42 research outputs found

    Epithelial p38α Controls Immune Cell Recruitment in the Colonic Mucosa

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    Intestinal epithelial cells (IECs) compose the first barrier against microorganisms in the gastrointestinal tract. Although the NF-κB pathway in IECs was recently shown to be essential for epithelial integrity and intestinal immune homeostasis, the roles of other inflammatory signaling pathways in immune responses in IECs are still largely unknown. Here we show that p38α in IECs is critical for chemokine expression, subsequent immune cell recruitment into the intestinal mucosa, and clearance of the infected pathogen. Mice with p38α deletion in IECs suffer from a sustained bacterial burden after inoculation with Citrobacter rodentium. These animals are normal in epithelial integrity and immune cell function, but fail to recruit CD4+ T cells into colonic mucosal lesions. The expression of chemokines in IECs is impaired, which appears to be responsible for the impaired T cell recruitment. Thus, p38α in IECs contributes to the host immune responses against enteric bacteria by the recruitment of immune cells

    The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity

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    Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA+ plasma cells remain poorly understood. Here, we report that the B cell–expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37−/−) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA+ plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37–deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37−/− mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37−/− mice. To demonstrate the importance of CD37—which can associate with the pattern-recognition receptor dectin-1—in immunity to infection, CD37−/− mice were exposed to Candida albicans. We report that CD37−/− mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans–specific IgA antibodies. Importantly, adoptive transfer of CD37−/− serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response

    Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

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    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to resistance; and strengthen the case for a role in survival of systems involved in manganese and iron homeostasis

    A modern thermo-kinetic warm fog dispersal system /

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    An extensive investigation has been made to arrive at optimum specifications for a thermo-kinetic warm fog dispersal system. This study included passive heat tests, sub-scale heat/momentum tests, and tests with a single full-scale runway combustor and an approach zone combustor. These tests were augmented with extensive analytical modeling of buoyant jets under coflowing and counterflowing wind conditions. The landing category and the operational requirements within each category are the primary factors affecting the size of the thermal fog dispersal system (TFDS). A Cat 2 TFDS employs 22 percent fewer combustors and uses 50 percent less fuel than a Cat 1 TFDS. The combustor specification and orientation are presented for both Cat 1 and Cat 2 systems. (Author).Research supported by the Air Force Geophysics Laboratory, Air Force Systems Command, United States Air Force, Hanscom AFB, Massachusetts.Meteorology Division Project 2093."14 November 1978."Includes bibliographical references (pages 27-28).An extensive investigation has been made to arrive at optimum specifications for a thermo-kinetic warm fog dispersal system. This study included passive heat tests, sub-scale heat/momentum tests, and tests with a single full-scale runway combustor and an approach zone combustor. These tests were augmented with extensive analytical modeling of buoyant jets under coflowing and counterflowing wind conditions. The landing category and the operational requirements within each category are the primary factors affecting the size of the thermal fog dispersal system (TFDS). A Cat 2 TFDS employs 22 percent fewer combustors and uses 50 percent less fuel than a Cat 1 TFDS. The combustor specification and orientation are presented for both Cat 1 and Cat 2 systems. (Author).Mode of access: Internet

    The air quality and noise impact of a warm fog dispersal system using momentum driven heat sources /

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    The impact of a Warm Fog Dispersal System (WFDS) on the air quality and noise level is assessed. The WFDS, designed by AFGL, uses various combinations of heat and thrust to disperse the fog over the runway and approach zones. Emission and noise levels that are within the state-of-the-art are used in this assessment. Calculations show that within the cleared area the pollution concentrations, on the average, are within the EPA standards. (Author).Research supported by the Air Force Geophysics Laboratory, Air Force Systems Command, United States Air Force, Hanscom AFB, Massachusetts.Meteorology Division Project 2093."ADA033623 (from http://www.dtic.mil)."1 September 1976."Includes bibliographical references (page 21).The impact of a Warm Fog Dispersal System (WFDS) on the air quality and noise level is assessed. The WFDS, designed by AFGL, uses various combinations of heat and thrust to disperse the fog over the runway and approach zones. Emission and noise levels that are within the state-of-the-art are used in this assessment. Calculations show that within the cleared area the pollution concentrations, on the average, are within the EPA standards. (Author).Mode of access: Internet

    Interaction of a buoyant turbulent round jet with a co-flowing wind /

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    A broad effort is being conducted to develop an operational Warm Fog Dispersal System (WFDS) using ground-based heat sources. In order to determine the optimum heat and thrust for the combustors in the WFDS, investigations have been made of the buoyant motion in round- and plane-heated turbulent jets in co-flowing (that is, same direction) wind fields. This report describes a method of calculating the round jet case. The method can be used for jet velocities of 100m/sec or less, wind velocities below or equal to the jet velocity, and jet temperatures up to 3 times the ambient value. Initial jet velocities of 5 and 20m/sec and temperature excesses, relative to the ambient temperature, of .3 and 1 were selected for the calculations."Meteorology Laboratory Project 2093.""ADA021470 (from http://www.dtic.mil).""11 November 1975."Includes bibliographical references (page 35).A broad effort is being conducted to develop an operational Warm Fog Dispersal System (WFDS) using ground-based heat sources. In order to determine the optimum heat and thrust for the combustors in the WFDS, investigations have been made of the buoyant motion in round- and plane-heated turbulent jets in co-flowing (that is, same direction) wind fields. This report describes a method of calculating the round jet case. The method can be used for jet velocities of 100m/sec or less, wind velocities below or equal to the jet velocity, and jet temperatures up to 3 times the ambient value. Initial jet velocities of 5 and 20m/sec and temperature excesses, relative to the ambient temperature, of .3 and 1 were selected for the calculations.Mode of access: Internet

    Thermal and chemical fog dissipation : results of field experiments at Vandenberg AFB, California during July 1972 /

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    Results of thermal and chemical fog dispersal tests, conducted by AFCRL during July 1972, are presented and discussed. Forty-three tests were conducted in fog, thirty-three of which were suitable for analysis. Ninety-six additional heat tests were conducted in clear air. Two wide-area urea seeding tests were also performed. An instrumented 200-ft tower, a lidar, and a ground network of visibility sensors and droplet sampler were used to monitor the effects of the tests on the foggy environment. The seeding tests were unsuccessful. Improper execution of the wide-area seeding pattern due to a lack of knowledge of the winds at the seeding location was responsible for the failure of the seeding tests. (Modified author abstract)."Meteorology Laboratory Project 7605."AD0768671 (From http://www.dtic.mil)."8 August 1973."Includes bibliographical references (page 41).Results of thermal and chemical fog dispersal tests, conducted by AFCRL during July 1972, are presented and discussed. Forty-three tests were conducted in fog, thirty-three of which were suitable for analysis. Ninety-six additional heat tests were conducted in clear air. Two wide-area urea seeding tests were also performed. An instrumented 200-ft tower, a lidar, and a ground network of visibility sensors and droplet sampler were used to monitor the effects of the tests on the foggy environment. The seeding tests were unsuccessful. Improper execution of the wide-area seeding pattern due to a lack of knowledge of the winds at the seeding location was responsible for the failure of the seeding tests. (Modified author abstract).Mode of access: Internet
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