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141.
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143.
Dar‐Bin Shieh Rui‐You Li Jiuan‐Miaw Liao Gin‐Den Chen Ying‐Ming Liou 《Journal of cellular physiology》2010,223(2):423-434
This study was performed to define the roles of actin‐binding proteins in the regulation of actin filament assembly associated with cellular signal transduction pathways in stromal cell proliferation. Genistein, a tyrosine protein kinase inhibitor, decreased the intracellular Ca2+ and attenuated cell proliferation and DNA synthesis through the β‐catenin and cyclin D1 pathway in human umbilical CD105‐positive cells. Immunoprecipitation studies using anti‐β‐actin antibody revealed that several actin‐binding proteins implicated in cells include formin‐2 (FMN‐2), caldesmon (CaD), tropomyosin (Tm), and profilin. Protein levels of these proteins in whole cell lysates were not significantly changed by genistein. Three Tm isoforms, Tm‐1, Tm‐2, and Tm‐4, were found to be present in cells. Genistein caused a reduction in levels of mRNAs coding for Tm‐1 and Tm‐4, but had no significant effect on Tm‐2 mRNA levels. Immunofluorescence confocal scanning microscopy indicated that changes in the subcellular distribution of Tm and CaD, in which the diffuse cytosolic staining was shifted to show colocalization with actin stress fibers. In contrast, genistein‐induced accumulation of FMN‐2 and profilin in the peri‐nuclear area. Silencing of FMN‐2 by small interfering RNA resulted in increases of intracellular Ca2+ and rendered genistein resistance in decreasing intracellular Ca2+ in cells. These results provide the novel findings that genistein acts by modulating the cellular distribution of actin‐binding proteins in association with alterations of cellular signal transduction pathways in human stromal cell proliferation. J. Cell. Physiol. 223: 423–434, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
144.
Li-Ying Liou Kevin B. Walsh Arineh R. Vartanian Daniel Beltran-Valero de Bernabe Megan Welch Kevin P. Campbell Michael B. A. Oldstone Stefan Kunz 《PloS one》2010,5(3)
Background
Alpha-dystroglycan (α-DG) is a cell surface receptor providing a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. During its biosynthesis, α-DG undergoes specific and unusual O-glycosylation crucial for its function as a high-affinity cellular receptor for ECM proteins.Methodology/Principal Findings
We report that expression of functionally glycosylated α-DG during thymic development is tightly regulated in developing T cells and largely confined to CD4−CD8− double negative (DN) thymocytes. Ablation of DG in T cells had no effect on proliferation, migration or effector function but did reduce the size of the thymus due to a significant loss in absolute numbers of thymocytes. While numbers of DN thymocytes appeared normal, a marked reduction in CD4+CD8+ double positive (DP) thymocytes occurred. In the periphery mature naïve T cells deficient in DG showed both normal proliferation in response to allogeneic cells and normal migration, effector and memory T cell function when tested in acute infection of mice with either lymphocytic choriomeningitis virus (LCMV) or influenza virus.Conclusions/Significance
Our study demonstrates that DG function is modulated by glycosylation during T cell development in vivo and that DG is essential for normal development and differentiation of T cells. 相似文献145.
Hong CJ Tsai PJ Cheng CY Chou CK Jheng HF Chuang YC Yang CN Lin YT Hsu CW Cheng IH Chen SY Tsai SJ Liou YJ Tsai YS 《PloS one》2010,5(12):e15333
Background
Obesity is a multifactorial disease that arises from complex interactions between genetic predisposition and environmental factors. Leptin is central to the regulation of energy metabolism and control of body weight in mammals.Methodology/Principal Findings
To better recapitulate the complexity of human obesity syndrome, we applied N-ethyl-N-nitrosourea (ENU) mutagenesis in combination with a set of metabolic assays in screening mice for obesity. Mapping revealed linkage to the chromosome 6 within a region containing mouse Leptin gene. Sequencing on the candidate genes identified a novel T-to-A mutation in the third exon of Leptin gene, which translates to a V145E amino acid exchange in the leptin propeptide. Homozygous Leptin145E/145E mutant mice exhibited morbid obesity, accompanied by adipose hypertrophy, energy imbalance, and liver steatosis. This was further associated with severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyperleptinemia, characteristics of human obesity syndrome. Hypothalamic leptin actions in inhibition of orexigenic peptides NPY and AgRP and induction of SOCS1 and SOCS3 were attenuated in Leptin145E/145E mice. Administration of exogenous wild-type leptin attenuated hyperphagia and body weight increase in Leptin145E/145E mice. However, mutant V145E leptin coimmunoprecipitated with leptin receptor, suggesting that the V145E mutation does not affect the binding of leptin to its receptor. Molecular modeling predicted that the mutated residue would form hydrogen bond with the adjacent residues, potentially affecting the structure and formation of an active complex with leptin receptor within that region.Conclusions/Significance
Thus, our evolutionary, structural, and in vivo metabolic information suggests the residue 145 as of special function significance. The mouse model harboring leptin V145E mutation will provide new information on the current understanding of leptin biology and novel mouse model for the study of human obesity syndrome. 相似文献146.
147.
This study is to improve the digestion pattern of miniprepped plasmid analyzed on gel. Frequently, some ambiguous DNA bands, which are suspected to be denatured DNA molecules, appear during electrophoresis of enzyme digested miniprepped plasmids. By employing Southern hybridization of two identical gels, one had been treated with denaturation-neutralization step and another without such treatment, we confirmed that many of these ambiguous DNA bands were single-stranded (SS) DNA molecules. The presence of SS DNA was due to the use of excess amount of NaOH during plasmid DNA purification with the conventional alkaline lysis method. We, therefore, modified the procedure and recommend that a half amount of NaOH (0.1N instead of 0.2N) should be used when isolating small quantity of plasmid DNA with the method. 相似文献
148.
149.
Milko E. van der Boom Shyh-Yeon Liou Yehoshoa Ben-David 《Inorganica chimica acta》2004,357(13):4015-4023
Reaction of NiI2 with the PCP-ligand {1-Et-2,6-(CH2PiPr2)2-C6H3} (1) results in selective activation of the strong sp2-sp3 aryl-ethyl bond to afford the aryl-nickel complex [Ni{2,6-(CH2PiPr2)2-C6H3}I] (2), whereas reaction of NiI2 with {1,3,5-(CH3)3-2,6-(CH2PiPr2)2-C6H} (4) leads to the formation of the benzylic complex [Ni{1-CH2-2,6-(CH2PiPr2)2-3,5-(CH3)2-C6H}I] (5) by selective C-H bond activation. Thermolysis of 5 results in formation of [Ni{2,6-(CH2PiPr2)2-3,5-(CH3)2-C6H}I] (6) by activation of the sp2-sp3 C-C bond. The identity of the new 16-electron complexes 2 and 6 was confirmed by reaction of NiI2 with {1,3-(CH2PiPr2)2-C6H4} (3) and {1,3-(CH3)2-4,6-(CH2PiPr2)2-C6H2} (7), respectively, lacking the aryl-alkyl groups between the “phosphines arms” (alkyl=ethyl, methyl). Complexes 2 and 5 have been fully characterized by X-ray analysis. Nickel-based activation of an unstrained C-O single bond was observed as well. Reaction of the aryl-methoxy bisphosphine {1-OMe-2,6-(CH2PiPr2)2-C6H3} (8) with NiI2 results in the formation of the phenoxy complex [Ni{1-O-2,6-(CH2PiPr2)2-C6H3}I] (9) by selective sp3-sp3 C-O bond activation. 相似文献
150.
Intestinal fatty acid binding protein (IFABP) and liver FABP (LFABP), homologous proteins expressed at high levels in intestinal absorptive cells, employ markedly different mechanisms for the transfer of fatty acids (FAs) to acceptor membranes. Transfer from IFABP occurs during protein-membrane collisional interactions, while for LFABP, transfer occurs by diffusion through the aqueous phase. Earlier, we had shown that the helical domain of IFABP is critical in determining its collisional FA transfer mechanism. In the study presented here, we have engineered a pair of chimeric proteins, one with the "body" (ligand binding domain) of IFABP and the alpha-helical region of LFABP (alphaLbetaIFABP) and the other with the ligand binding pocket of LFABP and the helical domain of IFABP (alphaIbetaLFABP). The objective of this work was to determine whether the change in the alpha-helical domain of each FABP would alter the rate and mechanism of transfer of FA from the chimeric proteins in comparison with those of the wild-type proteins. The fatty acid transfer properties of the FABP chimeras were examined using a fluorescence resonance transfer assay. The results showed a significant modification of the absolute rate of FA transfer from the chimeric proteins compared to that of the wild type, indicating that the slower rate of FA transfer observed for wild-type LFABP relative to that of wild-type IFABP is, in part, determined by the helical domain of the proteins. In addition to these quantitative changes, it was of great interest to observe that the apparent mechanism of FA transfer also changed when the alpha-helical domain was exchanged, with transfer from alphaLbetaIFABP occurring by aqueous diffusion and transfer from alphaIbetaLFABP occurring via protein-membrane collisional interactions. These results demonstrate that the alpha-helical region of LFABP is responsible for its diffusional mechanism of fatty acid transfer to membranes. 相似文献