Evidence map›Paper›PMID 32815370›Full record

ArticleJournal of the American Chemical Society2020

Activity-Based Sensing with a Metal-Directed Acyl Imidazole Strategy Reveals Cell Type-Dependent Pools of Labile Brain Copper.

Sumin Lee, Clive Yik-Sham Chung, Pei Liu, Laura Craciun, Yuki Nishikawa, Kevin J Bruemmer, Itaru Hamachi, Kaoru Saijo, Evan W Miller, Christopher J Chang

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 91 citations in OpenAlex.

  1. Article
  2. Article
  3. Simultaneous Imaging of CuAngewandte Chemie (International ed. in English) · 2026
    Article
  4. Development of AuACS applied materials & interfaces · 2026
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  5. Review
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  8. A practical COBeilstein journal of organic chemistry · 2026
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  11. Article
  12. Review
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  14. Article
  15. A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
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  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Clive Yik-Sham ChungORCID 0000-0003-1382-719X
Laura Craciun
Yuki NishikawaDepartment of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
Itaru HamachiDepartment of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.ORCID 0000-0002-3327-3916
Christopher J ChangORCID 0000-0001-5732-9497
University of California, Berkeley · USKyoto University · JPUniversity of Hong Kong · HK

Funding

Molecular Imaging Probes To Study Redox BiologyR01GM079465 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Christopher J. Chang · 2006 to 2026
$7.8M
Neuroscience Training Program at UC BerkeleyT32NS095939 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI BATEUP, HELEN S. · 2016 to 2025
$6.3M
Estrogen receptor (ER)β-mediated repression of prenatal inflammation in fetal microglia and its impact on autismR01HD092093 · NICHD · UNIVERSITY OF CALIFORNIA BERKELEY · PI SAIJO, KAORU · 2017 to 2021
$1.6M
New Chemical Tools for Exploring Cellular PhysiologyR35GM119855 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MILLER, EVAN WALKER · 2016 to 2020
$1.3M
NICHD NIH HHS R01 HD092093NIGMS NIH HHS R01 GM079465NIGMS NIH HHS R35 GM119855NINDS NIH HHS T32 NS095939
6 · The paper itself

Abstract

Copper is a required nutrient for life and particularly important to the brain and central nervous system. Indeed, copper redox activity is essential to maintaining normal physiological responses spanning neural signaling to metabolism, but at the same time copper misregulation is associated with inflammation and neurodegeneration. As such, chemical probes that can track dynamic changes in copper with spatial resolution, especially in loosely bound, labile forms, are valuable tools to identify and characterize its contributions to healthy and disease states. In this report, we present an activity-based sensing (ABS) strategy for copper detection in live cells that preserves spatial information by a copper-dependent bioconjugation reaction. Specifically, we designed copper-directed acyl imidazole dyes that operate through copper-mediated activation of acyl imidazole electrophiles for subsequent labeling of proximal proteins at sites of elevated labile copper to provide a permanent stain that resists washing and fixation. To showcase the utility of this new ABS platform, we sought to characterize labile copper pools in the three main cell types in the brain: neurons, astrocytes, and microglia. Exposure of each of these cell types to physiologically relevant stimuli shows distinct changes in labile copper pools. Neurons display translocation of labile copper from somatic cell bodies to peripheral processes upon activation, whereas astrocytes and microglia exhibit global decreases and increases in intracellular labile copper pools, respectively, after exposure to inflammatory stimuli. This work provides foundational information on cell type-dependent homeostasis of copper, an essential metal in the brain, as well as a starting point for the design of new activity-based probes for metals and other dynamic signaling and stress analytes in biology.

Indexed as

Coordination ComplexesCopperFluorescent DyesHEK293 CellsHumansImidazolesMolecular StructureOptical ImagingCoordination ComplexesCopperFluorescent DyesimidazoleImidazoles

Identifiers

PMID32815370
PMCPMC7877313
OpenAlexW3080711624

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.