The Mouse Cytomegalovirus Gene m42 Targets Surface Expression of the Protein Tyrosine Phosphatase CD45 in Infected Macrophages

The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264.7 macrophage cell line led to comparable regulation of CD45 expression. In immunocompetent mice infected with an m42 deletion mutant lower viral titers were observed in all tissues examined when compared to wildtype MCMV, indicating an important role of m42 for viral replication in vivo. The m42 gene product was identified as an 18 kDa protein expressed with early kinetics and is predicted to be a tailanchored membrane protein. Tracking of surface-resident CD45 molecules revealed that m42 induces internalization and degradation of CD45. The observation that the amounts of the E3 ubiquitin ligases Itch and Nedd4 were diminished in cells expressing m42 and that disruption of a PY motif in the N-terminal part of m42 resulted in loss of function, suggest that m42 acts as an activator or adaptor for these Nedd4-like ubiquitin ligases, which mark CD45 for lysosomal degradation. In conclusion, the down-modulation of CD45 expression in MCMV-infected myeloid cells represents a novel pathway of virus-host interaction

Diffusion of Innovations: Interplay of Social, Economic, Technological, and Policy Drivers in the Solar Industry—Summary of UT Austin Student Capstone Research Projects

The University of Texas at Austin’s Policy Research Project (PRP), a nine-month (two semesters) capstone, is a keystone of the core curriculum at the LBJ School of Public Affairs. In PRPs, small groups of students, under the mentorship of a faculty director, take on real-world problems that require special knowledge and skill sets. PRPs expose students to challenges in formulating and executing research, and in communicating academic research and related complex data to broader stakeholder communities and decision makers. The PRP structure is an innovative and effective approach for integrating research within the teaching and training of graduate students who are preparing themselves to address important real-world problems at the intersection of society, economics, technology, and policy. The project summaries below describe seven papers developed during September 2017 – May 2018 as part of a PRP on “Diffusion of Innovations: Interplay of Social, Economic, Technological, and Policy Drivers in the Solar Industry.” Twenty graduate students, drawn from the LBJ School’s Masters in Public Affairs and Masters in Global Policy Studies programs and the Jackson School Geoscience’s Energy and Earth Resources program, participated in this PRP. Dr. Varun Rai, Associate Professor and Associate Dean for Research at the LBJ School, directed the PRP, with support from his research team including: Dr. Ariane Beck, Dr. Ashok Sekar, D. Cale Reeves, and Erik Funkhouser. Clients for the project included the U.S. Department of Energy (Casey Canfield), Lawrence Berkeley National Laboratory (Ben Hoen, Galen Barbose Joachim Seel, Naïm Darghouth, Ryan Wiser), and National Renewable Energy Laboratory (Benjamin Sigrin, Eric O’Shaughnessy). The seven projects separately addressed one of the following topics: (1) low- and middle-income PV adoption, (2) modeling economic and information intervention design, (3) evaluation of DOE’s Solar in Your Community Challenge, (4) property value impacts near large-scale solar facilities, (5) solar market maturity and evolution of business models, (6) social media data for predicting PV adoption, and (7) individual-level variation in adoption of innovations. Many of the papers relied on data collected and curated by Lawrence Berkeley National Laboratory, including data embedded within the annual Tracking the Sun and Utility-Scale Solar reports. Each of the seven teams in the PRP prepared a research paper. The PRP culminated with a full-day conference at UT Austin in May 2018 to present findings from the seven projects in this PRP to a broad audience of about 75 experts from academia, national labs, industry, and government from across the country

Resiliency in the Age of COVID-19: A Policy Toolkit

Twenty-nine LBJ School authors have come together to craft interdisciplinary and resilience-based policy solutions in one toolkit called Resiliency in the Age of COVID-19. In 18 articles that span public management, climate change, economic development, national security and more, LBJ School policy authors provide a forward-thinking lens on what went wrong and what leadership, public policies and initiatives it will take to fix the system flaws exposed by the pandemic. Published during the LBJ School’s 50th anniversary year, the toolkit also provides a snapshot of the school’s depth and breadth of policy and research engagement at this moment in time.Public Affair

Conventional versus minimally invasive extracorporeal circulation in patients undergoing cardiac surgery: protocol for a randomised controlled trial (COMICS)

Introduction: Despite low mortality, cardiac surgery patients may experience serious life-threatening post-operative complications, often due to extracorporeal circulation and reperfusion. Miniaturised cardiopulmonary bypass (minimally invasive extracorporeal circulation) has been developed aiming to reduce the risk of post-operative complications arising with conventional extracorporeal circulation. Methods: The COMICS trial is a multi-centre, international, two-group parallel randomised controlled trial testing whether type II, III or IV minimally invasive extracorporeal circulation is effective and cost-effective compared to conventional extracorporeal circulation in patients undergoing elective or urgent coronary artery bypass grafting, aortic valve replacement or coronary artery bypass grafting + aortic valve replacement. Randomisation (1:1 ratio) is concealed and stratified by centre and surgical procedure. The primary outcome is a composite of 12 serious complications, objectively defined or adjudicated, 30 days after surgery. Secondary outcomes (at 30 days) include other serious adverse events (primary safety outcome), use of blood products, length of intensive care and hospital stay and generic health status (also at 90 days). Status of the trial: Two centres started recruiting on 08 May 2018; 10 are currently recruiting and 603 patients have been randomised (11 May 2020). The recruitment rate from 01 April 2019 to 31 March 2020 was 40-50 patients/month. About 80% have had coronary artery bypass grafting only. Adherence to allocation is good. Conclusions: The trial is feasible but criteria for progressing to a full trial were not met on time. The Trial Steering and Data Monitoring Committees have recommended that the trial should currently continue