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At the core of the mammalian circadian feedback loop, CLOCK (NPAS2)-BMAL1 is the positive element to activate transcription of downstream genes encoding the negative elements PERs and CRYs. Here we show that CNOT1 associates with both CLOCK and BMAL1, promotes their phosphorylation and increases their protein stability, and in turn inhibits the transcriptional activity of CLOCK-BMAL1. Expression of either CLOCK, BMAL1 or CNOT1 could interact with endogenous Protein Kinase A (PKA) as assessed by co-immunoprecipitation (Co-IP) and kinase assays. PKA could phosphorylate CLOCK and BMAL1 and this was promoted by CNOT1. Genetic deletion of PKA-Cα by CRISPR-Cas9 results in a longer period of the circadian rhythm; while overexpression of PKA-Cα induces a shorter period. Furthermore, we demonstrate that CNOT1 associates with CLOCK and BMAL1 in the mouse liver and promotes their phosphorylation. PER2, but not CRY2, is also a PKA target. Our results suggest that CNOT1 and PKA play a critical role in the mammalian circadian clock, revealing a conserved function in eukaryotic circadian regulations.

To demonstrate the relation between yttrium oxide-based (Y2O3-based) ceramics and plasma etching behavior, Y2O3-based ceramics were prepared by adding different amounts of alumina to the matrix, and the effect of the different amounts of alumina on its plasma etching resistance was investigated. Xe plasma flow generated by Hall Thruster was used for sputtering the surface of the samples to evaluate the plasma etching resistance. XRD, XPS, SEM, and AFM were used to characterize the phase composition and morphologies of as-made composite ceramics before and after Xe plasma etching. The results suggest that the introduction of alumina reduces the etching resistance of Y2O3-based ceramics. When the main phases of the sintered ceramics are Y2O3, Y3Al5O12 (YAG) and Y3Al5O12+Al2O3 (YAGA), the etching rates are 23 nm min−1, 59 nm min−1 and 152 nm min−1, respectively. Xe plasma is found to homogeneously etch the surfaces of the sintered Y2O3 matrix ceramic materials, yet the etching rates on different crystal surfaces are different, regardless of the phase composition of the materials. Overall, the high-density YAG ceramics can maintain both the etching rate per unit time and the surface roughness at a low level, which is a kind of complementary material to replace Y2O3 ceramics.

The conduction of a bilayer sample consisting of a ZnO layer and an additive segregation layer was investigated. It was found that (1) the DC V-I characteristics of the sample behave like those of nonohmic ZnO ceramics and can be adjusted by changing the resistance of the ZnO layer. Ceramics with large nonlinearity can be obtained by changing the resistance of the AnO grains. >