Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP

The human nucleotide pool sanitization enzyme, MTH1, hydrolyzes 2-hydroxy-dATP and 8-hydroxy-dATP in addition to 8-hydroxy-dGTP. We report here that human MTH1 is highly specific for 2-hydroxy-ATP, among the cognate ribonucleoside triphosphates. The pyrophosphatase activities for 8-hydroxy-GTP, 2-hydroxy-ATP and 8-hydroxy-ATP were measured by high-performance liquid chromatography. The kinetic parameters thus obtained indicate that the catalytic efficiencies of MTH1 are in the order of 2-hydroxy-dATP > 2-hydroxy-ATP > 8-hydroxy-dGTP > 8-hydroxy-dATP >> dGTP > 8-hydroxy-GTP > 8-hydroxy-ATP. Notably, MTH1 had the highest affinity for 2-hydroxy-ATP among the known substrates. ATP is involved in energy metabolism and signal transduction, and is a precursor in RNA synthesis. We suggest that the 2-hydroxy-ATP hydrolyzing activity of MTH1 might prevent the perturbation of these ATP-related pathways by the oxidized ATP.

Potent Inhibition of Ribulose-Bisphosphate Carboxylase by an Oxidized Impurity in Ribulose-1,5-Bisphosphate1

Oxidation of d-ribulose-1,5-bisphosphate (ribulose-P2) during synthesis and/or storage produces d-glycero-2,3-pentodiulose-1,5-bisphosphate (pentodiulose-P2), a potent slow, tight-binding inhibitor of spinach (Spinacia oleracea L.) ribulose-P2 carboxylase/oxygenase (Rubisco). Differing degrees of contamination with pentodiulose-P2 caused the decline in Rubisco activity seen during Rubisco assay time courses to vary between different preparations of ribulose-P2. With some ribulose-P2 preparations, this compound can be the dominant cause of the decline, far exceeding the significance of the catalytic by-product, d-xylulose-1,5-bisphosphate. Unlike xylulose-1,5-bisphosphate, pentodiulose-P2 did not appear to be a significant by-product of catalysis by wild-type Rubisco at saturating CO2 concentration. It was produced slowly during frozen storage of ribulose-P2, even at low pH, more rapidly in Rubisco assay buffers at room temperature, and particularly rapidly on deliberate oxidation of ribulose-P2 with Cu2+. Its formation was prevented by the exclusion of transition metals and O2. Pentodiulose-P2 was unstable and decayed to a variety of other less-inhibitory compounds, particularly in the presence of some buffers. However, it formed a tight, stable complex with carbamylated spinach Rubisco, which could be isolated by gel filtration, presumably because its structure mimics that of the enediol intermediate of Rubisco catalysis. Rubisco catalyzes the cleavage of pentodiulose-P2 by H2O2, producing P-glycolate.

SoxR, a [2Fe-2S] transcription factor, is active only in its oxidized form.

SoxR protein is known to function both as a sensor and as a transcriptional activator for a superoxide response regulon in Escherichia coli. The activity of SoxR was tested by its ability to enable the transcription of its target gene, soxS, in vitro. The activity of the oxidized form was lost when its [2Fe-2S] clusters were reduced by dithionite under anaerobic conditions, and it was rapidly restored by autooxidation. This result is consistent with the hypothesis that induction of the regulon is effected by the univalent oxidation of the Fe-S centers of SoxR. In vivo, this oxidation may be caused by an alteration of the redox balance of electron chain intermediates that normally maintains soxR in an inactive, reduced state. Oxidized SoxR was about twice as effective as reduced SoxR in protecting the soxS operator from endonucleolytic cleavage. However, this difference could not account for a greater than 50-fold difference in their activities and therefore could not support a model in which oxidation activates SoxR by enabling it to bind to DNA. NADPH, ferredoxin, flavodoxin, or ferredoxin (flavodoxin):NADP+ reductase could not reduce SoxR directly in vitro at a measurable rate. The midpoint potential for SoxR was measured at -283 mV.

The 94- to 97-kDa mouse macrophage membrane protein that recognizes oxidized low density lipoprotein and phosphatidylserine-rich liposomes is identical to macrosialin, the mouse homologue of human CD68.

We have previously reported the partial purification of a 94- to 97-kDa plasma membrane protein from mouse peritoneal macrophages that binds oxidatively modified low density lipoprotein (OxLDL) and phosphatidylserine-rich liposomes. We have now identified that protein as macrosialin, a previously cloned macrophage-restricted membrane protein in the lysosomal-associated membrane protein family (mouse homologue of human CD68). Early in the course of purification of the 94- to 97-kDa protein, a new OxLDL-binding band at 190-200 kDa appeared and copurified with the 94- to 97-kDa protein. The HPLC pattern of tryptic peptides from this higher molecular mass ligand-binding band closely matched that derived from the 94- to 97-kDa band. Specifically, the same three macrosialin-derived tryptic peptides (9, 9, and 15 residues) were present in the purified 94- to 97-kDa band and in the 190- to 200-kDa band and antisera raised against peptide sequences in macrosialin recognized both bands. An antiserum against macrosialin precipitated most of the 94- to 97-kDa OxLDL-binding material. We conclude that the binding of OxLDL to mouse macrophage membranes is in part attributable to macrosialin. Our previous studies show that OxLDL competes with oxidized red blood cells and with apoptotic thymocytes for binding to mouse peritoneal macrophages. Whether macrosialin plays a role in recognition of OxLDL and oxidatively damaged cells by intact macrophages remains uncertain.

T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein.

Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characterized by cholesterol deposition, fibrosis, and inflammation. The presence of activated T lymphocytes and macrophages and high expression of HLA class II molecules are indicative of a local immunologic activation in the atherosclerotic plaque, but the antigen(s) involved has not yet been identified. We established T-cell clones from human atherosclerotic plaques using polyclonal mitogens as stimuli and exposed the clones to potential antigens in the presence of autologous monocytes as antigen-presenting cells. Four of the 27 CD4+ clones responded to oxidized low density lipoprotein (oxLDL) by proliferation and cytokine secretion; this response was dependent on autologous antigen-presenting cells and restricted by HLA-DR. All clones that responded to oxLDL secreted interferon gamma upon activation, but only one produced interleukin 4, suggesting that the response to oxLDL results in immune activation and inflammation but may not be a strong stimulus to antibody production. No significant response to oxLDL could be detected in CD4+ T-cell clones derived from the peripheral blood of the same individuals. Together, the present data suggest that the inflammatory infiltrate in the atherosclerotic plaque is involved in a T-cell-dependent, autoimmune response to oxLDL.

The Environmental Health and Safety of Carbon Nanotubes: Risk, Perception, and Policy

The production and use of carbon nanotubes (CNTs) can negatively impact human health and the environment through occupational, environmental, and product life-cycle exposures. Research is underway to evaluate the known, potential, and perceived hazards associated with CNTs. Recent research and policy analyses regarding CNTs were reviewed extensively. A facility engaged in research, development, and manufacture of CNTs was observed handling CNTs and associated individuals were informally interviewed. The combined investigation characterizes the current state of the art of our understanding and implementation of policy needed to address the impacts of CNTs to human health and the environment. A gap analysis is performed of regulations, policy, and CNT control methods; conclusions and recommendations are made from the results of this analysis.

Single wall carbon nanotubes loaded with Pd and NiPd nanoparticles for H2 sensing at room temperature

Pd and bimetallic Ni50Pd50 nanoparticles protected by polyvinylpyrrolidone (PVP) have been synthesized by the reduction-by-solvent method and deposited on single wall carbon nanotubes (SWCNTs) to be tested as H2 sensors. The SWCNTs were deposited by drop casting from different suspensions. The Pd nanoparticles-based sensors show a very reproducible performance with good sensitivity and very low response times (few seconds) for different H2 concentrations, ranging from 0.2% to 5% vol. H2 in air at atmospheric pressure. The influence of the metal nanoparticle composition, the quality of SWCNTs suspension and the metal loading have been studied, observing that all these parameters play an important role in the H2 sensor performance. Evidence for water formation during the H2 detection on Pd nanoparticles has been found, and its repercussion on the behaviour of the assembled sensors is discussed. The sensor preparation procedure detailed in this work has proven to be simple and reproducible to prepare cost-effective and highly efficient H2 sensors that perform very well under real application conditions.

Improving the Photoelectrochemical Response of TiO2 Nanotubes upon Decoration with Quantum-Sized Anatase Nanowires

TiO2 nanotubes (NTs) have been widely used for a number of applications including solar cells, photo(electro)chromic devices, and photocatalysis. Their quasi-one-dimensional morphology has the advantage of a fast electron transport although they have a relatively reduced interfacial area compared with nanoparticulate films. In this study, vertically oriented, smooth TiO2 NT arrays fabricated by anodization are decorated with ultrathin anatase nanowires (NWs). This facile modification, performed by chemical bath deposition, allows to create an advantageous self-organized structure that exhibits remarkable properties. On one hand, the huge increase in the electroactive interfacial area induces an improvement by 1 order of magnitude in the charge accumulation capacity. On the other hand, the modified NT arrays display larger photocurrents for water and oxalic acid oxidation than bare NTs. Their particular morphology enables a fast transfer of photogenerated holes but also efficient mass and electron transport. The importance of a proper band energy alignment for electron transfer from the NWs to the NTs is evidenced by comparing the behavior of these electrodes with that of NTs modified with rutile NWs. The NT-NW self-organized architecture allows for a precise design and control of the interfacial surface area, providing a material with particularly attractive properties for the applications mentioned above.

Growth of Carbon Nanotubes on Surfaces: The Effects of Catalyst and Substrate

We report a study of synthesising air-stable, nearly monodispersed bimetallic colloids of Co/Pd and Fe/Mo of varying compositions as active catalysts for the growth of carbon nanotubes. Using these catalysts we have investigated the effects of catalyst and substrate on the carbon nanostructures formed in a plasma-enhanced chemical vapour deposition (PECVD) process. We will show how it is possible to assess the influence of both the catalyst and the support on the controlled growth of carbon nanotube and nanofiber arrays. The importance of the composition of the catalytic nuclei will be put into perspective with other results from the literature. Furthermore, the influence of other synthetic parameters such as the nature of the nanoparticle catalysts will also be analysed and discussed in detail.

Chiral rhodium complexes covalently anchored on carbon nanotubes for enantioselective hydrogenation

Chiral rhodium hybrid nanocatalysts have been prepared by covalent anchorage of pyrrolidine-based diphosphine ligands onto functionalized CNTs. This work constitutes the first attempt at covalent anchoring of homogeneous chiral catalysts on CNTs. The catalysts, prepared with two different chiral phosphines, were characterized by ICP, XPS, N2 adsorption and TEM, and have been tested in the asymmetric hydrogenation of two different substrates: methyl 2-acetamidoacrylate and α-acetamidocinnamic acid. The hybrid nanocatalysts have shown to be active and enantioselective in the hydrogenation of α-acetamidocinnamic acid. A good recyclability of the catalysts with low leaching and without loss of activity and enantioselectivity was observed.

On the origin of the high capacitance of nitrogen-containing carbon nanotubes in acidic and alkaline electrolytes

The synthesis of nitrogenated carbon nanotubes (N-CNTs) with up to 6.1 wt% N, via the use of pyridine as the nitrogen containing carbon precursor, can provide a facile route to significantly enhance the low intrinsic specific capacitance of carbon nanotubes. The nitrogen functionalities determine this, at least, five-fold increase of the specific capacitance.

Palladium and Bimetallic Palladium–Nickel Nanoparticles Supported on Multiwalled Carbon Nanotubes: Application to Carbon–Carbon Bond-Forming Reactions in Water

Palladium and bimetallic Pd–Ni nanoparticles (NPs) protected by polyvinylpyrrolidone were prepared by the reduction-by-solvent method and deposited on multiwalled carbon nanotubes (MWCNTs). The catalytic activity of these NPs to carbon–carbon bond-forming reactions was studied by using 0.1 mol % Pd loading, at 120 °C for 1 h and water as a solvent under ligand-free conditions. The Suzuki–Miyaura reaction took place quantitatively for the cross-coupling of 4-bromoanisole with phenylboronic acid, better than those obtained with potassium phenyltrifluoroborate, with Pd50Ni50/MWCNTs as a catalyst and K2CO3 as a base and TBAB as an additive, with good recyclability during 4 cycles with some Ni leaching. The Hiyama reaction of 4-iodoanisole with trimethoxyphenylsilane, under fluoride-free conditions using 50 % aqueous NaOH solution, was performed with Pd/MWCNTs as a catalyst in 83 % yield with low recyclability. For the Mizoroki-Heck reaction 4-iodoanisole and styrene gave the corresponding 4-methoxystilbene quantitatively with Pd50Ni50/MWCNTs using K2CO3 as a base and TBAB as an additive although the recycle failed. In the case of the Sonogashira-Hagihara reaction, Pd/MWCNTs had to be used as a catalyst and pyrrolidine as a base for the coupling of 4-iodoanisole with phenylacetylene under copper-free conditions. The corresponding 4-methoxytolane was quantitatively obtained allowing the recycling of the catalyst during 3 cycles.

Functionalization of carbon nanotubes using aminobenzene acids and electrochemical methods. Electroactivity for the oxygen reduction reaction

Functionalized carbon nanotubes (CNTs) using three aminobenzene acids with different functional groups (carboxylic, sulphonic, phosphonic) in para position have been synthesized through potentiodynamic treatment in acid media under oxidative conditions. A noticeable increase in the capacitance for the functionalized carbon nanotubes mainly due to redox processes points out the formation of an electroactive polymer thin film on the CNTs surface along with covalently bonded functionalities. The CNTs functionalized using aminobenzoic acid rendered the highest capacitance values and surface nitrogen content, while the presence of sulfur and/or phosphorus groups in the aminobenzene structure yielded a lower functionalization degree. The oxygen reduction reaction (ORR) activity of the functionalized samples was similar to that of the parent CNTs, independently of the functional group present in the aminobenzene acid. Interestingly, a heat treatment in N2 atmosphere with a very low O2 concentration (3125 ppm) at 800 °C of the CNTs functionalized with aminobenzoic acid produced a material with high amounts of surface oxygen and nitrogen groups (12 and 4% at., respectively), that seem to modulate the electron-donor properties of the resulting material. The onset potential and limiting current for ORR was enhanced for this material. These are promising results that validates the use of electrochemistry for the synthesis of novel N-doped electrocatalysts for ORR in combination with adequate heat treatments.

Synthesis of palladium nanoparticles over graphite oxide and carbon nanotubes by reduction in ethylene glycol and their catalytic performance on the chemoselective hydrogenation of para-chloronitrobenzene

Pd nanoparticles have been synthesized over carbon nanotubes (CNT) and graphite oxide (GO) by reduction with ethylene glycol and by conventional impregnation method. The catalysts were tested on the chemoselective hydrogenation of p-chloronitrobenzene and the effect of the synthesis method and surface chemistry on their catalytic performance was evaluated. The catalysts were characterized by N2 adsorption/desorption isotherms at 77 K, TEM, powder X-ray diffraction, thermogravimetry, infrared and X-ray photoelectron spectroscopy and ICP-OES. It was observed that the synthesis of Pd nanoparticles employing ethylene glycol resulted in metallic palladium particles of smaller size compared to those prepared by the impregnation method and similar for both supports. The presence of oxygen groups on the support surface favored the activity and diminished the selectivity. It seems that ethylene glycol reacted with the surface groups of GO, this favoring the selectivity. The activity was higher over the CNT-based catalysts and both catalysts prepared by reduction in ethylene glycol were quite stable upon recycling.