Influence of translation efficiency of homologous viral proteins on the endogenous presentation of CD8+ T cell epitopes

A significant proportion of endogenously processed CD8+ T cell epitopes are derived from newly synthesized proteins and rapidly degrading polypeptides (RDPs). It has been hypothesized that the generation of rapidly degrading polypeptides and CD8+ T cell epitopes from these RDP precursors may be influenced by the efficiency of protein translation. Here we address this hypothesis by using the Epstein-Barr virus–encoded nuclear antigen 1 protein (EBNA1), with or without its internal glycine-alanine repeat sequence (EBNA1 and EBNA1ΔGA, respectively), which display distinct differences in translation efficiency. We demonstrate that RDPs constitute a significant proportion of newly synthesized EBNA1 and EBNA1ΔGA and that the levels of RDPs produced by each of these proteins directly correlate with the translation efficiency of either EBNA1 or EBNA1ΔGA. As a consequence, a higher number of major histocompatibility complex–peptide complexes can be detected on the surface of cells expressing EBNA1ΔGA, and these cells are more efficiently recognized by virus-specific cytotoxic T lymphocytes compared to the full-length EBNA1. More importantly, we also demonstrate that the endogenous processing of these CD8+ T cell epitopes is predominantly determined by the rate at which the RDPs are generated rather than the intracellular turnover of these proteins

Closing the gap on nurse retention: a scoping review of implications for undergraduate education

Objectives: Newly qualified nurses leave the profession at a higher rate than any other year of experience. Undergraduate education influences nurse retention following qualification. However, it is unclear if strategies to overcome the common factors associated with intent to leave once qualified are included within undergraduate programmes. A scoping review was conducted to explore the literature within nursing as well as social work undergraduate education to obtain viewpoints from an allied profession with similar staff retention concerns. Design and data sources: Following PRISMA extension guidelines for a scoping review, the research question used to explore the literature was: What is the impact of undergraduate nurse and social work education on retention when newly qualified? Databases searched were BNI, CINAHL complete, Science Direct, PsycINFO, Medline Complete, Academic Search Complete and ERIC. Review method: One author undertook a comprehensive electronic and hand search of relevant research articles. These were then discussed with two authors for inclusion within the review and data extracted for thematic analysis. Results: Limited through search inclusion and quality of research, ten research papers met the criteria for this review. Main themes identified were resilience and commitment, perceived knowledge and confidence, preparation for transition and expectation of supervision. Conclusion: The literature presents the need to strengthen resilience-building within undergraduate education in the transition to newly qualified practitioner, support to cope with the emotional and physical impact of professional practice as well as developing confidence in one’s skills, guidance for career progression, promotion of authentic leadership in work-place mentors and commitment of both the University and health or social organisation to support staff to be healthy and feel valued

Novel approach to the formulation of an Epstein-Barr virus antigen-based nasopharyngeal carcinoma vaccine

Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad- SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs

Novel Approach to the Formulation of an Epstein-Barr Virus Antigen-Based Nasopharyngeal Carcinoma Vaccine ▿

Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad-SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs

Preregistration student nurses' self-reported preparedness for practice before and after the introduction of a capstone subject

Aims and objectives. To assess changes in perceptions of confidence and preparedness for practice of preregistration nursing students before and after the introduction of a capstone subject, and factors associated with perceptions of preparedness. Background. Preregistration nursing student 'readiness' or 'preparedness' for practice has been highlighted in the literature in recent years, along with employer concerns that university graduate nurses are not work ready. Few studies have examined Australian preregistration nursing students' perceptions of preparedness for clinical practice following their final clinical placement or assessed whether preregistration student nurses' perceptions of preparedness change as the result of undertaking a capstone subject. Design. A capstone subject was introduced at a regional northern Australian university in 2013. Perceptions of preparedness were assessed in two different cohorts of final year nursing students; one of which undertook a capstone subject. Methods. Two separate cohorts of third year nursing students were surveyed regarding their perceptions of preparedness for practice at the conclusion of their final 240 hour clinical placement. The 2012 cohort did not experience a capstone subject, whereas the 2013 cohort were the first nursing students to experience the new capstone subject

Persistent summer expansion of the Atlantic Warm Pool during glacial abrupt cold events.

Palaeoclimate records and numerical model simulations indicate that changes in tropical and subtropical sea surface temperatures and in the annual average position of the intertropical convergence zone are linked to high-latitude climate changes on millennial to glacial interglacial timescales. It has recently been suggested that cooling in the high latitudes associated with abrupt climate-change events is evident primarily during the northern hemisphere winter, implying increased seasonality at these times. However, it is unclear whether such a seasonal bias also exists for the low latitudes. Here we analyse the Mg/Ca ratios of surface-dwelling foraminifera to reconstruct sea surface temperatures in the northeastern Gulf of Mexico for the past 300,000 years. We suggest that sea surface temperatures are controlled by the migration of the northern boundary of the Atlantic Warm Pool, and hence the position of the intertropical convergence zone during boreal summer, and are relatively insensitive to winter conditions. Our results suggest that summer Atlantic Warm Pool expansion is primarily affected by glacialinterglacial variability and low-latitude summer insolation. Because a clear signature of rapid climate-change events, such as the Younger Dryas cold event, is lacking in our record, we conclude that high-latitude events seem to influence only the winter Caribbean climate conditions, consistent with the hypothesis of extreme northern-hemisphere seasonality during abrupt cooling events

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease