High-Protein Diet Induces Hyperuricemia in a New Animal Model for Studying Human Gout.

Hyperuricemia is a central risk factor for gout and increases the risk for other chronic diseases, including cardiometabolic disease, kidney disease, and hypertension. Overproduction of urate is one of the main reasons for hyperuricemia, and dietary factors including seafoods, meats, and drinking are contributed to the development of it. However, the lack of a suitable animal model for urate metabolism is one of the main reasons for the delay and limitations of hyperuricemia research. Combining evolutionary biological studies and clinical studies, we conclude that chicken is a preferred animal model for hyperuricemia. Thus, we provided chickens a high-protein diet (HPD) to evaluate the changes in the serum urate levels in chickens. In our study, the HPD increased the serum urate level and maintained it at a long-term high level in chickens. Long-term high serum urate levels induced an abnormal chicken claw morphology and the precipitation of monosodium urate (MSU) in joint synovial fluid. In addition, a long-term HPD also decreased the glomerular filtration rate and induced mild renal injury. Most importantly, allopurinol and probenecid displayed the positive effects in decreasing serum urate and then attenuated hyperuricemia in chicken model. These findings provide a novel model for hyperuricemia and a new opportunity to further investigate the effects of long-term hyperuricemia on other metabolic diseases.

The DSL ligand APX-1 is required for normal ovulation in C. elegans.

DSL ligands activate the Notch receptor in many cellular contexts across metazoa to specify cell fate. In addition, Notch receptor activity is implicated in post-mitotic morphogenesis and neuronal function. In C. elegans, the DSL family ligand APX-1 is expressed in a subset of cells of the proximal gonad lineage, where it can act as a latent proliferation-promoting signal to maintain proximal germline tumors. Here we examine apx-1 in the proximal gonad and uncover a role in the maintenance of normal ovulation. Depletion of apx-1 causes an endomitotic oocyte (Emo) phenotype and ovulation defects. We find that lag-2 can substitute for apx-1 in this role, that the ovulation defect is partially suppressed by loss of ipp-5, and that lin-12 depletion causes a similar phenotype. In addition, we find that the ovulation defects are often accompanied by a delay of spermathecal distal neck closure after oocyte entry. Although calcium oscillations occur in the spermatheca, calcium signals are abnormal when the distal neck does not close completely. Moreover, oocytes sometimes cannot properly transit through the spermatheca, leading to fragmentation of oocytes once the neck closes. Finally, abnormal oocytes and neck closure defects are seen occasionally when apx-1 or lin-12 activity is reduced in adult animals, suggesting a possible post-developmental role for APX-1 and LIN-12 signaling in ovulation.

[Morphological abnormalities in the cibarium of Lutzomyia evansi (Diptera: Psychodidae, Phlebotominae) caught in Trujillo, Venezuela]. / Anomalías morfológicas en los dientes del cibario de Lutzomyia evansi (Diptera: Psychodidae) en el estado Trujillo, Venezuela.

INTRODUCTION: Lutzomyia evansi is a recognized vector of Leishmania infantum in Colombia and Venezuela. OBJECTIVE: To describe and illustrate the morphological abnormalities in Lu. evansi females captured in a rural focus of visceral leishmaniasis in Trujillo, Venezuela. MATERIALS AND METHODS: Phlebotomine sand flies were collected using CDC light traps, Shannon traps and aspiration in resting places. The identification was performed according to Young & Duncan (1994) and drawings were made using a microscope with camara lucida . RESULTS: Abnormalities in the cibarium of Lu. evansi were detected in 4 (0.12%) females of the 3,477 adults that were studied. CONCLUSION: Lutzomyia evansi can have uncommon morphological variants associated with an increase in the number of teeth in the cibarium and their arrangement, which may lead to errors in the taxonomic identification of anomalous specimens. The study of such deformities can serve to avoid taxonomic identification errors.

Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/ß-catenin signaling.

Receptor-like tyrosine kinase (RYK) functions as a transmembrane receptor for the Wnt family of secreted protein ligands. Although RYK undergoes endocytosis in response to Wnt, the mechanisms that regulate its internalization and concomitant activation of Wnt signaling are unknown. We discovered that RYK both physically and functionally interacts with the E3 ubiquitin ligase Mindbomb 1 (MIB1). Overexpression of MIB1 promotes the ubiquitination of RYK and reduces its steady-state levels at the plasma membrane. Moreover, we show that MIB1 is sufficient to activate Wnt/ß-catenin (CTNNB1) signaling and that this activity depends on endogenous RYK. Conversely, in loss-of-function studies, both RYK and MIB1 are required for Wnt-3A-mediated activation of CTNNB1. Finally, we identify the Caenorhabditis elegans orthologue of MIB1 and demonstrate a genetic interaction between ceMIB and lin-18/RYK in vulva development. These findings provide insights into the mechanisms of Wnt/RYK signaling and point to novel targets for the modulation of Wnt signaling.

Micro-structure and chemical composition of vateritic deformities occurring in the bivalve Corbicula fluminea (Müller, 1774).

Vateritic deformities occurring in the invasive heterodont bivalve Corbicula fluminea from several locations in the UK were characterised in detail for the first time using scanning electron microscopy, X-ray diffraction and different geochemical techniques (electron microprobe, ICP-AES, and mass spectrometry). Large volumes of vaterite are produced abnormally in the animals' shells in the form of yellow-green bulges. These are distinguished from the aragonitic parts of the shell by their characteristic micro-structures, content of organic material, trace elemental composition and carbon stable isotope signatures. The most commonly observed micro-structures include columnar vaterite, lamellar vaterite and different irregular structures occurring in all parts of the shell. There are indications that organic material is present largely as intracrystalline impurities or nano-scale phases and not as envelopes around microstructural units. These micro-structures are novel, nothing equivalent having yet been described for other vateritic systems. Euhedral vaterite crystals also occur occasionally. The vaterite has generally higher Mg/Ca and lower Na/Ca, K/Ca than the aragonite. In addition, δ¹³C is also always lower. Microstructural characteristics would suggest loss of biological control probably due to physiological stress(es) inducing the switch to vaterite production. The vaterite might be stabilised by its higher content of organic material and magnesium.

Zebrafish type XVII collagen: gene structures, expression profiles, and morpholino "knock-down" phenotypes.

The human COL17A1 gene encodes type XVII collagen (also known as the 180-kDa bullous pemphigoid antigen), an integral component of hemidesmosomes, attachment complexes providing integrity to the dermal-epidermal junction. Zebrafish, a useful model system to study skin development, displays fully developed hemidesmosomes at approximately 5 days post-fertilization (dpf). We have identified two COL17A1 orthologues in the zebrafish genome, col17a1a and col17a1b, which are expressed in the skin and the neural system, respectively. The proteins coded by these genes have structural module organizations homologous to the human type XVII collagen. "Knock-down" of the expression of col17a1a with a specific morpholino targeting the 5' UTR of the gene resulted in a blistering phenotype and in perturbations in the basement membrane zone. "Knock-down" of col17a1b expression resulted in ablation or in marked reduction of neuromasts in the lateral line. Thus, zebrafish has two COL17A1 orthologues which may have evolved tissue-specific functions during vertebrate development. Collectively, zebrafish provides a model system to study the molecular aspects of skin development and offers insights into the corresponding human diseases.

Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice.

The protease a disintegrin and metalloprotease (ADAM) 17 cleaves tumor necrosis factor (TNF), L-selectin, and epidermal growth factor receptor (EGF-R) ligands from the plasma membrane. ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer. ADAM17-deficient mice are not viable. Conditional ADAM17 knockout models demonstrated proinflammatory activities of ADAM17 in septic shock via shedding of TNF. We used a novel gene targeting strategy to generate mice with dramatically reduced ADAM17 levels in all tissues. The resulting mice called ADAM17(ex/ex) were viable, showed compromised shedding of ADAM17 substrates from the cell surface, and developed eye, heart, and skin defects as a consequence of impaired EGF-R signaling caused by failure of shedding of EGF-R ligands. Unexpectedly, although the intestine of unchallenged homozygous ADAM17(ex/ex) mice was normal, ADAM17(ex/ex) mice showed substantially increased susceptibility to inflammation in dextran sulfate sodium colitis. This was a result of impaired shedding of EGF-R ligands resulting in failure to phosphorylate STAT3 via the EGF-R and, consequently, in defective regeneration of epithelial cells and breakdown of the intestinal barrier. Besides regulating the systemic availability of the proinflammatory cytokine TNF, our results demonstrate that ADAM17 is needed for vital regenerative activities during the immune response. Thus, our mouse model will help investigate ADAM17 as a potential drug target.

Jun and JunD-dependent functions in cell proliferation and stress response.

Jun is essential for fetal development, as fetuses lacking Jun die at mid-gestation with multiple cellular defects in liver and heart. Embryos expressing JunD in place of Jun (Jun(d/d)) can develop to term with normal fetal livers, but display cardiac defects as observed in fetuses lacking Jun. Jun(d/d) mouse embryonic fibroblasts (MEFs) exhibit early senescence, which can be rescued by EGF and HB-EGF stimulation, probably through activation of Akt signaling. Thus, JunD cannot functionally replace Jun in regulating fibroblast proliferation. In Jun(-/-) fetal livers, increased hydrogen peroxide levels are detected and expression of Nrf1 and Nrf2 (nuclear erythroid 2-related transcription factors) is downregulated. Importantly, increased oxidative stress as well as expression of Nrf1 and Nrf2 is rescued by JunD in Jun(d/d) fetal livers. These data show that Jun is of critical importance for cellular protection against oxidative stress in fetal livers and fibroblasts, and Jun-dependent cellular senescence can be restored by activation of the epidermal growth factor receptor pathway.

[Bilateral anomaly in the style of Sciopemyia sordellii (Shannon & Del Ponte) (Diptera, Psychodidae)]. / Anomalia bilateral no gonóstilo de Sciopemyia sordellii (Shannon & Del Ponte) (Diptera, Psychodidae).

This paper presents a male specimen of Sciopemyia sordellii with a rare bilateral anomaly, consisting in eight spines in a style and five in the other. Tis species has four spines in each style as its normal number. The specimen was captured using a CDC light trap, in a forested area in the State Park "Floresta Estadual Edmundo Navarro de Andrade", in May 2004, located in the city of Rio Claro, São Paulo State, Brazil. Similar anomaly was once described but this is the first specimen found with a bilateral alteration. It may cause confusion in taxonomic identification and even lead to description of new species, increasing the number of synonymies.

Anomalia bilateral no gonóstilo de Sciopemyia sordellii (Shannon & Del Ponte) (Diptera, Psychodidae) / Bilateral anomaly in the style of Sciopemyia sordellii (Shannon & Del Ponte) (Diptera, Psychodidae)

Relata-se o encontro de um exemplar macho da espécie Sciopemyia sordellii (Shannon & Del Ponte, 1927) com uma rara anomalia, apresentando oito espinhos em um gonóstilo e cinco no outro. Para essa espécie, o número de espinhos normalmente esperado em cada gonóstilo é quatro. O espécime foi capturado por meio de armadilha luminosa automática do tipo CDC, em área de mata da Floresta Estadual Edmundo Navarro de Andrade, em maio de 2004, no município de Rio Claro, Estado de São Paulo. Anomalia semelhante já foi relatada nessa espécie, sendo pela primeira vez encontrada bilateralmente. Tais achados podem causar confusão na identificação específica e levar à descrição de novas espécies, aumentando a lista de sinonímias do grupo.

This paper presents a male specimen of Sciopemyia sordellii with a rare bilateral anomaly, consisting in eight spines in a style and five in the other. This species has four spines in each style as its normal number. The specimen was captured using a CDC light trap, in a forested area in the State Park "Floresta Estadual Edmundo Navarro de Andrade", in May 2004, located in the city of Rio Claro, São Paulo State, Brazil. Similar anomaly was once described but this is the first specimen found with a bilateral alteration. It may cause confusion in taxonomic identification and even lead to description of new species, increasing the number of synonymies.

Craniofacial cartilage morphogenesis requires zebrafish col11a1 activity.

The zebrafish ortholog of the human COL11A1 gene encoding the cartilage collagen XI proalpha1 chain was characterized to explore its function in developing zebrafish using the morpholino-based knockdown strategy. We showed that its expression in zebrafish is developmentally regulated. A low expression level was detected by real-time PCR during the early stages of development. At 24 hpf, a sharp peak of expression was observed. At that stage, in situ hybridization indicated that col11a1 transcripts are restricted to notochord. At 48 hpf, they were exclusively detected in the craniofacial skeleton, endoskeleton of pectoral fins and in otic vesicles. Collagen XI alpha1-deficient zebrafish embryos developed defects in craniofacial cartilage formation and in notochord morphology. Neural crest specification and mesenchymal condensation occurred normally in morpholino-injected embryos. Col11a1 depletion affected the spatial organization of chondrocytes, the shaping of cartilage elements, and the maturation of chondrocytes to hypertrophy. Knockdown of col11a1 in embryos stimulated the expression of the marker of chondrocyte differentiation col2a1, resulting in the deposit of abnormally thick and sparse fibrils in the cartilage extracellular matrix. The extracellular matrix organization of the perichordal sheath was also altered and led to notochord distortion. The data underscore the importance of collagen XI in the development of a functional cartilage matrix. Moreover, the defects observed in cartilage formation resemble those observed in human chondrodysplasia such as the Stickler/Marshall syndrome. Zebrafish represent a novel reliable vertebrate model for collagen XI collagenopathies.

Defect of hepatocyte growth factor activator inhibitor type 1/serine protease inhibitor, Kunitz type 1 (Hai-1/Spint1) leads to ichthyosis-like condition and abnormal hair development in mice.

Hepatocyte growth factor activator inhibitor type 1 (HAI-1)/serine protease inhibitor, Kunitz type 1 (SPINT1) is a membrane-bound, serine proteinase inhibitor initially identified as an inhibitor of hepatocyte growth factor activator. It also inhibits matriptase and prostasin, both of which are membrane-bound serine proteinases that have critical roles in epidermal differentiation and function. In this study, skin and hair phenotypes of mice lacking the Hai-1/Spint1 gene were characterized. Previously, we reported that the homozygous deletion of Hai-1/Spint1 in mice resulted in embryonic lethality attributable to impaired placental development. To test the role of Hai-1/Spint1 in mice, the placental function of Hai-1/Spint1-mutant mice was rescued. Injection of Hai-1/Spint1(+/+) blastocysts with Hai-1/Spint1(-/-) embryonic stem cells successfully generated high-chimeric Hai-1/Spint1(-/-) embryos (B6Hai-1(-/-High)) with normal placentas. These embryos were delivered without apparent developmental abnormalities, confirming that embryonic lethality of Hai-1/Spint1(-/-) mice was caused by placental dysfunction. However, newborn B6Hai-1(-/-High) mice showed growth retardation and died by 16 days. These mice developed scaly skin because of hyperkeratinization, reminiscent of ichthyosis, and abnormal hair shafts that showed loss of regular cuticular septation. The interfollicular epidermis showed acanthosis with enhanced Akt phosphorylation. Immunoblot analysis revealed altered proteolytic processing of profilaggrin in Hai-1/Spint1-deleted skin with impaired generation of filaggrin monomers. These findings indicate that Hai-1/Spint1 has critical roles in the regulated keratinization of the epidermis and hair development.

An antennal-specific role for bowl in repressing supernumerary appendage development in Drosophila.

In Drosophila, antennae and legs are serially homologous appendages, and yet they develop into organs of very different structure and function. This implies that different genetic mechanisms operate onto a common developmental ground state to produce antennae and legs. Still few such mechanisms have been uncovered. During leg development, bowl, a member of the odd-skipped gene family, has been shown to participate in the formation of the leg segmental joints. Here we report that, in the antennal disc, bowl has a dramatically different role: bowl is expressed in the ventral antennal disc to prevent inappropriate expression of wg early during development. The removal of bowl function leads to the activation of wg in the dpp-expressing domain. This ectopic expression of wg, together with dpp, results in a new proximo-distal axis that promotes non-autonomous antennal duplications. The role of bowl in suppressing a supernumerary PD axis is maintained even when the antennal disc is homeotically transformed into a leg-like appendage. Therefore, bowl is part of a genetic program that suppresses the formation of supernumerary appendages specifically in the fly's head.

Gynomorphic mandible morphology in the dobsonfly, Corydalus cornutus.

Two aberrant males of Corydalus cornutus (L.) (Insecta: Megaloptera), which exhibit unusually short mandibles with discrete dentition, are recorded from a locality in Missouri. Morphological details of the specimens, as well as implications for the overall morphological variation of the genus and species are discussed. The term gynomorphic is suggested as the best descriptor of this case, given that little explanatory information is available to classify these specimens as true gynandromorphs.

Diseases, lesions and malformations in the long-beaked common dolphin Delphinus capensis from the Southeast Pacific.

Miscellaneous lesions of the head, skull, teeth, trunk, appendages, skin and genital tract were observed in 120 of 930 long-beaked common dolphins Delphinus capensis taken in fisheries off Peru between 1985 and 2000. Seven subsamples were defined according to the varying field sampling protocols. Forty-two dolphins showed at least 2 types of injuries or diseases affecting 1 or more organs. The majority (5 of 7) of traumas encountered were diagnosed as caused by violent, fisheries-related interactions, and the skin in 20.4 % of specimens (n = 54) showed healed scars from such interactions. Prevalences of malformations and traumas of crania (n = 103) were 2.9 and 1.9%, respectively. Lytic cranial lesions were present in 31.1% of dolphins (n = 103) and accounted for 84.2% of all bone injuries. Skull damage diagnostic for Crassicauda sp. infestation was encountered in 26.5% of dolphins (n = 98) and did not differ among sex and age classes. Crassicauda sp. and tooth infections were responsible for, respectively, 78.8 and 6.1% of the lytic lesions. Adult dolphins showed a high prevalence of worn and broken teeth (35%, n = 20) as well as damaged alveoli (20%, n = 70). Prevalence of 'paired teeth', a congenital condition, was 9.4% (n = 32). Lesions of the head, body and appendages were present in 10 dolphins and included traumas, deformations (e.g. scoliokyphosis and brachygnathia) and chronic mastitis. Ovarian cysts suggestive of follicular cysts were observed in 1 of 24 females. Chronic orchitis affected 1 of 78 males. Of 12 dolphins 2 had vesicular lesions of the penis. Prevalence of cutaneous lesions, abnormalities and scars ranged between 1.8% (n = 56) and 48.2% (n = 27).

[Local anomalies in ticks larvae (Acari: Ixodida)]. / Anomalie lokalne u larw kleszczy (Acari: Ixodida).

Three anomalies in the anus structure of Hyalomma marginatum marginatum larvae, two anomalies in Argas reflexus larvae, i.e. the lack of the left chelicera and the second pair of limbs at the right side, and disorder in chetotaxy of Argas persicus larvae were examined in this research. These anomalies have not been described so far in the literature.

[The cases of teratology in Mallophaga of South Africa]. / Przypadki teratologii wsród wszolów (Mallophaga) z Afryki poludniowej.

The following types ofteratology were found in the collection of 1278 individuals of Mallophaga coming from the birds of South Africa origin: deformity clypeus in Quadraceps kilimandjarensis (KELL.) from Stephanibyx coronatus (BURCH.), partial atrophy of one of the antennae of two males Q. kilimandjarensis and abdomen plates deformity of two females Q. kilimandjarensis, in male and female Quadraceps chorleyi TIMM. from Hoplopterus armatus (BURCH.), in female Saemundssonia africana TIMM. from Stephanibyx coronatus (BODD.) and male Plegadiphilus threskiornis (BEDF.) from Threskiornis aethiopicus (LATH.) the only representative of Amblycera (the other teratology belonged to Ischnocera suborder). Generally teratology was found in 0.70% of the collection.

Decapod crustacean chelipeds: an overview.

The structure, growth, differentiation and function of crustacean chelipeds are reviewed. In many decapod crustaceans growth of chelae is isometric with allometry level reaching unity till the puberty moult. Afterwards the same trend continues in females, while in males there is a marked spurt in the level of allometry accompanied by a sudden increase in the relative size of chelae. Subsequently they are differentiated morphologically into crusher and cutter making them heterochelous and sexually dimorphic. Of the two, the major chela is used during agonistic encounters while the minor is used for prey capture and grooming. Various biotic and abiotic factors exert a negative effect on cheliped growth. The dimorphic growth pattern of chelae can be adversely affected by factors such as parasitic infection and substrate conditions. Display patterns of chelipeds have an important role in agonistic and aggressive interactions. Of the five pairs of pereiopods, the chelae are versatile organs of offence and defence which also make them the most vulnerable for autotomy. Regeneration of the autotomized chelipeds imposes an additional energy demand called "regeneration load" on the incumbent, altering energy allocation for somatic and/or reproductive processes. Partial withdrawal of chelae leading to incomplete exuviation is reported for the first time in the laboratory and field in Macrobrachium species.