Reaction Sites in Thermo- and Photo-induced CO Oxidation on Stepped Pt(113) and the Collimation of Product Desorption(CO oxidation on Pt(113))

The reaction sites in the thermal and photolytic CO oxidation on Pt(s)2(111)x(001) were examined through analysis of the angular and velocity distributions of desorbing product CO_2. In the former, the CO_2 desorption is sharply collimated but fairly shifted from the site normal, although the reaction proceeds on hollow sites of (100) and (111) patches. On the other hand, CO_2 produced in the photo-reaction is desorbed sharply along the (100) and (111) plane normal. This difference in the collimation is explained by reducing surface smoothing effect due to high velocity of desorbing CO_2

Modeling Pathogenic Mutations of Human Twinkle in Drosophila Suggests an Apoptosis Role in Response to Mitochondrial Defects

The human gene C10orf2 encodes the mitochondrial replicative DNA helicase Twinkle, mutations of which are responsible for a significant fraction of cases of autosomal dominant progressive external ophthalmoplegia (adPEO), a human mitochondrial disease caused by defects in intergenomic communication. We report the analysis of orthologous mutations in the Drosophila melanogaster mitochondrial DNA (mtDNA) helicase gene, d-mtDNA helicase. Increased expression of wild type d-mtDNA helicase using the UAS-GAL4 system leads to an increase in mtDNA copy number throughout adult life without any noteworthy phenotype, whereas overexpression of d-mtDNA helicase containing the K388A mutation in the helicase active site results in a severe depletion of mtDNA and a lethal phenotype. Overexpression of two d-mtDNA helicase variants equivalent to two human adPEO mutations shows differential effects. The A442P mutation exhibits a dominant negative effect similar to that of the active site mutant. In contrast, overexpression of d-mtDNA helicase containing the W441C mutation results in a slight decrease in mtDNA copy number during the third instar larval stage, and a moderate decrease in life span in the adult population. Overexpression of d-mtDNA helicase containing either the K388A or A442P mutations causes a mitochondrial oxidative phosphorylation (OXPHOS) defect that significantly reduces cell proliferation. The mitochondrial impairment caused by these mutations promotes apoptosis, arguing that mitochondria regulate programmed cell death in Drosophila. Our study of d-mtDNA helicase overexpression provides a tractable Drosophila model for understanding the cellular and molecular effects of human adPEO mutations

Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/ multidrug resistance-associated protein 2, OATP1B1/multi

ABSTRACT Until recently, it was generally believed that the transport of various organic anions across the bile canalicular membrane was mainly mediated by multidrug resistance-associated protein 2 (MRP2/ABCC2). However, a number of new reports have shown that some organic anions are also substrates of multidrug resistance 1 (MDR1/ABCB1) and/or breast cancer resistance protein (BCRP/ABCG2), implying MDR1 and BCRP could also be involved in the biliary excretion of organic anions in humans. In the present study, we constructed new doubletransfected Madin-Darby canine kidney II (MDCKII) cells expressing organic anion-transporting polypeptide 1B1 (OATP1B1)/MDR1 and OATP1B1/BCRP, and we investigated the transcellular transport of four kinds of organic anions, estradiol-17␤-D-glucuronide (EG), estrone-3-sulfate (ES), pravastatin (PRA), and cerivastatin (CER), to identify which efflux transporters mediate the biliary excretion of compounds using double-transfected cells. We observed the vectorial transport of EG and ES in all the double transfectants. MRP2 showed the highest efflux clearance of EG among these efflux transporters, whereas BCRP-mediated clearance of ES was the highest in these double transfectants. In addition, two kinds of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, CER and PRA, were also substrates of all these efflux transporters. The rank order of the efflux clearance of PRA mediated by each transporter was the same as that of EG, whereas the contribution of MDR1 to the efflux of CER was relatively greater than for PRA. This experimental system is very useful for identifying which transporters are involved in the biliary excretion of organic anions that cannot easily penetrate the plasma membrane. Biliary excretion is one of the major pathways for the elimination of unnecessary compounds from blood circulation. In the common process of hepatic clearance, compounds are taken up into liver, converted to more hydrophilic metabolites by metabolizing enzymes responsible for oxidation (e.g., cytochrome P450) and/or conjugation (e.g., UDP-glucuronosyl transferases and sulfotransferases), and subsequently excreted into bile. Several kinds of ATP-binding cassette (ABC) transporters on the bile canalicular membrane play an important role in this biliary excretion. It is generally accepted that multidrug resistance-associated protein 2 (MRP2/ABCC2) is responsible for the biliary excretion of a wide variety of organic anions including glutathione and glucuronide conjugate

The translational energy of desorbing products in NO and N2O decomposition on Pd (110)

The angular and velocity distributions of desorbing N2, N2O, and NO molecules were studied in the decomposition of NO and also N2O on a palladium (110) surface by means of angle-resolved thermal desorption combined with cross-correlation time-of-flight techniques. The results were quite similar in both cases although the desorption of N 2, N2O, and NO concurrently peaked at 490 K in the NO decomposition and, in the N 2O decomposition, the desorption of N 2 and N2O peaked at 140 K. The desorption of N2O and NO showed a cosine angular distribution and a Maxwellian velocity distribution at the surface temperature. On the other hand, the N2 desorption collimated sharply at ±41°–43° off the surface normal in a plane along the [001] direction. Then the velocity distributions of N2 involved two hyperthermal components with the mean translational energy of 0.47 and 0.22 eV, respectively. A mechanism for the inclined N2 desorption was proposed to be due to a highly exothermic reaction of N2O(ad) --> N2(g) + O(ad) and the strong repulsive force operative on the product N2 from the surface

Angular and velocity distributions of desorbing product carbon dioxide from two reaction sites on platinum(110)(1×2)

The angular and velocity distributions of desorbing product CO2 were studied on a platinum(110)(1×2) surface over a wide range of CO coverages by means of angle-resolved thermal desorption combined with a cross-correlation time-of-flight (TOF) technique. Heating the coadsorption layer of CO and oxygen yields four CO2 formation peaks P1–CO2 (~400 K), P2–CO2 (300 K), P3–CO2 (250 K), and P4–CO2 (170 K)]. The angular distribution of each CO2 produced at high CO coverages consists of three desorption components. Two of them show desorption collimated along the inclined terrace normal; the other shows it along the bulk surface normal. The former is assigned to reaction on the inclined terrace, and the latter mostly to reaction on the bottom of the trough. The translational temperature of each desorption component is derived by deconvoluting the TOF spectrum. This temperature reaches 1000–1500 K. The maximum translational temperature is always observed in the normal direction of each reaction site. For P2–and P3–CO2, the maximum translational temperature of the normal-directional component is lower than that of the inclined components. For P4–CO2, on the other hand, the maximum translational temperature of the normal-directional component is close to that of the inclined components. A transfer mechanism of reaction sites is proposed

Transformation of iridium(110) (1×1) into (1×2) and spatial distribution of reactive carbon dioxide desorption

The spatial distribution of the desorption flux of CO2 produced on Ir(110) (1x 1) and (1x 2) surfaces was studied by means of angle-resolved thermal desorption and low-energy electron diffraction. The distribution is collimated along the bulk surface normal on (1x1). It is sharp in the [001] direction and sharper in the [11-bar 0] direction. This distribution is consistent with the model that the reactive desorption occurs on a short bridge site. On (1x2) surfaces, two-directional desorption was observed, which was collimated along the axis at the polar angle of 26 deg in both [001] and [001-bar] directions. The distribution in the [11-bar 0] direction is collimated along the bulk surface normal. The reactive desorption was suggested to take place on a threefold hollow site on the declining terrace. The spatial distribution changed from the (1x 1) type to the (1x 2) type during the transformation of the surface structure. This structure change was confirmed by low-energy electron diffraction

Anisotropic velocity distribution of desorbing product in carbon monoxide oxidation on palladium (110)

Significant anisotropy was found in the velocity distributions of desorbing product CO2 from a Pd(110) surface. The velocity distributions were determined by a cross-correlation time-of-flight technique combined with angle-resolved thermal desorption. Heating the coadlayer of CO and oxygen produces five peaks in the CO2 formation spectrum; P1– (around 420 K), P2– (~370 K), P3– (~300 K), P4– (~230 K), and P5–CO2 (~170 K). The translational temperature of each CO2 is much higher than the corresponding surface temperature, and increases in the sequence of P1– <P2– <P3– <P4– <P5–CO2. It decreases rapidly with an increase in the desorption angle perpendicular to the surface trough and more slowly parallel to it. This anisotropy is correlated to the reaction site symmetry