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John Schneekloth (Jay)

@jschneek.bsky.social
1.5K followers 1.4K following 39 posts

Chemical Biologist. Interested in RNA and DNA targeting, medicinal chemistry, and all things chemical biology. Follow my research here: bit.ly/4fpxjan

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John Schneekloth (Jay) @jschneek.bsky.social · 25/06/2025
Honored to see that our collaborative work with Pratyush Tiwary and Adrian Ferré-D'Amaré on the ZTP riboswitch was selected as a very important paper by @angewandtechemie.bsky.social! onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com
Machine Learning‐Augmented Molecular Dynamics Simulations (MD) Reveal Insights Into the Disconnect Between Affinity and Activation of ZTP Riboswitch Ligands
This study combines computational and experimental approaches to study how natural and synthetic small molecules interact with the ZTP riboswitch, a bacterial RNA element that regulates gene expressi....
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John Schneekloth (Jay) @jschneek.bsky.social · 28/05/2025
Hear-hear! Science making amazing progress and saving lives despite increasing barriers is something to be celebrated.
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John Schneekloth (Jay) @jschneek.bsky.social · 28/05/2025
Out now in @natchem.nature.com! Lots to unpack here, but in short - we show that SMM enabled fragment based design is useful on RNAs to improve chemical properties like affinity and brightness of fluorophore ligands. www.nature.com/articles/s41...
nature.com
Structure-informed design of an ultrabright RNA-activated fluorophore - Nature Chemistry
Fluorogenic RNA aptamers such as Mango are powerful tools for RNA imaging. An ultrabright RNA-activated fluorophore with improved photophysical performance has now been developed using a structure-inf...
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John Schneekloth (Jay) @jschneek.bsky.social · 08/05/2025
New work from the lab - With Pratyush Tiwary and Adrian Ferre-D'Amare, we study ligands that activate the ZTP riboswitch. Experimental and theoretical approaches show that ligand on rates influence activity by non-obvious mechanisms when targeting RNA! onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com
Machine learning‐augmented molecular dynamics simulations (MD) reveal insights into the disconnect between affinity and activation of ZTP riboswitch ligands
The challenge of targeting RNA with small molecules necessitates a better understanding of RNA-ligand interaction mechanisms. However, the dynamic nature of nucleic acids, their ligand-induced stabil...
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ACS BIOL: Division of Biochemistry and Chemical Biology @acsbiol.bsky.social · 06/05/2025
Congratulations to Evan J. Burke, a grad student in the Krebs and Bollinger labs in Penn State's Department of Chemistry, on being named a 2025 #ACSBIOL Young Investigator! @jmarbol21.bsky.social
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John Schneekloth (Jay) @jschneek.bsky.social · 30/04/2025
Another new piece of work from the lab - I played a small role in this really exciting work coming out of the Pearson lab at Sick Kids in Toronto dealing with preclinical studies on CAG repeat instability in Huntington disease. Check it out: www.biorxiv.org/content/10.1...
biorxiv.org
Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence.
Huntington disease (HD) is caused by inherited CAG expansions, which continue expanding somatically in affected brain regions to hasten disease onset and progression. Therapeutically diminishing somat...
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John Schneekloth (Jay) @jschneek.bsky.social · 25/04/2025
Hey, check it out - new work from the lab! We report the design of design traceless, reversible small molecule photocrosslinking probes that can be used to photochemically control the translation of mRNAs just using molecular recognition! Congrats to all! onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com
Harnessing Molecular Recognition for Small‐Molecule‐Mediated Reversible Photochemical Control Over mRNA Translation
A small molecule ligand undergoes traceless, reversible photocrosslinking to PreQ1 RNA aptamer in a selective manner, dependent on both the RNA sequence/structure and ligand chemical structure. A cag...
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Luke Lavis @rhodamine110.bsky.social · 11/04/2025
We're looking for 1-2 enthusiastic early career chemists to join our Open Chemistry team at @hhmijanelia.bsky.social. Come help us create amazing dyes and share them with the world. Please share with the best recent/soon-to-be B.S. chemists you know! bit.ly/42w8C6N
bit.ly
Research Technician - Open Chemistry
Primary Work Address: 19700 Helix Drive, Ashburn, VA, 20147 Current HHMI Employees, click here to apply via your Workday account. Summary: Open Chemistry is a collaborative research group whose missio...
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Jordan Meier @doc-jlmeier.bsky.social · 10/04/2025
Great news: NIH postbac program is recruiting again! If your grad school plans were affected by program cutbacks or admissions freezes this year I highly encourage you to apply, this could be a perfect opportunity. Please repost. www.training.nih.gov/research-tra...
training.nih.gov
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John Schneekloth (Jay) @jschneek.bsky.social · 04/04/2025
New work from my awesome colleague @vidigaljoana.bsky.social!
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ACS BIOL: Division of Biochemistry and Chemical Biology @acsbiol.bsky.social · 26/03/2025
The final #ACSBIOL sessions of #ACSSpring2025 are tomorrow morning, Thursday the 27th: 📰 Current Topics in #Biochem and #ChemBio, Room 31A 👩‍🎓 Undergraduate and Graduate Research, Hal G/H Room 8 Be sure to check out these excellent presentations!
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ACS BIOL: Division of Biochemistry and Chemical Biology @acsbiol.bsky.social · 25/03/2025
#ACSBIOL Sessions on Wednesday, 26th at #ACSSpring2025: Morning, Room 31A: 🏆 Eli Lilly Award to @brianliau.bsky.social Afternoon, Room 31A: 🏆 ACS Chemical Biology Young Investigator Award to @jeremybaskin.bsky.social Evening, Hall B2/C: 📜 Poster Session, Current Topics @pubs.acs.org
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John Schneekloth (Jay) @jschneek.bsky.social · 13/03/2025
Congrats @rche54.bsky.social, nice work!
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John Schneekloth (Jay) @jschneek.bsky.social · 22/01/2025
Check out this awesome paper from my colleague @eunayoo.bsky.social about activity-based probes for USP18! www.nature.com/articles/s41...
nature.com
Chemical tools to define and manipulate interferon-inducible Ubl protease USP18 - Nature Communications
USP18 is a multifunctional cysteine protease involved in IFN pathways. Here, the authors report chemical probes and chemoproteomics platforms that allow to detect and perturb USP18 activity in complex...
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John Schneekloth (Jay) @jschneek.bsky.social · 19/12/2024
We often focus on publicizing our work to other scientists but it's just as important to have journalists communicate with non-scientists as well!
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Ingo Hartung @hartungingo.bsky.social · 19/12/2024
I am about to survive my 1047th week in medicinal chemistry. This editorial is a visit on memory lane. Yes, starting in MedChem initially looks very daunting. MedChems love abbreviations & specialist slang to scare off laymen. But overcoming these hurdles is so rewarding in many dimensions.
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John Schneekloth (Jay) @jschneek.bsky.social · 19/12/2024
What a week! Really proud to share this work with Venkat Gopalan and Damien Wilburn in Nucleic Acids Research. We show that our SMM platform can be used to identify allosteric chemical inhibitors of an archaeal RNase P, an ancient ribozyme. academic.oup.com/nar/advance-...
academic.oup.com
Use of a small molecule microarray screen to identify inhibitors of the catalytic RNA subunit of Methanobrevibacter smithii RNase P
Abstract. Despite interest in developing therapeutics that leverage binding pockets in structured RNAs—whose dysregulation leads to diseases—such drug disc
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John Schneekloth (Jay) @jschneek.bsky.social · 19/12/2024
Thrilled to see our work in @pnas.org this week! With Pratyush Tiwary, we show that "thermodynamic maps" can be used to infer and predict information about RNA 3D structural ensembles! Proud to have played a small role in this exciting work. www.pnas.org/doi/10.1073/...
pnas.org
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John Schneekloth (Jay) @jschneek.bsky.social · 19/12/2024
This is deeply concerning!
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Our World in Data @ourworldindata.org · 09/12/2024
Americans are now one-third less likely to die from cancer at the same ages as Americans in 1990
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John Schneekloth (Jay) @jschneek.bsky.social · 09/12/2024
Really excited to see this work out! In collaboration with Prof. Jen Prescher, we showed that their cyclopropenone labeling strategy can be applied to structured RNA! Thrilled to work with this fantastic team of scientists. pubs.acs.org/doi/10.1021/...
pubs.acs.org
Bioorthogonal Cyclopropenones for Investigating RNA Structure
RNA sequences encode structures that impact protein production and other cellular processes. Misfolded RNAs can also potentiate disease, but a complete picture is lacking. To establish more comprehens...
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Altmetric @altmetric.com · 03/12/2024
One of the reasons Bluesky is seeing more engagement: other platforms have adopted the behaviour of de-prioritising external links (like, say, to research papers) due to Ad models. See this: bsky.app/profile/alt... Here links can be freely shared without being drowned out or de-emphasized
bsky.app
@altmetric.com on Bluesky
We’re no experts but this sounds like it might be suboptimal for disseminating research. [contains quote post or other embedded content]
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Giedroc Lab @giedroclab.bsky.social · 02/12/2024
🎉 Our grad student @katherinelegg.bsky.social is a co-author on a new preprint about the genetic requirements and nutrient needs for Staphylococcus aureus growth in cystic fibrosis sputum. Congrats to @gramnegativity.bsky.social and all involved! shorturl.at/yfZQA 🧬 #CysticFibrosis #Microbiology
pmc.ncbi.nlm.nih.gov
Analysis of genetic requirements and nutrient availability for Staphylococcus aureus growth in cystic fibrosis sputum
Staphylococcus aureus is one of the most common pathogens isolated from the lungs of people with cystic fibrosis (CF), but little is known about its ability to colonize this niche. We performed a Tn-s...
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John Rubinstein @johnrubinstein.bsky.social · 02/04/2024
Years after the idea and preliminary experiments, Claire Coupland's amazing structure of the endogenous vacuolar- or vesicular-ATPase in its NATIVE vesicle is now in bioRxiv "High resolution cryo-EM of V-ATPase in native synaptic vesicles" www.biorxiv.org/content/10.1...
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Stu Cantrill @stuartcantrill.com · 02/12/2024
So @altmetric.com is now tracking on @bsky.app too! Flagging for #Chemsky
A screengrab of a paper being tracked on Altmetric.com; the Altmetric donut score is 89 and the title of the paper is 'Photocatalytic low-temperature defluorination of PFASs'. The 'Bluesky' source tab is the one highlighted showing one post that mentions the paper in question.
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Marc Lensink @marclensink.bsky.social · 01/12/2024
The CASP16 conference has started. Collectively predictors predicted coordinates of over one billion atoms
Collectively predictors predicted coordinates of over one billion atoms
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Prasad Jallepalli, MD, PhD @prasad.bsky.social · 01/12/2024
“NIH produces an astounding return on investment to the American taxpayer. In Fiscal Year 2022, NIH research funding supported 568,585 jobs and generated $96.84 billion in economic activity — that’s $2.64 of economic activity for every $1 of research funding.” www.researchamerica.org/2023-oped-us...
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Abhishek Chatterjee @achemsynbio.bsky.social · 01/12/2024
Got the chance to put together the "Click of Chemical Biologists" starter pack v1 and v2 over the Thanksgiving Break. Feel free to ping me on who else I might be missing! V1: go.bsky.app/3P5i7nJ V2: go.bsky.app/Cr4ej7
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Stephen Floor @snf.bsky.social · 27/11/2024
sunburn is from ribosomes stalled by UV damage to RNA? super cool www.sciencedirect.com/science/arti...
sciencedirect.com
The ribotoxic stress response drives acute inflammation, cell death, and epidermal thickening in UV-irradiated skin in vivo
Solar UVB light causes damage to the outermost layer of skin. This insult induces rapid local responses, such as dermal inflammation, keratinocyte cel…
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Karla Neugebauer @karlaneugebauer.bsky.social · 27/11/2024
We are happy to share the development of Co-transcriptional Structure Tracking by @leoschaerfen.bsky.social, which measures RNA structure formation during its synthesis in vivo. We are excited to discover the activity of helicases on nascent rRNA! www.biorxiv.org/content/10.1...
biorxiv.org
Rapid folding of nascent RNA regulates eukaryotic RNA biogenesis
An RNA′s catalytic, regulatory, or coding potential depends on RNA structure formation. Because base pairing occurs during transcription, early structural states can govern RNA processing events and d...
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Steven Silverman @asymtmm.bsky.social · 27/11/2024
So excited to see this published! Thionucleosides can be incredibly challenging to make due to the need for oxidation state changes at sulfur during the synthesis. Collaborating with the Britton group, we’ve been able to make them using a short, selective sequence! pubs.rsc.org/en/content/a...
pubs.rsc.org
A flexible and scalable synthesis of 4′-thionucleosides
4′-Thionucleosides (thNAs) are synthetic nucleoside analogues that have attracted attention as leads for drug discovery in oncology and virology. Here we report a de novo thNA synthesis that relies on...
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Ross Cheloha @rche54.bsky.social · 27/11/2024
Happy and proud to see this paper from postdoc Shubhra Saha and myself come out in JACS Au! This was a project where I really had no idea if we could get the design to work but IT DID and I think it’s quite cool. A brief rundown 1/n
pubs.acs.org
Chemically Induced Dimerization via Nanobody Binding Facilitates in Situ Ligand Assembly and On-Demand GPCR Activation
Methods that enable the on-demand synthesis of biologically active molecules offer the potential for a high degree of control over the timing and context of target activation; however, such approaches often require extensive engineering to implement. Tools to restrict the localization of assembly also remain limited. Here we present a new approach for stimulus-induced ligand assembly that helps to address these challenges. This methodology relies on the high affinity and specificity recognition exhibited by antibody fragments (nanobodies, Nbs). By using Nbs that recognize short peptide epitopes to create semisynthetic conjugates, we develop a bioengineering platform termed peptide epitope dimerization (PED) in which the addition of heterodimeric peptide composed of two Nb epitopes stimulates the proximity-induced synthesis of a functional ligand for the parathyroid hormone receptor-1, a G protein-coupled receptor. We further demonstrate that high efficiency assembly can be achieved on the cell surface via Nb-based delivery of template. This approach opens the door for the on-demand generation of bioactive receptor ligands preferentially at a desired biological niche.
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Micha Rapé Lab @micharapelab.bsky.social · 26/11/2024
Excited to report our discovery of an important component of the oxidative stress response: the E3 ligase TRIP12. It acts as a chain elongation factor that amplifies CUL3-KEAP1 activity to drive NRF2 degradation as cells recover from stress. www.biorxiv.org/content/10.1...
biorxiv.org
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12
The oxidative stress response is centered on the transcription factor NRF2 and protects cells from reactive oxygen species (ROS). While ROS inhibit the E3 ligase CUL3-KEAP1 to stabilize NRF2 and elici...
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ACS BIOL: Division of Biochemistry and Chemical Biology @acsbiol.bsky.social · 24/11/2024
We are so back Where my other #chemtwitter #chemsky #chembio #chemicalbiology #realtimechem homies at?
media.tenor.com
a cartoon character from the emperor 's new groove is holding a fan and says boom baby
Alt: Emperor Cuzco from the animated movie "The Emperor's New Groove" bursts into a room shouting "BOOM BABY!", representing the american chemical society division of biochemistry and chemical biology's presence on BlueSky should be known, celebrated, and perhaps feared by the #chembio #chemsky #chemtwitter #chemicalbiology #realtimechem and other communities. The jovial reference to a children's movie likewise signifies the division's interest in making this online space fun and inclusive for scientists of all ages and career stages, and likely foretells of future memes to be posted by this account.
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John Schneekloth (Jay) @jschneek.bsky.social · 26/11/2024
Check it out! New review article from the group discussing structural factors that make RNA-protein interactions favorable for targeting/drug discovery efforts. I was proud to contribute to this issue in honor of Stephen Neidle! link.springer.com/article/10.1...
link.springer.com
Targeting RNA-protein interactions with small molecules: promise and therapeutic potential - Medicinal Chemistry Research
The therapeutic potential of targeting protein-RNA interactions has not been fully explored. While several approaches to block the interactions between various RNA and protein partners have been devel...
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John Schneekloth (Jay) @jschneek.bsky.social · 22/11/2024
Amazing work!
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Michael E. Mann @michaelemann.bsky.social · 21/11/2024
"Scientists as political advocates" | Must-read commentary in Science Magazine mentions my #ScienceUnderSiege co-author Dr. Peter Hotez and me in the context of the dual assault by the right on both climate and public health science: www.science.org/doi/10.1126/...
science.org
Scientists as political advocates
Science, both teaching and doing, is under attack. The recent US presidential election of a person and platform with anti-science bias exemplifies this. The study of climate processes and patterns and...
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Anne Simon 🧪🌱🐴🦠🍊🇨🇦🇺🇦 @annealiz1.bsky.social · 21/11/2024
🧪#RNA #RNASky Really cool article from earlier this year. Ribozyme polymerase replicating another ribozyme with high fidelity. More ammunition for the RNA World? www.pnas.org/doi/10.1073/...
pnas.org
RNA-catalyzed evolution of catalytic RNA | PNAS
An RNA polymerase ribozyme that was obtained by directed evolution can propagate a functional RNA through repeated rounds of replication and select...
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Stephan Hacker @stephanhacker2.bsky.social · 21/11/2024
If you are interested in #ChemicalBiology #ChemBio, check out the Virtual @chembiotalks.bsky.social and already block your agenda for September 20th, 2025. If you have ideas for speakers for next year or for general changes to the format, please reply to the below post.
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Jeff Coller @jmcoller.bsky.social · 18/11/2024
Proud to be a founding member of this organization. The work we are doing is vital as we move into the next few years. mrnamedicines.org
mrnamedicines.org
Alliance for mRNA Medicines
The Alliance for mRNA Medicines (AMM) is the leading global organization dedicated to advancing and advocating for mRNA medicines and next-generation coding RNA therapies for the benefit of patients, ...
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Dr. Catherine Macdonald @drcatmac.bsky.social · 17/11/2024
A frustrating component of many scientists believing “we just need to teach people facts to change their behavior” is an inability to recognize most people don’t think or operate the way scientists do. (Scientists, in theory, are carefully trained to change our minds/views in response to new data).
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Yamuna Krishnan @krishnanyamuna.bsky.social · 18/11/2024
Interesting list! Highly recommend to also follow @laurakiessling.bsky.social @carolynbertozzi.bsky.social @clarknano.bsky.social Amazing chemical biologists who happen to be women.
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Jake Yeston @jakeyeston.bsky.social · 17/11/2024
For new arrivals, I’m the chemistry editor* at Science Magazine and more generally the supervisory editor of the whole physical sciences group there. I’m excited that the population of chemists is growing so rapidly here. Remember to use the chemsky tag for chem-related posts!
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John Schneekloth (Jay) @jschneek.bsky.social · 18/11/2024
This really matters. What can be done to build public trust in science?
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John Schneekloth (Jay) @jschneek.bsky.social · 18/11/2024
Great list of folks to follow!!
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Stephan Hacker @stephanhacker2.bsky.social · 17/11/2024
The 2025 Bioorganic Gordon Research Conference organized by Denise Field and @doc-jlmeier.bsky.social has an amazing lineup of speakers. Sadly, I will not be able to travel, but if you are interested in #ChemicalBiology, #BioorganicChemistry or #ChemicalProteomics, make sure to check it out. (1/4)
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John Schneekloth (Jay) @jschneek.bsky.social · 16/11/2024
Loving the growth in community here! Happy Friday everyone.
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Danny IncaRNAto @incarnatolab.bsky.social · 15/11/2024
Fellow #RNA lovers, please repost 🙏: 2 ERC-funded Post-doc positions are available in our lab to investigate #RNA structural ensemble and their dynamics in living cells. Application link: t.co/pYJ3H3j705
t.co
https://www.rug.nl/about-ug/work-with-us/job-opportunities/?details=00347-02S000B06P
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