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  • Basic Science Research, Cell Signaling/Signal Transduction, Mechanisms, Smooth Muscle Proliferation and Differentiation, Vascular Biology  (1)
  • Regional effects  (1)
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  • 1
    Publication Date: 2022-05-25
    Description: Author Posting. © American Meteorological Society, 2013. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 26 (2013): 9247–9290, doi:10.1175/JCLI-D-12-00593.1.
    Description: This is the second part of a three-part paper on North American climate in phase 5 of the Coupled Model Intercomparison Project (CMIP5) that evaluates the twentieth-century simulations of intraseasonal to multidecadal variability and teleconnections with North American climate. Overall, the multimodel ensemble does reasonably well at reproducing observed variability in several aspects, but it does less well at capturing observed teleconnections, with implications for future projections examined in part three of this paper. In terms of intraseasonal variability, almost half of the models examined can reproduce observed variability in the eastern Pacific and most models capture the midsummer drought over Central America. The multimodel mean replicates the density of traveling tropical synoptic-scale disturbances but with large spread among the models. On the other hand, the coarse resolution of the models means that tropical cyclone frequencies are underpredicted in the Atlantic and eastern North Pacific. The frequency and mean amplitude of ENSO are generally well reproduced, although teleconnections with North American climate are widely varying among models and only a few models can reproduce the east and central Pacific types of ENSO and connections with U.S. winter temperatures. The models capture the spatial pattern of Pacific decadal oscillation (PDO) variability and its influence on continental temperature and West Coast precipitation but less well for the wintertime precipitation. The spatial representation of the Atlantic multidecadal oscillation (AMO) is reasonable, but the magnitude of SST anomalies and teleconnections are poorly reproduced. Multidecadal trends such as the warming hole over the central–southeastern United States and precipitation increases are not replicated by the models, suggesting that observed changes are linked to natural variability.
    Description: The authors acknowledge the support of NOAA/Climate Program Office/Modeling, Analysis, Predictions and Projections (MAPP) program as part of the CMIP5 Task Force.
    Description: 2014-06-01
    Keywords: North America ; Regional effects ; Coupled models ; Decadal variability ; Interannual variability ; Intraseasonal variability
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Format: application/pdf
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  • 2
    Publication Date: 2017-11-22
    Description: Objective—Drug-eluting stent delivery of mTORC1 (mechanistic target of rapamycin complex 1) inhibitors is highly effective in preventing intimal hyperplasia after coronary revascularization, but adverse effects limit their use for systemic vascular disease. Understanding the mechanism of action may lead to new treatment strategies. We have shown that rapamycin promotes vascular smooth muscle cell differentiation in an AKT2-dependent manner in vitro. Here, we investigate the roles of AKT (protein kinase B) isoforms in intimal hyperplasia.Approach and Results—We found that germ-line–specific or smooth muscle–specific deletion of Akt2 resulted in more severe intimal hyperplasia compared with control mice after arterial denudation injury. Conversely, smooth muscle–specific Akt1 knockout prevented intimal hyperplasia, whereas germ-line Akt1 deletion caused severe thrombosis. Notably, rapamycin prevented intimal hyperplasia in wild-type mice but had no therapeutic benefit in Akt2 knockouts. We identified opposing roles for AKT1 and AKT2 isoforms in smooth muscle cell proliferation, migration, differentiation, and rapamycin response in vitro. Mechanistically, rapamycin induced MYOCD (myocardin) mRNA expression. This was mediated by AKT2 phosphorylation and nuclear exclusion of FOXO4 (forkhead box O4), inhibiting its binding to the MYOCD promoter.Conclusions—Our data reveal opposing roles for AKT isoforms in smooth muscle cell remodeling. AKT2 is required for rapamycin’s therapeutic inhibition of intimal hyperplasia, likely mediated in part through AKT2-specific regulation of MYOCD via FOXO4. Because AKT2 signaling is impaired in diabetes mellitus, this work has important implications for rapamycin therapy, particularly in diabetic patients.
    Keywords: Basic Science Research, Cell Signaling/Signal Transduction, Mechanisms, Smooth Muscle Proliferation and Differentiation, Vascular Biology
    Print ISSN: 1079-5642
    Electronic ISSN: 1524-4636
    Topics: Medicine
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