A temperature sensitive variant of p53 drives p53-dependent MicroRNA expression without evidence of widespread post-transcriptional gene silencing

The p53 tumour suppressor is a transcription factor that can regulate the expression of numerous ge

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The p53 protein induces stable miRNAs that have the potential to modify subsequent p53 responses

The p53 tumour suppressor is a transcription factor that can increase the expression of mRNAs and microRNAs (miRNAs). HT29-tsp53 cells expressing a temperature sensitive variant of p53 have provided a useful model to rapidly and reversibly control p53 activity. In this model, the majority of p53-responsive mRNAs were upregulated rapidly but they were short-lived leading to rapid decay of the p53 response at the restrictive temperature. Here we used oligonucleotide microarrays and reverse transcriptase PCR to show that p53-induced miRNAs exhibited a distinct temporal pattern of expression. Whereas p53-induced miRNAs like miR-143-3p, miR-145-5p, miR-34a-5p and miR-139-5p increased as fast as mRNAs, they were extremely stable persisting long after p53 induced mRNAs and even their corresponding primary miRNAs had decayed to baseline levels. Three p53-induced mRNAs (MDM2, BTG2 and CDKN1A) are experimentally verified targets of one or more of these specific miRNAs so we hypothesized that the sustained expression of p53-induced miRNAs could be explained by a post-transcriptional feedback loop. Activation of consecutive p53 responses separated by a period of recovery led to the selective attenuation of a subset of p53 regulated mRNAs corresponding to those targeted by one or more of the p53-responsive miRNAs. Our results indicate that the long term expression of p53 responsive miRNAs leads to an excess of miRNAs during the second response and this likely prevents the induction of MDM2, BTG2 and CDKN1A mRNA and/or protein. These observations are likely to have important implications for daily cancer therapies that activate p53 in normal tissues and/or tumour cells

Real-time feature-based image morphing for memory-efficient impostor rendering and animation on GPU

Real-time rendering of large animated crowds consisting of thousands of virtual humans is important for several applications including simulations, games, and interactive walkthroughs but cannot be performed using complex polygonal models at interactive frame rates. For that reason, methods using large numbers of precomputed image-based representations, called impostors, have been proposed. These methods take advantage of existing programmable graphics hardware to compensate for computational expense while maintaining visual fidelity. Thanks to these methods, the number of different virtual humans rendered in real time is no longer restricted by computational power but by texture memory consumed for the variety and discretization of their animations. This work proposes a resource-efficient impostor rendering methodology that employs image morphing techniques to reduce memory consumption while preserving perceptual quality, thus allowing higher diversity or resolution of the rendered crowds. Results of the experiments indicated that the proposed method, in comparison with conventional impostor rendering techniques, can obtain 38 % smoother animations or 87 % better appearance quality by reducing the number of key-frames required for preserving the animation quality via resynthesizing them with up to 92 % similarity on real time