Venestatin from parasitic helminths interferes with receptor for advanced glycation end products (RAGE)-mediated immune responses to promote larval migration

Parasitic helminths can reside in humans owing to their ability to disrupt host protective immunity. Receptor for advanced glycation end products (RAGE), which is highly expressed in host skin, mediates inflammatory responses by regulating the expression of pro-inflammatory cytokines and endothelial adhesion molecules. In this study, we evaluated the effects of venestatin, an EF-hand Ca²⁺-binding protein secreted by the parasitic helminth Strongyloides venezuelensis, on RAGE activity and immune responses. Our results demonstrated that venestatin bound to RAGE and downregulated the host immune response. Recombinant venestatin predominantly bound to the RAGE C1 domain in a Ca²⁺-dependent manner. Recombinant venestatin effectively alleviated RAGE-mediated inflammation, including footpad edema in mice, and pneumonia induced by an exogenous RAGE ligand. Infection experiments using S. venezuelensis larvae and venestatin silencing via RNA interference revealed that endogenous venestatin promoted larval migration from the skin to the lungs in a RAGE-dependent manner. Moreover, endogenous venestatin suppressed macrophage and neutrophil accumulation around larvae. Although the invasion of larvae upregulated the abundance of RAGE ligands in host skin tissues, mRNA expression levels of tumor necrosis factor-α, cyclooxygenase-2, endothelial adhesion molecules vascular cell adhesion protein-1, intracellular adhesion molecule-1, and E-selectin were suppressed by endogenous venestatin. Taken together, our results indicate that venestatin suppressed RAGE-mediated immune responses in host skin induced by helminthic infection, thereby promoting larval migration. The anti-inflammatory mechanism of venestatin may be targeted for the development of anthelminthics and immunosuppressive agents for the treatment of RAGE-mediated inflammatory diseases.     

Development of the external genitalia in fetuses of the southern minke whale, Balaenoptera acutorostrata

The developmental changes of the anogenital distance and external genitalia were studied in 81 fetuses of the southern minke whale. It was difficult to sex the fetuses with less than 55.8 mm crown-rump length (CRL) even by histological means, but it was easy in the fetuses with more than 77.0 mm CRL and less than 110.0 mm CRL. The histologically determined male fetuses had a ratio of anogenital distance to CRL or body length of more than 5%, while females had a value of less than 4%. At later stages with a CRL of more than 113.0 mm, male fetuses had an umbilicus-directed genital tubercle, while in females a tail-directed tubercle was observed. The present study suggests that the stage with sexual dimorphism might be earlier in the southern minke whale than that previously reported.     

Deglycosylation and label-free quantitative LC-MALDI MS applied to efficient serum biomarker discovery of lung cancer

Background  

Serum is an ideal source of biomarker discovery and proteomic profiling studies are continuously pursued on serum samples. However, serum is featured by high level of protein glycosylations that often cause ionization suppression and confound accurate quantification analysis by mass spectrometry. Here we investigated the effect of N-glycan and sialic acid removal from serum proteins on the performance of label-free quantification results.     

Lifespan of Commodities,Part II

Lifespan of commodities is essential information for material flow analysis and material stock accounting. Lifespan data is available in the literature; however, it varies in definition and in methodology employed. This article reviews and categorizes different types of lifespan distribution and distribution estimation methodologies, and investigates the relationship and differences between lifespan definitions and estimation methodologies. Lifespan distribution of commodities can be classified into five types from two perspectives: base year for which the distribution is drawn, and vertical axis of the distribution. The methodologies for estimating lifespan distribution were classified into four types and the details of each methodology and the relationship to the definition of lifespan were also clarified. This article also examines differences in actual lifespan data—between the types of distribution, the definitions, and the employed methodologies—by comparing reported data in literature. Any of the four methodologies are theoretically applicable and provide the same value of a lifespan; however unless accurate data such as census statistics are available, lifespan data can vary, and therefore we must be very cautious about the representativeness of sample data.     

Lifespan of Commodities,Part I

Lifespan is an essential parameter for the accounting and analysis of material stocks and flows, one of the main research topics in industrial ecology. Lifespan is also important as a parameter that portrays the current and historical situation of industrial metabolism, which is an area of interest to industrial ecologists. In the present article, the available information from various reports on product lifespan was reviewed. Although we found a large number of data for many durables, the definition of lifespan in published articles varied, which limited our ability to compare reported values. We therefore first defined lifespan and then compared the international and historical data. We compiled more than 1,300 data sets from various sources and identified some differences among the types of goods and among regions. With the reviewed data noted in this article, we established a database, named LiVES (Lifespan Database for Vehicles, Equipment, and Structures), and will disclose it on the Internet to share the information.     

5-Oxo-eicosatetraenoic acid-induced chemotaxis: identification of a responsible receptor hGPCR48 and negative regulation by G protein G(12/13)

While screening genes encoding G protein-coupled receptors (GPCRs) in the human genome, we and other groups have identified a GPCR named hGPCR48 as a high affinity receptor for 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is arachidonic acid metabolite and an endogenous chemoattractant for granulocytes. Using Chinese hamster ovary (CHO) cells stably expressing hGPCR48, we show here that activation of the receptor causes the chemotaxis of the cells toward 5-oxo-ETE. We also show that the chemotaxis of human granulocytes toward 5-oxo-ETE is inhibited by pretreatment with anti-hGPCR48 antibodies, indicating that hGPCR48 is an endogenous receptor responsible for chemotaxis of granulocytes toward 5-oxo-ETE. In addition, we show that the chemotaxis of CHO cells expressing hGPCR48 is suppressed by pretreatment with pertussis toxin, and enhanced by overexpression of the carboxy terminal peptides of Galpha (12/13) subunits or a regulator of the G protein signaling domain of p115RhoGEF, both of which are known to suppress G(12/13)-dependent signaling pathways. These results indicate that hGPCR48 couples with G(i/o) and G(12/13) proteins, which then initiate or attenuate the chemotaxis of the cells toward 5-oxo-ETE, respectively.     

Reactive oxygen species play a role in regulating a fungus-perennial ryegrass mutualistic interaction

Although much is known about the signals and mechanisms that lead to pathogenic interactions between plants and fungi, comparatively little is known about fungus-plant mutualistic symbioses. We describe a novel role for reactive oxygen species (ROS) in regulating the mutualistic interaction between a clavicipitaceous fungal endophyte, Epichlo? festucae, and its grass host, Lolium perenne. In wild-type associations, E. festucae grows systemically in intercellular spaces of leaves as infrequently branched hyphae parallel to the leaf axis. A screen to identify symbiotic genes isolated a fungal mutant that altered the interaction from mutualistic to antagonistic. This mutant has a single-copy plasmid insertion in the coding region of a NADPH oxidase gene, noxA. Plants infected with the noxA mutant lose apical dominance, become severely stunted, show precocious senescence, and eventually die. The fungal biomass in these associations is increased dramatically, with hyphae showing increased vacuolation. Deletion of a second NADPH oxidase gene, noxB, had no effect on the E. festucae-perennial ryegrass symbiosis. ROS accumulation was detected cytochemically in the endophyte extracellular matrix and at the interface between the extracellular matrix and host cell walls of meristematic tissue in wild-type but not in noxA mutant associations. These results demonstrate that fungal ROS production is critical in maintaining a mutualistic fungus-plant interaction.     

Application of chaotic dynamics in a recurrent neural network to control: hardware implementation into a novel autonomous roving robot

Originating from a viewpoint that complex/chaotic dynamics would play an important role in biological system including brains, chaotic dynamics introduced in a recurrent neural network was applied to control. The results of computer experiment was successfully implemented into a novel autonomous roving robot, which can only catch rough target information with uncertainty by a few sensors. It was employed to solve practical two-dimensional mazes using adaptive neural dynamics generated by the recurrent neural network in which four prototype simple motions are embedded. Adaptive switching of a system parameter in the neural network results in stationary motion or chaotic motion depending on dynamical situations. The results of hardware implementation and practical experiment using it show that, in given two-dimensional mazes, the robot can successfully avoid obstacles and reach the target. Therefore, we believe that chaotic dynamics has novel potential capability in controlling, and could be utilized to practical engineering application.     

Identification and Characterization of Sulfated Carbohydrate-Binding Protein from Lactobacillus reuteri

We previously purified a putative sulfated-galactosylceramide (sulfatide)-binding protein with a molecular weight of 47 kDa from the cell surface of Lactobacillus reuteri JCM1081. The aim of this study was to identify the 47-kDa protein, examine its binding to sulfated glycolipids and mucins, and evaluate its role in bacterial adhesion to mucosal surfaces. By cloning and sequencing analysis, the 47-kDa protein was identified as elongation factor-Tu (EF-Tu). Adhesion properties were examined using 6×Histidine-fused EF-Tu (His₆-EF-Tu). Surface plasmon resonance analysis demonstrated pH-dependent binding of His₆-EF-Tu to sulfated glycolipids, but not to neutral or sialylated glycolipids, suggesting that a sulfated galactose residue was responsible for EF-Tu binding. Furthermore, His₆-EF-Tu was found to bind to porcine gastric mucin (PGM) by enzyme-linked immunosorbent assay. Binding was markedly reduced by sulfatase treatment of PGM and in the presence of acidic and desialylated oligosaccharide fractions containing sulfated carbohydrate residues prepared from PGM, demonstrating that sulfated carbohydrate moieties mediated binding. Histochemical staining revealed similar localization of His₆-EF-Tu and high iron diamine staining in porcine mucosa. These results indicated that EF-Tu bound PGM via sulfated carbohydrate moieties. To characterize the contribution of EF-Tu to the interaction between bacterial cells and PGM, we tested whether anti-EF-Tu antibodies could inhibit the interaction. Binding of L. reuteri JCM1081 to PGM was significantly blocked in a concentration-dependent matter, demonstrating the involvement of EF-Tu in bacterial adhesion. In conclusion, the present results demonstrated, for the first time, that EF-Tu bound sulfated carbohydrate moieties of sulfated glycolipids and sulfomucin, thereby promoting adhesion of L. reuteri to mucosal surfaces.