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c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of the TGF-β Type II Receptor
Zuo, W.,Huang, F.,Chiang, Y.,Li, M.,Du, J.,Ding, Y.,Zhang, T.,Lee, H.,Jeong, L.,Chen, Y.,Deng, H.,Feng, X.H.,Luo, S.,Gao, C.,Chen, Y.G. Cell Press 2013 Molecular cell Vol.49 No.3
Transforming growth factor β (TGF-β) is a potent antiproliferative factor in multiple types of cells. Deregulation of TGF-β signaling is associated with the development of many cancers, including leukemia, though the molecular mechanisms are largely unclear. Here, we show that Casitas B-lineage lymphoma (c-Cbl), a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-β signaling by neddylating and stabilizing the type II receptor (TβRII). Knockout of c-Cbl decreases the TβRII protein level and desensitizes hematopoietic stem or progenitor cells to TGF-β stimulation, while c-Cbl overexpression stabilizes TβRII and sensitizes leukemia cells to TGF-β. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TβRII at Lys556 and Lys567. Neddylation of TβRII promotes its endocytosis to EEA1-positive early endosomes while preventing its endocytosis to caveolin-positive compartments, therefore inhibiting TβRII ubiquitination and degradation. We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant TβRII neddylation and leukemia development.
Development of a Dynamic System Simulating Pig Gastric Digestion
Chiang, C.-C.,Croom, J.,Chuang, S.-T.,Chiou, P.W.S.,Yu, B. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.10
The objective of this study was to develop a model for simulating gastric digestion in the pig. The model was constructed to include the chemical and physical changes associated with gastric digestion such as enzyme release, digestion product removal and gastric emptying. Digesta was collected from the stomach cannula of pigs to establish system parameters and to document the ability of the model to simulate gastric digestion. The results showed that the average pH of gastric digesta increased significantly from 2.47 to 4.97 after feed consumption and then decreased 140 min postprandial. The model described the decrease in pH within the pigs' stomach as $pH_t=5.182e^{-0.0014t}$, where t represents the postprandial time in minutes. The cumulative distribution function of liquid digesta was $V_t=64.509e^{0.0109t}$. The average pepsin activity in the liquid digesta was 317Anson units/mL. There was significant gastric emptying 220 min after feed consumption. The cybernetic dynamic system of gastric digestion was set according to the above data in order to compare with in vivo changes. The time course of crude protein digestion predicted by the model was highly correlated with observed in vivo digestion (r = 0.97; p = 0.0001), Model prediction for protein digestion was higher than that observed for a traditional static in vitro method (r = 0.89; p = 0.0001).
E-beam lithography and electrodeposition fabrication of thick nanostructured devices
Lo, T N,Chen, Y T,Chiu, C W,Liu, C J,Wu, S R,Lin, I K,Su, C I,Chang, W D,Hwu, Y,Shew, B Y,Chiang, C C,Je, J H,Margaritondo, G Institute of Physics [etc.] 2007 Journal of Physics. D, Applied Physics Vol.40 No.10
<P>A nanofabrication approach based on advanced e-beam lithography and electrodeposition successfully produced high-resolution (≈40 nm line width) metal structures with high aspect ratio (>12) and high density. The combination of these characteristics is essential for hard-x-ray optical components such as zone plates, for x-ray lithography masks and for other devices.</P>