53 research outputs found

    Genetically encoded intrabody sensors report the interaction and trafficking of β-arrestin 1 upon activation of G protein-coupled receptors

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    Agonist stimulation of G protein-coupled receptors (GPCRs) typically leads to phosphorylation of GPCRs and binding to multifunctional proteins called β-arrestins (βarrs). The GPCR-βarr interaction critically contributes to GPCR desensitization, endocytosis, and downstream signaling, and GPCR-βarr complex formation can be used as a generic readout of GPCR and βarr activation. Although several methods are currently available to monitor GPCR-βarr interactions, additional sensors to visualize them may expand the toolbox and complement existing methods. We have previously described antibody fragments (FABs) that recognize activated βarr1 upon its interaction with the vasopressin V2 receptor C-terminal phosphopeptide (V2Rpp). Here, we demonstrate that these FABs efficiently report the formation of a GPCR-βarr1 complex for a broad set of chimeric GPCRs harboring the V2R C terminus. We adapted these FABs to an intrabody format by converting them to single-chain variable fragments (ScFvs) and used them to monitor the localization and trafficking of βarr1 in live cells. We observed that upon agonist simulation of cells expressing chimeric GPCRs, these intrabodies first translocate to the cell surface, followed by trafficking into intracellular vesicles. The translocation pattern of intrabodies mirrored that of βarr1, and the intrabodies co-localized with βarr1 at the cell surface and in intracellular vesicles. Interestingly, we discovered that intrabody sensors can also report βarr1 recruitment and trafficking for several unmodified GPCRs. Our characterization of intrabody sensors for βarr1 recruitment and trafficking expands currently available approaches to visualize GPCR-βarr1 binding, which may help decipher additional aspects of GPCR signaling and regulation

    Simulations of the 2004 North American Monsoon: NAMAP2

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    The second phase of the North American Monsoon Experiment (NAME) Model Assessment Project (NAMAP2) was carried out to provide a coordinated set of simulations from global and regional models of the 2004 warm season across the North American monsoon domain. This project follows an earlier assessment, called NAMAP, that preceded the 2004 field season of the North American Monsoon Experiment. Six global and four regional models are all forced with prescribed, time-varying ocean surface temperatures. Metrics for model simulation of warm season precipitation processes developed in NAMAP are examined that pertain to the seasonal progression and diurnal cycle of precipitation, monsoon onset, surface turbulent fluxes, and simulation of the low-level jet circulation over the Gulf of California. Assessment of the metrics is shown to be limited by continuing uncertainties in spatially averaged observations, demonstrating that modeling and observational analysis capabilities need to be developed concurrently. Simulations of the core subregion (CORE) of monsoonal precipitation in global models have improved since NAMAP, despite the lack of a proper low-level jet circulation in these simulations. Some regional models run at higher resolution still exhibit the tendency observed in NAMAP to overestimate precipitation in the CORE subregion; this is shown to involve both convective and resolved components of the total precipitation. The variability of precipitation in the Arizona/New Mexico (AZNM) subregion is simulated much better by the regional models compared with the global models, illustrating the importance of transient circulation anomalies (prescribed as lateral boundary conditions) for simulating precipitation in the northern part of the monsoon domain. This suggests that seasonal predictability derivable from lower boundary conditions may be limited in the AZNM subregion.open131

    The climatic impacts of land surface change and carbon management, and the implications for climate-change mitigation policy

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    http://www.sciencedirect.com/science/journal/14693062Strategies to mitigate anthropogenic climate change recognize that carbon sequestration in the terrestrial biosphere can reduce the build-up of carbon dioxide in the Earth’s atmosphere. However, climate mitigation policies do not generally incorporate the effects of these changes in the land surface on the surface albedo, the fluxes of sensible and latent heat to the atmosphere, and the distribution of energy within the climate system. Changes in these components of the surface energy budget can affect the local, regional, and global climate. Given the goal of mitigating climate change, it is important to consider all of the effects of changes in terrestrial vegetation and to work toward a better understanding of the full climate system. Acknowledging the importance of land surface change as a component of climate change makes it more challenging to create a system of credits and debits wherein emission or sequestration of carbon in the biosphere is equated with emission of carbon from fossil fuels. Recognition of the complexity of human-caused changes in climate does not, however, weaken the importance of actions that would seek to minimize our disturbance of the Earth’s environmental system and that would reduce societal and ecological vulnerability to environmental change and variability

    Building a Digital Wind Farm

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    Analysis 03: Future Scenario—OWF Development Within German EEZ

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    Synthesis, structure and three way catalytic activity of Ce<SUB>1-x</SUB>Pt<SUB>x/2</SUB>Rh<SUB>x/2</SUB>O<SUB>2-&#948;</SUB> (x = 0.01 and 0.02) nano-crystallites: synergistic effect in bimetal ionic catalysts

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    Bimetal ionic Ce1-xPtx/2Rhx/2O2-&#948; (x = 0.01 and 0.02) catalysts have been synthesized by a single step solution combustion method. CO and C2H4 oxidation and NO reduction activities of the bimetal ionic catalysts are compared with mono-metal ionic Ce1-xPtxO2-&#948; (x = 0.01 and 0.02) and Ce1-xRhxO2-&#948; (x = 0.01 and 0.02) catalysts. X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) studies show incorporation of Pt2+ and Rh3+ ions in CeO2 lattice. Low temperature hydrogen uptake at 0 &#176;C and below over bimetal ionic catalyst shows enhanced redox property over the corresponding mono-metal ionic analogues. The TOF for CO oxidation over Ce0.99Pt0.005Rh0.005O2-&#948; is 0.035 s-1 at 120 &#176;C, compared to 0.003 s-1 over Ce0.99Pt0.01O2-&#948; and 0.035 s-1 over Ce0.99Rh0.01O2-&#948; at 135 &#176;C. Enhanced catalytic activity of Ce1-xPtx/2Rhx/2O2-&#948; (x = 0.01) bimetal ionic catalysts compared to mono-metal ionic catalysts, Ce1-xPtxO2-&#948; and Ce1-xRhxO2-&#948;, is attributed to synergism brought about by the easy reduction of Rh3+ ion by Pt2+ ion

    A preferred scale for landscape forced mesoscale circulations?

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    The Regional Atmospheric Modeling System was used in two previous studies to simulate mesoscale circulations forced by surface heterogeneity in the Central U. S. and Amazonia. In this work, spectral analysis is used to compare the horizontal length scales of these simulated circulations with the scale of the surface heterogeneity. For both cases, the organized mesoscale circulations are confined within a preferred length scale range (10–20 km) that is significantly different from the dominant length scale of the surface heterogeneity. Multiscale landscape patchiness in these two regions tend to produce eddies at a wide range of scales, but the land‐atmosphere interaction processes act as a medium‐pass filter to select intermediate‐scale circulations. This scale of response remains relatively unchanged despite significant day‐to‐day variations in the synoptic situation and the mean surface heat flux
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