figure 4 in Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs

figure 4 Phylogenetic relationships of Dimorphilus oophagus sp. nov. A: Maximum likelihood phylogenetic tree; numbers in nodes indicate bootstrap support. Branches with support values under 50 were collapsed. B: coi sequence identity among the species and/or populations of Dimorphilus.Published as part of Giglio, Matías L., Salcedo, Paula Flórez, Watkins, Maren & Olivera, Baldomero, 2023, Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs, pp. 97-111 in Contributions to Zoology 92 (2) on page 105, DOI: 10.1163/18759866-bja10038, http://zenodo.org/record/834992

figure 1 in Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs

figure 1 Distribution and phylogeny of cone snails. A: Distribution of Conus ermineus (orange) and Conus purpurascens (purple), modified from Monnier et al. (2018); Red stars: collection sites. B: Phylogenetic tree of fish-hunting species of Conus, modified from Ramiro et al. (2022).Published as part of Giglio, Matías L., Salcedo, Paula Flórez, Watkins, Maren & Olivera, Baldomero, 2023, Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs, pp. 97-111 in Contributions to Zoology 92 (2) on page 102, DOI: 10.1163/18759866-bja10038, http://zenodo.org/record/834992

figure 2 in Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs

figure 2 Egg capsules of Conus ermineus. A: Living specimen retracted inside the shell. Photo by Samuel Espino. B: Egg masses attached to coral-like rocks. C: Detail of an egg capsule. D: Schematic representation of an egg capsule; left = convex wall, center = concave wall, right = lateral view. E: Detail of the eggs. Scale bars: A = 1 cm, B = 10 mm, C = 2 mm, D = 2 mm, E= 500μm.Published as part of Giglio, Matías L., Salcedo, Paula Flórez, Watkins, Maren & Olivera, Baldomero, 2023, Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs, pp. 97-111 in Contributions to Zoology 92 (2) on page 103, DOI: 10.1163/18759866-bja10038, http://zenodo.org/record/834992

figure 5 in Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs

figure 5 Dimorphilus oophagus sp. nov. A: Adult female, dorsal view; cb: ciliary bands, e: eyespot, oo: intracelomic oocytes, pm: pharyngeal musculature, p: pygidium, tc: tuft of cilia. S1–S6 = segment 1–6 B: Juvenile female. C: Immunohistochemistry showing the prostomial ciliary arrangement of an adult female. Acb = anterior ciliary band, pcb = posterior ciliary band D: Immunohistochemistry showing the segmental ciliary bands of an adult female. E: Reconstruction of an adult female of Dimorphilus oophagus sp. nov. Scale bars: A= 100μm, B= 100μm, C= 50μm, D= 100μm.Published as part of Giglio, Matías L., Salcedo, Paula Flórez, Watkins, Maren & Olivera, Baldomero, 2023, Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs, pp. 97-111 in Contributions to Zoology 92 (2) on page 106, DOI: 10.1163/18759866-bja10038, http://zenodo.org/record/834992

figure 3 in Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs

figure 3 Contents of the capsules of Conus ermineus. A: External appearance of non-infested (left) and infested (right) capsules. B: Contents of capsules filled with eggs (left) and infested with worms (right). Insets: comparison of unaffected (left) and affected (right) eggs. C: Specimens of Dimorphilus oophagus sp. nov.; arrowheads = egg-like contents. D: Enhanced resolution image of a specimen of D. oophagus sp. nov. eating C. ermineus eggs. a = cone snail egg, b = cone snail egg-like content in the gut of the worm, c = worm oocytes. Scale bars: B = 2 mm, C = 1 mm, D = 1 mm.Published as part of Giglio, Matías L., Salcedo, Paula Flórez, Watkins, Maren & Olivera, Baldomero, 2023, Insights into a putative polychaete-gastropod symbiosis from a newly identiFIed annelid worm that predates upon Conus ermineus eggs, pp. 97-111 in Contributions to Zoology 92 (2) on page 104, DOI: 10.1163/18759866-bja10038, http://zenodo.org/record/834992

Design of Thermoresponsive Polyamine Cross-Linked Perfluoropolyether Hydrogels for Imaging and Delivery Applications

[Image: see text] Perfluorocarbons are versatile compounds with applications in (19)F magnetic resonance imaging (MRI) and chemical conjugation to drugs and pH sensors. We present a novel thermoresponsive perfluorocarbon emulsion hydrogel that can be detected by (19)F MRI. The developed hydrogel contains perfluoro(polyethylene glycol dimethyl ether) (PFPE) emulsion droplets that are stabilized through ionic cross-linking with polyethylenimine (PEI). Specifically, PFPE ester undergoes hydrolysis upon contact with aqueous PEI solution, resulting in an ionic bond between the PFPE acid and charged PEI amino groups. Due to the ionic nature of the PFPE/PEI bond, potassium buffer is required to preserve the hydrogel’s pH and rheological and emulsion droplet stability. The presence of the surface cross-linked PFPE droplets does not affect the hydrogel’s rheological behavior, drug loading, or drug release, and the hydrogel is nontoxic. We propose that the presented hydrogel can be adapted to a broad range of biomedical imaging and delivery applications

Reconstructing the Origins of the Somatostatin and Allatostatin-C Signaling Systems Using the Accelerated Evolution of Biodiverse Cone Snail Toxins

Somatostatin and its related peptides (SSRPs) form an important family of hormones with diverse physiological roles. The ubiquitous presence of SSRPs in vertebrates and several invertebrate deuterostomes suggests an ancient origin of the SSRP signaling system. However, the existence of SSRP genes outside of deuterostomes has not been established, and the evolutionary history of this signaling system remains poorly understood. Our recent discovery of SSRP-like toxins (consomatins) in venomous marine cone snails (Conus) suggested the presence of a related signaling system in mollusks and potentially other protostomes. Here, we identify the molluscan SSRP-like signaling gene that gave rise to the consomatin family. Following recruitment into venom, consomatin genes experienced strong positive selection and repeated gene duplications resulting in the formation of a hyperdiverse family of venom peptides. Intriguingly, the largest number of consomatins was found in worm-hunting species (>400 sequences), indicating a homologous system in annelids, another large protostome phylum. Consistent with this, comprehensive sequence mining enabled the identification of SSRP-like sequences (and their corresponding orphan receptor) in annelids and several other protostome phyla. These results established the existence of SSRP-like peptides in many major branches of bilaterians and challenge the prevailing hypothesis that deuterostome SSRPs and protostome allatostatin-C are orthologous peptide families. Finally, having a large set of predator–prey SSRP sequences available, we show that although the cone snail’s signaling SSRP-like genes are under purifying selection, the venom consomatin genes experience rapid directional selection to target receptors in a changing mix of prey

Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor

The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this venom insulin, Con-Ins G1, has unique characteristics relevant to the design of new insulin therapeutics. Here, we show that fish-hunting cone snails provide a rich source of minimized ligands of the vertebrate insulin receptor. Insulins from C. geographus, Conus tulipa and Conus kinoshitai exhibit diverse sequences, yet all bind to and activate the human insulin receptor. Molecular dynamics reveal unique modes of action that are distinct from any other insulins known in nature. When tested in zebrafish and mice, venom insulins significantly lower blood glucose in the streptozotocin-induced model of diabetes. Our findings suggest that cone snails have evolved diverse strategies to activate the vertebrate insulin receptor and provide unique insight into the design of novel drugs for the treatment of diabetes

A previously unrecognized superfamily of macro-conotoxins includes an inhibitor of the sensory neuron calcium channel Cav2.3.

Animal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.1, which defines a new class of conotoxins evolutionarily related to the well-known con-ikot-ikots and 2 additional conotoxin classes not previously described. The crystal structure of recombinant Mu8.1 displays a saposin-like fold and shows structural similarity with con-ikot-ikot. Functional studies demonstrate that Mu8.1 curtails calcium influx in defined classes of murine somatosensory dorsal root ganglion (DRG) neurons. When tested on a variety of recombinantly expressed voltage-gated ion channels, Mu8.1 displayed the highest potency against the R-type (Cav2.3) calcium channel. Ca2+ signals from Mu8.1-sensitive DRG neurons were also inhibited by SNX-482, a known spider peptide modulator of Cav2.3 and voltage-gated K+ (Kv4) channels. Our findings highlight the potential of Mu8.1 as a molecular tool to identify and study neuronal subclasses expressing Cav2.3. Importantly, this multidisciplinary study showcases the potential of uncovering novel structures and bioactivities within the largely unexplored group of macro-conotoxins