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BACKGROUND: Chronic kidney disease (CKD) impairs the anti-inflammatory effects of high-density lipoprotein (HDL) and increases cardiovascular mortality. Though the potential role of dietary interventions to manage HDL is well studied, the clinical trials aimed to increase HDL levels have failed to reduce cardiovascular risk, rendering HDL function to be explored as a more relevant clinical parameter. This study investigates the effects of rice endosperm protein (REP), a plant-based protein, on the anti-inflammatory properties of HDL and renal injury-driven atherosclerosis in comparison with casein, an animal protein. MATERIALS AND METHODS: Ten-week-old apolipoprotein E-deficient hyperlipidemic mice underwent uninephrectomy. The mice (n = 6 each) were pair-fed a normal casein-based diet or a REP-based diet (both with 20.0% protein content) for seven weeks. Atherosclerotic lesions were detected by en face Sudan IV staining of the aorta. RESULTS: The number and sizes of the atherosclerotic lesions were significantly lower in the REP-based diet-fed group than the casein-based diet-fed group (p = 0.038). However, the REP-based diet neither elicited an ameliorative effect on kidney function or histology nor impacted the cholesterol profiles. Furthermore, HDL from the REP-based diet-fed mice significantly suppressed the inflammatory cytokine response of human umbilical vein endothelial cells than that from the casein-based diet-fed mice (MCP-1, p = 0.010; IL-6, p = 0.011; IL-1β, p = 0.028). CONCLUSIONS: The REP-based diet has a higher potential to lessen the atherosclerotic lesions accelerated by renal mass reduction than a casein-based diet, which could be associated with the anti-inflammatory effects of HDL.

Carotenoids are naturally synthesized in some species of bacteria, archaea, and fungi (including yeasts) as well as all photosynthetic organisms. Escherichia coli has been the most popular bacterial host for the heterologous production of a variety of carotenoids, including even xanthophylls unique to photosynthetic eukaryotes such as lutein, antheraxanthin, and violaxanthin. However, conversion efficiency of these epoxy-xanthophylls (antheraxanthin and violaxanthin) from zeaxanthin remained substantially low. We here examined several factors affecting their productivity in E. coli. Two sorts of plasmids were introduced into the bacterial host, i.e., a plasmid to produce zeaxanthin due to the presence of the Pantoea ananatis crtE, crtB, crtI, crtY, and crtZ genes in addition to the Haematococcus pluvialis IDI gene, and one containing each of zeaxanthin epoxidase (ZEP) genes originated from nine photosynthetic eukaryotes. It was consequently found that paprika (Capsicum annuum) ZEP (CaZEP) showed the highest conversion activity. Next, using the CaZEP gene, we performed optimization experiments in relation to E. coli strains as the production hosts, expression vectors, and ribosome-binding site (RBS) sequences. As a result, the highest productivity of violaxanthin (231 μg/g dry weight) was observed, when the pUC18 vector was used with CaZEP preceded by a RBS sequence of score 5000 in strain JM101(DE3).

Obesity and related disorders, which are increasing in adults worldwide, are closely linked to childhood diet and are associated with chronic inflammation. Rice endosperm protein (REP) intake during adulthood has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. However, the effects of REP intake during childhood on adulthood health are unclear. Therefore, we used a mouse model to experimentally investigate the preconditioning effects of REP intake during childhood on the development of obesity and related disorders in adulthood. Male C57BL/6J mice were pair-fed a normal-fat diet containing casein or REP during the juvenile period and then a high-fat diet (HFD) containing casein or REP during adulthood. Mice fed REP during the juvenile period showed better body weight, blood pressure, serum lipid profiles, lipopolysaccharide (LPS)-binding protein levels, and glucose tolerance in adulthood than those fed casein during the juvenile period. HFD-induced renal tubulo-glomerular alterations and hepatic microvesicular steatosis were less evident in REP-fed mice than in casein-fed ones. REP intake during the juvenile period improved HFD-induced dysbiosis (i.e., Escherichia genus proliferation and reduced gut microbiota diversity), thereby suppressing endotoxin-related chronic inflammation. Indeed, REP-derived peptides showed antibacterial activity against Escherichia coli, a major producer of LPS. In conclusion, REP supplementation during the juvenile period may regulate the gut microbiota and thus suppress the development of obesity and related disorders in adulthood in mice.

Angle-resolved photoelectron spectroscopy has been used to follow the valence band and near Fermi edge electronic band structure in the quasi-1D compound NaV 2 O 4 . In this current study we have acquired the very first high-quality, high-resolution ARPES data from this material. Our data clearly reveal two distinct dispersive bands that cross the Fermi level at different k F . This is a clear signature that the electronic properties of this material is affected by the presence of a mixed valence state on the different vanadium chains and possibly also the low-temperature magnetic spin order.

Arylative carboxylation of allenes proceeded in an intramolecular manner to afford the corresponding β,γ-unsaturated carboxylic acids in high yields using PdCl2/PAr3 (Ar = C6H4-p-CF3) and ZnEt2 under 1 atm of CO2. The intermediate of the cyclization/carboxylation sequence is thought to be a nucleophilic η1-allylethylpalladium, which reacts with CO2 at the γ-position of palladium. The products obtained could be efficiently converted into 3-substituted indole-2-carboxylate derivatives. One-pot synthesis of strychnocarpine, a β-carboline alkaloid, from the carboxylated product was also demonstrated.

In order to study a diffusive behavior of Li+ in Li intercalated graphites, we have measured muon spin relaxation (mu+SR) spectra for C6Li and C12Li synthesized with an electrochemical reaction bet ...

Introduction: Obesity is associated with lifestyle diseases such as type 2 diabetes and organ complications including kidney disease. Childhood diet has a great influence on the development of obesity and its related disorders. Rice endosperm protein (REP) has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. Therefore, we aimed to clarify the effects of REP intake during childhood on the development of high-fat-diet (HFD)-induced obesity and its related disorders during adulthood in mice. Methods: Four-week-old male C57BL/6J mice were pair-fed a normal-fat diet containing casein or REP for 6 weeks (childhood), and subsequently, an HFD containing casein or REP for 12 weeks (adulthood). Mice were then tested for oral glucose tolerance and subjected to the analyses of growth status, biochemical parameters, kidney histology, and fecal gut microbiota by 16S rRNA gene sequencing. Antibacterial activity of REP-derived peptides against gut microbiota was evaluated in vitro. Results: Mice fed REP in childhood showed less increase in body weight, total fat mass, blood pressure, serum total cholesterol, triglyceride, and lipopolysaccharide (LPS)-binding protein, and better glucose tolerance than those fed casein in childhood followed by HFD with casein or REP. Furthermore, HFD-induced glomerular hypertrophy, mesangial expansion, and vacuolar formation in proximal tubules were suppressed in mice fed REP than those fed casein in childhood. The intake of REP in childhood ameliorated dysbiosis caused by HFD. Additionally, REP-derived peptides showed antibacterial activity against E. coli, a major producer of LPS. Conclusion: These results indicate that the intake of REP during childhood can inhibit the progression of HFD-induced metabolic disorders and kidney disease in adulthood, probably through the effects of REP on gut microbiota. Disclosure Y. Higuchi: None. M. Hosojima: Research Support; Self; Astellas Pharma Inc., Biotech Japan Corporation, Daiichi Sankyo Co.,Ltd., Eli Lilly Japan K.K., Forica Foods Co.,Ltd., Kameda Seika Co.,Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novo Nordisc Pharma Ltd., Sato Foods Industries Co.,Ltd., Taisho Toyama Pharmaceutical.Co.,Ltd., Takeda Pharmaceutical Co.,Ltd. H. Kabasawa: Research Support; Self; Astellas Pharma Inc., Biotec Japan Corporation, Daiichi Sankyo Company, Limited, Forica Foods CO.,LTD., KAMEDA SEIKA CO., LTD., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K, Novo Nordisc Pharma Ltd, Sato Foods Industries CO.,LTD., Taisho Toyama Pharmaceutical.CO.,LTD., Takeda Pharmaceutical Company Limited. S. Kuwahara: None. R. Kaseda: None. H. Arao: None. T. Tanaka: None. I. Narita: None. A. Saito: None.

Stress induces various neurobiological responses and causes psychiatric disorders, including depression. Monoamine oxidase A (MAO-A) plays an important role in various functions of the brain, such as regulation of mood, anxiety and aggression, and dysregulation of MAO-A is observed in stress-related psychiatric disorders. This study addressed the question whether acute social stress induces changes to transcriptional and/or post-transcriptional regulation of MAO-A expression in the brain. Using male Nile tilapia (Oreochromis niloticus), we investigated whether acute social stress, induced by the presence of a dominant male fish, changes the expression of MAO-A. We measured gene expression of MAO-A by quantitative PCR, enzymatic activity of MAO-A by the luminescent method, and 5-HT and 5-HIAA levels by liquid chromatography–mass spectrometry in the brain of socially stressed and control fish. Socially stressed males showed decreased MAO-A mRNA levels, consistent MAO-A enzymatic activity, increased 5-HT turnover in the brain, and elevated plasma cortisol levels, compared to controls. Our results suggest that acute social stress suppresses the transcription of MAO-A gene, enhances 5-HT metabolism but does not affect the production of MAO-A protein.

By using a new catalytic system (PdCl2[P( n-Bu)3]2 in combination with ZnEt2), various 3-indolylmethanol derivatives were successfully carboxylated with CO2 (1 atm) via dearomatization of the indole nucleus, affording 3-methyleneindoline-2-carboxylates. In contrast, carboxylation of 2-indolylmethanol derivatives afforded unexpected doubly carboxylated products, which are useful synthetic precursors for biologically active compounds.

By using a palladium catalyst with ZnEt2, activated vinylcyclopropanes were successfully converted into the corresponding β,γ-unsaturated carboxylic acids in high yields under a CO2 atmosphere (1 atm). The intermediate in this reaction is thought to be a nucleophilic η(1)-allylethylpalladium species, which would be produced from π-allylpalladium and ZnEt2 (umpolung reactivity).

The synthesis and catalytic activity of several classes of NHC–Ni(0) pre-catalysts stabilized by electron-withdrawing alkenes are described. Variations in the structure of fumarate and acrylate ligands modulate the reactivity and stability of the NHC–Ni(0) pre-catalysts and lead to practical and versatile catalysts for a variety of transformations. The catalytic activity and efficiency of representative members of this class of catalysts have been evaluated in reductive couplings of aldehydes and alkynes and in N-arylations of aryl chlorides.

In the presence of CsF, a wide range of α-substituted α-siloxy silanes were carboxylated under a CO2 atmosphere (1 atm) via Brook rearrangement. A variety of α-substituents including aryl, alkenyl, and alkyl groups were tolerated to afford α-hydroxy acids in moderate-to-high yields. One-pot synthesis from aldehydes using PhMe2SiLi and CO2 was also possible, providing α-hydroxy acids without the isolation of an α-hydroxy silane.

By using a palladium catalyst with ZnEt2, activated vinylcyclopropanes were successfully converted into the corresponding β,γ-unsaturated carboxylic acids in high yields under a CO2 atmosphere (1 atm). The intermediate in this reaction is thought to be a nucleophilic η1-allylethylpalladium species, which would be produced from π-allylpalladium and ZnEt2 (umpolung reactivity).

Allylic alcohols are carboxylated in the presence of a catalytic amount of PdCl2 and PPh3 using stoichiometric ZnEt2 as transmetalation agent under CO2 atmosphere.

Stable isotope analysis using Laser Ablation Assisted Resonant Ionization Mass Spectrometry (LA-RIMS) is discussed. For the case of the 87Sr/86Sr isotope ratio measurements with a single color two-photon excitation scheme, the mass discrimination effects, which occur in LA-RIMS, are analyzed and a precision of 0.6% was extracted. For preparation of LA-RIMS on Hf isotopes, a novel two-color resonant excitation scheme with subsequent non-resonant ionization has been established using a high repetition-rate Ti:Sapphire laser system.

Various allylic alcohols were carboxylated in the presence of a catalytic amount of PdCl2 and PPh3 using ZnEt2 as a stoichiometric transmetalation agent under a CO2 atmosphere (1 atm). This carboxylation proceeded in a highly regioselective manner to afford branched carboxylic acids predominantly. The β,γ-unsaturated carboxylic acid thus obtained was successfully converted into an optically active γ-butyrolactone, a known intermediate of (R)-baclofen.

We have developed and assessed LA-RIMS as the isotope analysis method for trace inorgac elements in agricultural products. We used magnesium isotope analysis to verify that LA-RIMS had the capability to identify the production areas with the required precision of 0.3%. We demonstrated direct measurements of trace strontium (sub ppm level) in brown rice and confirmed that the isotope analysis precision was improved through the signal intensity enhancement by increasing the ablation power and expanding the laser spot. For the present system, we estimated the strontium isotope ratio of 87Sr/86Sr to be 0.69±0.10 (14%). We concluded that the direct isotope analysis for trace inorganic elements such as strontium in brown rice using LA-RIMS had an advantage under the serious situation of isobaric interference and had sufficient capability to identify agricultural production areas.

On the basis of growth rate at low pH, yield of lactic acid from glucose, and optical purity of lactic acid produced, we selected lactic acid bacteria favorable for production of optically pure L-lactic acid from defatted rice bran without sterilization. Of 21 strains tested, strains Nos. 13 and 16 produced 27-29kgm-3 of lactic acid with high optical purity from 100kgm-3 of unsterilized defatted rice bran in simultaneous saccharification and fermentation (SSF) with MRS medium at pH 4.5, a level at which the growth of indigenous lactic acid bacteria in defatted rice bran was suppressed. In a SSF process using strain No. 16 in which McIlvaine buffer (pH 4.5) was used instead of MRS medium, no growth of indigenous lactic acid bacteria was observed in defatted rice bran, and 28kgm-3 of lactic acid with 92% L-type content was produced from 100kgm-3 of unsterilized defatted rice bran. In SSF using McIlvaine buffer (pH 4.5), the protein fraction of defatted rice bran was found to play a significant role as a nitrogen source for the growth of lactic acid bacteria. By increasing the initial cell concentration to OD660=1.0 for SSF using strain No. 16 and McIlvaine buffer (pH 4.5), the proportion of L-lactic acid produced was enhanced to 95%.

In the presence of CsF, a wide range of α-substituted α-siloxy silanes were carboxylated under a CO2 atmosphere (1 atm) via Brook rearrangement. A variety of α-substituents including aryl, alkenyl, and alkyl groups were tolerated to afford α-hydroxy acids in moderate-to-high yields. One-pot synthesis from aldehydes using PhMe2SiLi and CO2 was also possible, providing α-hydroxy acids without the isolation of an α-hydroxy silane.

In order to investigate the microscopic magnetic nature of a sodium phospho- olivine, we have measured μ+SR spectra for NaxFePO4 using a powder sample in the temperature range between 2 and 500 K. ZF-μ+ SR measurements below 200 K at TRIUMF showed the appearance of static magnetic order below TN ~ 61 K, where the susceptibility-vs.- temperature curve exhibits a sharp maximum due to an antiferromagnetic (AF) transition. The wide distribution found for the internal magnetic field (Hint) was explained by the formation of AF order with the spread in Hint due to random distribution of Na vacancies. At higher temperatures, the ZF-spectrum for Na0.7FePO4, obtained at J-PARC, is found to change from a low-T static behavior to a high-T dynamic behavior above ~ 300 K. This is consistent with the fact that Na+ ions are reversibly extracted from and intercalated into the NaxFePO4 lattice, while there is no NMR study on Na-diffusion in NaxFePO4 due to large Fe moments.

α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid can be divided into three basic components: an aldehyde, an amine, and carbon dioxide (CO(2)). We report herein that a one-step synthesis of α-amino acids has been successfully achieved from these three basic and inexpensive chemicals with a single operation, in which the mixture of an aldehyde, a sulfonamide, and gaseous CO(2) was heated at 100 °C in the presence of Bu(3)Sn-SnBu(3) and CsF. In this one-pot sequential protocol, two important intermediates (imine and α-amino stannane) are involved and the stannyl anion generated in situ plays a crucial role, particularly for the efficient stannylation of the imine in the presence of proton sources and for promoting retrostannylation of the undesired α-alkoxy stannane owing to its high stability and tolerance of the presence of proton sources. This methodology enabled the synthesis of a wide range of racemic arylglycine derivatives in high yields.

α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid can be divided into three basic components: an aldehyde, an amine, and carbon dioxide (CO(2)). We report herein that a one-step synthesis of α-amino acids has been successfully achieved from these three basic and inexpensive chemicals with a single operation, in which the mixture of an aldehyde, a sulfonamide, and gaseous CO(2) was heated at 100 °C in the presence of Bu(3)Sn-SnBu(3) and CsF. In this one-pot sequential protocol, two important intermediates (imine and α-amino stannane) are involved and the stannyl anion generated in situ plays a crucial role, particularly for the efficient stannylation of the imine in the presence of proton sources and for promoting retrostannylation of the undesired α-alkoxy stannane owing to its high stability and tolerance of the presence of proton sources. This methodology enabled the synthesis of a wide range of racemic arylglycine derivatives in high yields.

The preparation of the synthetically important intermediates proceeds under milder conditions and tolerates more substituents than previous methods which used organometallic stannides.

In the presence of TMSSnBu(3) and CsF, stannylation of N-Boc- and N-Cbz-α-amido sulfones proceeded very well to afford the corresponding α-amido stannanes in moderate-to-high yields. This reaction tolerated α-aryl-, alkenyl-, and alkyl-substituted α-amido sulfones as well as substrates containing either an ester or cyano moiety, which might be reactive with lithium or magnesium stannides employed in conventional stannylation.

Pharmacokinetics of sparfloxacin (5-amino-l-cyclopropyl-7-(cis-3, 5-dimethyl-1-piperazinyl)-6, 8-difluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid, SPFX), a new synthetic antibacterial agent, was investigated in rats, dogs and monkeys after oral and intravenous administration of 5 mg/kg. The results were as follows :1. SPFX was well absorbed (60-90% of the dose) from the gastrointestinal tract in all species examined. After oral dosing at a dose of 5mg/kg, plasma levels of SPFX in rats, dogs and monkeys reached a peak of 0.67, 1.32 and 0.45μg/ml, respectively, and decreased with apparent elimination half-lives of 3. 5, 8. 2 and 5. 6h, respectively.2. There were no sex-related differences in the pharmacokinetics of SPFX in rats.3. The pharmacokinetics of SPFX in rats was not affected with its 7-day consecutive administration.4. The plasma concentration-time profile in rats with D-galactosamine-induced hepatic disorder was in good agreement with that in normal rats.5. In dogs, SPFX was well distributed in many tissues at concentrations exceeding the plasma levels, but was poorly distributed in the central nervous system.6. The glucuronic acid conjugate of SPFX was found together with the unchanged drug in the urine of all species. No metabolites were detected in rat feces.7. Urinary and fecal excretion in rats after oral dosing accounted for 15.8 % and 81.9% of the dose, respectively. A total amount excreted in the urine was 14.3% of the dose in dogs and 17.3% in monkeys.

In order to clarify the reason why the hydrogen desorption temperature (Td) of MgH2 is lowered by milling, we have studied the change in a local nuclear magnetic field with temperature by means of μ+SR. We have found a very clear oscillation in the ZF-spectrum at 2 K for the "milled" and "milled with Nb2O5" samples, while such oscillation is weaker for the "as prepared" MgH2. It was also found that the oscillation signal is stable up to 250 K and is assigned mainly due to the formation of a H-μ-H system. At temperatures above ambient T, we also found that the ZF-μ+SR spectrum exhibits a static Kubo-Toyabe behavior due to the nuclear magnetic field of 1H. Furthermore, it was clarified that rapid H diffusion starts well below Td only in the milled samples, leading to the conclusion that the consequent enhanced diffusion rate in MgH2 is essential to accelerate the desorption reaction and to decrease Td.

In order to elucidate the magnetic nature for a novel one-dimensional zigzag chain compound, NaCr2O4, we have measured μ+SR spectra using a powder sample in the temperature range between 2 and 200 K. Weak transverse field (wTF-) μ+SR measurements indicated that the whole volume of the sample enters into an antiferromagnetic (AF) phase below TN = 125 K. The zero field (ZF-) μ+SR spectrum obtained below TN exhibits a clear oscillation with a single muon-spin precession frequency (fμ). This suggests that static AF order is formed below TN and that all the implanted muons sense the same internal magnetic field. The temperature dependence of fμ was found to be very similar to that for the intensity of the magnetic Bragg peak in neutron diffraction (ND) measurements. On the other hand, the ZF-μ+SR spectrum for the isostructural compound, β-CaCr2O4, showed a rapidly damped oscillation below TN = 21 K, supporting the formation of incommensurate AF order, as proposed by ND.

To investigate the nuclear transmutation of Cs into Pr reported in this journal by Iwamura and coworkers, we have measured the amount of Pr atoms in the range as low as ∼1×1010 cm-2 using inductively coupled plasma mass spectrometry for Cs-ion-implanted Pd/CaO multilayer complexes before and after deuterium permeation. The amount of Pr was initially at most 2.0×1011 cm-2 and it increased up to 1.6×1012 cm-2 after deuterium permeation. The increase in the amount of Pr could be explained neither by deuterium permeation-stimulated segregation of Pr impurities nor by external contamination from the experimental environment during the permeation. No increase in Pr was observed for permeation with hydrogen. These findings suggest that the observed increase in Pr with deuterium permeation can be attributed to a nuclear origin, as reported by Iwamura and coworkers, although the amount of the increase in Pr is two orders of magnitude less than that reported by them.

We have suggested a novel concept of Resonance Ionization Mass Spectrometry using Inductively Coupled Plasma as an atom source (ICP-RIMS). Atomic sample vapor produced by an Inductively Coupled Plasma (ICP) can be analyzed using element-selective resonance ionization process, therefore, no chemical preparation for sample and isotopic standard are required. In addition, atoms thermally excited into metastable states by the ICP can be easily ionized by visible lasers in ICP-RIMS. We have demonstrated that the resonance ionization scheme via the metastable states is available through preliminary experiments in which a laser ablation process was used as an excited atom source instead of the ICP. From these features, isotope ratio analysis by ICP-RIMS is expected to be convenient technique with high throughput and no chemical preparation.

We have considered the applicability of strontium isotope analysis, using Laser Ablation-assisted Resonance Ionization Mass Spectrometry (LA-RIMS), to the determination of bone origin. We separated the uncertainty into two categories: ion counting statistics, and short-term or uncontrollable shifts of experimental conditions; only the former decreases with increasing signal intensity. Additionally, we confirmed that long-term shifts of isotope ratio in LA-RIMS can be cancelled by an internal correction method. We preliminarily estimated the precision of our technique to be 0.7% (1σ) for 105 laser shots; the accuracy is also confirmed within the present uncertainty through the comparison with a reference value.