Cancer-specific loss of activation sensitizes glioblastoma to DNA damage.

Most glioblastomas (GBMs) achieve cellular immortality by acquiring a mutation in the telomerase reverse transcriptase () promoter. promoter mutations create a binding site for a GA binding protein (GABP) transcription factor complex, whose assembly at the promoter is associated with reactivation and telomere maintenance. Here, we demonstrate increased binding of a specific GABPB1L-isoform-containing complex to the mutant promoter.

Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner.

TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic disruption of GABPβ1L (β1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner.

A Rapid Induction Mechanism for Lin28a in Trophic Responses.

Environmental cues provoke rapid transitions in gene expression to support growth and cellular plasticity through incompletely understood mechanisms. Lin28 RNA-binding proteins have evolutionarily conserved roles in post-transcriptional coordination of pro-growth gene expression, but signaling pathways allowing trophic stimuli to induce Lin28 have remained uncharacterized. We find that Lin28a protein exhibits rapid basal turnover in neurons and that mitogen-activated protein kinase (MAPK)-dependent phosphorylation of the RNA-silencing factor HIV TAR-RNA-binding protein (TRBP) promotes binding and stabilization of Lin28a, but not Lin28b, with an accompanying reduction in Lin28-regulated miRNAs, downstream of brain-derived neurotrophic factor (BDNF).

Differences in stress-related ratings between research center and home environments in dementia caregivers using ecological momentary assessment.

Background: Clinicians and researchers working with dementia caregivers typically assess caregiver stress in a clinic or research center, but caregivers' stress is rooted at home where they provide care. This study aimed to compare ratings of stress-related measures obtained in research settings and in the home using ecological momentary assessment (EMA).

Methods: EMA of 18 caregivers (mean age 66.

Assessing sleep architecture in dementia caregivers at home using an ambulatory polysomnographic system.

Findings from previous research assessing sleep quality in caregivers are inconsistent due to differences in sleep assessment methods. This study evaluated sleep in dementia caregivers using a comprehensive sleep assessment utilizing an ambulatory polysomnography (PSG) device. A total of 20 caregivers and 20 noncaregivers rated their perceived sleep quality, stress, and depressive symptoms; provided samples of cortisol and inflammatory biomarkers; and completed an objective sleep assessment using a portable PSG device.