Role of Endothelial Cell Lipoprotein Lipase for Brown Adipose Tissue Lipid and Glucose Handling

Cold-induced activation of brown adipose tissue (BAT) has an important impact on systemic lipoprotein metabolism by accelerating the processing of circulating triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) expressed by adipocytes is translocated via endothelial to the capillary lumen, where LPL acts as the central enzyme for the vascular lipoprotein processing. Based on preliminary data showing that LPL is not only expressed in adipocytes but also in endothelial cells of cold-activated BAT, we aimed to dissect the relevance of endothelial versus adipocyte LPL for lipid and energy metabolism in the context of adaptive thermogenesis. By metabolic studies we found that cold-induced triglyceride uptake into BAT, lipoprotein disposal, glucose uptake and adaptive thermogenesis were not impaired in mice lacking Lpl exclusively in endothelial cells. This finding may be explained by a compensatory upregulation in the expression of adipocyte-derived Lpl and endothelial lipase (Lipg)

ESCAPADE: Mars' first smallsat science mission will unveil its unique hybrid magnetosphere

International audienceMulti-spacecraft missions after 2000 (Cluster II, THEMIS, Van Allen Probes, and MMS) have revolutionized our understanding of the causes, patterns and variability of a wide array of plasma phenomena in the terrestrial magnetospheric environment. ESCAPADE is a twin-spacecraft Mars mission that will similarly revolutionize our understanding of how solar wind momentum and energy flows throughout Mars' magnetosphere to drive ion and sputtering escape, two processes which have helped shape Mars' climate evolution over solar system history. ESCAPADE will measure magnetic field strength and topology, ion plasma distributions, as well as suprathermal electron flows and thermal electron and ion densities, from elliptical, 65° inclination ~160 km x ~7000 km orbits. ESCAPADE are small spacecraft (<125 kg dry mass), following ballistic Hohmann transfers to Mars. ESCAPADE's strategically-designed 1-year, 2-part scientific campaign of temporally and spatially-separated multipoint measurements in different regions of Mars' diverse plasma environment, will allow the cause-and-effect of solar wind control of ion and sputtering escape to be unraveled for the first time. ESCAPADE is currently in Phase C with launch scheduled for summer or fall 2024 as an as-yet-unscheduled rideshare. We will report on science goals, engineering and mission design challenges, and provide a status update

ESCAPADE: coordinated multipoint observations of the Martian magnetosphere

International audienceIn the last 20 years, multi-spacecraft missions like Cluster II, THEMIS, Van Allen Probes, and MMS have revolutionized our understanding of the causes, patterns, and variability of a wide array of space plasma phenomena in the Earth's magnetospheric environment. ESCAPADE is a twin-spacecraft Mars mission that will similarly revolutionize our understanding of how solar wind momentum and energy flows throughout Mars' magnetosphere to drive ion and sputtering escape, two processes which have helped shape Mars' climate evolution over solar system history.ESCAPADE will measure magnetic field strength and topology, ion plasma distributions (separated into light and heavy masses), as well as suprathermal electron flows and thermal electron and ion densities from elliptical, 200 km x ~7000 km orbits. ESCAPADE consists of two small spacecraft (<90 kg), traveling to Mars via solar electric propulsion as a rideshare with the Psyche metal-asteroid mission in August 2022, matching Mars' heliocentric orbit until capture and spiral-down to science orbits. ESCAPADE's strategically-designed, 1-year, 2-part scientific campaign of temporally and spatially-separated multipoint measurements in different parts of Mars' diverse plasma environment will for the first time unravel the cause-and-effect of solar wind control of ion and sputtering escape. Figure 1 shows ESCAPADE's orbits within a hybrid simulation of the solar wind interaction with Mars, where the color scale represents ion velocity, blue lines are magnetic field, while white lines are sample proton trajectories and spacecraft orbits.ESCAPADE has been selected for Phase A/B study by NASA as one of three finalists in the SIMPLEX-II program. We will report on ESCAPADE's science goals, objectives, and requirements, as well as provide a status update

ESCAPADE: unveiling Mars' hybrid magnetosphere with Class D Smallsats

International audienceMulti-spacecraft missions after 2000 (Cluster II, THEMIS, Van Allen Probes, and MMS) have revolutionized our understanding of the causes, patterns and variability of a wide array of plasma phenomena in the terrestrial magnetospheric environment. ESCAPADE is a twin-spacecraft Mars mission concept that will similarly revolutionize our understanding of how solar wind momentum and energy flows throughout Mars' magnetosphere to drive ion and sputtering escape, two processes which have helped shape Mars' climate evolution over solar system history.ESCAPADE will measure magnetic field strength and topology, ion plasma distributions as well as suprathermal electron flows and thermal electron and ion densities, from precessing elliptical 150 x ~8500 km orbits. ESCAPADE are small spacecraft (<125 kg dry mass), following ballistic Hohmann transfers to Mars. Our strategically-designed 1-year, 2-part scientific campaign of temporally and spatially-separated multipoint measurements in different regions of Mars' diverse plasma environment, will allow the cause-and-effect of solar wind control of ion and sputtering escape to be unraveled for the first time.ESCAPADE is a Category 3 Class D Tailored small satellite mission selected under the SIMPLEX program and funded by NASA's Heliophysics division, with a PI-managed cost cap of <$60 million. Designing, developing, and operating two spacecraft at Mars for this budget necessarily entails a combination of high heritage instrumentation, streamlined processes, a higher risk tolerance than is common for many scientific missions, and an innovative approach to rideshare. ESCAPADE is due to launch on a VADR (Venture-class Acquisition of Dedicated Rideshare)-procured vehicle in mid to late 2024. This presentation will focus on lessons learned by NASA and the ESCAPADE team that may be applied to future low-cost deep space missions

ESCAPADE: unveiling Mars' hybrid magnetosphere with Class D Smallsats

International audienceMulti-spacecraft missions after 2000 (Cluster II, THEMIS, Van Allen Probes, and MMS) have revolutionized our understanding of the causes, patterns and variability of a wide array of plasma phenomena in the terrestrial magnetospheric environment. ESCAPADE is a twin-spacecraft Mars mission concept that will similarly revolutionize our understanding of how solar wind momentum and energy flows throughout Mars' magnetosphere to drive ion and sputtering escape, two processes which have helped shape Mars' climate evolution over solar system history.ESCAPADE will measure magnetic field strength and topology, ion plasma distributions as well as suprathermal electron flows and thermal electron and ion densities, from precessing elliptical 150 x ~8500 km orbits. ESCAPADE are small spacecraft (<125 kg dry mass), following ballistic Hohmann transfers to Mars. Our strategically-designed 1-year, 2-part scientific campaign of temporally and spatially-separated multipoint measurements in different regions of Mars' diverse plasma environment, will allow the cause-and-effect of solar wind control of ion and sputtering escape to be unraveled for the first time.ESCAPADE is a Category 3 Class D Tailored small satellite mission selected under the SIMPLEX program and funded by NASA's Heliophysics division, with a PI-managed cost cap of <$60 million. Designing, developing, and operating two spacecraft at Mars for this budget necessarily entails a combination of high heritage instrumentation, streamlined processes, a higher risk tolerance than is common for many scientific missions, and an innovative approach to rideshare. ESCAPADE is due to launch on a VADR (Venture-class Acquisition of Dedicated Rideshare)-procured vehicle in mid to late 2024. This presentation will focus on lessons learned by NASA and the ESCAPADE team that may be applied to future low-cost deep space missions

ESCAPADE: A Twin-Spacecraft Simplex Mission to Unveil Mars' Unique Hybrid Magnetosphere

International audienceCan you really send two capable scientific spacecraft to Mars for <$80 million? ESCAPADE, launching in 2024, will test this hypothesis

ESCAPADE: A Twin-Spacecraft Simplex Mission to Unveil Mars' Unique Hybrid Magnetosphere

International audienceCan you really send two capable scientific spacecraft to Mars for <$80 million? ESCAPADE, launching in 2024, will test this hypothesis

PITX2 deficiency leads to atrial mitochondrial dysfunction

Background. Reduced left atrial PITX2 is associated with atrial cardiomyopathy and atrial fibrillation. PITX2 is restricted to left atrial cardiomyocytes in the adult heart. The links between PITX2 deficiency, atrial cardiomyopathy and atrial fibrillation are not fully understood. Methods. To identify mechanisms linking PITX2 deficiency to atrial fibrillation, we generated and characterized PITX2-deficient human atrial cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) and their controls. Results. PITX2-deficient hiPSC-derived atrial cardiomyocytes showed shorter and disorganised sarcomeres and increased mononucleation. Electron microscopy found an increased number of smaller mitochondria compared to the control. Mitochondrial protein expression was altered in PITX2-deficient hiPSC-derived atrial cardiomyocytes. Single-nuclear RNA-sequencing found differences in cellular respiration pathways and differentially expressed mitochondrial and ion channel genes in PITX2-deficient hiPSC-derived atrial cardiomyocytes. PITX2 repression in hiPSC-derived atrial cardiomyocytes replicated dysregulation of cellular respiration. Mitochondrial respiration was shifted to increased glycolysis in PITX2-deficient hiPSC-derived atrial cardiomyocytes. PITX2-deficient human hiPSC-derived atrial cardiomyocytes showed higher spontaneous beating rates. Action potential duration was more variable with an overall prolongation of early repolarization, consistent with metabolic defects. Gene expression analyses confirmed changes in mitochondrial genes in left atria from 42 patients with atrial fibrillation compared to 43 patients in sinus rhythm. Dysregulation of left atrial mitochondrial (COX7C) and metabolic (FOXO1) genes was associated with PITX2 expression in human left atria. Conclusions. In summary, PITX2 deficiency causes mitochondrial dysfunction and a metabolic shift to glycolysis in human atrial cardiomyocytes. PITX2-dependent metabolic changes can contribute to the structural and functional defects found in PITX2-deficient atria.<br/