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1. Differential clock comparisons with a multiplexed optical lattice clock

   https://doi.org/10.1038/s41586-021-04344-y  

   Zheng, Xin ; Dolde, Jonathan ; Lochab, Varun ; Merriman, Brett N. ; Li, Haoran ; Kolkowitz, Shimon ( February 2022 , Nature)
2. Normative References for Graphomotor and Latency Digital Clock Drawing Metrics for Adults Age 55 and Older: Operationalizing the Production of a Normal Appearing Clock

   https://doi.org/10.3233/JAD-201249  

   Davoudi, Anis ; Dion, Catherine ; Formanski, Erin ; Frank, Brandon E. ; Amini, Shawna ; Matusz, Emily F. ; Wasserman, Victor ; Penney, Dana ; Davis, Randall ; Rashidi, Parisa ; et al ( June 2021 , Journal of Alzheimer's Disease)

   Background: Relative to the abundance of publications on dementia and clock drawing, there is limited literature operationalizing ‘normal’ clock production. Objective: To operationalize subtle behavioral patterns seen in normal digital clock drawing to command and copy conditions. Methods: From two research cohorts of cognitively-well participants age 55 plus who completed digital clock drawing to command and copy conditions (n = 430), we examined variables operationalizing clock face construction, digit placement, clock hand construction, and a variety of time-based, latency measures. Data are stratified by age, education, handedness, and number anchoring. Results: Normative data are provided in supplementary tables. Typical errors reported in clock research with dementia were largely absent. Adults age 55 plus produce symmetric clock faces with one stroke, with minimal overshoot and digit misplacement, and hands with expected hour hand to minute hand ratio. Data suggest digitally acquired graphomotor and latency differences based on handedness, age, education, and anchoring. Conclusion: Data provide useful benchmarks from which to assess digital clock drawing performance in Alzheimer’s disease and related dementias. 

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3. NF-κB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1

   https://doi.org/10.1371/JOURNAL.PGEN.1009933  

   Shen, Yang ; Endale, Mehari ; Wang, Wei ; Morris, Andrew R. ; Francey, Lauren J. ; Harold, Rachel L. ; Hammers, David W. ; Huo, Zhiguang ; Partch, Carrie L. ; Hogenesch, John B. ; et al ( November 2021 , PLOS Genetics)

   Kramer, Achim (Ed.)

   In mammals, the circadian clock coordinates cell physiological processes including inflammation. Recent studies suggested a crosstalk between these two pathways. However, the mechanism of how inflammation affects the clock is not well understood. Here, we investigated the role of the proinflammatory transcription factor NF-κB in regulating clock function. Using a combination of genetic and pharmacological approaches, we show that perturbation of the canonical NF-κB subunit RELA in the human U2OS cellular model altered core clock gene expression. While RELA activation shortened period length and dampened amplitude, its inhibition lengthened period length and caused amplitude phenotypes. NF-κB perturbation also altered circadian rhythms in the master suprachiasmatic nucleus (SCN) clock and locomotor activity behavior under different light/dark conditions. We show that RELA, like the clock repressor CRY1, repressed the transcriptional activity of BMAL1/CLOCK at the circadian E-box cis-element. Biochemical and biophysical analysis showed that RELA binds to the transactivation domain of BMAL1. These data support a model in which NF-kB competes with CRY1 and coactivator CBP/p300 for BMAL1 binding to affect circadian transcription. This is further supported by chromatin immunoprecipitation analysis showing that binding of RELA, BMAL1 and CLOCK converges on the E-boxes of clock genes. Taken together, these data support a significant role for NF-κB in directly regulating the circadian clock and highlight mutual regulation between the circadian and inflammatory pathways. 

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4. A Single-Clock-Phase Sense Amplifier Architecture with 9x Smaller Clock-to-Q Delay Compared to the StrongARM & 6.3dB Lower Noise Compared to Double-Tail

   https://doi.org/10.1109/VLSITechnologyandCir46769.2022.9830355  

   Lin, X. ; Megahed, M. ; Anand, T. ( June 2022 , International Symposium on VLSI Technology Systems and Application)

   A single-clock-phase sense amplifier architecture with a strong regeneration is proposed. Designed in 22nm FinFET, the proposed architecture has a 9x smaller t CQ delay compared to the conventional StrongARM latch and 6.3dB lower input referred noise compared to the Double-Tail architecture for similar input transistor size and power consumption. 

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5. Circadian regulation of the GLYCINE-RICH RNA-BINDING PROTEIN gene by the master clock protein CIRCADIAN CLOCK-ASSOCIATED 1 is important for plant innate immunity

   https://doi.org/10.1093/jxb/erac445  

   Gao, Min ; Zhang, Chong ; Angel, William ; Kwak, Owen ; Allison, Jessica ; Wiratan, Linda ; Hallworth, Amelia ; Wolf, Julie ; Lu, Hua ; Jones, ed., Matt ( November 2022 , Journal of Experimental Botany)

   Recent studies have demonstrated the importance of temporal regulation of pathogen defense by the circadian clock. However, our understanding of the molecular basis underlying this role of the circadian clock is still in its infancy. We report here the mechanism by which the Arabidopsis master clock protein CCA1 regulates an output target gene GRP7 for its circadian expression and function in pathogen defense. Our data firmly establish that CCA1 physically associates with the GRP7 promoter via the predicted CCA1-binding motif, evening element (EE). A site-directed mutagenesis study showed that while individual EE motifs differentially contribute to robust circadian expression of GRP7, abolishing all four EE motifs in the proximal GRP7 promoter disrupts rhythmicity of GRP7 expression and results in misalignment of defense signaling mediated by GRP7 and altered pathogen responses. This study provides a mechanistic link of the circadian regulation of an output gene to its biological function in pathogen defense, underscoring the importance of temporal control of plant innate immunity.

    

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