Exportin Crm1 is important for Swi6 nuclear shuttling and MBF transcription activation in Saccharomyces cerevisiae.

BACKGROUND: Swi6 acts as a transcription factor in budding yeast, functioning in two different heterodimeric complexes, SBF and MBF, that activate the expression of distinct but overlapping sets of genes. Swi6 undergoes regulated changes in nucleocytoplasmic localization throughout the cell cycle that correlate with changes in gene expression. This study investigates how nucleocytoplasmic transport by multiple transport factors may influence specific Swi6 activities. RESULTS: Here we show that the exportin Crm1 is important for Swi6 nuclear export and activity. Loss of a putative Crm1 NES or inhibition of Crm1 activity results in changes in nucleocytoplasmic Swi6 localization. Alteration of the Crm1 NES in Swi6 results in decreased MBF-mediated gene expression, but does not affect SBF reporter expression, suggesting that export of Swi6 by Crm1 regulates a subset of Swi6 transcription activation activity. Finally, alteration of the putative Crm1 NES in Swi6 results in cells that are larger than wild type, and this increase in cell size is exacerbated by deletion of Msn5. CONCLUSIONS: These data provide evidence that Swi6 has at least two different exportins, Crm1 and Msn5, each of which interacts with a distinct nuclear export signal. We identify a putative nuclear export signal for Crm1 within Swi6, and observe that export by Crm1 or Msn5 independently influences Swi6-regulated expression of a different subset of Swi6-controlled genes. These findings provide new insights into the complex regulation of Swi6 transcription activation activity and the role of nucleocytoplasmic shuttling in regulated gene expression.

Myocarditis.

Myocarditis is an inflammatory disease of the heart that can cause devastating disease in otherwise healthy children. Inciting agents such as viral infection cause direct damage to the myocardial cells, which triggers an inflammatory response that enhances myocardial toxicity and associated morbidity. Severe cases typically present with respiratory distress and cardiovascular collapse, whereas subclinical cases are unnoticed by the medical community. The initial workup in suspected cases should include an electrocardiogram, chest radiograph, and cardiac troponin T. Treatment is concentrated on hemodynamic stabilization with optimization of heart failure management, dysrhythmia protocol, and supportive therapy. The purpose of this review was to provide the emergency medicine practitioner a concise and current review of the basic pathophysiology as well as a functional and evidence-based approach to the diagnosis and treatment of myocarditis in the pediatric population.