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. 2023 Jul 5;11:108. doi: 10.1186/s40478-023-01601-1

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© The Author(s) 2023

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 7 — Metabolic stress triggers spectrin cleavage without activation of MPT-driven necrosis. a-b hOLs treated with CsA at 2 µM and 10 µM in combination with N1 and NG conditions did not cause a reduction in cell number or increase in PI-positive cells after 4 days of treatment. Each dot in the graphs corresponds to an independent biological sample. Mean ± SEM for each condition is shown in the figure. Statistical significance was assessed using a ANOVA/Dunnett’s test. c Genes presenting significant differences in their transcriptional expression in hOLs compared to HeLa cells were categorised according to pathways involved in MPT-driven necrosis. Genes upregulated are shown in red and downregulated in blue. HeLa cell data was obtained from publicly available databases [1, 10, 17]. hOLs data was obtained from a bulk RNA sequencing database that we have previously published [31]. d Comparison of the enrichment score of genes related to MPT-driven necrosis in N1 and NG conditions in vitro. Mean ± SEM for each condition shown in the figure. Statistical significance was assessed using a Student’s t-test: *(< 0.05). e Enrichment score of genes related to MPT-driven necrosis in MS cases compared to “control” individuals. Mean ± SEM for each condition shown in the figure. Statistical significance was assessed using a Student’s t-test: *(< 0.05)