Feasibility and Acceptability of Ecological Momentary Assessment of Psychosocial Factors and Self-Management Behaviors Among Veterans With Type 2 Diabetes.

Comorbid symptoms such as post-traumatic stress and pain are common barriers to optimal self-management among veterans with type 2 diabetes. Additionally, self-management behaviors occur in the context of veterans' daily routines and social environments. This study evaluated the feasibility and acceptability of ecological momentary assessment (EMA) among veterans with type 2 diabetes. Ten veterans with type 2 diabetes were asked to respond to random EMA surveys during preprogrammed intervals five times per day for 14 days. EMA surveys were delivered via a mobile application and assessed momentary physical location, activities, social interactions, mood, stress, and pain. The last survey of each day included additional items about daily post-traumatic stress symptoms, diabetes distress, social support, physical activity, self-management behaviors, and functioning. Participants completed interviews assessing their experience in the study and barriers to responding and indicated their likelihood of participating in similar studies. The mean survey response rate was 96%, providing 675 observations. The majority of participants completed the five momentary surveys in <1 minute and the daily EMA surveys in <5 minutes. Results revealed substantial individual day-to-day variability across symptoms and self-management behaviors that is not captured by aggregated means across all participants. Participants generally reported enjoying responding to surveys and experiencing few barriers. Nine of 10 participants reported being "extremely likely" to participate in a similar study. These pilot data suggest that intensive EMA designs are feasible and acceptable for veterans with type 2 diabetes and can inform the design of future larger studies.

An RNA binding regulatory cascade controls the switch from proliferation to differentiation in the Drosophila male germ line stem cell lineage.

The switch from precursor cell proliferation to onset of differentiation in adult stem cell lineages must be carefully regulated to produce sufficient progeny to maintain and repair tissues, yet prevent overproliferation that may enable oncogenesis. In the Drosophila male germ cell lineage, spermatogonia produced by germ line stem cells undergo a limited number of transit amplifying mitotic divisions before switching to the spermatocyte program that sets up meiosis and eventual spermatid differentiation. The number of transit amplifying divisions is set by accumulation of the bag-of-marbles (Bam) protein to a critical threshold. In bam mutants, spermatogonia proliferate through several extra rounds of mitosis then die without becoming spermatocytes. Here we show that the key role of Bam for the mitosis to differentiation switch is repressing expression of Held Out Wings (how), homolog of mammalian Quaking. Knock down of how in germ cells was sufficient to allow spermatogonia mutant for bam or its partner benign gonial cell neoplasm (bgcn) to differentiate, while forced expression of nuclear-targeted How protein in spermatogonia wild-type for bam resulted in continued proliferation at the expense of differentiation. Our findings suggest that Bam targets how RNA for degradation by acting as an adapter to recruit the CCR4-NOT deadenylation complex via binding its subunit, Caf40. As How is itself an RNA binding protein with roles in RNA processing, our findings reveal that the switch from proliferation to meiosis and differentiation in the Drosophila male germ line adult stem cell lineage is regulated by a cascade of RNA-binding proteins.

Tunable Transcriptional Interference at the Endogenous Alcohol Dehydrogenase Gene Locus in Drosophila melanogaster.

Neighboring sequences of a gene can influence its expression. In the phenomenon known as transcriptional interference, transcription at one region in the genome can repress transcription at a nearby region in cis Transcriptional interference occurs at a number of eukaryotic loci, including the alcohol dehydrogenase (Adh) gene in Drosophila melanogasterAdh is regulated by two promoters, which are distinct in their developmental timing of activation. It has been shown using transgene insertion that when the promoter distal from the Adh start codon is deleted, transcription from the proximal promoter becomes de-regulated. As a result, the Adh proximal promoter, which is normally active only during the early larval stages, becomes abnormally activated in adults. Whether this type of regulation occurs in the endogenous Adh context, however, remains unclear. Here, we employed the CRISPR/Cas9 system to edit the endogenous Adh locus and found that removal of the distal promoter also resulted in the untimely expression of the proximal promoter-driven mRNA isoform in adults, albeit at lower levels than previously reported. Importantly, transcription from the distal promoter was sufficient to repress proximal transcription in larvae, and the degree of this repression was dependent on the degree of distal promoter activity. Finally, upregulation of the distal Adh transcript led to the enrichment of histone 3 lysine 36 trimethylation over the Adh proximal promoter. We conclude that the endogenous Adh locus is developmentally regulated by transcriptional interference in a tunable manner.