Identification of antiviral roles for the exon-junction complex and nonsense-mediated decay in flaviviral infection.

West Nile virus (WNV) is an emerging mosquito-borne flavivirus, related to dengue virus and Zika virus. To gain insight into host pathways involved in WNV infection, we performed a systematic affinity-tag purification mass spectrometry (APMS) study to identify 259 WNV-interacting human proteins. RNA interference screening revealed 26 genes that both interact with WNV proteins and influence WNV infection. We found that WNV, dengue and Zika virus capsids interact with a conserved subset of proteins that impact infection. These include the exon-junction complex (EJC) recycling factor PYM1, which is antiviral against all three viruses. The EJC has roles in nonsense-mediated decay (NMD), and we found that both the EJC and NMD are antiviral and the EJC protein RBM8A directly binds WNV RNA. To counteract this, flavivirus infection inhibits NMD and the capsid-PYM1 interaction interferes with EJC protein function and localization. Depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that WNV sequesters PYM1 to protect viral RNA from decay. Together, these data suggest a complex interplay between the virus and host in regulating NMD and the EJC

Marine Low Cloud Sensitivity to An Idealized Climate Change: The CGILS LES Intercomparison

Subtropical marine low cloud sensitivity to an idealized climate change is compared in six large-eddy simulation (LES) models as part of CGILS. July cloud cover is simulated at three locations over the subtropical northeast Pacific Ocean, which are typified by cold sea surface temperatures (SSTs) under well-mixed stratocumulus, cool SSTs under decoupled stratocumulus, and shallow cumulus clouds overlying warmer SSTs. The idealized climate change includes a uniform 2 K SST increase with corresponding moist-adiabatic warming aloft and subsidence changes, but no change in free-tropospheric relative humidity, surface wind speed, or CO2. For each case, realistic advective forcings and boundary conditions are generated for the control and perturbed states which each LES runs for 10 days into a quasi-steady state. For the control climate, the LESs correctly produce the expected cloud type at all three locations. With the perturbed forcings, all models simulate boundary-layer deepening due to reduced subsidence in the warmer climate, with less deepening at the warm-SST location due to regulation by precipitation. The models do not show a consistent response of liquid water path and albedo in the perturbed climate, though the majority predict cloud thickening (negative cloud feedback) at the cold-SST location and slight cloud thinning (positive cloud feedback) at the cool-SST and warm-SST locations. In perturbed climate simulations at the cold-SST location without the subsidence decrease, cloud albedo consistently decreases across the models. Thus, boundary-layer cloud feedback on climate change involves compensating thermodynamic and dynamic effects of warming and may interact with patterns of subsidence change

Marine Low Cloud Sensitivity to An Idealized Climate Change: The CGILS LES Intercomparison

Subtropical marine low cloud sensitivity to an idealized climate change is compared in six large-eddy simulation (LES) models as part of CGILS. July cloud cover is simulated at three locations over the subtropical northeast Pacific Ocean, which are typified by cold sea surface temperatures (SSTs) under well-mixed stratocumulus, cool SSTs under decoupled stratocumulus, and shallow cumulus clouds overlying warmer SSTs. The idealized climate change includes a uniform 2 K SST increase with corresponding moist-adiabatic warming aloft and subsidence changes, but no change in free-tropospheric relative humidity, surface wind speed, or CO2. For each case, realistic advective forcings and boundary conditions are generated for the control and perturbed states which each LES runs for 10 days into a quasi-steady state. For the control climate, the LESs correctly produce the expected cloud type at all three locations. With the perturbed forcings, all models simulate boundary-layer deepening due to reduced subsidence in the warmer climate, with less deepening at the warm-SST location due to regulation by precipitation. The models do not show a consistent response of liquid water path and albedo in the perturbed climate, though the majority predict cloud thickening (negative cloud feedback) at the cold-SST location and slight cloud thinning (positive cloud feedback) at the cool-SST and warm-SST locations. In perturbed climate simulations at the cold-SST location without the subsidence decrease, cloud albedo consistently decreases across the models. Thus, boundary-layer cloud feedback on climate change involves compensating thermodynamic and dynamic effects of warming and may interact with patterns of subsidence change

The Community Climate System Model version 4

Author Posting. © American Meteorological Society, 2011. 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 24 (2011): 4973–4991, doi:10.1175/2011JCLI4083.1.The fourth version of the Community Climate System Model (CCSM4) was recently completed and released to the climate community. This paper describes developments to all CCSM components, and documents fully coupled preindustrial control runs compared to the previous version, CCSM3. Using the standard atmosphere and land resolution of 1° results in the sea surface temperature biases in the major upwelling regions being comparable to the 1.4°-resolution CCSM3. Two changes to the deep convection scheme in the atmosphere component result in CCSM4 producing El Niño–Southern Oscillation variability with a much more realistic frequency distribution than in CCSM3, although the amplitude is too large compared to observations. These changes also improve the Madden–Julian oscillation and the frequency distribution of tropical precipitation. A new overflow parameterization in the ocean component leads to an improved simulation of the Gulf Stream path and the North Atlantic Ocean meridional overturning circulation. Changes to the CCSM4 land component lead to a much improved annual cycle of water storage, especially in the tropics. The CCSM4 sea ice component uses much more realistic albedos than CCSM3, and for several reasons the Arctic sea ice concentration is improved in CCSM4. An ensemble of twentieth-century simulations produces a good match to the observed September Arctic sea ice extent from 1979 to 2005. The CCSM4 ensemble mean increase in globally averaged surface temperature between 1850 and 2005 is larger than the observed increase by about 0.4°C. This is consistent with the fact that CCSM4 does not include a representation of the indirect effects of aerosols, although other factors may come into play. The CCSM4 still has significant biases, such as the mean precipitation distribution in the tropical Pacific Ocean, too much low cloud in the Arctic, and the latitudinal distributions of shortwave and longwave cloud forcings.National Science Foundation, which sponsors NCAR and the CCSM Project. The project is also sponsored by the U.S. Department of Energy (DOE). Thanks are also due to the many other software engineers and scientists who worked on developing CCSM4, and to the Computational and Information Systems Laboratory at NCAR, which provided the computing resources through the Climate Simulation Laboratory. Hunke was supported within theClimate, Ocean and Sea Ice Modeling project at Los Alamos National Laboratory, which is funded by the Biological and Environmental Research division of the DOE Office of Science. The Los Alamos National Laboratory is operated by theDOENationalNuclear Security Administration under Contract DE-AC52-06NA25396. Raschwas supported by theDOEOffice of Science, Earth System Modeling Program, which is part of the DOE Climate Change Research Program. The Pacific Northwest National Laboratory is operated forDOEbyBattelle Memorial Institute under Contract DE-AC06-76RLO 1830. Worley was supported by the Climate Change Research Division of the Office of Biological and Environmental Research and by the Office ofAdvanced Scientific Computing Research, both in the DOE Office of Science, under Contract DE-AC05-00OR22725 with UT-Batelle, LLC

Disproportionate declines of formerly abundant species underlie insect loss

Studies have reported widespread declines in terrestrial insect abundances in recent years1,2,3,4, but trends in other biodiversity metrics are less clear-cut5,6,7. Here we examined long-term trends in 923 terrestrial insect assemblages monitored in 106 studies, and found concomitant declines in abundance and species richness. For studies that were resolved to species level (551 sites in 57 studies), we observed a decline in the number of initially abundant species through time, but not in the number of very rare species. At the population level, we found that species that were most abundant at the start of the time series showed the strongest average declines (corrected for regression-to-the-mean effects). Rarer species were, on average, also declining, but these were offset by increases of other species. Our results suggest that the observed decreases in total insect abundance2 can mostly be explained by widespread declines of formerly abundant species. This counters the common narrative that biodiversity loss is mostly characterized by declines of rare species8,9. Although our results suggest that fundamental changes are occurring in insect assemblages, it is important to recognize that they represent only trends from those locations for which sufficient long-term data are available. Nevertheless, given the importance of abundant species in ecosystems10, their general declines are likely to have broad repercussions for food webs and ecosystem functioning

CGILS: Results From The First Phase of An International Project to Understand The Physical Mechanisms of Low Cloud Feedbacks in Single Column Models

CGILS—the CFMIP-GASS Intercomparison of Large Eddy Models (LESs) and single column models (SCMs)—investigates the mechanisms of cloud feedback in SCMs and LESs under idealized climate change perturbation. This paper describes the CGILS results from 15 SCMs and 8 LES models. Three cloud regimes over the subtropical oceans are studied: shallow cumulus, cumulus under stratocumulus, and well-mixed coastal stratus/stratocumulus. In the stratocumulus and coastal stratus regimes, SCMs without activated shallow convection generally simulated negative cloud feedbacks, while models with active shallow convection generally simulated positive cloud feedbacks. In the shallow cumulus alone regime, this relationship is less clear, likely due to the changes in cloud depth, lateral mixing, and precipitation or a combination of them. The majority of LES models simulated negative cloud feedback in the well-mixed coastal stratus/stratocumulus regime, and positive feedback in the shallow cumulus and stratocumulus regime. A general framework is provided to interpret SCM results: in a warmer climate, the moistening rate of the cloudy layer associated with the surface-based turbulence parameterization is enhanced; together with weaker large-scale subsidence, it causes negative cloud feedback. In contrast, in the warmer climate, the drying rate associated with the shallow convection scheme is enhanced. This causes positive cloud feedback. These mechanisms are summarized as the “NESTS” negative cloud feedback and the “SCOPE” positive cloud feedback (Negative feedback from Surface Turbulence under weaker Subsidence—Shallow Convection PositivE feedback) with the net cloud feedback depending on how the two opposing effects counteract each other. The LES results are consistent with these interpretations

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

Microvessel changes after post-ischemic benign and malignant hyperemia: experimental study in rats

<p>Abstract</p> <p>Background</p> <p>The present investigation was designed to elucidate the use of dynamic contrast enhanced perfusion MR imaging (DCE pMRI) in characterizing hyperemia, including microvessel changes, and to examine whether DCE pMRI can predict benign or malignant hyperemia.</p> <p>Methods</p> <p>Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) by intraluminal suture placement. All rats were randomized to 4 groups: MCAO for 0.5 hours followed by saline treatment (10 ml/kg; group 1); MCAO for 3 hours followed by treatment with saline (group 2) or urokinase (25000 IU/kg; group 3); and MCAO for 6 hours followed by urokinase treatment (group 4). Relative cerebral blood volume (rCBV) and relative maximum slope of increase of the signal intensity time curve (rMSI) were quantitatively analyzed from MRI. Microvessel diameter and blood-brain barrier disruption obtained by laser scanning confocal microscopy (LSCM) as well as transmission electron microscopy (TEM) were obtained for correlative study.</p> <p>Results</p> <p>Benign hyperemia was noticed only in group 1; malignant hyperemia was seen in group 3. Although the rCBV of malignant hyperemia was slightly higher than in benign hyperemia (<it>P </it>> 0.05), the rMSI, on the other hand, was significantly lower (<it>P </it>< 0.05). Fluoro-isothiocyanate dextran (FITC-dextran) extravasations, marked glial end-foot process swelling, and significant vasodilatation were seen in malignant hyperemia, while no or mild leakage of FITC-dextran and slight glial end-foot process swelling occurred in benign hyperemia.</p> <p>Conclusion</p> <p>Our findings indicate that DCE pMRI can characterize post-ischemic hyperemia and correlates well with microvascular damage.</p

Environmental Modeling and Exposure Assessment of Sediment-Associated Pyrethroids in an Agricultural Watershed

Synthetic pyrethroid insecticides have generated public concerns due to their increasing use and potential effects on aquatic ecosystems. A modeling system was developed in this study for simulating the transport processes and associated sediment toxicity of pyrethroids at coupled field/watershed scales. The model was tested in the Orestimba Creek watershed, an agriculturally intensive area in California' Central Valley. Model predictions were satisfactory when compared with measured suspended solid concentration (R2 = 0.536), pyrethroid toxic unit (0.576), and cumulative mortality of Hyalella azteca (0.570). The results indicated that sediment toxicity in the study area was strongly related to the concentration of pyrethroids in bed sediment. Bifenthrin was identified as the dominant contributor to the sediment toxicity in recent years, accounting for 50–85% of predicted toxicity units. In addition, more than 90% of the variation on the annual maximum toxic unit of pyrethroids was attributed to precipitation and prior application of bifenthrin in the late irrigation season. As one of the first studies simulating the dynamics and spatial variability of pyrethroids in fields and instreams, the modeling results provided useful information on new policies to be considered with respect to pyrethroid regulation. This study suggested two potential measures to efficiently reduce sediment toxicity by pyrethroids in the study area: [1] limiting bifenthrin use immediately before rainfall season; and [2] implementing conservation practices to retain soil on cropland