Evolution of the Radular Apparatus in Conoidea (Gastropoda: Neogastropoda) as Inferred from a Molecular Phylogeny

International audienceThe radular anatomy and evolution of the radular apparatus in predatory marine gastropods, superfamily Conoidea, is reconstructed on the basis of a molecular phylogeny, based on three mitochondrial genes (COI, 12S and 16S) for 101 species. A unique feeding mechanism involving use of individual marginal radular teeth at the proboscis tip for stabbing and envenomation of prey at the proboscis tip appeared at the earliest stages of evolution of the group. The initial major evolutionary event in Conoidea was the divergence to two main branches. One is characterized by mostly hypodermic marginal teeth and absence of an odontophore, while the other possesses a radula with primarily duplex marginal teeth, a strong subradular membrane and retains a fully functional odontophore. The radular types that have previously been considered most ancestral, "prototypic" for the group (flat marginal teeth; multicuspid lateral teeth of Drilliidae; solid recurved teeth of Pseudomelatoma and Duplicaria), were found to be derived conditions. Solid recurved teeth appeared twice, independently, in Conoidea-in Pseudomelatomidae and Terebridae. The Terebridae, the sister group of Turridae, are characterized by very high radular variability, and the transformation of the marginal radular teeth within this single clade repeats the evolution of the radular apparatus across the entire Conoidea

A critical review of Antarctic Conoidea (Neogastropoda)

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A new lineage of Conoidea (Gastropoda: Neogastropoda) revealed by morphological and molecular data

International audienceThe hyperdiverse group of venomous Conoidea has eluded attempts to construct a robust and stable classification owing to the absence of a robust and stable phylogenetic framework. New molecular data have greatly enhanced our understanding of conoidean evolution, allowing the construction of a new family-level classification. This expanding framework has also allowed the discovery of several independent lineages that merit recognition at family rank. One of these, based on seven specimens collected over more than 20 years from deep waters off New Caledonia, represents an unique, monotypic lineage closely related to Mitromorphidae, which we here name Bouchetaiidae, fam. nov. This new lineage bears a unique combination of teleoconch, protoconch and anatomical characters previously unknown within the Conoidea, including a translucent, fusiform shell with sculpture of strong axial ribs crossed by spiral cords, a multi-spiral protoconch of only 2.5 whorls with punctate sculpture, hypodermic marginal teeth, and a multi-layered venom bulb with two layers of muscle separated by connective tissue. This unique lineage may represent the sole survivor of a previously more diverse clade, or is simply one of many unique taxa that has arisen among the isolated sea mounts off New Caledonia

A quest for the lost types of Lophiotoma (Gastropoda: Conoidea: Turridae): integrative taxonomy in a nomenclatural mess

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Venom Diversity and Evolution in the Most Divergent Cone Snail Genus Profundiconus

Profundiconus is the most divergent cone snail genus and its unique phylogenetic position, sister to the rest of the family Conidae, makes it a key taxon for examining venom evolution and diversity. Venom gland and foot transcriptomes of Profundiconus cf. vaubani and Profundiconus neocaledonicus were de novo assembled, annotated, and analyzed for differential expression. One hundred and thirty-seven venom components were identified from P. cf. vaubani and 82 from P. neocaledonicus, with only four shared by both species. The majority of the transcript diversity was composed of putative peptides, including conotoxins, profunditoxins, turripeptides, insulin, and prohormone-4. However, there were also a significant percentage of other putative venom components such as chymotrypsin and L-rhamnose-binding lectin. The large majority of conotoxins appeared to be from new gene superfamilies, three of which are highly different from previously reported venom peptide toxins. Their low conotoxin diversity and the type of insulin found suggested that these species, for which no ecological information are available, have a worm or molluscan diet associated with a narrow dietary breadth. Our results indicate that Profundiconus venom is highly distinct from that of other cone snails, and therefore important for examining venom evolution in the Conidae family

Molecular Diversity and Gene Evolution of the Venom Arsenal of Terebridae Predatory Marine Snails

Venom peptides from predatory organisms are a resource for investigating evolutionary processes such as adaptive radiation or diversification, and exemplify promising targets for biomedical drug development. Terebridae are an understudied lineage of conoidean snails,which also includes cone snails and turrids. Characterization of cone snail venompeptides, conotoxins, has revealed a cocktail of bioactive compounds used to investigate physiological cellular function, predator-prey interactions, and to develop novel therapeutics. However, venom diversity of other conoidean snails remains poorly understood. The present research applies a venomics approach to characterize novel terebrid venom peptides, teretoxins, from the venom gland transcriptomes of Triplostephanus anilis and Terebra subulata. Next-generation sequencing and de novo assembly identified 139 putative teretoxins that were analyzed for the presence of canonical peptide features as identified in conotoxins. To meet the challenges of de novo assembly, multiple approaches for cross validation of findings were performed to achieve reliable assemblies of venom duct transcriptomes and to obtain a robust portrait of Terebridae venom. Phylogenetic methodology was used to identify 14 teretoxin gene superfamilies for the first time, 13 of which are unique to the Terebridae. Additionally, basic local algorithm search tool homologybased searches to venom-related genes and posttranslational modification enzymes identified a convergence of certain venom proteins, suchas actinoporin, commonly foundinvenoms. This research provides novel insights intovenomevolutionandrecruitment in Conoidean predatory marine snails and identifies a plethora of terebrid venom peptides that can be used to investigate fundamental questions pertaining to gene evolution

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Out of Australia: Belloliva (Neogastropoda: Olividae) in the Coral Sea and New Caledonia

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Rare, deep-water and similar: revision of Sibogasyrinx (Conoidea: Cochlespiridae)

The genus Sibogasyrinx has to date included only four species of rare deep-water Conoidea, each known from few specimens. In shell characters it strongly resembles three distantly-related genera, two of which, Comitas and Leucosyrinx, belong to a different family, the Pseudomelatomidae. A molecular phylogenetic analysis of a large amount of material of Conoidea has revealed the existence of much additional undescribed diversity within Sibogasyrinx from the central Indo-Pacific and temperate Northern Pacific. Based on partial sequences of the mitochondrial cox1 gene and morphological characters of 54 specimens, 10 species hypotheses are proposed, of which six are described as new species: S. subula sp. nov., S. lolae sp. nov., S. maximei sp. nov., S. clausura sp. nov., S. pagodiformis sp. nov. and S. elbakyanae Kantor, Puillandre & Bouchet sp. nov. One of the previously described species was absent in our material. Most of the new species are very similar and are compared to Leucosyrinx spp. Species of Sibogasyrinx are unique among Conoidea on account of the high intrageneric variability in radular morphology. Three distinct radula types are found within Sibogasyrinx, two of which are confined to highly supported subclades

Rare, deep-water and similar: revision of Sibogasyrinx (Conoidea: Cochlespiridae)

The genus Sibogasyrinx has to date included only four species of rare deep-water Conoidea, each known from few specimens. In shell characters it strongly resembles three distantly-related genera, two of which, Comitas and Leucosyrinx, belong to a different family, the Pseudomelatomidae. A molecular phylogenetic analysis of a large amount of material of Conoidea has revealed the existence of much additional undescribed diversity within Sibogasyrinx from the central Indo-Pacific and temperate Northern Pacific. Based on partial sequences of the mitochondrial cox1 gene and morphological characters of 54 specimens, 10 species hypotheses are proposed, of which six are described as new species: S. subula sp. nov., S. lolae sp. nov., S. maximei sp. nov., S. clausura sp. nov., S. pagodiformis sp. nov. and S. elbakyanae Kantor, Puillandre & Bouchet sp. nov. One of the previously described species was absent in our material. Most of the new species are very similar and are compared to Leucosyrinx spp. Species of Sibogasyrinx are unique among Conoidea on account of the high intrageneric variability in radular morphology. Three distinct radula types are found within Sibogasyrinx, two of which are confined to highly supported subclades