118 research outputs found

    Cooperation between Mast Cells and Neurons Is Essential for Antigen-Mediated Bronchoconstriction

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    Mast cells are important sentinels guarding the interface between the environment and the body: a breach in the integrity of this interface can lead to the release of a plethora of mediators which engage the foreign agent, recruit leukocytes, and initiate adaptive physiological changes in the organism. While these capabilities make mast cells critical players in immune defense, it also makes them important contributors to the pathogenesis of diseases such as asthma. Mast cell mediators induce dramatic changes in smooth muscle physiology, and the expression of receptors for these factors by smooth muscle suggests that they act directly to initiate constriction. Contrary to this view, we show here that mast cell-mediated bronchoconstriction is observed only in animals with intact innervation of the lung and that serotonin release alone is required for this action. While ablation of sensory neurons does not limit bronchoconstriction, constriction after antigen challenge is absent in mice in which the cholinergic pathways are compromised. Linking mast cell function to the cholinergic system likely provides an important means of modulating the function of these resident immune cells to physiology of the lung, but may also provide a safeguard against life-threatening anaphylaxis during mast cell degranulation

    Focused Ion Beam Fabrication

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    Contains reports on thirteen research projects and a list of publications.Defense Advanced Research Projects Agency/U.S. Army Research Office Contract DAAL03-88-K-0108National Science Foundation Grant ECS 89-21728MIT Lincoln Laboratory Innovative Research ProgramSEMATECH Contract 90-MC-503Micrion Contract M08774U.S. Army Research Office Contract DAAL03-87-K-0126IBM Corporatio

    Focused Ion Beam Microfabrication

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    Contains an introduction, reports on seven research projects and a list of publications.Defense Advanced Research Projects Agency/U.S. Army Research Office Contract DAAL03-88-K-0108National Science Foundation Grant ECS 89-21728U.S. Army Research Office Contract DAAL03-87-K-0126U.S. Navy - Naval Research Laboratory/Micrion Agreement M08774SEMATEC

    Incarceration as a key variable in racial disparities of asthma prevalence

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    <p>Abstract</p> <p>Background</p> <p>Despite the disproportionate incarceration of minorities in the United States, little data exist investigating how being incarcerated contributes to persistent racial/ethnic disparities in chronic conditions. We hypothesized that incarceration augments disparities in chronic disease.</p> <p>Methods</p> <p>Using data from the New York City Health and Nutrition Examination Study, a community-based survey of 1999 adults, we first estimated the association between having a history of incarceration and the prevalence of asthma, diabetes, hypertension using propensity score matching methods. Propensity scores predictive of incarceration were generated using participant demographics, socioeconomic status, smoking, excessive alcohol and illicit drug use, and intimate partner violence. Among those conditions associated with incarceration, we then performed mediation analysis to explore whether incarceration mediates racial/ethnic disparities within the disease.</p> <p>Results</p> <p>Individuals with a history of incarceration were more likely to have asthma compared to those without (13% vs. 6%, p < 0.05) and not more likely to have diabetes or hypertension, after matching on propensity scores. Statistical mediation analysis revealed that increased rates of incarceration among Blacks partially contribute to the racial disparity in asthma prevalence.</p> <p>Conclusion</p> <p>Having been incarcerated may augment racial disparities in asthma among NYC residents. Eliminating health disparities should include a better understanding of the role of incarceration and criminal justice policies in contributing to these disparities.</p

    The Effect of Iron Limitation on the Transcriptome and Proteome of Pseudomonas fluorescens Pf-5

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    One of the most important micronutrients for bacterial growth is iron, whose bioavailability in soil is limited. Consequently, rhizospheric bacteria such as Pseudomonas fluorescens employ a range of mechanisms to acquire or compete for iron. We investigated the transcriptomic and proteomic effects of iron limitation on P. fluorescens Pf-5 by employing microarray and iTRAQ techniques, respectively. Analysis of this data revealed that genes encoding functions related to iron homeostasis, including pyoverdine and enantio-pyochelin biosynthesis, a number of TonB-dependent receptor systems, as well as some inner-membrane transporters, were significantly up-regulated in response to iron limitation. Transcription of a ribosomal protein L36-encoding gene was also highly up-regulated during iron limitation. Certain genes or proteins involved in biosynthesis of secondary metabolites such as 2,4-diacetylphloroglucinol (DAPG), orfamide A and pyrrolnitrin, as well as a chitinase, were over-expressed under iron-limited conditions. In contrast, we observed that expression of genes involved in hydrogen cyanide production and flagellar biosynthesis were down-regulated in an iron-depleted culture medium. Phenotypic tests revealed that Pf-5 had reduced swarming motility on semi-solid agar in response to iron limitation. Comparison of the transcriptomic data with the proteomic data suggested that iron acquisition is regulated at both the transcriptional and post-transcriptional levels

    Comparative genomics of plant-asssociated Pseudomonas spp.: Insights into diversity and inheritance of traits involved in multitrophic interactions

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    We provide here a comparative genome analysis of ten strains within the Pseudomonas fluorescens group including seven new genomic sequences. These strains exhibit a diverse spectrum of traits involved in biological control and other multitrophic interactions with plants, microbes, and insects. Multilocus sequence analysis placed the strains in three sub-clades, which was reinforced by high levels of synteny, size of core genomes, and relatedness of orthologous genes between strains within a sub-clade. The heterogeneity of the P. fluorescens group was reflected in the large size of its pan-genome, which makes up approximately 54% of the pan-genome of the genus as a whole, and a core genome representing only 45–52% of the genome of any individual strain. We discovered genes for traits that were not known previously in the strains, including genes for the biosynthesis of the siderophores achromobactin and pseudomonine and the antibiotic 2-hexyl-5-propyl-alkylresorcinol; novel bacteriocins; type II, III, and VI secretion systems; and insect toxins. Certain gene clusters, such as those for two type III secretion systems, are present only in specific sub-clades, suggesting vertical inheritance. Almost all of the genes associated with multitrophic interactions map to genomic regions present in only a subset of the strains or unique to a specific strain. To explore the evolutionary origin of these genes, we mapped their distributions relative to the locations of mobile genetic elements and repetitive extragenic palindromic (REP) elements in each genome. The mobile genetic elements and many strain-specific genes fall into regions devoid of REP elements (i.e., REP deserts) and regions displaying atypical tri-nucleotide composition, possibly indicating relatively recent acquisition of these loci. Collectively, the results of this study highlight the enormous heterogeneity of the P. fluorescens group and the importance of the variable genome in tailoring individual strains to their specific lifestyles and functional repertoir
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