Proton conductivity in mixed cation phosphate, KMg1-xH2x(PO3)·yH2O, with a layered structure at low-intermediate temperatures.

Proton solid electrolytes, which exhibit high proton conductivity at a wide range of low-intermediate temperatures (150-300 °C), are key materials for the development of fuel cells for automobiles and cogeneration systems. In this study, a benitoite-type polyphosphate, KMg1-xH2x(PO3)·yH2O, which has a non-combustible and layered structure, was investigated as a new proton conductor. The benitoite-type KMg1-xH2x(PO3)·yH2O was synthesised by a coprecipitation method. The solid solution formed in the range of x = 0-0.100 in KMg1-xH2x(PO3)3·yH2O. Multi-step weight loss due to dehydration was observed for TG/DTA measurement at 30 °C and 150 °C. We observed enhanced peaks of the vibration bands at around 1117 cm-1 and 1229 cm-1, which were attributed to the symmetric and asymmetric PO2 vibration modes, and at 743 cm-1 and 970 cm-1 due to the ns(P-O-P) and nas(P-O-P) modes as well as broad absorbance peaks at 2300 cm-1 and 2700 cm-1 corresponding to the vibration modes of ns(P-O-H) with increasing x for FTIR spectra, which suggest the introduction of protons to the crystal structure. Proton conductivity increased from x = 0 to 0.10 and then decreased at x = 0.125, where the impurity phase was observed. The sample with x = 0.10 in benitoite-type KMg1-xH2x(PO3)3·yH2O exhibited high proton conductivity of 1.4 × 10-3 S cm-1 at 150 °C and 6.5 × 10-3 S cm-1 at 250 °C under a non-humidified N2 gas flow.

Retromer and Rab2-dependent trafficking mediate PS1 degradation by proteasomes in endocytic disturbance.

Accumulating evidence suggests that endocytic pathway deficits are involved in Alzheimer's disease pathogenesis. Several reports show that endocytic disturbance affects ß-amyloid peptide (Aß) cleavage from ß-amyloid precursor protein (APP). Presenilin-1 (PS1) is the catalytic core of the γ-secretase complex required for Aß generation. Previously, we showed that aging induces endocytic disturbance, resulting in the accumulation of Aß and APP in enlarged endosomes. It remains unclear, however, whether PS1 localization and function are affected with endocytic disturbance. Here, we report that in endocytic disturbance, PS1 is transported from endosomes to ER/Golgi compartments via retromer trafficking, and that PS1 interacts with vacuolar protein sorting-associated protein 35 both in vitro and in vivo. Moreover, PS1 is degraded by proteasomes via a Rab2-dependent trafficking pathway, only during endocytic disturbance. These findings suggest that PS1 levels and localization in endosomes are regulated by retromer trafficking and ER-associated degradation system, even if endocytic disturbance significantly induces the endosomal accumulation of APP and ß-site APP-cleaving enzyme 1. Results of this study also suggest that retromer deficiency can affect PS1 localization in endosomes, where Aß cleavage mainly occurs, possibly leading to enhanced Aß pathology. We proposed the following mechanism for intracellular transport of presenilin-1 (PS1). When endosome/lysosome trafficking is disturbed, PS1 is transported from endosome to endoplasmic reticulum (ER)/Golgi compartments via retromer and Rab2-mediated trafficking, and then degraded by endoplasmic reticulum-associated degradation (ERAD). Perturbations in this trafficking can cause abnormal endosomal accumulation of PS1, and then may lead to exacerbated Aß pathology. Cover Image for this issue: doi: 10.1111/jnc.13318.

Molecular cloning and sequencing of the cDNAs encoding the bat interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12p40, and tumor necrosis factor-alpha.

This is the first report on the cDNA sequences of bat interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 p40, and tumor necrosis factor (TNF)-alpha. The cDNAs of bat IL-2, IL-4, IL-6, IL-10, IL-12 p40, and TNF-alpha comprise 459, 405, 624, 537, 990, and 699 base pairs respectively. Moreover, each of the cDNAs of bat IL-2, IL-4, IL-6, IL-10, IL-12 p40, and TNF-alpha contain a single open reading frames encoding 152, 134, 207, 178, 329, and 232 amino acids, respectively. The comparison of bat cytokines with Perrissodactyla (horse), Carnivora (dog and cat), and Cetartiodactyla (cattle and pig) orthologs revealed a high degree of homology. Although the N-terminal amino acids and cysteine residues are highly conserved in each mature cytokine, the deduced N-linked glycosylation sites vary across species.

Effect of corosolic acid on gluconeogenesis in rat liver.

Corosolic acid (CRA), an active component of Banaba leaves (Lagerstroemia speciosa L.), decreases blood glucose in diabetic animals and humans. In this study, we investigated the mechanism of action of CRA on gluconeogenesis in rat liver. CRA (20-100 microM) dose-dependently decreased gluconeogenesis in perfused liver and in isolated hepatocytes. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic intermediate, plays a critical role in hepatic glucose output by regulating gluconeogenesis and glycolysis in the liver. CRA increased the production of F-2,6-BP along with a decrease in intracellular levels of cAMP both in the presence and in the absence of forskolin in isolated hepatocytes. While a cAMP-dependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes. These results indicate that CRA inhibits gluconeogenesis by increasing the production of F-2,6-BP by lowering the cAMP level and inhibiting PKA activity in isolated hepatocytes. Furthermore, CRA increased glucokinase activity in isolated hepatocytes without affecting glucose-6-phosphatase activity, suggesting the promotion of glycolysis. These effects on hepatic glucose metabolism may underlie the various anti-diabetic actions of CRA.