Search for Near-Infrared Pulsation of the Anomalous X-ray Pulsar 4U 0142+61

We have searched for pulsation of the anomalous X-ray pulsar (AXP) 4U 0142+61 in the K' band ($\lambda_{\rm eff} = 2.11$ $\mu$m) using the fast-readout mode of IRCS at the Subaru 8.2-m telescope. We found no significant signal at the pulse frequency expected by the precise ephemeris obtained by the X-ray monitoring observation with RXTE. Nonetheless, we obtained a best upper limit of 17% (90% C.L.) for the root-mean-square pulse fraction in the K' band. Combined with i' band pulsation (Dhillon et al. 2005), the slope of the pulsed component ($F_\nu \propto \nu^\alpha$) was constrained to $\alpha > -0.87$ (90% C.L.) for an interstellar extinction of $A_{V} = 3.5$.Comment: 11 pages, 3 figures, Accepted for publication in PAS

JTP-109192, a novel G protein-coupled receptor 119 agonist, prevents atherosclerosis by improving hypercholesterolemia in congenic spontaneously hyperlipidaemic mice

G protein‐coupled receptor 119 (GPR119) expression in pancreatic β‐cells and intestinal L‐cells is a potential therapeutic target for the treatment of type 2 diabetes. Previously, we have reported that the GPR119 agonist JTP‐109192 improves glucose metabolism with single and repeated administration. Conversely, overexpression of the Gpr119 gene reportedly regulates cholesterol transporter expression in animal models, and a natural GPR119 agonist, oleoylethanolamide (OEA), improves atherosclerosis. Therefore, improving dyslipidaemia is considered a possible feature of GPR119 agonists. In the present study, the lipid‐lowering effect of JTP‐109192 was examined in BALB/c background spontaneously hyperlipidaemic (SHL) mice with repeated administration, once daily for 12 weeks. On repeated administration, JTP‐109192 revealed a cholesterol‐lowering effect and improved atherosclerosis following histopathological examination. With further investigation, the cholesterol‐lowering effect and subsequent antiatherosclerotic effect of JTP‐109192 was attributed to changes in intestinal cholesterol metabolism gene expression. Based on these results, JTP‐109192 represents a new potential antihypercholesterolaemic agent for the treatment of dyslipidaemia

An artificial amino acid, 4-iodo-L-meta-tyrosine: Biodistribution and excretion via kidney

金沢大学大学院医学系研究科We evaluated the use of radiolabeled 4-iodo-L-meta-tyrosine as an amino acid transport marker. The pharmacologic features of this compound, particularly the biodistribution and excretion, were examined by conducting in vivo and in vitro studies using 4-125I-iodo-L-meta-tyrosine (4- 125I-mTyr). Results obtained for L-14C-Tyr and 3- 125I-iodo-α-methyl-L-tyrosine (125I-IMT) were used for comparison. Methods: In vivo biodistribution studies of 4- 125I-mTyr were performed in male ddY mice. Urinary excretion of 4-125I-mTyr and 125I-IMT with administration of probenecid was studied. Local distribution of 4-125I-mTyr and 125I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-125I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-125I-mTyr were compared with those of 125I-IMT and the parent L-14C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK1 in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na +-free medium, and at 4°C. Results: 4-125I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of 125I-IMT. Blood clearance of 4-125I-mTyr was faster than that of 125I-IMT. Three hours after administration, >70% of 4-125I-mTyr was excreted via the urine, whereas 98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-125I-mTyr into LLC-PK1 cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4°C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-14C-Tyr and 125I-IMT showed similar results; however, uptake of 125I-IMT was enhanced by 0.1 mmol/L 2,4-dinitrophenol (165.1%), an inhibitor of generation of energy-rich phosphates. Conclusion: The artificial amino acid 4-125I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radioiabeled L-Tyr analogs. 4-125I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-125I-mTyr demonstrates different pharmacologic features than those of 125I-IMT, particularly in renal handling. 4-125I-mTyr may potentially be applied as a new amino acid transport marker

Uranium–Lead Systematics of Lunar Basaltic Meteorite Northwest Africa 2977

Northwest Africa (NWA) 2977 is a lunar basaltic meteorite that was found in 2005 and has been classified as an olivine cumulate gabbro. This meteorite contains a shock melt vein (SMV) induced by an intense shock event. We report herein on an in-situ analysis of phosphates in the host gabbro and the shock vein for the U–Pb dating of NWA 2977 using an ion microprobe, NanoSIMS. The majority of the analyzed phosphates, in both the SMV and host-rock, lie on a linear regression in 238U/206Pb–207Pb/206Pb–204Pb/206Pb three-dimensional space, indicating a total Pb/U isochron age of 3.15±0.12 Ga (95% confidence level), which is consistent ages determined in previous isotopic studies of NWA 2977 (Sm–Nd age of 3.10±0.05 Ga, Rb–Sr age of 3.29±0.11 Ga, and Pb–Pb baddeleyite age of 3.12±0.01 Ga), and identical to the age of the U–Pb phosphate in a paired meteorite NWA 773, 3.09±0.20 Ga, derived from our dataset. There was no clear difference in the formation age between the phosphates found in the SMV and host-rock, although the shape and size of the grains and the Raman spectra show the evidence of intense shock metamorphism. Based on these findings, the cooling rate of the phosphate was very rapid, constrained to be larger than 140 K/s