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. 2018 Mar 1;9:897. doi: 10.1038/s41467-018-03355-0

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© The Author(s) 2018

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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Fig. 1 — A genetic screen identifies C. elegans manf-1 in regulating hsp-4p::GFP. a Exemplar GFP fluorescence and Nomarski images showing constitutive activation of hsp-4p::GFP in the dma1 mutant isolated from mutagenesis screens. Wild type and mutant L4-stage animals (indicated by arrows) are aligned in the same field to compare GFP intensity at low (above) or high (bottom) magnification. Scale bars, 100 µM. b Schematic of manf-1 gene structure with various manf-1 alleles and extrachromosomal arrays (Ex) indicated. c Summary table for the hsp-4p::GFP phenotype of the wild type compared with various mutants, with indicated levels of GFP intensity in the intestine, the major site of hsp-4p::GFP expression, and penetrance (N ≥ 100 for each genotype). d Integrated manf-1p::Venus transcriptional reporter indicating the widespread expression of manf-1. e Exemplar GFP fluorescence images showing the rescue of the hsp-4p::GFP phenotype in the manf-1 null tm3603 mutant by C. elegans manf-1(+) and human MANF driven by the manf-1 promoter. Transgenic rescuing arrays are marked by unc-54p::mCherry expressed in body wall muscles. f Summary table showing the rescuing effect of various transgenes on hsp-4p::GFP of the manf-1(tm3603) mutant with indicated GFP intensity levels and penetrance (N ≥ 100 for each genotype)