Correction: Distinct SUMO Ligases Cooperate with Esc2 and Slx5 to Suppress Duplication-Mediated Genome Rearrangements.

[This corrects the article DOI: 10.1371/journal.pgen.1003670.].

Distinct SUMO ligases cooperate with Esc2 and Slx5 to suppress duplication-mediated genome rearrangements.

Suppression of duplication-mediated gross chromosomal rearrangements (GCRs) is essential to maintain genome integrity in eukaryotes. Here we report that SUMO ligase Mms21 has a strong role in suppressing GCRs in Saccharomyces cerevisiae, while Siz1 and Siz2 have weaker and partially redundant roles. Understanding the functions of these enzymes has been hampered by a paucity of knowledge of their substrate specificity in vivo. Using a new quantitative SUMO-proteomics technology, we found that Siz1 and Siz2 redundantly control the abundances of most sumoylated substrates, while Mms21 more specifically regulates sumoylation of RNA polymerase-I and the SMC-family proteins. Interestingly, Esc2, a SUMO-like domain-containing protein, specifically promotes the accumulation of sumoylated Mms21-specific substrates and functions with Mms21 to suppress GCRs. On the other hand, the Slx5-Slx8 complex, a SUMO-targeted ubiquitin ligase, suppresses the accumulation of sumoylated Mms21-specific substrates. Thus, distinct SUMO ligases work in concert with Esc2 and Slx5-Slx8 to control substrate specificity and sumoylation homeostasis to prevent GCRs.

Regional Anesthetic Approaches for Postoperative Analgesia Following Vertebral Body Tethering: A Case Series.

Vertebral body tethering (VBT) is an innovative surgical technique used to treat juvenile and adolescent idiopathic scoliosis. The optimal anesthetic technique, including the preferred management of postoperative pain, is not known. In this case series, we describe 3 patients with adolescent idiopathic scoliosis who received either continuous erector spinae plane block (ESPB) catheters or intercostal liposomal bupivacaine for postoperative pain management after bilateral VBT via minithoracotomy.

Inheritance of CENP-A Nucleosomes during DNA Replication Requires HJURP.

Centromeric chromatin defines the site of kinetochore formation and ensures faithful chromosome segregation. Centromeric identity is epigenetically specified by the incorporation of CENP-A nucleosomes. DNA replication presents a challenge for inheritance of centromeric identity because nucleosomes are removed to allow for replication fork progression. Despite this challenge, CENP-A nucleosomes are stably retained through S phase. We used BioID to identify proteins transiently associated with CENP-A during DNA replication. We found that during S phase, HJURP transiently associates with centromeres and binds to pre-existing CENP-A, suggesting a distinct role for HJURP in CENP-A retention. We demonstrate that HJURP is required for centromeric nucleosome inheritance during S phase. HJURP co-purifies with the MCM2-7 helicase complex and, together with the MCM2 subunit, binds CENP-A simultaneously. Therefore, pre-existing CENP-A nucleosomes require an S phase function of the HJURP chaperone and interaction with MCM2 to ensure faithful inheritance of centromere identity through DNA replication.

The Impact of "See the City You Serve" Field Trip: An Educational Tool for Teaching Social Determinants of Health.

BACKGROUND: There has been limited evaluation of tools for teaching social determinants of health (SDOH). OBJECTIVE: We evaluated a field trip as a tool for teaching SDOH to incoming medical interns. METHODS: Incoming interns from The George Washington University participated in a bus field trip of Washington, DC, guided by community partners. The field trip introduced trainees to local neighborhoods. Pre- and postactivity surveys developed by the authors were analyzed using a Wilcoxon signed rank test. Reflection responses were recorded and counted for recurrent themes. RESULTS: Incoming interns participated in 2015 (85 of 90, 94%) and in 2016 (96 of 116, 83%). Postactivity, basic knowledge of DC geographic health disparities increased, and a greater percentage of interns reported being at least somewhat comfortable understanding the neighborhoods from which their patients come (2015: 58% versus 89%, P < .0001; 2016: 65% versus 88%, P < .0001); identifying challenges to health care that affect low-income patients (2015: 74% versus 90%, P < .0023); describing community resources (2015: 29% versus 67%, P < .0001; 2016: 29% versus 50%, P < .0001); and referring patients to local community resources (2015: 25% versus 64%, P < .0001; 2016: 36% versus 52%, P < .0001). Interns reported that this experience improved their understanding of patients' background and local resources, and that they would change the way they practice. CONCLUSIONS: A bus field trip guided by community partners is a feasible way to increase residents' perception of their understanding of local disparities and comfort in addressing SDOH.

Framing choice: The origins and impact of consumer rhetoric in US health care debates.

This paper examines the origins of consumerist discourse in health care from a communication perspective via a historical textual analysis of health writing in popular magazines from 1930 to 1949. The focus is on Consumers Union's Consumer Reports and the American Medical Association's lay health magazine, Hygeia. Findings from Consumer Reports show that the consumer movement of the 1930s-40s staunchly advocated for universal health insurance. Whereas consumer rights language nowadays tends towards individual choice and personal responsibility, consumerism in health care during that era articulated ideas about consumer citizenship, framing choice and responsibility in collectivist terms and health care as a social good. This paper also illuminates the limits and weaknesses of a central tenet in consumerism-freedom of choice-by analyzing stories in Hygeia about the doctor-patient relationship. A textual analysis finds that the AMA's justification in the 1930s-40s against socialized medicine, i.e., the freedom to choose a doctor, was in practice highly controlled by the medical profession. Findings show that long before the rhetoric of the "empowered consumer" became popular, some patients exercised some choice even in an era when physicians achieved total professional dominance. But these patients were few and tend to occupy the upper socioeconomic strata of US society. In reality choice was an illusion in a fee-for-service era when most American families could not afford the costs of medical care.