Internal Ribosomal Entry Site-Mediated Translation Is Important for Rhythmic PERIOD1 Expression

The mouse PERIOD1 (mPER1) plays an important role in the maintenance of circadian rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap-independent translation mediated by an internal ribosomal entry site (IRES) in the 5′ untranslated region (UTR). Here, we compared mPer1 IRES activity with other cellular IRESs. We also found critical region in mPer1 5′UTR for heterogeneous nuclear ribonucleoprotein Q (HNRNPQ) binding. Deletion of HNRNPQ binding region markedly decreased IRES activity and disrupted rhythmicity. A mathematical model also suggests that rhythmic IRES-dependent translation is a key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will help define the post-transcriptional regulation of the core clock genes

Thirty years experience with heart valve surgery: isolated aortic valve replacement.

BackgroundThirty years have elapsed since the commencement of open-heart surgery in South Australia. A retrospective study was performed to evaluate mortality and complication rates and to identify factors associated with poor outcomes in all patients who underwent prosthetic aortic valve replacement during this period.MethodsQuestionnaires and personal contact have been used to generate a combined database of pre-operative and post-operative information and long-term follow-up on 1322 patients who underwent isolated prosthetic aortic valve replacement at the Cardio-Thoracic Surgical Unit of the Royal Adelaide Hospital between 1963 and 1992.ResultsComplete survival follow-up data were obtained for 94% (1241) of the patients. The Bjork-Shiley valve was used in 66% (875) of the patients, a Starr-Edwards prosthesis in 31% (412), a St Jude prosthesis in 2% (26), and only 0.7% (9) bioprosthetic valves were inserted. The hospital mortality rate for the 30-year period was 2.9%. Progressively older and less fit patients have undergone surgery in recent years. The long-term survival of patients with aortic stenosis and aortic incompetence was not significantly different. Long-term survival was significantly shorter for patients with higher New York Heart Association (NYHA) functional classifications, and for patients in pre-operative atrial fibrillation. Pre-operative dyspnoea was significantly improved following aortic valve replacement. The rates of postoperative haemorrhagic and embolic complications were low by comparison with other published series.ConclusionsAortic valve replacement can be performed with low hospital mortality and complication rates, and significant symptomatic improvement can be expected. Aortic valve recipients have a favourable prognostic outcome compared with an age- and sex-matched population, and risk factors that determine long-term survival can be identified pre-operatively