Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM.

Cellular target engagement technologies enable quantification of intracellular drug binding; however, simultaneous assessment of drug-associated phenotypes has proven challenging. Here, we present cellular target engagement by accumulation of mutant as a platform that can concomitantly evaluate drug-target interactions and phenotypic responses using conditionally stabilized drug biosensors. We observe that drug-responsive proteotypes are prevalent among reported mutants of known drug targets.

PARP enzyme de novo synthesis of protein-free poly(ADP-ribose).

PARP enzymes transfer ADP-ribose from NAD onto proteins as a covalent modification that regulates multiple aspects of cell biology. Here, we identify an undiscovered catalytic activity for human PARP1: de novo generation of free PAR molecules that are not attached to proteins. Free PAR production arises when a molecule of NAD or ADP-ribose docks in the PARP1 acceptor site and attaches to an NAD molecule bound to the donor site, releasing nicotinamide and initiating ADP-ribose chains that emanate from NAD/ADP-ribose rather than protein.

A PARP2-specific active site α-helix melts to permit DNA damage-induced enzymatic activation.

PARP1 and PARP2 recognize DNA breaks immediately upon their formation, generate a burst of local PARylation to signal their location, and are co-targeted by all current FDA-approved forms of PARP inhibitors (PARPi) used in the cancer clinic. Recent evidence indicates that the same PARPi molecules impact PARP2 differently from PARP1, raising the possibility that allosteric activation may also differ. We find that unlike for PARP1, destabilization of the autoinhibitory domain of PARP2 is insufficient for DNA damage-induced catalytic activation.

Safety net patients' satisfaction with oral health services by provider type and intent to return for more care.

Objectives: This study examined patients' satisfaction with services provided by different oral health providers, their intent to return for additional care, and associations with patients' demographics and service characteristics.

Methods: Descriptive analyses and multivariable ordinal logistic regressions were conducted using survey data from 898 patients who received care at Apple Tree Dental (ATD) in Minnesota during 2021. The questionnaire included 12 statements on patient satisfaction with the clinician's ability to explain the dental diagnosis and treatment options, to be considerate of the patient's needs and dental anxiety, and to provide technically competent services.

The Impact of Pandemic Concerns on Consumers' Teledentistry Use During the First Months of the COVID-19 Pandemic.

Objectives: The COVID-19 pandemic affected consumers' access to oral health care. This study evaluated factors associated with teledentistry use among US adults from June 2019 through June 2020.

Methods: We used data from a nationally representative survey of 3500 consumers.