it has been much easier and faster to identify more toxins and predict their functions with bioinformatics pipelines, which pave the way for novel drug developments. Here we provide an overview of related bioinformatics pipelines that have been supported by a combination of transcriptomics and proteomics for identification and function prediction of novel marine toxins. Full article

Millions of years of evolution have fine-tuned the ability of venom peptides to rapidly incapacitate both prey and potential predators. Toxicofera reptiles are characterized by serous-secreting mandibular or maxillary glands with heightened levels of protein expression. These glands are the core anatomical components of the toxicoferan venom system, which exists in myriad points along an evolutionary continuum. Neofunctionalisation of toxins is facilitated by positive selection at functional hotspots on the ancestral protein and venom proteins have undergone dynamic diversification in helodermatid and varanid lizards as well as advanced snakes. A spectacular point on the venom system continuum is the long-glanded blue coral snake (Calliophis bivirgatus), a specialist feeder that preys on fast moving, venomous snakes which have both a high likelihood of prey escape but also represent significant danger to the predator itself. The maxillary venom glands of C. bivirgatus extend one quarter of the snake’s body length and nestle within the rib cavity. Despite the snake’s notoriety its venom has remained largely unstudied. Here we show that the venom uniquely produces spastic paralysis, in contrast to the flaccid paralysis typically produced by neurotoxic snake venoms. The toxin responsible, which we have called calliotoxin (δ-elapitoxin-Cb1a), is a three-finger toxin (3FTx). Calliotoxin shifts the voltage-dependence of Na_V1.4 activation to more hyperpolarised potentials, inhibits inactivation, and produces large ramp currents, consistent with its profound effects on contractile force in an isolated skeletal muscle preparation. Voltage-gated sodium channels (Na_V) are a particularly attractive pharmacological target as they are involved in almost all physiological processes including action potential generation and conduction. Accordingly, venom peptides that interfere with Na_V function provide a key defensive and predatory advantage to a range of invertebrate venomous species including cone snails, scorpions, spiders, and anemones. Enhanced activation or delayed inactivation of sodium channels by toxins is associated with the extremely rapid onset of tetanic/excitatory paralysis in envenomed prey animals. A strong selection pressure exists for the evolution of such toxins where there is a high chance of prey escape. However, despite their prevalence in other venomous species, toxins causing delay of sodium channel inhibition have never previously been described in vertebrate venoms. Here we show that Na_V modulators, convergent with those of invertebrates, have evolved in the venom of the long-glanded coral snake. Calliotoxin represents a functionally novel class of 3FTx and a structurally novel class of Na_V toxins that will provide significant insights into the pharmacology and physiology of Na_V. The toxin represents a remarkable case of functional convergence between invertebrate and vertebrate venom systems in response to similar selection pressures. These results underscore the dynamic evolution of the Toxicofera reptile system and reinforces the value of using evolution as a roadmap for biodiscovery. Full article

Fish venom remains a virtually untapped resource. There are so few fish toxin sequences for reference, which increases the difficulty to study toxins from venomous fish and to develop efficient and fast methods to dig out toxin genes or proteins. Here, we utilized Chinese yellow catfish (Pelteobagrus fulvidraco) as our research object, since it is a representative species in Siluriformes with its venom glands embedded in the pectoral and dorsal fins. In this study, we set up an in-house toxin database and a novel toxin-discovering protocol to dig out precise toxin genes by combination of transcriptomic and proteomic sequencing. Finally, we obtained 15 putative toxin proteins distributed in five groups, namely Veficolin, Ink toxin, Adamalysin, Za2G and CRISP toxin. It seems that we have developed a novel bioinformatics method, through which we could identify toxin proteins with high confidence. Meanwhile, these toxins can also be useful for comparative studies in other fish and development of potential drugs. Full article

Graphene has attracted enormous attention owing to its extraordinary properties, while graphene-based nanocomposites hold promise for many applications. In this paper, we present a two-step exploitation method for preparation of graphene oxides and a facile solvothermal route for preparation of few-layer graphene nanosheets and graphene/WO₃ nanocomposites in an ethanol-distilled water medium. The as-synthesized samples were characterized by using field emission scanning electron microscopy (FE-SEM), high-resolution transmission electron microscopy (HRTEM), ultraviolet-visible (UV-vis) spectroscopy, Raman spectroscopy, X-ray diffraction (XRD), thermogravimetric-differential thermal analysis (TG-DTA) and gas-sensing test. The resistivity of the thick-film gas sensors based on sandwich-like graphene/WO₃ nanocomposites can be controlled by varying the amount of graphene in the composites. Graphene/WO₃ nanocomposites with graphene content higher than 1% show fast response, high selectivity and fine sensitivity to NO_x. Full article

Oxidative stress plays a critical role in the etiology and pathogenesis of neurodegenerative disorders, and the molecular mechanisms that control the neuron response to ROS have been extensively studied. However, the oxidative stress-effect on miRNA expression in hippocampal neurons has not been investigated, and little is known on the effect of ROS-modulated miRNAs on cell function. In this study, H₂O₂ was used to stimulate the mouse primary hippocampal neurons to develop an oxidative stress cell model. The alterations of miRNAs expression were detected by microarray analysis and five miRNAs were validated by real-time RT-PCR. The bioinformatic analysis of deregulated miRNAs was performed to determine their potential roles in the pathogenesis of neurological disorders. We found that H₂O₂ mediated a total of 101 deregulated miRNAs, which mainly took part in the regulation of the MAPK pathway. Among them, miR-135b and miR-708 were up-regulated significantly and their targets were predicted to be involved in DNA recombination, protein ubiquitination, protein autophosphorylation and development of neurons. These results demonstrated that oxidative stress alters the miRNA expression profile of hippocampal neurons, and the deregulated miRNAs might play a potential role in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD). Full article