Effects of Air Pollution and the Introduction of the London Low Emission Zone on the Prevalence of Respiratory and Allergic Symptoms in Schoolchildren in East London: A Sequential Cross-Sectional Study

The adverse effects of traffic-related air pollution on children’s respiratory health have been widely reported, but few studies have evaluated the impact of traffic-control policies designed to reduce urban air pollution. We assessed associations between traffic-related air pollutants and respiratory/allergic symptoms amongst 8–9 year-old schoolchildren living within the London Low Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained using a parent-completed questionnaire and linked to modelled annual air pollutant concentrations based on the residential address of each child, using a multivariable mixed effects logistic regression analysis. Exposure to traffic-related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI 1.00–1.02), NO₂ (1.03, 1.00–1.06), PM₁₀ (1.16, 1.04–1.28) and PM_2.5 (1.38, 1.08–1.78), all per μg/m³ of pollutant, but not with other respiratory/allergic symptoms. The LEZ did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied. These data confirm the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis. Importantly, the London LEZ has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions.     

Statistical modeling of biomedical corpora: mining the Caenorhabditis Genetic Center Bibliography for genes related to life span

Background  

The statistical modeling of biomedical corpora could yield integrated, coarse-to-fine views of biological phenomena that complement discoveries made from analysis of molecular sequence and profiling data. Here, the potential of such modeling is demonstrated by examining the 5,225 free-text items in the Caenorhabditis Genetic Center (CGC) Bibliography using techniques from statistical information retrieval. Items in the CGC biomedical text corpus were modeled using the Latent Dirichlet Allocation (LDA) model. LDA is a hierarchical Bayesian model which represents a document as a random mixture over latent topics; each topic is characterized by a distribution over words.     

Implications of the kynurenine pathway and quinolinic acid in Alzheimer's disease

Summary

Ozone, though not a free radical species, mediates its toxic effects through free radical reactions as a consequence of its high redox potential. Upon inspiration the first physical interface encountered by ozone is a thin layer of aqueous material, the epithelium lining fluid (ELF) which overlays, and is partially derived from, the underlying pulmonary epithelium. ELF is the first physical interface encountered by ozone and the majority of its primary actions are confined to this compartment. ELF contains a range of antioxidants, including the small molecular weight antioxidants: uric acid (UA), ascorbic acid (AH₂) and reduced glutathione (GSH). These compounds are present in large quantities and display high intrinsic reactivities toward ozone, consistent with their role as sacrificial substrates in this setting. In this paper we examine the concept that antioxidants, in ELF, represent the first tier of defence against the oxidizing effects of ozone. Since the concentration of these antioxidants appears to differ between individuals, we propose that these protective substances may dictate, in part, an individual's sensitivity to oxidizing air pollutants such as ozone.     

Estimating the rate of evolution of the rate of molecular evolution

A simple model for the evolution of the rate of molecular evolution is presented. With a Bayesian approach, this model can serve as the basis for estimating dates of important evolutionary events even in the absence of the assumption of constant rates among evolutionary lineages. The method can be used in conjunction with any of the widely used models for nucleotide substitution or amino acid replacement. It is illustrated by analyzing a data set of rbcL protein sequences.      

An in vitro and in vivo investigation of the effects of diesel exhaust on human airway lining fluid antioxidants

Breathing high concentrations of diesel exhaust (DE) induces pulmonary inflammation, bronchoconstriction, increased airway reactivity, and oxidative stress in healthy subjects. To examine if these responses occur at environmentally relevant concentrations of DE, we exposed 25 healthy subjects to DE (PM(10) 100 microg/m(3), 0.6 ppm NO(2) for 2-h) and filtered air on separate occasions. Immediately following DE exposure, subjects displayed an increase in subjective symptoms and a mild bronchoconstriction. Six hours following the cessation of DE exposure neither airway inflammation, nor antioxidant depletion (ascorbate, urate, and reduced glutathione), was seen at any level of the respiratory tract. Instead, an increased flux of reduced glutathione into the bronchial (p < 0.01) and nasal airways (p < 0.05) was observed. In separate, in vitro experiments, DE was found to have comparable oxidative activity to the transition metal rich residual oil fly ash (ROFA) particle, significantly depleting lung lining fluid ascorbic acid and reduced glutathione in a transition metal and superoxide-dependent mechanism. Together, these data indicate that even though DE has marked oxidative activity, this effect is not observed to any great extent in the airways of healthy subjects. We interpret these findings as being indicative that the antioxidant network at the air-lung interface in healthy subjects is capable of dealing with the oxidative challenge posed by DE at ambient concentrations.     

Evaluation of a candidate International Standard for Meningococcal Group C polysaccharide

Meningococcal group C (MenC) plain polysaccharide (PS) and conjugate vaccines are primarily evaluated by physicochemical methods to ensure that batches are consistently manufactured. As different assays are employed to quantify the MenC PS content of final formulations and bulk intermediaries, there is a need for an International MenC PS Standard to calibrate internal references used in the different laboratories. Twelve laboratories from nine different countries participated in a collaborative study to determine the MenC PS content of a candidate International Standard MenC PS preparation (08/214) and to assess its suitability. On the basis of the results from this study the candidate standard 08/214 was established as an International Standard for the quantification of MenC PS content in vaccines and components. It has a content of 1.192 ± 0.192 mg MenC PS/ampoule (expanded uncertainty with coverage factor of k = 2.365 corresponding to a 95% level of confidence), as determined by the resorcinol assays carried out by eight of the participating laboratories. The standard is available from The National Institute of Biological Standards and Control who act as guardians and distributors of the material under the auspices of WHO.     

Depletion of urate in human nasal lavage following in vitro ozone exposure

Ozone, a strong oxidant present in summer smog, is thought to primarily react with antioxidant molecules found in the epithelial lining fluid of the respiratory tract. In humans, as much as 40% of inhaled ozone can be removed in the nasal cavity where the major extracellular antioxidant has been identified as uric acid. The present study was undertaken to examine urate/oxidant interactions in human nasal lavage fluid following in vitro exposure to ozone at concentrations relevant to the U.K. Lavage fluid was collected from 8 volunteers using a modified Foley catheter which permits prolonged contact of isotonic saline with the anterior nasal cavity. Nasal lavage samples in multiwell plates were exposed to ozone at concentrations of 50, 100 and 250 ppb. Samples were removed at intervals from 15 to 240 min following exposure and assayed for uric acid depletion. Uric acid concentrations in the nasal lavage were found to fall from 8.52 (time zero) to 3.99 μM, 0.05 and 0.07 μM after 240 min at 50, 100 and 250 ppb ozone respectively. At a non-environmentally relevant ozone concentration of 1000 ppb, uric acid was completely depleted after 60 min. Regression analysis showed a linear correlation between rate of loss of urate and ozone concentration (R² = 0.97). A novel, non-invasive technique is described to investigate antioxidant compromise and its importance in individual subjects. We conclude that uric acid in nasal lavage samples is scavenged by ozone in a dose and time dependant manner.     

Ensemble attribute profile clustering: discovering and characterizing groups of genes with similar patterns of biological features

Background  

Ensemble attribute profile clustering is a novel, text-based strategy for analyzing a user-defined list of genes and/or proteins. The strategy exploits annotation data present in gene-centered corpora and utilizes ideas from statistical information retrieval to discover and characterize properties shared by subsets of the list. The practical utility of this method is demonstrated by employing it in a retrospective study of two non-overlapping sets of genes defined by a published investigation as markers for normal human breast luminal epithelial cells and myoepithelial cells.     

Alpha tocopherol supplementation elevates plasma apolipoprotein A1 isoforms in normal healthy subjects

Plasma alpha-tocopherol (AT) concentrations are inversely related to cardiovascular (CV) risk; however, intervention studies with AT have failed to show any consistent benefit against CV disease (CVD). Proteomics offers the opportunity to examine novel effects of AT supplementation on protein expression and therefore improve our understanding of the physiological roles of AT. Thus, to investigate the effects of AT supplementation on the plasma proteome of healthy subjects we have undertaken a double-blind, randomised, parallel design supplementation study in which healthy subjects (n = 32; 11 male and 21 female) consumed AT supplements (134 or 268 mg/day) or placebo capsules for up to 28 days. Plasma samples were obtained before supplementation and after 14 and 28 days of supplementation for analysis of changes in the plasma proteome using 2-DE and MALDI-MS. Using semiquantitative proteomics, we observed that proapolipoprotein A1 (identified by MS and Western blotting) was altered at least two-fold. Using quantitative ELISA techniques, we confirmed a significant increase in plasma apolipoprotein A1 concentration following supplementation with AT which was both time and dose dependent (p < 0.01 after 28 days supplementation with 268 mg AT/day). These data demonstrate the time and dose sensitivity of the plasma proteome to AT supplementation.