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Graphical abstract, Over recent years, there has been a rapid development of membrane-mimetic systems to encapsulate and stabilize planar segments of phospholipid bilayers in solution. One such system has been the use of amphipathic copolymers to solubilize lipid bilayers into nanodiscs. The attractiveness of this system, in part, stems from the capability of these polymers to solubilize membrane proteins directly from the host cell membrane. The assumption has been that the native lipid annulus remains intact, with nanodiscs providing a snapshot of the lipid environment. Recent studies have provided evidence that phospholipids can exchange from the nanodiscs with either lipids at interfaces, or with other nanodiscs in bulk solution. Here we investigate kinetics of lipid exchange between three recently studied polymer-stabilized nanodiscs and supported lipid bilayers at the silicon-water interface. We show that lipid and polymer exchange occurs in all nanodiscs tested, although the rate and extent differs between different nanodisc types. Furthermore, we observe adsorption of nanodiscs to the supported lipid bilayer for one nanodisc system which used a polymer made using reversible addition-fragmentation chain transfer polymerization. These results have important implications in applications of polymer-stabilized nanodiscs, such as in the fabrication of solid-supported films containing membrane proteins.

Objective: To study the impact of multiphase quality improvement efforts to enhance appropriate use of chemical and mechanical venous thromboembolism (VTE) prophylaxis (VTEP) on the rate of hospital-acquired VTE and determine whether efforts have been associated with increased bleeding complications. Patients and Methods: All adult inpatients discharged between January 1, 2005, and December 31, 2015, were included in the study. Retrospective interrupted time series analysis compared VTEP performance, VTE outcomes, and unintended consequences (derived from linked administrative and clinical data) across 5 improvement phases: baseline (January 1, 2005-December 31, 2006), paper order set phase (January 1, 2007-February 9, 2009), electronic order set phase (February 10, 2009-December 16, 2009), active reminder phase (December 17, 2009-May 31, 2012), and maintenance phase (June 1, 2012-September 30, 2015). Results: Guideline VTEP plan adherence at the end of the study period (including documenting contraindications) reached 88.8% (654,138 of 736,384 patient days). Delivery of pharmacological VTEP increased from 43.9% (49,155 of 111,906 patients) to 60.8% (75,784 of 124,676 patients); delivery of mechanical or pharmacological VTEP increased less (65.0% [431,791 of 664,087 patient days] to 67.4% [496,625 of 736,384 patient days]). Mean VTE rates decreased from 4.6 per 1000 hospitalizations (21.7 VTEs per month) at baseline to 4.3 per 1000 hospitalizations (18.0 VTEs per month) during the maintenance phase (P

RNA polymerase II (Pol II) surveils the genome, pausing as it encounters DNA lesions and base modifications and initiating signals for DNA repair among other important regulatory events. Recent work suggests that Pol II pauses at 5-carboxycytosine (5caC), an epigenetic modification of cytosine, because of a specific hydrogen bond between the carboxyl group of 5caC and a specific residue in fork loop 3 of Pol II. This hydrogen bond compromises productive NTP binding and slows down elongation. Apart from this specific interaction, the carboxyl group of 5caC can potentially interact with numerous charged residues in the cleft of Pol II. However, it is not clear how other interactions between Pol II and 5caC contribute to pausing. In this study, we use Markov state models (a type of kinetic network models) built from extensive molecular dynamics simulations to comprehensively study the impact of 5caC on Pol II translocation. We describe two translocation intermediates with specific interactions that prevent the template base from loading into the Pol II active site. In addition to the previously observed state with 5caC constrained by fork loop 3, we discovered a new intermediate state with a hydrogen bond between 5caC and fork loop 2. Surprisingly, we find that 5caC may curb translocation by suppressing kinking of the helix bordering the active site (the bridge helix) because its high flexibility is critical to translocation. Our work provides new insights into how epigenetic modifications of genomic DNA can modulate Pol II translocation, inducing pauses in transcription.