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Megadroughts are multidecadal periods of aridity more persistent than most droughts during the instrumental period. Paleoclimate evidence suggests that megadroughts occur in many parts of the world, including North America, Central America, western Europe, eastern Asia, and northern Africa. It remains unclear to what extent such megadroughts require external forcing or whether they can arise from internal climate variability alone. A novel statistical–dynamical approach is used to evaluate the possibility that such events arise solely as a function of interannual tropical sea surface temperature (SST) variations. A statistical emulator of tropical SST variations is constructed by using an empirical moving‐blocks bootstrap approach that randomly samples multiyear sequences of the observational SST record. This approach preserves the power spectrum, seasonal cycle, and spatial pattern of El Niño‐Southern Oscillation (ENSO) but removes longer timescale fluctuations embedded in the observational record. These resampled SST anomalies are then used to force an atmospheric model (the Community Atmosphere Model Version 5). As megadroughts emerge in this run, they should, therefore, be solely a consequence of La Niña sequences combined with internal atmospheric variability and persistence driven by soil moisture storage and other land‐surface processes. We indeed find that megadroughts in this simulation have an amplitude‐duration rate that is generally indistinguishable from the rate documented in paleoclimate records of the western United States. Our findings support the idea that megadroughts may occur randomly when the unforced climate system evolves freely over a sufficiently long period of time, implying that an unforced unusual but statistically plausible series of La Niña events may be sufficient to generate megadrought. Key Points: Low‐frequency variability in the tropical Pacific is not critical for producing megadroughts in the US SouthwestA hybrid modeling approach confirms the statistically significant occurrence of megadrought in the SWUS similar to paleoclimate recordsA statistically plausible series of La Niña events may be sufficient to generate megadrought [ABSTRACT FROM AUTHOR]

Why do citizens indicate support for protest movements such as the Tea Party and Occupy Wall Street? There have been two general sets of explanations. One set emphasizes that support comes from those for whom the existing party system, and the ideological differentiation that corresponds to party divisions, are irrelevant. The second set takes the opposite tack, and emphasizes that the only thing that supporters of protests movements find lacking in the party system is extremity. Using some underexplored data, we present evidence that both accounts are incorrect for the case of these recent movements (Occupy and the Tea Party): what provokes support for protest movements is not ideology itself but a fundamental rejection of the current state of the party system, which we call disgruntlement. What ideology does for supporters is provide a sense of political friends and enemies (or near and far), which then can channel the direction that this disgruntlement takes. Further, ideologues with more education are more resistant to the appeal of the protest movement associated with the other political camp. [ABSTRACT FROM AUTHOR]

The estrogen sulfotransferase SULT1E1 sulfates and inactivates estrogen, which is reactivated via desulfation by steroid sulfatase, thus regulating estrogen homeostasis. Phenobarbital (PB), a clinical sedative, activates Sult1e1 gene transcription in mouse livers. Here, the molecular mechanism by which the nuclear receptors CAR, which is targeted by PB, and RORα communicate through phosphorylation to regulate Sult1e1 activation has been studied. RORα, a basal activity repressor of the Sult1e1 promoter, becomes phosphorylated at serine 100 and converts to an activator of the Sult1e1 promoter in response to PB. CAR regulates both the RORα phosphorylation and conversion. Our findings suggest that PB signals CAR to communicate with RORα via serine 100 phosphorylation, converting RORα from transcription repressor to activator of the Sult1e1 gene and inducing SULT1E1 expression in mouse livers. [ABSTRACT FROM AUTHOR]

Abstract: Various drugs such as phenobarbital (PB) trigger translocation of constitutive active/adrostane receptor (CAR) from the cytoplasm into the nucleus of mouse liver cells without directly binding to the receptor. We have now characterized the guanine nucleotide exchange factor epithelial cell-transforming gene 2 (ECT2) as a PB-inducible factor as well as a cellular signal that represses PB-triggered nuclear translocation of CAR. When CFP-tagged ECT2 was co-expressed with YFP-tagged CAR in the liver of Car −/− mice, ECT2 repressed CAR nuclear translocation. Coexpression of various deletion mutants delineated this repressive activity to the tandem Dbl homology/pleckstrin homology domains of ECT2 and to their cytosolic expression. CAR directly bound to the PH domain. Thus, ECT2 may comprise a part of the PB response signal regulating the intracellular trafficking of CAR. [Copyright &y& Elsevier]

Abstract: The nuclear receptor constitutive active/androstane receptor CAR is a drug-sensing transcription factor. Upon activation by various drugs such as phenobarbital (PB), CAR translocates from the cytoplasm into the nucleus to regulate the genes that encode enzymes and proteins involved in hepatic metabolism. Here, we have shown the presence of CAR at the cell membrane of mouse livers, using Car +/+ and Car −/− mice. Levels of the cell membrane CAR increased after PB treatment. The CAR exists as a large approximately 160kDa complex. Thus, CAR undergoes PB-induced translocation to the cell membrane, indicating that CAR may exert a non-genomic action. [Copyright &y& Elsevier]

The nuclear receptor CAR, a phenobarbital (PB)-responsive transcription factor, translocates into the nucleus of hepatocytes after PB induction. In non-induced mice, CAR forms a physical complex with heat shock protein 90 (HSP90) in the cytoplasm. In response to PB induction, protein phosphatase 2A is recruited to the CAR:HSP90 complex. This recruitment may lead CAR to translocate into the nucleus, consistent with the inhibitions of nuclear CAR accumulation in PB-induced mouse primary hepatocytes by okadaic acid as well as by geldanamycin. [Copyright &y& Elsevier]