Tissue-specific activity of the proximal human calcitonin receptor promoter is mediated by Sp1 and an epigenetic phenomenon

AbstractTo identify cis-acting sequences transcriptionally regulating the human calcitonin receptor (hCTR) gene, hCTR promoter/luciferase gene constructs were transiently or stably transfected into hCTR-positive and -negative cell lines. Luciferase assays demonstrated that the proximal hCTR promoter (hCTRP1) was transcriptionally active in all cell lines tested. High-level hCTRP1 activity depended on an 11 bp Sp1/Sp3 binding site. Electrophoretic mobility shift assay showed that this region bound the transcription factors Sp1 and Sp3. We further showed that hCTRP1 was strongly activated by the 11 bp Sp1/Sp3 binding site in hCTRP1/luciferase-, Sp1-transfected Drosophila S2 cells. Bisulphite-mediated sequencing of genomic DNA from hCTR-expressing and -non-expressing cell lines demonstrated that the endogenous hCTRP1 was hypomethylated in all cell lines tested. These results suggest that the hCTRP1 is activated by the tissue-ubiquitous transcription factor Sp1 and that an epigenetic process unrelated to CpG methylation represses its activity in hCTR-negative tissues

Architectures by Design: The Iterative Development of an Integrated Intelligent Agent

Abstract In this paper we demonstrate how a design-based methodology can be used to iteratively produce designs for an information-processing architecture that integrates various intelligent capabilities. This methodology allows us to explain system performance in terms of changes to an existing architecture design, with the explanations being supported by performance data from an implementation of the design. We present an instance of this design methodology applied to the development of an architecture that integrates anytime deliberative capabilities with reactive behaviours and goal management. Iterations of the design are implemented and evaluated in the computer game Unreal Tournament.

AGN STORM 2. I. First results: A Change in the Weather of Mrk 817

We present the first results from the ongoing, intensive, multiwavelength monitoring program of the luminous Seyfert 1 galaxy Mrk 817. While this active galactic nucleus was, in part, selected for its historically unobscured nature, we discovered that the X-ray spectrum is highly absorbed, and there are new blueshifted, broad, and narrow UV absorption lines, which suggest that a dust-free, ionized obscurer located at the inner broad-line region partially covers the central source. Despite the obscuration, we measure UV and optical continuum reverberation lags consistent with a centrally illuminated Shakura-Sunyaev thin accretion disk, and measure reverberation lags associated with the optical broad-line region, as expected. However, in the first 55 days of the campaign, when the obscuration was becoming most extreme, we observe a de-coupling of the UV continuum and the UV broad emission-line variability. The correlation recovered in the next 42 days of the campaign, as Mrk 817 entered a less obscured state. The short C iv and Lyα lags suggest that the accretion disk extends beyond the UV broad-line region. © 2021. The American Astronomical Society. All rights reserved..Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]