The Tat protein of the human immunodeficiency virus (HIV) is a powerful activator of HIV gene expression. Genetic and biochemical evidence suggests that one or more cellular cofactors may be important for Tat activity. We have used two-hybrid interactive cloning in yeast to identify a partial cDNA clone (clone 10) from a human B-lymphoblastoid library that specifically interacts with the N-terminal 31 amino acids of HIV-1 Tat which contains the essential cysteine-rich portion of the Tat activation domain. The encoded protein also binds to purified Tat in vitro. Mutation of single essential cysteine residues in Tat abolishes interaction between Tat and clone 10, suggesting that interaction with the encoded protein is important for Tat activity. We have identified the full-length cDNA for the Tat binding protein and shown that overexpression of the encoded protein, Tip60 (Tat interactive protein, 60 kDa), results in a fourfold augmentation of Tat transactivation of the HIV-1 promoter in transient expression assays without increasing the basal activity of the HIV promoter or activating the heterologous RSV promoter. These data together with the genetic and in vitro binding data support the notion that Tip60 might be a cofactor of Tat involved in the regulation of HIV gene expression.

Interleukin 6 (IL-6) induces the acute phase response, differentiation of B cells, proliferation of T cells, thymocytes, hematopoietic progenitors, hybridoma and plasmacytoma cells. Monocytes, T cells, fibroblasts, epithelial and endothelial cells secrete IL-6. Since IL-6 responsive cell-types may participate in the pathogenesis of glomerular inflammation, we studied the secretion of IL-6 by rat MCs, using the IL-6 dependent hybridoma cell line B9. The results of our studies indicate that MCs secrete IL-6 with a molecular weight of 17-42 kDa and isoelectric point of 4.0 to 5.3 MC-IL-6 activity could be blocked by a polyclonal antimurine-IL-6 antibody. MC express IL-6 mRNA as determined by Northern blot. Furthermore, our data demonstrate that IL-6 acts as an autocrine growth factor for MC. Incubation of subconfluent MC with recombinant IL-6 results in a dose-dependent increase of 3H-thymidine incorporation and number of MCs. Moreover, reverse phase HPLC fractions of MC-CM containing IL-6 activity increase 3H-thymidine incorporation by MC. In addition to its possible paracrine role in mediating the immune response in the glomerulus, MC-IL-6 may also be one of the autocrine signals leading to mesangial cell proliferation in vivo.

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Social determinants of health (SDH) are the major drivers of health and disparate health outcomes across communities and populations. Given this, the authors assert that competency in recognizing and mitigating SDH should become a vital component of graduate medical education in all specialties. Although the most effective approaches to educating trainees about SDH are uncertain, in this Invited Commentary, the authors offer several key principles for implementing curricula focusing on SDH. These include universalization of the material, integration into clinical education, identification of space for trainee introspection, clarification of specific competencies in identification and mitigation of SDH, and creation of robust faculty development programming. The authors highlight several examples of curricular approaches to SDH, touching on orientation, experiential learning, community-based and service-learning opportunities, interprofessional activities, and the hidden curriculum. The authors argue that all clinical trainees must learn to recognize and mitigate SDH and that doing so will allow them to achieve meaning and mastery in medicine and to better meet society's pressing health needs.

In the international expansion of universities, the branch campus, also known as the franchise campus and the joint venture campus (among other terms), is perhaps the most intrusive yet least monitored form of cross-border educational provision. Generally designed as an offshore satellite of a Western university, branch campuses are located in an ever-increasing number of countries. Typically charged full fees, international students complete their courses in whole or in part at the branch campus, which may include instruction by staff members of the “main” university. This article discusses the evolution of the branch campus in Southeast Asia, with an emphasis on Australian institutional expansion in the region. Drawing on an empirical study, the article culminates in a discussion of the British Quality Assurance Agency and the Australian Universities Quality Agency, bodies that represent independent and governmental efforts to extend quality assurance oversight to transnational educational activities.

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