Poly(ADP-ribose) polymerases, PARPs, transfer ADP-ribose onto target proteins from nicotinamide adenine dinucleotide (NAD + ). Current mass spectrometric analytical methods require proteolysis of target proteins, limiting the study of dynamic ADP-ribosylation on contiguous proteins. Herein, we present a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method that facilitates multisite analysis of ADP-ribosylation. We observe divergent ADP-ribosylation dynamics for the catalytic domains of PARPs 14 and 15, with PARP15 modifying more sites on itself (+3–4 ADP-ribose) than the closely related PARP14 protein (+1–2 ADP-ribose)—despite similar numbers of potential modification sites. We identify, for the first time, a minimal peptide fragment (18 amino-acids) that is preferentially modified by PARP14. Finally, we demonstrate through mutagenesis and chemical treatment with hydroxylamine that PARPs 14/15 prefer acidic residues. Our results highlight the utility of MALDI-TOF in the analysis of PARP target modifications and in elucidating the biochemical mechanism governing PARP target selection.

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Purpose This study investigated the impact of a PhD-led research infrastructure on scholarly output for an orthopedic residency program. We hypothesized that a research infrastructure leveraging non-surgeon faculty and medical students could increase research capacity and productivity in an orthopedic residency program. Methods In 2018, a PhD kinesiologist was hired by a community-based university-affiliated medical center to augment research in collaboration with volunteer clinical faculty orthopedic surgeons. Initiatives implemented included: (1) standardized patient reported outcome collection tools (2) creation of a seven-year retrospective joint registry for a high-volume (> 600/year) arthroplasty surgeon, with continued prospective collection (3) expansion of research staff with three data collection employees (4) creation of a monthly research lecture series for medical students conducted by the kinesiologist. Publications before and after implementation of the research infrastructure (2011-2021) were recorded through PubMed and annual faculty surveys. Results Peer-reviewed, indexed publications substantially increased by 491% and 305% for residents and faculty, respectively, since the inception of the kinesiologist-led research program. Over three years, 244 authorships on publications, presentations, and abstracts have been provided for medical students and residents through the lecture series. In subsequent years, a peer mentorship program was established, with senior medical students and residents serving as research mentors under faculty supervision. Conclusion A PhD-led orthopedic research program leveraging medical students resulted in a substantial increase in peerreviewed publications. This model may be attractive to community medical centers with volunteer clinical faculty seeking to enhance their scholarly environment and provide additional research opportunities for residents and students.

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