Autophagy promotes cell survival by maintaining NAD levels.

Autophagy is an essential catabolic process that promotes the clearance of surplus or damaged intracellular components. Loss of autophagy in age-related human pathologies contributes to tissue degeneration through a poorly understood mechanism. Here, we identify an evolutionarily conserved role of autophagy from yeast to humans in the preservation of nicotinamide adenine dinucleotide (NAD) levels, which are critical for cell survival. In respiring mouse fibroblasts with autophagy deficiency, loss of mitochondrial quality control was found to trigger hyperactivation of stress responses mediated by NADases of PARP and Sirtuin families. Uncontrolled depletion of the NAD(H) pool by these enzymes ultimately contributed to mitochondrial membrane depolarization and cell death. Pharmacological and genetic interventions targeting several key elements of this cascade improved the survival of autophagy-deficient yeast, mouse fibroblasts, and human neurons. Our study provides a mechanistic link between autophagy and NAD metabolism and identifies targets for interventions in human diseases associated with autophagic, lysosomal, and mitochondrial dysfunction.

Multimodal mixed reality visualisation for intraoperative surgical guidance.

PURPOSE: In the last decade, there has been a great effort to bring mixed reality (MR) into the operating room to assist surgeons intraoperatively. However, progress towards this goal is still at an early stage. The aim of this paper is to propose a MR visualisation platform which projects multiple imaging modalities to assist intraoperative surgical guidance. METHODOLOGY: In this work, a MR visualisation platform has been developed for the Microsoft HoloLens. The platform contains three visualisation components, namely a 3D organ model, volumetric data, and tissue morphology captured with intraoperative imaging modalities. Furthermore, a set of novel interactive functionalities have been designed including scrolling through volumetric data and adjustment of the virtual objects' transparency. A pilot user study has been conducted to evaluate the usability of the proposed platform in the operating room. The participants were allowed to interact with the visualisation components and test the different functionalities. Each surgeon answered a questionnaire on the usability of the platform and provided their feedback and suggestions. RESULTS: The analysis of the surgeons' scores showed that the 3D model is the most popular MR visualisation component and neurosurgery is the most relevant speciality for this platform. The majority of the surgeons found the proposed visualisation platform intuitive and would use it in their operating rooms for intraoperative surgical guidance. Our platform has several promising potential clinical applications, including vascular neurosurgery. CONCLUSION: The presented pilot study verified the potential of the proposed visualisation platform and its usability in the operating room. Our future work will focus on enhancing the platform by incorporating the surgeons' suggestions and conducting extensive evaluation on a large group of surgeons.