Transdermal Delivery of Scopolamine by Natural Submicron Injectors: In-Vivo Study in Pig

Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts), comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with Tmax of 30 minutes and Cmax 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery

The cnidarian parasite Ceratonova shasta utilizes inherited and recruited venom-like compounds during infection

Background Cnidarians are the most ancient venomous organisms. They store a cocktail of venom proteins inside unique stinging organelles called nematocysts. When a cnidarian encounters chemical and physical cues from a potential threat or prey animal, the nematocyst is triggered and fires a harpoon-like tubule to penetrate and inject venom into the prey. Nematocysts are present in all Cnidaria, including the morphologically simple Myxozoa, which are a speciose group of microscopic, spore-forming, obligate parasites of fish and invertebrates. Rather than predation or defense, myxozoans use nematocysts for adhesion to hosts, but the involvement of venom in this process is poorly understood. Recent work shows some myxozoans have a reduced repertoire of venom-like compounds (VLCs) relative to free-living cnidarians, however the function of these proteins is not known. Methods We searched for VLCs in the nematocyst proteome and a time-series infection transcriptome of Ceratonova shasta, a myxozoan parasite of salmonid fish. We used four parallel approaches to detect VLCs: BLAST and HMMER searches to preexisting cnidarian venom datasets, the machine learning tool ToxClassifier, and structural modeling of nematocyst proteomes. Sequences that scored positive by at least three methods were considered VLCs. We then mapped their time-series expressions in the fish host and analyzed their phylogenetic relatedness to sequences from other venomous animals. Results We identified eight VLCs, all of which have closely related sequences in other myxozoan datasets, suggesting a conserved venom profile across Myxozoa, and an overall reduction in venom diversity relative to free-living cnidarians. Expression of the VLCs over the 3-week fish infection varied considerably: three sequences were most expressed at one day post-exposure in the fish’s gills; whereas expression of the other five VLCs peaked at 21 days post-exposure in the intestines, coinciding with the formation of mature parasite spores with nematocysts. Expression of VLC genes early in infection, prior to the development of nematocysts, suggests venoms in C. shasta have been repurposed to facilitate parasite invasion and proliferation within the host. Molecular phylogenetics suggested some VLCs were inherited from a cnidarian ancestor, whereas others were more closely related to sequences from venomous non-Cnidarian organisms and thus may have gained qualities of venom components via convergent evolution. The presence of VLCs and their differential expression during parasite infection enrich the concept of what functions a “venom” can have and represent targets for designing therapeutics against myxozoan infections

The myxozoan parasite Myxobolus bejeranoi (Cnidaria: Myxozoa) infection dynamics and host specificity in hybrid tilapia aquaculture

Nile × blue tilapia hybrid (Oreochromis niloticus × O. aureus) has become an important food fish in intensive freshwater aquaculture. Recently, the parasite Myxobolus bejeranoi (Cnidaria: Myxozoa) was found to infect hybrid tilapia gills at high prevalence, causing immune suppression and high mortality. Here, we explored additional characteristics of M. bejeranoi–tilapia interaction, which enable efficient proliferation of this parasite inside its specific host. Highly sensitive quantitative polymerase chain reaction (qPCR) and in situ hybridization analyses of fry collected from fertilization ponds provided evidence to an early-life infection of fish by a myxozoan parasite, occurring less than 3 weeks post-fertilization. Because Myxobolus species are highly host-specific, we next compared infection rates in hybrid tilapia and in both its parental species following a 1-week exposure to infectious pond water. Analysis by qPCR and histological sections showed that while blue tilapia was as susceptible to M. bejeranoi as the hybrid, Nile tilapia appeared to be resistant. This is the first report of differential susceptibility of a hybrid fish vs its parental purebreds to a myxozoan parasite. These findings advance our understanding of the relationship between M. bejeranoi and tilapia fish and raise important questions regarding the mechanisms that allow the parasite to distinguish between very closely related species and to infect a specific organ at very early-life stages

Exploring Digitalization of Animal-Assisted Reading

Animal-assisted reading is a form of animal-assisted activity where children interact with and read aloud to specially trained therapy dogs. Such activities have been shown to have positive impact on literacy skills, reading motivation and sense of empowerment and self-esteem in children. Mobile technologies and facets of engagement in digital reading are increasingly studied in the context of child learning and education. This short paper presents some first results of our ongoing study exploring potential ways in which mobile technology can be used to enhance and support animal-assisted reading activities for children

A Modified View on Octocorals: Heteroxenia fuscescens Nematocysts Are Diverse, Featuring Both an Ancestral and a Novel Type

Cnidarians are characterized by the presence of stinging cells containing nematocysts, a sophisticated injection system targeted mainly at prey-capture and defense. In the anthozoan subclass Octocorallia nematocytes have been considered to exist only in low numbers, to be small, and all of the ancestral atrichous-isorhiza type. This study, in contrast, revealed numerous nematocytes in the octocoral Heteroxenia fuscescens. The study demonstrates the applicability of cresyl-violet dye for differential staining and stimulating discharge of the nematocysts. In addition to the atrichous isorhiza-type of nematocysts, a novel type of macrobasic-mastigophore nematocysts was found, featuring a shaft, uniquely comprised of three loops and densely packed arrow-like spines. In contrast to the view that octocorals possess a single type of nematocyst, Heteroxenia fuscescens features two distinct types, indicating for the first time the diversification and complexity of nematocysts for Octocorallia

A remote sensing approach for exploring the dynamics of jellyfish, relative to the water current

Abstract Drifting in large numbers, jellyfish often interfere in the operation of nearshore electrical plants, cause disturbances to marine recreational activity, encroach upon local fish populations, and impact food webs. Understanding the dynamic mechanisms behind jellyfish behavior is of importance in order to create migration models. In this work, we focus on the small-scale dynamics of jellyfish and offer a novel method to accurately track the trajectory of individual jellyfish with respect to the water current. The existing approaches for similar tasks usually involve a surface float tied to the jellyfish for location reference. This operation may induce drag on the jellyfish, thereby affecting its motion. Instead, we propose to attach an acoustic tag to the jellyfish’s bell and then track its geographical location using acoustic beacons, which detect the tag’s emissions, decode its ID and depth, and calculate the tag’s position via time-difference-of-arrival acoustic localization. To observe the jellyfish’s motion relative to the water current, we use a submerged floater that is deployed together with the released tagged jellyfish. Being Lagrangian on the horizontal plane while maintaining an on-demand depth, the floater drifts with the water current; thus, its trajectory serves as a reference for the current’s velocity field. Using an acoustic modem and a hydrophone mounted to the floater, the operator from the deploying boat remotely changes the depth of the floater on-the-fly, to align it with that of the tagged jellyfish (as reported by the jellyfish’s acoustic tag), thereby serving as a reference for the jellyfish’s 3D motion with respect to the water current. We performed a proof-of-concept to demonstrate our approach over three jellyfish caught and tagged in Haifa Bay, and three corresponding floaters. The results present different dynamics for the three jellyfish, and show how they can move with, and even against, the water current

Direct Electricity Production from <i>Nematostella</i> and <i>Arthemia</i>’s Eggs in a Bio-Electrochemical Cell

In recent years, extensive efforts have been made to develop clean energy technologies to replace fossil fuels to assist the struggle against climate change. One approach is to exploit the ability of bacteria and photosynthetic organisms to conduct external electron transport for electricity production in bio-electrochemical cells. In this work, we first show that the sea anemones Nematostella vectensis and eggs of Artemia (brine shrimp) secrete redox-active molecules that can reduce the electron acceptor Cytochrome C. We applied 2D fluorescence spectroscopy and identified NADH or NADPH as secreted species. Finally, we broaden the scope of living organisms that can be integrated with a bio-electrochemical cell to the sea anemones group, showing for the first time that Nematostella and eggs of Artemia can produce electrical current when integrated into a bio-electrochemical cell