The EAR and NotI repeat genes of Epstein-Barr virus (EBV) are oriented head to head and separated by a 1,000-base-pair (bp) divergent promoter region. We have identified functional domains within this divergent promoter which are important for regulation of the rightward EAR gene. Both the R transactivator (Rta) and the Z transactivator (Zta) increase the abundance of correctly initiated EAR transcripts. A 258-bp fragment (-114 to-372 from the EAR cap site) contained the primary Rta and Zta response elements and was capable of transferring Rta and Zta activity to a heterologous promoter in an orientationand position-independent manner. Rta activated this 258-bp enhancer region in both EBV-positive and EBV-negative cells. However, Zta activity appeared to be dependent on another EBV gene product, since Zta activated the enhancer efficiently (500to 2,000-fold) in EBV-positive cells but had little or no activity in EBV-negative cells. The combination of Rta and Zta produced a striking synergistic effect on the enhancer in the absence of any additional EBV components, suggesting that the interaction between Zta and Rta accounts for the Zta response observed in EBV-positive cells. An Rta response element was mapped to a domain located 60 bp away from a Zta-binding site within the enhancer. Although Rta activated the enhancer and other early promoters without additional EBVor B-cell-specific factors, it did not activate the lytic cycle of EBV, in contrast to Zta. Immunofluorescence patterns of Rta and Zta with antipeptide antisera indicated that they have overlapping but different subcellular localizations. Both transactivators were found in the nucleus, but Rta was also found in the cytoplasm.

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Many oral medication classes are available for the treatment of diabetes. Within each class, there are multiple agents with specifi c indications, side eff ects, dosing, warnings, and contraindications. The purpose of this article is to provide a quick reference to these medications for use in day-today practice. Recommendations from the 2022 American Diabetes Association (ADA) Standards of Care regarding oral diabetes therapies highlight the use of sodium-glucose cotransporter-2 inhibitors (SGLT-2) as a possible fi rst-line option in the treatment of type 2 diabetes. Metformin remains fi rst-line for the majority of people, but additive or alternative therapies may be considered if additional compelling indications, such as chronic kidney disease, heart failure, or atherosclerotic cardiovascular disease, are present and data regarding benefi t exist, regardless of baseline A1C. The 2022 ADA Standards of Care also suggest patient-centered therapy selection (eg, past medical history, cost, access considerations). The SGLT-2 inhibitors (canaglifl ozin, dapaglifl ozin, empaglifl ozin, ertuglifl ozin) were originally approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes to lower blood glucose in conjunction with healthy eating and physical activity. Since their initial approval, some of these agents have received additional FDA-approved indications based on randomized controlled trials (see reference list). Canaglifl ozin is also approved to reduce risk of major cardiovascular (CV) events in persons with type 2 diabetes with established cardiovascular disease (CVD) and to reduce risk of end-stage Comprehensive Oral Diabetes Medication Resource