Suppression of the cellular apoptotic program by the oncogenic herpesvirus Epstein-Barr virus (EBV) is. We now report that LMP1 drives bfl-1 promoter activity through interactions with components of the tumor necrosis factor receptor (TNFR)/CD40 signaling pathway. We present evidence that this process is NF-B dependent, involves the recruitment of TNFR-associated factor 2, and is mediated to a greater extent by the carboxyl-terminal activating region 2 (CTAR2) relative to the CTAR1 domain of LMP1. Activation of CD40 receptor also led to increased bfl-1 mRNA levels and an NF-B-dependent increase in bfl-1 promoter activity in Burkitt's lymphoma-derived cell lines. We have delineated a 95-bp region of the promoter that functions as an LMP1-dependent transcriptional enhancer in this cellular context. This sequence contains a novel NF-B-like binding motif that is essential for transactivation of bfl-1 by LMP1, CD40, and the NF-B subunit protein p65. These findings highlight the role of LMP1 as a mediator of EBV-host cell interactions and may indicate an important route by which it exerts its cellular growth transforming properties.

Protein fusion technology has enormously facilitated the efficient production and purification of individual recombinant proteins. The use of genetically engineered affinity and solubility-enhancing polypeptide "tags" has increased greatly in recent years and there now exists a considerable repertoire of these that can be used to solve issues related to the expression, stability, solubility, folding, and purification of their fusion partner. In the case of large-scale proteomic studies, the development of purification procedures tailored to individual proteins is not practicable, and affinity tags have therefore become indispensable tools for structural and functional proteomic initiatives that involve the expression of many proteins in parallel. Here, the rationale and applications of a range of established and more recently developed solubility-enhancing and affinity tags are outlined.

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Background Medical School programme workloads challenge the physical and mental health of students particularly in compressed graduate entry programmes. There is evidence that physical activity (PA) can improve holistic care and help maintain wellness among medical students. We tested the feasibility of introducing an exercise programme to the medical school curriculum which would educate and promote health and well-being among its students. Methods This study was conducted in a single graduate entry medical school at the University of Limerick (UL). The ‘MED-WELL’ programme was a six-week programme of 1 hour-long weekly sessions, each involving a different type of PA (45 min). These sessions were prefaced by an interactive lecture about how to incorporate exercise theory into daily medical practice (15 min). The study was conducted in a single graduate entry medical school at UL and involved year one and year two graduate entry medical students. Three parameters were used to test feasibility: 1. Recruitment and retention of participants, 2. Acceptability of the programme and 3. Efficacy in terms of health and well-being. The latter was assessed by administering questionnaires pre and post the intervention. The questionnaires used the following validated measurement scales: EQ-VAS; WHO-5 Well-Being Index; 3-item Loneliness Scale; Social Support Measure 3-item scale. Free text boxes also encouraged participants to discuss the merits of the programme. Results In total, 26% (74/286 students) participated in the programme. Of those who participated, 69 students (93%) attended one or more sessions of the programme and completed questionnaires at baseline and at follow-up. Significant improvements were seen in scores after the programme in the WHO-5 Well-Being Index which increased from 63.2 (95%CI: 48–78.4) to 67.5 (95%CI: 55.1–79.9); (P < 0.01), the sleep scale which increased from 3.1 (95%CI: 2.2–4.0) to 3.5 (95%CI: 2.5–4.5); (P < 0.001), and the loneliness scale which decreased from 4.1 (95%CI: 2.7–5.5) to 3.5 (95%CI: 2.5–4.5); (P < 0.005). Students level of PA during a typical week also increased from 3.7 (95%CI: 2.1–5.4) to 4.0 (95%CI, 3.5–4.5); (P < 0.05). Conclusion This study has shown it is feasible to deliver this programme in a medical school’s curriculum. The programme seems to be of benefit and is acceptable to students. Well-designed randomised controlled trials are needed to measure outcomes, durability of effect, and cost effectiveness.

The human herpesvirus Epstein-Barr virus (EBV) infects resting B lymphocytes, transforming them into permanently growing lymphoblastoid cell lines (LCLs) (for a review, see reference 27). Efficient virus-driven immortalization of B cells requires the expression of a subset of the thirteen known EBV latent genes, including several nuclear antigens (EBNAs),