Zinc is an essential component for the catalytic activity of numerous zinc-requiring enzymes. However, until recently little has been known about the molecules involved in the pathways required for supplying zinc to these enzymes. We showed recently (Suzuki, T., Ishihara, K., Migaki, H., Matsuura, W., Kohda, A., Okumura, K., Nagao, M., Yamaguchi-Iwai, Y., and Kambe, T. (2005) J. Biol. Chem. 280, 637-643) that zinc transporters, ZnT5 and ZnT7, are required for the activation of zinc-requiring enzymes, alkaline phosphatases (ALPs), by transporting zinc into the lumens of the Golgi apparatus and the vesicular compartments where ALPs locate and converting apoALPs to holoALPs. ZnT6 is also located in the vesicular compartments like ZnT5 and ZnT7. However, the functions of ZnT6 and relationships among these three transporters have not been characterized yet. Here, we characterized the cellular function of ZnT6 together with ZnT5 and ZnT7 by gene-targeting studies using DT40 cells. ZnT6-deficient DT40 cells showed low ALP activity, suggesting that ZnT6 is required for the activation of zincrequiring enzymes like ZnT5 and ZnT7. Combined disruptions of three transporter genes and re-expressions of transgenes revealed that ZnT5 and ZnT6 work in the same pathway, whereas ZnT7 acts alone. Furthermore, co-immunoprecipitation studies revealed that ZnT5 and ZnT6 formed hetero-oligomers, whereas ZnT7 formed homo-oligomers. Interestingly, the Ser-rich loop in ZnT6, a potential zinc-binding site, was dispensable for the zinc-supplying function of ZnT5/ZnT6 hetero-oligomers, suggesting that the His-rich loop in ZnT5 may be important for zinc binding and that the loop in ZnT6 may acquire another function in the hetero-oligomer formation. These results suggest that two different zinc transport complexes operate to activate ALPs.

The surface oxidized layer of a TiN barrier metal thin film grown on a Pt electrode was used as a resistive switching material. The fabricated memory cell shows bipolar resistive switching on a nanosecond order. A TiO2 anatase layer of about 2.5nm thick on TiN thin film was characterized by high-resolution scanning transmission electron microscopy. The results suggested that the high-speed resistive change was derived from the Mott transition in the TiO2 anatase nanolayer, and the obtained results could relate to the formation of filament paths previously reported in binary transition metal oxide thin films exhibiting resistive switching.

(-)-Hydroxycitrate (HCA) is an active ingredient that is extracted from the rind of the Indian fruit, Garcinia cambogia, which is available as an herbal supplement and is used to lose weight. In this study, the acute and chronic effects of HCA on energy metabolism were examined in male Std ddY mice. Mice were placed into metabolic chambers and administered 10 mg HCA or water (control) orally. Serum free fatty acid levels were significantly higher 100 min after administration in the HCA group, but the respiratory exchange ratio was not different from that in the control group. The concentration of glycogen in the gastrocnemius muscle was higher in the HCA group 16 h after administration, and in a separate study, the maximum swimming time until fatigue was slightly longer (P: = 0. 21) than that in the control group on d 1. The difference was significant on d 3 after 3 d of HCA or water administration. Other mice were administered 10 mg HCA or water orally twice a day for 25 d. On d 26, they were placed into metabolic chambers after administration and allowed to rest for 1 h, followed by 1 h of running at 15 m/min. Respiratory gas was monitored. The respiratory exchange ratio was significantly lower in the HCA group during both resting and exercising conditions. These results suggest that chronic administration of HCA promotes lipid oxidation and spares carbohydrate utilization in mice at rest and during running.

A new forced-swimming apparatus for determining maximum swimming time in mice was devised for use in the evaluation of the endurance capacity of Std and ddY and CDF1 mice after various diet and drug treatments. With the apparatus, a water current is generated by circulating water with a pump in a swimming pool. A spout and suction slit were contrived to generate a constant current while the strength of the current is regulated by a valve. The decrease in the leg-kicking intervals of mice accompanying the increase in the current speed confirmed that the workload is adjustable by regulation of the current speed. Compared with the number of forelimb strokes, that of the hindlimb kicks was greater. The swimming time until fatigue was observed to decrease with increasing current speed in the two strains of mice. As biochemical indexes, the blood lactate and muscle glycogen levels corroborated the correlation between current speed and increase in workload. These results indicate that the apparatus employed in the present study is suitable for the evaluation of the endurance capacity of mice and that is useful for detecting the effects of dietary differences and drug pretreatments on this capacity.