Chromosome 17 and the inducible nitric oxide synthase gene in human essential hypertension

Essential hypertension is a common multifactorial trait that results in a significantly increased risk for heart attack and stroke. The condition has a genetic basis, although at present the number of genes is unknown. In order to identify such genes, we are utilising a linkage scanning approach using microsatellite markers and affected sibships. Here we provide evidence for the location of at least one hypertension susceptibility locus on chromosome 17. Analysis of 177 affected sibpairs gave evidence for significant excess allele sharing to D17S949 (SPLINK: P=0.0029; MAPMAKER SIBS: P=0.0033; ASPEX: P=0.0061; GENEHUNTER: P=0.0096; ANALYZE (SIBPAIR): P=0.0025) on 17q22–24, with significant allele sharing also indicated for an additional marker, D17S799 (SPLINK: P=0.025; MAPMAKER SIBS: P= 0.025) located close to the centromere. Since these two genomic regions are well separated, our results indicate that there may be more than one chromosome 17 locus affecting human blood pressure. Moreover, further investigation of this chromosome, utilizing a polymorphism within the promoter of the iNOS candidate gene, NOS2A, revealed both increased allele sharing among sibpairs (SPLINK: P=0.02; ASPEX: P=0.00004) and positive association (P= 0.034) of NOS2A to essential hypertension. Hence these results indicate that chromosome 17 and, more specifically, the NOS2A gene may play a role in human essential hypertension.

Graphene-based thin film supercapacitor with graphene oxide as dielectric spacer

Thin film supercapacitors are produced by using electrochemically exfoliated graphene (G) and wet-chemically produced graphene oxide (GO). Either G/GO/G stacked film or sole GO film are sandwiched by two Au films to make devices, where GO is the dielectric spacer. The addition of graphene film for charge storage can increase the capacitance about two times, compared to the simple Au electrode. It is found that the GO film has very high dielectric constant, accounting for the high capacitance of these devices. AC measurements reveal that the relative permittivity of GO is in the order of 104 within the frequency range of 0.1–70 Hz.

Examination of the role of nitric oxide synthase and renal kallikrein as candidate genes for essential hypertension

Nitric oxide synthase and renal kallikrein are both involved in blood pressure regulation. Genes for these enzymes may, therefore, be considered candidates for hypertension pathogenesis. 2. In the present study, genotypes for nitric oxide synthase and renal kallikrein microsatellite markers were determined in a cross-sectional association analysis of hypertensive patients and normotensive control subjects. 3. Results from this study did not indicate an association of either of the candidate gene polymorphisms with essential hypertension. Hence, findings for this study do not support a role for these genes in human hypertension.

Migraine association and linkage studies of an endothelial nitric oxide synthase (NOS3) gene polymorphism

Migraine shows strong familial aggregation. However, the number of genes involved in the disorder is unknown and not identified. Nitric oxide is involved in the central processing of pain stimuli and plays an important role in the regulation of basal or stimulated vasodilation. Nitric oxide synthase, which controls the synthesis of nitric oxide, could possibly be a cause, or candidate gene, in migraine etiology. In this study, we detected a polymorphism for endothelial nitric oxide synthase by polymerase chain reaction and tested this for association and linkage to migraine. Results from the study did not show an association of the nitric oxide synthase microsatellite when tested in 91 affected and 85 unaffected individuals. Using the FASTLINK program for parametric linkage analysis, the polymorphism did not show significant linkage to migraine when tested in four migraine pedigrees composed of 116 individuals, 52 affected. Total LOD scores excluded linkage up to 8.5 cM between the nitric oxide synthase polymorphism and migraine. Results using the nonparametric affected pedigree member form of analysis also did not support a role for this gene in migraine etiology.

A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5′ and 3′ regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5′ region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5′ repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5′ and 3′ genetic variants were investigated.

Effects of hyperbaric oxygen and inducible nitric oxide synthase inhibitor treatment on femoral head osteonecrosis in a rat model

Introduction: Apoptosis is the final destiny of many cells in the body, though this process has been observed in some pathological processes. One of these pathological processes is femoral head non-traumatic osteonecrosis. Among many pro/anti-apoptotic factors, nitric oxide has recently been an area of further interest. Osteocyte apoptosis and its relation to pro-apoptotic action invite further research, and the inducible form of nitric oxide synthase (iNOS)—which produces a high concentration of nitric oxide—has been flagged. The aim of this study was to investigate the effect of hyperbaric oxygen (HBO) and inducible NOS suppressor (Aminoguanidine) in prevention of femoral head osteonecrosis in an experimental model of osteonecrosis in spontaneous hypertensive rats (SHRs). Methods: After animal ethic approval 34 SHR rats were divided into four groups. Ten rats were allocated to the control group without any treatment, and eight rats were allocated to three treatment groups namely: HBO, Aminoguanidine (AMG), and the combination of HBO and AMG treatments (HBO+AMG). The HBO group received 250 kPa of oxygen via hyperbaric chamber for 30 days started at their 5th week of life; the AMG group received 1mg/ml of AMG in drinking water from the fifth week till the 17th week of life; and the last group received a combination of these treatments. Rats were sacrificed at the end of the 17th week of life and both femurs were analysed for evidence of osteonecrosis using Micro CT scan and H&E staining. Also, osteocyte apoptosis and the presence of two different forms of NOS (inducible (iNOS) and endothelial (eNOS)) were analysed by immunostaining and apoptosis staining (Hoechst and TUNEL). Results: Bone morphology of metaphyseal and epiphyseal area of all rats were investigated and analysed. Micro CT findings revealed significantly higher mean fractional trabecular bone volume (FBV) of metaphyseal area in untreated SHRs compared with all other treatments (HBO, P<0.05, HBO+AMG, P<0.005, and AMG P<0.001). Bone surface to volume ratio also significantly increased with HBO+AMG and AMG treatments when compared with the control group (18.7 Vs 20.8, P<0.05, and 18.7 Vs 21.1, P<0.05). Epiphyseal mean FBV did not change significantly among groups. In the metaphyseal area, trabecular thickness and numbers significantly decreased with AMG treatment, while trabecular separation significantly increased with both AMG and HBO+AMG treatment. Histological ratio of no ossification and osteonecrosis was 37.5%, 43.7%, 18.7% and 6.2% of control, HBO, HBO+AMG and AMG groups respectively with only significant difference observed between HBO and AMG treatment (P<0.01). High concentration of iNOS was observed in the region of osteonecrosis while there was no evidence of eNOS activity around that region. In comparison with the control group, the ratio of osteocyte apoptosis significantly reduced in AMG treatment (P<0.005). We also observed significantly fewer apoptotic osteocytes in AMG group comparing with HBO treatment (P<0.05). Conclusion: None of our treatments prevents osteonecrosis at the histological or micro CT scan level. High concentration of iNOS in the region of osteonecrosis and significant reduction of osteocyte apoptosis with AMG treatment were supportive of iNOS modulating osteocyte apoptosis in SHRs.

Hydrothermally formed functional niobium oxide doped tungsten nanorods

Nanorod forms of metal oxides is recognised as one of the most remarkable morphologies. Their structure and functionality have driven important advancements in a vast range of electronic devices and applications. In this work, we postulate a novel concept to explain how numerous localised surface states can be engineered into the bandgap of niobium oxide nanorods using tungsten. We discuss their contributions as local state surface charges for the modulation of a Schottky barrier height, relative dielectric constant and their respective conduction mechanisms. Their effect on the hydrogen gas molecule interactions mechanisms are also examined herein. We synthesised niobium tungsten oxide (Nb17W2O25) nanorods via a hydrothermal growth method and evaluated the Schottky barrier height, ideality factor, dielectric constant and trap energy level from the measured I-V vs temperature characteristics in the presence of air and hydrogen to show the validity of our postulations.

Yttrium barium copper oxide thin films on yttria-stabilized zirconia: growth and properties

Y Ba Cu oxide thin films were grown epitaxially on single cryst. yttria-stabilized zirconia substrates by laser deposition. [on SciFinder(R)]

Very thin yttrium barium copper oxide films made by coevaporation

Superconducting YBa2Cu3O7 thin films with various thicknesses from 100 Å to 5000 Å were deposited on (100) SrTiO3 substrates with std. BaF2 coevaporation process. The films had crit. temps. of up to 93 K. The best crit. currents were 1 × 106 A/cm2 at 77 K and 3 × 107 A/cm2 at 4.2 K. The crit. current was generally higher for thinner films. Two different etching methods were used to pattern the films for jc measurements: Ar ion etching and EDTA wet etching. The wet etching was found to work well for thicker films (>1000 Å). For the thinner films, the ion etching process was preferred because of the reduced film surface degrdn. [on SciFinder(R)]

Production of metal oxide nanoparticles

Particles having at least regions of at least one metal oxide having nano-sized grains are produced by providing particles of a material having an initial, nonequiaxed particle shape, prepg. a mixt. of these particles and at last one metal oxide precursor, and treating the mixt. such that the precursor reacts with the particles. The process can be a co-pptn. process, sol-gel synthesis, micro-emulsion method, surfactant-based process, or a process that uses polymers. Complex metal oxide nanoparticles are produced by (a) prepg. a soln. contg. metal cations, (b) mixing the soln. with a surfactant to form micelles within the soln., and (c) heating the micellar liq. to form metal oxide and to remove the surfactant. The formed metal oxide particles have essentially the same morphol. (particle size and shape) as the initial morphol. of the material particles provided. [on SciFinder(R)]

Multi-wall carbon nanotube coating of fluorine-doped tin oxide as an electrode surface modifier for polymer solar cells

A controlled layer of multi-wall carbon nanotubes (MWCNT) was grown directly on top of fluorine-doped tin oxide (FTO) glass electrodes as a surface modifier for improving the performance of polymer solar cells. By using low-temperature chemical vapor deposition with short synthesis times, very short MWCNTs were grown, these uniformly decorating the FTO surface. The chemical vapor deposition parameters were carefully refined to balance the tube size and density, while minimizing the decrease in conductivity and light harvesting of the electrode. As created FTO/CNT electrodes were applied to bulk-heterojunction polymer solar cells, both in direct and inverted architecture. Thanks to the inclusion of MWCNT and the consequent nano-structuring of the electrode surface, we observe an increase in external quantum efficiency in the wavelength range from 550 to 650 nm. Overall, polymer solar cells realized with these FTO/CNT electrodes attain power conversion efficiency higher than 2%, outclassing reference cells based on standard FTO electrodes.

Electrocrystallization of phase I, CuTCNQ (TCNQ= 7, 7, 8, 8-tetracyanoquinodimethane), on indium tin oxide and boron-doped diamond electrodes

The electrochemical reduction of TCNQ to TCNQ•- in acetonitrile in the presence of [Cu(MeCN)4]+ has been undertaken at boron-doped diamond (BDD) and indium tin oxide (ITO) electrodes. The nucleation and growth process at BDD is similar to that reported previously at metal electrodes. At an ITO electrode, the electrocrystallization of more strongly adhered, larger, branched, needle-shaped phase I CuTCNQ crystals is detected under potential step conditions and also when the potential is cycled over the potential range of 0.7 to −0.1 V versus Ag/AgCl (3 M KCl). Video imaging can be used at optically transparent ITO electrodes to monitor the growth stage of the very large branched crystals formed during the course of electrochemical experiments. Both in situ video imaging and ex situ X-ray diffraction and scanning electron microscopy (SEM) data are consistent with the nucleation of CuTCNQ taking place at a discrete number of preferred sites on the ITO surface. At BDD electrodes, ex situ optical images show that the preferential growth of CuTCNQ occurs at the more highly conducting boron-rich areas of the electrode, within which there are preferred sites for CuTCNQ formation.

Effect of the mediator in feedback mode-based SECM interrogation of indium tin-oxide and boron-doped diamond electrodes

Indium tin-oxide (ITO) and polycrystalline boron-doped diamond (BDD) have been examined in detail using the scanning electrochemical microscopy technique in feedback mode. For the interrogation of electrodes made from these materials, the choice of mediator has been varied. Using Ru(CN) 4− 6 (aq), ferrocene methanol (FcMeOH), Fe(CN) 3− 6 (aq) and Ru(NH 3) 3+ 6 (aq), approach curve experiments have been performed, and for purposes of comparison, calculations of the apparent heterogeneous electron transfer rates (k app) have been made using these data. In general, it would appear that values of k app are affected mainly by the position of the mediator reversible potential relative to the relevant semiconductor band edge (associated with majority carriers). For both the ITO (n type) and BDD (p type) electrodes, charge transfer is impeded and values are very low when using FcMeOH and Fe(CN) 3− 6 (aq) as mediators, and the use of Ru(NH 3) 3+ 6(aq) results in the largest value of k app. With ITO, the surface is chemically homogeneous and no variation is observed for any given mediator. Data is also presented where the potential of the ITO electrode is fixed using a ratio of the mediators Fe(CN) 3− 6(aq) and Fe(CN) 4− 6(aq). In stark contrast, the BDD electrode is quite the opposite and a range of k app values are observed for all mediators depending on the position on the surface. Both electrode surfaces are very flat and very smooth, and hence, for BDD, variations in feedback current imply a variation in the electrochemical activity. A comparison of the feedback current where the substrate is biased and unbiased shows a surprising degree of proportionality.

Investigation of mediated oxidation of ascorbic acid by ferrocenemethanol using large-amplitude fourier transformed ac voltammetry under quasi-reversible electron-transfer conditions at an indium tin oxide electrode

The ability of the technique of large-amplitude Fourier transformed (FT) ac voltammetry to facilitate the quantitative evaluation of electrode processes involving electron transfer and catalytically coupled chemical reactions has been evaluated. Predictions derived on the basis of detailed simulations imply that the rate of electron transfer is crucial, as confirmed by studies on the ferrocenemethanol (FcMeOH)-mediated electrocatalytic oxidation of ascorbic acid. Thus, at glassy carbon, gold, and boron-doped diamond electrodes, the introduction of the coupled electrocatalytic reaction, while producing significantly enhanced dc currents, does not affect the ac harmonics. This outcome is as expected if the FcMeOH (0/+) process remains fully reversible in the presence of ascorbic acid. In contrast, the ac harmonic components available from FT-ac voltammetry are predicted to be highly sensitive to the homogeneous kinetics when an electrocatalytic reaction is coupled to a quasi-reversible electron-transfer process. The required quasi-reversible scenario is available at an indium tin oxide electrode. Consequently, reversible potential, heterogeneous charge-transfer rate constant, and charge-transfer coefficient values of 0.19 V vs Ag/AgCl, 0.006 cm s (-1) and 0.55, respectively, along with a second-order homogeneous chemical rate constant of 2500 M (-1) s (-1) for the rate-determining step in the catalytic reaction were determined by comparison of simulated responses and experimental voltammograms derived from the dc and first to fourth ac harmonic components generated at an indium tin oxide electrode. The theoretical concepts derived for large-amplitude FT ac voltammetry are believed to be applicable to a wide range of important solution-based mediated electrocatalytic reactions.