Accelerated apoptotic death and <i>in vivo</i> turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2

The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk−/−) and corresponding wild-type mice (msk+/+). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk−/− and msk+/+ mice, but reticulocyte count was significantly increased in msk−/− mice. Cell membrane PS exposure was similar in untreated msk−/− and msk+/+ erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk−/− erythrocytes than in msk+/+ erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk−/− erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk−/− mice. The spleens from msk−/− mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk+/+ mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice

The Environmental Design Space: Modeling and Performance Updates

Presented at AIAA SciTech Forum 2021The Environmental Design Space (EDS) is a modeling and simulation environment devised for the design and evaluation of subsonic aircraft. One of the main features that sets it apart from other similar frameworks is its capability to perform aircraft performance and sizing, exhaust emissions, and noise prediction. These three elements are seamlessly executed due to the integration of multiple industry-standard tools. Since its conception in 2008, EDS has been used to support multiple research entities and projects for the evaluation of current and future aircraft concepts and technologies. Its results and assumptions have been calibrated and revised through the years in conjunction with panels of experts in the field. Therefore, it has undergone continuous development that has increased its capability, allowing it to model not only traditional tube-and-wing aircraft, but also unconventional configurations. At the writing of this paper, its capabilities extend beyond standard single and dual spool engines to include geared fans, ultra high bypass turbofans, open rotors, and partially turboelectric propulsion architectures. This paper presents an overview of how EDS has been used to support major research efforts. Then, an approach to develop and calibrate engine and aircraft models to match existing open-source data is presented. Finally, a summary of available advanced engine and aircraft architectures is shown. The results demonstrate EDS capability to create models that closely match existing systems performance, and its flexibility to keep supporting future aircraft design and technology development studies