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. 2022 Aug 10;29(8):831–840. doi: 10.1038/s41594-022-00814-7

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 6 — Extended Data Figure 6. (a) Treatment of Prnp^ZH1/ZH1 COCS shows toxicity of POM1 and toxic pomologs to be dependent on PrP^C, see also Supplementary Fig. 1a. **: p=0.003, ordinary one-way Anova with Dunnett’s multiple comparisons test. Innocuous pomologs are highlighted in green, POM1 and toxic pomologs are highlighted in red. (b) Morphometric quantification of Prnp-overexpressing tga20 COCS treated with pomologs, see also Fig. 4. Color coding according to panel (A). 100%=untreated COCS, comparison of untreated versus treated groups. N.s.: not significant, ***: p < 0.0001, ** ^hcY101A: p=0.0035, ** ^hcY104A: p=0.0019, ordinary one-way Anova with Dunnett’s multiple comparisons test. (c) Morphometric quantification of fluorescence intensity from images depicted in Supplementary Fig. 1b. §: 1 outlier was excluded (y=2046.3%, p < 0.05, extreme studentized deviate method). Values = % of untreated control. Pairwise comparison in the presence or absence of rmPrP_23–231. ***: p < 0.0001, * GFAP-POM1: p=0.0148, ** GFAP-^lcY101A: p=0.0009, ** F4/80-POM1: p=0.0005, * F4/80-^lcY101A: p=0.0261, ordinary one-way Anova with Šídák’s multiple comparisons test. (d) Toxicity of high-affinity pomolog ^lcS32A ablated by POM2. 100%=POM1 + rmPrP_23–231 (bars 1–4) or 100%=^lcS32 + rmPrP_23–231 (bars 5–7). ** p=0.0003, *** p < 0.0001, ordinary one-way Anova with Šídák’s multiple comparisons test. (e) Titration of minimal toxic dosage of POM1 in tga20 COCS. 100%=POM1 + rmPrP_23–231. ***: p < 0.0001, ordinary one-way Anova with Dunnett’s multiple comparisons test. (f) ^hcY104A prevented POM1-induced toxicity. 100%=Prnp^0/0 COCS treated with POM1 + ^hcY104A. ** p=0.0078, ***(left): p=0.0009, ***(right): p < 0.0001, ordinary one-way Anova with Dunnett’s multiple comparisons test. (g) Quantification of Fig. 4b. 100%=untreated+NBH. ***: p < 0.0001, ordinary one-way Anova with Dunnett’s multiple comparisons test. (h) Quantification of Fig. 4c. 100% = Prnp^ZH3/ZH3 + 22 L. *: p=0.032, ordinary one-way Anova with Šídák’s multiple comparisons test. (i) Quantification of Fig. 4d. 100%=untreated+NBH. *: p=0.0203, **(left): p=0.0036, **(right): p=0.005, ordinary one-way Anova with Dunnett’s multiple comparisons test. All graphs: one datapoint corresponds to one biological replicate.

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