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Liu, Haidan,Hwang, Joonsung,Li, Wei,Choi, Tae Woong,Liu, Kangdong,Huang, Zunnan,Jang, Jae-Hyuk,Thimmegowda, N.R.,Lee, Ki Won,Ryoo, In-Ja,Ahn, Jong-Seog,Bode, Ann M.,Zhou, Xinmin,Yang, Yifeng,Erikson, American Association for Cancer Research 2014 CANCER PREVENTION RESEARCH Vol.7 No.1
<P>Mitogen- and stress-activated kinase 1 (MSK1) is a nuclear serine/threonine protein kinase that acts downstream of both extracellular signal-regulated kinases and p38 mitogen-activated protein kinase in response to stress or mitogenic extracellular stimuli. Increasing evidence has shown that MSK1 is closely associated with malignant transformation and cancer development. MSK1 should be an effective target for cancer chemoprevention and chemotherapy. However, very few MSK1 inhibitors, especially natural compounds, have been reported. We used virtual screening of a natural products database and the active conformation of the C-terminal kinase domain of MSK1 (PDB id 3KN) as the receptor structure to identify chrysin and its derivative, compound 69407, as inhibitors of MSK1. Compared with chrysin, compound 69407 more strongly inhibited proliferation and 12-<I>O</I>-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells with lower cytotoxicity. Western blot data demonstrated that compound 69407 suppressed phosphorylation of the MSK1 downstream effector histone H3 in intact cells. Knocking down the expression of MSK1 effectively reduced the sensitivity of JB6 P+ cells to compound 69407. Moreover, topical treatment with compound 69407 before TPA application significantly reduced papilloma development in terms of number and size in a two-stage mouse skin carcinogenesis model. The reduction in papilloma development was accompanied by the inhibition of histone H3 phosphorylation at Ser10 in tumors extracted from mouse skin. The results indicated that compound 69407 exerts inhibitory effects on skin tumorigenesis by directly binding with MSK1 and attenuates the MSK1/histone H3 signaling pathway, which makes it an ideal chemopreventive agent against skin cancer. <I>Cancer Prev Res; 7(1); 74–85. ©2013 AACR</I>.</P>
Production of Useful Secondary Metabolites in Plants : Functional Genomics Approaches
Liu, Jang Ryol,Choi, Dong-Woong,Chung, Hwa-Jee,Woo, Sung-Sick 한국식물학회 2002 Journal of Plant Biology Vol.45 No.1
The paradigm of biological research has been changed by recent developments in genomics, high-throughput biology, and bioinformatics. Conventional biology often was based on empirical, labor-intensive, and time-consuming methods. In the new paradigm, biological research e is driven by a holistic approach on the basis of rational, automatic, and high-throughput methods. New functional compounds can be discovered by using high-throughput screening systems. Secondary metabolite pathways and the genes involved in those pathways are then determined by studying functional genomics in conjunction with the data-mining tools of bioinformatics. In addition, these advances in metabolic engineering enable researchers to confer new secondary metabolic pathways to crops by transferring three to five, or more, heterologous genes taken from various other species. In the future, engineering for the production of useful compounds will be designed by a set of software tools that allows the user to specify a cell's genes, proteins, and other molecules, as well as their individual interactions.
Jang R. Liu,김석원,유욱준,정순천,Sung Hee Ban,Hwa-Jee Chung,Suk Min Ko 한국생물공학회 2007 Biotechnology and Bioprocess Engineering Vol.12 No.6
When whole cell extracts are subjected to proton nuclear magnetic resonance spectroscopy (1H NMR), metabolite profiles are generated that contain overlapping signals of the majority of compounds within the extract. In order to determine whether pattern recognition based on the metabolite profiles of higher plants is able to genetically discriminate between plants, we analyzed leaf samples of eight cultivars of Catharanthus roseus by 1H NMR. Hierarchical dendrograms, based on the principal component analysis of the 1H NMR total, aliphatic, carbohydrate, and aromatic region data, revealed possible relationships between the cultivars. The dendrogram based on the aromatic region data was in general agreement with the genetic relationships determined by conventional DNA fingerprinting methods. Secologanin and polyphenols were assigned to the signals of the 1H NMR spectra, and contributed most profoundly to the discrimination between cultivars. The overall results indicate that the genetic relationships between C. roseus cultivars are reflected in the differences of the aromatic compounds in the leaves.
A miR-155–Peli1–c-Rel pathway controls the generation and function of T follicular helper cells
Liu, Wen-Hsien,Kang, Seung Goo,Huang, Zhe,Wu, Cheng-Jang,Jin, Hyun Yong,Maine, Christian J.,Liu, Yi,Shepherd, Jovan,Sabouri-Ghomi, Mohsen,Gonzalez-Martin, Alicia,Xu, Shunbin,Hoffmann, Alexander,Zheng, The Rockefeller University Press 2016 The Journal of experimental medicine Vol.213 No.9
<P>MicroRNA (miRNA) deficiency impairs the generation of T follicular helper (Tfh) cells, but the contribution of individual miRNAs to this phenotype remains poorly understood. In this study, we performed deep sequencing analysis of miRNAs expressed in Tfh cells and identified a five-miRNA signature. Analyses of mutant mice deficient of these miRNAs revealed that miR-22 and miR-183/96/182 are dispensable, but miR-155 is essential for the generation and function of Tfh cells. miR-155 deficiency led to decreased proliferation specifically at the late stage of Tfh cell differentiation and reduced CD40 ligand (CD40L) expression on antigen-specific CD4<SUP>+</SUP> T cells. Mechanistically, miR-155 repressed the expression of Peli1, a ubiquitin ligase that promotes the degradation of the NF-κB family transcription factor c-Rel, which controls cellular proliferation and CD40L expression. Therefore, our study identifies a novel miR-155–Peli1–c-Rel pathway that specifically regulates Tfh cell generation and function.</P>
Power Converters Based Advanced Experimental Platform for Integrated Study of Power and Controls
Liu, Wenxin,Kim, Jang-Mok,Wang, Cheng,Im, Won-Sang,Liu, Liming,Xu, Hao IEEE 2018 IEEE TRANSACTIONS ON INDUSTRIAL INFORMATICS - Vol.14 No.11
<P>With increasing interest in smart grid and renewable energy, significant investments have been allocated to promote related studies. Since there is a wide spectrum of topics to study, it is necessary to have an advanced experimental platform that can accommodate both system- and component-level studies, both hardware and algorithm designs, and both teaching and research. Unfortunately, such experimental platform is not commercially available. In this paper, an advanced power electronics based experimental platform is introduced. The system is consisted of one OPAL-RT real-time simulator, two one-bus microgrid testbeds, and two modular multilevel converters. The subsystems can form a multiple-bus microgrid testbed if connected through emulated power lines. The system can provide real-time simulation, controller hardware-in-the-loop (HIL) simulation, and power HIL simulation for power systems study. Various converter topologies can be configured with the modular converters for power electronics study. Both real-time simulator and DSP control boards can be used to implement advanced control algorithms. The designs and experiences shared in the paper will benefit many researchers that are in need of such system and promote power and energy related studies.</P>