Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22phox gene on vascular superoxide production in atherosclerosis.

BACKGROUND:

Increased superoxide anion production increases oxidative stress and reduces nitric oxide bioactivity in vascular disease states. NAD(P)H oxidase is an important source of superoxide in human blood vessels, and some studies suggest a possible association between polymorphisms in the NAD(P)H oxidase CYBA gene and atherosclerosis; however, no functional data address this hypothesis. We examined the relationships between the CYBA C242T polymorphism and direct measurements of superoxide production in human blood vessels.

METHODS AND RESULTS:

Vascular NAD(P)H oxidase activity was determined in human saphenous veins obtained from 110 patients with coronary artery disease and identified risk factors. Immunoblotting, reverse-transcription polymerase chain reaction, and DNA sequencing showed that p22phox protein, mRNA, and 242C/T allelic variants are expressed in human blood vessels. Vascular superoxide production, both basal and NADH-stimulated, was highly variable between patients, but the presence of the CYBA 242T allele was associated with significantly reduced vascular NAD(P)H oxidase activity, independent of other clinical risk factors for atherosclerosis.

CONCLUSIONS:

Association of the CYBA 242T allele with reduced NAD(P)H oxidase activity in human blood vessels suggests that genetic variation in NAD(P)H oxidase components may play a significant role in modulating superoxide production in human atherosclerosis.

The effects of a volunteer mentoring programme on reading outcomes among eight- to nine-year-old children: A follow up randomized controlled trial

This article presents the findings of a randomized controlled trial evaluation of the effects of a revised version of the volunteer mentoring programme, Time to Read. Participating children received two 30-minute mentoring sessions per week from volunteer mentors who carried out paired reading activities with the children. The current trial involved 512 children aged eight to nine years from 50 primary schools. The programme was found to be effective in improving decoding skills (d=+.15), reading rate (d=+.22) and reading fluency (d=+.14) and there was some evidence of a positive effect in relation to the children’s aspirations for the future (d=+.11). However, no evidence was found of the programme having an effect on reading comprehension or reading confidence and enjoyment of reading. The article concludes by suggesting that mentoring programmes using non-specialist volunteers can be effective in improving foundational reading skills but would appear to be less effective in terms of improving higher-order skills such as comprehension. The article also suggests that such programmes are likely to be most effective if concentrating on core reading activities rather than attempting to address reading outcomes indirectly through improving children’s confidence or wider enjoyment of reading.

A high C/O ratio and weak thermal inversion in the atmosphere of exoplanet WASP-12b

The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmosphere can also differ from those in the Solar System. The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry of the transiting hot-Jupiter WASP-12b (ref. 6) that reveals C/O>=1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T>2,500K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres.

Spitzer Secondary Eclipses of WASP-18b

The transiting exoplanet WASP-18b was discovered in 2008 by the Wide Angle Search for Planets project. The Spitzer Exoplanet Target of Opportunity Program observed secondary eclipses of WASP-18b using Spitzer's Infrared Array Camera in the 3.6 µm and 5.8 µm bands on 2008 December 20, and in the 4.5 µm and 8.0 µm bands on 2008 December 24. We report eclipse depths of 0.30% ± 0.02%, 0.39% ± 0.02%, 0.37% ± 0.03%, 0.41% ± 0.02%, and brightness temperatures of 3100 ± 90, 3310 ± 130, 3080 ± 140, and 3120 ± 110 K in order of increasing wavelength. WASP-18b is one of the hottest planets yet discovered—as hot as an M-class star. The planet's pressure-temperature profile most likely features a thermal inversion. The observations also require WASP-18b to have near-zero albedo and almost no redistribution of energy from the day side to the night side of the planet.

Range expansion in an invasive small mammal: influence of life-history and habitat quality.

Invasive species pose a major threat to biodiversity but provide an opportunity to describe the processes that lead to changes in a species’ range. The bank vole (Myodes glareolus) is an invasive rodent that was introduced to Ireland in the early twentieth century. Given its continuing range expansion, the substantial empirical data on its spread thus far, and the absence of any eradication program, the bank vole in Ireland represents a unique model system for studying the mechanisms influencing the rate of range expansion in invasive small mammals. We described the invasion using a reaction–diffusion model informed by empirical data on life history traits and demographic parameters. We subsequently modelled the processes involved in its range expansion using a rule-based spatially explicit simulation. Habitat suitability interacted with density-dependent parameters to influence dispersal, most notably the density at which local populations started to donate emigrating individuals, the number of dispersing individuals and the direction of dispersal. Whilst local habitat variability influenced the rate of spread, on a larger scale the invasion resembled a simple reaction–diffusion process. Our results suggest a Type 1 range expansion where the rate of expansion is generally constant over time, but with some evidence for a lag period following introduction. We demonstrate that a two-parameter empirical model and a rule-based spatially explicit simulation are sufficient to accurately describe the invasion history of a species that exhibits a complex, density-dependent pattern of dispersal.

Therapeutic revascularisation of ischaemic tissue. The opportunities and challenges for therapy using vascular stem/ progenitor cells

Ischaemia-related diseases such as peripheral artery disease and coronary heart disease constitute a major issue in medicine as they affect millions of individuals each year and represent a considerable economic burden to healthcare systems. If the underlying ischaemia is not sufficiently resolved it can lead to tissue damage, with subsequent cell death. Treating such diseases remains difficult and several strategies have been used to stimulate the growth of blood vessels and promote regeneration of ischaemic tissues, such as the use of recombinant proteins and gene therapy. Although these approaches remain promising, they have limitations and results from clinical trials using these methods have had limited success. Recently, there has been growing interest in the therapeutic potential of using a cell-based approach to treat vasodegenerative disorders. In vascular medicine, various stem cells and adult progenitors have been highlighted as having a vasoreparative role in ischaemic tissues. This review will examine the clinical potential of several stem and progenitor cells that may be utilised to regenerate defunct or damaged vasculature and restore blood flow to the ischaemic tissue. In particular, we focus on the therapeutic potential of endothelial progenitor cells as an exciting new option for the treatment of ischaemic diseases. © 2012 BioMed Central Ltd