Loss of ND4 in a mitochondrial nd4 mutant is characterized by a membrane arm assembly defect, similar to that exhibited by loss of AMC1. These results suggest AMC1 is required for the production of mitochondrially-encoded complex I subunits, specifically ND4. We discuss the possible modes of action of AMC1 in mitochondrial gene expression and complex I biogenesis. Copyright © 2020, Genetics.R-loops are a common chromatin feature with essential functions in multiple cellular processes and diseases. However, little is known about the dynamic patterns of R-loops in a given organism. Here, using our recently developed genome-wide R-loop profiling method, we generated a comprehensive atlas quantifying the R-loop patterns of Arabidopsis thaliana at 53 points during development and responses to environmental stimuli. The R-loop patterns were fairly stable in plants at the vegetative stage and in response to different light spectra and other environmental stimuli. Notably, the R-loops showed turnover during the plant lifecycle, with patterns switching between generations. Importantly, R-loop dynamics were not strongly associated with RNA abundance, indicating that the mechanisms regulating R-loop formation and RNA accumulation are independent. We also observed enrichments of R-loops in transcription factor-binding regions, suggesting that R-loops could function as potential cis transcriptional regulators. This study provides the first overview of R-loop dynamics in Arabidopsis during development and stress responses, highlights the unique dynamics of R-loops in the flowering plant Arabidopsis, and lays the groundwork for elucidating the functions of R-loops. © 2020 American Society of Plant Biologists. All rights reserved.Plastids differentiate into various functional types (chloroplasts, leucoplasts, chromoplasts, etc.) that have distinct proteomes depending on the specific tissue. Most plastid proteins are encoded by the nuclear genome, synthesized as higher molecular mass preproteins with an N-terminal transit peptide, and then post-translationally imported from the cytosol. Evidence for tissue-specific regulation of import into plastids, and subsequent modulation of plastid proteomes, has been lacking. We quantified protein import into isolated pea leaf chloroplasts and root leucoplasts and identified two transit-peptide motifs that specifically enhance preprotein import into root leucoplasts. Using a plastid preprotein expressed in both leaves and roots of stable transgenic plants, we showed that losing one of the leucoplast motifs interfered with its function in root leucoplasts but had no effect on its function in leaf chloroplasts. We assembled a list of all Arabidopsis plastid preproteins encoded by recently duplicated genes and show that, within a duplicated preprotein pair, the isoform bearing the leucoplast motif usually has greater root protein abundance. Our findings represent a clear demonstration of tissue-specific regulation of organelle protein import and suggest that it operates by selective evolutionary retention of transit-peptide motifs, which enhances import into specific plastid types. © 2020 American Society of Plant Biologists. All rights reserved.INTRODUCTION Lifestyle factors in combination have been hypothesised to be associated with the prevention of type 2 diabetes (T2D) and mortality among individuals with T2D. The aim was to conduct a systematic review and meta-analysis to quantify the association between lifestyle indices and incident T2D as well as mortality in individuals with T2D. METHODS PubMed and Web of Science were searched up to September 2019. We included prospective cohort studies investigating at least three lifestyle factors in association with T2D, or all-cause mortality in individuals with diabetes.  https://www.selleckchem.com/products/Decitabine.html  We conducted pairwise and dose-response meta-analyses to calculate summary relative risks (SRR) by using random effects model. RESULTS In total, 19 studies were included. Adhering to a healthy lifestyle (mostly favourable diet, physical activity, non-smoking, moderate alcohol intake and normal weight) was associated with a reduced SRR of 78% for T2D (SRR 0.22; 95% CI 0.16 to 0.32; n=14) and 57% for mortality (SRR 0.43; 95% CI 0.31 to 0.58; n=5) compared with low adherence to a healthy lifestyle. In dose-response analyses, the adherence to every additional healthy lifestyle factor was associated with a reduced relative risk of 32% (95% CI 28% to 36%) for T2D and 21% (95% CI 15% to 26%) for mortality. CONCLUSIONS Our findings underline the importance of the joint adherence to healthy lifestyle factors to prevent T2D and improve survival among individuals with diabetes. Adherence to every additional health lifestyle factor play a role in the T2D prevention and progression. PROSPERO REGISTRATION NUMBER CRD42018091409. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Very old (aged ≥80 years) adults constitute an increasing proportion of the global population. Currently, this subgroup of patients represents an important percentage of patients admitted to the intensive care unit. Community-acquired pneumonia (CAP) frequently affects very old adults. However, there are no specific recommendations for the management of critically ill very old CAP patients. Multiple morbidities, polypharmacy, immunosenescence and frailty contribute to an increased risk of pneumonia in this population. CAP in critically ill very old patients is associated with higher short- and long-term mortality; however, because of its uncommon presentation, diagnosis can be very difficult. Management of critically ill very old CAP patients should be guided by their baseline characteristics, clinical presentation and risk factors for multidrug-resistant pathogens. Hospitalisation in intermediate care may be a good option for critical ill very old CAP patients who do not require invasive procedures and for whom intensive care is questionable in terms of benefit. Copyright ©ERS 2020.IFN regulatory factor 3 (IRF3) is critical for the transcription of type I IFNs in defensing virus and promoting inflammatory responses. Although several kinds of posttranslational modifications have been identified to modulate the activity of IRF3, whether atypical ubiquitination participates in the function regulation, especially the DNA binding capacity of IRF3, is unknown. In this study, we found that the ovarian tumor domain containing deubiquitinase OTUD1 deubiquitinated IRF3 and attenuated its function. An atypical ubiquitination, K6-linked ubiquitination, was essential for the DNA binding capacity of IRF3 and subsequent induction of target genes. Mechanistically, OTUD1 cleaves the viral infection-induced K6-linked ubiquitination of IRF3, resulting in the disassociation of IRF3 from the promoter region of target genes, without affecting the protein stability, dimerization, and nuclear translocation of IRF3 after a viral infection. Otud1 -/- cells as well as Otud1 -/- mice produced more type I IFNs and proinflammatory cytokines after viral infection.