Promoting Physical Activity in Low Income African Americans: Project LAPS

Low income African Americans are at increased risk for physical inactivity and related chronic illnesses. Thus, effective interventions are needed to address these health disparities. The current study examined the efficacy of a home-based physical activity intervention among a low income African American sample with high rates of chronic illnesses (obesity, hypertension, diabetes, high cholesterol). Participants (n=214) were randomly assigned to either the home-based physical activity intervention (self-help print materials, five monthly newsletters, two telephone counseling sessions) or an attention control condition, which promoted healthy diet. Results indicated that the intervention did not produce significantly greater increases in physical activity from baseline to six months than the control group. Lessons learned from the current study include the importance of using proactive retention strategies with low income African American participants and taking into consideration the cultural relevance of the intervention

Helicobacter pylori phagosome maturation in primary human macrophages

Extent: 14p.Background: Helicobacter pylori (H. pylori) is a micro-aerophilic, spiral-shaped, motile bacterium that is the principal cause of gastric and duodenal ulcers in humans and is a major risk factor for the development of gastric cancer. Despite provoking a strong innate and adaptive immune response in the host, H. pylori persists in the gastric mucosa, avoiding eradication by macrophages and other phagocytic cells, which are recruited to the site of infection. Here we have characterised the critical degradative process of phagosome maturation in primary human macrophages for five genotypically and phenotypically distinct clinical strains of H. pylori. Results: All of the H. pylori strains examined showed some disruption to the phagosome maturation process, when compared to control E. coli. The early endosome marker EEA1 and late endosome marker Rab7 were retained on H. pylori phagosomes, while the late endosome-lysosome markers CD63, LAMP-1 and LAMP-2 were acquired in an apparently normal manner. Acquisition of EEA1 by H. pylori phagosomes appeared to occur by two distinct, strain specific modes. H. pylori strains that were negative for the cancer associated virulence factor CagA were detected in phagosomes that recruited large amounts of EEA1 relative to Rab5, compared to CagA positive strains. There were also strain specific differences in the timing of Rab7 acquisition which correlated with differences in the rate of intracellular trafficking of phagosomes and the timing of megasome formation. Megasomes were observed for all of the H. pylori strains examined. Conclusions: H. pylori appeared to disrupt the normal process of phagosome maturation in primary human macrophages, appearing to block endosome fission. This resulted in the formation of a hybrid phagosome-endosome-lysosome compartment, which we propose has reduced degradative capacity. Reduced killing by phagocytes is consistent with the persistence of H. pylori in the host, and would contribute to the chronic stimulation of the inflammatory immune response, which underlies H. pylori-associated disease.Glenn N Borlace, Hilary F Jones, Stacey J Keep, Ross N Butler, Doug A Brook

In the Shadow of the Accretion Disk: Higher Resolution Imaging of the Central Parsec in NGC 4261

The physical conditions in the inner parsec of accretion disks believed to orbit the central black holes in active galactic nuclei can be probed by imaging the absorption (by ionized gas in the disk) of background emission from a radio counterjet. We report high angular resolution VLBI observations of the nearby (about 40 Mpc) radio galaxy NGC 4261 that confirm free-free absorption of radio emission from a counterjet by a geometrically thin, nearly edge-on disk at 1.6, 4.8, and 8.4 GHz. The angular width and depth of the absorption appears to increase with decreasing frequency, as expected. We derive an average electron density of ~10E4 per cc at a disk radius of about 0.2 pc, assuming that the inner disk inclination and opening angles are the same as at larger radii. Pressure balance between the thermal gas and the magnetic field in the disk implies an average field strength of 0.1 milligauss at a radius of 0.2 pc. These are the closest-in free-free absorption measurements to date of the conditions in an extragalactic accretion disk orbiting a black hole with a well-determined mass. If a standard advection-dominated accretion flow exists in the disk center, then the transition between thin and thick disk regions must occur at a radius less than 0.2 pc (4000 Schwarzschild radii).Comment: 20 pages including 12 figures. Accepted for publication in Ap

Adsorbate-Induced Segregation of Cobalt from PtCo Nanoparticles: Modeling Au Doping and Core AuCo Alloying for the Improvement of Fuel Cell Cathode Catalysts

Platinum, when used as a cathode material for the oxygen reduction reaction, suffers from high overpotential and possible dissolution, in addition to the scarcity of the metal and resulting cost. Although the introduction of cobalt has been reported to improve reaction kinetics and decrease the precious metal loading, surface segregation or complete leakage of Co atoms causes degradation of the membrane electrode assembly, and either of these scenarios of structural rearrangement eventually decreases catalytic power. Ternary PtCo alloys with noble metals could possibly maintain activity with a higher dissolution potential. First-principles-based theoretical methods are utilized to identify the critical factors affecting segregation in Pt–Co binary and Pt–Co–Au ternary nanoparticles in the presence of oxidizing species. With a decreasing share of Pt, surface segregation of Co atoms was already found to become thermodynamically viable in the PtCo systems at low oxygen concentrations, which is assigned to high charge transfer between species. While the introduction of gold as a dopant caused structural changes that favor segregation of Co, creation of CoAu alloy core is calculated to significantly suppress Co leakage through modification of the electronic properties. The theoretical framework of geometrically different ternary systems provides a new route for the rational design of oxygen reduction catalysts

The Generation of Successive Unmarked Mutations and Chromosomal Insertion of Heterologous Genes in Actinobacillus pleuropneumoniae Using Natural Transformation

We have developed a simple method of generating scarless, unmarked mutations in Actinobacillus pleuropneumoniae by exploiting the ability of this bacterium to undergo natural transformation, and with no need to introduce plasmids encoding recombinases or resolvases. This method involves two successive rounds of natural transformation using linear DNA: the first introduces a cassette carrying cat (which allows selection by chloramphenicol) and sacB (which allows counter-selection using sucrose) flanked by sequences to either side of the target gene; the second transformation utilises the flanking sequences ligated directly to each other in order to remove the cat-sacB cassette. In order to ensure efficient uptake of the target DNA during transformation, A. pleuropneumoniae uptake sequences are added into the constructs used in both rounds of transformation. This method can be used to generate multiple successive deletions and can also be used to introduce targeted point mutations or insertions of heterologous genes into the A. pleuropneumoniae chromosome for development of live attenuated vaccine strains. So far, we have applied this method to highly transformable isolates of serovars 8 (MIDG2331), which is the most prevalent in the UK, and 15 (HS143). By screening clinical isolates of other serovars, it should be possible to identify other amenable strains

A novel system for spatial and temporal imaging of intrinsic plant water use efficiency

Instrumentation and methods for rapid screening and selection of plants with improved water use efficiency are essential to address current issues of global food and fuel security. A new imaging system that combines chlorophyll fluorescence and thermal imaging has been developed to generate images of assimilation rate (A), stomatal conductance (gs), and intrinsic water use efficiency (WUEi) from whole plants or leaves under controlled environmental conditions. This is the first demonstration of the production of images of WUEi and the first to determine images of gs from themography at the whole-plant scale. Data are presented illustrating the use of this system for rapidly and non-destructively screening plants for alterations in WUEi by comparing Arabidopsis thaliana mutants (OST1-1) that have altered WUEi driven by open stomata, with wild-type plants. This novel instrument not only provides the potential to monitor multiple plants simultaneously, but enables intra- and interspecies variation to be taken into account both spatially and temporally. The ability to measure A, gs, and WUEi progressively was developed to facilitate and encourage the development of new dynamic protocols. Images illustrating the instrument's dynamic capabilities are demonstrated by analysing plant responses to changing photosynthetic photon flux density (PPFD). Applications of this system will augment the research community's need for novel screening methods to identify rapidly novel lines, cultivars, or species with improved A and WUEi in order to meet the current demands on modern agriculture and food production. © The Author 2013. Published by Oxford University Press on behalf of the Society for Experimental Biology

A Glimpse of the Stellar Populations and Elemental Abundances of Gravitationally Lensed, Quiescent Galaxies at z≳1z\gtrsim 1 with Keck Deep Spectroscopy

Gravitational lenses can magnify distant galaxies, allowing us to discover and characterize the stellar populations of intrinsically faint, quiescent galaxies that are otherwise extremely difficult to directly observe at high redshift from ground-based telescopes. Here, we present the spectral analysis of two lensed, quiescent galaxies at $z\gtrsim 1$ discovered by the ASTRO 3D Galaxy Evolution with Lenses survey: AGEL1323 ($M_*\sim 10^{11.1}M_{\odot}$, $z=1.016$, $\mu \sim 14.6$) and AGEL0014 ($M_*\sim 10^{11.3}M_{\odot}$, $z=1.374$, $\mu \sim 4.3$). We measured the age, [Fe/H], and [Mg/Fe] of the two lensed galaxies using deep, rest-frame-optical spectra (S/N $\gtrsim$ 40\AA$^{-1}$) obtained on the Keck I telescope. The ages of AGEL1323 and AGEL0014 are $5.6^{+0.8}_{-0.8}$ Gyr and $3.1^{+0.8}_{-0.3}$ Gyr, respectively, indicating that most of the stars in the galaxies were formed less than 2 Gyr after the Big Bang. Compared to nearby quiescent galaxies of similar masses, the lensed galaxies have lower [Fe/H] and [Mg/H]. Surprisingly, the two galaxies have comparable [Mg/Fe] to similar-mass galaxies at lower redshifts, despite their old ages. Using a simple analytic chemical evolution model connecting the instantaneously recycled element Mg with the mass-loading factors of outflows averaged over the entire star formation history, we found that the lensed galaxies may have experienced enhanced outflows during their star formation compared to lower-redshift galaxies, which may explain why they quenched early.Comment: 18 pages, 11 figures, submitted to ApJ; comments welcom

Loss of Expression and Promoter Methylation of SLIT2 Are Associated with Sessile Serrated Adenoma Formation.

Serrated adenomas form a distinct subtype of colorectal pre-malignant lesions that may progress to malignancy along a different molecular pathway than the conventional adenoma-carcinoma pathway. Previous studies have hypothesised that BRAF mutation and promoter hypermethylation plays a role, but the evidence for this is not robust. We aimed to carry out a whole-genome loss of heterozygosity analysis, followed by targeted promoter methylation and expression analysis to identify potential pathways in serrated adenomas. An initial panel of 9 sessile serrated adenomas (SSA) and one TSA were analysed using Illumina Goldengate HumanLinkage panel arrays to ascertain regions of loss of heterozygosity. This was verified via molecular inversion probe analysis and microsatellite analysis of a further 32 samples. Methylation analysis of genes of interest was carried out using methylation specific PCR (verified by pyrosequencing) and immunohistochemistry used to correlate loss of expression of genes of interest. All experiments used adenoma samples and normal tissue samples as control. SSA samples were found on whole-genome analysis to have consistent loss of heterozygosity at 4p15.1–4p15.31, which was not found in the sole TSA, adenomas, or normal tissues. Genes of interest in this region were PDCH7 and SLIT2, and combined MSP/IHC analysis of these genes revealed significant loss of SLIT2 expression associated with promoter methylation of SLIT2. Loss of expression of SLIT2 by promoter hypermethylation and loss of heterozygosity events is significantly associated with serrated adenoma development, and SLIT2 may represent a epimutated tumour suppressor gene according to the Knudson “two hit” hypothesis