Search

The five NF-κB family members and three nuclear IκB proteins play important biological roles, but the mechanisms by which distinct members of these protein families contribute to selective gene transcription remain poorly understood, especially at a genome-wide scale. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent and IκBζ-dependent genes in Toll-like receptor 4 (TLR4)-activated macrophages. Key immunoregulatory genes, including Il6 , Il1b , Nos2 , Lcn2, and Batf, are among the p50-IκBζ-codependent genes. IκBζ-bound genomic sites are occupied at earlier time points by NF-κB dimers. However, p50-IκBζ codependence does not coincide with preferential binding of either p50 or IκBζ, as RelA co-occupies hundreds of genomic sites with the two proteins. A common feature of p50-IκBζ-codependent genes is a nearby p50/RelA/IκBζ-cobound site exhibiting p50-dependent binding of both RelA and IκBζ. This and other results suggest that IκBζ acts in concert with RelA:p50 heterodimers. Notably, p50-IκBζ-codependent genes comprise a high percentage of genes exhibiting the greatest differential expression between TLR4-stimulated and tumor necrosis factor receptor (TNFR)-stimulated macrophages. Thus, our genome-centric analysis reveals a defined p50-IκBζ pathway that selectively activates a set of key immunoregulatory genes and serves as an important contributor to differential TNFR and TLR4 responses., (© 2024 Daly et al.; Published by Cold Spring Harbor Laboratory Press.)

Mindfulness-based interventions (MBIs) have demonstrated therapeutic efficacy for various psychological conditions, and smartphone apps that facilitate mindfulness practice can enhance the reach and impact of MBIs. The goal of this review was to summarize the published evidence on the impact of mindfulness apps on the psychological processes known to mediate transdiagnostic symptom reduction after mindfulness practice. A literature search from January 1, 1993, to August 7, 2023 was conducted on three databases, and 28 randomized controlled trials involving 5963 adults were included. Across these 28 studies, 67 outcome comparisons were made between a mindfulness app group and a control group. Between-group effects tended to favor the mindfulness app group over the control group in three psychological process domains: repetitive negative thinking, attention regulation, and decentering/defusion. Findings were mixed in other domains (i.e., awareness, nonreactivity, non-judgment, positive affect, and acceptance). The range of populations examined, methodological concerns across studies, and problems with sustained app engagement likely contributed to mixed findings. However, effect sizes tended to be moderate to large when effects were found, and gains tended to persist at follow-up assessments two to six months later. More research is needed to better understand the impact of these apps on psychological processes of change. Clinicians interested in integrating apps into care should consider app-related factors beyond evidence of a clinical foundation and use app databases to identify suitable apps for their patients, as highlighted at the end of this review., (© 2024. The Author(s).)