Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza.

Controlled, transient cytokine production by monocytes depends heavily upon rapid mRNA degradation, conferred by 3 untranslated region-localized AU-rich elements (AREs) that associate with RNA-binding proteins. The ARE-binding protein AUF1 forms a complex with cap-dependent translation initiation factors and heat shock proteins to attract the mRNA degradation machinery. We refer to this protein assembly as the AUF1-and signal transduction-regulated complex, ASTRC. Rapid degradation of ARE-bearing mRNAs (AREmRNAs) requires ubiquitination of AUF1 and its destruction by proteasomes. Activation of monocytes by adhesion to capillary endothelium at sites of tissue damage and subsequent proinflammatory cytokine induction are prominent features of inflammation, and ARE-mRNA stabilization plays a critical role in the induction process. Here, we demonstrate activation-induced subunit rearrangements within ASTRC and identify chaperone Hsp27 as a novel subunit that is itself an ARE-binding protein essential for rapid ARE-mRNA degradation. As Hsp27 has well-characterized roles in protein ubiquitination as well as in adhesion-induced cytoskeletal remodeling and cell motility, its association with ASTRC may provide a sensing mechanism to couple proinflammatory cytokine induction with monocyte adhesion and motility.Many mRNAs encoding proteins transiently required for inflammatory responses, cell proliferation, and intracellular signaling are labile due to AU-rich elements (AREs) in their 3Ј untranslated regions (UTRs) (14,21,57). ARE association by ELAV-like (embryonic lethal, abnormal vision) proteins, such as HuR, blocks ARE-mediated mRNA decay (AMD) (31). By contrast, association of proteins such as AUF1, tristetraprolin (TTP), BRF1 (butyrate-responsive factor-1), K-homology splicing regulatory protein (KSRP), ring finger K-homology domain 1 (RKHD1), polymyositisscleroderma 75-kDa antigen (PM-Scl75), or microRNA miR16 or miR289 with an ARE promotes AMD (6,8,12,18,24,34,43). The phosphorylation state of TTP, BRF1, and AUF1 affects AMD efficiency (3,37,51,56), indicating that signal transduction networks regulate this pathway.AUF1 has four protein isoforms-p37, p40, p42, and p45-generated by alternative pre-mRNA splicing (50). Based upon extensive biochemical studies of AUF1, we proposed an integrated, three-step model for induction of AMD by AUF1 via assembly of a trans-acting complex that targets the mRNA for degradation (52). The first step is dynamic AUF1 dimer binding to an ARE and formation of an oligomeric AUF1 complex (7, 52). Stabilizing ARE-binding proteins (AUBPs) may compete with AUF1 for binding to the ARE during this step, thus preventing AUF1 oligomerization and subsequent factor recruitment (25). Binding of AUF1 to an ARE then permits the second step involving recruitment of additional trans-acting factors including eukaryotic translation initiation factor eIF4G, poly(A)-binding protein, dual-functional heat shock/AUBPs Hsp/Hsc70 (27), and additional unknown proteins, forming a multisubunit AUF1-and signal tra...

This is a repository copy of Making a picture worth a thousand numbers: recommendations for graphically displaying patient-reported outcomes data.

Patients are increasingly being asked to complete standardized, validated questionnaires with regard to their symptoms, functioning, and well-being [ie, patient-reported outcomes (PROs)] as part of routine care. These PROs can be used to inform patients’ care and management, which we refer to as “PRO-cision Medicine.” For PRO-cision Medicine to be most effective, clinicians and patients need to be able to understand what the PRO scores mean and how to act on the PRO results. The papers in this supplement to Medical Care describe various methods that have been used to address these issues. Specifically, the supplement includes 14 papers: 6 describe different methods for interpreting PROs and 8 describe how different PRO systems have addressed interpreting PRO scores and/or acting on PRO results. As such, this “Methods Toolkit” can inform clinicians and researchers aiming to implement routine PRO reporting into clinical practice by providing methodological fundamentals and real-world examples to promote personalized patient care.

No abstract