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Constant-pressure heat capacities (CPs) of crystalline benzoic acid (BAh) and its deuterated analogue (C6H5COOD, BAd) were measured by adiabatic calorimetry, and the phonon density (g(ω)) of states was determined from their CP data using a real-coded genetic algorithm (RCGA) with just generation gap + real-coded ensemble cross-over. The distribution of g(ω) was in reasonable agreement with the spectroscopic one observed for molecular vibration modes, indicating sufficient reliability of g(ω) determined by the RCGA. Based on the fact that CPs reveals an inverse-isotope effect in the temperature range 30-130 K, the determined g(ω)s were used to investigate the molecular mechanism of the effect: g(ω) of BAd revealed blue shifts in the ranges of ω = 80-100 and 150-230 K, as referred to that of BAh. It was suggested from the combined considerations on g(ω) and spectroscopic results that an anticooperative correlation exists between O-H···O hydrogen bonds and interdimer interactions in BA.

PurposeTo investigate retinal sensitivity of highly myopic eyes without choroidal neovascularisation (CNV) or patchy chorioretinal atrophy (PCA) and investigated its association with anatomical characteristics including melanin distribution at the retinal pigment epithelium (RPE), which was evaluated with polarisation-sensitive optical coherence tomography (PS-OCT).DesignRetrospective consecutive observational cohort study.MethodsWe included highly myopic eyes (refractive error ≤−8.0 dioptres or axial length of ≥26.5 mm) from patients at the University of Tokyo Hospital. Retinal sensitivity was measured by microperimetry at 25 sectors within 6 degrees from the fovea. Depolarisation value, which reflected melanin pigmentation, was measured by a clinical prototype of PS-OCT and was parameterised as polarimetric entropy. Retinal sensitivity or entropy at the RPE in high myopia was compared with emmetropic control subjects. The association of retinal sensitivity with age, axial length, entropy, or choroidal thickness was assessed in per-eye and per-sector analysis.ResultsTwenty-three highly myopic eyes (age, 66.6±12.3 years) were included. The average retinal sensitivity was 25.3±3.0 dB, which was significantly decreased compared with the control (pConclusionsDecreased depolarisation at the RPE measured with PS-OCT, which reflected altered melanin pigmentation, was independently associated with reduced retinal sensitivity in patients with early stages of myopic maculopathy without CNV or PCA.

Intermediate species formed on Ag(110) surfaces under the presence of ethylene and oxygen in the sub-Torr pressure range were studied by near-ambient-pressure X-ray photoelectron spectroscopy (XPS)...

Utilization of carbon dioxide (CO2) molecules leads to increased interest in the sustainable synthesis of methane (CH4) or methanol (CH3OH). The representative reaction intermediate consisting of a carbonyl or formate group determines yields of the fuel source during catalytic reactions. However, their selective initial surface reaction processes have been assumed without a fundamental understanding at the molecular level. Here, we report direct observations of spontaneous CO2 dissociation over the model rhodium (Rh) catalyst at 0.1 mbar CO2. The linear geometry of CO2 gas molecules turns into a chemically active bent-structure at the interface, which allows non-uniform charge transfers between chemisorbed CO2 and surface Rh atoms. By combining scanning tunneling microscopy, X-ray photoelectron spectroscopy at near-ambient pressure, and computational calculations, we reveal strong evidence for chemical bond cleavage of O‒CO* with ordered intermediates structure formation of (2 × 2)-CO on an atomically flat Rh(111) surface at room temperature. Direct observation of carbon dioxide dissociation provides an origin of catalytic conversion for industrial chemical reactions. Here, the authors reveal their molecular interactions on the rhodium catalyst at near-ambient pressure by interface science techniques and computational calculations.

This study was conducted to examine retinal sensitivity (RS) in eyes with pachychoroid diseases and to analyze its association with the presence or absence of quiescent choroidal neovascularization (CNV), that can be protective against retinal dysfunction or atrophy in other macular diseases such as age-related macular degeneration. A total of 12 eyes of 12 patients aged ≥45 years having the characteristic findings of central serous chorioretinopathy but not presenting any exudative changes were included in this study. Choroidal vascular hyper permeability (CVH) was identified by indocyanine green angiography, and the presence or absence of CNV was evaluated by optical coherence tomography angiography. RS at 68 points was examined by microperimetry. The average RS corresponding to within and outside CVH was compared. The association between the difference in RS and the presence or absence of CNV was also analyzed. CNV was detected in six eyes (50%). In eyes without CNV, the RS within CVH was similar compared with that outside CVH. However, in eyes with CNV, the RS within CVH was significantly decreased compared with that outside CVH. Multiple regression analysis revealed the presence of CNV as an independent factor associated with RS. In eyes with pachychoroid diseases, RS decreased within the CVH area under the coexistence of nonexudative CNV.

We have previously shown that podocyte injury increases the glomerular filtration of liver-derived angiotensinogen (Agt) and the generation of intrarenal angiotensin (Ang) II and that the filtered Agt is reabsorbed by proximal tubules in a manner dependent on megalin. In the present study, we aimed to study the role of megalin in the generation of renal Ang II and sodium handling during nephrotic syndrome. We generated proximal tubule-specific megalin knockout (KO) mice and crossed these animals with NEP25 mice, in which podocyte-specific injury can be induced by injection of the immunotoxin LMB2. Without podocyte injury, renal Agt staining was markedly diminished and urinary Agt increased in KO mice. However, renal Ang II was similar between KO and control mice on average: 117 (95% CI 101–134) vs. 101 (68–133) fmol/g tissue. We next tested the effect of megalin KO on intrarenal Ang II generation with podocyte injury. Control NEP25 mice showed markedly increased renal Agt staining and renal Ang II levels: 450 (336–565) fmol/g tissue. Megalin KO/NEP25 mice showed markedly diminished Agt reabsorption and attenuated renal Ang II: 199 (156–242) fmol/g tissue (p < 0.001). Compared with control NEP25 mice, megalin KO/NEP25 mice excreted 5-fold more sodium in the urine. Western blot analysis showed that megalin KO decreased NHE3 and the cleaved α and γ forms of ENaC. These data indicate that Agt reabsorbed by proximal tubules via megalin in nephrotic syndrome is converted to Ang II, which may contribute to sodium retention and edema formation by activating NHE3 and ENaC. SUMMARY: This study shows that in nephrotic syndrome, plasma angiotensinogen leaked into the renal tubular lumen is reabsorbed by proximal tubules via megalin and converted to angiotensin II, which may contribute to sodium retention and edema formation by activating NHE3 and ENaC.

The active oxygen species for ethylene epoxidation on Ag surfaces has been a long-standing issue. We conducted in situ observations of Ag(111) surfaces under exposure to ethylene and oxygen gases w...

Purpose To investigate the three-dimensional distribution and associating demographic factors of depolarization, using polarization-sensitive optical coherence tomography (PS-OCT), to evaluate melanin pigmentation in the retinal pigment epithelium (RPE) and choroid in healthy eyes. Methods In total, 39 unaffected healthy eyes of 39 subjects were examined using a PS-OCT clinical prototype. The degree of depolarization, expressed as the polarimetric entropy, was assessed in the RPE, the superficial and the total choroid layer, especially in the center, the inner, or the outer areas centered at the fovea. The values and their association with the demographic data were analyzed. Near-infrared fundus autofluorescence (NIRAF) was also used, in the same manner, for the comparison. Twenty-eight of 39 eyes were measured twice to evaluate intrasession repeatability. Results Both the polarimetric entropy in the RPE and the gray level in NIRAF, decreased from the center to the periphery (P < 0.001). The polarimetric entropy in the RPE was significantly associated with age in each area (P ≤ 0.001). In the RPE and the superficial choroid, the polarimetric entropy was negatively associated with axial length in each area (P ≤ 0.002). The intraclass correlation coefficient of the polarimetric entropy in the same session was excellent in each area of the RPE, superficial choroid, or total choroid layer (0.94-0.98). Conclusions The distribution of fundus melanin pigment-related depolarization was evaluated using PS-OCT. The depolarization was associated with the subjects' demographic data, such as age or axial length. Translational Relevance The presented information in healthy eyes provides an essential basis for the investigation into a variety of chorioretinal pathologies.

Purpose To report the clinical findings of the patients with retinal pigment epithelium (RPE) aperture secondary to age-related macular degeneration (AMD). Methods A retrospective data analysis was conducted of patients at the University of Tokyo Hospital eye clinic, from the year September 1st, 2012 to 2019. Review of the medical records of patients with RPE aperture accompanied by AMD was performed. We investigated age, best-corrected visual acuity (BCVA), images of spectral domain optical coherence tomography, short-wave fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography, and retinal sensitivity measured with microperimetry. The change in visual acuity or the area of the aperture during the follow-up period was analyzed. Results Five eyes of 5 patients (4 men, one woman) were included in the analysis. The mean age at presentation was 78.6 ± 9.1 years. The average length of follow-up was 23.6 ± 17.9 months. The RPE apertures appeared as round, either at the apex or at the base of PED, with no evidence of accompanying CNV but subretinal detachment (SRD) above the aperture. On FAF, the apertures appeared as sharply demarcated round areas of hypoautofluorescence. The FA revealed sharply demarcated round areas of window defects in the early and mid-phase with leakage in the late phase corresponding to SRD. The area of apertures enlarged during the follow-up period. Mean BCVA got worse from 0.20 logMAR at the initial presentation to 0.39 logMAR at the last visit. The retinal sensitivity was reduced but partly preserved above the area of aperture. Conclusions and importance RPE aperture was found in some patients with drusenoid PED secondary to AMD. It enlarged during follow-up. Visual acuity was declined. Retinal sensitivity was decreased but partly preserved.

NO reduction by CO on Rh(111) was investigated by near-ambient pressure X-ray photoelectron spectroscopy, mass spectrometry, and kinetic analysis. Under exposure to NO + CO mixed gases and with heating the surface from room temperature to 450 °C, NO dissociation and NO reduction reaction start simultaneously independent of gas pressure ratio of NO/CO, which indicates that NO dissociation triggers this reaction. From kinetic analyses based on observed adsorbate coverages under reaction conditions, the following two points are suggested: (i) NOhollow is a reactive species for N2 and N2O formation via N + NO reaction. (ii) At low temperatures, the N + NO reaction is dominant for N2 production, whereas above around 400 °C, the N + N reaction becomes dominant, which leads to an increase in N2 selectivity at the higher temperatures. Compared with the NO + CO reaction on Ir(111) surfaces, which exhibits a high N2 selectivity, the adsorption site of reactive NO and the availability of vacant surface sites could b...

Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl − cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl − cotransporter phosphorylation. Accordingly, a Na + -Cl − cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl − cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor–epithelial sodium channel–Na + -Cl − cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the phenotype of apparent mineralocorticoid excess.

The constructional details and performance of a low-temperature ac calorimetric system for extremely small single crystal samples of molecule-based compounds of which sensing parts is consisting of commercially available micro-chip device of XEN-39390 are reported. We succeeded to detect the thermal anomaly related to the glass formation of the ethylene conformation in a charge transfer complex of κ-(BEDT-TTF) 2 Cu[N(CN) 2 ]Br, where BEDT-TTF is bisethylenedithiotetrathiafulvalene. From the analyses of temperature and frequency dependences of heat capacity, we suggest that XEN-39390 can give similar experimental resolution as that of TCG-3880 with much smaller single crystals less than 100 ng. We also observed a glass-like freezing of molecular dynamics in the large asymmetric cations in EtMe 3 Sb[Pd(dmit) 2 ] 2 which are known as a spin liquid compound by single piece of crystal where dmit is 1,3-dithiole-2-thione-4,5-dithiolate. The comparison with the relaxation calorimetry result with absolute precision is performed.

The nitric oxide (NO) reduction by carbon monoxide (CO) on Ir(111) surfaces under near ambient pressure conditions was studied by a combination of near-ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS) and mass spectrometry (MS), particularly paying attention to the dominant reaction pathway to formation of molecular nitrogen (N2). Under a relatively low CO pressure condition (50 mTorr NO + 10 mTorr CO), two reaction pathways to form N2 are clearly observed at different ignition temperatures (280 and 400 °C) and attributed to a reaction of NO adsorbed at atop site (NOatop) with atomic nitrogen (Nad) and associative desorption of Nad, respectively. Since the adsorption of NOatop is inhibited by CO adsorbed at atop site (COatop), the ignition of the NOatop + Nad reaction strongly depends on the coverage of COatop; the ignition temperature shifts to higher temperature as increasing CO pressure. In contrast, for the Nad + Nad reaction the ignition temperature keeps almost constant (∼400 °C). The onl...

Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in both groups of mice. In cultured vascular smooth muscle cells, Wnt5a and angiotensin II (Ang II) increased p-MYPT1 expression but knockdown of Wnt5a with siRNA abolished Ang II–induced upregulation of p-MYPT1, indicating that Wnt5a is indispensable for Ang II–induced Rho/ROCK activation. Notably, Klotho inhibited Wnt5a- and Ang II–induced upregulation of p-MYPT1. Consistently, Klotho supplementation ameliorated HS-induced augmentation of reduced renal blood flow (RBF) response to intra-arterial infusion of Ang II and the thromboxane A(2) analog U46619, which activated RhoA in both groups of mice and were associated with the inhibition of BP elevation, suggesting that abnormal response of RBF to Ang II contributes to HS-induced BP elevation. Thus, Klotho deficiency underlies aging-associated salt-sensitive hypertension through vascular non-canonical Wnt5a/RhoA activation.

Background Regulation of sodium chloride transport in the aldosterone-sensitive distal nephron is essential for fluid homeostasis and BP control. The chloride-bicarbonate exchanger pendrin in β-intercalated cells, along with sodium chloride cotransporter (NCC) in distal convoluted tubules, complementarily regulate sodium chloride handling, which is controlled by the renin-angiotensin-aldosterone system. Methods Using mice with mineralocorticoid receptor deletion in intercalated cells, we examined the mechanism and roles of pendrin upregulation via mineralocorticoid receptor in two different models of renin-angiotensin-aldosterone system activation. We also used aldosterone-treated NCC knockout mice to examine the role of pendrin regulation in salt-sensitive hypertension. Results Deletion of mineralocorticoid receptor in intercalated cells suppressed the increase in renal pendrin expression induced by either exogenous angiotensin II infusion or endogenous angiotensin II upregulation via salt restriction. When fed a low-salt diet, intercalated cell-specific mineralocorticoid receptor knockout mice with suppression of pendrin upregulation showed BP reduction that was attenuated by compensatory activation of NCC. In contrast, upregulation of pendrin induced by aldosterone excess combined with a high-salt diet was scarcely affected by deletion of mineralocorticoid receptor in intercalated cells, but depended instead on hypokalemic alkalosis through the activated mineralocorticoid receptor-epithelial sodium channel cascade in principal cells. In aldosterone-treated NCC knockout mice showing upregulation of pendrin, potassium supplementation corrected alkalosis and inhibited the pendrin upregulation, thereby lowering BP. Conclusions In conjunction with NCC, the two pathways of pendrin upregulation, induced by angiotensin II through mineralocorticoid receptor activation in intercalated cells and by alkalosis through mineralocorticoid receptor activation in principal cells, play important roles in fluid homeostasis during salt depletion and salt-sensitive hypertension mediated by aldosterone excess.

International audience; The surface chemical states of Pd(100) during CO oxidation were investigated using ambient pressure x-ray photoelectron spectroscopy and mass spectroscopy. Under the reactant ratio of CO/O2 = 0.1, i.e. an oxygen-rich reaction condition, the formation of surface oxides was observed with the onset of CO oxidation reaction at T = 525 K. As the reactant ratio (CO/O2) increased from 0.1 to 1.0, ∼ 90 % surface oxides remains on surface during the reaction. Upon the formation of surface oxides, the core level shift of oxygen gas phase peak was observed, indicating that change of surface work function. As CO oxidation takes places, i.e. making a transition from CO covered surface to the oxidic surface, the work functions of surface oxide on Pd(100) and Pt(110) display opposite behavior.

High-intensity focused ultrasound (HIFU) treatment is a non-invasive method of cancer treatment. In a HIFU treatment, ultrasound is focused on a target tumor tissue leading to temperature rise that coagulates the tissue. The treatment has a problem of long treatment time because a tumor is usually larger than the focal spot of HIFU. To reduce the treatment time, cavitation bubbles can be used for accelerating ultrasonic heating. Additionally, the heat conducting away from a focal spot can be utilized by properly scanning the focus. In this study, three sequences of scanning the focus to form six foci were compared by observing cavitation bubbles and measuring temperature rise in an excised chicken breast tissue and an agarose gel as well as a thin slice of tissue sandwiched between agarose gels. The results showed that there were differences in the behavior of bubbles and the efficient sequence between the tissue and the gel.

Reduction of oxidized Rh catalysts under carbon monoxide (CO) exposure and reaction conditions were studied by using ambient-pressure x-ray photoelectron spectroscopy. First, Rh powders pressed into a pellet were deeply oxidized and the reduction process under 100 mTorr CO environment was monitored in situ at different temperatures. The oxidized Rh surfaces are composed of Rh2O3 and RhO2, the latter of which is more segregated near the surface. Both oxide species are reduced simultaneously to the metallic state; kinetic analyses indicate that the activation energy of the reduction of the Rh oxides is 1.68 eV, which is a little larger than those for Pd oxides, probably due to a stronger Rh–O interaction. Reduction of oxidized Rh nano-particles deposited on SiO2 under two reaction conditions (CO + O2 and CO + NO + O2) was observed with increasing temperature. It was found that the reduction temperature shifts to the higher temperature in the presence of NO, even though the S-factors are almost the same. The NO molecule more strongly prevents the reduction of oxidized Rh catalyst compared to O2.

Epigenetic modulation may underlie the progression of diabetic nephropathy (DN). Involvement of TGFB1 in mesangial fibrosis of DN led us to hypothesize that Tgfb1 DNA demethylation contributes to progression of DN. In primary mesangial cells from diabetic (db/db) mouse kidneys, demethylation of Tgfb1 DNA and upregulation of Tgfb1 mRNA progressed simultaneously. USF1 binding site in Tgfb1 promoter region were demethylated, and binding of USF1 increased, with decreased binding of DNMT1 in db/db compared with control. Given downregulation of Tgfb1 expression by folic acid, antioxidant Tempol reversed DNA demethylation, with increased and decreased recruitment of DNMT1 and USF1 to the promoter, resulting in decreased Tgfb1 expression in db/db mice. Addition of H2O2 to mesangial cells induced DNA demethylation and upregulated Tgfb1 expression. Finally, Tempol attenuated mesangial fibrosis in db/db mice. We conclude that aberrant DNA methylation of Tgfb1 due to ROS overproduction play a key to mesangial fibrosis during DN progression.

The study of CO oxidation on Pt(1 1 0) surface is revisited using ambient pressure x-ray photoemission spectroscopy. When the surface temperature reaches the activation temperature for CO oxidation under elevated pressure conditions, both the α-phase of PtO2 oxide and chemisorbed oxygen are formed simultaneously on the surface. Due to the exothermic nature of CO oxidation, the temperature of the Pt surface increases as CO oxidation takes place. As the CO/O2 ratio increases, the production of CO2 increases continuously and the surface temperature also increases. Interestingly, within the diffusion limited regions, the amount of surface oxide changes little while the chemisorbed oxygen is reduced.

The renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, increasing levels of the Cl-/HCO3- exchanger pendrin in β-intercalated cells and the Na+-Cl- cotransporter (NCC) in distal convoluted tubules. However, the independent roles of AngII and aldosterone in regulating these levels remain unclear. In C57BL/6J mice receiving a low-salt diet or AngII infusion, we evaluated the membrane protein abundance of pendrin and NCC; assessed the phosphorylation of the mineralocorticoid receptor, which selectively inhibits aldosterone binding in intercalated cells; and measured BP by radiotelemetry in pendrin-knockout and wild-type mice. A low-salt diet or AngII infusion upregulated NCC and pendrin levels, decreased the phosphorylation of mineralocorticoid receptor in β-intercalated cells, and increased plasma aldosterone levels. Notably, a low-salt diet did not alter BP in wild-type mice, but significantly decreased BP in pendrin-knockout mice. To dissect the roles of AngII and aldosterone, we performed adrenalectomies in mice to remove aldosterone from the circulation. In adrenalectomized mice, AngII infusion again upregulated NCC expression, but did not affect pendrin expression despite the decreased phosphorylation of mineralocorticoid receptor. By contrast, AngII and aldosterone coadministration markedly elevated pendrin levels in adrenalectomized mice. Our results indicate that aldosterone is necessary for AngII-induced pendrin upregulation, and suggest that pendrin contributes to the maintenance of normal BP in cooperation with NCC during activation of the renin-angiotensin-aldosterone system by dietary salt restriction.

A cytocompatible inkjet bioprinting approach that enables the use of a variety of bioinks to produce hydrogels with a wide range of characteristics is developed. Stabilization of bioinks is caused by horseradish peroxidase (HRP)-catalyzed cross-linking consuming hydrogen peroxide (H2 O2 ). 3D cell-laden hydrogels are fabricated by the sequential dropping of a bioink containing polymer(s) cross-linkable through the enzymatic reaction and H2 O2 onto droplets of another bioink containing the polymer, HRP, and cells. The ≈95% viability of enclosed mouse fibroblasts and subsequent elongation of the cells in a bioprinted hydrogel consisting of gelatin and hyaluronic acid derivatives suggest the high cytocompatibility of the developed printing approach. The existence of numerous polymers, including derivatives of polysaccharides, proteins, and synthetic polymers, cross-linkable through the HRP-catalyzed reaction, means the current approach shows great promise for biofabrication of functional and structurally complex tissues.

Background and objective Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10−7 M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10−7 M aldosterone for 3 h by microarray. Results 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10−9 M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases.

Due to the high cation exchange capacity and large potential of swelling when wet, bentonite is the promising material for use in the disposal of the high-level radioactive waste. However, its swelling ability is affected by cations leached from both concrete barrier container and groundwater. This paper describes the phenominetic model of bentonite swelling in electrolyte solution, forcing on that for montmorillonite that is the main component in bentonite, to elucidate the effect of kind of cation on its swelling ability. It was assumed that swelling of montmorillonite caused according to two different steps：First step was the swelling of tactoids that were the assembles of basic layered element, so-called clay lamella, of montmorillonite and then second step, which was the rearrangement of structure in solution, was occurred. Swelling tactoids can be calculated from slit like pore model between two parallel plates considering the intermolecular forces between plates. As for rearrangement of aggregate structure of tactoid, it was assumed the actoides were aggregated and formed diamond-shaped structure, and to chemical potential in bulk solution that was equilibriumed to the solution in the slit pore. The later assumption required the when the slit distance was small, the chemical potential of bulk solution was influenced by the intermolecular forces between plates. The deformation due to rearrangement of structure could be calculated from difference between the experimental volume and the swelling volume of tactoids. It could be found that there was a good relationship between chemical potential and deformation due to rearrangement of structure despite the kind of cation. This enable the authors to estimate the effect of kind of cation on swelling of montmorillonite in electrolyte solutions.本研究では陽イオンによるモンモリロナイト（Mo）の膨潤モデルの構築を行った。Moの体積変化は（1）Moの基本構造の単位層の集合体であるTactoid（Ta）の膨潤による体積変化と、（2）Taが形成する粗大構造の膨潤による体積変化の総和と考えた。前者は2平板の分子間力を考慮したモデルより算出し、後者の粗大構造の変化は実測した体積変化とTaの膨張による体積変化の差から算出した。粗大構造中の溶液とTa中の単位層間の溶液は一様であると考え、その化学ポテンシャルを2平板間の分子間力により決定した。その結果、粗大構造と化学ポテンシャルにはイオン種によらず関係性が見られ、化学ポテンシャルに基づくMoの膨潤予測モデルの構築ができた。

Shigeto Fujimura,1,2 Kohei Ueda,1 Yoko Nomura,1 Yasuo Yanagi3,4 1Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 2Department of Ophthalmology, Kanazawa University School of Medicine, Ishikawa, Japan; 3Singapore Eye Research Institute, 4Medical Retina Department, Singapore National Eye Centre, Singapore Purpose: To assess the relationship between combined serum lutein and zeaxanthin (L+Z) concentration and macular pigment optical density (MPOD), and to investigate the effect of L+Z+docosahexaenoic acid (DHA) dietary supplementation on the spatial distribution of MPOD.Methods: Twenty healthy fellow eyes with unilateral wet age-related macular degeneration or chronic central serous chorioretinopathy were included. All participants received a dietary supplement for 6 months that contained 20 mg L, 1 mg Z, and 200 mg DHA. The best-corrected visual acuity and contrast sensitivity (CS) were measured at baseline and at 1, 3, and 6 months. Serum L+Z concentrations were measured at baseline and at 3 months. MPOD was calculated at each time point using fundus autofluorescent images.Results: Serum L+Z concentration was correlated with MPOD at 1°–2° eccentricity at baseline (r=0.63, P=0.003) and 3 months (r=0.53, P=0.015). Serum L+Z concentration increased by a factor of 2.3±1.0 (P

Sodium dehydroacetate (DHA-S) is used as a food additive, preservative and antimicrobial agent. Repeated oral administration of DHA-S in rats induced severe hemorrhage in multiple organs and prolongation of blood coagulation factors. To determine the mechanism of hemorrhage, the protective effect of vitamin K (VK) was investigated. Increased VK-dependent blood coagulation parameters, a prolonged prothrombin time (PT) and an activated partial thromboplastin time (APTT) were observed in rats when DHA-S alone was administered, while only a slight change was observed in animals that received a single injection of vitamin K2 following the DHA-S dosing. These results suggest that DHA-S-induced hemorrhage is caused by a deficiency of vitamin K. In addition, the inhibitory effect of DHA-S on vitamin K1 epoxide reductase (VKOR) activity was measured with an in vitro system using liver microsomes of normal male rats. DHA-S concentration-dependently inhibited VKOR activity similar to warfarin, but the inhibitory concentration was high. Therefore, it was concluded that the DHA-S-induced hemorrhage was caused by a depletion of blood VK, associated with any factors including VKOR inhibition.

Postsurgical peritoneal adhesion is a serious surgical complication. In situ hydrogel formation on the surface of tissues, which will develop adhesions, is a recent feasible approach to prevent peritoneal adhesion. Here, we report on-tissue surface formation of a hyaluronic acid-based hydrogel by administration of a pre-hydrogel aqueous solution. The hydrogelation was initiated by contact with body fluid containing glucose on tissue surfaces. During the hydrogelation, a hyaluronic acid derivative possessing phenolic hydroxyl moieties (HA-Ph) was cross-linked by a cascade reaction of glucose oxidase (GOx) and horseradish peroxidase (HRP). About 5 s of hydrogelation was accomplished using a solution containing 1.5% (w/v) HA-Ph, 5 U/mL HRP, and 2.5 U/mL GOx in 1 mg/mL glucose that is equivalent to the normal blood glucose concentration. The hydrogel was degradable by hyaluronidase and much softer than rat peritoneal sidewalls. We confirmed the efficiency of the hydrogel to prevent post-operative peritoneal adhesions by applying the solution containing HA-Ph, GOx, and HRP to animals with bowel abrasion-abdominal sidewall defects. A significant reduction in the development of peritoneal adhesions was found compared with animals applied with phosphate-buffered saline or saline containing HA-Ph alone. Statement of Significance Postsurgical peritoneal adhesion is a serious surgical complication. In this paper, we report a novel system for preventing it through an on-tissue surface formation of a biodegradable and biocompatible hyaluronic acid-based hydrogel by administration of a pre-hydrogel aqueous solution. The in situ hydrogelation is mediated by a cascade enzyme reaction of glucose oxidase (GOx) and horseradish peroxidase (HRP) initiated by contacting with body fluid containing glucose. The efficiency of the system was confirmed by applying the system to animals with bowel abrasion-abdominal sidewall defects.

Pulmonary fibrosis is the result of abnormal processes of repair that occur after lung injury. Transforming growth factor (TGF)-beta is a key molecule in the progression of pulmonary fibrosis. Although clinical use of interferon (IFN)-beta did not improve survival in patients with idiopathic pulmonary fibrosis, because some preclinical studies have suggested that IFN-beta is a potent inhibitor of fibrogenesis, beneficial effects of IFN-beta have been expected. We therefore attempted to determine effects of IFN-beta and investigated the mechanism of action of IFN-beta in bleomycin-induced pulmonary fibrosis. Bleomycin at Day 0 and IFN-beta for 4 wk were administered intravenously to ICR mice. At 28 d after bleomycin injection, histologic and chemical analysis was performed for evaluation of effects of IFN-beta. Tissue distribution and amounts of TGF-beta1 and thrombospondin (TSP)-1/2 were analyzed. IFN-beta attenuated prolylhydroxylase activity, resulting in inhibition of pulmonary fibrosis. Bleomycin-induced increase in TGF-beta1 in epithelial cells and extracellular matrix was attenuated by IFN-beta. TSP-1/2 was limited in platelets of control mice, but was present in foamy cells in fibrotic regions induced by bleomycin. These findings suggest that the antifibrotic effect of IFN-beta is inhibition of TGF-beta and its activation via decrease in TSP-1/2 in lung tissue and change in location of TSP-1/2 from platelets to foamy cells.

The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of chronic kidney disease (CKD) progression. Aliskiren, a direct renin inhibitor, inhibits the rate-limiting step of the RAAS without any alternative pathway. It is proven to reduce albuminuria in CKD patients treated with angiotensin blockade. However, there are few reports which evaluate the advantage of aliskiren as the first-line drug against CKD progression in RAAS-activated hypertensive patients.Tsukuba hypertensive mice (THM), double transgenic mice carrying both the human renin and human angiotensinogen genes, were fed a high-salt diet and treated with hydraladine, ramipril and aliskiren for 10 weeks. Blood pressure and urinary albumin excretion were measured every 2 weeks during the experimental period. We evaluated renal histological changes and gene expression. Plasma angiotensin concentration was measured to evaluate the RAAS inhibitory effect.High-salt-loaded THM showed severe hypertension and renal injury. All antihypertensive drugs suppressed blood pressure and prevented renal disease progression. RAAS blockade showed a higher renoprotective effect than hydraladine despite an equivalent blood pressure lowering effect. Aliskiren exhibited even stronger renoprotection than ramipril. Plasma angiotensin concentration was increased in THM fed both normal salt and high salt. Hydraladine did not alter the plasma angiotensin concentration. Ramipril significantly decreased angiotensin II concentration. Aliskiren treatment almost completely suppressed angiotensin I and resulted in lower angiotensin II concentration than ramipril treatment.Aliskiren prevents renal disease progression by suppressing both angiotensin I and II in RAAS-activated pathology. Our data suggest the application of a renin inhibitor for preventing kidney disease progression in CKD patients.

Experiments with hyperaldosteronemic animals suggest that, despite lowering plasma aldosterone, salt worsens renal injury by paradoxical activation of the mineralocorticoid receptor (MR). Salt and aldosterone synergistically contribute to renal impairment through Rac1-mediated activation of the MR, but whether angiotensin II also promotes renal injury through this mechanism is unknown. Here, we placed angiotensin II-overproducing double transgenic Tsukuba hypertensive mice on a low- or high-salt intake for 6 weeks and treated some animals with adrenalectomy, the MR antagonist eplerenone, the Rac inhibitor EHT1864, or hydralazine. High-salt intake, but not low-salt intake, led to hypertension and prominent kidney injury. Adrenalectomy prevented angiotensin II/salt-induced nephropathy in mice receiving high-salt intake, which was recapitulated by aldosterone supplementation, suggesting the involvement of aldosterone/MR signaling. Plasma aldosterone levels, however, were lower in high- than low-salt conditions. Instead, angiotensin II/salt-evoked MR activation associated with Rac1 activation and was not dependent on plasma aldosterone level. Both EHT1864 and eplerenone repressed the augmented MR signaling and mitigated kidney injury with partial but significant reduction in BP with high-salt intake. Hydralazine similarly reduced BP, but it neither suppressed the Rac1-MR pathway nor ameliorated the nephropathy. Taken together, these results show that angiotensin II and salt accelerate kidney injury through Rac1-mediated MR activation. Rac inhibition may be a promising strategy for the treatment of CKD.

Tritium labelled gaseous hydrogen was used to clarify the role of gaseous hydrogen in coal liquefaction. Datong coal was hydrogenated under 5.9 MPa (initial pressure) of tritium-labelled hydrogen in tetralin at 400°C in the presence or absence of NiMoAl2O3 catalyst. The catalyst accelerates both the hydrogen transfer from gaseous hydrogen and the hydrocracking of coal products. At the initial stage of the liquefaction without catalyst, the amount of hydrogen transferred from tetralin to coal was twice as large as that from gaseous hydrogen. In the presence of the catalyst, the hydrogen exchange between coal and molecular hydrogen was very rapid even at the initial stage of the liquefaction. In the absence of the catalyst, hydrogen transfer from gas phase to coal remarkably increased for rise from 300 to 350°C in temperature while that from solvent to coal suddenly increased at 400°C.

Objective: TheWFS1gene encodes an endoplasmic reticulum (ER) membrane-embedded protein. HomozygousWFS1gene mutations cause Wolfram syndrome, characterized by insulin-deficient diabetes mellitus and optic atropy. Pancreatic β-cells are selectively lost from the patient’s islets. ER localization suggests that WFS1 protein has physiological functions in membrane trafficking, secretion, processing and/or regulation of ER calcium homeostasis. Disturbances or overloading of these functions induces ER stress responses, including apoptosis. We speculated that WFS1 protein might be involved in these ER stress responses.Design and methods: Islet expression of the Wfs1 protein was analyzed immunohistochemically. Induction of Wfs1 upon ER stress was examined by Northern and Western blot analyses using three different models: human skin fibroblasts, mouse pancreatic β-cell-derived MIN6 cells, and Akita mouse-derivedIns296Y/Yinsulinoma cells. The humanWFS1gene promoter-luciferase reporter analysis was also conducted.Result: Islet β-cells were the major site ofWfs1expression. This expression was also found in δ-cells, but not in α-cells.WFS1expression was transcriptionally up-regulated by ER stress-inducing chemical insults. Treatment of fibroblasts and MIN6 cells with thapsigargin or tunicamycin increasedWFS1mRNA. WFS1 protein also increased in response to thapsigargin treatment in these cells.WFS1gene expression was also increased inIns296Y/Yinsulinoma cells. In these cells, ER stress was intrinsically induced by mutant insulin expression. TheWFS1gene promoter-luciferase reporter system revealed that the humanWFS1promoter was activated by chemically induced ER stress in MIN6 cells, and that the promoter was more active inIns296Y/Ycells thanIns2wild/wildcells.Conclusion:Wfs1expression, which is localized to β- and δ-cells in pancreatic islets, increases in response to ER stress, suggesting a functional link betweenWfs1and ER stress.

We have studied the nucleation and growth processes of silicon nanowires (SiNWs) by means of transmission electron microscopy and scanning tunneling microscopy. SiNWs are grown on hydrogen-terminated Si surface via the VLS (Vapor-Liquid-Solid) mechanism using silane (SiH4) as source gas. We have classified the growth process of SiNWs into three stages: the formation of nanocatalysts on a substrate, the nucleation of SiNWs in nanocatalysts, followed by the growth of SiNWs. We have shown that the structures of SiNWs are varied in several ways in each stage, and accordingly the structural properties of grown SiNWs can be modified to great extents. At the present moment, the phenomena at the each stage are not fully controlled, and this prevents us utilizing silicon nanowires more effectively.

Glutamate dehydrogenase (GDH) catalyzes reversible oxidative deamination of l-glutamate to α-ketoglutarate. Enzyme activity is regulated by several allosteric effectors. Recognition of a new form of hyperinsulinemic hypoglycemia, hyperinsulinism/hyperammonemia (HI/HA) syndrome, which is caused by gain-of-function mutations in GDH, highlighted the importance of GDH in glucose homeostasis. GDH266C is a constitutively activated mutant enzyme we identified in a patient with HI/HA syndrome. By overexpressing GDH266C in MIN6 mouse insulinoma cells, we previously demonstrated unregulated elevation of GDH activity to render the cells responsive to glutamine in insulin secretion. Interestingly, at low glucose concentrations, basal insulin secretion was exaggerated in such cells. Herein, to clarify the role of GDH in the regulation of insulin secretion, we studied cellular glutamate metabolism using MIN6 cells overexpressing GDH266C (MIN6-GDH266C). Glutamine-stimulated insulin secretion was associated with increased glutamine oxidation and decreased intracellular glutamate content. Similarly, at 5 mmol/l glucose without glutamine, glutamine oxidation also increased, and glutamate content decreased with exaggerated insulin secretion. Glucose oxidation was not altered. Insulin secretion profiles from GDH266C-overexpressing isolated rat pancreatic islets were similar to those from MIN6-GDH266C, suggesting observation in MIN6 cells to be relevant in native β-cells. These results demonstrate that, upon activation, GDH oxidizes glutamate to α-ketoglutarate, thereby stimulating insulin secretion by providing the TCA cycle with a substrate. No evidence was obtained supporting the hypothesis that activated GDH produced glutamate, a recently proposed second messenger of insulin secretion, by the reverse reaction, to stimulate insulin secretion.