62 research outputs found

    Growth in Cities

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    Recent theories of economic growth, including Romer (1986), Porter (1989) and Jacobs (1969), have stressed the role of technological spillovers in generating growth. Because such knowledge spillovers are particularly effective in cities, where communication between people is more extensive, data on the growth of industries in different cities allows us to test some of these theories. Using a new data set on the growth of large industries in 170 U.S. cities between 1956 and 1987, we find that local competition and urban variety, but not regional specialization, encourage employment growth in industries. The evidence suggests that important knowledge spillovers might be between, rather than within industries, consistent with the theories of Jacobs (1969).

    Silencing of directional migration in roundabout4 knockdown endothelial cells

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    <p>Abstract</p> <p>Background</p> <p>Roundabouts are axon guidance molecules that have recently been identified to play a role in vascular guidance as well. In this study, we have investigated gene knockdown analysis of endothelial Robos, in particular <it>roundabout 4 </it>(<it>robo4</it>), the predominant Robo in endothelial cells using small interfering RNA technology <it>in vitro</it>.</p> <p>Results</p> <p><it>Robo1 and Robo4 </it>knockdown cells display distinct activity in endothelial cell migration assay. The knockdown of <it>robo4 </it>abrogated the chemotactic response of endothelial cells to serum but enhanced a chemokinetic response to Slit2, while <it>robo1 </it>knockdown cells do not display chemotactic response to serum or VEGF. <it>Robo4 </it>knockdown endothelial cells unexpectedly show up regulation of Rho GTPases. Zebrafish Robo4 rescues both Rho GTPase homeostasis and serum reduced chemotaxis in <it>robo4 </it>knockdown cells. Robo1 and Robo4 interact and share molecules such as Slit2, Mena and Vilse, a Cdc42-GAP. In addition, this study mechanistically implicates IRSp53 in the signaling nexus between activated Cdc42 and Mena, both of which have previously been shown to be involved with Robo4 signaling in endothelial cells.</p> <p>Conclusion</p> <p>This study identifies specific components of the Robo signaling apparatus that work together to guide directional migration of endothelial cells.</p

    Validation of a rapid, non-radioactive method to quantify internalisation of G-protein coupled receptors

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    Agonist exposure can cause internalisation of G-protein coupled receptors (GPCRs), which may be a part of desensitisation but also of cellular signaling. Previous methods to study internalisation have been tedious or only poorly quantitative. Therefore, we have developed and validated a quantitative method using a sphingosine-1-phosphate (S1P) receptor as a model. Because of a lack of suitable binding studies, it has been difficult to study S1P receptor internalisation. Using a N-terminal HisG-tag, S1P1 receptors on the cell membrane can be visualised via immunocytochemistry with a specific anti-HisG antibody. S1P-induced internalisation was concentration dependent and was quantified using a microplate reader, detecting either absorbance, a fluorescent or luminescent signal, depending on the antibodies used. Among those, the fluorescence detection method was the most convenient to use. The relative ease of this method makes it suitable to measure a large number of data points, e.g. to compare the potency and efficacy of receptor ligands

    Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage

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    Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family

    Growth in Cities.

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    Recent theories of economic growth, including those of P. Romer (1986, 1990), M. Porter (1990), and J. Jacobs (1969, 1984), have stressed the role of technological spillovers in generating growth. Because such knowledge spillovers are particularly effective in cities, where communication between people is more extensive, data on the growth of industries in different cities allow the authors to test some of these theories. Using a new data set on the growth of large industries in 170 U.S. cities between 1956 and 1987, they find that local competition and urban variety, but not regional specialization, encourage employment growth in industries. The evidence suggests that important knowledge spillovers might occur between rather than within industries. Copyright 1992 by University of Chicago Press.
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