Graphical Abstract Highlights d Chronic viral infection causes long-term transcriptome and proteome changes in the liver d Hepatocyte-intrinsic type I interferon (IFN-I) signaling regulates hepatic metabolism d IFN-I signaling reprograms the urea cycle in hepatocytes and alters serum metabolites d Serum levels of arginine and ornithine modulate T cell responses and pathology

ObjectiveThere is a growing body of research that investigates how the residential neighbourhood context relates to individual diet. However, previous studies ignore participants’ time spent in the residential environment and this may be a problem because time-use studies show that adults’ time-use pattern can significantly vary. To better understand the role of exposure duration, we designed a study to examine ‘time spent at home’ as a moderator to the residential food environment-diet association.DesignCross-sectional observational study.SettingsCity of Toronto, Ontario, Canada.Participants2411 adults aged 25–65.Primary outcome measureFrequency of vegetable and fruit intake (VFI) per day.ResultsTo examine how time spent at home may moderate the relationship between residential food environment and VFI, the full sample was split into three equal subgroups—short, medium and long duration spent at home. We detected significant associations between density of food stores in the residential food environment and VFI for subgroups that spend medium and long durations at home (ie, spending a mean of 8.0 and 12.3 h at home, respectively—not including sleep time), but no associations exist for people who spend the lowest amount of time at home (mean=4.7 h). Also, no associations were detected in analyses using the full sample.ConclusionsOur study is the first to demonstrate that time spent at home may be an important variable to identify hidden population patterns regarding VFI. Time spent at home can impact the association between the residential food environment and individual VFI.

Antibody secretion by plasma cells provides acute and long-term protection against pathogens. The high secretion potential of plasma cells depends on the unfolded protein response, which is controlled by the transcription factor Xbp1. Here, we analyzed the Xbp1-dependent gene expression program of plasma cells and identified Bhlha15 (Mist1) as the most strongly activated Xbp1 target gene. As Mist1 plays an important role in other secretory cell types, we analyzed in detail the phenotype of Mist1-deficient plasma cells in Cd23-Cre Bhlha15fl/fl mice under steady-state condition or upon NP-KLH immunization. Under both conditions, Mist1-deficient plasma cells were 1.4-fold reduced in number and exhibited increased IgM production and antibody secretion compared to control plasma cells. At the molecular level, Mist1 regulated a largely different set of target genes compared with Xbp1. Notably, expression of the Blimp1 protein, which is known to activate immunoglobulin gene expression and to contribute to antibody secretion, was 1.3-fold upregulated in Mist1-deficient plasma cells, which led to a moderate downregulation of most Blimp1-repressed target genes in the absence of Mist1. Importantly, a 2-fold reduction of Blimp1 (Prdm1) expression was sufficient to restore the cell number and antibody expression of plasma cells in Prdm1Gfp/+Cd23-Cre Bhlha15fl/fl mice to the same level seen in control mice. Together, these data indicate that Mist1 restricts antibody secretion by restraining Blimp1 expression, which likely contributes to the viability of plasma cells.