IL-17 can be protective or deleterious in murine pneumococcal pneumonia

Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains

Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa

Chronic pulmonary infection with Pseudomonas aeruginosa is a feature of cystic fibrosis (CF) and other chronic lung diseases. Cytokines of the IL-17 family have been proposed as important in the host response to P. aeruginosa infection through augmenting antibacterial immune responses, although their pro-inflammatory effect may contribute to lung damage that occurs as a result of chronic infection. We set out to explore the role of IL-17 in the host response to chronic P. aeruginosa infection. We used a murine model of chronic pulmonary infection with CF-related strains of P. aeruginosa. We demonstrate that IL-17 cytokine signaling is essential for survival and prevention of chronic infection at 2 weeks post-inoculation using two different P. aeruginosa strains. Following infection, there was a marked expansion of cells within mediastinal lymph nodes, comprised mainly of innate lymphoid cells (ILCs); ∼90% of IL-17 producing cells had markers consistent with Group 3 ILCs. A smaller percentage of IL-17+ cells had markers consistent with a B1 phenotype. In lung homogenates 14 days following infection, there was a significant expansion of IL-17+ cells – about 50% of these were CD3+, split equally between CD4+ Th17 cells and γδ T cells, while the CD3- IL-17+ cells were almost exclusively Group 3 ILCs. Further experiments with B cell deficient mice showed that B cell production of IL-17 or natural antibodies did not provide any defence against chronic P. aeruginosa infection. Thus, IL-17 rather than antibody is a key element in host defence against chronic pulmonary infection with P. aeruginosa

Precursor ion scanning for detection and structural characterization of heterogeneous glycopeptide mixtures

AbstractThe structure of N-linked glycans is determined by a complex, anabolic, intracellular pathway but the exact role of individual glycans is not always clear. Characterization of carbohydrates attached to glycoproteins is essential to aid understanding of this complex area of biology. Specific mass spectral detection of glycopeptides from protein digests may be achieved by on-line HPLC-MS, with selected ion monitoring (SIM) for diagnostic product ions generated by cone voltage fragmentation, or by precursor ion scanning for terminal saccharide product ions, which can yield the same information more rapidly. When glycosylation is heterogeneous, however, these approaches can result in spectra that are complex and poorly resolved. We have developed methodology, based around precursor ion scanning for ions of high m/z, that allows site specific detection and structural characterization of glycans at high sensitivity and resolution. These methods have been developed using the standard glycoprotein, fetuin, and subsequently applied to the analysis of the N-linked glycans attached to the scrapie-associated prion protein, PrPSc. These glycans are highly heterogeneous and over 30 structures have been identified and characterized site specifically. Product ion spectra have been obtained on many glycopeptides confirming structure assignments. The glycans are highly fucosylated and carry Lewis X or sialyl Lewis X epitopes and the structures are in-line with previous results. [Abbreviations: Hex–Hexose, C6H12O6 carbohydrates, including mannnose and galactose; HexNAc—N-acetylhexosamine, C8H15NO6 carbohydrates, including N-acetylglucosamine and N-acetylgalactosamine; GlcNAc—N-acetylglucosamine; GalNAc—N-acetylgalactosamine; Fuc–Fucose; NeuAC—N-acetylneuraminic acid or sialic acid; TSE—Transmissible Spongiform Encephalopathy.

Two-Electron Photon Emission From Metallic Quantum Wells

Unusual emission of visible light is observed in scanning tunneling microscopy of the quantum well system Na on Cu(111). Photons are emitted at energies exceeding the energy of the tunneling electrons. Model calculations of two-electron processes which lead to quantum well transitions reproduce the experimental fluorescence spectra, the quantum yield, and the power-law variation of the intensity with the excitation current.Comment: revised version, as published; 4 pages, 3 figure

Impacts of boundary layer turbulence and land surface process parameterizations on simulated sea breeze characteristics

This paper investigates the sensitivity of sea breeze (SB) simulations to combinations of boundary-layer turbulence and land-surface process parameterizations implemented in the MM5 mesoscale meteorological mode for an observed SB case over the Swedish west coast. Various combinations from four different planetary boundary layer (PBL) schemes [Blackadar, Gayno-Seaman (GS), Eta, MRF], and two land surface model (LSM) schemes (SLAB, Noah) with different complexity are designed to simulate a typical SB case over the Swedish west coast. The simulations are conducted using two-way interactively nested grids. Simulated 10-m winds are compared against observed near-surface wind data from the GÖTE2001 campaign to examine the diurnal cycle of wind direction and speed for SB timing. The SB (vertical) circulation is also compared in the different experiments. The results show that the different combinations of PBL and LSM parameterization schemes result in different SB timing and vertical circulation characteristics. All experiments predict a delayed SB. The vertical component of the SB circulation varies in the experiments, among which the GS PBL scheme produces the strongest SB circulation. Evident differences between the SLAB and Noah LSMs are also found, especially in maximum of updraft and downdraft velocities of the SB vertical circulation. The results have significant implications for convective initiation, air quality studies and other environmental problems in coastal areas

The role of institutional and family embeddedness in the failure of Sub-Saharan African migrant family businesses

There is considerable interest among European politicians and policymakers in how to integrate migrants in the local and national economy. Drawing on in-depth qualitative interviews with 20 owners of Sub-Saharan African migrant family businesses (SSAMBs) in the United Kingdom, this article critically examines why SSAMBs fail or underperform. This investigation draws upon three streams of literature – notably migrant business failure, institutional theory and family embeddedness. The findings highlight the challenges of doing business and the reasons for business failure among this group. These are different from other small businesses and include culture, family interference and ethnicity. The main contribution of the article lies in the development of a conceptual model that highlights the relationships between institutional contexts and migrant family business outcomes. The model proposes that institution and family embeddedness results in the enactment of ethnic behaviours that drive migrant businesses into cultural markets leading to business underperformance or failure

Some Empirical Criteria for Attributing Creativity to a Computer Program

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Secondhand Goods, Firsthand Knowledge: An Organizational Structure Exercise At The Local Flea Market

We developed a unique and enjoyable field trip exercise to challenge students to identify various organizational structures and their properties and dimensions present in the local flea market. Drawing on students’ review of common organizational structures, i.e., simple, functional, multi-divisional, and network, this exercise requires that individuals or small groups of students visit a local flea market to observe and analyze the numerous organizational structures apparent. Students then use a given report format to identify: the properties of organizations; distinct organizational structures on varying levels of analysis (the market as a whole, areas of specialization, and vendors); and the dimensions seen in organizations (specialization, span of control, formalization, and centralization). In-class discussion of the topic, using discussion questions provided, further clarifies the concepts that students viewed in practice at the flea market

Energy-level pinning and the 0.7 spin state in one dimension: GaAs quantum wires studied using finite-bias spectroscopy

We study the effects of electron-electron interactions on the energy levels of GaAs quantum wires (QWs) using finite-bias spectroscopy. We probe the energy spectrum at zero magnetic field, and at crossings of opposite-spin-levels in high in-plane magnetic field B. Our results constitute direct evidence that spin-up (higher energy) levels pin to the chemical potential as they populate. We also show that spin-up and spin-down levels abruptly rearrange at the crossing in a manner resembling the magnetic phase transitions predicted to occur at crossings of Landau levels. This rearranging and pinning of subbands provides a phenomenological explanation for the 0.7 structure, a one-dimensional (1D) nanomagnetic state, and its high-B variants.Comment: 6 pages, 4 figure