| 1. |
- Bauer, S, et al.
(author)
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Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR
- 2022
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In: Metabolites. - : MDPI AG. - 2218-1989. ; 12:9
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Journal article (peer-reviewed)abstract
- Coronary artery disease (CAD) is a complex, multifactorial disease caused, in particular, by inflammation and cholesterol metabolism. At the molecular level, the role of tissue-specific signaling pathways leading to CAD is still largely unexplored. This study relied on two main resources: (1) genes with impact on atherosclerosis/CAD, and (2) liver-specific transcriptome analyses from human and mouse studies. The transcription factor activating transcription factor 3 (ATF3) was identified as a key regulator of a liver network relevant to atherosclerosis and linked to inflammation and cholesterol metabolism. ATF3 was predicted to be a direct and indirect (via MAF BZIP Transcription Factor F (MAFF)) regulator of low-density lipoprotein receptor (LDLR). Chromatin immunoprecipitation DNA sequencing (ChIP-seq) data from human liver cells revealed an ATF3 binding motif in the promoter regions of MAFF and LDLR. siRNA knockdown of ATF3 in human Hep3B liver cells significantly upregulated LDLR expression (p < 0.01). Inflammation induced by lipopolysaccharide (LPS) stimulation resulted in significant upregulation of ATF3 (p < 0.01) and subsequent downregulation of LDLR (p < 0.001). Liver-specific expression data from human CAD patients undergoing coronary artery bypass grafting (CABG) surgery (STARNET) and mouse models (HMDP) confirmed the regulatory role of ATF3 in the homeostasis of cholesterol metabolism. This study suggests that ATF3 might be a promising treatment candidate for lowering LDL cholesterol and reducing cardiovascular risk.
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| 3. |
- Szabo, P. S., et al.
(author)
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Experimental Insights Into Space Weathering of Phobos : Laboratory Investigation of Sputtering by Atomic and Molecular Planetary Ions
- 2020
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In: Journal of Geophysical Research - Planets. - : AMER GEOPHYSICAL UNION. - 2169-9097 .- 2169-9100. ; 125:12
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Journal article (peer-reviewed)abstract
- Investigating the space weathering of the Martian moon Phobos represents an important step toward understanding the development from its origin to its present-day appearance. Depending on Phobos' orbital position, its surface is continuously sputtered by the solar wind and planetary ions that originate in the Martian atmosphere. Based on Mars Atmosphere and Volatile Evolution measurements, it has been proposed that sputtering by planetary O+ and O-2(+) ions dominates in the Martian tail region, where the planet mostly shadows Phobos from the solar wind. In these models, uncertainties for sputtering yield inputs still exist due to the lack of sufficient analog experiments. Therefore, sputtering measurements with O+, O-2(+), C+, and CO2+ ions between 1 and 5 keV were performed using augite samples as Phobos analogs. The experimental results for O+ irradiations show smaller mass changes than predicted by SDTrimSP simulations, which probably can be attributed to O implantation enabled by the Fe content of the target. Sputtering with O-2(+) and CO2+ in the low keV range shows no deviations in the sputtering yields attributable to molecular effects. Therefore, CO2+ ions will most likely be negligible for the sputtering of Phobos according to the current understanding of ion fluxes on the Martian moon. Ultimately, our experiments suggest that the sputtering contribution on Phobos by O ions is about 50% smaller than previously assumed. This does not change the qualitative outcome from previous modeling stating that planetary O ions are by far the dominant sputtering contribution on Phobos in the Martian tail region.
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