Angiocrine Wnt signaling controls liver growth and metabolic maturation in mice
HEPATOLOGY
Authors: Leibing, Thomas; Geraud, Cyrill; Augustin, Iris; Boutros, Michael; Augustin, Hellmut G.; Okun, Juergen G.; Langhans, Claus-Dieter; Zierow, Johanna; Wohlfeil, Sebastian A.; Olsavszky, Victor; Schledzewski, Kai; Goerdt, Sergij; Koch, Philipp-Sebastian
Abstract
Postnatal liver development is characterized by hepatocyte growth, proliferation, and functional maturation. Notably, canonical Wnt signaling in hepatocytes has been identified as an important regulator of final adult liver size and metabolic liver zonation. The cellular origin of Wnt ligands responsible for homeostatic liver/body weight ratio (LW/BW) remained unclear, which was also attributable to a lack of suitable endothelial Cre driver mice. To comprehensively analyze the effects of hepatic angiocrine Wnt signaling on liver development and metabolic functions, we used endothelial subtype-specific Stab2-Cre driver mice to delete Wls from hepatic endothelial cells (HECs). The resultant Stab2-Cre(tg/wt);Wls(fl/fl) (Wls-HECKO) mice were viable, but showed a significantly reduced LW/BW. Specifically, ablation of angiocrine Wnt signaling impaired metabolic zonation in the liver, as shown by loss of pericentral, -catenin-dependent target genes such as glutamine synthase (Glul), RhBg, Axin2, and cytochrome P450 2E1, as well as by extended expression of periportal genes such as arginase 1. Furthermore, endothelial subtype-specific expression of a c-terminally YFP-tagged Wls fusion protein in Wls-HECKO mice (Stab2-Cre(tg/wt);Wls(fl/fl);Rosa26:Wls-YFPfl/wt [Wls-rescue]) restored metabolic liver zonation. Interestingly, lipid metabolism was altered in Wls-HECKO mice exhibiting significantly reduced plasma cholesterol levels, while maintaining normal plasma triglyceride and blood glucose concentrations. On the contrary, zonal expression of Endomucin, LYVE1, and other markers of HEC heterogeneity were not altered in Wls-HECKO livers. Conclusion: Angiocrine Wnt signaling controls liver growth as well as development of metabolic liver zonation in mice, whereas intrahepatic HEC zonation is not affected. (Hepatology 2017).
Evaluation of Typhoon Waves Simulated by WaveWatch-III Model in Shallow Waters Around Zhoushan Islands
JOURNAL OF OCEAN UNIVERSITY OF CHINA
Authors: Sheng, Yexin; Shao, Weizeng; Li, Shuiqing; Zhang, Yuming; Yang, Hongwei; Zuo, Juncheng
Abstract
In this study, we simulated typhoon waves in the shallow waters around the Zhoushan Islands using the WaveWatch-III (WW3) model version 5.16, the latest version released by the National Oceanic and Atmospheric Administration. Specifically, we used in-situ measurements to evaluate the performance of seven packages of input/dissipation source terms in the WW3 model. We forced the WW3 model by wind fields derived from a combination of the parametric Holland model and high-resolution European Center for Medium-Range Weather Forecasts (ECMWF) wind data in a 0.125 degrees grid, herein called H-E winds. We trained the H-E winds by fitting a shape parameter B to buoy-measured observations, which resulted in a smallest root mean square error (RMSE) of 3 m s(-1) for B, when treated as a constant 0.4. Then, we applied the seven input/dissipation terms of WW3, labelled ST1, ST2, ST2+STAB2, ST3, ST3+STAB3, ST4, and ST6, to simulate the significant wave height (SWH) up to 5 m during typhoons Fungwong and Chan-hom around the Zhoushan Islands. We then compared the SWHs of the simulated waves with those measured by the in-situ buoys. The results indicate that the simulation using ST2 performs best with an RMSE of 0.79 m for typhoon Fung-wong and an RMSE of 1.12 m for typhoon Chan-hom. Interestingly, we found the simulated SWH results to be relatively higher than those of the observations in the area between Hangzhou Bay and the Zhoushan Islands. This behavior is worthy of further investigation in the future.