18 results on '"Huang, Guiqing"'
Search Results
2. The Adaptive Alternation of Intestinal Microbiota and Regulation of Host Genes Jointly Promote Pigs to Digest Appropriate High-Fiber Diets.
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Zhang, Yunchao, Li, Hui, Li, Bengao, He, Jiayi, Peng, Chen, Xie, Yanshe, Huang, Guiqing, Zhao, Pengju, and Wang, Zhengguang
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HIGH-fiber diet ,GUT microbiome ,GENETIC regulation ,GENE expression ,SWINE ,WHEAT bran ,WHEAT breeding ,DIETARY fiber - Abstract
Simple Summary: Tunchang pigs are known for their good performance on roughage tolerance, which may alleviate the conflict between humans and livestock for grain resources. This study observed that Tunchang pigs can adapt to a high-fiber diet containing 5% crude fiber. The adaptive alterations in intestinal microbiota and the regulation of genes collectively facilitated the digestion of high-fiber diets in the host. These findings provide insight into the roughage tolerance of Tunchang pigs, and contribute to further exploration of host–microbiota interactions. Although studies have revealed the significant impact of dietary fiber on growth performance and nutrient digestibility, the specific characteristics of the intestinal microbiota and gene regulation in pigs capable of digesting high-fiber diets remained unclear. To investigate the traits associated with roughage tolerance in the Chinese indigenous pig breed, we conducted comparative analysis of growth performance, apparent fiber digestibility, intestinal microbiota, SCFA concentrations and intestinal transcriptome in Tunchang pigs, feeding them diets with different wheat bran levels. The results indicated that the growth performance of Tunchang pigs was not significantly impacted, and the apparent total tract digestibility of crude fiber was significantly improved with increasing dietary fiber content. High-fiber diets altered the diversity of intestinal microbiota, and increased the relative abundance of Prevotella, CF231, as well as the concentrations of isobutyrate, valerate and isovalerate. The LDA analysis identified potential microbial biomarkers that could be associated with roughage tolerance, such as Prevotella stercorea, and Eubacterium biforme. In addition, appropriate high-fiber diets containing 4.34% crude fiber upregulated the mRNA expressions of PYY, AQP8, and SLC5A8, while downregulating the mRNA expressions of CKM and CNN1.This indicated that appropriate high-fiber diets may inhibit intestine motility and increase the absorption of water and SCFAs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Red Phosphorus Grafted High‐Index (116) Faceted Anatase TiO2 for Z‐Scheme Photocatalytic Pure Water Splitting.
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Zhu, Yukun, Ren, Jun, Huang, Guiqing, Dong, Chung‐Li, Huang, Yu‐Cheng, Lu, Ping, Tang, Hua, Liu, Yiming, Shen, Shaohua, and Yang, Dongjiang
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CUCURBITURIL ,VALENCE bands ,CHEMICAL vapor deposition ,TITANIUM dioxide ,CONDUCTION bands ,PHOSPHORUS - Abstract
Red phosphorus (RP) is an emerging visible‐light‐responsive photocatalyst, yet the rapid charge recombination has limited photocatalytic hydrogen production activity. In this work, a Z‐scheme heterostructure with RP nanolayer coated on high‐index (116) faceted anatase TiO2 nanoparticles (TiO2@RP) is designed and fabricated via chemical vapor deposition. Compared with pristine TiO2 and RP, the optimized TiO2@RP Z‐scheme heterostructure exhibits a significantly boosted photocatalytic activity for pure water splitting, with hydrogen evolution rate reaching 12.9 µmol·h−1, under simulated solar light irradiation. The strong interfacial interaction and staggered band alignment between (116) faceted TiO2 and RP result in the formation of built‐in electric field, which can drive the directional charge migration from the conduction band (CB) of TiO2 to the valance band (VB) of RP under light irradiation, with photoelectrons and holes of high redox ability maintained at the CB of RP and the VB of TiO2, respectively. This well‐designed heterostructure greatly promotes photogenerated charge separation and migration via a direct Z‐scheme charge transfer pathway. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Delivery of Herpes Simplex Virus to Retinal Ganglion Cell Axon Is Dependent on Viral Protein Us9HSV Us9 in Axonal Delivery of Viral Genome
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Draper, Jolene M, Huang, Guiqing, Stephenson, Graham S, Bertke, Andrea S, Cortez, Daniel A, and LaVail, Jennifer H
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Infectious Diseases ,Eye Disease and Disorders of Vision ,Sexually Transmitted Infections ,HIV/AIDS ,Neurosciences ,Genetics ,2.2 Factors relating to the physical environment ,Underpinning research ,Aetiology ,1.1 Normal biological development and functioning ,Infection ,Animals ,Axons ,Cell Line ,DNA ,Viral ,Disease Models ,Animal ,Eye Infections ,Viral ,Gene Expression Regulation ,Viral ,Genome ,Viral ,Male ,Mice ,Mice ,Inbred BALB C ,Polymerase Chain Reaction ,Retinal Ganglion Cells ,Simplexvirus ,Viral Envelope Proteins ,Viral Proteins ,Biological Sciences ,Medical and Health Sciences ,Ophthalmology & Optometry - Abstract
PurposeHow herpes simplex virus (HSV) is transported from the infected neuron cell body to the axon terminal is poorly understood. Several viral proteins are candidates for regulating the process, but the evidence is controversial. We compared the results of Us9 deletions in two HSV strains (F and NS) using a novel quantitative assay to test the hypothesis that the viral protein Us9 regulates the delivery of viral DNA to the distal axon of retinal ganglion cells in vivo. We also deleted a nine-amino acid motif in the Us9 protein of F strain (Us9-30) to define the role of this domain in DNA delivery.MethodsThe vitreous chambers of murine eyes were infected with equivalent amounts of F or NS strains of HSV. At 3, 4, or 5 days post infection (dpi), both optic tracts (OT) were dissected and viral genome was quantified by qPCR.ResultsAt 3 dpi, the F strain Us9- and Us9-30 mutants delivered less than 10% and 1%, respectively, of the viral DNA delivered after infection with the Us9R (control) strain. By 4 and 5 dpi, delivery of viral DNA had only partially recovered. Deletion of Us9 in NS-infected mice has a less obvious effect on delivery of new viral DNA to the distal OT. By 3 dpi the NS Us9-strain delivered 22% of the DNA that was delivered by the NS wt, and by 4 and 5 dpi the amount of Us9-viral DNA was 96% and 81%, respectively.ConclusionsA highly conserved acidic cluster within the Us9 protein plays a critical role for genome transport to the distal axon. The transport is less dependent on Us9 expression in the NS than in the F strain virus. This assay can be used to compare transport efficiency in other neurotropic viral strains.
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- 2013
5. The Transcription Factor ZNF217 Is a Prognostic Biomarker and Therapeutic Target during Breast Cancer Progression
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Littlepage, Laurie E, Adler, Adam S, Kouros-Mehr, Hosein, Huang, Guiqing, Chou, Jonathan, Krig, Sheryl R, Griffith, Obi L, Korkola, James E, Qu, Kun, Lawson, Devon A, Xue, Qing, Sternlicht, Mark D, Dijkgraaf, Gerrit JP, Yaswen, Paul, Rugo, Hope S, Sweeney, Colleen A, Collins, Colin C, Gray, Joe W, Chang, Howard Y, and Werb, Zena
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Women's Health ,Stem Cell Research ,Precision Medicine ,Cancer ,Breast Cancer ,Genetics ,Stem Cell Research - Nonembryonic - Human ,Aetiology ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,2.1 Biological and endogenous factors ,Animals ,Antibiotics ,Antineoplastic ,Biomarkers ,Tumor ,Blotting ,Western ,Breast Neoplasms ,Cell Line ,Tumor ,Cell Proliferation ,Disease Progression ,Doxorubicin ,Drug Resistance ,Neoplasm ,Female ,Gene Expression Profiling ,Gene Expression Regulation ,Neoplastic ,Humans ,MCF-7 Cells ,Mice ,NIH 3T3 Cells ,Neoplastic Stem Cells ,Oligonucleotide Array Sequence Analysis ,Prognosis ,Reverse Transcriptase Polymerase Chain Reaction ,Ribonucleosides ,Survival Analysis ,Trans-Activators ,Xenograft Model Antitumor Assays ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
UnlabelledThe transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs in 20% to 30% of primary human breast cancers and that correlates with poor prognosis. We show that Znf217 overexpression drives aberrant differentiation and signaling events, promotes increased self-renewal capacity, mesenchymal marker expression, motility, and metastasis, and represses an adult tissue stem cell gene signature downregulated in cancers. By in silico screening, we identified candidate therapeutics that at low concentrations inhibit growth of cancer cells expressing high ZNF217. We show that the nucleoside analogue triciribine inhibits ZNF217-induced tumor growth and chemotherapy resistance and inhibits signaling events [e.g., phospho-AKT, phospho-mitogen-activated protein kinase (MAPK)] in vivo. Our data suggest that ZNF217 is a biomarker of poor prognosis and a therapeutic target in patients with breast cancer and that triciribine may be part of a personalized treatment strategy in patients overexpressing ZNF217. Because ZNF217 is amplified in numerous cancers, these results have implications for other cancers.SignificanceThis study finds that ZNF217 is a poor prognostic indicator and therapeutic target in patients with breast cancer and may be a strong biomarker of triciribine treatment efficacy in patients. Because previous clinical trials for triciribine did not include biomarkers of treatment efficacy, this study provides a rationale for revisiting triciribine in the clinical setting as a therapy for patients with breast cancer who overexpress ZNF217.
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- 2012
6. End-Sequence Profiling: Sequence-Based Analysis of Aberrant Genomes
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Volik, Stanislav, Zhao, Shaying, Chin, Koei, Brebner, John H., Herndon, David R., Tao, Quanzhou, Kowbel, David, Huang, Guiqing, Lapuk, Anna, Kuo, Wen-Lin, Magrane, Gregg, de Jong, Pieter, Gray, Joe W., and Collins, Colin
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- 2003
7. The effect of flashlamp pulsed dye laser on the expression of connective tissue growth factor in keloids
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Yang, Qiaorong, Ma, Ying, Zhu, Rongyi, Huang, Guiqing, Guan, Ming, Avram, Mathew M., and Lu, Zhong
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- 2012
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8. Phox homology domains specifically bind phosphatidylinositol phosphates
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Song, Xi, Xu, Wei, Zhang, Aihua, Huang, Guiqing, Liang, Xiaoshan, Virbasius, Joseph V., Czech, Michael P., and Zhou, G. Wayne
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Biochemistry -- Research ,Phosphates -- Research ,Phosphatidylinositol -- Research ,Homology (Biology) -- Physiological aspects ,Proteins -- Research ,Biological sciences ,Chemistry - Abstract
Research has been conducted on the specific cytosolic proteins. The experiments demonstrate that the representatives of the Phox homology domains selectively bind to specific phosphatidylinositol phosphates.
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- 2001
9. Multiple roles of the candidate oncogene ZNF217 in ovarian epithelial neoplastic progression
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Li, Peixiang, Maines-Bandiera, Sarah, Kuo, Wen-Lin, Guan, Yinghui, Sun, Yu, Hills, Mark, Huang, Guiqing, Collins, Collin C., Leung, Peter C.K., Gray, Joe W., and Auersperg, Nelly
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- 2007
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10. ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction
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Huang, Guiqing, Krig, Sheryl, Kowbel, David, Xu, Hongmei, Hyun, Bill, Volik, Stas, Feuerstein, Burt, Mills, Gordon B., Stokoe, David, Yaswen, Paul, and Collins, Colin
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- 2005
11. Phosphorus-doped polymeric carbon nitride nanosheets for enhanced photocatalytic hydrogen production.
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Zhu, Yukun, Li, Junzhi, Cao, Junming, Lv, Chunxiao, Huang, Guiqing, Zhang, Gaolian, Xu, Yan, Zhang, Shuchao, Meng, Pingping, Zhan, Tianrong, and Yang, Dongjiang
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HYDROGEN production ,NITRIDES ,SOLAR energy conversion ,HYDROGEN evolution reactions ,CHARGE transfer ,ENERGY conversion ,CARBON - Abstract
Photocatalytic hydrogen production by water splitting is one of the most effective strategies for solar energy conversion and utilization. The metal-free polymeric carbon nitride (CN) has been widely used as an efficient photocatalyst for the photocatalytic hydrogen evolution reaction (HER). However, to date, the solar to hydrogen conversion efficiency of the CN-based photocatalysts is still low. Herein, to boost the photocatalytic activity of CN, controllable phosphorus atoms were introduced to form P-doped CN (PCN) via an evacuated ampoule calcination strategy. Compared with bare CN, the optimized PCN exhibits remarkably enhanced photocatalytic HER activity, with the HER rate up to 261.2 µmol h
−1 and 171.6 µmol h−1 under the simulated solar light and visible-light illumination, respectively. It was revealed that the boosted photocatalysis for HER is mainly ascribed to the P dopants that can synergetically increase the visible-light absorption and facilitate the charge transfer process. This present work highlights improving the photocatalytic energy conversion efficiency by controllable tuning of the heteroatom doping degree in photocatalysts. [ABSTRACT FROM AUTHOR]- Published
- 2020
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12. Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins.
- Author
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Huang, Mingdong, Rigby, Alan C, Morelli, Xavier, Grant, Marianne A, Huang, Guiqing, Furie, Bruce, Seaton, Barbara, and Furie, Barbara C
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VITAMIN K ,PROTEINS ,BLOOD coagulation ,PROTEIN binding ,PHOSPHATIDYLSERINES ,ENZYMES - Abstract
In a calcium-dependent interaction critical for blood coagulation, vitamin K-dependent blood coagulation proteins bind cell membranes containing phosphatidylserine via ?-carboxyglutamic acid-rich (Gla) domains. Gla domain-mediated protein-membrane interaction is required for generation of thrombin, the terminal enzyme in the coagulation cascade, on a physiologic time scale. We determined by X-ray crystallography and NMR spectroscopy the lysophosphatidylserine-binding site in the bovine prothrombin Gla domain. The serine head group binds Gla domain-bound calcium ions and Gla residues 17 and 21, fixed elements of the Gla domain fold, predicting the structural basis for phosphatidylserine specificity among Gla domains. Gla domains provide a unique mechanism for protein-phospholipid membrane interaction. Increasingly Gla domains are being identified in proteins unrelated to blood coagulation. Thus, this membrane-binding mechanism may be important in other physiologic processes. [ABSTRACT FROM AUTHOR]
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- 2003
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13. Efficient photoelectrocatalytic degradation of tylosin on TiO2 nanotube arrays with tunable phosphorus dopants.
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Zhang, Gaolian, Huang, Guiqing, Yang, Chen, Chen, Shuai, Xu, Yan, Zhang, Shuchao, Lu, Ping, Sun, Jin, Zhu, Yukun, and Yang, Dongjiang
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TYLOSIN ,TITANIUM dioxide ,DOPING agents (Chemistry) ,WASTEWATER treatment ,CHARGE transfer ,PHOSPHORUS ,ANTIBIOTIC residues ,PHOSPHORESCENCE - Abstract
• Phosphorus-doped TiO 2 nanotube arrays (TNTAs/P) was synthesized by calcination red phosphorus with TNTAs in sealed ampoule. • TNTAs/P exhibits enhanced photoelectrocatalytic tylosin removal activity. • P dopants could improve light absorption and charge separation in TNTAs. • •OH radicals and holes are the dominant reactive species for tylosin degradation. Photoelectrocatalytic (PEC) degradation of antibiotics residues is one of the most effective strategies for wastewater treatment. TiO 2 has been widely used as an efficient photoelectrode material for pollutant removal. However, the degradation efficiency of UV light-driven TiO 2 -based photoelectrodes is still low. In this study, phosphorus-doped TiO 2 nanotube arrays (TNTAs/P) were fabricated by calcination TNTAs with amorphous red phosphorus in sealed ampoules. By tuning the amount of P dopants, the optimized TNTAs/P(0.75) photoelectrode exhibits excellent PEC degradation performance under the Xenon lamp (100 mW/cm
2 , λ > 300 nm) light irradiation, with 79 % tylosin removal within 250 min.. The TNTAs/P(0.75) photoelectrode also displays about 4-fold photocurrent enhancement than bare TNTAs. It is suggested that the P-doping treatment could improve the light-harvesting ability and accelerate the separation efficiency of photo-induced electron-hole pairs in TNTAs, which benefits the production of •OH radicals and thus leads to the enhancement in tylosin degradation activity. This present work demonstrates a facile approach for improving the PEC degradation efficiency by doping heteroatoms in the photoelectrode. Capsule: P-doped TiO 2 nanotube arrays were fabricated for boosting photoelectrocatalytic tylosin degradation activity due to the enhanced light absorption and charge transfer efficiency. [ABSTRACT FROM AUTHOR]- Published
- 2021
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14. Carbon fibers-coated Co@N-doped porous carbon derived from ZIF-67/alginate fibers for efficient oxygen reduction reaction.
- Author
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Jia, Nana, Li, Daohao, Huang, Guiqing, Sun, Jin, Lu, Ping, Wan, Li, Hui, Bin, She, Xilin, and Zhao, Xiaoliang
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- 2020
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15. Hybridization alters the gut microbial and metabolic profile concurrent with modifying intestinal functions in Tunchang pigs.
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He J, Zhang Y, Li H, Xie Y, Huang G, Peng C, Zhao P, and Wang Z
- Abstract
Introduction: Hybridization has been widely used among Chinese wild boars to improve their growth performance and maintain meat quality. Most studies have focused on the genetic basis for such variation. However, the differences in the gut environment between hybrid and purebred boars, which can have significant impacts on their health and productivity, have been poorly understood., Methods: In the current study, metagenomics was used to detect the gut microbial diversity and composition in hybrid Batun (BT, Berkshire × Tunchang) pigs and purebred Tunchang (TC) pigs. Additionally, untargeted metabolomic analysis was used to detect differences in gut metabolic pathways. Furthermore, multiple molecular experiments were conducted to demonstrate differences in intestinal functions., Results: As a result of hybridization in TC pigs, a microbial change was observed, especially in Prevotella and Lactobacillus . Significant differences were found in gut metabolites, including fatty acyls, steroids, and steroid derivatives. Furthermore, the function of the intestinal barrier was decreased by hybridization, while the function of nutrient metabolism was increased., Discussion: Evidences were shown that hybridization changed the gut microbiome, gut metabolome, and intestinal functions of TC pigs. These findings supported our hypothesis that hybridization altered the gut microbial composition, thereby modifying the intestinal functions, even the host phenotypes. Overall, our study highlights the importance of considering the gut microbiome as a key factor in the evaluation of animal health and productivity, particularly in the context of genetic selection and breeding programs., Competing Interests: HL was employed by Long Jian Animal Husbandry Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 He, Zhang, Li, Xie, Huang, Peng, Zhao and Wang.)
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- 2023
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16. A sequence-based survey of the complex structural organization of tumor genomes.
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Raphael BJ, Volik S, Yu P, Wu C, Huang G, Linardopoulou EV, Trask BJ, Waldman F, Costello J, Pienta KJ, Mills GB, Bajsarowicz K, Kobayashi Y, Sridharan S, Paris PL, Tao Q, Aerni SJ, Brown RP, Bashir A, Gray JW, Cheng JF, de Jong P, Nefedov M, Ried T, Padilla-Nash HM, and Collins CC
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- Cell Line, Tumor, Chromosome Mapping, Chromosomes, Artificial, Bacterial, DNA Breaks, Gene Library, Humans, Polymorphism, Single Nucleotide, Recombination, Genetic, Sequence Analysis, DNA, Transcription, Genetic, Carcinoma genetics, Gene Order, Genes, Neoplasm, Genome, Human
- Abstract
Background: The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using end sequencing profiling, which relies on paired-end sequencing of cloned tumor genomes., Results: In the present study brain, breast, ovary, and prostate tumors, along with three breast cancer cell lines, were surveyed using end sequencing profiling, yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization confirmed translocations and complex tumor genome structures that include co-amplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms revealed candidate somatic mutations and an elevated rate of novel single nucleotide polymorphisms in an ovarian tumor., Conclusion: These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than was previously appreciated and that genomic fusions, including fusion transcripts and proteins, may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.
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- 2008
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17. Decoding the fine-scale structure of a breast cancer genome and transcriptome.
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Volik S, Raphael BJ, Huang G, Stratton MR, Bignel G, Murnane J, Brebner JH, Bajsarowicz K, Paris PL, Tao Q, Kowbel D, Lapuk A, Shagin DA, Shagina IA, Gray JW, Cheng JF, de Jong PJ, Pevzner P, and Collins C
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- Cell Line, Tumor, Chromosomes, Artificial, Bacterial metabolism, Chromosomes, Human, Female, Gene Expression Profiling methods, Genome, Human, Humans, In Situ Hybridization, Fluorescence, Molecular Sequence Data, Polymerase Chain Reaction, Reproducibility of Results, Breast Neoplasms genetics, Sequence Analysis, DNA methods, Transcription, Genetic
- Abstract
A comprehensive understanding of cancer is predicated upon knowledge of the structure of malignant genomes underlying its many variant forms and the molecular mechanisms giving rise to them. It is well established that solid tumor genomes accumulate a large number of genome rearrangements during tumorigenesis. End Sequence Profiling (ESP) maps and clones genome breakpoints associated with all types of genome rearrangements elucidating the structural organization of tumor genomes. Here we extend the ESP methodology in several directions using the breast cancer cell line MCF-7. First, targeted ESP is applied to multiple amplified loci, revealing a complex process of rearrangement and co-amplification in these regions reminiscent of breakage/fusion/bridge cycles. Second, genome breakpoints identified by ESP are confirmed using a combination of DNA sequencing and PCR. Third, in vitro functional studies assign biological function to a rearranged tumor BAC clone, demonstrating that it encodes anti-apoptotic activity. Finally, ESP is extended to the transcriptome identifying four novel fusion transcripts and providing evidence that expression of fusion genes may be common in tumors. These results demonstrate the distinct advantages of ESP including: (1) the ability to detect all types of rearrangements and copy number changes; (2) straightforward integration of ESP data with the annotated genome sequence; (3) immortalization of the genome; (4) ability to generate tumor-specific reagents for in vitro and in vivo functional studies. Given these properties, ESP could play an important role in a tumor genome project.
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- 2006
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18. Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2alpha.
- Author
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Liu L, Song X, He D, Komma C, Kita A, Virbasius JV, Huang G, Bellamy HD, Miki K, Czech MP, and Zhou GW
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- Amino Acid Sequence, Animals, Binding Sites, Crystallization, Dimerization, Mice, Molecular Sequence Data, Phosphatidylinositol 3-Kinases metabolism, Phospholipids metabolism, Protein Structure, Tertiary, Phosphatidylinositol 3-Kinases chemistry
- Abstract
Phosphatidylinositide (PtdIns) 3-kinase catalyzes the addition of a phosphate group to the 3'-position of phosphatidyl inositol. Accumulated evidence shows that PtdIns 3-kinase can provide a critical signal for cell proliferation, cell survival, membrane trafficking, glucose transport, and membrane ruffling. Mammalian PtdIns 3-kinases are divided into three classes based on structure and substrate specificity. A unique characteristic of class II PtdIns 3-kinases is the presence of both a phox homolog domain and a C2 domain at the C terminus. The biological function of the C2 domain of the class II PtdIns 3-kinases remains to be determined. We have determined the crystal structure of the mCPK-C2 domain, which is the first three-dimensional structural model of a C2 domain of class II PtdIns 3-kinases. Structural studies reveal that the mCPK-C2 domain has a typical anti-parallel beta-sandwich fold. Scrutiny of the surface of this C2 domain has identified three small, shallow sulfate-binding sites. On the basis of the structural features of these sulfate-binding sites, we have studied the lipid binding properties of the mCPK-C2 domain by site-directed mutagenesis. Our results show that this C2 domain binds specifically to PtdIns(3,4)P(2) and PtdIns(4,5)P(2) and that three lysine residues at SBS I site, Lys-1420, Lys-1432, and Lys-1434, are responsible for the phospholipid binding affinity.
- Published
- 2006
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