Vaccinia Virus Proteins A52 and B14 Share a Bcl-2–Like Fold but Have Evolved to Inhibit NF-κB rather than Apoptosis

Vaccinia virus (VACV), the prototype poxvirus, encodes numerous proteins that modulate the host response to infection. Two such proteins, B14 and A52, act inside infected cells to inhibit activation of NF-κB, thereby blocking the production of pro-inflammatory cytokines. We have solved the crystal structures of A52 and B14 at 1.9 Å and 2.7 Å resolution, respectively. Strikingly, both these proteins adopt a Bcl-2–like fold despite sharing no significant sequence similarity with other viral or cellular Bcl-2–like proteins. Unlike cellular and viral Bcl-2–like proteins described previously, A52 and B14 lack a surface groove for binding BH3 peptides from pro-apoptotic Bcl-2–like proteins and they do not modulate apoptosis. Structure-based phylogenetic analysis of 32 cellular and viral Bcl-2–like protein structures reveals that A52 and B14 are more closely related to each other and to VACV N1 and myxoma virus M11 than they are to other viral or cellular Bcl-2–like proteins. This suggests that a progenitor poxvirus acquired a gene encoding a Bcl-2–like protein and, over the course of evolution, gene duplication events have allowed the virus to exploit this Bcl-2 scaffold for interfering with distinct host signalling pathways

It's About Time Physicians' Perceptions of Time Constraints in Primary Care Medical Practice in Three National Healthcare Systems

Background: As physicians are pressured to deliver an increasing number of preventive services, follow guidelines, engage in evidence-based practice, and deliver patient-centered care in managerially driven organizations, they struggle with how much control they have over their time. Methods: A secondary analysis was conducted with data from 3 parallel studies of clinical decision making in Germany, the United Kingdom, and the United States with 128 physicians per country. Physicians reported how much time they were allocated and how much time they needed for high-quality care for new patient appointments, routine consultations, and complete physicals. They also reported how much control they had over their time in the office and spending adequate time with patients. Results: German, British, and American physicians were allocated (on average) 16/11/32 minutes for a new patient appointment, 6/10/18 minutes for a routine visit, and 12/20/36 minutes for a complete physical, but felt that they needed more time. Over half of German and American physicians felt that they always or usually had control over the hours they were required to be in their office or spending sufficient time with their patients while less than half of British physicians felt this way. Conclusion: German physicians had the least time allocated and needed for most types of appointment. American physicians had the most time allocated and needed for each type of appointment. However, British physicians felt they had the least control over time in their office and spending sufficient time with patients