Usability and ease of use of long-term remote monitoring of physical activity for individuals with acquired brain injury in community: a qualitative analysis.

Introduction: Objective and continuous monitoring of physical activity over the long-term in the community is perhaps the most important step in the paradigm shift toward evidence-based practice and personalized therapy for successful community integration. With the advancement in technology, physical activity monitors have become the go-to tools for objective and continuous monitoring of everyday physical activity in the community. While these devices are widely used in many patient populations, their use in individuals with acquired brain injury is slowly gaining traction. The first step before using activity monitors in this population is to understand the patient perspective on usability and ease of use of physical activity monitors at different wear locations. However, there are no studies that have looked at the feasibility and patient perspectives on long-term utilization of activity monitors in individuals with acquired brain injury. Methods: This pilot study aims to fill this gap and understand patient-reported aspects of the feasibility of using physical activity monitors for long-term use in community-dwelling individuals with acquired brain injury. Results: This pilot study found that patients with acquired brain injury faced challenges specific to their functional limitations and that the activity monitors worn on the waist or wrist may be better suited in this population. Discussion: The unique wear location-specific challenges faced by individuals with ABI need to be taken into account when selecting wearable activity monitors for long term use in this population.

Long non-coding RNA generated from CDKN1A gene by alternative polyadenylation regulates p21 expression during DNA damage response.

Alternative Polyadenylation (APA) is an emerging mechanism for dynamic changes in gene expression. Previously, we described widespread APA occurrence in introns during the DNA damage response (DDR). Here, we show that a DDR-activated APA event occurs in the first intron of CDKN1A, inducing an alternate last exon-containing lncRNA. We named this lncRNA SPUD (Selective Polyadenylation Upon DNA Damage). SPUD localizes to polysomes in the cytoplasm and is detectable as multiple isoforms in available high-throughput studies. SPUD has low abundance compared to the CDKN1A full-length isoform under non-stress conditions, and SPUD is induced in cancer and normal cells under a variety of DNA damaging conditions in part through p53. The RNA binding protein HuR binds to and promotes the stability of SPUD precursor RNA. SPUD induction increases p21 protein, but not mRNA levels, affecting p21 functions in cell-cycle, CDK2 expression and cell growth. Like CDKN1A full-length isoform, SPUD can bind two competitive p21 translational regulators, the inhibitor calreticulin and the activator CUGBP1; SPUD alters their association with CDKN1A full-length in a DDR-dependent manner, promoting CDKN1A translation. Together, these results show a new regulatory mechanism by which a lncRNA controls p21 expression post-transcriptionally, highlighting lncRNA relevance in DDR progression and cell-cycle.

Long Non-Coding RNA Generated from CDKN1A Gene by Alternative Polyadenylation Regulates p21 Expression during DNA Damage Response.

Alternative Polyadenylation (APA) is an emerging mechanism for dynamic changes in gene expression. Previously, we described widespread APA occurrence in introns during the DNA damage response (DDR). Here, we show that a DNA damage activated APA event occurs in the first intron of CDKN1A , inducing an alternate last exon (ALE)-containing lncRNA. We named this lncRNA SPUD (Selective Polyadenylation Upon Damage). SPUD localizes to polysomes in the cytoplasm and is detectable as multiple isoforms in available high throughput studies. SPUD has low abundance compared to the CDKN1A full-length isoform and is induced in cancer and normal cells under a variety of DNA damaging conditions in part through p53 transcriptional activation. RNA binding protein (RBP) HuR and the transcriptional repressor CTCF regulate SPUD levels. SPUD induction increases p21 protein, but not CDKN1A full-length levels, affecting p21 functions in cell-cycle, CDK2 expression, and cell viability. Like CDKN1A full-length isoform, SPUD can bind two competitive p21 translational regulators, the inhibitor calreticulin and the activator CUGBP1; SPUD can change their association with CDKN1A full-length in a DDR-dependent manner. Together, these results show a new regulatory mechanism by which a lncRNA controls p21 expression post-transcriptionally, highlighting lncRNA relevance in DDR progression and cellcycle.