Lectin histochemistry of feline sphingomyelinosis.

The brain from a Siamese cat with sphingomyelinosis was examined with lectin histochemistry. Swollen neurons were stained with Canavalia ensiformis agglutinin (Con A). Some of them were also stained with Ricinus communis agglutinin-I (RCA-I) and Ulex europaeus agglutinin-I (UEA-I). A small number of axonal spheroids and glia cells were positive for Con A, RCA-I, UEA-I and wheat germ agglutinin. Control tissues were weakly stained with Con A, but not with any of the other lectins. These results indicate that affected neurons contain mannose and glucose residues in addition to sphingomyelin. This study points to the possibility that the characteristics of lectin histochemical study might be helpful for the diagnosis of sphingomyelinosis.     

Cooperative interaction between hepatocyte nuclear factor 4 alpha and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8

Cholesterol homeostasis is maintained by coordinate regulation of cholesterol synthesis and its conversion to bile acids in the liver. The excretion of cholesterol from liver and intestine is regulated by ATP-binding cassette half-transporters ABCG5 and ABCG8. The genes for these two proteins are closely linked and divergently transcribed from a common intergenic promoter region. Here, we identified a binding site for hepatocyte nuclear factor 4alpha (HNF4alpha) in the ABCG5/ABCG8 intergenic promoter, through which HNF4alpha strongly activated the expression of a reporter gene in both directions. The HNF4alpha-responsive element is flanked by two conserved GATA boxes that were also required for stimulation by HNF4alpha. GATA4 and GATA6 bind to the GATA boxes, coexpression of GATA4 and HNF4alpha leads to a striking synergistic activation of both the ABCG5 and the ABCG8 promoters, and binding sites for HNF4alpha and GATA were essential for maximal synergism. We also show that HNF4alpha, GATA4, and GATA6 colocalize in the nuclei of HepG2 cells and that a physical interaction between HNF4alpha and GATA4 is critical for the synergistic response. This is the first demonstration that HNF4alpha acts synergistically with GATA factors to activate gene expression in a bidirectional fashion.     

NADPH oxidases in fungi: diverse roles of reactive oxygen species in fungal cellular differentiation

Synthesis of reactive oxygen species (ROS) by specific NADPH oxidases (Nox) can serve both defense and differentiation signaling roles in animals and plants. Fungi have three subfamilies of NADPH oxidase. NoxA and NoxB have a structure very similar to the human gp91(phox). NoxC has in addition a Ca(2+) binding motif as found in the human Nox5 and plant Rboh families of NADPH oxidases. A survey of fungal genomes identified up to four Nox genes in some fungal species, but Nox genes are absent from available genomes of the hemiascomycete yeasts, unicellular Basidiomycetes and Zygomycetes, reflecting the diversity of fungal life forms. Specific isoforms of Nox have been shown by genetic analysis to be required for various physiological processes and cellular differentiations, including development of sexual fruiting bodies, ascospore germination, hyphal defense, hyphal growth in both mutualistic and antagonistic plant-fungal interactions. This review provides an overview of our current knowledge of fungal NADPH oxidases, including Nox distribution in the fungal kingdom, Nox structure and regulation, and known biological functions of this important group of enzymes.     

Dynamic Substance Flow Analysis of Neodymium and Dysprosium Associated with Neodymium Magnets in Japan

Recycling of neodymium and dysprosium is of great interest because of the rapid growth in their demand and limited supply of new resources. To promote recovery from end‐of‐life (EoL) products, it is desirable to quantify the recycling potentials of neodymium and dysprosium by their end use. This study characterized the substance flows of neodymium and dysprosium associated with neodymium magnets in Japan by conducting a dynamic substance flow analysis. A bottom‐up approach was employed in the analysis to estimate annual consumption by end use. Factors used in the analysis were the amounts of rare earth contents, weight of a magnet used for each product, adoption ratios of neodymium magnet usage in each product, and lifetime of products. It was found that the amount of neodymium entering use was approximately half of the domestic consumption; the balance existing in final products that were exported from Japan. The economic feasibility of recycling neodymium magnets was evaluated for their largest two end uses: driving motors in hybrid electric vehicles (HEVs) and compressors in air conditioners. It was found that recycling the neodymium magnets used in the driving motors has the potential for economic feasibility in Japan. The result showed that lower transportation costs for recovered magnets can make the recycling economically feasible regardless of the content rate and the price of metals. The future increase of EoL HEVs contributes to the feasibility of recycling with a profit in the upcoming years. Strategies for more profitable recycling are concentrating scrap motors or magnets among recycling factories or selecting specific factories that deal with EoL HEVs.     

Dynamic regulation of Emi2 by Emi2-bound Cdk1/Plk1/CK1 and PP2A-B56 in meiotic arrest of Xenopus eggs

In vertebrates, unfertilized eggs are arrested at metaphase of meiosis II by Mos and Emi2, an inhibitor of the APC/C ubiquitin ligase. In Xenopus, Cdk1 phosphorylates Emi2 and both destabilizes and inactivates it, whereas Mos recruits PP2A phosphatase to antagonize the Cdk1 phosphorylation. However, how Cdk1 phosphorylation inhibits Emi2 is largely unknown. Here we show that multiple N-terminal Cdk1 phosphorylation motifs bind cyclin B1-Cdk1 itself, Plk1, and CK1δ/ε to inhibit Emi2. Plk1, after rebinding to other sites by self-priming phosphorylation, partially destabilizes Emi2. Cdk1 and CK1δ/ε sequentially phosphorylate the C-terminal APC/C-docking site, thereby cooperatively inhibiting Emi2 from binding the APC/C. In the presence of Mos, however, PP2A-B56β/ε bind to Emi2 and keep dephosphorylating it, particularly at the APC/C-docking site. Thus, Emi2 stability and activity are dynamically regulated by Emi2-bound multiple kinases and PP2A phosphatase. Our data also suggest a general role for Cdk1 substrate phosphorylation motifs in M phase regulation.