Interferon regulatory factor-5 (IRF-5) is a mediator of virus-induced immune activation and type I interferon (IFN) gene regulation. In human primary plasmacytoid dendritic cells (PDC), IRF-5 is transcribed into four distinct alternatively spliced isoforms (V1, V2, V3, and V4), whereas in human primary peripheral blood mononuclear cells two additional new isoforms (V5 and V6) were identified. The IRF-5 V1, V2, and V3 transcripts have different noncoding first exons and distinct insertion/ deletion patterns in exon 6. Here we showed that V1 and V3 have distinct transcription start sites and are regulated by two discrete promoters. The V1 promoter (P-V1) is constitutively active, contains an IRF-E consensusbinding site, and is further stimulated in virus-infected cells by IRF family members. In contrast, endogenous V3 transcripts were up-regulated by type I IFNs, and the V3 promoter (P-V3) contains an IFN-stimulated responsive element-binding site that confers responsiveness to IFN through binding of the ISGF3 complex. In addition to V5 and V6, we have identified three more alternatively spliced IRF-5 isoforms (V7, V8, and V9); V5 and V6 were expressed in peripheral blood mononuclear cells from healthy donors and in immortalized B and T cell malignancies, whereas expression of V7, V8, and V9 transcripts were detected only in human cancers. The results of this study demonstrated the existence of multiple IRF-5 spliced isoforms with distinct cell typespecific expression, cellular localization, differential regulation, and dissimilar functions in virus-mediated type I IFN gene induction.

To address the critical problem of inadequate physician supply in rural British Columbia, The University of British Columbia (UBC) launched an innovative, expanded and distributed medical program in 2004-2005. Medical students engage in a common curriculum at three geographically distinct sites across B.C.: in Vancouver, Prince George and Victoria. The distribution of the core Histology course required a thorough revision of our instructional methodology. We here report our progress and address the question "How does one successfully distribute Histology teaching to remote sites while maintaining the highest of educational standards?" The experience at UBC points to three specific challenges in developing a distributed Histology curriculum: (i) ensuring equitable student access to high quality histological images, (ii) designing and implementing a reliable, state-of-the-art technological infrastructure that allows for real-time teaching and interactivity across geographically separate sites and (iii) ensuring continued student access to faculty content expertise. High quality images--available through any internet connection--are provided within a new virtual slide box library of 300 light microscopic and 190 electron microscopic images. Our technological needs are met through a robust and reliable videoconference system that allows for live, simultaneous communication of audio/visual materials across the three sites. This system also ensures student access to faculty content expertise during all didactic teaching sessions. Student examination results and surveys demonstrate that the distribution of our Histology curriculum has been successful.

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This efficacious model of supporting and advancing a complex distributed medical program over more than a decade of pivotal change will be of interest to faculties and programs that are contemplating or navigating similar pursuits.