Why Neighborhoods (and How We Study Them) Matter for Adolescent Development

Adolescence is a sensitive developmental period marked by significant changes that unfold across multiple contexts. As a central context of development, neighborhoods capture—in both physical and social space—the stratification of life chances and differential distribution of resources and risks. For some youth, neighborhoods are springboards to opportunities; for others, they are snares that constrain progress and limit the ability to avoid risks. Despite abundant research on “neighborhood effects,” scant attention has been paid to how neighborhoods are a product of social stratification forces that operate simultaneously to affect human development. Neighborhoods in the United States are the manifestation of three intersecting social structural cleavages: race/ethnicity, socioeconomic class, and geography. Many opportunities are allocated or denied along these three cleavages. To capture these joint processes, we advocate a “neighborhood-centered” approach to study the effects of neighborhoods on adolescent development. Using nationally representative data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we demonstrate the complex ways that these three cleavages shape specific neighborhood contexts and can result in stark differences in well-being. A neighborhood-centered approach demands more rigorous and sensitive theories of place, as well as multidimensional classification and measures. We discuss an agenda to advance the state of theories and research, drawing explicit attention to the stratifying forces that bring about distinct neighborhood types that shape developmental trajectories during adolescence and beyond

Role of the endothelium and COX-1 in prostacyclin generation by whole vessels stimulated with different agonists

Prostacyclin is an important cardioprotective hormone produced by the vascular wall, whose synthesis is dependent on cyclo-oxygenase (COX) enzymes. In healthy vessels the endothelium is thought to be the main site of prostacyclin release (Moncada et al 1977). Two isoforms of COX exist, and we have recently published data demonstrating that it is COX-1 rather than COX-2 that drives the production of prostacyclin in mouse aorta (Kirkby et al 2012). In this study we aimed to extend these observations by investigating what proportion of the COX-1 driven aortic prostacyclin production that comes from the endothelium versus the rest of the vessel wall (smooth muscle layers and adventitia). To do this, we explored how removal of the endothelium would influence the ability of aortic tissue to release prostacyclin in response to a range of agonists that are known to activate the endothelium and the vessel wallNon peer reviewe

Role of COX-1 and COX-2 in the release of prostanoids in murine lung and isolated lung fibroblasts

Cyclooxygenase (COX) is the first enzyme in the conversion of arachidonic acid to prostanoids. There are two isoforms of COX; COX-1, which is constitutively expressed with a homeostatic role in most tissues, and COX-2, which while constitutively expressed in some discreet sites is generally inducible by growth factors and during inflammation. In the current study, we have used tissues and cells from knock-out mice to investigate the relative contributions of COX-1 and COX-2 to PGE2 production by lung tissue ex vivo and by proliferating lung fibroblasts in vitro. Lung tissues from WT (C57Bl6), COX-1-/- and COX-2-/- mice were immediately dissected (<15 min after death) and incubated (37 °C) for 30 min in DMEM containing 50 µM calcium ionophore (A23187). Release of PGE2 was determined by competitive immunoassay. In parallel studies, murine lung fibroblasts from COX-1-/- and COX-2-/- mice were explanted and cultured before being seeded in 96-well plates at sub-confluence (5000-8000/well) and incubated for 24-48 hours in the presence of 10% FCS. Accumulated release of PGE2 was then measured as above. Over 30 min PGE2 was released by lung pieces from wild type (1117 ± 55 pg/ml) and COX-2-/- (2013 ± 255 pg/ml) but not from COX-1-/- (<61pg/ml) mice (n=4). In contrast, proliferating lung fibroblasts from COX-1-/- (4978.9 ± 1392 pg/ml) mice released higher levels of PGE2 than cells from COX-2-/- (1194 ± 617 ng/ml) mice (n=4 using cells from 2-3 separate mice for each genotype). These results show that COX-1 activity underpins the stimulated release of PGE2 in healthy mouse lung tissue. Conversely, COX-2 activity predominates in proliferating lung fibroblasts, which may be important as COX-derived PGE2 mediates proliferation of lung fibroblasts (Trends Immunol.2004;25(1):40-6). Our results suggest a switch in COX isoform in lung cells during proliferation which could be relevant to our understanding of conditions such as idiopathic pulmonary fibrosis.Non peer reviewedFinal Accepted Versio

Role of shear stress in endothelial cell morphology and expression of cyclooxygenase isoforms

MEDLINE® is the source for the MeSH terms of this document.Objective-: The goal of this study was to examine the effect of chronic heterogeneous shear stress, applied using an orbital shaker, on endothelial cell morphology and the expression of cyclooxygenases 1 and 2. Methods and results-: Porcine aortic endothelial cells were plated on fibronectin-coated Transwell plates. Cells were cultured for up to 7 days either under static conditions or on an orbital shaker that generated a wave of medium inducing shear stress over the cells. Cells were fixed and stained for the endothelial surface marker CD31 or cyclooxygenases 1 and 2. En face confocal microscopy and scanning ion conductance microscopy were used to show that endothelial cells were randomly oriented at the center of the well, aligned with shear stress nearer the periphery, and expressed cyclooxygenase-1 under all conditions. Lipopolysaccharide induced cyclooxygenase-2 and the production of 6-keto-prostaglandin F1α in all cells. Conclusion-: Cyclooxygenase-1 is expressed in endothelial cells cultured under chronic shear stress of high or low directionality.Peer reviewedSubmitted Versio

Hypoxia modulates platelet purinergic signalling pathways.

BACKGROUND:  Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. METHODS:  Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. RESULTS:  Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. CONCLUSION:  Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation

Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing

This work was funded in part by grants from the Wellcome Trust (0852551Z108/Z, to J.A.M.) and British Heart Foundation (FS/16/1/31699, to NSK). SM is a recipient of a PhD award from the King of Saud University, AT is a recipient of a MRC PhD studentship

Magnetic Reconnection in Extreme Astrophysical Environments

Magnetic reconnection is a basic plasma process of dramatic rearrangement of magnetic topology, often leading to a violent release of magnetic energy. It is important in magnetic fusion and in space and solar physics --- areas that have so far provided the context for most of reconnection research. Importantly, these environments consist just of electrons and ions and the dissipated energy always stays with the plasma. In contrast, in this paper I introduce a new direction of research, motivated by several important problems in high-energy astrophysics --- reconnection in high energy density (HED) radiative plasmas, where radiation pressure and radiative cooling become dominant factors in the pressure and energy balance. I identify the key processes distinguishing HED reconnection: special-relativistic effects; radiative effects (radiative cooling, radiation pressure, and Compton resistivity); and, at the most extreme end, QED effects, including pair creation. I then discuss the main astrophysical applications --- situations with magnetar-strength fields (exceeding the quantum critical field of about 4 x 10^13 G): giant SGR flares and magnetically-powered central engines and jets of GRBs. Here, magnetic energy density is so high that its dissipation heats the plasma to MeV temperatures. Electron-positron pairs are then copiously produced, making the reconnection layer highly collisional and dressing it in a thick pair coat that traps radiation. The pressure is dominated by radiation and pairs. Yet, radiation diffusion across the layer may be faster than the global Alfv\'en transit time; then, radiative cooling governs the thermodynamics and reconnection becomes a radiative transfer problem, greatly affected by the ultra-strong magnetic field. This overall picture is very different from our traditional picture of reconnection and thus represents a new frontier in reconnection research.Comment: Accepted to Space Science Reviews (special issue on magnetic reconnection). Article is based on an invited review talk at the Yosemite-2010 Workshop on Magnetic Reconnection (Yosemite NP, CA, USA; February 8-12, 2010). 30 pages, no figure

Importance of exposure route for behavioural responses in Lumbriculus variegatus Müller (Oligochaeta: Lumbriculida) in short-term exposures to Pb

Abstract Goal, Scope and Background Lumbriculus variegatus Müller (Oligochaeta), a common freshwater sediment-dweller, has frequently been used in toxicokinetic studies, although has been less used in ecotoxicity tests. Methods For the first time the Multispecies Freshwater Biomonitor® (MFB) was applied in a short-term whole-sediment toxicity test. The MFB automatically and quantitatively recorded the spontaneous locomotory behaviour of Lumbriculus variegatus in exposures with two compartments, water and sediment. The study questioned, whether the animals altered their locomotion depending on the compartment which was spiked with lead (Pb). Results and Discussion As in the exposures to Pb-contaminated water/clean sediment, the animals exposed to Pb-contaminated sediment/clean water showed higher activities in intermediate Pb-concentrations. This indicates, that spontaneous locomotory activity is affected by Pb-concentrations at sublethal levels regardless of whether the Pb-concentration is found in the water or in the sediment, because these animals use both environmental compartments simultaneously. However, within the same Pb-levels, the animals showed higher locomotory activity in contaminated water compared with contaminated sediment. This indicates a possible tendency to withdraw from (‘avoidance’) contaminated water into the clean sediment compartment, whereas there was no withdrawal from contaminated sediment into clean water. The latter might be explained by the fact that withdrawal from sediment to water might increase the risk of predation and drift in nature, whereas retracting to sediment might provide shelter. Conclusions The study showed that spontaneous locomotory responses of L. variegatus to Pb depend on whether the water or sediment is contaminated. The study also concluded that the Multispecies Freshwater Biomonitor® can be applied effectively in sediment toxicity testing. Recommendations and Perspectives More emphasis should be given to the interactions of water/sediment in sediment ecotoxicity tests to better simulate field conditions and increase ecological realism in risk assessment, especially as quantitative recording methods exisit

The effect of autonomy, training opportunities, age and salaries on job satisfaction in the South East Asian retail petroleum industry

South East Asian petroleum retailers are under considerable pressure to improve service quality by reducing turnover. An empirical methodology from this industry determined the extent to which job characteristics, training opportunities, age and salary influenced the level of job satisfaction, an indicator of turnover. Responses are reported on a random sample of 165 site employees (a 68% response rate) of a Singaporean retail petroleum firm. A restricted multivariate regression model of autonomy and training opportunities explained the majority (35.4%) of the variability of job satisfaction. Age did not moderate these relationships, except for employees >21 years of age, who reported enhanced job satisfaction with additional salary. Human Capital theory, Life Cycle theory and Job Enrichment theory are invoked and explored in the context of these findings in the South East Asian retail petroleum industry. In the South East Asian retail petroleum industry, jobs providing employees with the opportunity to undertake a variety of tasks that enhanced the experienced meaningfulness of work are likely to promote job satisfaction, reduce turnover and increase the quality of service