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971.
Yeung CK Lin RC Lei F Robson C Hung le M Liang W Zhou F Han L Li SH Yang X 《Molecular phylogenetics and evolution》2011,61(1):192-202
The parrotbills (Paradoxornithidae, meaning "birds of paradox," Aves) are a group of Old World passerines with perplexing taxonomic histories due to substantial morphological and ecological variation at various levels. In this study, phylogenetic relationships of the parrotbills were reconstructed based on sequences of two mitochondrial segments and three nuclear coding regions. Three major clades with characteristic body size and plumage coloration were found in both mtDNA and nuclear gene trees. However, mtDNA phylogeny suggested that the Paradoxornithidae is paraphyletic and relationships among three major parrotbill clades were poorly resolved. On the contrary, apparent and well-supported monophyletic relationships among the three major clades of Paradoxornithidae were revealed by concatenated nuclear dataset. Since paraphyly based on mtDNA data has commonly been found within avian taxa, the conflicting phylogenetic signal between mtDNA and nuclear loci revealed in this study indicates that results obtained from mtDNA dataset alone need to be evaluated with caution. Taxonomic implications of our phylogenetic findings are discussed. These phylogenies also point out areas for future investigation regarding the rapid diversification, morphological evolution and environmental adaptation of various parrotbill species or species complexes. 相似文献
972.
973.
Adams PD Afonine PV Bunkóczi G Chen VB Echols N Headd JJ Hung LW Jain S Kapral GJ Grosse Kunstleve RW McCoy AJ Moriarty NW Oeffner RD Read RJ Richardson DC Richardson JS Terwilliger TC Zwart PH 《Methods (San Diego, Calif.)》2011,55(1):94-106
X-ray crystallography is a critical tool in the study of biological systems. It is able to provide information that has been a prerequisite to understanding the fundamentals of life. It is also a method that is central to the development of new therapeutics for human disease. Significant time and effort are required to determine and optimize many macromolecular structures because of the need for manual interpretation of complex numerical data, often using many different software packages, and the repeated use of interactive three-dimensional graphics. The Phenix software package has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on automation. This has required the development of new algorithms that minimize or eliminate subjective input in favor of built-in expert-systems knowledge, the automation of procedures that are traditionally performed by hand, and the development of a computational framework that allows a tight integration between the algorithms. The application of automated methods is particularly appropriate in the field of structural proteomics, where high throughput is desired. Features in Phenix for the automation of experimental phasing with subsequent model building, molecular replacement, structure refinement and validation are described and examples given of running Phenix from both the command line and graphical user interface. 相似文献
974.
Huynh QK Wise SJ Koch KA Castonguay LA Reid BG Pagratis EE Koditek D Glascock CB Pitts KR Turner BA Liu X Hung M Han B Pagratis N 《Journal of biomolecular screening》2011,16(7):724-733
Transforming growth factor β (TGF-β) type I receptor (activin receptor-like kinase 5, ALK5) has been identified as a promising target for fibrotic diseases. To find a novel inhibitor of ALK5, the authors performed a high-throughput screen of a library of 420,000 compounds using dephosphorylated ALK5. From primary hits of 1521 compounds, 555 compounds were confirmed. In total, 124 compounds were then selected for follow-up based on their unique structures and other properties. Repeated concentration-response testing and final interference assays of the above compounds resulted in the discovery of a structurally novel ALK5 inhibitor (compound 8) (N-(thiophen 2-ylmethyl)-3-(3,4,5 trimethoxyphenyl)imidazo[1,2β]pyridazin 6-amine) with a low IC(50) value of 0.7 μM. Compound 8 also inhibited the TGF-β-induced nuclear translocation of SMAD with an EC(50) value of 0.8 μM. Kinetic analysis revealed that compound 8 inhibited ALK5 via mixed-type inhibition, suggesting that it may bind to ALK5 differently than other published adenosine triphosphate site inhibitors. 相似文献
975.
Hsu JM Chen CT Chou CK Kuo HP Li LY Lin CY Lee HJ Wang YN Liu M Liao HW Shi B Lai CC Bedford MT Tsai CH Hung MC 《Nature cell biology》2011,13(2):174-181
Epidermal growth factor receptor (EGFR) can undergo post-translational modifications, including phosphorylation, glycosylation and ubiquitylation, leading to diverse physiological consequences and modulation of its biological activity. There is increasing evidence that methylation may parallel other post-translational modifications in the regulation of various biological processes. It is still not known, however, whether EGFR is regulated by this post-translational event. Here, we show that EGFR Arg?1175 is methylated by an arginine methyltransferase, PRMT5. Arg?1175 methylation positively modulates EGF-induced EGFR trans-autophosphorylation at Tyr?1173, which governs ERK activation. Abolishment of Arg?1175 methylation enhances EGF-stimulated ERK activation by reducing SHP1 recruitment to EGFR, resulting in augmented cell proliferation, migration and invasion of EGFR-expressing cells. Therefore, we propose a model in which the regulatory crosstalk between PRMT5-mediated Arg?1175 methylation and EGF-induced Tyr?1173 phosphorylation attenuates EGFR-mediated ERK activation. 相似文献
976.
977.
Ming‐Szu Hung Jian‐Hua Mao Zhidong Xu Cheng‐Ta Yang Jau‐Song Yu Chansonette Harvard Yu‐Ching Lin Dawn Therese Bravo David M. Jablons Liang You 《Journal of cellular and molecular medicine》2011,15(2):350-358
Cullin 4A (Cul4A) is important in cell survival, development, growth and the cell cycle, but its role in mesothelioma has not been studied. For the first time, we identified amplification of the Cul4A gene in four of five mesothelioma cell lines. Consistent with increased Cul4A gene copy number, we found that Cul4A protein was overexpressed in mesothelioma cells as well. Cul4A protein was also overexpressed in 64% of primary malignant pleural mesothelioma (MPM) tumours. Furthermore, knockdown of Cul4A with shRNA in mesothelioma cells resulted in up‐regulation of p21 and p27 tumour suppressor proteins in a p53‐independent manner in H290, H28 and MS‐1 mesothelioma cell lines. Knockdown of Cul4A also resulted in G0/G1 cell cycle arrest and decreased colony formation in H290, H28 and MS‐1 mesothelioma cell lines. Moreover, G0/G1 cell cycle arrest was partially reversed by siRNA down‐regulation of p21 and/or p27 in Cul4A knockdown H290 cell line. In the contrary, overexpression of Cul4A resulted in down‐regulation of p21 and p27 proteins and increased colony formation in H28 mesothelioma cell line. Both p21 and p27 showed faster degradation rates in Cul4A overexpressed H28 cell line and slower degradation rates in Cul4A knockdown H28 cell line. Our study indicates that Cul4A amplification and overexpression play an oncogenic role in the pathogenesis of mesothelioma. Thus, Cul4A may be a potential therapeutic target for MPM. 相似文献
978.
A simple, rapid and sensitive colorimetric dipstick assay for the detection of the organophosphorous insecticide methyl parathion (MPT) residue in vegetables was developed. The assay was based on the hydrolysis of MPT by a recombinant methyl parathion hydrolase (recMPH), the encoding gene of which was isolated from Burkholderia cepacia, a soil bacterium indigenous to Thailand. This reaction generates protons leading to a change in pH that correlates with the amount of MPH present. Hence, the pH indicator bromothymol blue was used to monitor the MPH hydrolysis as the associated color changes can be observed by the naked eye. The recMPH was immobilized on a PVDF membrane to establish a dipstick assay format. The assays could detect MPT residues in spiked vegetable samples at the concentration of 1 mg/L without using analytical instrumentation. The test is reusable and stable for up to 3 months in the absence of any preservatives. 相似文献
979.
Musculoskeletal fibromatosis remains a disease of unknown etiology. Surgical excision is the standard of care, but the recurrence rate remains high. Superficial fibromatosis typically presents as subcutaneous nodules caused by rapid myofibroblast proliferation followed by slow involution to dense acellular fibrosis. In this study, we demonstrate that fibromatosis stem cells (FSCs) can be isolated from palmar nodules but not from cord or normal palm tissues. We found that FSCs express surface markers such as CD29, CD44, CD73, CD90, CD105, and CD166 but do not express CD34, CD45, or CD133. We also found that FSCs are capable of expanding up to 20 passages, that these cells include myofibroblasts, osteoblasts, adipocytes, chondrocytes, hepatocytes, and neural cells, and that these cells possess multipotentiality to develop into the three germ layer cells. When implanted beneath the dorsal skin of nude mice, FSCs recapitulated human fibromatosis nodules. Two weeks after implantation, the cells expressed immunodiagnostic markers for myofibroblasts such as α-smooth muscle actin and type III collagen. Two months after implantation, there were fewer myofibroblasts and type I collagen became evident. Treatment with the antifibrogenic compound Trichostatin A (TSA) inhibited the proliferation and differentiation of FSCs in vitro. Treatment with TSA before or after implantation blocked formation of fibromatosis nodules. These results suggest that FSCs are the cellular origin of fibromatosis and that these cells may provide a promising model for developing new therapeutic interventions. 相似文献
980.