Unilateral radiographic presentation of autosomal dominant polycystic kidney disease is detected only rarely in infants and may suggest the presence of a complex cystic mass. We report such a case ...and review the literature concerning unilateral presentation of autosomal dominant polycystic kidney disease in infants and children.
Symbionts often exhibit significant reductions in genome complexity while pathogens often exhibit increased complexity through acquisition and diversification of virulence determinants. A few ...organisms have evolved complex life cycles in which they interact as symbionts with one host and pathogens with another. How the predicted and opposing influences of symbiosis and pathogenesis affect genome evolution in such instances, however, is unclear. The Polydnaviridae is a family of double-stranded (ds) DNA viruses associated with parasitoid wasps that parasitize other insects. Polydnaviruses (PDVs) only replicate in wasps but infect and cause severe disease in parasitized hosts. This disease is essential for survival of the parasitoid's offspring. Thus, a true mutualism exists between PDVs and wasps as viral transmission depends on parasitoid survival and parasitoid survival depends on viral infection of the wasp's host. To investigate how life cycle and ancestry affect PDVs, we compared the genomes of
Campoletis sonorensis ichnovirus (
CsIV) and
Microplitis demolitor bracovirus (
MdBV). CsIV and MdBV have no direct common ancestor, yet their encapsidated genomes share several features including segmentation, diversification of virulence genes into families, and the absence of genes required for replication. In contrast, CsIV and MdBV share few genes expressed in parasitized hosts. We conclude that the similar organizational features of PDV genomes reflect their shared life cycle but that PDVs associated with ichneumonid and braconid wasps have likely evolved different strategies to cause disease in the wasp's host and promote parasitoid survival.
We report a case in which papillary lesions developed in an ileal conduit that had been constructed for management of nonmalignant disease. Pathological diagnosis was nephrogenic adenoma, an entity ...previously thought to occur only in the urothelium. The pathogenesis of this unusual tumor is discussed.
Kidney formation requires the coordinated growth of multiple cell types including the collecting ducts, nephrons, vasculature and interstitium. There is a long-held belief that interactions between ...progenitors of the collecting ducts and nephrons are primarily responsible for kidney development. However, over the last several years, it has become increasingly clear that multiple aspects of kidney development require signaling from the interstitium. How the interstitium orchestrates these various roles is poorly understood. Here, we show that during development the interstitium is a highly heterogeneous patterned population of cells that occupies distinct positions correlated to the adjacent parenchyma. Our analysis indicates that the heterogeneity is not a mere reflection of different stages in a linear developmental trajectory but instead represents several novel differentiated cell states. Further, we find that β-catenin has a cell autonomous role in the development of a medullary subset of the interstitium and that this non-autonomously affects the development of the adjacent epithelia. These findings suggest the intriguing possibility that the different interstitial subtypes may create microenvironments that play unique roles in development of the adjacent epithelia and endothelia.
Chromosome studies were done on phytohemagglutinin‐stimulated peripheral blood from 17 patients with Sézary syndrome. A chromosomally abnormal clone was found in five patients: each patient had an ...abnormal chromosome 6 and four had an abnormal chromosome 1. Six patients without abnormal clones had more than 20% metaphases with random heteroploidy and sporadic structural anomalies. Only normal metaphases were seen in four patients, and no metaphases were found in two. Four of the five patients with an abnormal clone died, and their median survival from chromosome analysis was 6 months; only one of these patients died of lymphoma. The six patients with increased heteroploidy had long survivals and no apparent malignant process. Two of the four patients with normal metaphases died of malignant disease: one had lymphoma and the other squamous cell carcinoma. A third patient with normal chromosomes died of extensive visceral cutaneous T‐cell lymphoma.
Heritable symbionts are common in insects with many contributing to host defence. Hamiltonella defensa is a facultative, bacterial symbiont of the pea aphid, Acyrthosiphon pisum that provides ...protection against the endoparasitoid wasp Aphidius ervi. Protection levels vary among strains of H. defensa that are differentially infected by bacteriophages named APSEs. By contrast, little is known about mechanism(s) of resistance owing to the intractability of host-restricted microbes for functional study. Here, we developed methods for culturing strains of H. defensa that varied in the presence and type of APSE. Most H. defensa strains proliferated at 27°C in co-cultures with the TN5 cell line or as pure cultures with no insect cells. The strain infected by APSE3, which provides high levels of protection in vivo, produced a soluble factor(s) that disabled development of A. ervi embryos independent of any aphid factors. Experimental transfer of APSE3 also conferred the ability to disable A. ervi development to a phage-free strain of H. defensa. Altogether, these results provide a critical foundation for characterizing symbiont-derived factor(s) involved in host protection and other functions. Our results also demonstrate that phage-mediated transfer of traits provides a mechanism for innovation in host restricted symbionts.
Ingestion of vertebrate blood is essential for egg maturation and transmission of disease-causing parasites by female mosquitoes. Prior studies with the yellow fever mosquito, Aedes aegypti, ...indicated blood feeding stimulates egg production by triggering the release of hormones from medial neurosecretory cells in the mosquito brain. The ability of bovine insulin to stimulate a similar response further suggested this trigger is an endogenous insulin-like peptide (ILP). A. aegypti encodes eight predicted ILPs. Here, we report that synthetic ILP3 dose-dependently stimulated yolk uptake by oocytes and ecdysteroid production by the ovaries at lower concentrations than bovine insulin. ILP3 also exhibited metabolic activity by elevating carbohydrate and lipid storage. Binding studies using ovary membranes indicated that ILP3 had an IC₅₀ value of 5.9 nM that was poorly competed by bovine insulin. Autoradiography and immunoblotting studies suggested that ILP3 binds the mosquito insulin receptor (MIR), whereas loss-of-function experiments showed that ILP3 activity requires MIR expression. Overall, our results identify ILP3 as a critical regulator of egg production by A. aegypti.
Heparin is known to influence the growth, proliferation, and migration of vascular cells, but the precise mechanisms are unknown. We previously demonstrated that unfractionated heparin (UH) binds to ...the platelet integrin αIIbβ3, and enhances ligand binding. To help define the specificity and site(s) of heparin-integrin interactions, we employed the erythroleukemic K562 cell line, transfected to express specific integrins (αvβ3, αvβ5, and αIIbβ3). By comparing K562 cells expressing a common α subunit (Kαvβ3, Kαvβ5) with cells expressing a common β subunit (Kαvβ3, KαIIbβ3), we observed that heparin differentially modulated integrin-mediated adhesion to vitronectin. UH at 0.5-7.5 μg ml consistently enhanced the adhesion of β3expressing cells (Kαvβ3,KαIIbβ3). In contrast, UH at 0.5-7.5 μg ml inhibited Kαvβ5adhesion. Experiments using integrin-blocking antibodies, appropriate control ligands, and nontransfected native K562 cells revealed that heparin's actions were mediated by the specific integrins under study. Preincubation of heparin with Kαvβ3cells enhanced adhesion, while preincubation of heparin with the adhesive substrate (vitronectin) had minimal effect. There was a structural specificity to heparin's effect, in that a low molecular weight heparin and chondroitin sulfate showed significantly less enhancement of adhesion. These findings suggest that heparin's modulation of integrin-ligand interactions occurs through its action on the integrin. The inhibitory or stimulatory effects of heparin depend on the β subunit type, and the potency is dictated by structural characteristics of the glycosaminoglycan.
Summary There is a greater prevalence of neuroinflammatory diseases in females than males. Microglia, the major immunocompetent cells of the central nervous system, play a key role in ...neuroinflammation. We aimed to determine if inherent differences in toll-like receptor 4 mediated pro-inflammatory response in glia could possibly contribute to the skewed female prevalence of neuroinflammatory disorders. In addition, in order to identify if estradiol (E2), the major female sex steroid contributes to a heightened pro-inflammatory response, estradiol was added both in vivo and in vitro . Microglia and astrocytes were isolated from neonatal pups and stimulated with lipopolysaccharide (LPS) in the presence and absence of E2. Hippocampal microglia were isolated from adult male and female rats and stimulated ex vivo with LPS. Male neonatal microglia and astrocytes produced greater IL-1β mRNA than females. However, when co-incubated with varying doses of estradiol (E2), the E2 produced anti-inflammatory effects in the male microglia but a pro-inflammatory effect in female microglia. LPS-induced IL-1β mRNA was attenuated by E2 in female but not male adult hippocampal microglia. However, females supplemented with E2 in vivo produced a potentiated IL-1β mRNA response. TLR4 mRNA was decreased by LPS in both microglia and astrocytes but was not affected by sex or E2. CD14 mRNA was increased by LPS and may be elevated more in females than males in microglia but not astrocytes. Therefore, sexual dimorphic differences do occur in both neonatal and adult microglia though maturity of the microglia at the time of isolation influences the pro-inflammatory response.
The role of bivalve mariculture in the CO₂ cycle has been commonly evaluated as the balance between respiration, shell calcium carbonate sequestration and CO₂ release during biogenic calcification. ...However, this approach neglects the ecosystem implications of cultivating bivalves at high densities, e.g. the impact on phytoplankton dynamics and benthic–pelagic coupling, which can significantly contribute to the CO₂ cycle. Therefore, an ecosystem approach that accounts for the trophic interactions of bivalve aquaculture, including dissolved and particulate organic and inorganic carbon cycling, is needed to provide a rigorous assessment of the role of bivalve mariculture in the CO₂ cycle. On the other hand, the discussion about the inclusion of shells of cultured bivalves into the carbon trading system should be framed within the context of ecosystem goods and services. Humans culture bivalves with the aim of producing food, not sequestering CO₂ in their shells, therefore the main ecosystem good provided by bivalve aquaculture is meat production, and shells should be considered as by-products of this human activity. This reasoning provides justification for dividing up respired CO₂ between meat and shell when constructing a specific bivalve CO₂ budget for potential use of bivalve shells in the carbon trading system. Thus, an integrated ecosystem approach, as well as an understanding of the ecosystems goods and services of bivalve aquaculture, are 2 essential requisites for providing a reliable assessment of the role of bivalve shells in the CO₂ cycle.
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