ABSTRACT
The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1ß (IL-1ß) and IL-18. We found here that activation of the NLRP3 inflammasome was restricted to interphase of the cell cycle by NEK7, a serine-threonine kinase previously linked to mitosis. Activation of the NLRP3 inflammasome required NEK7, which bound to the leucine-rich repeat domain of NLRP3 in a kinase-independent manner downstream of the induction of mitochondrial reactive oxygen species (ROS). This interaction was necessary for the formation of a complex containing NLRP3 and the adaptor ASC, oligomerization of ASC and activation of caspase-1. NEK7 promoted the NLRP3-dependent cellular inflammatory response to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune encephalitis in mice. Our findings suggest that NEK7 serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division.
Subject(s)
Carrier Proteins/immunology , Macrophages/immunology , Mitosis/immunology , Protein Serine-Threonine Kinases/immunology , Animals , Apoptosis , Apoptosis Regulatory Proteins , CARD Signaling Adaptor Proteins , Carrier Proteins/genetics , Caspase 1 , Chromatography, Gel , Colony-Forming Units Assay , Cytokines , Cytoskeletal Proteins , Dendritic Cells , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Flow Cytometry , HEK293 Cells , Humans , Immunoprecipitation , In Vitro Techniques , Inflammasomes/genetics , Inflammasomes/immunology , Macrophages, Peritoneal/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/metabolism , Monocytes , NIMA-Related Kinases , NLR Family, Pyrin Domain-Containing 3 Protein , Protein Serine-Threonine Kinases/genetics , Reactive Oxygen Species , Spinal Cord/immunologyABSTRACT
Integrating anatomic nomenclature with geometric anatomic data via a web interface and providing illustration and visualization tools presents numerous challenges. We have developed a library of anatomic models and methods for navigating anatomic nomenclature. Based on the library and tools, we have developed a simple, yet powerful, open web-based tool that uses tree navigation and selection for assembling and downloading self-documenting anatomic scenes in Virtual Reality Modeling Language.
Subject(s)
Internet , Models, Anatomic , Terminology as Topic , Computer Simulation , Humans , Information Storage and Retrieval , Programming Languages , United States , User-Computer InterfaceABSTRACT
Creating a library of binary segmentation mask sequences for the abdominal anatomy hierarchy of SNOMED and developing a quick, flexible automatic method for generating iso-surface models from these named structure masks has been a primary goal in our research. This paper describes our development of a clear path for computing visualizations of arbitrary groups of organs from these masks (typically generated from Visible Human data). One use of these methods is teaching the anatomy of various organ systems in the human body using virtual reality environments.
Subject(s)
Computer Simulation , Diagnostic Imaging/instrumentation , Models, Anatomic , Human Body , Imaging, Three-Dimensional , Libraries, Medical , Systematized Nomenclature of Medicine , United StatesABSTRACT
BACKGROUND: Understanding the spatial relationships among the liver segments, and intrahepatic portal and hepatic veins is essential for surgical treatment of liver diseases. Teleimmersive virtual reality enables improved visualization over conventional media because it supports stereo vision, viewer-centered perspective, large angles of view, and interactivity with remote locations. We report a successful pilot study teaching hepatic surgical principles using teleimmersion. METHODS: We developed a teleimmersive environment for teaching with biomedical models including virtual models of the liver segments and portal and hepatic veins. Using the environment, 1 instructor gave a workshop to 6 senior general surgery residents at 2 physical locations. A 24-question (36-point) examination was administered before and after the workshop. RESULTS: The workshop produced significant improvements in the mean test scores between the pretests and posttests (17.67 to 23.67, P <.02). We found no differences between residents who were with the instructor and those at the remote location. Six-month delayed testing demonstrated complete retention of new knowledge. CONCLUSIONS: The teleimmersive environment enabled surgeons to overcome some of the barriers to teaching complex surgical anatomic principles. Using teleimmersive environments, surgical educators and trainees can interact from locations worldwide using virtual anatomic information to achieve their educational goals.