Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target.

Translational Research on Caregiver Reading and Playing Behaviors: Evidence from an In Vivo Community-based Intervention throughout the COVID-19 Pandemic.

This study provides a rigorous assessment of a community-based early child development (ECD) intervention to understand the drivers of caregivers' reading and playing practices in a low-resourced township in South Africa. Mentors visited 157 homes biweekly (2474 observations from 2019-21; children ages 0-5), completing surveys regarding caregiver behaviors and engagement. One hundred and fifty-seven caregivers (mostly Black, Zulu women) participated in the program during this time period and completed surveys biannually on their support system (modified version of the Multidimensional Scale of Perceived Support) and ECD beliefs (modified versions of the Parental Play Beliefs Scale and the Parent Opinion Survey).