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  • 1
  • 2
    Publication Date: 2018-11-08
    Description: We report the supersonic gas flow for crush and mechanochemical synthesis. The key instrument parameters for production of supersonic particle flow, such as annular nozzle, expansion angle and length of the accelerating duct, are theoretically designed and optimized. Based on the theoretical results, supersonic gas flow equipment is fabricated. The capacity of the present equipment for production of supersonic particle flow is demonstrated by particle image velocimetry measurement, and the maximum transient velocity of the particles achieves as much as 550 m s –1 . Additionally, the present equipment is applied for continuous and physical preparation of ultrafine Si powders with a high scalability and mechanochemical synthesis of TiO 2 and TiN x nanopowders at a high production rate.
    Keywords: materials science
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 3
    Publication Date: 2011-01-21
    Description: When light illuminates a rough metallic surface, hotspots can appear, where the light is concentrated on the nanometre scale, producing an intense electromagnetic field. This phenomenon, called the surface enhancement effect, has a broad range of potential applications, such as the detection of weak chemical signals. Hotspots are believed to be associated with localized electromagnetic modes, caused by the randomness of the surface texture. Probing the electromagnetic field of the hotspots would offer much insight towards uncovering the mechanism generating the enhancement; however, it requires a spatial resolution of 1-2 nm, which has been a long-standing challenge in optics. The resolution of an optical microscope is limited to about half the wavelength of the incident light, approximately 200-300 nm. Although current state-of-the-art techniques, including near-field scanning optical microscopy, electron energy-loss spectroscopy, cathode luminescence imaging and two-photon photoemission imaging have subwavelength resolution, they either introduce a non-negligible amount of perturbation, complicating interpretation of the data, or operate only in a vacuum. As a result, after more than 30 years since the discovery of the surface enhancement effect, how the local field is distributed remains unknown. Here we present a technique that uses Brownian motion of single molecules to probe the local field. It enables two-dimensional imaging of the fluorescence enhancement profile of single hotspots on the surfaces of aluminium thin films and silver nanoparticle clusters, with accuracy down to 1.2 nm. Strong fluorescence enhancements, up to 54 and 136 times respectively, are observed in those two systems. This strong enhancement indicates that the local field, which decays exponentially from the peak of a hotspot, dominates the fluorescence enhancement profile.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cang, Hu -- Labno, Anna -- Lu, Changgui -- Yin, Xiaobo -- Liu, Ming -- Gladden, Christopher -- Liu, Yongmin -- Zhang, Xiang -- England -- Nature. 2011 Jan 20;469(7330):385-8. doi: 10.1038/nature09698.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21248848" target="_blank"〉PubMed〈/a〉
    Keywords: Aluminum/chemistry ; *Electromagnetic Fields ; Fluorescence ; Fluorescent Dyes/analysis/chemistry ; *Hot Temperature ; Luminescent Measurements/*methods ; Metal Nanoparticles/*chemistry ; Microscopy, Fluorescence/*methods ; Molecular Imaging/*methods ; Motion ; Quartz ; Silver/chemistry ; Surface Properties
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2012-01-13
    Description: Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267575/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267575/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jinghui -- Ding, Li -- Holmfeldt, Linda -- Wu, Gang -- Heatley, Sue L -- Payne-Turner, Debbie -- Easton, John -- Chen, Xiang -- Wang, Jianmin -- Rusch, Michael -- Lu, Charles -- Chen, Shann-Ching -- Wei, Lei -- Collins-Underwood, J Racquel -- Ma, Jing -- Roberts, Kathryn G -- Pounds, Stanley B -- Ulyanov, Anatoly -- Becksfort, Jared -- Gupta, Pankaj -- Huether, Robert -- Kriwacki, Richard W -- Parker, Matthew -- McGoldrick, Daniel J -- Zhao, David -- Alford, Daniel -- Espy, Stephen -- Bobba, Kiran Chand -- Song, Guangchun -- Pei, Deqing -- Cheng, Cheng -- Roberts, Stefan -- Barbato, Michael I -- Campana, Dario -- Coustan-Smith, Elaine -- Shurtleff, Sheila A -- Raimondi, Susana C -- Kleppe, Maria -- Cools, Jan -- Shimano, Kristin A -- Hermiston, Michelle L -- Doulatov, Sergei -- Eppert, Kolja -- Laurenti, Elisa -- Notta, Faiyaz -- Dick, John E -- Basso, Giuseppe -- Hunger, Stephen P -- Loh, Mignon L -- Devidas, Meenakshi -- Wood, Brent -- Winter, Stuart -- Dunsmore, Kimberley P -- Fulton, Robert S -- Fulton, Lucinda L -- Hong, Xin -- Harris, Christopher C -- Dooling, David J -- Ochoa, Kerri -- Johnson, Kimberly J -- Obenauer, John C -- Evans, William E -- Pui, Ching-Hon -- Naeve, Clayton W -- Ley, Timothy J -- Mardis, Elaine R -- Wilson, Richard K -- Downing, James R -- Mullighan, Charles G -- CA114766/CA/NCI NIH HHS/ -- CA98413/CA/NCI NIH HHS/ -- CA98543/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- P30 CA021765-33/CA/NCI NIH HHS/ -- P30CA021765/CA/NCI NIH HHS/ -- U01GM92666/GM/NIGMS NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Jan 11;481(7380):157-63. doi: 10.1038/nature10725.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computational Biology and Bioinformatics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22237106" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Child ; DNA Copy Number Variations/genetics ; Genes, ras/genetics ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; Genomics ; Hematopoiesis/genetics ; Histones/metabolism ; Humans ; Janus Kinases/genetics/metabolism ; Leukemia, Myeloid, Acute/drug therapy/genetics/pathology ; Molecular Sequence Data ; Mutation/*genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/*genetics/pathology ; Receptors, Interleukin-7/genetics ; Sequence Analysis, DNA ; Signal Transduction/genetics ; Stem Cells/metabolism/pathology ; T-Lymphocytes/metabolism/pathology ; Translocation, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-01-13
    Description: Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289956/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289956/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jinghui -- Benavente, Claudia A -- McEvoy, Justina -- Flores-Otero, Jacqueline -- Ding, Li -- Chen, Xiang -- Ulyanov, Anatoly -- Wu, Gang -- Wilson, Matthew -- Wang, Jianmin -- Brennan, Rachel -- Rusch, Michael -- Manning, Amity L -- Ma, Jing -- Easton, John -- Shurtleff, Sheila -- Mullighan, Charles -- Pounds, Stanley -- Mukatira, Suraj -- Gupta, Pankaj -- Neale, Geoff -- Zhao, David -- Lu, Charles -- Fulton, Robert S -- Fulton, Lucinda L -- Hong, Xin -- Dooling, David J -- Ochoa, Kerri -- Naeve, Clayton -- Dyson, Nicholas J -- Mardis, Elaine R -- Bahrami, Armita -- Ellison, David -- Wilson, Richard K -- Downing, James R -- Dyer, Michael A -- CA21765/CA/NCI NIH HHS/ -- CA64402/CA/NCI NIH HHS/ -- EY014867/EY/NEI NIH HHS/ -- EY018599/EY/NEI NIH HHS/ -- GM81607/GM/NIGMS NIH HHS/ -- R01 CA155202/CA/NCI NIH HHS/ -- R01 EY014867/EY/NEI NIH HHS/ -- R01 EY014867-02/EY/NEI NIH HHS/ -- R01 EY018599/EY/NEI NIH HHS/ -- R01 EY018599-03/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jan 11;481(7381):329-34. doi: 10.1038/nature10733.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computational Biology and Bioinformatics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22237022" target="_blank"〉PubMed〈/a〉
    Keywords: Aneuploidy ; Animals ; Cell Death/drug effects ; Cell Line ; Cell Survival/drug effects ; Chromosomal Instability/genetics ; Epigenesis, Genetic/*genetics ; Gene Expression Regulation, Neoplastic ; Genes, Retinoblastoma/genetics ; *Genomics ; Humans ; Intracellular Signaling Peptides and Proteins/antagonists & ; inhibitors/genetics/metabolism ; Mice ; *Molecular Targeted Therapy ; Mutation/genetics ; Protein Kinase Inhibitors/*pharmacology/therapeutic use ; Protein-Tyrosine Kinases/antagonists & inhibitors/genetics/metabolism ; Retinoblastoma/*drug therapy/*genetics/pathology ; Retinoblastoma Protein/deficiency/genetics ; Sequence Analysis, DNA ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2012-02-22
    Description: Both genome-wide genetic and epigenetic alterations are fundamentally important for the development of cancers, but the interdependence of these aberrations is poorly understood. Glioblastomas and other cancers with the CpG island methylator phenotype (CIMP) constitute a subset of tumours with extensive epigenomic aberrations and a distinct biology. Glioma CIMP (G-CIMP) is a powerful determinant of tumour pathogenicity, but the molecular basis of G-CIMP remains unresolved. Here we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), establishes G-CIMP by remodelling the methylome. This remodelling results in reorganization of the methylome and transcriptome. Examination of the epigenome of a large set of intermediate-grade gliomas demonstrates a distinct G-CIMP phenotype that is highly dependent on the presence of IDH mutation. Introduction of mutant IDH1 into primary human astrocytes alters specific histone marks, induces extensive DNA hypermethylation, and reshapes the methylome in a fashion that mirrors the changes observed in G-CIMP-positive lower-grade gliomas. Furthermore, the epigenomic alterations resulting from mutant IDH1 activate key gene expression programs, characterize G-CIMP-positive proneural glioblastomas but not other glioblastomas, and are predictive of improved survival. Our findings demonstrate that IDH mutation is the molecular basis of CIMP in gliomas, provide a framework for understanding oncogenesis in these gliomas, and highlight the interplay between genomic and epigenomic changes in human cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351699/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351699/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turcan, Sevin -- Rohle, Daniel -- Goenka, Anuj -- Walsh, Logan A -- Fang, Fang -- Yilmaz, Emrullah -- Campos, Carl -- Fabius, Armida W M -- Lu, Chao -- Ward, Patrick S -- Thompson, Craig B -- Kaufman, Andrew -- Guryanova, Olga -- Levine, Ross -- Heguy, Adriana -- Viale, Agnes -- Morris, Luc G T -- Huse, Jason T -- Mellinghoff, Ingo K -- Chan, Timothy A -- R01 CA154767/CA/NCI NIH HHS/ -- R01CA154767-01/CA/NCI NIH HHS/ -- U54 CA143798/CA/NCI NIH HHS/ -- U54-CA143798/CA/NCI NIH HHS/ -- England -- Nature. 2012 Feb 15;483(7390):479-83. doi: 10.1038/nature10866.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22343889" target="_blank"〉PubMed〈/a〉
    Keywords: Astrocytes/cytology/metabolism ; Cell Survival/genetics ; Cells, Cultured ; CpG Islands/genetics ; DNA Methylation/*genetics ; Epigenesis, Genetic ; Epigenomics ; Gene Expression Regulation ; Glioblastoma/genetics/pathology ; Glioma/*genetics/pathology ; HEK293 Cells ; Histones/metabolism ; Humans ; Isocitrate Dehydrogenase/*genetics/metabolism ; Metabolome/genetics ; Mutation/*genetics ; *Phenotype ; Tumor Cells, Cultured
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2012-02-22
    Description: Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from alpha-ketoglutarate. Here we report that 2HG-producing IDH mutants can prevent the histone demethylation that is required for lineage-specific progenitor cells to differentiate into terminally differentiated cells. In tumour samples from glioma patients, IDH mutations were associated with a distinct gene expression profile enriched for genes expressed in neural progenitor cells, and this was associated with increased histone methylation. To test whether the ability of IDH mutants to promote histone methylation contributes to a block in cell differentiation in non-transformed cells, we tested the effect of neomorphic IDH mutants on adipocyte differentiation in vitro. Introduction of either mutant IDH or cell-permeable 2HG was associated with repression of the inducible expression of lineage-specific differentiation genes and a block to differentiation. This correlated with a significant increase in repressive histone methylation marks without observable changes in promoter DNA methylation. Gliomas were found to have elevated levels of similar histone repressive marks. Stable transfection of a 2HG-producing mutant IDH into immortalized astrocytes resulted in progressive accumulation of histone methylation. Of the marks examined, increased H3K9 methylation reproducibly preceded a rise in DNA methylation as cells were passaged in culture. Furthermore, we found that the 2HG-inhibitable H3K9 demethylase KDM4C was induced during adipocyte differentiation, and that RNA-interference suppression of KDM4C was sufficient to block differentiation. Together these data demonstrate that 2HG can inhibit histone demethylation and that inhibition of histone demethylation can be sufficient to block the differentiation of non-transformed cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478770/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478770/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Chao -- Ward, Patrick S -- Kapoor, Gurpreet S -- Rohle, Dan -- Turcan, Sevin -- Abdel-Wahab, Omar -- Edwards, Christopher R -- Khanin, Raya -- Figueroa, Maria E -- Melnick, Ari -- Wellen, Kathryn E -- O'Rourke, Donald M -- Berger, Shelley L -- Chan, Timothy A -- Levine, Ross L -- Mellinghoff, Ingo K -- Thompson, Craig B -- R01 CA078831/CA/NCI NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- U54CA143798/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 15;483(7390):474-8. doi: 10.1038/nature10860.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22343901" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/cytology/drug effects/metabolism ; Animals ; Astrocytes/cytology/drug effects ; Cell Differentiation/drug effects/*genetics ; Cell Line, Tumor ; Cell Lineage/genetics ; DNA Methylation/drug effects ; Enzyme Induction/drug effects ; Gene Expression Regulation/drug effects ; Glioma/enzymology/genetics/pathology ; Glutarates/metabolism/pharmacology ; HEK293 Cells ; Histones/*metabolism ; Humans ; Isocitrate Dehydrogenase/antagonists & inhibitors/*genetics/metabolism ; Jumonji Domain-Containing Histone Demethylases/antagonists & ; inhibitors/deficiency/genetics/metabolism ; Methylation/drug effects ; Mice ; Mutation/*genetics ; Neural Stem Cells/metabolism ; Promoter Regions, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2013-06-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lei -- Xin, Feng-Jiao -- Wang, Jue -- Hu, Jicheng -- Zhang, Yuan-Yuan -- Wan, Shuo -- Cao, Lu-Sha -- Lu, Chang -- Li, Peng -- Yan, S Frank -- Neumann, Dietbert -- Schlattner, Uwe -- Xia, Bin -- Wang, Zhi-Xin -- Wu, Jia-Wei -- England -- Nature. 2013 Jun 13;498(7453):E8-10. doi: 10.1038/nature12189.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MOE Key Laboratory of Protein Sciences and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23765502" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*chemistry/*metabolism ; Adenosine Diphosphate/*metabolism/*pharmacology ; Animals
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2013-05-31
    Description: Many neurodegenerative disorders, such as Alzheimer's, Parkinson's and polyglutamine diseases, share a common pathogenic mechanism: the abnormal accumulation of disease-causing proteins, due to either the mutant protein's resistance to degradation or overexpression of the wild-type protein. We have developed a strategy to identify therapeutic entry points for such neurodegenerative disorders by screening for genetic networks that influence the levels of disease-driving proteins. We applied this approach, which integrates parallel cell-based and Drosophila genetic screens, to spinocerebellar ataxia type 1 (SCA1), a disease caused by expansion of a polyglutamine tract in ataxin 1 (ATXN1). Our approach revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice. Importantly, pharmacological inhibitors of components of this pathway also decrease ATXN1 levels, suggesting that these components represent new therapeutic targets in mitigating SCA1. Collectively, these data reveal new therapeutic entry points for SCA1 and provide a proof-of-principle for tackling other classes of intractable neurodegenerative diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020154/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020154/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Jeehye -- Al-Ramahi, Ismael -- Tan, Qiumin -- Mollema, Nissa -- Diaz-Garcia, Javier R -- Gallego-Flores, Tatiana -- Lu, Hsiang-Chih -- Lagalwar, Sarita -- Duvick, Lisa -- Kang, Hyojin -- Lee, Yoontae -- Jafar-Nejad, Paymaan -- Sayegh, Layal S -- Richman, Ronald -- Liu, Xiuyun -- Gao, Yan -- Shaw, Chad A -- Arthur, J Simon C -- Orr, Harry T -- Westbrook, Thomas F -- Botas, Juan -- Zoghbi, Huda Y -- HD024064/HD/NICHD NIH HHS/ -- MC_U127081014/Medical Research Council/United Kingdom -- NS42179/NS/NINDS NIH HHS/ -- P30 HD024064/HD/NICHD NIH HHS/ -- R01 NS027699/NS/NINDS NIH HHS/ -- R01 NS042179/NS/NINDS NIH HHS/ -- T32 GM007526/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 20;498(7454):325-31. doi: 10.1038/nature12204. Epub 2013 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23719381" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Ataxin-1 ; Ataxins ; Cell Line, Tumor ; Disease Models, Animal ; Down-Regulation/drug effects ; Drosophila melanogaster/genetics/*metabolism ; Female ; Humans ; MAP Kinase Signaling System/drug effects ; Male ; Mice ; Mitogen-Activated Protein Kinases/*metabolism ; Molecular Sequence Data ; Molecular Targeted Therapy ; Nerve Tissue Proteins/chemistry/genetics/*metabolism/*toxicity ; Nuclear Proteins/chemistry/genetics/*metabolism/*toxicity ; Phosphorylation ; Protein Stability/drug effects ; Ribosomal Protein S6 Kinases, 90-kDa/deficiency/genetics/*metabolism ; Spinocerebellar Ataxias/*metabolism/*pathology ; Transgenes ; ras Proteins/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2013-10-18
    Description: The Cancer Genome Atlas (TCGA) has used the latest sequencing and analysis methods to identify somatic variants across thousands of tumours. Here we present data and analytical results for point mutations and small insertions/deletions from 3,281 tumours across 12 tumour types as part of the TCGA Pan-Cancer effort. We illustrate the distributions of mutation frequencies, types and contexts across tumour types, and establish their links to tissues of origin, environmental/carcinogen influences, and DNA repair defects. Using the integrated data sets, we identified 127 significantly mutated genes from well-known (for example, mitogen-activated protein kinase, phosphatidylinositol-3-OH kinase, Wnt/beta-catenin and receptor tyrosine kinase signalling pathways, and cell cycle control) and emerging (for example, histone, histone modification, splicing, metabolism and proteolysis) cellular processes in cancer. The average number of mutations in these significantly mutated genes varies across tumour types; most tumours have two to six, indicating that the number of driver mutations required during oncogenesis is relatively small. Mutations in transcriptional factors/regulators show tissue specificity, whereas histone modifiers are often mutated across several cancer types. Clinical association analysis identifies genes having a significant effect on survival, and investigations of mutations with respect to clonal/subclonal architecture delineate their temporal orders during tumorigenesis. Taken together, these results lay the groundwork for developing new diagnostics and individualizing cancer treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927368/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927368/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kandoth, Cyriac -- McLellan, Michael D -- Vandin, Fabio -- Ye, Kai -- Niu, Beifang -- Lu, Charles -- Xie, Mingchao -- Zhang, Qunyuan -- McMichael, Joshua F -- Wyczalkowski, Matthew A -- Leiserson, Mark D M -- Miller, Christopher A -- Welch, John S -- Walter, Matthew J -- Wendl, Michael C -- Ley, Timothy J -- Wilson, Richard K -- Raphael, Benjamin J -- Ding, Li -- P01 CA101937/CA/NCI NIH HHS/ -- P01CA101937/CA/NCI NIH HHS/ -- R01 CA180006/CA/NCI NIH HHS/ -- R01 HG005690/HG/NHGRI NIH HHS/ -- R01CA180006/CA/NCI NIH HHS/ -- R01HG005690/HG/NHGRI NIH HHS/ -- U01 HG006517/HG/NHGRI NIH HHS/ -- U01HG006517/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54HG003079/HG/NHGRI NIH HHS/ -- England -- Nature. 2013 Oct 17;502(7471):333-9. doi: 10.1038/nature12634.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Institute, Washington University in St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24132290" target="_blank"〉PubMed〈/a〉
    Keywords: Carcinogenesis/*genetics ; Cell Cycle/genetics ; Clone Cells/metabolism/pathology ; Cohort Studies ; DNA Repair/genetics ; Humans ; INDEL Mutation/genetics ; Mitogen-Activated Protein Kinases/genetics ; Models, Genetic ; Mutation/*genetics ; Neoplasms/*classification/*genetics/metabolism/pathology ; Oncogenes/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Point Mutation/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Survival Analysis ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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