Role of oxidative stress on diesel-enhanced influenza infection in mice

Numerous studies have shown that air pollutants, including diesel exhaust (DE), reduce host defenses, resulting in decreased resistance to respiratory infections. This study sought to determine if DE exposure could affect the severity of an ongoing influenza infection in mice, and examine if this could be modulated with antioxidants. BALB/c mice were treated by oropharyngeal aspiration with 50 plaque forming units of influenza A/HongKong/8/68 and immediately exposed to air or 0.5 mg/m3 DE (4 hrs/day, 14 days). Mice were necropsied on days 1, 4, 8 and 14 post-infection and lungs were assessed for virus titers, lung inflammation, immune cytokine expression and pulmonary responsiveness (PR) to inhaled methacholine. Exposure to DE during the course of infection caused an increase in viral titers at days 4 and 8 post-infection, which was associated with increased neutrophils and protein in the BAL, and an early increase in PR. Increased virus load was not caused by decreased interferon levels, since IFN-β levels were enhanced in these mice. Expression and production of IL-4 was significantly increased on day 1 and 4 p.i. while expression of the Th1 cytokines, IFN-γ and IL-12p40 was decreased. Treatment with the antioxidant N-acetylcysteine did not affect diesel-enhanced virus titers but blocked the DE-induced changes in cytokine profiles and lung inflammation. We conclude that exposure to DE during an influenza infection polarizes the local immune responses to an IL-4 dominated profile in association with increased viral disease, and some aspects of this effect can be reversed with antioxidants

Comparative lung toxicity of engineered nanomaterials utilizing in vitro, ex vivo and in vivo approaches

BackgroundAlthough engineered nanomaterials (ENM) are currently regulated either in the context of a new chemical, or as a new use of an existing chemical, hazard assessment is still to a large extent reliant on information from historical toxicity studies of the parent compound, and may not take into account special properties related to the small size and high surface area of ENM. While it is important to properly screen and predict the potential toxicity of ENM, there is also concern that current toxicity tests will require even heavier use of experimental animals, and reliable alternatives should be developed and validated. Here we assessed the comparative respiratory toxicity of ENM in three different methods which employed in vivo, in vitro and ex vivo toxicity testing approaches.MethodsToxicity of five ENM (SiO2 (10), CeO2 (23), CeO2 (88), TiO2 (10), and TiO2 (200); parentheses indicate average ENM diameter in nm) were tested in this study. CD-1 mice were exposed to the ENM by oropharyngeal aspiration at a dose of 100μg. Mouse lung tissue slices and alveolar macrophages were also exposed to the ENM at concentrations of 22–132 and 3.1-100μg/mL, respectively. Biomarkers of lung injury and inflammation were assessed at 4 and/or 24hr post-exposure.ResultsSmall-sized ENM (SiO2 (10), CeO2 (23), but not TiO2 (10)) significantly elicited pro-inflammatory responses in mice (in vivo), suggesting that the observed toxicity in the lungs was dependent on size and chemical composition. Similarly, SiO2 (10) and/or CeO2 (23) were also more toxic in the lung tissue slices (ex vivo) and alveolar macrophages (in vitro) compared to other ENM. A similar pattern of inflammatory response (e.g., interleukin-6) was observed in both ex vivo and in vitro when a dose metric based on cell surface area (μg/cm2), but not culture medium volume (μg/mL) was employed.ConclusionExposure to ENM induced acute lung inflammatory effects in a size- and chemical composition-dependent manner. The cell culture and lung slice techniques provided similar profiles of effect and help bridge the gap in our understanding of in vivo, ex vivo, and in vitro toxicity outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-014-0047-3) contains supplementary material, which is available to authorized users

Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices

BackgroundEmissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments.MethodsSize-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100μg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8mm diameter lung slices from CD-1 mice were exposed (11μg) ± co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound.ResultsOn an equi-mass basis, coarse ENCF-1PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-α, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB.ConclusionsThe findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations

Flute Studio Recital

Program listing performers and works performe

The Vehicle, Spring 2009

Table of Contents Idyllic Has an EndJustine Fittonpage 28 The RemedyJosh Boykinpage 29 True NatureStephen Garciapage 30 We Are All Eaters of SoulsDan Davispage 31 Scarlet on the WindJustin Sudkamppage 34 IlluminatedRashelle McNairpage 35 Lightning RodKim Hunter-Perkinspage 36 TrialDan Davispage 49 Dear GodKristi Kohlenbergpage 50 A Cheap Metaphor Is What We Have for DeathKeith Stewartpage 51 Sad MoonJennifer O\u27Neilpage 52 The Transported ManStephen Garciapage 61 Divine InsanityGrace Lawrencepage 62 Moonglow MemoriesJustin Sudkamppage 63 Poetry The Habits of HusbandsKim Hunter-Perkinspage 4 Young AmericanMaria Rhodespage 5 Kevin Doesn\u27t Live Here AnymoreJustine Fittonpage 6 Summer VacationMary Lieskepage 8 PerfectChristie Cheatlepage 9 Hate for OneMiranda Whitepage 10 The Witch\u27s GraveDan Davispage 16 Medicine WomanLindsey Durbinpage 18 Epistle to a BombshellKim Hunter-Perkinspage 19 GuardedAaron Dillardpage 20 Lean and Hungry in YesteryearTim Ernstpage 21 Dirty TearsBrittany Morganpage 27 I Left the Radio OnSerena Heathpage 83 Untitled, for CourtneyKellen Fasnachtpage 84 Ermine DriveStephen Garciapage 85 Prose TwigDaniel Paquinpage 11 Coyote MoonDan Davispage 22 BloodGretchen Schaiblepage 32 IntroductionSam Sottosantopage 53 The Guitar ManDan Davispage 75 Art Picasso InspirationAlycia Rockeycover StageSarah Fairchildpage 37 ConnectedBrittany Morganpage 65 SpringAnthony Travis Shootpage 66 BodhisattvaSarah Fairchildpage 67 What About Love?Justin Sudkamppage 68 Angry MoonJennifer O\u27Neilpage 69 HauntedKellen Fasnachtpage 70 Haiku #1Justin Sudkamppage 72 ImmobileRashelle McNairpage 73 The ChurningJosh Boykinpage 74 The Old Boat DockJosh Boykinpage 79 Saltwater RaindropsTim Ernstpage 80 Slow MotionGrace Lawrencepage 81 Solid AdviceAnthony Travis Shootpage 82 TreeAlycia Rockeypage 38 TireSarah Fairchildpage 39 What to WearKristy Pearsonpage 40 Figure 1Sean Walkerpage 41 GreenhouseAlycia Rockeypage 42 RomeAlycia Rockeypage 43 Me at the Lamp PostElizabeth Surbeckpage 44 Little Miss LizKristy Pearsonpage 45 DoudnaAlycia Rockeypage 46 FlagAlycia Rockeypage 47 Flag ProtestAlycia Rockeypage 48 Features Note From the EditorRebecca Griffithpage 1 Fall 2008-Spring 2009 Vehicle Award Winnerspage 2 James K. Johnson Creative Writing Awardpage 86 Winning Entry (Nonfiction)Daniel Paquinpage 87 Winning Entries (Poetry)Anthony Travis Shootpage 98 Contributorspage 103https://thekeep.eiu.edu/vehicle/1091/thumbnail.jp

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Radically Practical: Rabbi Emil G. Hirsch’s Response to Modernity

This project examines the theological thought and social practice of Rabbi Emil G. Hirsch from 1880 -1923 to demonstrate how he bridged the gap between Judaic faith and modernity within American Reform Judaism. I argue that Hirsch’s approach to the problems associated with modernity were neither fringe or radical, but practical and part of a greater logic within one rabbi’s theological thought. I pursue this argument through close analysis of Hirsch’s writings, sermons, and congregational notes. I use the important secondary literature on American Reform Judaism to help contextualize Hirsch’s work. At the same time, I critique the assertion that rabbi Hirsch should be a forgotten voice within American Reform Judaism due to his controversial positions on topics, such as Zionism. I executed this through a series of chapters that lead the reader through Hirsch’s place at Chicago Sinai, the logic behind his view on Jewish identity within and outside the community, and why he could not be a Zionist to show that the rabbi acted in an ordered manner in responding to his congregation’s problems in the face of modernity