ALBERT

Description: Cardiac hypertrophy, an adaptive process that responds to increased wall stress, is characterized by the enlargement of cardiomyocytes and structural remodeling. It is stimulated by various growth signals, of which the mTORC1 pathway is a well-recognized source. Here, we show that loss of Flcn , a novel AMPK–mTOR interacting molecule, causes severe cardiac hypertrophy with deregulated energy homeostasis leading to dilated cardiomyopathy in mice. We found that mTORC1 activity was upregulated in Flcn -deficient hearts, and that rapamycin treatment significantly reduced heart mass and ameliorated cardiac dysfunction. Phospho-AMP-activated protein kinase (AMPK)-alpha (T172) was reduced in Flcn -deficient hearts and nonresponsive to various stimulations including metformin and AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide). ATP levels were elevated and mitochondrial function was increased in Flcn -deficient hearts, suggesting that excess energy resulting from up-regulated mitochondrial metabolism under Flcn deficiency might attenuate AMPK activation. Expression of Ppargc1a, a central molecule for mitochondrial metabolism, was increased in Flcn -deficient hearts and indeed, inactivation of Ppargc1a in Flcn -deficient hearts significantly reduced heart mass and prolonged survival. Ppargc1a inactivation restored phospho-AMPK-alpha levels and suppressed mTORC1 activity in Flcn -deficient hearts, suggesting that up-regulated Ppargc1a confers increased mitochondrial metabolism and excess energy, leading to inactivation of AMPK and activation of mTORC1. Rapamycin treatment did not affect the heart size of Flcn/Ppargc1a doubly inactivated hearts, further supporting the idea that Ppargc1a is the critical element leading to deregulation of the AMPK–mTOR-axis and resulting in cardiac hypertrophy under Flcn deficiency. These data support an important role for Flcn in cardiac homeostasis in the murine model.

Description: Addibischoffite (IMA 2015-006), Ca 2 Al 6 Al 6 O 20 , is a new calcium aluminate mineral that occurs with hibonite, perovskite, kushiroite, Ti-kushiroite, spinel, melilite, anorthite, and FeNi-metal in the core of a Ca-Al-rich inclusion (CAI) in the Acfer 214 CH3 carbonaceous chondrite. The mean chemical composition of type addibischoffite measured by electron probe microanalysis is (wt%) Al 2 O 3 44.63, CaO 15.36, SiO 2 14.62, V 2 O 3 10.64, MgO 9.13, Ti 2 O 3 4.70, FeO 0.46, total 99.55, giving rise to an empirical formula of (Ca 2.00 )(Al 2.55 Mg 1.73 V 1. 3+ 08 Ti 3+ 0.50 Ca 0.09 Fe 2+ 0.05 ) 6.01 (Al 4.14 Si 1.86 )O 20 . The general formula is Ca 2 (Al,Mg,V,Ti) 6 (Al,Si) 6 O 20 . The end-member formula is Ca 2 Al 6 Al 6 O 20 . Addibischoffite has the P aenigmatite structure with a = 10.367 Å, b = 10.756 Å, c = 8.895 Å, α = 106.0°, β = 96.0°, = 124.7°, V = 739.7 Å 3 , and Z = 2, as revealed by electron backscatter diffraction. The calculated density using the measured composition is 3.41 g/cm 3 . Addibischoffite is a new member of the warkite (Ca 2 Sc 6 Al 6 O 20 ) group and a new refractory phase formed in the solar nebula, most likely as a result of crystallization from an 16 O-rich Ca, Al-rich melt under high-temperature (~1575 °C) and low-pressure (~10 –4 to 10 –5 bar) conditions in the CAI-forming region near the protosun, providing a new puzzle piece toward understanding the details of nebular processes. The name is in honor of Addi Bischoff, cosmochemist at University of Münster, Germany, for his many contributions to research on mineralogy of carbonaceous chondrites, including CAIs in CH chondrites.