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The heterodimeric splicing factor U2AF plays an important role in 3' splice site selection, but the division of labor between the two subunits in vivo remains unclear. In vitro assays led to the proposal that the human large subunit recognizes 3' splice sites with extensive polypyrimidine tracts independently of the small subunit. We report in vivo analysis demonstrating that all five domains of spU2AFLG are essential for viability; a partial deletion of the linker region, which forms the small subunit interface, produces a severe growth defect and an aberrant morphology. A small subunit zinc-binding domain mutant confers a similar phenotype, suggesting that the heterodimer functions as a unit during splicing in Schizosaccharomyces pombe. As this is not predicted by the model for metazoan 3' splice site recognition, we sought introns for which the spU2AFLG and spU2AFSM make distinct contributions by analyzing diverse splicing events in strains harboring mutations in each partner. Requirements for the two subunits are generally parallel and, moreover, do not correlate with the length or strength of the 3' pyrimidine tract. These and other studies performed in fission yeast support a model for 3' splice site recognition in which the two subunits of U2AF functionally collaborate in vivo.

Osteoarthritis (OA) of the knee is one of the most common joint diseases affecting adults in the United States. For elderly patients with multiple medical comorbidities who do not wish to undergo total knee arthroplasty (TKA), lifestyle modification, pharmacologic management, and injections are the mainstay of therapy. Previously, pain management interventions were limited to intra-articular joint injections and viscosupplementation with hyaluronic acid. Fluoroscopic-guided techniques for radiofrequency ablation (RFA) of the genicular nerves have been previously described and a recent cadaveric study suggests that ultrasound-guided genicular nerve blocks can be performed accurately. We performed an ultrasound-guided radiofrequency ablation of the genicular nerves in 88-year-old woman who had deferred surgical management given her age. Following successful ultrasound guided diagnostic genicular nerve blocks, she proceeded to RFA using the same ultrasound guided technique. The procedure resulted in significant pain relief and improvement in overall function for greater than 6 months. The use of ultrasound provides a relatively rapid and noninvasive method to directly visualize genicular nerves and surrounding vasculature. Our case suggests that, for genicular nerve blockade and RFA, ultrasound may be a useful alternative to fluoroscopy. Not only did the procedure result in significant pain relief that has persisted for greater than 6 months but also more importantly her function status and quality of life were improved.

Mediastinal mass syndrome (MMS) is a complex case that poses many challenges to the anesthesiologist. The cornerstone of management focuses on the potential hemodynamic changes associated with this syndrome. We describe the anesthetic management of a patient with a previously undiagnosed mediastinal mass presenting for emergency neurosurgical surgery.