SUPPLEMENT Brooks, Ian M.; Yelland, Margaret J.; Upstill-Goddard, Robert C. ...
Bulletin of the American Meteorological Society,
05/2009, Letnik:
90, Številka:
5
Journal Article
We have demonstrated that treatment with 200 nM okadaic acid (OA) for 1 h followed by a 15-min heat shock (HS) at 45 degrees C (termed OA-->HS treatment) leads to a rapid transactivation of grp78, ...the gene for the 78-kDa glucose-regulated protein, in 9L rat brain tumor cells. The level of Grp78 mRNA rose 15-fold in 60 min after the combined treatment. Nuclear extracts from cells subjected to OA-->HS treatment, compared to those of treatment with OA or HS alone, exhibited an increased binding activity toward an oligonucleotide probe containing the cAMP-responsive element-like (CRE-like, TGACGTGA) regulatory element in electrophoretic mobility shift assays (EMSA). The binding resulted in the formation of two protein-EMSA probe complexes exhibiting different association and dissociation rates in kinetic studies. The protein factors in the upper band (complex I) and lower band (complex II) were identified as the activating transcription factor-2 (ATF-2) and the CRE binding factor 1 (CREB-1), respectively, by antibody interference assays. In addition, the identity of CREB-1 was confirmed by supershift analysis. The binding activity, as well as the transactivation of the grp78 gene, can be abolished by a 1-h treatment with the cAMP-dependent protein kinase (PKA) inhibitor but not with protein kinase C or Ca2+/calmodulin-dependent protein kinase II inhibitors. Accumulation of steady-state level of ATF-2 was observed and was also modulated by treatment with H-89, a PKA inhibitor. From these results, we conclude that the CRE-like element plays an important role in the rapid transactivation of the grp78 gene and that the PKA signaling pathway is involved. In addition, PKA-mediated transcriptional regulation of grp78 in OA-->HS treatment is through regulation of protein phosphorylation as well as de novo synthesis of ATF-2.
We perform a joint analysis of the counts and weak lensing signal of redMaPPer clusters selected from the Dark Energy Survey (DES) Year 1 dataset. Our analysis uses the same shear and source ...photometric redshifts estimates as were used in the DES combined probes analysis. Our analysis results in surprisingly low values for \(S_8 =\sigma_8(\Omega_{\rm m}/0.3)^{0.5}= 0.65\pm 0.04\), driven by a low matter density parameter, \(\Omega_{\rm m}=0.179^{+0.031}_{-0.038}\), with \(\sigma_8-\Omega_{\rm m}\) posteriors in \(2.4\sigma\) tension with the DES Y1 3x2pt results, and in \(5.6\sigma\) with the Planck CMB analysis. These results include the impact of post-unblinding changes to the analysis, which did not improve the level of consistency with other data sets compared to the results obtained at the unblinding. The fact that multiple cosmological probes (supernovae, baryon acoustic oscillations, cosmic shear, galaxy clustering and CMB anisotropies), and other galaxy cluster analyses all favor significantly higher matter densities suggests the presence of systematic errors in the data or an incomplete modeling of the relevant physics. Cross checks with X-ray and microwave data, as well as independent constraints on the observable--mass relation from SZ selected clusters, suggest that the discrepancy resides in our modeling of the weak lensing signal rather than the cluster abundance. Repeating our analysis using a higher richness threshold (\(\lambda \ge 30\)) significantly reduces the tension with other probes, and points to one or more richness-dependent effects not captured by our model.
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