Gilquiniid cestodes (Trypanorhyncha) from elasmobranch fishes off New Caledonia with descriptions of two new genera and a new species

Cestodes were collected from deep-sea sharks caught off New Caledonia, South Pacific. Vittirhynchus squali n. g., n. sp. (Trypanorhyncha: Gilquiniidae) is described from the spiral valve of Squalus melanurus Fourmanoir & Rivaton. The new genus possesses four bothria and a typical heteroacanthous metabasal armature but has a file of three macrohooks forming a short chainette on the internal surface of the basal armature. Sagittirhynchus aculeatus n. g., n. sp., from the spiral valve of Centrophorus sp. (undescribed), also has four bothria and a typical heteroacanthous armature but lacks a distinctive basal swelling and has the final hooks of each principal row prominently enlarged. Gilquinia minor n. sp., from the spiral valve of Centrophorus sp. (undescribed), is distinguished by the presence of only five hooks per principal row compared with eight in congeners. Gilquinia sp. is reported from Squalus melanurus. G. robertsoni Beveridge, 1990 is reported from S. megalops (Macleay).     

Thaumatocotyle pseudodasybatis Hargis, 1955 (Monogenea: Monocotylidae) from Aetobatus cf. narinari, with a comparison of specimens from Australia, French Polynesia and New Caledonia

Thaumatocotyle pseudodasybatis Hargis, 1955, has previously been described from Aetobatus narinari in the Atlantic and subsequently recorded from the Pacific. Aetobatus cf. narinari is now considered a species complex; as monocotylids are often strictly species specific, we test the hypothesis that detailed examination of specimens of monocotylids from rays from various localities could reveal morphological differences and eventually help our understanding of the systematics of the host. T. pseudodasybatis, previously known from seven specimens only, is redescribed from an additional 26 specimens from the South Pacific (off New Caledonia, Australia and Ranguiroa, French Polynesia), all from Aetobatus cf. narinari. The female reproductive organs are described in detail. The distal extremity of the male sclerotised copulatory organ, described in detail for the first time, shows a characteristic pattern of longitudinal striations on its edge that might be useful for future distinction from other species. The development of the male and female organs in juveniles is described, showing that growth of the male sclerotised copulatory organ begins with its basal part and precedes development of the ejaculatory bulb. Specimens from New Caledonia, Australia and French Polynesia had similar measurements and morphology, especially in the shape of the distal end of the male sclerotised copulatory organ; they were also similar to the holotype from the Atlantic. This suggests that all specimens from the Pacific and Atlantic belong to a single species; T. pseudodasybatis thus cannot be used to differentiate populations of Aetobatus cf. narinari, perhaps because this monocotylid is not strictly species-specific.

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Résumé Thaumatocotyle pseudodasybatis Hargis, 1955 a été décrit d’Aetobatus narinari dans l’Atlantique, et plus tard retrouvé dans le Pacifique. Aetobatus cf. narinari est maintenant considéré comme un complexe d’espèces. Parce que les Monocotylidae sont souvent strictement spécifiques de leur espèce-hôte, nous testons l’hypothèse qu’un examen détaillé des spécimens de Monocotylidae de raies de localités variées pourrait révéler des différences morphologiques et finalement aider à comprendre la systématique de l’hôte. T. pseudodasybatis, connu précédemment par seulement sept spécimens, est redécrit à partir de 26 spécimens supplémentaires de l’Océan Pacifique Sud (Nouvelle-Calédonie, Australie, et Ranguiroa, Polynésie Française), tous de Aetobatus cf. narinari. Les organes reproducteurs femelles sont décrits en détail. L’extrémité distale de l’appareil copulateur sclérifié mâle, décrite en détail pour la première fois, montre un patron caractéristique de striations longitudinales sur son bord, qui pourrait être utile à l’avenir pour différencier cette espèce. Le développement des organes mâles et femelles chez les juvéniles est décrit; cela montre que la croissance de l’appareil copulateur sclérifié mâle commence par son extrémité basale et précède le développement du bulbe éjaculateur. Les spécimens de Nouvelle-Calédonie, Australie et Polynésie Française ont une morphologie et des mensurations similaires, en particulier pour la forme de l’extrémité distale de l’appareil copulateur sclérifié mâle. Ils sont aussi similaires à l’holotype, qui vient de l’Atlantique. Ceci suggère que tous les spécimens du Pacifique et de l’Atlantique appartiennent à une même espèce. T. pseudodasybatis ne peut donc pas être utilisé pour différencier les populations d’Aetobatus cf. narinari, peut-être parce que ce Monocotylidae n’est pas strictement spécifique.

     

Three nematode species from elasmobranchs off New Caledonia

Nematode specimens of three species, Terranova scoliodontis (Baylis, 1931) (Ascaridida, Anisakidae), Echinocephalus sinensis Ko, 1975 and E. overstreeti Deardorff & Ko, 1983 (both Spirurida, Gnathostomatidae) were collected from the tiger shark Galeocerdo cuvier, the ray Aetobatus cf. narinari and the blotched fantail ray Taeniura meyeni, respectively, from the coastal waters of New Caledonia, South Pacific. Their examination, including scanning electron microscopy (SEM), made it possible to obtain some new data on their morphology, e.g. in relation to the number and arrangement of male caudal papillae in T. scoliodontis and both Echinocephalus spp., the presence of ventral cuticular ornamentations in T. scoliodontis and the number of transverse spines on the cephalic bulb in Echinocephalus spp. All these species are reported for the first time from New Caledonian waters and G. cuvier is a new host species for T. scoliodontis. SEM examination of the fourth-stage larvae of E. overstreeti from the type-host showed the presence of anterior dorsal and ventral groups of minute spines on the cephalic bulb to be an important taxonomic feature for␣the interspecific distinction of Echinocephalus larvae and questions previous data on the occurrence of E. overstreeti larvae in many elasmobranch fishes and molluscs in Australian waters.

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Résumé Des Nématodes appartenant à trois espèces, Terranova scoliodontis (Baylis, 1931) (Ascaridida, Anisakidae), Echinocephalus sinensis Ko, 1975 et E. overstreeti Deardorff & Ko, 1983 (tous deux Spirurida, Gnathostomatidae) ont été collectés respectivement du requin tigre Galeocerdo cuvier et des raies Aetobatus cf. narinari et Taeniura meyeni, des eaux côtières de Nouvelle-Calédonie, Pacifique Sud. Leur étude, en particulier en microscopie électronique à balayage (MEB) a permis d’obtenir de nouvelles informations sur leur morphologie, par exemple sur le nombre et la disposition des papilles caudales mâles chez T. scoliodontis et␣les deux espèces d’Echinocephalus, la présence d’ornementations cuticulaires ventrales chez T. scoliodontis, et le nombre d’épines transversales sur le bulbe céphalique des Echinocephalus. Toutes ces espèces sont mentionnées pour la première fois des eaux de Nouvelle-Calédonie et G. cuvier est un nouvel hôte pour T.␣scoliodontis. L’examen au MEB de la larve de quatrième stade d’E. overstreeti, provenant de l’hôte-type, a montré que les groupes antérieurs et postérieurs de petites épines sur le bulbe céphalique sont un caractère taxonomique important pour la distinction interspécifique des larves d’Echinocephalus et met en doute des informations antérieures sur la présence de larves d’E. overstreeti chez de nombreux Élasmobranches et Mollusques des eaux d’Australie.

     

The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement

Complement is one of primary defense mechanisms against intravascular microorganisms and could play a role in the immune response to malignancy and hence its clinical behavior. We evaluated if the sole coding polymorphism of C1qA associates with outcome in patients with breast carcinoma. Genotyping for C1qA_[276A/G] was performed in 63 breast cancer subjects with localized tumor and compared with that in 38 breast cancer subjects with metastasis. Established risk factors for clinical outcome were considered and evaluated in multivariable analysis. Breast cancer subjects with heterozygous or homozygous C1qA_[276G] genotype had a higher rate of metastasis than subjects with the homozygous C1qA_[276A] genotype [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.1–4.1]. This association was stronger when only metastatic sites associated with hematogenous spread, i.e., to the bone, liver, and brain, were considered (HR 3.5, 95% CI 1.4–5.6) and remained statistically significant after adjustment for the number of positive lymph nodes, estrogen receptor status, and progesterone receptor status. There was no statistical difference in the C1qA_[276A/G] allelic distribution between all subjects with breast cancer and controls. These results suggest there could be an association of a single nucleotide polymorphism at position 276 of the C1qA component of complement with breast cancer metastasis to sites linked to hematogenous spread of disease. The C1qA polymorphism associated with decreased distant metastasis has also been correlated with an increased incidence of subcutaneous systemic lupus and C1q deficiencies, suggesting that an altered immune response may play a role in the observed association. Supported in part by National Institute of Health grant R21-CA90822, Friends You Can Count On! grant 1-87093-00, and the Woody and Louise White Cancer Research Fund.     

Thermodynamic stability, unfolding kinetics, and aggregation of the N-terminal actin-binding domains of utrophin and dystrophin

Muscular dystrophy (MD) is the most common genetic lethal disorder in children. Mutations in dystrophin trigger the most common form of MD, Duchenne, and its allelic variant Becker MD. Utrophin is the closest homologue and has been shown to compensate for the loss of dystrophin in human disease animal models. However, the structural and functional similarities and differences between utrophin and dystrophin are less understood. Both proteins interact with actin through their N-terminal actin-binding domain (N-ABD). In this study, we examined the thermodynamic stability and aggregation of utrophin N-ABD and compared with that of dystrophin. Our results show that utrophin N-ABD has spectroscopic properties similar to dystrophin N-ABD. However, utrophin N-ABD has decreased denaturant and thermal stability, unfolds faster, and is correspondingly more susceptible to proteolysis, which might account for its decreased in vivo half-life compared to dystrophin. In addition, utrophin N-ABD aggregates to a lesser extent compared with dystrophin N-ABD, contrary to the general behavior of proteins in which decreased stability enhances protein aggregation. Despite these differences in stability and aggregation, both proteins exhibit deleterious effects of mutations. When utrophin N-ABD mutations analogous in position to the dystrophin disease-causing mutations were generated, they behaved similarly to dystrophin mutants in terms of decreased stability and the formation of cross-β aggregates, indicating a possible role for utrophin mutations in disease mechanisms.     

Fish oil prevents high-saturated fat diet-induced impairments in adiponectin and insulin response in rodent soleus muscle

High saturated fatty acid (SFA) diets contribute to the development of insulin resistance, whereas fish oil-derived n-3 polyunsaturated fatty acids (PUFA) increase the secretion of adiponectin (Ad), an adipocyte-derived protein that stimulates fatty acid oxidation (FAO) and improves skeletal muscle insulin response. We sought to determine whether fish oil could prevent and/or restore high SFA diet-induced impairments in Ad and insulin response in soleus muscle. Sprague-Dawley rats were fed 1) a low-fat control diet (CON group), 2) high-SFA diet (SFA group), or 3) high SFA with n-3 PUFA diet (SFA/n-3 PUFA group). At 4 wk, CON and SFA/n-3 PUFA animals were terminated, and SFA animals were either terminated or fed SFA or SFA/n-3 PUFA for an additional 2 or 4 wk. The effect of diet on Ad-stimulated FAO, insulin-stimulated glucose transport, and expression of Ad, insulin and inflammatory signaling proteins was determined in the soleus muscle. Ad stimulated FAO in CON and 4 wk SFA/n-3 PUFA (+36%, +39%, respectively P ≤ 0.05) only. Insulin increased glucose transport in CON, 4 wk SFA/n-3 PUFA, and 4 wk SFA + 4 wk SFA/n-3 PUFA (+82%, +33%, +25%, respectively P ≤ 0.05); this effect was lost in all other groups. TLR4 expression was increased with 4 wk of SFA feeding (+24%, P ≤ 0.05), and this was prevented in 4 wk SFA/n-3 PUFA. Suppressor of cytokine signaling-3 expression was increased in SFA and SFA/n-3 PUFA (+33 and +18%, respectively, P ≤ 0.05). Our results demonstrate that fish oil can prevent high SFA diet-induced impairments in both Ad and insulin response in soleus muscle.     

Multiple Binding Sites on the Pyrin Domain of ASC Protein Allow Self-association and Interaction with NLRP3 Protein

A key process underlying an innate immune response to pathogens or cellular stress is activation of members of the NOD-like receptor family, such as NLRP3, to assemble caspase-1-activating inflammasome complexes. Activated caspase-1 processes proinflammatory cytokines into active forms that mediate inflammation. Activation of the NLRP3 inflammasome is also associated with common diseases including cardiovascular disease, diabetes, chronic kidney disease, and Alzheimer disease. However, the molecular details of NLRP3 inflammasome assembly are not established. The adaptor protein ASC plays a key role in inflammasome assembly. It is composed of an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain, which are protein interaction domains of the death fold superfamily. ASC interacts with NLRP3 via a homotypic PYD interaction and recruits procaspase-1 via a homotypic caspase recruitment domain interaction. Here we demonstrate that ASC PYD contains two distinct binding sites important for self-association and interaction with NLRP3 and the modulatory protein POP1. Modeling of the homodimeric ASC PYD complex formed via an asymmetric interaction using both sites resembles a type I interaction found in other death fold domain complexes. This interaction mode also permits assembly of ASC PYDs into filaments. Furthermore, a type I binding mode is likely conserved in interactions with NLRP3 and POP1, because residues critical for interaction of ASC PYD are conserved in these PYDs. We also demonstrate that ASC PYD can simultaneously self-associate and interact with NLRP3, rationalizing the model whereby ASC self-association upon recruitment to NLRP3 promotes clustering and activation of procaspase-1.     

Increased energy promotes size-based niche availability in marine mollusks

Variation in chemical energy, that is food availability, is posited to cause variation in body size. However, examinations of the relationship are rare and primarily limited to amniotes and zooplankton. Moreover, the relationship between body size and chemical energy may be impacted by phylogenetic history, clade-specific ecology, and heterogeneity of chemical energy in space and time. Considerable work remains to both document patterns in body size over gradients in food availability and understanding the processes potentially generating them. Here, we examine the functional relationship between body size and chemical energy availability over a broad assortment of marine mollusks varying in habitat and mobility. We demonstrate that chemical energy availability is likely driving body size patterns across habitats. We find that lower food availability decreases size-based niche availability by setting hard constraints on maximum size and potentially on minimum size depending on clade-specific ecology. Conversely, higher food availability promotes greater niche availability and potentially promotes evolutionary innovation with regard to size. We posit based on these findings and previous work that increases in chemical energy are important to the diversification of Metazoans through size-mediated niche processes.     

Calretinin interacts with huntingtin and reduces mutant huntingtin‐caused cytotoxicity

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expansion of CAG trinucleotide repeats encoding for polyglutamine (polyQ) in the huntingtin (Htt) gene. Despite considerable effort, the mechanisms underlying the toxicity of the mutated Htt protein remains largely uncertain. To identify novel therapeutic targets, we recently employed the approach of tandem affinity purification and discovered that calretinin (Cr), a member of the EF‐hand family of calcium‐binding proteins, is preferentially associated with mHtt, although it also interacts with wild‐type Htt. These observations were supported by coimmunoprecipitation and by colocalization of Cr with mHtt in neuronal cultures. Over‐ expression of Cr reduced mHtt‐caused cytotoxicity in both non‐neuronal and neuronal cell models of HD, whereas knockdown of Cr expression in the cells enhanced mHtt‐caused neuronal cell death. In addition, over‐expression of Cr was also associated with reduction of intracellular free calcium and activation of Akt. These results suggest that Cr may be a potential therapeutic target for treatment of HD.     

Matrilin-3 switches from anti- to pro-anabolic upon integration to the extracellular matrix

The extracellular matrix (ECM) has long been viewed primarily as an organized network of solid-phase ligands for integrin receptors. During degenerative processes, such as osteoarthritis, the ECM undergoes deterioration, resulting in its remodeling and in the release of some of its components. Matrilin-3 (MATN3) is an almost cartilage specific, pericellular protein acting in the assembly of the ECM of chondrocytes. In the past, MATN3 was found required for cartilage homeostasis, but also involved in osteoarthritis-related pro-catabolic functions. Here, to better understand the pathological and physiological functions of MATN3, its concentration as a circulating protein in articular fluids of human osteoarthritic patients was determined and its functions as a recombinant protein produced in human cells were investigated with particular emphasis on the physical state under which it is presented to chondrocytes. MATN3 down-regulated cartilage extracellular matrix (ECM) synthesis and up-regulated catabolism when administered as a soluble protein. When artificially immobilized, however, MATN3 induced chondrocyte adhesion via a α5β1 integrin-dependent mechanism, AKT activation and favored survival and ECM synthesis. Furthermore, MATN3 bound directly to isolated α5β1 integrin in vitro. TGFβ1 stimulation of chondrocytes allowed integration of exogenous MATN3 into their ECM and ECM-integrated MATN3 induced AKT phosphorylation and improved ECM synthesis and accumulation. In conclusion, the integration of MATN3 to the pericellular matrix of chondrocytes critically determines the direction toward which MATN3 regulates cartilage metabolism. These data explain how MATN3 plays either beneficial or detrimental functions in cartilage and highlight the important role played by the physical state of ECM molecules.