The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information)

Feasibility Study For A Spaceborne Ozone/Aerosol Lidar System

Because ozone provides a shield against harmful ultraviolet radiation, determines the temperature profile in the stratosphere, plays important roles in tropospheric chemistry and climate, and is a health risk near the surface, changes in natural ozone layers at different altitudes and their global impact are being intensively researched. Global ozone coverage is currently provided by passive optical and microwave satellite sensors that cannot deliver high spatial resolution measurements and have particular limitations in the troposphere. Vertical profiling DIfferential Absorption Lidars (DIAL) have shown excellent range-resolved capabilities, but these systems have been large, inefficient, and have required continuous technical attention for long term operations. Recently, successful, autonomous DIAL measurements have been performed from a high-altitude aircraft (LASE - Lidar Atmospheric Sensing Experiment), and a space-qualified aerosol lidar system (LITE - Laser In-space Technology Experiment) has performed well on Shuttle. Based on the above successes, NASA and the Canadian Space Agency are jointly studying the feasibility of developing ORACLE (Ozone Research with Advanced Cooperative Lidar Experiments), an autonomously operated, compact DIAL instrument to be placed in orbit using a Pegasus class launch vehicle

Tumor Necrosis Factor-α-mediated Regulation of the Inositol 1,4,5-Trisphosphate Receptor Promoter*

Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, has been implicated as a central mediator in multiple homeostatic and pathologic processes. Signaling cascades downstream of its cellular cognate receptors, as well as the resultant transcriptional responses have received intense interest in regards to how such signals impact cellular physiology. Notably, TNF-α was shown to potentiate neuronal Ca2+ signaling by enhancing type-1 inositol 1,4,5-trisphosphate receptor (IP3R) steady-state mRNA levels. In the present study, we sought to determine the promoter region ultimately responsive to TNF-α exposure. We report that a sequence encompassing a specificity protein 1 (SP-1) binding site is necessary for TNF-α regulation. Electrophoretic mobility shift analysis demonstrated specific binding to this sequence, while site-directed mutagenesis of this site abrogated both JNK-mediated regulation as well as transcription factor binding. Expression of a dominant-negative SP-1 eliminated both the enhanced promoter activity and the elevated IP3R-mediated Ca2+ signals observed with TNF-α exposure. Overall, these data delineate a key pathway by which TNF-α in a neuronal environment modulates IP3R expression and intracellular Ca2+ homeostasis