Kinase translocation reporters (KTRs) are powerful tools for single-cell measurement of time-integrated kinase activity but suffer from restricted dynamic range and limited sensitivity, particularly in neurons. To address these limitations, we developed enhanced KTRs (eKTRs) for protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) by (i) increasing KTR size, which reduces the confounding effect of KTR diffusion through the nuclear pore, and (ii) modulating the strength of the bipartite nuclear localization signal (bNLS) in their kinase sensor domains, to ensures that the relative distribution of the KTR between the nucleus and cytoplasmic is determined by active nuclear import, active nuclear export, and relative activity of their cognate kinase. The resultant sets of ePKA-KTRs and eERK-KTRs display high sensitivity, broad dynamic range, and cell type-specific tuning.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic led to widespread adoption of virtual communication platforms. Virtual study visits were implemented in the pilot cluster randomized trial (CRT) stage of Teen Adherence in KidnEy transplant Improving Tracking To Optimize Outcomes (TAKE-IT TOO). The present study aimed to understand study coordinators' perspectives on conducting a behavioral intervention with adolescent kidney transplant recipients using virtual conferencing platforms.
View Article and Find Full Text PDFPurpose: To present an overview of current definitions of informal caregiving and informal caregivers for persons living with dementia (PLWD). We suggest definitional criteria of informal caregiving for dementia caregiving research that incorporate current dementia caregiving policy and programs.
Method: A multi-pronged review and analysis was performed of the scientific literature from 2014 to 2024 and online documents from professional, public advocacy, and government organizations for definitions of informal caregiving and applications to informal caregiving of PLWD.
Kinase translocation reporters (KTRs) are powerful tools for single-cell measurement of time-integrated kinase activity but suffer from restricted dynamic range and limited sensitivity, particularly in neurons. To address these limitations, we developed enhanced KTRs (eKTRs) for protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) that display high sensitivity, rapid response kinetics, broad dynamic range, cell type-specific tuning, and an ability to detect PKA and ERK activity in primary sensory neurons. Moreover, co-expression of optically separable eKTRs for PKA and ERK revealed the kinetics of expected and unexpected crosstalk between PKA, ERK, protein kinase C, and calcium signaling pathways, demonstrating the utility of eKTRs for live cell monitoring of diverse and interacting signaling pathways.
View Article and Find Full Text PDFBackground: Smoking is a leading cause of premature death globally. Quitting smoking reduces the risk of all-cause mortality by 11%-34%. Smartphone app-based smoking cessation (SASC) interventions have been developed and are widely used.
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