Nature

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Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I NBR1 mediates selective autophagy of MHC-I Autophagy inhibition enhances anti-tumour immunity Basal autophagy determines immunogenicity Autophagy inhibition sensitizes PDAC to dual ICB Discussion Online content Fig. 1 MHC-I is enriched in lysosomes of PDAC cells and displays reduced cell surface expression. Fig. 2 NBR1 promotes MHC-I trafficking to the lysosome through an autophagy-dependent pathway. Fig. 3 Autophagy inhibition enhances anti-tumour T cell response. Fig. 4 Autophagy inhibition sensitizes PDAC to dual ICB. Extended Data Fig. 1 Heterogeneous distribution of MHC-I in KRAS-mutant cancers. Extended Data Fig. 2 Inhibition of autophagy and lysosomes restores MHC-I levels and plasma membrane localization. Extended Data Fig. 3 Inhibition of macroautophagy, but not LAP/LANDO, restores MHC-I levels. Extended Data Fig. 4 The UBA domain of NBR1 is required for interaction with MHC-I. Extended Data Fig. 5 Autophagy inhibition restores MHC-I expression, leading to enhanced anti-tumour T cell response in vitro. Extended Data Fig. 6 Autophagy inhibition modulates anti-tumour immunity in both orthotopic tumours and liver metastasis. Extended Data Fig. 7 Tumour regression after autophagy inhibition is rescued by depletion of CD8+ T cells or ablation of cell surface MHC-I. Extended Data Fig. 8 Separation of PDAC cells with distinct autophagy flux using the GFP–LC3–RFP reporter. Extended Data Fig. 9 Basal autophagy flux determines immunogenicity of PDAC cells. Extended Data Fig. 10 Autophagy inhibition synergizes with dual ICB. s41586-020-2238-4.pdf Childhood vaccines and antibiotic use in low- and middle-income countries Vaccine effects against antibiotic use Analysing aetiological fractions using vaccine effects Antibiotic use in LMICs Pathogen-attributable antibiotic use Vaccine-preventable antibiotic use Discussion Online content Fig. 1 Effectiveness of pneumococcal and rotavirus vaccines against illness and antibiotic treatment. Fig. 2 Estimates of the attributable fraction for vaccine-preventable infections. Fig. 3 Estimated incidence across countries of ARI and diarrheal illnesses per 100 children. Fig. 4 Total vaccine-preventable antibiotic consumption and incidence per 100 children. Extended Data Fig. 1 Potential effect of pneumococcal serotype replacement. Extended Data Fig. 2 Bias that occurs when using the odds ratio to approximate the relative risk. Extended Data Fig. 3 Fitted association of improved water and sanitation access with diarrhoea risk. Extended Data Fig. 4 Fitted association of GDP per capita with antibiotic treatment of ARI, by region. Extended Data Fig. 5 Fitted association of GDP per capita with antibiotic treatment of diarrhoea, by region. Extended Data Fig. 6 Out-of-sample performance of the extrapolated incidence estimation. s41586-020-2231-y.pdf Plant 22-nt siRNAs mediate translational repression and stress adaptation Massive production of 22-nt siRNAs 22-nt siRNAs repress mRNA translation AGO1 is required for 22-nt siRNA activity 22-nt siRNAs in stress adaptation Discussion Online content Fig. 1 Disruption of cytoplasmic RNA decay and DCL4 triggers massive production of 22-nt siRNAs and causes growth disorders. Fig. 2 22-nt siRNAs repress mRNA translation. Fig. 3 22-nt siRNAs mediate translational repression and siRNA amplification in an AGO1-dependent manner. Fig. 4 Functional analysis and environmental induction of 22-nt siRNAs. Extended Data Fig. 1 Differential expression analysis of siRNAs in ein5-1 dcl4-2 and ski2-2 dcl4-2 plants. Extended Data Fig. 2 NIA1 and NIA2 mRNA and protein levels in ein5-1 dcl4-2 and ski2-2 dcl4-2 plants, and translational states of GTE2/7 in ein5-1 dcl4-2 plants. Extended Data Fig. 3 Accumulation of siRNAs and polysome profiles of the ein5-1 ski2-3 mutant. Extended Data Fig. 4 Genetic combinations of ein5-1 dcl4-2, ski2-2 dcl4-2 and sRNA-pathway-component mutants. Extended Data Fig. 5 AGO1 associates with 22-nt sRNAs in ein5-1 dcl4-2 plants. Extended Data Fig. 6 Scheme for RNA silencing by 21- and 22-nt siRNAs in vitro. Extended Data Fig. 7 The ago1 mutant rescues the growth defects and eliminates the accumulation of 22-nt siRNAs in ein5-1 dcl4-2 and ski2-2 dcl4-2 plants. Extended Data Fig. 8 Root growth and phloem formation are impaired in ein5-1 dcl4-2 and ski2-2 dcl4-2 plants. Extended Data Fig. 9 Transcriptome profiles and gene-ontology analysis of differentially expressed genes in ein5-1 dcl4-2 and ski2-2 dcl4-2 plants. Extended Data Fig. 10 ABA and salt treatments induce the production of 22-nt siRNAs from NIA1 and NIA2 loci. s41586-020-2201-4.pdf Pharmacologic fibroblast reprogramming into photoreceptors restores vision A set of five compounds transforms fibroblasts to CiPCs CiPCs express photoreceptor genes CiPC transplantation in rd1 mice NF-κB induces ASCL1 during conversion to CiPCs Reactive oxygen species activate NF-κB The five compounds promote Axin2 mitolocalization Discussion Online content Fig. 1 Conversion of fibroblasts and the molecular characterization of CiPCs. Fig. 2 Functional analysis of CiPCs in a mouse model of retinal degeneration. Fig. 3 The mROS–NF-κB–ASCL1 signalling axis determines the reprogramming of fibroblasts to CiPCs. Fig. 4 Mitochondria-translocated AXIN2 causes mROS generation and the reprogramming of fibroblasts to CiPCs. Extended Data Fig. 1 Preparation of Nrl–DsRed lentiviral reporter construct and lineage tracing. Extended Data Fig. 2 BrdU staining, transcriptome analysis and functional testing of CiPCs. Extended Data Fig. 3 Functional analysis CiPCs in retinal degeneration mice (rd1). Extended Data Fig. 4 Transplanted CiPCs express photoreceptor-specific markers and connected to the inner retina three months after transplantation. Extended Data Fig. 5 Effect of NF-κB knockdown, H2O2, TNFα and the overexpression of Ascl1 on the reprogramming of fibroblasts to CiPCs. Extended Data Fig. 6 NF-κB–luciferase activity and generation of mROS during the reprogramming of fibroblasts to CiPCs. Extended Data Fig. 7 Mitochondrial localization of AXIN2 in converted cells and a mito-stress test for CiPCs. Extended Data Fig. 8 Conversion of human fibroblasts into CiPCs and in vivo functional testing of mouse CiPCs. Extended Data Fig. 9 Gene expression and chromatin analysis of CiPCs. Extended Data Fig. 10 Schematic of the transplantation study and the mechanism of reprogramming fibroblasts to CiPCs. s41586-020-2200-5.pdf Injured adult neurons regress to an embryonic transcriptional growth state Three stages of CST regeneration TRAP of regenerating CST neurons RNA-seq of regenerating CST neurons Regeneration prolongs the injury transcriptome Reversion to a neural development state Unique transcriptional networks over time Htt is essential for CST regeneration Discussion Online content Fig. 1 Three distinct anatomical stages characterize the regeneration of corticospinal axons that is triggered by NPC grafts. Fig. 2 Transcriptomic analysis of regenerating corticospinal neurons reveals injury-induced reversal to an immature developmental state that is sustained upon regeneration. Fig. 3 Transcriptomic analysis of regenerating corticospinal neurons identifies Htt as a potential upstream regulator of regeneration. Fig. 4 Htt is essential for regeneration of corticospinal axons. Extended Data Fig. 1 TRAP of regenerating corticospinal neurons. Extended Data Fig. 2 Sample Pearson correlation identifies unique populations of mRNAs derived from CST neurons (TRAPed samples) and from whole motor cortex (unbound samples) after TRAP. Extended Data Fig. 3 In situ hybridization data from the Allen Mouse Brain Atlas confirms layer-5b-specific mRNA expression of genes highly enriched by TRAP from intact Glt25d2-eGFP-L10a mice. Extended Data Fig. 4 Neuronal genes are enriched in the TRAPed samples from layer-5b neurons. Extended Data Fig. 5 Verification of RNA-seq data via immunolabelling for ATG7, SOX9 and PAX2. Extended Data Fig. 6 Heat map of the top 1,000 significantly differentially regulated transcripts (FDR