eScholarship@UMassChan Repository at UMass Chan Medical School

eScholarship@UMassChan

Sherman Center building at UMass Chan Medical School at night

eScholarship@UMassChan is a digital repository for UMass Chan Medical School's research and scholarship, including journal articles, theses, datasets and more. We welcome submissions from our faculty, staff, and students. eScholarship@UMassChan is a service of the Lamar Soutter Library, Worcester, MA, USA. See also our open access journal publishing services.

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  • The IR Venn Diagram: Diversity in Technology, Content, Users, and Roles in Specialized Institutional Repositories

    Kubilius, Ramune K.; Burke, Michael; Jerome, Erin; Lovett, Julia; O'Brien, Emily Ping; Palmer, Lisa A. (2024-07-15)
    In this poster, librarians from six academic libraries – representing various sectors including science, technology, engineering, medicine, music, and large universities – collaborated to explore and reflect on the academic IR community that encompasses specialized libraries, collections, and formats. The authors answered self-survey questions and responses were analyzed for visualization in the poster. The poster spotlights diversity in technology, content, users, roles, priorities, and challenges. It also illustrates some of the common threads and opportunities that have relevance and implications in both the special library and the broader IR landscape.
  • Demographics and Employment Outcomes: Selected Findings from NIDILRR-funded Disability Employment Research in the 21st Century

    Russinova, Zlatka; Bloch, Philippe (2024-06-28)
    A systematic scoping review of research published between 2000 and 2020 on employment of people with disabilities, that was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) was conducted by CeKTER researchers. All papers comparing people with disabilities to those without have been excluded from the systematic scoping review. Among over 100 publications reviewed there was a wide and very disparate array of findings with numerous variables used and varying research questions. This result belies summative findings. There are numerous ways of organizing the disparate findings. This brief is the first in a series of findings from the systematic scoping review. In this brief we report on findings categorized by the demographic characteristics of education, gender, marital status, race, and age. Please note that all comparisons are always about corresponding peers with disabilities.
  • Ethical Frameworks in Periviable Decision-Making: Patient Perspectives and Provider Patterns

    Delaney, Kathryn (2024-06-25)
    Background: Periviability counseling involves engaging in difficult ethical decisions. The ethical frameworks used by patients and their healthcare providers to discuss this topic have not been previously studied. Objectives: This study assessed the ethical frameworks used by patients and by providers during periviability counseling and subsequent decision making. Study Design: This mixed methods study included patients between gestation ages 21 weeks 0 days through 24 weeks 6 days who required periviability counseling, and the providers performing this counseling. Counseling sessions between providers and patients were recorded, as were semi-structured follow-up interviews with patients. These recordings were transcribed and analyzed using thematic analysis. Demographic surveys were given to providers, and patient demographic, obstetric, and delivery information was abstracted from medical records. Results: A total of 11 patients and 11 providers participated in either a recorded counseling session, a follow-up interview, or both. Qualitative analysis revealed the following themes: 1) decisions regarding periviable intervention are the patient’s to make, 2) desire to avoid pain or suffering of the fetus/newborn, especially as it related to CPR, 3) doing what is best for the family, including partners and other children at home, 4) “doing everything” as a good in itself, and 5) periviable complications disrupt expectations about parenthood or pregnancy which then need to be reimagined. These themes corresponded to four distinct ethical frameworks: principlism, care ethics, virtue ethics, and narrative ethics. All of the patients, and approximately three-quarters of providers used at least one of these ethical frameworks; most used a combination of frameworks. Conclusions: Patients and providers engaging in decision making surrounding periviable intervention use commonly accepted ethical frameworks to discuss and decide how to proceed with these pregnancies.
  • Individual Development Plan for Career Development Professionals

    Ismael, Amber; Campbell, Brian; Chremos, Ioannis Vasileios; Fuhrmann, Cynthia N; Nordell, Shawn (2024-06-21)
    The Individual Development Plan for Career Development Professionals is an IDP worksheet to guide individuals who are pursuing careers in graduate/postdoctoral career development through the process of creating their own IDP. The worksheet is designed as an IDP tool for all career levels, including those preparing to enter this field, practitioners seeking to grow within their current positions, or those looking to advance or pursue a career transition. The tool includes prompts to guide one through exercises that help one assess their skills, values, interests, progress and growth; set goals and define an action plan; and consider the resources, mentorship, and community that they may need to help develop a fulfilling career. Though designed for professionals in the career development field, this tool may also be helpful for those in other academic administration or education roles. This tool was designed by members of the Professional Development Committee of the Graduate Career Consortium, an international member organization to help individuals advance the field of graduate and postdoctoral career and professional development.
  • NexGen Eulogy

    Sarkar, Amber (2024-06-20)
    Introduction: This week we have a poem again. This time from Dr. Amber Sarkar who is faculty at Family Health Center of Worcester. She is writing here about the transition from one EHR to another EHR. I think most of us have experienced this at least once - I have experienced 8 different EHRs so this really resonates with me. We come to spend more time with our EHR than we do our children! We form a warped bond with it. Like our phones, it gets a grasp on us. We talk about it like it is a living entity. And then sometimes we have to say goodbye. And hope the new one will be better than the old. Amber captures all of this well in her poem.
  • Racial Disparities and Trends in Anticoagulant Use among Ambulatory Care Patients with Atrial Fibrillation and Atrial Flutter in the United States from 2007-2019 [preprint]

    Kan, Vincent; Lapane, Kate L; McManus, David D; Baek, Jonggyu; Darling, Chad E; Alcusky, Matthew J (2024-06-15)
    Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly increasing the risk of stroke. The introduction of direct oral anticoagulants (DOACs) since 2010 has transformed anticoagulation therapy, offering an alternative to warfarin with improved safety profiles. Despite the increased adoption of DOACs, disparities in their use among different racial and ethnic groups in the United States remain understudied. Methods This study utilized a repeated cross-sectional design, analyzing data from the National Ambulatory Medical Care Survey (NAMCS) from 2007 to 2019. The study population included adults diagnosed with AF or atrial flutter (AFL). We analyzed the temporal trends of DOAC and warfarin use from 2007 to 2019. We examined the prevalence of DOAC versus warfarin use and assessed associations between race/ethnicity, patient characteristics, and DOAC utilization from 2011 to 2019. Multivariable modified Poisson regression models were used to calculate adjusted prevalence ratios (aPR) for the associations. Results From 2011 to 2019, NAMCS recorded 3,224 visits involving AF or AFL, representing a weighted estimate of 103.6 million visits. DOAC use increased significantly, with apixaban becoming the predominant anticoagulant by 2016. Non-Hispanic Black patients were less likely to use DOACs compared to non-Hispanic White patients over time (aPR 0.75; 95% CI, 0.63-0.90). Patients with Medicaid insurance were also less likely to use DOACs (aPR 0.14; 95% CI: 0.04-0.46). Conclusion Despite the shift from warfarin to DOACs for AF and AFL treatment, significant racial and socioeconomic disparities persist. Non-Hispanic Black patients and those with Medicaid insurance are less likely to use DOACs. These findings highlight the need for targeted strategies to ensure equitable access to advanced anticoagulant therapies.
  • Calcineurin coordinates cell cycle progression with adaptation to environmental stress

    Flynn, Mackenzie J (2024-06-14)
    Sudden exposure to environmental stress threatens the viability of single-celled microbes and cells within complex tissues. In order to survive, cells must sense environmental changes and coordinate a transient cell cycle arrest with the appropriate adaptive response. Cells have several stress-responsive pathways that promote adaptation to distinct stressors, but how these pathways interact with one another is poorly understood. Here, we examined the response to calcium chloride stress, which activates the phosphatase calcineurin and the MAPK Hog1 in Saccharomyces cerevisiae. We discovered that calcineurin extends Hog1 activation, which causes prolonged downregulation of cell cycle-regulated genes and delays progression through multiple cell cycle phases. At the G1/S transition, crosstalk between calcineurin and Hog1 dramatically increases the duration of calcium-induced arrest. I found that Hog1 triggers arrest independent of calcineurin by decreasing G1 cyclin transcription and calcineurin maintains this arrest by extending Hog1-dependent activation of the G1 CDK inhibitor Cip1. These results suggest that stress-response pathway interactions tailor cell cycle arrest with adaptation to environmental stress. The immediate response to stress is well-characterized, but how cells maintain viability in challenging environments after recovering from a stress-induced arrest is unknown. I investigated the response to prolonged growth in calcium stress and found that calcineurin maintains fitness by promoting cell division and suppressing death. I determined that calcineurin helps cells proliferate and survive prolonged calcium exposure by two mechanisms, which differentially require a downstream transcription factor. Together, these findings highlight the importance of stress-response pathways during both acute and chronic environmental stress.
  • Depressive Symptoms in Adolescence as a Predictor of Young Adult Employment Quality: Findings from the National Longitudinal Study of Adolescent to Adult Health

    Sabella, Kathryn (2024-06-13)
    This study uses longitudinal data from a nationally representative sample of adolescents, The National Longitudinal Study of Adolescent to Adult Health, to investigate the association between depressive symptomatology in adolescence and indicators of employment quality in young adulthood. A better understanding of the long-term impacts of adolescent depressive symptoms on employment quality during young adulthood would inform our understanding of how economic and mental health trajectories of individuals with a history of depression unfold.
  • A Scribe's Tribute

    Street, Ashley (2024-06-13)
    Introduction: This week I have the pleasure of sharing the first of two letters prepared by this year’s Scribe Fellows. The scribes were asked to write a letter to a provider they really connected with, someone who inspired them and helped them think about their future physician-self. The scribes could also reflect on a patient who made an impact. As you will read, Ashley Street’s future physician-self was informed by what she learned this year scribing and witnessing patient care at Hahnemann. In August, she will join us as a member of the Class of 2028! I think we can all say we look forward to seeing her. Congratulations to Ashley and all who inspired her.
  • Correction of multiplexing artefacts in multi-pinhole SPECT through temporal shuttering, de-multiplexing of projections, and alternating reconstruction

    Pells, Sophia; Zeraatkar, Navid; Kalluri, Kesava S; Moore, Stephen C; May, Micaehla; Furenlid, Lars R; Kupinski, Matthew A; Kuo, Phillip H; King, Michael A (2024-06-06)
    Objective.Single-photon emission computed tomography (SPECT) with pinhole collimators can provide high-resolution imaging, but is often limited by low sensitivity. Acquiring projections simultaneously through multiple pinholes affords both high resolution and high sensitivity. However, the overlap of projections from different pinholes on detectors, known as multiplexing, has been shown to cause artefacts which degrade reconstructed images.Approach.Multiplexed projection sets were considered here using an analytic simulation model of AdaptiSPECT-C-a brain-dedicated multi-pinhole SPECT system. AdaptiSPECT-C has fully adaptable aperture shutters, so can acquire projections with a combination of multiplexed and non-multiplexed frames using temporal shuttering. Two strategies for reducing multiplex artefacts were considered: an algorithm to de-multiplex projections, and an alternating reconstruction strategy for projections acquired with a combination of multiplexed and non-multiplexed frames. Geometric and anthropomorphic digital phantoms were used to assess a number of metrics.Main results.Both de-multiplexing strategies showed a significant reduction in image artefacts and improved fidelity, image uniformity, contrast recovery and activity recovery (AR). In all cases, the two de-multiplexing strategies resulted in superior metrics to those from images acquired with only mux-free frames. The de-multiplexing algorithm provided reduced image noise and superior uniformity, whereas the alternating strategy improved contrast and AR.Significance.The use of these de-multiplexing algorithms means that multi-pinhole SPECT systems can acquire projections with more multiplexing without degradation of images.
  • UMCCTS Newsletter, June 2024

    UMass Center for Clinical and Translational Science (2024-06-03)
    This is the June 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
  • ACR Appropriateness Criteria® Female Breast Cancer Screening: 2023 Update

    Niell, Bethany L; Jochelson, Maxine S; Amir, Tali; Brown, Ann; Adamson, Megan; Baron, Paul; Bennett, Debbie L; Chetlen, Alison; Dayaratna, Sandra; Freer, Phoebe E; et al. (2024-06-01)
    Early detection of breast cancer from regular screening substantially reduces breast cancer mortality and morbidity. Multiple different imaging modalities may be used to screen for breast cancer. Screening recommendations differ based on an individual's risk of developing breast cancer. Numerous factors contribute to breast cancer risk, which is frequently divided into three major categories: average, intermediate, and high risk. For patients assigned female at birth with native breast tissue, mammography and digital breast tomosynthesis are the recommended method for breast cancer screening in all risk categories. In addition to the recommendation of mammography and digital breast tomosynthesis in high-risk patients, screening with breast MRI is recommended. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
  • Apheresis practice variation during the COVID-19 pandemic: Results of a survey

    Tanhehco, Yvette C; Alsammak, Mohamed; Chhibber, Vishesh; Ibeh, Nnaemeka; Li, Yanhua; Stephens, Laura D; Noland, Daniel K; Wu, Ding Wen; Zantek, Nicole D; DeChristopher, Phillip J; et al. (2024-06-01)
    Background: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. Study design and methods: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. Results: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. Conclusion: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.
  • Kinetics of Pre-mRNA 3’ End Cleavage

    Torres Ulloa, Leslie (2024-05-31)
    3’ end cleavage and polyadenylation are required steps in pre-mRNA maturation. The rate at which 3’ end cleavage occurs can determine the temporal availability of mRNA for subsequent function throughout the cell and is likely tightly regulated. While there are numerous high-throughput methods for global profiling of RNA maturation rates, the study of pre-mRNA 3’ end cleavage kinetics has remained limited to low-throughput approaches, and the temporal regulation of polyadenylation site choice that determines the composition of the 3’ UTRs of mRNAs remains poorly understood. This research project seeks to address this gap by introducing a novel genome-wide, site-specific methodology for estimating rates of pre-mRNA 3’ end cleavage, using metabolic labeling of nascent RNA, high-throughput sequencing, and mathematical modeling. Using in-silico simulations of nascent RNA-seq data, we show that our approach can accurately and precisely estimate cleavage half-lives for both constitutive and alternative sites. In Drosophila melanogaster S2 cells, we find that cleavage rates are fast but highly variable across sites, with alternative events being slowest. This variability in rates is underpinned by distinctive sequence elements, where an A-rich region upstream of the cleavage site, a U-rich element downstream of the cleavage site, and a higher density of polyadenylation signals, lead to faster cleavage reactions. Assessment of Polymerase II dynamics around cleavage sites reveals that cleavage rates are associated with the localization of RNA Polymerase II at the end of a gene and faster cleavage leads to quicker degradation of downstream read-through RNA. This approach for estimating pre-mRNA 3’ end cleavage kinetics opens new possibilities in the study of co-transcriptional regulation of mRNA expression and transcription termination across cellular states.
  • SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C)

    Rahman, Asif; Russell, Michael; Zheng, Wanhong; Eckrich, Daniel; Ahmed, Imtiaz (2024-05-30)
    Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.
  • Variation in Depth of Sedation Targeted and Achieved among Mechanically Ventilated Patients and Associated Outcomes

    Rucci, Justin M (2024-05-30)
    Introduction: Sedative agents are commonly administered to patients receiving mechanical ventilation (MV). Practice guidelines recommend provision of light sedation within validated scoring systems (e.g., Richmond Agitation Sedation Scale [RASS]), but recognize some circumstances require deeper sedation. The real-world approaches to depth of sedation, and the impact of hospital sedation practices on patient outcomes, remain uncharacterized. Methods: We used the US based eICU collaborative research database to identify adult patients who received MV > 24 hours, who did not have a diagnosis that may require sedatives for indications other than facilitating MV, and who had recorded RASS goals and scores. We used mixed effects regression models to determine factors associated with initial RASS goals and rates of RASS score-goal concordance. We organized hospitals into quartiles of risk-adjusted RASS score-goal concordance, and used g-computation to evaluate differences in ventilator free days (VFD) at hospital day 28. Results: We identified a study sample of 1,650 adult patients (at 21 hospitals) who met inclusion/exclusion criteria. Hospital-level risk-adjusted initial RASS goals ranged from -1.4 to 0.2, and hospital-level risk-adjusted RASS score-goal concordance ranged from 27% to 64%. Patients admitted to hospitals in the highest quartile of score-goal concordance (quartile 4) were generally targeted for deeper sedation (median RASS goal -1.31) than patients admitted to hospitals in the lowest quartile (quartile 1) (median RASS goal -0.58). Compared to patients admitted to quartile 1 hospitals, patients at quartile 4 hospitals experienced fewer VFDs (adjusted incidence risk difference -2.4, 95% CI -4.26 to -0.36). Conclusion: US hospitals prescribe RASS goals in line with guideline recommendations for light sedation, but there is wide variation in achieving these RASS goals. Hospitals with higher RASS score-goal concordance typically prescribed deeper RASS goals, and patients admitted to these hospitals experienced fewer VFD.
  • Burnout Among Young Adults With Type 1 Diabetes

    Perez, Danielle; Sullivan-Bolyai, Susan L; Bova, Carol A; Fain, James A (2024-05-30)
    Purpose: The purpose of this qualitative descriptive study was to describe the experience of diabetes burnout in young adults with type 1 diabetes (T1DM). In addition, aims included participant perspectives of risk and protective factors associated with burnout and ways to balance everyday life with diabetes self-management (DSM). Methods: Young adults with T1DM (N = 11) were recruited through social media platforms and modified snowball sampling and interviewed. Informational redundancy was achieved. Qualitative thematic coding and analysis were conducted within and across transcripts. Results: Diabetes burnout was described as the willingness to put diabetes and DSM on the "back burner" and let things slide due to exhaustion, frustration, apathy, and the desire to be like everyone else for a while. Risk and protective factors were identified along with strategies to achieve balance of DSM in everyday life. Conclusions: This study identified a clear definition of diabetes burnout and acknowledges this concept as distinct and separate from other psychosocial conditions. Health care providers can utilize this information to identify individuals at risk for diabetes burnout and offer more effective support to lessen the overall burden associated with T1DM.
  • What Do You Know, and How Do You Know it?

    Singer, Robert E (2024-05-30)
    Introduction: This week I am thrilled to share with you a reflection of an alum who has written many FMMs over the years, Bob Singer. Bob was a resident in the UMass Family Practice Residency Program from 1978 to 1981 when the Family Health Center of Worcester was called the Family Health and Social Service Center. As we enter our 50th year celebration for the department, we welcome more stories, poems and reflections from alumni. In this piece, Bob offers some sage advice about giving advice.
  • Pairtools: From sequencing data to chromosome contacts

    Abdennur, Nezar; Fudenberg, Geoffrey; Flyamer, Ilya M; Galitsyna, Aleksandra A; Goloborodko, Anton; Imakaev, Maxim; Venev, Sergey V (2024-05-29)
    The field of 3D genome organization produces large amounts of sequencing data from Hi-C and a rapidly-expanding set of other chromosome conformation protocols (3C+). Massive and heterogeneous 3C+ data require high-performance and flexible processing of sequenced reads into contact pairs. To meet these challenges, we present pairtools-a flexible suite of tools for contact extraction from sequencing data. Pairtools provides modular command-line interface (CLI) tools that can be flexibly chained into data processing pipelines. The core operations provided by pairtools are parsing of.sam alignments into Hi-C pairs, sorting and removal of PCR duplicates. In addition, pairtools provides auxiliary tools for building feature-rich 3C+ pipelines, including contact pair manipulation, filtration, and quality control. Benchmarking pairtools against popular 3C+ data pipelines shows advantages of pairtools for high-performance and flexible 3C+ analysis. Finally, pairtools provides protocol-specific tools for restriction-based protocols, haplotype-resolved contacts, and single-cell Hi-C. The combination of CLI tools and tight integration with Python data analysis libraries makes pairtools a versatile foundation for a broad range of 3C+ pipelines.
  • Dual engagement of the nucleosomal acidic patches is essential for deposition of histone H2A.Z by SWR1C

    Baier, Alexander S; Gioacchini, Nathan; Eek, Priit; Leith, Erik M; Tan, Song; Peterson, Craig L (2024-05-29)
    The yeast SWR1C chromatin remodeling enzyme catalyzes the ATP-dependent exchange of nucleosomal histone H2A for the histone variant H2A.Z, a key variant involved in a multitude of nuclear functions. How the 14-subunit SWR1C engages the nucleosomal substrate remains largely unknown. Studies on the ISWI, CHD1, and SWI/SNF families of chromatin remodeling enzymes have demonstrated key roles for the nucleosomal acidic patch for remodeling activity, however a role for this nucleosomal epitope in nucleosome editing by SWR1C has not been tested. Here, we employ a variety of biochemical assays to demonstrate an essential role for the acidic patch in the H2A.Z exchange reaction. Utilizing asymmetrically assembled nucleosomes, we demonstrate that the acidic patches on each face of the nucleosome are required for SWR1C-mediated dimer exchange, suggesting SWR1C engages the nucleosome in a 'pincer-like' conformation, engaging both patches simultaneously. Loss of a single acidic patch results in loss of high affinity nucleosome binding and nucleosomal stimulation of ATPase activity. We identify a conserved arginine-rich motif within the Swc5 subunit that binds the acidic patch and is key for dimer exchange activity. In addition, our cryoEM structure of a Swc5-nucleosome complex suggests that promoter proximal, histone H2B ubiquitylation may regulate H2A.Z deposition. Together these findings provide new insights into how SWR1C engages its nucleosomal substrate to promote efficient H2A.Z deposition.

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